Needle aspiration cytology of tumors at various body sites

CARL E. SILVER , M.D. is Professor of Surgery at the Albert Einstein College of Medicine and Chief of the Head and Neck Service, Department of Surgery, at the Montefiore Medical Center, Bronx, New York. Dr. Silver received his M.D. degree from the State University of New York, Upstate Medical Center in Syracuse. He is the author of a textbook on laryngeal surgery and has written on various aspects of head and neck surgery, including pharyngoesophageal reconstruction, laryngeal transplantation, thyroid and parathyroid surgery, and oral cavity cancer. LEOPOLD G. Koss, M.D. is Professor and Chairman, Department of Pathology, Albert Einstein College of Medicine, Montefiore Campus, and Chairman of the Department of Pathology at the Montefiore Medical Center. From 1952 until 1970, Dr. Koss was Attending Pathologist and Chief of Cytology Service at the Memorial Hospital for Cancer and Allied Diseases. He was also Associate Member and Head of the Section of Cytopathology at the Sloan Kettering Institute for Cancer Research and Associate Professor of Pathology at the Postgraduate Medical School of Cornell University. He has served as President of the American Society of Cytology. Dr. Koss was a member of the Board of Scientific Consultants to the Armed Forces Institute of Pathology. RICHARD J. BRAUER , M.D. is Assistant Professor of Otolaryngology at the Albert Einstein College of Medicine and Assistant Attending Otolaryngologist at Montefiore Medical Center, Bronx, New York. Dr. Brauer received his undergraduate degree from Vanderbilt University, Nashville, his medical degree from Hahnemann University, Philadelphia. He completed a residency at the New York University-Bellevue Medical Center and was a Fellow in Head and Neck Surgery at the Montefiore Medical Center. He has been interested in applications of needle aspiration cytology to diagnosis and management of head and neck tumors for several years.

STEPHAN L. KAMHOLZ, M.D. is currently Associate Professor of Medicine, Albert Einstein College of Medicine, and Adjunct Attending Physician (Department of Medicine) at the Montefiore Medical Center, Bronx, New York. Dr. Kamholz received his M.D. degree from New York Medical College in 1972. He completed his training in Internal Medicine and Pulmonary Diseases at the Montefiore Medical Center between 1972 and 1977, and is certified by the American Board of Internal Medicine in Internal Medicine and Pulmonary Diseases. Dr. Kamholz’s special areas of interest have included experimental and clinical lung transplantation, immunosuppressive therapy for transplantation, and evaluation of methods for invasive pulmonary diagnosis, including needle aspiration biopsy. KENNETH L.

PINSKER,

M.D.

is Associate Professor of Medicine, Albert Einstein College of Medicine, and Director, Pulmonary Medicine at the Montefiore Medical Center, Bronx, New York. He received his M.D. degree from the Chicago Medical School in 1968. His areas of interest include lung preservation and bronchial anastomotic healing in experimental lung transplantation, critical care medicine, and the use of needle aspiration biopsy in the diagnosis of pulmonary lesions. RUTH ROSENBLATT,

M.D.

is Associate Professor of Radiology at the Albert Einstein College of Medicine and Director of the Ultrasound Section of the Department of Radiology at Montefiore Medical Center, Bronx, New York. Dr. Rosenblatt received her M.D. degree from the Women’s Medical College of Pennsylvania. During the past 10 years, while developing the Ultrasound Service, she has been active in performing and teaching interventional procedures such as percutaneous biopsies using ultrasound as a guide. Dr. Rosenblatt is a Fellow of the American College of Radiol%Y. PIER-LUIGI E SPOSTI, M.D. is Associate Professor in the Department of Urological Oncology and Radiotherapy, Radiumhemmet, Karolinska Hospital, Stockholm. He received his Bachelor of Medicine degree in 1951 at the University of Pavia, Pavia, Italy. Dr. Esposti has been a pioneer in the field of urologic cytology and has written extensively on this subject.

BACKGROUND AND GENERAL PRINCIPLES SURGEONS, internists, radiotherapists, and oncologists played key roles in the development of aspiration biopsy methods using the needle-syringe system. Because this monograph is addressed mainly to surgeons, the contributions by the late Hayes Martin to the sequence of events are worthy of note. In the 192Os, Dr. James Ewing was Chief of Pathology at the Memorial Hospital for Cancer and Allied Diseases in New York City. Martin, a young surgeon who also dabbled in radiotherapy, was unwilling to treat patients with metastatic disease without a morphological diagnosis. As related to one of us (LGK) by Ewing’s successor, Dr. Fred W. Stewart, Ewing objected to incisional biopsy because he believed that it led to the spread of cancer. As a compromise, Martin, with the help of Ewing’s factotum and technician, Edward Ellis, began to experiment with aspirations of palpable tumors using an 18 caliber needle attached to a large syringe. The first aspirates were obtained from cadavers. The technique that finally evolved consisted of rapidly prepared, air-dried smears that were stained with hematoxylineosin; incidental tissue fragments aspirated during the procedure, called clots, were fixed in Formalin and processed as small biopsies. The choice of the simple instrumentation and procedural methods was deliberate to render the method accessible to all clinicians under appropriate circumstances. In the 1930 paper by Martin and Ellis64 the indications for the procedure were summarized as follows: The indications for biopsy by needle puncture and aspiration are tumor masses which lie below the surface of normal tissue where surgical exposure is deemed contraindicated for any reason. The common contraindications to biopsy by surgical exposure may be enumerated as follows: The danger of local or general dissemination of the disease or fungation of tumor tissue through the operative wound, the interference with subsequent therapeutic surgical procedures, the surgical risk (including hemorrhage and infection) in obtaining specimens from certain deep-seated masses, and the lack of justification for any procedure involving physical or mental discomfort or expense to the patient, where the information to be gained may be of doubtful value to the patient or of academic interest only. Biopsy by needle puncture and aspiration has, we believe, none of the above-mentioned disadvantages. The danger of local or general dissemination through the minute break in the tumor capsule produced by an l%gauge needle is comparatively slight. The procedure has not in our experience caused sufficient trauma to modify the clinical setting for any subsequent treatment and the surgical risk is negligible, if sterile precautions are observed. We have not considered aspiration of abdominal tumors advisable, but we have several times successfully obtained diagnostic material from masses within the lung, without any untoward symptom either immediate or late. In a clinic wholly devoted to the treatment of neoplastic diseases, we have several times obtained unsuspected pus or other fluid leading to the diagnosis of a benign lesion. The procedure is accepted 8

without question by the patient as it does not necessitate hospitalization, elaborate preparation, great discomfort, or more than a few minutes of time. It, therefore, makes possible histological diagnoses, otherwise either unobtainable or unnecessarily deferred. Although Ellis was an exceptionally clever technician, with experience in microscopy, neither he nor Martin was responsible

for the final diagnoses, which were rendered by Stewart. In two papers, one published by Stewart in 19331°5 and another coau-

thored with Martin in 1936,62 some of the problems of the

method were discussed, such as the interpretation of scanty specimens or specimens from lesions difficult to interpret, notably those of the thyroid. The early Memorial Hospital experience was extended to bone tumors by the orthopedic surgeon, Bradley Coley, who in 1931

published a paper on this subject based on experience with 35 lesions of the skeleton.13

The early experience with aspirates of

lung lesions was summarized in 1938 by Craver and Brinkley.‘*

The use of large-caliber needles under fluoroscopic control re-

sulted in a very large proportion of pneumothoraces. An excel-

lent summary of the Memorial Hospital experience may be

found in a paper by Godwin, published in 1956.32

Although the Memorial Hospital method was shown to be ex-

tremely simple and useful and is practiced to this day with only slight modifications, it has not been accepted in other institu-

tions in the United States. It is difficult to understand the rea-

sons for it, and they may be multiple. Perhaps the key two rea-

sons have been the reluctance of surgeons to replace a proved diagnostic procedure, i.e., tissue biopsy and frozen section, with a procedure with a potential margin for diagnostic error, and the lack of familiarity of most pathologists with the interpretation

of the smear. It is therefore of special interest that the Memorial Hospital experience was noticed and discussed in European countries, notably Sweden, the Netherlands, and, to a lesser extent, Great Britain, In Europe, where the method was modified, though not necessarily simplified, it attracted a great deal of attention.

The roots of European aspiration bi:gsy can be traced to he-

matology. As early as 1919 Hirschfeld,

working at the Charitd

Hospital in Berlin, reported on aspiration of tumors by means of a needle and a small-caliber syringe. In the same tradition,

Mannheimc’ in 1931 described the use of thin. needles, 1 mm in

diameter, for aspiration of tumors and reported on 43 cases. Although Guthrie of Johns Hopkins described the use of hematologic techniques for the diagnosis of lymph node aspirates in 1921,36 the method found its principal advocates in the Nether-

lands and in Sweden. Working in Delft and Leiden, the hematologist-internist Paul Lopes Cardozo began to implement aspiration cytology on a large scale in the 1940s and published a book on this subject in 1954. 55 In Sweden, Nils Soderstrom, a 9

professor of internal medicine at the University of Lund, began experimenting with thin needle aspirates at about the same time and published a summary of his experience in book form. I n 1968l’ Franzen,28 a radiotherapist-oncologist at the Radiumhemmet in Stockholm, together with his colleagues developed a single-grip syringe which initially was designed to facilitate the aspiration of prostatic lesions and was subsequently adapted to other targets. The writin s of Franzen, his student and co-worker the late Josef Zajicek, ifi2 and several other members of the Stockholm group, notably Esposti21 and Lowhagen and Willems, have had a profound influence on the development of aspiration biopsy in Europe, whence it crossed the Atlantic Ocean again to the United States. One may speculate almost ad infinitum why a method of diagnosis, first conceived of and applied on a large scale in the United States, had to travel to Europe and back before acceptance on its native soil. Perhaps the key reason for this sequence of events was the increased familiarity of pathologists with cell samples, based notably on the popular cervical smear (Papanicolaou smear). The recently improved imaging capability of internal organs led to increasingly frequent aspirations of spaceoccupying lesions by roentgenologists. Still, the recognition by some surgeons that thin needle biopsy allows a better preoperative triage of patients has been an indispensable step in these developments. What is the future of the aspiration biopsy in the United States? Once its value is more widely recognized and the number of pathologists trained to interpret the aspirated material is adequate, the benefits to the patient in terms of speed of diagnosis at low cost, the preoperative decision-making ability, will become evident. The aspiration biopsy will never fully replace usual tissue biopsy methods, but its use will become widespread. TA R G E T S

OF

A SPIRATION

Virtually any space-occupying lesion in the body may be sampled with relative impunity by transcutaneous needle biopsy. Palpable lesions require very simple instrumentation and, with small-caliber needles, may be aspirated on an outpatient basis, without anesthesia. Lesions of the skin, subcutaneous tissue, lymph nodes, thyroid, breast, and prostate may be sampled with palpation guidance. Lesions of internal organs require roentgenologic or ultrasound guidance. Lesions of the lung and mediastinum may be aspirated under fluoroscopic or computed tomographic (CT) guidance. Lesions of abdominal organs require ultrasound or CT as guiding tools. Special procedures and instrumentation are required for needle aspiration of the skeleton, brain, eye, and retroperitoneal lymph nodes. 10

GENERAL C OMMENTS ON OF A SPIRATION B IOPSY

THE

T ECHNIQUE

The simple array of instruments required for aspiration biopsy is shown in Figure 1. In its contemporary form the aspiration biopsy is performed by means of small-caliber-hence “thin” or “fine’‘-needles. The gauge and the length of the needles may vary according to the target and the method of preparation of material. In this monograph we consider the use of needles varying in caliber from gauge 19, used for transcutaneous aspiration of thyroid and of intrathoracic lesions, to gauge 23, used in the aspiration of intra-abdominal organs. The advantages of thin needles lie mainly in their acceptability by the patients, because they cause minimal discomfort, and in their great relative safety. Perforations of viscera and of blood vessels apparently seal spontaneously and very rapidly because complicationshemorrhage or peritonitis-are exceedingly rare. Pneumothorax, on the other hand, does occur in a substantial proportion of patients undergoing aspiration of peripheral lung lesions, but rarely requires treatment.50 The cardinal steps in aspiration biopsy are shown in Figure 2. The purpose of the procedure is to obtain an adequate sample of cells of diagnostic value. With solid masses, the material contained within the needle is usually adequate for preparation of diagnostic material. A cardinal point in the aspiration process is the release of the negative pressure prior to withdrawal of the

Fig l.-Instruments used in thin needle aspiration of palpable lesions. The singlegrip syringe holder, invented by Franzen, is shown fitted with a lo-ml disposable syringe. The syringe holder allows single-handed aspiration of lesions, as shown in Figure 10. A syringe with an eccentric tip and two thin needles of different length are shown in the lower part of the figure. (Courtesy of Dr. Torsten Lowhagen, Stockholm, Sweden. From Koss L.G., et aL5’ Reproduced by permission.) 11

Inserting

Flg P.-The steps in aspiration of a paloable lesion. Step 3 indicates hbw the needle should be redirected within the target, and step 4 emphasizes the importance of releasing the negative pressure before withdrawal of the needle. (From Koss L.G., et aL5’ Reproduced by permission.)

the

needle

I’ Aspiration

Redirecting the needle within the target

3 Q+

Release before

of

negative

withdrawal

of

pressure needle

needle from the target. If this is not done and aspiration is con-

tinued as the needle is withdrawn from the target, the cells enter the barrel of the syringe and are irretrievably lost. The only exception to this rule is aspiration of the contents of cystic or necrotic lesions, during which some fluid or semifluid material usually enters the barrel of the syringe. Such material must be centrifuged prior to preparation of the smears. It is also very important to sample the target extensively by short-amplitude withdrawal and reinsertion of the needle while still within the lesion. At least three and sometimes more areas should be sampled unless the lesion is very small. It is not uncommon to find tiny fragments of tissue in the aspirate. The European cytologists advocate crushing such fragments and preparing them as smears. Because in the United States the aspirates are usually interpreted by trained surgical pathologists, it is preferable to remove such fragments with a fine forceps and save them in Bouin’s solution or other appropriate fixative for processing as a minute tissue biopsy specimen. The information provided by such preparations is often of considerable diagnostic value and confirms or adds to the diagnosis based on smear. 12

The size of the syringes used in the aspiration process varies from 2 to 50 ml, depending on the target and the preference of the operator. A syringe holder invented by Franzen and currently widely available* permits the aspiration to be performed with a single hand while the other hand fixes the palpable target. Some surgeons prefer not to use the Franzen holder and perform the aspiration with both hands, as described in the procedure for abdominal organs. The methods of smear preparation vary. European cytologists and some American investigators prefer hematologic type of preparation, using thin, air-dried smears and hematologic stains such as May-Gruenwald-Giemsa. Most American pathologists find it easier to use material fixed in alcohol (50%-70% ethanol) because of better preservation of nuclear features. A good compromise is to use a rapid hematologic stain, such as Diff-Quik (Harleco, Gibbstown, N.J.), for an initial smear to verify that the target has been reached and the material is adequate for a preliminary diagnosis. Subsequent smears may be fixed in alcohol and stained either with Papanicolaou stain or with hematoxylineosin for a definitive diagnosis. The first smear may be either preserved in its original state or restained using one half of the timing. For further data on processing of the material the reader is referred to other sources.5o HEAD AND NECK TUMORS Cytologic interpretation of material obtained by fine needle aspiration has provided a quantum leap in the diagnosis of many pathologic conditions of the head and neck, particularly those presenting as palpable masses. In many situations which previously required open biopsy or actual surgical resection of a lesion as the only means of obtaining an accurate diagnosis, needle aspiration biopsy (NAB) has afforded the surgeon valuable insight into the nature of a pathologic process in a rapid, costeffective, and minimally invasive manner. The accessibility of most areas of the head and neck to the biopsy needle guided by palpation renders this diagnostic modality particularly suitable for this anatomical area. The use of needle biopsy in the head and neck is not new. Martin and Ellis64 used the technique extensively in the 1930s. Recent developments in cytopathologic techniques permitting accurate diagnosis with minimal amounts of material obtained by fine needle aspiration have created a renaissance of interest in needle aspiration in the head and neck, as well as the other *Cameco Syringe Pistol, Precision Dynamics Corp., 3031 Thornton Ave., Burbank, CA 91504; or Aspir-Gun, Everest Co., 5 Sherman Street, Linden, NJ 07036. 13

anatomical regions discussed in this monograph. There is, nevertheless, considerable controversy compounded by confusion among surgeons in considering applications of NAB to the diagnosis and management of head and neck tumors. Confusion results from the many variable factors and approaches adopted and reported by different investigators. The needles employed vary from 18 to 27 gauge. Core biopsies (performed with VimSilverman and Tru-Cut devices) and drill biopsies,‘, 5g which are histologic methods, are often discussed simultaneously and confused with cytologic approaches to aspiration. The cytologic specimens obtained by aspiration may be handled by different methods, such as air drying or wet preparation, and the staining techniques also vary. Some authors have reported excellent results with large numbers of NABS, but with only limited numbers confirmed by operation. Inadequate aspiration is considered differently by various authors. We report our own techniques and experience and summarize the experience of others, as reported in the literature. NAB has been employed in four major areas of head and neck pathology: thyroid tumors, parathyroid lesions, salivary gland tumors, and various cervical masses. TECHNIQUE

OF

NAB

FOR

HEAD

AND

NECK LESIONS

For aspiration of masses in the head and neck, we use a 20ml syringe with a 19- or 21-gauge needle. A Franz&-type syringe holder is employed to permit operation of the syringe with one hand while the target is stabilized with the other. Aspirations are performed with the patient supine. A rolled sheet is placed under the patient’s shoulders for aspiration of the thyroid and some neck masses. An assistant’s finger placed intraorally can be helpful for submental and submandibular masses. The needle is angled away from the carotid and facial arteries. Multiple passes are made through the lesion, and pressure is equalized by releasing the syringe piston before the needle is withdrawn. This will prevent aspirating needle contents into the barrel of the syringe. We emplor an immediate wet preparation method of specimen processing,’ facilitated by having a cytotechnician present at the procedure to handle the specimen. For aspirations performed in a private physician’s office, an air drying technique may be used, but it is preferable to employ the wet preparation. Needle contents are placed on slides premoistened with 95% ethanol, and smeared. The slides are transported to the laboratory in an alcohol-filled Coplin jar. This is obviously less convenient than the use of dry smears, which may be mailed. As with all medical and surgical techniques, the quality of the study varies with the skill with which it is performed. While 14

there is a tendency, as the techniques have become more popular, for more and more physicians to perform NAB, the quality of material recovered improves with increasing experience of the individual performing the aspiration. It is important to sample the contents of the mass fairly aggressively and in several areas in order to obtain an adequate and representative specimen. For thyroid nodules and most large neck masses, we have found that a 19-gauge needle yields the most satisfactory specimens, without increased complications. Smaller masses, and lesions situated in anatomically intricate areas, are aspirated with a 21-gauge needle. We have not found the use of needles finer than 21 gauge to offer any significant advantage for aspiration of head and neck masses. COMPLICATIONS In our series of 224 needle aspirations of thyroid nodules, the only complications were two instances of tracheal puncture, without sequelae. Complications were also minimal in 80 needle aspirations of cervical masses. One hematoma, following aspiration of a submandibular mass, was treated conservatively. Attempted aspiration of a neck mass, later proved by angiography to be a carotid body tumor, resulted in a large ecchymosis over the patient’s neck and upper chest that did not require a transfusion. Occasionally we have observed a hemorrhagic track in a thyroid specimen removed soon after aspiration. We have not seen evidence of needle track implantation after the use of NAB. Such instances were reported with core biopsies.l” Weymuller et al.ll’ reviewed the literature and found two cases of implantation associated with Vim-Silverman core biopsies, and none associated with fine needle aspiration. Engzel et a1.16 reported no evidence of tumor growth or extension attributable to NAB of 15’i1pleomorphic adenomas followed for lo15 years. Engzel et al. reported that 656 patients with metastatic carcinoma in neck nodes, diagnosed by NAB, had no evidence of spread of tumor attributed to the procedure. Sijderstrom’ reported two cases of pneumothorax in more than 1,000 thyroid aspirations. THYROID

NODULES

In North America, nodular goiter occurs in 4%-7% of the population.l’* Mortensen et a1.71 found a 49.5% incidence of nodularity in a postmortem study of subjects with an average age of 60 years and clinically normal thyroid glands. The relatively few patients with malignant disease must be selected from this large population. Prior to the availability of NAB, various clinical and laboratory features were employed to select patients for operation. 15

Clinical criteria such as firmness, uninodularity, recurrent laryngeal nerve paralysis, history of irradiation, and failure to respond to thyroid hormone therapy have been considered absolute or relative indications for operation.g3 Radioisotope scanning has been the most frequently employed laboratory study. More recently ultrasonography has been used to distinguish cystic from solid lesions; the decision as to whether or not to recommend operation was based on the fact that cystic lesions of the thyroid gland are most often benign.25’ 42 The clinical and laboratory procedures outlined above are plagued by numerous false positive and negative determinations. The use of radioisotope data as the chief indication for operation in nodular goiter produces a cancer yield of 17% among all such nodules operated on.2 Figg et a1.25 reviewed 142 thyroid cancers and found that 20% had been normal11 functioning or hot nodules. Hoffman, Thompson, and Heffron4 identified normally functioning or hot nodules in 26% of all thyroid cancers. Ashcraft and Van Herle’ reviewed 16 reported series with a total of 1,001 thyroids operated on and found a 7% incidence of malignancy in cystic lesions and a 12% incidence in mixed solid-cystic lesions. Thus, if operation is recommended only for solid hypofunctioning nodules, a significant number of cancers will be missed, and an excessive number of patients with benign nonneoplastic nodules will undergo operation that is of little benefit to them. Evaluation of false negative data is particularly complicated when patients who meet criteria for benign lesions are not operated on. This is due to the indolent nature of many thyroid carcinomas. Thus, in many cases, because the patient remains ostensibly well for a prolonged period of time and eventually is lost to follow-up, the clinician may remain unaware of having failed to diagnose a malignant tumor. Thyroid NAB at Montefiore Medical Center

We have performed 252 needle aspirations of 224 thyroid nodules and have obtained histologic confirmation in operative specimens in 134.i’ Specimens were interpreted as “positive,” “negative,” or “questionable.” Positive specimens demonstrated general characteristics of malignancy, such as anisocytosis, hyperchromasia, prominent nucleoli, and mitoses. In papillary carcinoma, specific features such as cobblestoning (overlap) of nuclei, nuclear vacuoles, psammoma bodies, and papillary structures were seen (Fig 3). Negative specimens demonstrated various features including colloid-filled macrofollicles and hemosiderin-laden macrophages in cases of colloid goiter or cysts, and Hiirthle cells with numerous lymphocytes in cases of thyroiditis. There was a rather large (51.5%) indeterminate or questionable category which included finding of atypical cells in varying degrees, and microfollicular structures (Fig 4). 16

Fig 3.-A, aspiration cytology specimen diagnostic of papillary carcinoma. Note the overlapping nuclei (“cobblestoning”), nuclear vacuoles (“Orphan Annie” nuclei), and papillary structure formation (x 450). B, in follicular carcinoma, the findings are less specific. Individual malignant cells are seen, demonstrating anisocytosis, hyperchromasia, prominent nucleoli, and mitoses. Although a semblance of follicle formation is seen here, characteristic features such as the cobblestoning and papillary structure formation seen in papillary carcinoma do not occur in pure follicular carcinoma. Diagnosis of follicular carcinoma is considerably more difficult than diagnosis of papillary carcinoma ( x 450).

If specimens were inadequate, aspiration was repeated until an adequately cellular specimen was obtained. Lesions in which repeated aspirations failed to produce an adequate specimen were eventually grouped in the “questionable” category. Our results are shown in Tables 1 and 2. There was one false positive examination in 24 patients with positive preoperative cytologic findings and there were three false negative examinations on 41 lesions with negative preoperative cytologic findings. Sixteen of 69 lesions (23%) with “questionable” cytology were found to be malignant. Thirty-four cystic lesions were aspirated. Thirteen cysts that recurred rapidly and/or were of positive or questionable cytology were excised. Two (15%) were found to be malignant. Anaplastic carcinoma was difficult to diagnose, probably because of large necrotic areas within the tumors. Males accounted for only 22% of the patients operated on. The incidence of cancer in males operated on was 28%, and in females 32%. Ninety patients in our study did not undergo operation. Twenty-one had positive or questionable cytologic findings and either refused operation, had severe medical contraindications, had confirmation of diagnosis by core biopsy, or were lost to follow-up. Sixty-nine patients with negative aspirates have been 17

Flg 4.-Microfollicular adenoma. Intact small follicles are seen. Ceils are uniform in size and contain abundant cytoplasm relative to the size of the nuclei (compare with Fig 3,B) (x 180).

maintained on suppressive therapy. Needle aspirations have been repeated yearly if possible and when necessary because of any change in the mass. This group is being followed regularly. Experience of Others

The experience of other investigators with thyroid NAB is summarized in Table 3. As the methods of interpreting and reporting results differ in the various publications, we have tried to equate the data by expressing results as percentage yield of malignancy in each of three categories of cytology reported as malignant, questionable, or benign. In some institutions,70’ ” cytologic interpretation is oriented almost exclusively to determinTABLE l.-NEEDLE ASPIRATION BIOPSY THYROID

NODULES:

OF

SURGICAL FINDINGS* HISTOLOGY

CYTOLOGY

Positive Negative Questionable Total

NO.OF CASES

Ben@

24 41 69 134

38 53 92

1

Malignant 23 3 16 42

(96%) (7%) (23%) (31%)

*From Brauer and Silver.” Reproduced by permission. 18

TABLE

S.-NEEDLE ASPIRATION BIOPSY DISTRIBUTION OFTHYROID TUMORSBY

OF

THYROID NODULES: H ISTOLOGIC T YPE* CYTOLOGY

NO.OF CASES Pos.

HISTOLOGY Papillary carcinoma Papillary and follicula .r carcinoma Follicular carcinoma Hurthle cell tumor Anaplastic carcinoma Medullary carcinoma Colloid adenoma Follicular adenoma? Thyroiditis Hemorrhagic cyst Occult carcinomat Other benign Total

Quest.

Neg.

15 6

9 4

5 2

1

I 9 3 2 34 41

I 2

6

1

1

1 1

10

1

2 13 32 6

2 2 3

21 9 3 2

1 1

134

24

1 2

69

41

*From Brauer and Silver.” Reproduced by permission. tTwo cases showed capsular invasion but are considered benign. $These incidentally found microscopic tumors are not counted as malignancies.

ing whether or not operation is indicated. Thus, in these series, cases with reasonably suspicious cytology were reported in the malignant group. This resulted in lower accuracy for this group than was reported by most other authors. In general, however, a consistent pattern can be seen. The diagnosis based on cytologic specimens that meet the criteria for malignancy is highly accurate, and only a small number of false positives are reported. Similarly, specimens that have a benign cellular pattern, with evidence suggestive of colloid goiter or of chronic thyroiditis, are reported as benign with a false negative TABLE

Q.-NEEDLE ASPIRATION BIOPSY OF THYROID NODULES: SUMMARY PUBLISHEDINTHE LITERATURE

OF

RESULTS

CYTOLOGY STUDY

NO.OF ITS.

Malignant (%)

Quest. (%)

Benign (%I

Schnurer and Widstromgo Schwartz et a1.91* Galvan2’ Lowhagen et a1.57 Miller et a1.70 Rosen et a1.s4 Brauer and Silver”

284 92 1,076 412 331 153 134

100 62.5 100 100 82 99 96

15.8

0.5 7.1 3.1 4.0 1.6 4 3

16 19.5 11 i s

*Questionable cytologies were reported as malignant. 19

rate generally below 5%. There remains an indeterminate, “questionable,” or “suspicious” group of cytologic specimens in the various reported series. Of course, the criteria for inclusion in his group vary from institution to institution, but generally the specimens demonstrate atypical cells or microfollicular features, without more conclusive criteria for malignancy. This group is analyzed in Table 4. There were 603 “questionable” specimens in a total of 2,237 thyroid cytology specimens reported in the literature, accounting for 27% of such reports; 16.7% of the cytologically “questionable” cases were found to be malignant at operation. The percentage of “questionable” reports varied from about 21% to 51% in the individual series. There was some tendency for the percentage of malignancy found to increase with the size of the “questionable” group. An overall malignancy rate of about 17% for the questionable group of cases would seem to indicate that surgical removal of the nodule should be strongly considered in each individual case. This decision can be tempered by various factors, including the actual experience of the individual institution, the degree of atypia or other adverse features in the specimen, the findings on repeat aspiration, and clinical features of the individual case. Thus, questionable cytology should be considered a relative rather than an absolute criterion for operation. S ELECTION

OF

P ATIENTS

FOR

OPERATION

We believe that our data and the data of others, cited above, establish NAB as a primary diagnostic modality for the selection of thyroid nodules for operation. NAB is the only test that can distinguish carcinoma in a hyperfunctioning nodule, in a nondominant mass, or in a cystic carcinoma. The “decision tree” outlined in Figure 5 demonstrates, the role of NAB, as employed on our service, in the selection of thyroid TABLE

4 . - N E E D L E AS P I R A T I O N B I O P S Y O F T H Y R O I D N O D U L E S : S I G N I F I C A N C E O F I N D E T E R M I N A T E ( Q U E S T I O N A B L E ) RE P O R T S INDETERMINATE NAB STUDY

No.

(%I

(No.)

12176 271230

(15)

241123 12/105 16/69

(19.5) (11)

Schnerer and Widstromgo Galvahzg Lowhagen et a1.67 Miller et a1.70 Brauer and Silver”

761264

(26.8)

23011,076 1231412 105/331 691134

(21.4) (29.9) (31.7) (51.5)

Total

60312,237

(27)

20

MALIGNANCY IN INDETERMINATE GROUP

101/603

(%I

(16) (23)

(16.7)

Scan I Needle Biopsy Solid Y

1

Pos. ,r L.’ N e g . pi$q

Cystic

Rapid Recurrence Pos. or Quest. Bx lSurgery1

Disappearance or Regression

/\ Growth or Suppression Foilure to Suppress Cantd. Neg. Bx or Quest. Bx [Surgeryl Fig 5.-Decision tree demonstrating role of NAB in selection of thyroid nodules for operation. (From Silver C.E., et aLs Reproduced by permission.)

nodules for operation. Clinical considerations are always weighed along with laboratory data, so the process described represents an oversimplification. Thyroid nodules that are clinically suspicious are usually operated on, despite negative laboratory data, while risk and other clinical factors which indicate that operation would not benefit the patient may outweigh laboratory tests that suggest operative treatment. Following clinical evaluation patients generally undergo both NAB and radioisotope scanning, usually with radioactive iodine. “Hot” nodules are not operated on unless the cytologic study is positive for malignancy, or as treatment of hyperthyroidism. Cystic nodules that disappear completely after aspiration and remain diminished in size, and are of negative cytology, are observed and may be reaspirated. Cystic lesions that recur rapidly after aspiration an&or are of positive or questionable cytology are excised surgically. Solid lesions are excised if the cytologic study is positive or questionable. Solid lesions of negative cytology are treated with thyroid hormone and observed. Biopsies may be repeated at appropriate intervals. The efficacy of NAB as a means of selecting patients for operation is demonstrated by our experience over the past decade.r’, g3 There was a 16% incidence of malignancy in 141 thyroidectomies performed on our service from 1974 to 1977. In 104 thyroid nodules operated on between Jan. 1, 1971 and Dec. 31, 1981, after the introduction of NAB, the incidence of malignancy was 35%. Similar conclusions were reached by Miller, Hamburger, and King,” who diagnosed 105 cases of papillary thyroid carcinoma over a 30-month period with the use of NAB. Prior to needle aspiration, 8 years had been required to diagnose the same number of cases. 21

CERVICAL

MASSES

Cervical masses of unknown etiology are an excellent target for application of NAB. In 1961 Hayes MartinG1 stressed the harmfulness of excisional biopsy of neck nodes without extensive evaluation to rule out primary malignancy. This approach is appropriate for squamous cell carcinoma but may lead to delay, morbidity, and unnecessary expense for patients with lymphomas or other benign or malignant neck masses. Needle aspiration, performed at initial evaluation as an office procedure, permits rapid, noninvasive, and accurate classification of the nature of the cervical mass and facilitates planning of an efficient and cost-effective workup. NAB is also most useful for evaluation of newly appearing masses in patients previously treated for a head and neck malignancy. Between 1980 and 1982 we performed 80 aspiration biopsies on neck masses that were not of obvious thyroid or salivary gland origin. Results of our experience have been reportedBg and are summarized in Table 5. Subsequent operative specimens were obtained from 53 patients. Thirty-five were new patients without other findings and 18 were patients previously treated for head and neck cancer. A correct diagnosis was obtained in 31 of the 35 new patients; 17 lesions were malignant and 14 were benign. The two false positive studies in this patient group were in a patient with a reactive lymph node diagnosed as lymphoma and a patient with submandibular pleomorphic adenoma diagnosed as adenoid cystic carcinoma. The two false negative tests were in a patient with squamous cell carcinoma and a patient with a metastatic papillary thyroid cancer; in both cases lesions were cystic. Needle aspiration proved particularly valuable for evaluation of neck masses in the 18 patients with previously treated head and neck malignancy. Twelve malignant and six benign lesions were correctly diagnosed. NAB proved particularly effective for the diagnosis of squamous cell carcinoma in both new and previously treated patients TABLE BIOPSY

L-NEEDLE A SPIRATION C E R V I C A L M ASSES *

OF

Total patients Inadequate specimens Histologic confirmation True positive True negative False positive False negative Sensitivity of NAB (%) Specificity of NAB (%o) % Correct

80 8 (10%) (ii,

(20) (2) (2) 94 91 92

*Modified from Schneider et al.*’ 22

Fig B.-Squamous cell carcinoma. Note the large cells (compare with etythrocytes), pleomorphism, and anisocytosis. The eosinophillic cytoplasm and keratin formation cannot be seen in this black-and-white photograph (x 450).

(Fig 6). With the exception of the one previously mentioned false negative study, cytologic findings were used to correctly diagnose the 13 other squamous cell carcinomas in the series. In previously untreated patients, NAB serves even more importantly to classify the type of lesion involved, rather than merely to differentiate benign from malignant tumors. Our experience indicates the procedure to be effective in this regard (Table 6). Seventeen of 19 malignant and 16 of 16 benign lesions were correctly classified as to tissue of origin (Fig 7). Frable and Frable27 reported a 95% sensitivity of NAB for malignancy and a 98% specificity for the absence of malignancy in TABLE 6.-ACCURACYOF MASSES

BY

TISSUE

Salivary Thyroid Lymphoid Squamous cell carcinoma cyst Other Total

NAB INCLASSIFYINGNECK TISSUE TYPE* CORRECT

INCORRECT

2 7

0 1

15

0 1

5 2 2 33

0 0 2

*From Schneider et al.” Reproduced by permission. 23

Flg 7.-A, malignant lymphoma is often difficult to diagnose by aspiration cytology. In this specimen the large cells (compare with erythrocytes), hyperchromatic nuclei, and mitotic figures seen are sufficient for diagnosis. The cells do not clump, as in carcinoma. Nevertheless, even if malignancy cannot be confirmed by cytology, lymphoid lesions can readily be distinguished from epithelial tumors in most instances (x450). 6, NAB of a solitary neck mass in a 65year-old woman revealed spindle cells and nuclei in parallel arrangement, with abundant cytoplasm. The findings are characteristic of schwannoma (x 450).

649 cervical lymph nodes aspirated. There was a 5% false positive rate and a 2.6% false negative rate in the series. The false positive nodes all contained reactive atypical lymphoid hyperplasia suspected of malignancy. As stated above, this factor does not adversely effect the value of the procedure, as classification of a lesion as lymphoid rather than metastatic carcinoma serves to initiate further appropriate workup. Sismanis et a1.l’ obtained surgical confirmation in 84 patients following preoperative NAB of various cervical masses. Forty-eight of 55 malignancies and 24 of 29 benign lesions were diagnosed preoperatively. There were six (6.6%) false negative and no false positive studies. The overall concurrence between histologic and cytologic methods of diagnosis was 80% but included nondiagnostic smears. Exclusion of the latter raised accuracy to 93.3%. Thus, we conclude that NAB is a valuable technique for evaluating both new and old patients presenting with neck masses that are not of obvious salivary or thyroid origin. It can determine accurately the diagnostic classification of a neck mass, independent of the issue of benignancy or malignancy. Aspirates that reveal atypical lymphoid tissue effectively rule out squamous cell carcinoma. Core biopsy or early open biopsy of such 24

lesions is indicated, rather than an extensive search for an occult primary that would entail panendoscopy and random biopsies. Information obtained from NAB is an effective guide to the simple and cost-effective evaluation and treatment of neck masses. A decision tree for evaluation of cervical masses based on information provided by initial NAB is shown in Figure 8. SALIVARY GLAND TUMORS Aspiration cytology has been employed for evaluation of tumors of parotid, submandibular, and minor salivary glands. Salivary gland tumors occur far less commonly than thyroid nodules, and the question of whether or not to recommend operation for a particular lesion is not usually based on NAB results. In general, the presence of a neoplastic mass of major or minor salivary gland origin is an indication for operation. No extraordinary efforts are usually made to distinguish benign from malignant lesions preoperatively. Nevertheless, NAB can be useful in distinguishing inflammatory lesions from neoplasms and in distinguishing lymphoid from epithelial tumors. It is also quite helpful, in planning surgical treatment, if a malignant lesion is identified preoperatively. In poor-risk patients the determination that a lesion is benign by multiple NAB S, possibly with confirmation by core biopsy, may serve a useful purpose in avoiding operation. NAB has also proved useful in distinguishing salivary gland lesions from cervical lymphadenopathy. This is particularly important in instances of primary carcinoma of the floor of the mouth, where a submandibular mass may be due Thyroldectomy + RND \

Complete Endoscapy

Surglcol s

Open or Core Bx

Appropriate

W/U

\

Fig E.-Decision tree for evaluation of neck masses based on information provided by aspiration cytology. With this approach the surgeon is oriented toward the correct diagnosis at an early stage, and subsequent diagnostic procedures can be planned in an efficient manner. Unnecessary procedures are avoided. SCC, squamous cell carcinoma. (From Schneider K.L., et al. Es Reproduced by permission.) 25

either to metastatic disease or to submandibular duct obstruction. Our experience with fine needle aspiration of 48 salivary gland tumors indicates that the procedure is generally useful but that false negative results occur with some frequency. The procedure should not be used to exclude operation in patients with clinically appropriate lesions. Tables 7 and 8 summarize the results in 31 aspirations confirmed operatively. In 20 benign lesions (see Table 7) exact diagnosis was made in nine (45%). Six other tumors were correctly classified as benign, yielding a total of 15 (75%) true negative results. There were two false positives (10%). Thus, the specificity of the procedure was 88%. Review of the 11 malignant lesions (see Table 8) demonstrates the major weakness of NAB in diagnosing salivary gland tumors. Exact diagnosis was made in three instances (27%) and a fourth was reported as malignant, producing a total of four TABLE 7.-RESULTS

OF

NAB

IN

BENIGN SALIVARYLESIONS

(MONTEFIORE

CYTOLOGY

True Negative HISTOLOGY

kal

RESULTS*

Exact Dx.

Benign

False Positive Malignant

Inadequate

5 6 9

3 1 5

2 3 1

0 1 1

0 1 2

20

9

6

2

3

NO.OFNAB

eomorphic adenoma arthin’s tumor flammatory

HOSPITAL)

*False positive: 2120 = 10%. True negative 15 Specificity = = 88%. False pos. + true neg. = fi

TABLE S.-RESULTS

OF NAB INMALIGNANT (MONTEFIORE HOSPITAL)

SALIVARY LESIONS

CYTOLOGY* True Positive HISTOLOGY Mucoepidermoid carcinoma Lymphoma Other nonsalivary Total

NO.OF NAB

Exact Dx.

Malignant

False Negative Benign

Inadequate

4

1

0

1

2

5 2

1 1

1 0

3 0

0 1

11

3

1

4

3

*False negative: 4/11 = 36%. True positive Sensitivity = False neg. + true pos. 26

4 - = 50%. 8

(36%) true positive results. There were, nevertheless, four false negative studies (36%), producing an unacceptably low sensitivity of 50%. Three of the false negatives occurred in lymphomas, and the difficulty of establishing this diagnosis by NAB has been discussed in connection with cervical masses. Because lymphomas occur with some frequency in parotid lesions, however, this difficulty produces a significant problem. Clinical judgment must be employed in interpreting an apparently inflammatory pattern of leukocytes in a cytologic specimen obtained from a painless, solid intraparotid mass. The possibility of lymphoma should be considered strongly in such an instance. Other investigators have reported more successful results from cplogic evaluation of salivary gland tumors. Frable and Frable 7 reported eight false negative aspirates in a series of 227 salivary gland lesions. They determined a 92% sensitivity and a 99% specificity for the procedure. There was one false positive study. Kline et a1.48 reported exact diagnoses in 27 of 47 salivary gland aspirates, with no false positives or negatives. Studies by other authors15’ 78, lz4 have yielded generally similar results. PARATHYROID Recently the detection of parathyroid tumors by NAB under ultrasonic guidance has been reported. Solbiate et a1.1°4 performed 52 aspirations on 42 patients. They detected 31 parathyroid tumors, while 14 lesions were of thyroid origin. Seven of their specimens were inadequate. The authors found the technique to be useful for preoperative localization of parathyroid tumors and currently perform it prior to operation in all patients with parathyroid tumors. Charboneau et al.” used the same technique to locate an adenoma in a patient undergoing a third operation for persistent hyperparathyroidism. CONCLUSION: NAB

FOR

HEAD

AND

NECKTUMORS

We believe that the above data firmly establish NAB as a safe, effective, diagnostic modality in the initial evaluation of many head and neck lesions. It is the only preoperative test available to evaluate thyroid nodules which are warm, hot, or cystic. NAB should play a primary role in the decision to operate on or observe a thyroid nodule and should be used in essentially every case. Obvious anaplastic lesions can often be spared unnecessary (and unsuccessful) operation with its application. NAB of cervical masses directs the evaluation toward a lymphoma, benign mass, or search for a primary squamous cell cancer. The procedure in no way interferes with subsequent treatment. The widespread use of NAB requires that surgeons recognize it as a diagnostic modality and not a substitute for histology. 27

Just as most tests, including chemical determinations, radiographs, or radioisotope scans, are repeated as necessary, so should NAB. Aspirations that produce inadequate material for evaluation should also be repeated. The use of fine needle aspiration of head and neck masses requires training and experience. In our experience with the technique we have realized a decreasing number of false positive and negative studies, as well as of inadequate aspirations. Close cooperation is required between the cytologist and the surgeon. Aspirates can be indeterminate when considered alone, but discussion with the cytologist can lead to a valid decision. BREAST LESIONS INDICATIONS

Martin and Ellis, the major initiators of aspiration biopsy, recognized its value in the assessment of lesions of the breast. In their second paper, published in 193463 and based on experience with 1,405 patients with documented cancer, the following comment was made: Chief value in breast tumors is in the diagnosis of doubtful cases. In this regard, one may consider the combination of clinical and psychological situations which are so frequently met with in breast tumors. A highly nervous and apprehensive woman who may have digested the current propaganda in regard to the early recognition of cancer discovers a lump in her breast. She immediately consults her surgeon, or is referred to a surgeon, for an opinion. A definite mass is found in the breast which in all probability is cancer, but which in the surgeon’s opinion might be of a benign character. . . . In any case, an apprehensive patient and the family are kept under suspense until the operation is completed, and the surgeon proceeds under the mental handicap of uncertainty, which he must in all fairness, confess to the family at least. If under the same circumstances, the surgeon suggests aspiration biopsy on the first visit, the atmosphere of doubt, uncertainty and indecision will, in most cases, be removed.

Almost exactly 50 years later, this comment by Martin and Ellis has retained its full value. In fact, several developments that took place during the intervening half-century further enhance the value of aspiration biopsy of the breast. If the concern for early diagnosis of breast cancer was already evident in 1934, current views have significantly enhanced the value of early breast cancer detection. In several demonstration projects conducted in the United States and elsewhere, it has been shown that small carcinomas without lymph node metastases offer a much better chance for long-term, disease-free survival than larger tumors.4gY g2 Cancer of the breast remains the most prevalent malignant tumor in women. The most common source of discovery of mam28

mar-y carcinoma is still careful palpation of the breast. In menstruating women cycle-related palpable abnormalities are sufficiently common to obviate an aggressive investigation in many instances. In other cases, findings are not always sufficiently obvious to warrant a diagnostic surgical procedure. In both situations it is not uncommon to have the patient return for repeat office visits, sometimes over a period of months and even years, occasionally with disastrous results for the patient, whose breast cancer may become obvious only after metastasis to lymph nodes. A thin needle aspiration biopsy of suspicious areas of the breast is the obvious diagnostic procedure of choice in such patients. Mammography has contributed significantly to the detection of early carcinomas of the breast. As has been pointed out by Kopans et a1.,4g the accuracy of mammography is significantly diminished when the lesions are small. The distinction between the small benign and malignant lesions may be so difficult that a true positive rate of only lo%-30% may be anticipated. In other words, anywhere from 70% to 90% of small lesions discovered by mammography may be benign.‘5 Ascertaining the nature of such lesions of the breast is of great value. For the small mammographically identified lesions of the breast, Bolmgren et al. have devised a stereotaxic apparatus that with the help of a “screw needle” devised by Nordenstrom (Fig 9) allows pinpoint aspiration of the small lesions, about 10% of which have been shown to be malignant. ‘, 74 Injection of carbon particles along the needle track facilitates accurate operative excision. The final and perhaps most important reason for the use of transcutaneous thin needle biopsy of the breast is the obvious desire of the patient to know as rapidly as possible the nature of the abnormality. In the case of breast cancer, the patient often wishes to participate in the therapeutic decision. For this rea-

Fig 9.-Screw needle invented by Nordenstrom. With stereoscopic guidance, the needle may be introduced into very small breast lesions to secure cytologic material of diagnostic value. The needle guide may also serve to introduce carbon particles along the needle track, thus facilitating the surgical exploration of the breast. (Needle available through Ursus Konsult, Stockholm.) (From Koss L.G., et aL5’ Reproduced by permission.) 29

son, the sequence of frozen section diagnosis of carcinoma immediately followed by mastectomy is often separated into two procedures: a diagnostic excision of the breast mass, followed at a later date by a therapeutic discussion that may lead either to a second surgical procedure or to radiotherapy. It will require many years of follow-up in a controlled study to determine whether an excisional biopsy of the breast prior to definitive therapy is harmless or not. It is not our intention to present thin needle aspiration biopsy of the breast as a diagnostic panacea. Even in experienced hands, the results of the procedure show a margin of error, as discussed below. Still, as an office or outpatient procedure, it is the closest approximation to a rapid diagnosis of cancer in most clinical situations. Thin needle aspiration must be compared with the cutting needle “core” biopsy. The latter does require at least local anesthesia, is quite painful and sometimes traumatic to the patient, can only be performed in the presence of a definitive tumor mass, and requires at least 18-24 hours for diagnosis. None of these restrictions applies to thin needle aspiration: no anesthesia is required, broad areas of the lesion may be sampled, and the diagnosis may be offered within minutes or hours. METHODS

The simple instrumentation required for a thin needle aspiration biopsy consists of an assortment of needles (usually gauge 22-24) of variable length, a 20-ml syringe, an optional syringe holder (see Fig l), clean microscopic glass slides, and a bottle with fixative (usually ethanol, 50% to 95%). For evacuation of cysts, a larger caliber needle should be used. The general principles of aspiration biopsy as described in the opening section and illustrated in Figure 2 are particularly applicable to the breast. The patient must be made comfortable, preferably in a recumbent position, and the target lesion identified by palpation. For very small masses, Linsk and Franz6n54 suggest the use of an emollient skin cream to increase the sensitivity of palpation. Once the lesion has been identified and immobilized between the index finger and the thumb of one hand, the needle attached to the syringe is rapidly inserted and guided to the target (Fig 10). A distinct change in the consistency of the tissues should be felt as the needle reaches the target. Once the needle is within the target, aspiration is performed. By short-amplitude withdrawals, while still within the target, the needle must be redirected to sample three or more areas of the lesion. Before the needle is withdrawn, the negative pressure on the syringe plunger must be released. 30

Fig lO.-The position of the operator’s hands during aspiration of a breast nodule. The left hand fixes the target, whereas the right hand is used to perform the aspiration. (Courtesy of Dr. Stanislaw Woyke, Szczecin, Poland.) (From Koss L.G., et aLso Reproduced by permission.)

To prepare smears, a tiny drop of the material contained in the needle is expelled onto a slide and covered with another slide. The slides are pulled apart and two smears are thus obtained. The procedure is repeated until all of the material contained in the needle is exhausted. One of the slides may be air dried and stained with Diff-Quik stain for an immediate assessment of the sample under the microscope. The remaining smears should be fixed for further study. Fragments of tissue may be preserved in fixative such as Bouin’s solution or 10% buffered Formalin for processing as minibiopsies. INTERPRETATION

OF

THE

SAMPLE

The principal goal of thin needle aspiration biopsy is to establish the diagnosis of mammary carcinoma and occasionally of other entities. The breast lesions most commonly aspirated are as follows: I. Benign 1. Breast cysts 2. Benign mastopathies Fibrocystic disease Sclerosing adenosis Papillomatosis 3. Fibroadenomas 4. Other, less common, benign tumors Papilloma Granular cell myoblastoma 31

5. Inflammatory lesions Chronic mastitis Fat necrosis Plasma cell mastitis Tuberculosis Other, rare inflammatory processes II. Malignant 1. Carcinoma Duct carcinoma Lobular carcinoma Less common types of carcinoma Colloid carcinoma Apocrine carcinoma Medullary carcinoma Tubular carcinoma Rare types of carcinoma 2. Sarcomas 3. Metastatic tumors to the breast III. Male breast 1. Gynecomastia 2. Carcinoma Benign Lesions of the Breast

In general the cells most commonly aspirated from benign epithelial lesions of the breast are epithelial cells. These tend to form orderly sheets and clusters within which the individual cells are readily identified. Myoepithelial cells are commonly present. The nuclei are generally of equal size and show no abnormalities. An example of a smear from a fibroadenoma is shown in Figure 11. Carcinoma

Aspirates of most ordinary breast carcinomas are characterized by a disturbance in the arrangement of cells, which are either detached from each other or form disorderly clusters. Nuclear abnormalities in the form of enlargement, hyperchromasia, large nucleoli, and abnormal mitoses are frequently observed. Figure 12 shows the smear from an aspirate of a mammary carcinoma. S OURCES

OF

DIAGNOSTIC DIFFICULTY

The most important source of diagnostic difficulty is an inadequate specimen, usually the result of inexperience. Some lesions, such as scirrhous carcinoma, may yield insufficient material, even when aspiration is performed by an experienced person. Uncommon tumors may be difficult to recognize accurately. 32

Fig 11 .-Fibroadenoma aspirate: a shows two cohesive clusters of benign epithelial cells. In the background of the smear there are numerous spindly cells of myoepithelial origin. b, one of the benign epithelial cell clusters from a is shown under higher magnification. The cluster is composed of uniform cells in an orderly arrangement. c, the tissue section corresponding to a and b. (Magnification: a, x 180; b, x 450; c, x 112.) (From Koss L.G., et aI.= Reproduced by permission.)

Ag 12.-Smear of an aspirate as Figure 10, b. The much larger served. Note also the variability in matic nuclei (x 450). (From Koss

of mammary carcinoma at the same magnification size of the dispersed cancer cells is readily obcell sizes and the markedly enlarged hyperchroL.G., et aI.= Reproduced by permission.) 33

RESULTS In 1979 Zajicek121 reviewed the published data from several sources comprising 8,641 aspirates in 4,927 mammary carcinomas. He noted that the overall rate of false positive diagnoses was 0.9% (range, O-2.5%) and the overall rate of false negative diagnoses was 11.2% (range, 4.6%-26.7%). Obviously, these published results reflect a broad variety of clinical conditions and expertise. Zajicek’s personal results in 1,009 benign breast lesions aspirated between 1955 and 1964 included 2.8% false suspicious and 0.1% false positive diagnoses (Table 9). Of 1,068 breast cancers studied during the same time period, 9.9% of smears were false negative, 13.0% of smears were suspicious, and 77.1% were positive (Table 10). Zajicek’s results improved with time. In 1974 there were 226 carcinomas. The false negative rate was 1.8%; 5.7% of the smears were suspicious and 92.5% were positive. The results of the experienced Swedish group must be compared with the more recent American experience. Frable26 reported findings in 600 consecutive breast aspirates, of which 35 were unsatisfactory. There were 26 aspirates diagnosed as “susFINDINGS IN 1,009 V ERIFIED B ENIGN L ESIONS S TUDIED 1955-1964*

TABLE 9.-CmoLoGIc

HISTOLOGICALLY

HISTOLOGY: NO.OF CASES

CYTOLOGIC REPORT

BENIGN LESIONS (S)

Negative for cancer 980 97.1 Carcinomasuspected 28 2.8 Carcinoma 1 0.1 *From Zajicek.“l Reproduced by permission. TABLE VERIFIED

lO.-CYTOLOGIC F INDINGS IN 1,068 H ISTOLOGICALLY MAMMARY CARCINOMAS STUDIED 1955-1964* AND IN 226 CARCINOMAS STUDIEDIN 1974* HISTOLOGICALLY DIAGNOSED CARCINOMAS 1955-1964: 1,068

Cases

CYTOLOGIC

REPORT

Negative for cancer Carcinomasuspected Carcinoma

No.

%t

106 139

9.9 (6.1) 13.0 (11.3)

623

77.1 (82.6)

*From Zajicek.‘21 Reproduced by permission. tFigures in brackets are from 1964. 34

1974: 226

Cases

No.

11 209

%

1.8 5.7

92.5

picious”; this group included 20 breast cancers and 6 benign lesions. There were 191 diagnoses of cancer with a single false positive report due to a cystosarcoma phyllodes with marked cellular atypia. There were 302 benign lesions reported; in this group 22 carcinomas were found. It may be seen from the above data that the diagnosis of mammary carcinoma established by a competent observer on an aspirate is extremely reliable. “Suspicious” smears, usually based on inadequate material, require histologic verification or repeat aspiration. The results from Montefiore Medical Center for the period July 1, 1978 to Oct. 1, 1982 were compiled by Dr. Marie Foo. There were 387 patients with either histologic documentation or adequate clinical follow-up; in this group were 72 documented carcinomas. The aspirates on these patients were inadequate in 9, considered benign in 6, suspicious in 12, and positive in 43. Five tumors metastatic to the breast were also identified correctly. Among the 316 patients with no evidence of breast cancer there was one unproved positive diagnosis in a 68-year-old woman with disseminated ovarian carcinoma, treated with chemotherapy, to which the patient responded very well. The breast lesion was biopsied after completion of therapy and no residual cancer could be documented. Two false suspicious diagnoses were made, one in a 48-year-old woman with fibrocystic disease and one in a 3i’-year-old man undergoing chemotherapy for malignant lymphoma. Surgical biopsy of the breast nodule in the man revealed gynecomastia with highly atypical epithelial lining, presumably due to therapy. Thus, even in this initial series, and from an institution in which breast aspiration was performed by a larger number of clinical observers, often without any prior experience, the value of a positive diagnosis was again fully confirmed. These results must be compared with frozen sections of breast lesions. Rosena reported diagnoses based on 556 consecutive frozen sections. In 145 cases the correct diagnosis of carcinoma was established with no false positive results. Of the remaining 381 frozen sections the diagnosis was deferred in 30 and the lesion was considered benign in 351. In this group there were 8 carcinomas, for a false negative rate of 2%. Thus, as is true for any diagnostic test, a negative frozen section or a negative aspirate does not necessarily rule out the possibility of a carcinoma. While the likelihood of a cancer in the presence of a negative diagnosis is low, clinical judgment must prevail in such situations, and a suspicious lesion must be investigated further either by additional aspiration or by histologic examination. C OMPLICATIONS

Except for an occasional hematoma, there are no known complications of aspiration biopsy of the breast. Berg and Robbins 35

compared the l&year survival of 370 breast cancer patients whose tumors were aspirated with a large-caliber needle with survival in 370 paired controls. No differences were observed either in crude or in actuarial survival rates. THORACIC LESIONS Even though needle biopsy of the lung was described 100 years ago,53’ 7 the procedure has only recently gained acceptance in the United States. Several factors account for the increasing popularity of NAB for diagnosis of thoracic lesions: (1) The development of fine6’ and ultrathinlo aspirating needles has substantially reduced the risk of serious coml$c$ions previously associated with pulmonary needle biopsy. ’ (2) cytopathology has emerged as a valid subspecialty, consistently able to provide reliable, specific diagnoses on material obtained by NAB.‘i (3) Improved techniques are now available for visualizing and localizing thoracic lesions, including image-intensification fluoroscopy (monoplane and biplane), ultrasonography, and CT.= Percutaneous NAB may be employed for the evaluation of lesions involving the chest wall, the ribs, the pleura, the pulmy garenchyma, and hilar and mediastinal struc31Y 7f 6gY 7g Paratracheal, subcarinal, and hilar lesions may also be approached using the Wang needle-catheter assembly for transbronchial needle aspiration; the assembly may be introduced using the flexible fiberoptic bronchoscope (FFB).ii4, ‘I5 Following the pioneering efforts of Nordenstrom76 in Sweden in the mid-1960s, several large series were published in which the results of percutaneous pulmonary NAB in the United States were reported. Poe and Tobin7’ have reviewed six of these published series, in which a total of 1,826 patients underwent pulmonary NAB. The overall true positive rate for the technique (in the diagnosis of malignant lesions) was 83%, and the true negative rate was 98%, confirming the high degree of sensitivity and specificity associated with the procedure. The clinical utility of thoracic NAB also extends to the evaluation of benign lesions and inflammatory/infectious disease, as has been demonstrated by Zavala and Schoell”’ and by our own experience.47 The timesaving potential of NAB has been emphasized by Jereb and UsKrasovec”-early diagnosis and treatment of small peripheral pulmonary neoplasms may improve prognosis and increase the cost-effectiveness of the workup of such lesions.73 INDICATIONS

AND

PATIENT SELECTION

FOR

THORACIC NAB

Percutaneous or transbronchial NAB may be performed for a variety of thoracic lesions. In many instances, percutaneous NAB is done because previous FFB examination (including fluo36

roscopically guided transbronchial biopsy) was nondiagnostic.319 47 The availability of a definitive cytopathologic diagnosis for the pulmonary nodule is important if (1) a preoperative diagnosis is essential because cardiopulmonary (or other systemic) disease makes thoracotomy undesirable, unless the contemplated pulmonary resection will be potentially curative; (2) the clinical setting is that of inoperable (or metastatic) neoplasia, and NAB is being performed to establish prognosis, and/or guide therapy; and (3) the lesion is likely to be benign or inflammatory.3 Transbronchial NAB is usually the preferred initial procedure for evaluation of pulmonary nodules. In patients with obstructive airway disease, ischemic coronary artery disease, cardiac arrhythmias, or advanced age, percutaneous NAB should be performed as the initial invasive diagnostic procedure, since bronchoscopy can be difficult and/or dangerous in these conditions. Thus, for chest wall, rib, pleural, and anterior and posterior mediastinal lesions, percutaneous thoracic NAB would be the initial procedure of choice. The size and location of parenchymal pulmonary lesions are factors that determine the likelihood of successful FFB biopsy.66, 88, ‘lo Lesions more than 2 cm in diameter are more likely to be successfully aspirated by the transbronchial approach. The significance of location of the lesion within the lung as a predictor of success in transbronchial aspiration is controversial.66F‘O It is our experience, however, that “central peripheral” lesions (within 1.5 cm of the hilum) are difficult to diagnose by fluoroscopically guided transbronchial biopsy because of the marked angulation of the instrument required to reach such lesions. Although pulmonary NAB has usually not been considered to be a helpful diagnostic modality in localized or diffuse nonmalignant infiltrative disease,31P 6g several series have em hasized the utility and relative safety of NAB in this setting.34* a7, lz5 Contraindications to the performance of thoracic NAB include the following: (1) bleeding diatheses, especially if the platelet count is below 50,00O/mm and/or the prothrombin time is prolonged 3 seconds in excess of control; (2) pulmonary arterial hypertension; (3) uncooperative or obtunded patient; (4) severe respiratory distress; (5) extensive bullous lung disease, and (6) the likelihood that the lesion is vascular.7gP g7 As with any invasive diagnostic procedure, the risk/benefit ratio must be carefully evaluated for the individual patient before thoracic NAB is recommended. T ECHNIQUE Percutaneous Transthoracic NAB

Numerous descriptions of the technique for ger-zr$a;;ous pulmonary NAB have been published.77 3 ’ 47P 6g, I ’ Among 37

the differences in the technique(s) are variation in insertion site and needle path to the lesions, size of the aspirating needle, and the respiratory maneuvers employed during aspiration. Some alternatives in methodology may arise as a result of the use of different imaging equipment. For example, the use of monoplane image intensification fluoroscopy may require that the patient be turned on the fluoroscopy table so that proper needle placement can be confirmed.47 These positioning maneuvers may not be necessary when biplane fluoroscopy or CT scan guidance are employed. For some peripheral pleural-based lung lesions, real-time ultrasonographic guidance may permit localization and successful NAB when other techniques have failed.43 Our technique4’ and that of Zavala and Sohoe are quite similar. The steps are described below. 1. A radiopaque marker (coin) is taped onto the chest over the proposed site of needle entry, and the position of the marker is adjusted (as necessary) until it remains closely associated with the lesion during fluoroscopic monitoring and some patient rotation. The entry site is chosen so that it is at the upper border of the inferior rib, and so that the aspirating needle traverses the minimum perpendicular distance between chest wall and lesion 47,125 2. ’ The skin is then gently indented by pressing over the marker. After removal of the marker, the skin is prepared with iodine and the subcutaneous tissue is anesthetized by infiltration of 1% lidocaine. A short 19-gauge guide needle (3.8 cm or less) is inserted perpendicular to the chest wall through the skin and muscle. The 23-gauge ll- or H-cm aspirating needle with stylet can then be inserted through the guide needle. The use of the guide needle avoids anl potential for seeding of the needle track by malignant cells,12 and also facilitates the insertion of the extremely flexible fine needle. 3. Advancement of the fine needle to the lesion, attachment of the 20-ml sterile disposable syringe, and actual aspiration of the lesion are all performed during very brief periods of suspended respiration (at functional residual capacity). 4. Aspirates are obtained by applying negative pressure through withdrawal of the syringe plunger, as the needle is gently advanced and withdrawn in the lesion. Aspirating pressure is released before the needle and syringe are removed from the thorax. 5. The cytotechnologist immediately prepares two smears of the aspirate. One is fixed for permanent staining, and the second is examined microscopically after Diff-Quik staining to determine whether the sample is adequate. Thus, the number of aspirates per procedure (usually one to three) may be minimized. 6. Cytocentrifuge and cell block preparations are made from material rinsed from the syringe barrel-needle with 2% carbowax in 50% ethanol. If an infectious etiology is suspected, ali38

quots of the aspirate are expelled into sterile tubes for appropriate microbiologic testing. 7. An expiratory chest roentgenogram is obtained at the conclusion of the procedure and reviewed immediately for the presence of pneumothorax. If a small pneumothorax is initially noted, films are repeated at 4 hours after conclusion of the procedure, or they are repeated at indicated intervals if the patient develops dyspnea or chest pain suggesting delayed pneumothorax. An alternative method of needle insertion has been suggested that utilizes a tangential approach. Proponents claim that the risk of seeding of the tract is thereby minimized.” Needle selection must be made after careful review of appropriate roentgenograms, CT scans, and/or tomograms. The length of the needle must be appropriate for the depth of the lesion. Fine (22- and 23-gauge) or ultrathin (24- and 25gauge) needles are usually preferred, as these appear to be associated with fewer complications. Differing opinions have been expressed about the respiratory patterns of the patient during aspiration. Concern has been expressed that breath-holding maneuvers during NAB will be followed by powerful inspiratory efforts, thereby increasing the risk of pneumothorax and air embolism.‘* Other investigators utilizing these respiratory maneuvers have not encountered this problem.31S 47, lz5 Transbronchial NAB The technique of transbronchial needle aspiration via the rigid bronchoscope114,‘15 and via FFB112, ‘13 have been well described. The role of this modality in the evaluation of hilar and mediastinal involvement accompanying bronchogenic carcinoma will undoubtedly increase, and it may replace anterior cervical mediastinoscopy in certain circumstances. We have noted that some posterior paraspinal parenchymal lesions and posterior mediastinal lesions cannot be visualized with fluoroscopy adequately for fine NAB. In these instances, successful NAB may be accomplished with CT scan guidance. COMPLICATIONS

OF

NAB

The most frequent complication of thoracic NAB is the development of pneumothorax. The reported incidence of pneumothorax has ran?;! from 8% when 24- or 25-gauge ultrathin needles were used to more than 50% when M-gauge aspirating needles were used.7 Thus, the frequency of pneumothorax is unquestionably related to the gauge of the needle, a higher incidence of pneumothorax occurring when larger diameter (numerically lower gauge) needles are employed. The incidence of pneumothorax requiring chest tube placement ranges from 4% to more than 20%,7Y 125 and again is probably related to needle 39

gauge. On the basis of experimental data, it has been suggested that the rate of pneumothorax formation can be slowed and sealing of the puncture site accelerated by placin the pleural puncture in a dependent position after aspiration. 67 The incidence of pneumothorax is higher when cavitating parenchymal lesions or mediastinal lesions are aspirated.’ In most instances, the visceral pleura will be punctured in two locations in order to aspirate an anterior or middle mediastinal lesion. This may account for the higher frequency of pneumothorax observed following mediastinal NAB. Localized hematoma at the site of aspiration, hemoptysis, and hemothorax have been reported in l%-26% of patients.7’ 47* 125 Death from massive hemorrhage, due to aspiration of blood, occurs rarely.7 Massive hemorrhage has not been a problem when fine or ultrathin needles are employed (less than 5% incidence of bleeding complications when 23- to 25gauge needles are used.)127 A recent report52 describes two patients in whom acute pericardial tamponade developed after fine needle aspiration biopsy of lesions adjacent to the mediastinum. Air embolism has been reported as an extremely rare complication of NAB.ll’ Although much concern has arisen over the potential for malignant seeding of the needle tract, in fact seeding has been extremely rare.” Pneumothorax, the most frequent complication, is easily treated. Therefore, the overall experience with NAB suggests that it is a high yield, low morbidity procedure. THORACIC NAB

AT

M ONTEFIORE M EDICAL CENTER

One hundred fifty-seven patients have undergone fluoroscopitally guided thoracic fine needle aspiration biopsy at the Montefiore Medical Center since March 1978. Complete diagnostic data and adequate follow-up are available for 143 patients (Table 11). Two thirds of the patients had malignant intrathoracic tumors, and more than half had primary pulmonary parenchyma1 neoplasms (Table 12). The overall diagnostic rate for malignant tumors was 89.4%. In patients with metastatic disease the yield was somewhat lower (77%), as has been the experience of other investigators.31*125 In six of seven patients (Table 13) with benign intrathoracic tumors, the diagnosis was suggested by cyTABLE

ll.-THORACIC NAB: PATIENT DATA (MARCH 1978--OCTOBER 1983)

Thoracic NAB performed in 157 ps. Adequate data/follow-up in 143 ps. Malignant thoracic tumors found in 10’7 ps. Inflammatory disease found in 29 ps. Benign tumors found in 7 ps.

40

TABLE XL-MALIGNANT

INTRATHORACIC

TUMORS CORRECT

NO. OF PS.

DIAGNOSES

E 23 33 20

73 (91%) 20 28 6 19

Pleural and mediastinal lesions Malignant mesothelioma Lymphoma Thymoma Plasmacytoma

11 4

10 (91%) 3

Metastatic tumors

13

CELLTYPE

Primary pulmonary parenchymal lesions Epidermoid carcinoma Adenocarcinoma Oat cell carcinoma Undifferentiated carcinoma (including large cell and spindle and giant cell)

;

i

1

1

10 (77%)

Overall 104* 93 (89.4%) *In three additional atients, a cytopathologic diagnosis of malignant tumor was made. I!owever, there was an error in identification of cell type (as determined by examination of subsequent surgical or postmortemspecimen).

TABLE IS.--BENIGNINTRATHoRAcIcTLJMoRS TUMOR

NO.OF PS.

CORRECT DIAGNOSIS

Fibrous mesothelioma Hamartoma Thyroid adenoma, (5 of 7 proved at thoracotomy)

3 3

2 3

1

1

tologic examination of NAB specimens. In five of these patients, NAB findings were confirmed at thoracotomy. One patient with a hamartoma diagnosed by NAB and one patient with an intrathoracic microfollicular thyroid adenoma have remained well under prolonged observation. Twenty-nine patients underwent NAB because of inflammatory disease, although in one third of these patients the clinical impression prior to aspiration was consistent with either neoplastic or inflammatory disease (Table 14). In all instances of inflammatory lesions, the NAB cytologic (or bacteriologic) diagnosis was completely consistent with findings at thoracotomy (11 patients) or was confirmed by an appropriate response to treatment initiated on the basis of NAB findings. Illustrative examples (chest roentgenogram and photomicrograph of needle aspirate), including mediastinal, pleural and parenchymal lesions, from our series are shown in Figures 13 through 16. 41

TABLE

14.--NEEDLE A SPIRATION B IOPSY INFLAMMATORY D ISEASE DIAGNOSIS

IN

NO. OF PS.

Granulomatous disease Tuberculosis Atypical mycobacteria Granuloma

Total = 12 10* 1 1t

Local and diffuse infiltrates Spherical pneumonia Idiopathic interstitial pneumonia Chronic nonspecific pneumonia Pneumonia (lesion resolved in treatment)

Total = 9 2 lf 1t 5

Miscellaneous Total = 8 Fibrous plaque ltScar tissue/chronic inflammation 2§ Bronchiectasis/lungabscess 411 Pericardial cyst l$ *Five proved at thoracotomy: two by direct positive AFB smear, three by response to treatment. tNecrotic granuloma on NAB, Wegener’s granulomatosis on open biopsy. *Proved at thoracotomy. §Stable on CXR at 1 year. wo roved by thoracotomy; two responded to antib%ics.’

Our complication rate was quite low. The most significant complication was pneumothorax (24 patients), although less than one third of the patients with pneumothorax required chest tube placement. No deaths occurred as a result of NAB. Three patients had minimal, self-limiting hemoptysis. No other complications were noted. The overall diagnostic yield of NAB for both inflammatory and neoplastic lesions exceeded 89%. This compares favorably with results reported by other investigators.31, 47Y “* lz5 The high diagnostic yield, relative ease of performance, and low incidence of serious complications associated with NAB make it an extremely valuable technique for the evaluation of a wide spectrum of thoracic lesions. ABDOMINAL TUMORS Percutaneous needle aspiration of intra-abdominal tumors is a diagnostic technique that in many instances has replaced the exploratory laparotomy. Imaging tools developed within the past several decades, combined with thin needle aspiration techniques and expertise in cytologic interpretation, have revolutionized our approach to diagnosis. Precise anatomical imaging allows planning of a safe access route and favors successful tar42

Fig 13.-A, PA roentgenogram demonstrating small right upper left nodule (arrow) overlying fourth rib posteriorly. B, photomicrograph of fine needle aspirate of right upper left nodule revealing a granuloma (Mycobacterium tuberculosis on culture).

Fig 14.-A, PA chest roentgenogram demonstrating large anterior mediastinal mass (arrows). B, lateral chest roentgenogram demonstrating anterior mediastinal mass (arrow). C, photomicrograph of fine needle aspirate of anterior mediastinal mass revealing a thymoma, spindle cell variant.

43

Fig 15.-A, PA chest roentgenogram demonstrating a right extrapleural mass (arrow). B, photomicrograph of fine needle aspirate of right extrapleural mass revealing adenocarcinoma (metastatic from prostate).

geting of lesions. Use of thin needles reduces the risk of complications. In selected cases aspiration may be performed on an outpatient basis, with obvious economic advantages. Percutaneous aspiration biopsy may be considered when any one of the imaging modalities discussed below demonstrates a lesion (usually in the liver or pancreas), if it can be determined that a safe percutaneous access route exists. The procedure often helps to distinguish between neoplastic or inflammatory disease. In the presence of a known primary cancer, aspiration can be used to establish metastases or recurrence. The guided aspiration technique is particularly useful in nonpalpable abdominal tumors or lymph nodes. RADIOLOGIC

M ONITORING

SYSTEMS

The principal imaging techniques used to guide aspiration of intra-abdominal tumors have been fluoroscopy, CT, and ultra-

Fig 15.-A, PA chest roentgenogram demonstrating right upper left paratracheal mass (arrows). B, photomicrograph of fine needle aspirate of right paratracheal mass revealing epidermoid carcinoma. 44

sound. The choice of imaging modality depends on a number of factors, such as availability of equipment, the anatomical location and size of the lesion, and the training and skill of the person performing the aspiration. Fluoroscopy The major advantage of fluoroscopy is that the required equipment is readily available in most hospitals and radiologists’ offices. Image intensifiers, in use for the past two decades, provide images of superb clarity on a television monitor, with significantly less radiation exposure than was experienced with older, conventional fluoroscopes. The examining table can be easily manipulated for positioning of patients. Unlike the situation with intrathoracic lesions, however, where the density of a parenchymal nodule surrounded by aerated lung tissue renders the lesion readily visible, unenhanced fluoroscopy is not adequate for targeting aspiration of abdominal tumors. Ingested or parenterally administered contrast media are required to opacify specific anatomical sites. Contrast techniques include angiography, lymphangiography, percutaneous transhepatic cholangiography (PTC), and endoscopic retrograde cholangiopancreatography (ERCP). Angiography may help identify a lesion by demonstrating encasement or displacement of vessels by tumor or by revealing a tumor “blush.” PTC and ERCP help localize lesions involving the common bile duct or pancreas. Pareiras et a1.77 have used a number of the above localization techniques for successful aspiration biopsy of abdominal and retroperitoneal tumors. Lymphangiography has been an excellent modality for displaying abnormal lymph nodes as a target for aspiration.33’ ’ After the lesion is localized, the needle is introduced and advanced using biplane or single-plane fluoroscopy. The position of the needle tip is verified prior to aspiration. Because precise localization is possible, a high level of success can be attained in biopsying deeply situated small lesions. Disadvantages of using fluoroscopy as a biopsy guide are that opacification techniques are technically difficult and time-consuming, and there is radiation exposure to both patient and radiologist. Computed Tomography CT is a radiographic imaging modality that provides a twodimensional display of anatomy, usually in the transverse plane. Sagittal images may be obtained by the use of computerized reconstruction techniques. Current CT equipment can generate anatomical slices within 2 seconds, virtually eliminating motion artifact. Intravenous contrast injection further enhances spatial resolution, which is generally in the range of 2-3 mm. Because the examination is entirely mechanized, reproducible images 45

can be obtained in any patient. Bone and soft tissues are equally well displayed on CT, and when an intra-abdominal mass is detected, its relationship to the surrounding organs and vessels can be evaluated. The precise distance from skin to lesion can be measured and the angle of approach to the lesion can be judged. CT has been used as a prebiopsy localization tool by many investigators.24l37T ‘lg CT provides the capacity to document and verify precisely the position of the needle tip prior to aspiration. Lesions best suited for sampling under CT guidance include small masses (3 cm) situated deeply, and lesions that are close to the bony pelvis or spine. The main limitation to the use of CT as a biopsy guide is that the technique is time-consuming. Many images may have to be generated before the precise slice is obtained showing the needle tip within the target. In departments with only a single CT scanner, its use as an aspiration guide may be impractical because of competing demand for it as a diagnostic tool. As with fluoroscopy, CT exposes the patient to some radiation, but the radiologist is not exposed. Ultrasound

Ultrasound provides a two-dimensional display of anatomy using high-frequency sound rather than ionizing radiation as an energy source. Significant technological improvements in ultrasound equipment in the past decade have taken place. These efforts have been directed to the dynamic display of anatomical information (real time) and have resulted in the ability to produce images of excellent spatial resolution. During the course of an examination, 15 to 30 frames per second, depending on equipment design, are generated on the viewing screen. This rapid display of information and the ease with which a beam of sound can be directed by the operator result in shorter examination times. Unlike fluoroscopy and CT, ultrasound requires no contrast media. In addition, the ultrasound study avoids radiation exposure, and the equipment is not as costly. For these reasons, ultrasound has been the preferred tool for prebiops localization of lesions that can be visualized by this technique. d ‘3 “, rol The limiting factor to the use of ultrasound for prebiopsy localization has been the difficulty in documenting location of the needle within the target prior to aspiration. Small lesions and lesions deep to the entry site have been missed (see following discussion on technique). Currently a number of manufacturers of ultrasound equipment have made available special biopsy kits designed to be used with the ultrasound transducer. Such a modification offers the possibility of guiding the needle to the target while simultaneously viewing the regional anatomy. Special needles with acoustical contrast-enhancing features have also been described, making it possible to demonstrate the needle within the tissue.38 These innovations appear promising, but their effectiveness in monitoring biopsy of small lesions remains

to be evaluated. Endoscopic ultrasonic examination with an intrarectal probe has been employed for monitoring percutaneous biopsy of the prostate. TECHNIQUE

OF

NAB OFABDOMINALLESIONS

To facilitate the routine performance of aspiration biopsies in the x-ray department, it has been the practice to prepare sterile biopsy trays holding the instruments used for the procedure (Fig 17). A variety of stainless steel aspiration needles are available for percutaneous biopsy. These needles vary in length between 11 and 20 cm and are 22 or 23 gauge (outer diameter, 0.75 or 0.64 mm). The shape of the needle tip may vary as well (Fig 18). The needles consist of two parts, a hollow outer sleeve for aspirating the material and a stylet which is in place as the needle is advanced to the target. Shortly before the procedure the prothrombin time is determined. Food and drink are withheld for 4-5 hours prior to abdominal NAB. If the procedure is performed on an ambulatory patient, he is observed for 3-4 hours following aspiration before being permitted to leave the department. In selecting a skin entry site for percutaneous aspiration, the shortest distance between the skin and target is favored, thereby diminishing the likelihood of deflection of the needle. Selection of the entry site is often influenced by the desire to avoid certain anatomical structures. For example, an angled approach to lesions in the left upper quadrant or high in the right lobe of the liver is used in order to avoid the costophrenic angles (Fig 19). Major vessels and distended hollow viscera should be avoided. The skin is cleansed and anesthetized. A small skin incision is made to facilitate passage of the biopsy needles. The needle is then inserted to a predetermined depth, based on previous ultrasound or CT scans, or advanced under fluoroscopic guidance if

Fig 17.-Tray containing sterile instruments used for percutaneous aspirations, including syringes, hemostat, scalpel, metal ruler. 47

Fig l&-Needles used for aspiration include Chiba (A), pencil point (B), and Greene (C). (From Koss L.G., et aL5’ Reproduced by permission.)

A

I3

C

the latter modality is used. At times, when considerable subcutaneous fat, scar tissue, or prominent muscle is encountered, it has been helpful to insert an obturated 1% or 19-gauge spinal needle partly through the abdominal wall. After the stylet is removed the thin aspiration needle is inserted through the spinal needle, which stabilizes and guides the aspiration needle. As the aspiration needle enters the target, the operator may sense a change in the consistency of the tissue. After a few rapid (2-3 mm) excursions through the target, the obturator is removed and suction is applied to the needle with a 20-ml disposable syringe. A few excursions through the tissue are again repeated, with negative pressure maintained. Suction on the syringe is released before the needle is withdrawn.

Fig 19.~-Diagram of anterior and posterior approaches to aspiration biopsy of liver masses. A, anterior approach shows a needle guide inserted through the abdominal wall to insure correct trajectory of the thin needle. 6, angled approach to lesions in posterior and superior locations in the liver. An angled approach is used in prone patients to avoid the costophrenic sulcus and thus prevent pneumothorax. (From Koss L.G., et aI.= Reproduced by permission.)

Posterior 48

\

Except for aspiration of cyst contents, the aspirated cytologic material should remain in the needle. The procedure is repeated three to four times through the same skin incision but with slight variations in angle and depth so that different areas of the lesion are sampled. The procedure for processing of aspirated material is identical to that described for handling of aspirates from thoracic lesions at Montefiore Medical Center (see previous section). Examination of preliminary specimens at the time of aspiration biopsy yields an immediate impression as to adequacy of material and/or presence of cancer cells. A modification in aspiration technique described by Wittenberg et al.ll’ can be employed to provide a thin tissue core using a 22-gauge needle. Cytologic biopsy and tissue core minibiopsy are often complementary procedures and add to the diagnostic accuracy of the aspirations by enabling a positive diagnosis to be made in cytologically negative cases. There are a number of reasons for false negative aspirations. The most common is failure to sample the lesion owing to deflection of the needle from the target. A deeply situated lesion that is less than 3 cm in diameter is most likely to be missed, particularly when the monitoring system does not permit verification of the location of the needle tip prior to aspiration. Occasionally a tumor of firm consistency will offer resistance to puncture, and the thin needle may buckle rather than pierce the lesion. Scirrhous tumors such as pancreatic carcinomas may contain varying amounts of connective tissue stroma and yield an aspirate too scanty in cellular content. Necrotic material within the tumor, or inflammatory reaction that is part of the tumor, may also contribute to false negative results. Finally, faulty processing techniques of the aspirated sample may lead to false negative interpretations. While the incidence of false negative studies varies with the size of the lesion, the monitoring system used, and the experience of the operator, no false positive studies have been encountered in our experience.86 C OMPLICATIONS

Significant bleeding (requiring treatment) as a result of thin needle aspiration is exceedingly rare.24 In a series of more than 2,500 liver aspirations, Lundquist58 reported one case of bleeding requiring surgical intervention. A bleeding diathesis is generally considered a contraindication for the procedure. One fatality has been reported due to hemorrhage after aspiration in a patient with cirrhosis and hepatoma.83 We have seen one case of bile peritonitis following aspiration of a pancreatic carcinoma and puncture of a dilated common bile duct. One case of tumor seeding of the needle tract has also been reported.5 49

S PECIFIC S ITES

AND

E XPERIENCE

Liver

The liver has been the most frequently biopsied organ as it is a common site of tumors. Lesions as small as 2-3 cm may be resolved with current ultrasound or CT equipment. Such small tumors, however, are difficult to aspirate as they present a small target and their position with reference to the skin entry site may change significantly with respiratory motion. When multiple small lesions are present in the right lobe, the conventional Menghini liver biopsy is recommended. Focal lesions over 3 cm in size and situated medially in the right or left lobe of the liver are beyond the reach of the relatively short Menghini needle, and the guided approach offers a better yield of positive aspirates (Fig 20).815 * In addition, with the use of thin needles, morbidity and discomfort are significantly reduced.41 The imaging modalities that have been used to guide biopsy of focal liver lesions include ultrasound, CT, fluoroscopy with angiography, and scintigraphy.s8 The overall reported success rate in providing diagnostic material with guided liver biopsies varies from 83% to 1OO%.23 In our experience with a series of 96 cases in which ultrasound was used as a guide, 78 lesions (81%) were correctly diagnosed as benign or malignant (Table 15). There were no false positive aspirates. Eleven of 18 cases negative for malignancy were correctly diagnosed as abscesses. When purulent material is encountered in a lesion greater than 3-4 cm, the thin exploring needle may be exchanged for a larger bore Teflon-sheathed needle (18- to 20-

Fig 20.-A 72-year-old man presented with anorexia and weight loss. Menghini biopsy of the liver was negative. A, transverse scan of the liver showing a large echogenic mass (arrows) extending from the posterior aspect of the left lobe (LL). An anterior approach to the mass was used. B, cytologic features of the aspirate suggest hepatocellular carcinoma (x 560). (From Rosenblatt R., et al.“j Copyright 1982 by the American Medical Association. Reproduced by permission.) 50

TABLE 15.-ASPIRATIONBIOPSIESOFABDOMINALTUMORS, MONTEFIORE MEDICAL CENTER, 1977-1983

LOCATION Liver Pancreas Kidney Misc. abdominal masses Total

TOTAL

TRUE POS.

TRUE NEG.

FALSE NEG.

18 15 29

fl 11 22

171

115

3’ . .. 21

INDETERMINATE

1

11 6 1 6

11

24

3’

gauge) and, by means of a guide wire technique, further exchange for an indwelling catheter can be accomplished.10g Such an exchange is best performed under fluoroscopic control. Numerous reports of percutaneous intra-abdominal abscess drainage have demonstrated it to be an effective means of nonoperative treatment of abscesses in selected cases.3o Best results have been obtained with single unilocular abscess cavities. However, the presence of more than one collection need not be a contraindication. Involvement and cooperation of surgical staff are essential for management of possible complications, as well as for drainage of the abscess should catheter drainage prove ineffective. Contraindications to liver aspiration are the suspicion of an echymococcal cyst (since spillage of its contents may produce anaphylactic shock), and highly vascular lesions such as angiosarcoma or cavernous hemangioma. As with all intra-abdominal aspiration procedures, a safe access route to the lesion must be available. Pancreas

Imaging modalities such as ultrasound and CT permit direct visualization of the pancreas. Carcinoma may produce focal or diffuse expansion of pancreatic contour, and focal zones of altered texture or density may be noted. Visualization of pancreatic tail lesions by ultrasound may be hampered by overlying gas in the stomach and small bowel, while CT usually provides excellent visualization of the entire pancreas. CT demonstration of the pancreas is enhanced if the patient ingests a dilute contrast medium to opacify the stomach and duodenum (Fig 21). Ferrucci and Wittenbergz3 have stressed the importance of documenting the position of the needle tip prior to aspiration biopsy of pancreatic lesions. When the ultrasound study is of sufficient clarity to demonstrate regional anatomy of the pancreas, lesions greater than 2-3 cm usually can be visualized. Our experience with aspiration of pancreatic carcinoma is similar to that noted by other groups-70%~80% positive diagnoses. 51

Fig 2t.-A 60-year-old woman with back pain. A, CT scan showing expansion of the head and body of the pancreas (arrows). The fat plane around the retropancreatic vessels is obliterated, suggesting advanced disease. Some contrast and air is seen in the stomach. B, prebiopsy localization ultrasound scan. Electronic calipers mark the distance between the skin and center of the pancreas, indicating the depth for the biopsy. Cytology was consistent with adenocarcinoma of the pancreas.

In these patients exploratory operation for diagnosis can often be avoided, while resectability can be established by angiograpk. Kidney and Retroperitoneum

Guided thin needle biopsy has been used successfully in the diagnosis of renal and perirenal masses. This is an extension of the established role of renal biopsy for parenchymal disease. In our experience the chief indications for performing aspiration biopsy of a renal mass have been (1) known primary cancer (to distinguish metastatic disease to kidney from primary renal tumor), (2) skeletal metastases, and (3) cases in which operation is not contemplated. The approach to most tumors is retroperitoneal. For very large masses, a transperitoneal anterior route may be used. Other Abdominal Tumors

Large intra-abdominal masses, often related to the stomach or bowel, may be safely biopsied using a guided approach. While such masses are usually palpable, use of an imaging modality helps the surgeon plan a safe percutaneous access route (Fig 22). 52

Fig 22.-Large epigastric mass in a 58-year-old woman. CT scan at the level of the liver and stomach shows opacification by a small amount of dilute barium. An aspiration needle is seen within a retroperitoneal mass. A small amount of air injected through the needle prior to aspiration readily verifies the location of the needle tip. The aspirate was consistent with sarcoma.

CONCLUSIONS: NAB

OF

ABDOMINALTUMORS

Percutaneous needle aspiration biopsy of tumors has become an accepted method of obtaining diagnoses rapidly and safely in selected cases. It improves patient care by avoiding costly, uncomfortable workup. The success of this method depends on an interdisciplinary team approach between clinician and cytopathologist. Technical developments in the field of radiology have revolutionized the study of anatomy and gross pathology in vivo by providing equipment which has the capability for superb anatomical resolution. An ability to view regional anatomy well has helped broaden the role of the radiologist to include more “hands-on” procedures. These procedures may be diagnostic, as in the case of needle biopsies of tumors, or therapeutic, as in the case of percutaneous abscess drainage, biliary decompression, or angioplasty. “Interventional radiology” is the term used to describe this range of activities. Important responsibilities accompanying the performance of such procedures include preprocedure and postprocedure patient management, awareness of complications, and close contact with surgical colleagues who can deal with complications requiring operation. PROSTATIC CARCINOMA

The great majority of the malignant tumors of the prostate arise from the glandular portion of the organ and are histologi53

tally defined as adenocarcinomas. Prostatic carcinoma is the most common type of malignancy in men in Sweden and the second most frequent cause of death from carcinoma in men in the United States. In autopsy material an overall incidence of 12.2% after the age of 50 has been reported, which increases to 80% by the ninth decade.72 Morphological confirmation of the type of malignancy is important in deciding on the therapeutic approach. A large variety of biopsy procedures have been described. “Open” biopsies are the most accurate but must be regarded as major surgical operations requiring time and skill. Transurethral resection of the prostate, performed mainly to relieve obstruction, may yield a diagnosis of prostatic carcinoma in advanced cases, but it is considered an inadequate therapeutic method in early cases: since early prostatic carcinoma is most often found in the posterior part of the gland, it would be necessary to resect practically the whole gland before reaching the cancer. Different types of needles have been devised to obtain cores of prostatic tissue for histologic diagnosis (e.g., Vim-Silverman, Turkel, True-Cut needles). Both the perineal and the transrectal routes have been used. Aspiration biopsy with fine needle was reported by Ferguson in 193022 using an l&gauge needle and a transperineal approach. Aspiration biopsy using a 22-gauge, 20-cm long needle and a special needle guide for the transrectal approach has been used at the Karolinska Hospital, Sweden, since the late 1950s.28 This technique has won general recognition as a fast, safe, and accurate procedure. FRANZI~N'S

INSTRUMENT

AND

PROCEDURE

The instrument originally devised by Franzen consists of a syringe, a needle, and a needle guide. The original syringe had a metal handle permitting a one-handed grip for aspiration. Any one-handed holder into which a lo-cc disposable plastic syringe is attached may be used in place of the original syringe (Fig 23). The needle is 20 cm long, fine (22 gauge), and flexible. The needle guide is a metal tube, slightly curved to fit the line of the palpating finger. The proximal end of the guide is funnel-shaped to facilitate introduction of the needle. On the distal end of the guide is fitted a steering ring for the index finger (Fig 24). The patient is usually placed in lithotomy position. An alternative position is standing and bending forward, as for a rectal examination. Neither previous preparation of the bowel nor anesthesia is required. The instrument is arranged on the operator’s left hand, as shown in Figure 24. After lubrication the finger, protected by a finger cot, is carefully introduced into the rectum and against the tumor-suspected area. The needle is 54

Fig 23.-Franz&v’s

instrument for transrectal aspiration biopsy of the prostate.

then advanced through the rectal wall into the lesion (Fig 25). The plunger of the syringe is then quickly retracted by the right hand, creating a vacuum in the system, while the needle is moved back and forth in the area three or four times. The pressure in the syringe is equalized by allowing the plunger to return to its neutral position. Only then is the needle pulled out of the prostate and back into the guide, which is pulled out from the rectum. The aspirated material in the needle is expressed onto a glass slide. If the aspirate is predominantly fluid it must be spread rapidly with a coverslip as for a blood smear. Large tissue fragments are gently squeezed by flat pressure with a cov-

Fig 24.-A, needle guide arranged on the operator’s left hand. Note metal ring around the distal part of the index finger, protected by a rubber cot. B, the apparatus arranged on the hand as during biopsy. 55

Fig

25.-Sagittal

section showing the needle inserted into the suspected area.

erslip. The smear is then air-dried and stained with May-Grunwald-Giemsa stain, or fixed in methanol and stained according to the Papanicolaou method. The procedure may be repeated in the same or in different target areas, using sterile needles each time. COMPLICATIONS

Serious complications are not frequent after transrectal aspiration biopsy of the prostate; four cases of colise sis were described after 14,000 biopsies had been performed. 1r Less serious complications such as transient febrile reactions or urinary contamination have been observed in 1% of cases. Though fewer and less serious complications are registered with fine needles than when thicker biopsy needles or punch biopsy instruments are used, fine needle transrectal aspiration biopsy of the prostate should be limited to patients with clinically suspected prostatic malignancy. CYTOLOGIC

FINDINGS

Several monographs exist describing in detail the morphology of prostatic aspirates in nonmalignant and malignant conditions.54’ i2’ In cases of prostatic carcinoma, needle aspirates generally contain abundant cell material, both free cells and clusters of cells, often exhibiting acinus-like structures (Fig 26). By evaluating the degree of cellular anaplasia (mainly nuclear atypia) and the degree of glandular differentiation, it is possible to cytologically divide prostatic carcinomas into three different categories, as described below. 56

Fig 26.-Cytologic aspects of aspiration biopsy smears of different prostatic lesions (MGG, x600). A, sheet of epithelial cells aspirated from a prostate with benign hyperplasia showing honeycomb structures, regular nuclei, and cytoplasmic granules. B, cell clusters from a highly differentiated prostatic carcinoma. Note microacinar structures. C, dissociated malignant cells from a poorly differentiated prostatic carcinoma. Nuclear polymorphism and enlarged nucleoli are evident.

Grade I or well-differentiated carcinoma: Few free cells are found in the smear. Where the pattern is dominated by regular acinar structures, the cytoplasm is crowded in a central mass and the nuclei are arranged in a peripheral circle. Slight nuclear atypia is present. Grade II or moderately well differentiated carcinoma: The cells exhibit frank characteristics of malignancy (nuclear enlargement, polymorphism) and appear partly as free cells, partly as irregular clusters with an atypical acinus-like pattern. Grade III or poorly differentiated carcinoma: Abundant free cells with pronounced nuclear atypia are found together with solid cell clusters, sometime mimicking acinar structures. However, these acinar structures are not found in the rare cases of completely undifferentiated tumors. When these morphological criteria were applied to patients with newly diagnosed prostatic carcinoma, successively treated with hormonal therapy, a significant correlation was found” among cytologic grading, tumor stage, response to therapy, and crude survival rate, in the sense that tumors with a higher grade of malignancy usually exhibited higher clinical stage, 57

worse response to therapy, and shorter survival than tumors of lower grade: cytologic malignancy correlated well with prognosis. In general, when different grades of differentiation were found in the same tumor, the highest grade was considered relevant for the prognosis. DIAGNOSTIC ACCURACY

A survey of reported evaluations of the accuracy of the method was recently publishedi” and is summarized in Table 16. Special reference is made to false negative and false positive cytologic reports, as compared to tissue histologic findings in large series of patients. It would appear that the best results have been obtained when the same person has performed the biopsy and read the smear. A convincing example is the results achieved at the Karolinska Hospital after more than 20 years of experience (see study by Esposti in Table 16). Satisfactory results may, however, be obtained when a trained urologic surgeon performs the aspiration and the samples are examined by an experienced cytopathologist. At least 100 aspirations must be performed by a beginner before the results are deemed satisfactory, and an average of 200 biopsies a year must be performed to maintain the acquired skill at an acceptable level. The accuracy of the method must be tested by comparing cytologic findings with histologic controls. With increased experience, as faulty technique and inadequate diagnostic skill are eliminated, the rate of false negative reports should be reduced to around 5%. This minimal false negative rate is unavoidable; false negative diagnoses are mostly observed in glands where foci of malignancy are present solely in the anterior part of the gland, difficult to reach by the transrectal route. These cases often remain unsuspected after rectal palpation of the gland and may be accidentally diagnosed by a transurethral resection. TABLE 16.-ACCURACY

OF CYTOLOGIC DIAGNOSISIN PROSTATIC CARCINOMA BY TR~NSRECTAL FINE NEEDLE ASPIRATION BIOPSY: CYTOLOGIC-HISTOLOGIC COMPARISON*

NO.OF CARCINOMAS/ STUDY,

YEARt

Kaulen & David&, 1972 Kirstaedter et al., 1972 Esposti, 1974 Droese et al, 1976 Lin et al., 1979

CASES BIOPSIED

CYTOLOGICALLY DIAGNOSED OR

CYTOLOGIC FALSE NEG.

CYTOLOGIC FALSE POS.

SUSPECTED

DIAGNOSES

DIAGNOSES

CA.3

1591454

153 (96.2%)

54045 2141350 781288 2181484

49 205 51 154

(90.8%) (95.8%) (65.4%) (10.6%)

6 (3.8%) 5 9 27 64

(9.2%) (4.2%) (34.7%) (29.4%)

191301 (6.3%) 2/96 (2.1%) 5/136 (3.7%) 13/210 (6.2%) 52/266 (19.5%)

*From Willems and Lowhagen’ls Reproduced by permission. tOnly series with at least 50 histologically proven prostatic carcinomas are included. 58

False positive cytologic diagnoses are not frequent in the published series. They are partly due to the faulty interpretation of tricky cases, such as aspirates containing atypical epithelium from the seminal vesicles. On the other hand, small subcapsular nodules of prostatic carcinoma easily detected by transrectal aspiration biopsy might not be histologically confirmed in tissue obtained by other, less accurate biopsy methods. Ideally, the whole gland should be examined by step section technique when the accuracy of the method is checked. In comparative studies in which radical prostatectomy was performed after a cytologic diagnosis of cancer was made, based on aspiration biopsy, the diagnosis of malignancy was histologically confirmed in all cases.la CONCLUSIONS: NAB

OF

PROSTATIC TUMORS

Transrectal aspiration biopsy of the prostate is gaining general acceptance as a fast, atraumatic method in the diagnosis of prostatic carcinoma. Serious complications are rare, and given the minimal discomfort, repeat biopsies are readily accepted by the patients. The method can be used as an office procedure for screening purposes or to check results of therapy. The cytologic malignancy grading of the tumor, easily determined by this technique, has importance in the prognosis and the choice of therapy. At the Karolinska Hospital, for example, patients with well-differentiated carcinomas without symptoms often remain untreated; the carcinomas are controlled clinically and cytologically at regular intervals. Patients with moderately differentiated tumors, considered nonoperable, are at present treated hormonally. Patients with poorly differentiated prostatic cancer without distant metastases are as a rule submitted to high-voltage radiation therapy. Finally, the epithelial plugs obtained by aspiration biopsy are ideal material for enzymatic analysis of the epithelial component of the prostate. Quantitative determination of acid phosphatase levels has been performed in prostatic carcinoma and compared with the level in other tumorszl; cells from prostatic carcinoma exhibit lower enzymatic activity than the benign prostatic cells. Acid phosphatase activity in benign as well as malignant prostatic epithelial cells, however, was always higher than that observed in cells aspirated from nonprostatic tumors. Increased DNA content in aspirated cells, expressing chromosomal abnormality, can be assessed by cytophotometry. The cytochemical analysis of individual cells, based on quantitative cytophotometric measurements of Feulgen-stained nuclei, showed that nuclei from benign lesions exhibited the normal diploid amount of DNA. On the other hand, cells from prostatic carcinomas were characterized by various degrees of heteroploidy. A 59

general correlation between degree of heteroploid&sand degree of clinical and cytologic malignancy seems to exist. At present research work is in progress using flow-cytofluorometric DNA analysis of cell material, as has already been done with other urologic tumors.i” DNA determinations of a large number of cells is possible. In the opinion of the author, the use of these two complementary methods-the quantitative DNA determination of a limited number of Feulgen-stained, morphologically well identified cells and rapid-flow cytophotometry of a large number of cells-will increase knowledge of the biologic properties of the tumor and offer additional information to morphological analysis in the malignancy grading and management of prostatic carcinoma. CONCLUSION: NEEDLE ASPIRATION CYTOLOGY AND THE SURGEON

The foregoing discussions have demonstrated that evaluation of cytologic material obtained by fine needle aspiration can lead to an accurate diagnosis of tumor masses situated in various parts of the body, and in a simple, cost-effective, and relatively noninvasive manner. In each instance, by actually obtaining a sample of the tissue which can then be studied microscopically, needle biopsy produces a higher level of diagnostic accuracy than can be achieved by most other diagnostic modalities. In all of the areas discussed in this monograph, employment of fine needle aspiration has reduced or eliminated the need for totally “blind” operative exploration and excision of tumors masses, and accurate diagnosis obtained only after histologic study of the material removed. Nevertheless, there is still considerable resistance among surgeons to the employment of fine needle aspiration biopsy in the various areas discussed in this monograph. For example, a chapter by an extremely distinguished group of authors in a recent textbook makes the following statement with regard to evaluation of thyroid nodules: “Although needle biopsy may be used in place of open surgical exploration, we do not recommend it. If the specimen obtained by needle biopsy is negative for cancer, one cannot be certain that the tissue is representative of the tumor or has been obtained from it. However, if the tissue is cancerous, the procedure may have an adverse effect, such as disturbing the cancer or permitting implantation of tumor cells in other tissues along the needle tract.“* That statement reflects an attitude that prevails among many surgeons and is often expressed at lectures, panel discussions, and other forums. The attitude simply reflects a misunderstanding of the appropriate role of needle aspiration in diagnosis and presupposes difficulties that do not actually exist. Specifically, with regard to the above statement concerning 60

thyroid nodules, needle aspiration is only a diagnostic test, not a substitute for operation. Needle biopsy has a higher degree of diagnostic accuracy than any other preoperative test employed, and as such it gives the surgeon valuable advice as to which thyroid nodules should be removed. The alternatives are either to operate on every thyroid nodule seen or to try to use other, less accurate methods for determining which thyroid nodules should be removed. In actual practice, otherwise unsuspected carcinomas have been detected, resulting in timely surgical intervention, far more often than has needle aspiration prevented a patient with malignancy from undergoing surgical exploration. We have not found a single reference in the literature that suggests that people with clinically suspicious thyroid cancer should not undergo operation because of negative findings on NAB. The situation with regard to breast tumors is similar. One of the great values of NAB is that it permits documentation of a negative lesion in cases that are not clinically suspicious, and which otherwise might be simply observed without surgical biopsy, and without other means of confirmation. Thus, an apparently innocuous mass in the breast, neck, or other location might be dismissed with a recommendation that it be “watched.” Confirmation of the benign nature of such a mass by needle aspiration is one of its most valuable applications. It gives the clinician a valuable tool for “watching” such a patient, and in our experience has occasionally resulted in the detection of an otherwise unsuspected malignancy. In the chest and abdomen, where an operation of considerable magnitude may be required to determine the nature of a mass lesion, the value of fine needle aspiration is even more striking. Information of the greatest diagnostic value may be obtained in a safe and simple manner and may result in avoidance of a truly major operation where such might be of only negative value to the patient. An interesting demonstration of the value of transthoracic needle aspiration occurred recently on our service, when a patient, 1 year following total laryngectomy, was noted to have pulmonary metastases on chest x-ray films. Transthoracic needle aspiration revealed that the metastases were from a prostatic carcinoma removed several years previously, and not from metastatic squamous cell carcinoma, as was originally believed. Institution of appropriate therapy was of great benefit to the patient, both in producing a remission and in avoiding the inappropriate chemotherapy which would have been directed at the squamous cell carcinoma. A real obstacle to widespread employment of fine needle aspiration cytology throughout the United States is the shortage of trained cytopathologists in many areas. Numerous colleagues have told us they would be most interested in employing the techniques but are hampered by lack of adequately trained individuals to interpret the material. This factor may indeed ac61

count for the slow acceptance of needle aspiration outside of major medical centers. Lack of a really good method of preparing and transporting specimens is another shortcoming. Nevertheless, these problems are inherently temporary and should not result in condemnation of the technique itself, but rather in a realization of the need to train more cytopathologists and to find a simple and effective means of fixing and transporting specimens from the physician’s office to the pathologist. Lastly, in this era of ever-increasing costs of medical care and limited resources with which to meet these costs, the cost-effectiveness of needle aspiration cytology is certainly a positive factor. For palpable masses the equipment involved is minimal and readily available in every hospital and office. Even the more complex aspiration procedures involving imaging guidance are relatively simple and inexpensive compared to numerous other diagnostic procedures that are far less accurate and effective. To paraphrase one of the authors cited in this monograph,73 “a straight thin needle” may indeed be “the shortest distance between two points.” REFERENCES 1 . Ashcraft M.W., Van Herle A.J.: Management of thyroid nodules: I. History and physical examination, blood tests, X-ray tests, and ultrasonography. Head Neck Surg. 3:216-230, 1981. 2 . Ashcraft M.W., VanHerle A.J.: Management of thyroid nodules: II. Scanning techniques, thyroid suppressive therapy, and fine needle aspiration. Head Neck Surg. 3:297-322, 1981. 3 . Baker R.R.: The role of percutaneous needle biopsy in the management of patients with peripheral pulmonary nodules. J. Thorac. Cardiovasc. Surg. 79:161-162, 1980. 4 . Beahrs O.H., Kiernan P.D., Hubert J.P.: Cancer of the thyroid gland, in Suen J.Y., Myers E.N.: Cancer of the Head and Neck. New York, Churchill Livingstone, 1981, pp. 599-632. 5 . Berg J.W., Robbins G.F.: A late look at the safety of aspiration biopsy. Cancer 15:826-827, 1962. 6 . Berger R.L., Dorgan E.L., Hung B.L.: Dissemination of cancer cells by needle biopsy of thelung. J. Thor&. Cardiovasc. Surg. 63:430-432, 1972. 7 . Berouist T.H., Bailey P.B.. Cortese D.A., et al.: Transthoracic needle biopsy! Accuracy and complications in relation to location and type of lesion. &lay0 Clin. Pioc. 55:475-481, 1980. 8 . Boev J.. Hsu C.. Wone J.. et al.: Fine needle asuiration versus drill needle biopsy of thyroid nodilesi A controlled clinical-trial. Surgery 91:611-615, 1982. 9 . Bolmgren J., Jacobson B., Nordenstrom B.: Stereotaxic instrument for needle biopsy of the mamma. AJR 129:121-125, 1977. 10. Brauer R.J., Silver C.E.: Needle aspiration biopsy of thyroid nodules. Laryngoscope 94:38-42, 1984. 11. Charboneau J.W., Grant S.C., James E.M., et al.: High-resolution ultrasound-guided percutaneous needle biopsy and intraoperative ultrasonography of a cervical parathyroid adenoma in a patient with persistent hyperparathyroidism. Mayo Clin. Proc. 58:497-500, 1983. 12. Clark O.H., Okerlund M.D., Cavalieri R.R., et al.: Diagnosis and treatment of thyroid, parathyroid, and thyroglossal duct cysts. J. Clin. Endocrinol. Metab. 48:983-988, 1979. 62

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SELF-ASSESSMENT ANSWERS

1. b 2. c 3. c,d

4 . a , c, d 5 . True

6. b, c, d 7. a,c,d,e

8. a 9. c 10. True

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