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Inaccuracy of Fine Needle Aspiration Biopsy
Inaccuracy of Fine Needle Aspiration Biopsy GREGORY B. KROHEL, MD,* DANIEL R. TOBIN, MD,* RICHARD M. CHAVIS, MDt
Abstract: Fine needle aspiration biopsy (FNAB) of orbital tumors has been recently advocated as a reliable diagnostic modality. An accuracy rate of 92% has been claimed by some authors. This figure remains unproven as most patients have not undergone simultaneous pathologic examination. We recently performed FNAB on 34 patients at the time of surgical biopsy. The procedure was performed with direct visualization and the tissue was obtained and prepared as described by Kennerdell. A definitive surgical biopsy was then obtained and submitted for routine pathologic examination. Cytologic diagnosis has been accurate in less than half of the cases biopsied. Reliance on fine needle aspiration biopsy alone in some patients would have resulted in inappropriate therapy. Fine needle aspiration biopsy should be limited to strongly suspected cases of orbital metastases or secondary tumors. [Key words: cytopathologic diagnosis, fine needle aspiration biopsy, histopathologic diagnosis, lymphoma, metastatic disease, optic nerve tumors, orbital tumors.] Ophthalmology 92:666-670, 1985
Fine needle aspiration biopsy (FNAB) has been proposed as a diagnostic technique for evaluating orbital tumors. This technique has been used in diagnosing neoplasms of various organs including thyroid, pancreas, lung, and abdomen. 1,2 Schyberg and Westman-Naeser and Naeser introduced fine needle aspiration biopsy in the evaluation of orbital tumors. 3 ,4 Kennerdell and colleagues refined the technique, (jescribing several sophisticated methods of obtaining biopsy material using computed tomography and ultrasound guidance. 5 ,6 It is difficult to evaluate the accuracy of fine needle aspiration biopsy versus permanent histopathologic examination of orbital tissue, as only one study has compared these methods.7 In that study of 13 patients, fine needle aspiration biopsy was accurate in eight patients, inaccurate in two patients and insufficient tissue was obtained in three patients. Kennerdell et al recommend using fine needle aspiration biopsy to diagnose a wide variety of orbital tumors, including secondary neoplasms, metastatic tumors, optic nerve tumors and the range of From the Department of Ophthalmology, Albany Medical College, Albany, New York: and Georgetown University Hospital, Washington, DC.t Presented at the Eighty-ninth Annual Meeting of the American Academy of Ophthalmology, Atlanta, Georgia, November 11-15, 1984. Supported by an unrestricted grant from Research to Prevent Blindness, Inc. Reprint Requests to Gregory B. Krohel, MD, Department of Ophthalmology, Albany Medical College, Albany, NY 12208.
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lymphoproliferative tumors froin inflammatory orbital pseudotumors to lymphomas. 7 In order to ascertain the accuracy of fine needle aspiration biopsy and its role in orbital tumor diagnosis, we recently performed fine needle aspiration biopsy on 34 patients at the time of definitive surgical biopsy. We report the results of that study and outline our limited indications for fine needle aspiration orbital biopsy.
MATERIALS AND METHODS Thirty-four consecutive patients were evaluated at the Albany Medical Center Hospital or Georgetown University Hospital over an II-month period. All of the operations were performed by one of the authors (GBK or RMC). All patients undergoing an open surgical biopsy through either an anterior or a lateral orbitotomy were simultaneously subjected to needle biopsies. the tumors were exposed during the operation and the fine needle aspiration was done under direct visualization using a 22- or 23-gauge needle on a 20 cc syringe. Tumors suspected of being encapsulated or potentially malignant (ie. benign mixed lacrimal gland tumors) were removed from the orbit and the needle biopsy was performed on the instrument table to prevent seeding of the tumor in the orbit. The slides for cytology were fixed in 95% alcohol and stained with the Papanicolaou technique according to
KROHEL, et
at
•
Table 1. Comparison of Cytologic Findings and Histopathologic Diagnosis Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34
Cytologic Findings Insufficient tissue Hemangiopericytoma Lymphocytes, no malignancy Dermoid Inflammatory cells, no malignancy Insufficient tissue Chronic inflammatory cells Insufficient tissue . Insufficient tissue Lymphoma, class III Lymphoma Lymphoma Adenocarcinoma Malignant melanoma Malignant cells Storage disorder Foamy histiocytes Spindle cell tumor Mucocele Epidermoid carcinoma Lymphoma Insufficient tissue Lymphoma Insufficient tissue Squamous cell carcinoma Insufficient tissue Dermoid Fibrous histiocytoma Insufficient tissue Insufficient tissue Spindle cells Dermoid Insufficient tissue Insufficient tissue
Histologic Diagnosis Benign mixed tumor Fibrous histiocytoma Benign lymphoid hyperplasia Epidermoid cyst Normal lacrimal gland Dacryoadenitis Inflammatory pseudotumor Dacryoadenitis Sclerosing pseudotumor Thyroid ophthalmopathy Lymphoma Lymphoma Adenocarcinoma Malignant melanoma Squamous cell carcinoma Dermoid Dermoid Neurilemoma Mucocele Hemangiopericytoma Lymphoma Leukemia Rhabdomyosarcoma Dermoid Squamous cell carcinoma Melanoma Dermoid Dermoid Orbital fibromatosis Squamous cell carcinoma Neurilemoma Dermoid Cavernous hemangioma Cavernous hemangioma
the protocol used by Kennerdell et al. 7 The cytologists were made aware of the preoperative diagnosis and operative findings but were not told the histopathologic diagnosis. Three different cytopathologists from the two institutions examined the cytologic material. The histopathologic diagnosis was then independently performed by several ophthalmic pathologists at the two institutions. The results of the fine needle aspiration orbital biopsy were compared to the histopathologic diagnoses and the patients were placed into one of three categories (Table 1). The categories included those patients whose needle aspiration diagnosis was compatable with the histopathologic diagnosis (Fig 1), those in whom the diagnosis was either inaccurate or misleading (Fig 2), and those patients in whom the needle biopsy yielded either no tissue or simply blood and/or fibrous tissue. It is noteworthy to reiterate that these fine needle aspiration biopsies were done under optimal conditions at the time of surgery and in all cases the tumor was directly visualized while the needle aspiration biopsy was being performed.
INACCURACY OF FNAB
RESULTS In 16 of 34 patients we obtained a cytologic diagnosis which was compatable with the histopathologic diagnosis. In seven of 34 patients the cytologic diagnosis was either inaccurate or misleading. In the latter group, interpretation of the fine needle aspiration biopsy without histopathologic confirmation would have resulted in further tests or therapy which was inappropriate. Finally, in 11 of 34 patients we obtained either no tissue, nonspecific fibrosis or blood on the slide and cytologic diagnosis was not possible.
DISCUSSION Kennerdell et al. reported 92% diagnostic accuracy in a series of fine needle aspiration biopsies of orbital disease processes. 8 Our comparative study ofFNAB and histopathologic diagnosis suggests a lower accuracy rate. Only 47% of our patients had a totally accurate cytopathologic diagnosis when compared to the confirmed histopathologic diagnosis. This is not surprising since our series contains a wide variety of orbital tumors versus a selected population. The wide variety of disease processes encountered in the orbit helps to explain the overall inaccuracy of fine needle aspiration biopsy. Two patients had cytopathologic diagnoses which were compatable with the histopathologic diagnosis, but the FNAB alone was not diagnostic. This level of accuracy might be acceptable in patients with known metastatic disease, secondary tumors or when previous histopathologic diagnosis had been obtained. Examples include patients with known metastatic disease or patients with sinus tumors invading the orbit where incomplete resections had been performed previously. Our low overall accuracy rate indicates that FNAB is not justified in patients with a new orbital disease process which does not fall into the metastatic or secondary tumor categories. Our fine needle aspiration biopsies were obtained under direct visualization and optimal conditions. One might expect a lower accuracy rate when dealing with blind fine needle aspiration biopsies or those done with CT or ultrasound guidance. Our results with FNAB in patients with lymphoma or orbital inflammatory pseudotumor also differ from previous reports. In our series of lymphoid lesions we obtained five correct diagnoses, two incorrect diagnoses, and two inadequate tissue samples. It is difficult to separate patients with lymphoid hyperplasia in the pseudotuinor group from those patients with malignant lymphomas, even with good histopathologic technique. Cell surface markers are still being investigated as a diagnostic modality in this group of disease processes. Evaluation of these lesions by electron microscopy has also been advocated. 9 Fine needle aspiration does not allow the use of cell surface markers nor does it allow one to obtain electron micrographs. Kennerdell has adapted a treatment protocol whereby 667
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Fig 1. Left. the cytologic specimen obtained by the technique of fine needle aspiration biopsy. One sees lymphocytes scattered throughout a field of red blood cells. A diagnosis of lymphoma was made by a cytopathologist based on this aspirate alone. Right. permanent histopathologic section from the same patient consistent with orbital lymphoma.
Fig 2. Left. cytologic aspirate was incorrectly interpreted by a cytopathologist as being consistent with orbital lymphoma. Right. correct diagnosis of rhabdomyosarcoma was made on permanent histopathologic sectioning.
all patients with lymphoid lesions are treated with radiation therapy. 8 Irradiation is the treatment of choice for orbital lymphomas and is an accepted treatment modality for patients with orbital inflammatory pseudotumors. We agree that orbital irradiation is the treatment of choice for orbital lymphomas, but do not feel that all patients with orbital pseudotumors should be irradiated. Many patients have spontaneous resolution of their lesions and some patients have permanent resolution following a course of corticosteroids. Orbital irradiation for a lymphoid lesion involves cataractogenic doses of radiation. We are reluctant to treat orbital pseudotumors in young patients with this technique. Our study did not include optic nerve tumors. The most common optic nerve tumors are optic nerve gliomas and optic nerve sheath meningiomas. Fine needle aspiration biopsy has been used in the diagnosis of these two entities. However, marked arachnoidal hyperplasia around an optic nerve glioma can mimic and optic nerve meningioma. 1O Fine needle aspiration
668
biopsy and superficial biopsy of the optic nerve can lead to an erroneous diagnosis of optic nerve sheath meningioma. The clinical findings in patients with optic nerve gliomas and optic nerve sheath meningiomas differ, as does the CT scan appearance. Coupled with a good clinical history and examination, CT scan can often separate these two groups of patients, obviating the need for biopsy. II Fine needle aspiration biopsy is useful in patients with strongly suspected metastatic tumors to the orbit or in those patients with secondary neoplasms (ie. sinus tumors) which have been biopsied previously. Many of our patients with disseminated metastases and a poor prognosis are spared biopsies of any type when their clinical and CT findings are consistent with a metastatic lesion. These patients are often irradiated without a tissue diagnosis under such circumstances. We agree with Kennerdell and co-workers that metastatic lesions constitute a primary indication for fine needle aspiration biopsy of the orbit.
KROHEL, et aI
•
INACCURACY OF FNAB
those patients with secondary neoplasms from contiguous orbital structures. Based on this study, fine needle aspiration biopsy does not have a role in the diagnosis of primary orbital disease processes.
It has been well documented that patients may have orbital inflammatory changes surrounding an orbital metastasis. 8,12 Fine needle aspiration can produce an erroneous diagnosis if only the inflammatory component is biopsied. An immunoperoxidase technique has recently been coupled with FNAB in the diagnosis of prostatic carcinoma. I3 Further advances in immunoperoxidase technique for cytohistochemical diagnosis may lead to increasing utilization of fine needle aspiration biopsy. Equivocal uses for needle aspiration biopsy include the presence of orbital abscess or hemorrhage. In both instances, definitive treatment involves a surgical drainage by lateral or anterior orbitotomy. In rare instances, an abscess is drained as a temporizing measure or for bacteriologic diagnosis before the patient can be taken for definitive surgical drainage. Drainage of an orbital hemorrhage might be partially accomplished by this technique, although it is not advocated as a definitive therapeutic measure. One would also be tempted to utilize FNAB for diagnosing suspected inflammatory lesions in the orbital apex. One is reluctant to perform a lateral orbitotomy in order to diagnose inflammatory orbital pseudotumor of the orbital apex as this procedure can produce considerable morbidity. A diagnostic trial of corticosteroids is often indicated in this clinical situation. One then follows the patient while on high dose corticosteroids, looking for a marked improvement in the clinical picture as well as an improvement or resolution of the lesion on CT scan. Fine needle aspiration biopsy may be helpful in these patients in several circumstances. If tissue compatible with inflammatory orbital pseudotumor is obtained, one has further reassurance that corticosteroid treatment is the proper therapy. If tissue consistent with metastatic disease or another neoplastic process is biopsied, an open biopsy becomes mandatory. In summary, we feel that fine needle aspiration biopsy of the orbit should be reserved for those patients with known or strongly suspected metastatic disease and
REFERENCES 1. Einhorn J, Franzen S. Thin-needle biopsy in the diagnosis of thyroid disease. Acta Radiol 1962; 58:321-36. 2. Schour L. Chu EW. Fine needle aspiration in the management of patients with neoplastic disease. Acta Cytol 1974; 18:472-6. 3. Schyberg E. Fine needle biopsy of orbital tumours. Acta Ophthalmol 1975; Suppl 125: 11 . 4. Westman-Naeser S, Naeser P. Tumours of the orbit diagnosed by fine needle biopsy. Acta Ophthalmol1978; 56:969-76. 5. Kennerdell JS, Dubois PJ, Dekker A, Johnson BL. CT·guided fine needle aspiration biopsy of orbital optic nerve tumors. Ophthalmology 1980; 87:491-6. 6. Spoor TC, Kennerdell JS, Dekker A, et al. Orbital fine needle aspiration biopsy with B·scan guidance. Am J Ophthalmol 1980; 89:274-7. 7. Kennerdell JS, Dekker A. Johnson BL, Dubois PJ. Fine·needle aspiration biopsy; its use in orbital tumors. Arch Ophthalmol 1979; 97:1315-7. 8. Kennerdell JS, Dekker A, Johnson BL. Orbital fine needle aspiration biopsy: the results of its use in 50 patients. Neuro·OphthalmoI1980; 1 :117-21. . 9. Jakobiec FA, Iwamoto T, Knowles OM II. Ocular adnexal lymphoid tumors; correlative ultrastructural and immunologic marker studies. Arch Ophthalmol 1982; 100:84-98. 10. Cooling RJ, Wright JE. Arachnoid hyperplasia in optic nerve glioma: confusion with orbital meningioma. Br J Ophthalmol 1979; 63:596-9. 11 . Jakobiec FA, Depot MJ, Kennerdell JS, et aI. Combined clinical and computed tomographic diagnosis of orbital glioma and menin· gioma. Ophthalmology 1984; 91:137-55. 12. Krohel GB, Perry S, Hepler RS. Acute hypertension with orbital carcinoid tumor. Arch Ophthalmol 1982; 100:106-8. 13. Reifler OM, Kini SR, Liu 0, Littleton RH. Orbital metastasis from prostatic carcinoma; identification by immunocytology. Arch Ophthalmol 1984; 102:292-5.
Discussion
by
John S. Kennerdell, MD The authors make an honest attempt to further evaluate the accuracy of the fine needle aspiration biopsy and more clearly define its best use. Unfortunately, the incorrect sampling in this study based on a lack of understanding the nature of cytology, together with an apparent lack of understanding of orbital lesions by the cytologists, makes this study an unfair evaluation of the fine needle aspiration technique for orbital lesions. In the past, Papanicolaou had a great deal of difficulty convincing his colleagues of the value of the cytology of the uterine cervix. Clearer understanding of the technique and its indications and limitations, has led it to be a standard screening technique for cervical cancer. The same applies to orbital fine From the Eye and Ear Hospital, 230 Lothrop Street, Pittsburgh.
needle aspiration biopsy. It is under criticism due to the lack of understanding of cytology by ophthalmic surgeons and lack of understanding of orbital pathology by cytologists. The authors have indiscriminately punctured orbital lesions, including resectable orbital tumors such as the hemangioma, which could not possibly be identified by a cytologist with no information about the nature of the orbital lesion. The same applies to hemangiopericytoma, neurofibromas, fibrous histiocytoma, and dermoid cysts. We have repeatedly stressed the indications for fine needle aspiration to nonresectable orbital lesions such as carcinomas, lymphoid lesions, or nonspecific orbital inflammations where the technique has a reasonable chance of harvesting cells-which, through clinical pathologic correlation with the ophthalmologist, cytologist and ophthalmic pathologist, can lead to appropriate management of the patient
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without a further open biopsy. Indeed, if the cytological attempt is negative, it does not preclude an open biopsy. Therefore, the authors have selected a significant number of orbital tumors which have no possibility of a positive identification, particularly when presented to a cytologist without clinical correlation. For instance, we would not recommend sampling what expected to be a benign mixed tumor, fibrous histiocytoma, hemangiopericytoma, neurolemmoma, or cavernous hemangioma. We have sampled two dermoids, in light of the fact that they had atypical presentations, but a dermoid was still part of the differential diagnosis in those patients. The present study sampled six dermoids of the 34 patients. Without a cytologist experienced in orbital lesions, I am surprised the authors identified two properly. Of the 34 patients subjected to this technique, only 15 would have been aspirated if in our hands. Of that group, 1 cannot understand failure in two dacryoadenitis cases with insufficient tissue. We found this a rather easy sampling area, but because of the superficial nature of these lesions, have limited the use of fine needle aspiration in lacrimal lesions, often preferring open biopsy. I wonder also why the authors sampled a normal lacrimal gland and found inflammatory cells. Some sort of inflammation or other disorder associated with the gland caused the authors to direct their attention to it in the first place. I also cannot understand how they could misdiagnose thyroid ophthalmopathy as lymphoma. Thyroid ophthalmopathy can and should be diagnosed without the needle aspiration. Therefore, this should be rare in the differential diagnosis. It is easy to see why difficult tumors such as a fibrous histiocytoma, rhabdomyoscarcoma, and hemangiopericytoma are confused. These are easily confused histologically under
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the best circumstances, and therefore should not be expected to be histologically diagnosed by fine needle aspiration, again bringing up the point that cytology does not usually provide a histologic diagnosis. It must be correlated appropriately with the clinical pathologic setting by an appropriate team. In summary, we would agree with the authors, although totally disagreeing with the design of their study, that fine needle aspiration is not a general orbital diagnostic technique. Neither is it a technique that, in experienced hands, needs to be limited to patients with known or strongly suspected metastatic disease, or patients with secondary contiguous orbital neoplasms. Our first paper I summarizing 50 patients revealed a positive identification of 92% with our criteria. This was largely due to the fact that we were sampling easier lesions involving some extending into the lids. Since we have become more experienced with the technique, we are about to report 156 patients with a positive identification of 80%. We now are nearing the repeatable percentage of positivity in experienced hands. We do recommend that those who are interested in the technique be well experienced in orbital disease and begin with patients, as recommended by the authors, that are easier to harvest and more predictable. Experience can be gained through identifying these patients with the cooperation of the cytologist and ophthalmic pathologist. Without a cooperative, interested team, one should avoid the use of this technique. Reference 1. Kennerdell JS, Dekker A, Johnson BL. Orbital fine needle aspiration biopsy: the results of its use in 50 patients. Neuro-OphthalmoI1980; 1 :1 17-21.
Abstract: Fine needle aspiration biopsy (FNAB) of orbital tumors has been recently advocated as a reliable diagnostic modality. An accuracy rate of 92% has been claimed by some authors. This figure remains unproven as most patients have not undergone simultaneous pathologic examination. We recently performed FNAB on 34 patients at the time of surgical biopsy. The procedure was performed with direct visualization and the tissue was obtained and prepared as described by Kennerdell. A definitive surgical biopsy was then obtained and submitted for routine pathologic examination. Cytologic diagnosis has been accurate in less than half of the cases biopsied. Reliance on fine needle aspiration biopsy alone in some patients would have resulted in inappropriate therapy. Fine needle aspiration biopsy should be limited to strongly suspected cases of orbital metastases or secondary tumors. [Key words: cytopathologic diagnosis, fine needle aspiration biopsy, histopathologic diagnosis, lymphoma, metastatic disease, optic nerve tumors, orbital tumors.] Ophthalmology 92:666-670, 1985
Fine needle aspiration biopsy (FNAB) has been proposed as a diagnostic technique for evaluating orbital tumors. This technique has been used in diagnosing neoplasms of various organs including thyroid, pancreas, lung, and abdomen. 1,2 Schyberg and Westman-Naeser and Naeser introduced fine needle aspiration biopsy in the evaluation of orbital tumors. 3 ,4 Kennerdell and colleagues refined the technique, (jescribing several sophisticated methods of obtaining biopsy material using computed tomography and ultrasound guidance. 5 ,6 It is difficult to evaluate the accuracy of fine needle aspiration biopsy versus permanent histopathologic examination of orbital tissue, as only one study has compared these methods.7 In that study of 13 patients, fine needle aspiration biopsy was accurate in eight patients, inaccurate in two patients and insufficient tissue was obtained in three patients. Kennerdell et al recommend using fine needle aspiration biopsy to diagnose a wide variety of orbital tumors, including secondary neoplasms, metastatic tumors, optic nerve tumors and the range of From the Department of Ophthalmology, Albany Medical College, Albany, New York: and Georgetown University Hospital, Washington, DC.t Presented at the Eighty-ninth Annual Meeting of the American Academy of Ophthalmology, Atlanta, Georgia, November 11-15, 1984. Supported by an unrestricted grant from Research to Prevent Blindness, Inc. Reprint Requests to Gregory B. Krohel, MD, Department of Ophthalmology, Albany Medical College, Albany, NY 12208.
666
lymphoproliferative tumors froin inflammatory orbital pseudotumors to lymphomas. 7 In order to ascertain the accuracy of fine needle aspiration biopsy and its role in orbital tumor diagnosis, we recently performed fine needle aspiration biopsy on 34 patients at the time of definitive surgical biopsy. We report the results of that study and outline our limited indications for fine needle aspiration orbital biopsy.
MATERIALS AND METHODS Thirty-four consecutive patients were evaluated at the Albany Medical Center Hospital or Georgetown University Hospital over an II-month period. All of the operations were performed by one of the authors (GBK or RMC). All patients undergoing an open surgical biopsy through either an anterior or a lateral orbitotomy were simultaneously subjected to needle biopsies. the tumors were exposed during the operation and the fine needle aspiration was done under direct visualization using a 22- or 23-gauge needle on a 20 cc syringe. Tumors suspected of being encapsulated or potentially malignant (ie. benign mixed lacrimal gland tumors) were removed from the orbit and the needle biopsy was performed on the instrument table to prevent seeding of the tumor in the orbit. The slides for cytology were fixed in 95% alcohol and stained with the Papanicolaou technique according to
KROHEL, et
at
•
Table 1. Comparison of Cytologic Findings and Histopathologic Diagnosis Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34
Cytologic Findings Insufficient tissue Hemangiopericytoma Lymphocytes, no malignancy Dermoid Inflammatory cells, no malignancy Insufficient tissue Chronic inflammatory cells Insufficient tissue . Insufficient tissue Lymphoma, class III Lymphoma Lymphoma Adenocarcinoma Malignant melanoma Malignant cells Storage disorder Foamy histiocytes Spindle cell tumor Mucocele Epidermoid carcinoma Lymphoma Insufficient tissue Lymphoma Insufficient tissue Squamous cell carcinoma Insufficient tissue Dermoid Fibrous histiocytoma Insufficient tissue Insufficient tissue Spindle cells Dermoid Insufficient tissue Insufficient tissue
Histologic Diagnosis Benign mixed tumor Fibrous histiocytoma Benign lymphoid hyperplasia Epidermoid cyst Normal lacrimal gland Dacryoadenitis Inflammatory pseudotumor Dacryoadenitis Sclerosing pseudotumor Thyroid ophthalmopathy Lymphoma Lymphoma Adenocarcinoma Malignant melanoma Squamous cell carcinoma Dermoid Dermoid Neurilemoma Mucocele Hemangiopericytoma Lymphoma Leukemia Rhabdomyosarcoma Dermoid Squamous cell carcinoma Melanoma Dermoid Dermoid Orbital fibromatosis Squamous cell carcinoma Neurilemoma Dermoid Cavernous hemangioma Cavernous hemangioma
the protocol used by Kennerdell et al. 7 The cytologists were made aware of the preoperative diagnosis and operative findings but were not told the histopathologic diagnosis. Three different cytopathologists from the two institutions examined the cytologic material. The histopathologic diagnosis was then independently performed by several ophthalmic pathologists at the two institutions. The results of the fine needle aspiration orbital biopsy were compared to the histopathologic diagnoses and the patients were placed into one of three categories (Table 1). The categories included those patients whose needle aspiration diagnosis was compatable with the histopathologic diagnosis (Fig 1), those in whom the diagnosis was either inaccurate or misleading (Fig 2), and those patients in whom the needle biopsy yielded either no tissue or simply blood and/or fibrous tissue. It is noteworthy to reiterate that these fine needle aspiration biopsies were done under optimal conditions at the time of surgery and in all cases the tumor was directly visualized while the needle aspiration biopsy was being performed.
INACCURACY OF FNAB
RESULTS In 16 of 34 patients we obtained a cytologic diagnosis which was compatable with the histopathologic diagnosis. In seven of 34 patients the cytologic diagnosis was either inaccurate or misleading. In the latter group, interpretation of the fine needle aspiration biopsy without histopathologic confirmation would have resulted in further tests or therapy which was inappropriate. Finally, in 11 of 34 patients we obtained either no tissue, nonspecific fibrosis or blood on the slide and cytologic diagnosis was not possible.
DISCUSSION Kennerdell et al. reported 92% diagnostic accuracy in a series of fine needle aspiration biopsies of orbital disease processes. 8 Our comparative study ofFNAB and histopathologic diagnosis suggests a lower accuracy rate. Only 47% of our patients had a totally accurate cytopathologic diagnosis when compared to the confirmed histopathologic diagnosis. This is not surprising since our series contains a wide variety of orbital tumors versus a selected population. The wide variety of disease processes encountered in the orbit helps to explain the overall inaccuracy of fine needle aspiration biopsy. Two patients had cytopathologic diagnoses which were compatable with the histopathologic diagnosis, but the FNAB alone was not diagnostic. This level of accuracy might be acceptable in patients with known metastatic disease, secondary tumors or when previous histopathologic diagnosis had been obtained. Examples include patients with known metastatic disease or patients with sinus tumors invading the orbit where incomplete resections had been performed previously. Our low overall accuracy rate indicates that FNAB is not justified in patients with a new orbital disease process which does not fall into the metastatic or secondary tumor categories. Our fine needle aspiration biopsies were obtained under direct visualization and optimal conditions. One might expect a lower accuracy rate when dealing with blind fine needle aspiration biopsies or those done with CT or ultrasound guidance. Our results with FNAB in patients with lymphoma or orbital inflammatory pseudotumor also differ from previous reports. In our series of lymphoid lesions we obtained five correct diagnoses, two incorrect diagnoses, and two inadequate tissue samples. It is difficult to separate patients with lymphoid hyperplasia in the pseudotuinor group from those patients with malignant lymphomas, even with good histopathologic technique. Cell surface markers are still being investigated as a diagnostic modality in this group of disease processes. Evaluation of these lesions by electron microscopy has also been advocated. 9 Fine needle aspiration does not allow the use of cell surface markers nor does it allow one to obtain electron micrographs. Kennerdell has adapted a treatment protocol whereby 667
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Fig 1. Left. the cytologic specimen obtained by the technique of fine needle aspiration biopsy. One sees lymphocytes scattered throughout a field of red blood cells. A diagnosis of lymphoma was made by a cytopathologist based on this aspirate alone. Right. permanent histopathologic section from the same patient consistent with orbital lymphoma.
Fig 2. Left. cytologic aspirate was incorrectly interpreted by a cytopathologist as being consistent with orbital lymphoma. Right. correct diagnosis of rhabdomyosarcoma was made on permanent histopathologic sectioning.
all patients with lymphoid lesions are treated with radiation therapy. 8 Irradiation is the treatment of choice for orbital lymphomas and is an accepted treatment modality for patients with orbital inflammatory pseudotumors. We agree that orbital irradiation is the treatment of choice for orbital lymphomas, but do not feel that all patients with orbital pseudotumors should be irradiated. Many patients have spontaneous resolution of their lesions and some patients have permanent resolution following a course of corticosteroids. Orbital irradiation for a lymphoid lesion involves cataractogenic doses of radiation. We are reluctant to treat orbital pseudotumors in young patients with this technique. Our study did not include optic nerve tumors. The most common optic nerve tumors are optic nerve gliomas and optic nerve sheath meningiomas. Fine needle aspiration biopsy has been used in the diagnosis of these two entities. However, marked arachnoidal hyperplasia around an optic nerve glioma can mimic and optic nerve meningioma. 1O Fine needle aspiration
668
biopsy and superficial biopsy of the optic nerve can lead to an erroneous diagnosis of optic nerve sheath meningioma. The clinical findings in patients with optic nerve gliomas and optic nerve sheath meningiomas differ, as does the CT scan appearance. Coupled with a good clinical history and examination, CT scan can often separate these two groups of patients, obviating the need for biopsy. II Fine needle aspiration biopsy is useful in patients with strongly suspected metastatic tumors to the orbit or in those patients with secondary neoplasms (ie. sinus tumors) which have been biopsied previously. Many of our patients with disseminated metastases and a poor prognosis are spared biopsies of any type when their clinical and CT findings are consistent with a metastatic lesion. These patients are often irradiated without a tissue diagnosis under such circumstances. We agree with Kennerdell and co-workers that metastatic lesions constitute a primary indication for fine needle aspiration biopsy of the orbit.
KROHEL, et aI
•
INACCURACY OF FNAB
those patients with secondary neoplasms from contiguous orbital structures. Based on this study, fine needle aspiration biopsy does not have a role in the diagnosis of primary orbital disease processes.
It has been well documented that patients may have orbital inflammatory changes surrounding an orbital metastasis. 8,12 Fine needle aspiration can produce an erroneous diagnosis if only the inflammatory component is biopsied. An immunoperoxidase technique has recently been coupled with FNAB in the diagnosis of prostatic carcinoma. I3 Further advances in immunoperoxidase technique for cytohistochemical diagnosis may lead to increasing utilization of fine needle aspiration biopsy. Equivocal uses for needle aspiration biopsy include the presence of orbital abscess or hemorrhage. In both instances, definitive treatment involves a surgical drainage by lateral or anterior orbitotomy. In rare instances, an abscess is drained as a temporizing measure or for bacteriologic diagnosis before the patient can be taken for definitive surgical drainage. Drainage of an orbital hemorrhage might be partially accomplished by this technique, although it is not advocated as a definitive therapeutic measure. One would also be tempted to utilize FNAB for diagnosing suspected inflammatory lesions in the orbital apex. One is reluctant to perform a lateral orbitotomy in order to diagnose inflammatory orbital pseudotumor of the orbital apex as this procedure can produce considerable morbidity. A diagnostic trial of corticosteroids is often indicated in this clinical situation. One then follows the patient while on high dose corticosteroids, looking for a marked improvement in the clinical picture as well as an improvement or resolution of the lesion on CT scan. Fine needle aspiration biopsy may be helpful in these patients in several circumstances. If tissue compatible with inflammatory orbital pseudotumor is obtained, one has further reassurance that corticosteroid treatment is the proper therapy. If tissue consistent with metastatic disease or another neoplastic process is biopsied, an open biopsy becomes mandatory. In summary, we feel that fine needle aspiration biopsy of the orbit should be reserved for those patients with known or strongly suspected metastatic disease and
REFERENCES 1. Einhorn J, Franzen S. Thin-needle biopsy in the diagnosis of thyroid disease. Acta Radiol 1962; 58:321-36. 2. Schour L. Chu EW. Fine needle aspiration in the management of patients with neoplastic disease. Acta Cytol 1974; 18:472-6. 3. Schyberg E. Fine needle biopsy of orbital tumours. Acta Ophthalmol 1975; Suppl 125: 11 . 4. Westman-Naeser S, Naeser P. Tumours of the orbit diagnosed by fine needle biopsy. Acta Ophthalmol1978; 56:969-76. 5. Kennerdell JS, Dubois PJ, Dekker A, Johnson BL. CT·guided fine needle aspiration biopsy of orbital optic nerve tumors. Ophthalmology 1980; 87:491-6. 6. Spoor TC, Kennerdell JS, Dekker A, et al. Orbital fine needle aspiration biopsy with B·scan guidance. Am J Ophthalmol 1980; 89:274-7. 7. Kennerdell JS, Dekker A. Johnson BL, Dubois PJ. Fine·needle aspiration biopsy; its use in orbital tumors. Arch Ophthalmol 1979; 97:1315-7. 8. Kennerdell JS, Dekker A, Johnson BL. Orbital fine needle aspiration biopsy: the results of its use in 50 patients. Neuro·OphthalmoI1980; 1 :117-21. . 9. Jakobiec FA, Iwamoto T, Knowles OM II. Ocular adnexal lymphoid tumors; correlative ultrastructural and immunologic marker studies. Arch Ophthalmol 1982; 100:84-98. 10. Cooling RJ, Wright JE. Arachnoid hyperplasia in optic nerve glioma: confusion with orbital meningioma. Br J Ophthalmol 1979; 63:596-9. 11 . Jakobiec FA, Depot MJ, Kennerdell JS, et aI. Combined clinical and computed tomographic diagnosis of orbital glioma and menin· gioma. Ophthalmology 1984; 91:137-55. 12. Krohel GB, Perry S, Hepler RS. Acute hypertension with orbital carcinoid tumor. Arch Ophthalmol 1982; 100:106-8. 13. Reifler OM, Kini SR, Liu 0, Littleton RH. Orbital metastasis from prostatic carcinoma; identification by immunocytology. Arch Ophthalmol 1984; 102:292-5.
Discussion
by
John S. Kennerdell, MD The authors make an honest attempt to further evaluate the accuracy of the fine needle aspiration biopsy and more clearly define its best use. Unfortunately, the incorrect sampling in this study based on a lack of understanding the nature of cytology, together with an apparent lack of understanding of orbital lesions by the cytologists, makes this study an unfair evaluation of the fine needle aspiration technique for orbital lesions. In the past, Papanicolaou had a great deal of difficulty convincing his colleagues of the value of the cytology of the uterine cervix. Clearer understanding of the technique and its indications and limitations, has led it to be a standard screening technique for cervical cancer. The same applies to orbital fine From the Eye and Ear Hospital, 230 Lothrop Street, Pittsburgh.
needle aspiration biopsy. It is under criticism due to the lack of understanding of cytology by ophthalmic surgeons and lack of understanding of orbital pathology by cytologists. The authors have indiscriminately punctured orbital lesions, including resectable orbital tumors such as the hemangioma, which could not possibly be identified by a cytologist with no information about the nature of the orbital lesion. The same applies to hemangiopericytoma, neurofibromas, fibrous histiocytoma, and dermoid cysts. We have repeatedly stressed the indications for fine needle aspiration to nonresectable orbital lesions such as carcinomas, lymphoid lesions, or nonspecific orbital inflammations where the technique has a reasonable chance of harvesting cells-which, through clinical pathologic correlation with the ophthalmologist, cytologist and ophthalmic pathologist, can lead to appropriate management of the patient
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without a further open biopsy. Indeed, if the cytological attempt is negative, it does not preclude an open biopsy. Therefore, the authors have selected a significant number of orbital tumors which have no possibility of a positive identification, particularly when presented to a cytologist without clinical correlation. For instance, we would not recommend sampling what expected to be a benign mixed tumor, fibrous histiocytoma, hemangiopericytoma, neurolemmoma, or cavernous hemangioma. We have sampled two dermoids, in light of the fact that they had atypical presentations, but a dermoid was still part of the differential diagnosis in those patients. The present study sampled six dermoids of the 34 patients. Without a cytologist experienced in orbital lesions, I am surprised the authors identified two properly. Of the 34 patients subjected to this technique, only 15 would have been aspirated if in our hands. Of that group, 1 cannot understand failure in two dacryoadenitis cases with insufficient tissue. We found this a rather easy sampling area, but because of the superficial nature of these lesions, have limited the use of fine needle aspiration in lacrimal lesions, often preferring open biopsy. I wonder also why the authors sampled a normal lacrimal gland and found inflammatory cells. Some sort of inflammation or other disorder associated with the gland caused the authors to direct their attention to it in the first place. I also cannot understand how they could misdiagnose thyroid ophthalmopathy as lymphoma. Thyroid ophthalmopathy can and should be diagnosed without the needle aspiration. Therefore, this should be rare in the differential diagnosis. It is easy to see why difficult tumors such as a fibrous histiocytoma, rhabdomyoscarcoma, and hemangiopericytoma are confused. These are easily confused histologically under
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the best circumstances, and therefore should not be expected to be histologically diagnosed by fine needle aspiration, again bringing up the point that cytology does not usually provide a histologic diagnosis. It must be correlated appropriately with the clinical pathologic setting by an appropriate team. In summary, we would agree with the authors, although totally disagreeing with the design of their study, that fine needle aspiration is not a general orbital diagnostic technique. Neither is it a technique that, in experienced hands, needs to be limited to patients with known or strongly suspected metastatic disease, or patients with secondary contiguous orbital neoplasms. Our first paper I summarizing 50 patients revealed a positive identification of 92% with our criteria. This was largely due to the fact that we were sampling easier lesions involving some extending into the lids. Since we have become more experienced with the technique, we are about to report 156 patients with a positive identification of 80%. We now are nearing the repeatable percentage of positivity in experienced hands. We do recommend that those who are interested in the technique be well experienced in orbital disease and begin with patients, as recommended by the authors, that are easier to harvest and more predictable. Experience can be gained through identifying these patients with the cooperation of the cytologist and ophthalmic pathologist. Without a cooperative, interested team, one should avoid the use of this technique. Reference 1. Kennerdell JS, Dekker A, Johnson BL. Orbital fine needle aspiration biopsy: the results of its use in 50 patients. Neuro-OphthalmoI1980; 1 :1 17-21.