- Email: [email protected]
Fresh-Frozen Sections in Head and Neck Surgery
Presh. Prozen Sections in Head and Neck Surgery EDGAR G. HARRISON, JR., M.D. LEWIS B. WOOLNER, M.D.
THE PURPOSE of this paper is to illustrate the value of using fresh-frozen sections as guides to proper surgical treatment of lesions of the head and neck. The advantages to the surgeon of immediate microscopic examination of tissue include such rather obvious features as identification and classification of malignant neoplasms, confirmation of the adequacy of excision of tumors, and guidance in the obtaining and subsequent proper handling of biopsy material. The advantages to the patient may include a reduction in the number of surgical procedures, a saving of hospital time and expense, or an actual alteration in the extent or type of operation performed for diagnosis or treatment. TECHNIQUE
A number of methods and a variety of microtomes are currently available for the preparation of fresh-frozen sections. The newer cryostats can provide a satisfactory permanent section stained with hematoxylin and eosin in five to seven minutes. For more than four decades, excellent fresh-frozen sections have been obtained in our laboratory by using the simple and inexpensive Spencer freezing microtome combined with a polychrome methylene blue stain. After a reasonable period of training, a technician using this method can produce beautifully detailed histologic preparations in one to two minutes. With the exception of calcified tissue or bone which cannot be cut and certain cartilaginous tumors which stain poorly with methylene blue, almost any tumor or tissue can be identified accurately by an experienced pathologist using the polychrome stain. Soft regions usually are present in bone tumors which allow sampling for diagnosis by frozen-section techniques. In practice, cases that are difficult to diagnose from frozen sections usually are found to be equally difficult on examination of permanent paraffin sections. The value of fresh-frozen section technique in head and neck 943
944
EDGAR
G.
HARRISON, JR., LEWIS
B.
WOOLNER
Fig.!. Pigmented lesions of the skin that are readily identified by frozen section. a, Seborrheic keratosis. b, Blue nevus. c, Malignant melanoma.
surgery can be illustrated best by a brief discussion of its use in the treatment of lesions in a number of specific sites. SKIN AND MUCOUS MEMBRANES
Immediate identification of a resected lesion as benign or malignant is a welcome aid to the surgeon using fresh-frozen sections as a guide to treatment. Although gross appearances of lesions on the skin or mucous membranes are usually fairly characteristic, proper management must include· microscopic examination to establish their true nature. Confusion may arise if gross examination alone is depended on for identification, since pigmented basal cell epithelioma, pigmented seborrheic keratosis, pigmented sclerosing hemangioma, or certain benign pigmented moles may simulate a malignant melanoma (Fig. 1, a, b and c).
Fresh-Frozen Sections in Head and Neck Surgery
945
Fig. 2. Indistinct tumor borders. a, Morphea-like basal cell carcinoma of malar region. b, Ulcerative basal cell carcinoma which invaded the orbit.
Also a keratoacanthoma may be confused with a rapidly growing squamous cell epithelioma, or a small inflammatory ulcerated area in leukoplakia of the lip may be mistaken for an early ulcerative squamous carcinoma. In all such instances, immediate information on the exact nature of the lesion is important in determining the extent of operation and particularly the amount of adjacent uninvolved tissue to be removed. Another advantage lies in the exact classification of malignant neoplasms. In the case of large, obviously malignant neoplasms, a biopsy specimen can be taken and examined immediately prior to definitive surgical treatment. Immediate determination of the adequacy of cancer-free margins also is helpful. In many cases gross examination cannot determine the border of a tumor, and microscopic study of multiple sections from the margin of the resected specimen is required. This is especially true in treatment of infiltrative basal cell epitheliomas in the region of the nose or orbit, where tumor cells may extend far beyond the grossly defined margins (Fig. 2, a and b). The limits of in situ squamous epitheliomas associated with leukoplakia likewise are difficult to define grossly, and immediate microscopic delineation of borders is extremely useful. Examination of the margins of surgically excised tissues for residual carcinoma is a major factor in the prevention of recurrent cancer; and this application of the method is, in itself, ample justification for use of the fresh-frozen technique.
946
EDGAR
G.
HARRISON, JR., LEWIS
B.
WOOLNER
Fig. 3. Cervical adenopathy. a, Metastatic papillary adenocarcinoma from an occult primary lesion in the thyroid gland. Surgical resection of thyroid gland can be accomplished following diagnosis from examination of frozen section of metastatically involved lymph node. b, Hodgkin's disease.
In situations where the surgeon is required only to identify a suspected primary lesion or to obtain suitable material for culture or other diagnostic procedures, fresh-frozen sections are valuable for determining whether or not a representative specimen has been obtained in the biopsy procedure. CERVICAL LYMPH NODES
Fresh-frozen sections of enlarged cervical lymph nodes may demonstrate, among other things, primary lymphoma, metastatic carcinoma, granuloma, or nonspecific lymphadenitis or "hyperplastic" lymph nodes. Although the diagnosis of primary lymphoma (especially its exact histologic classification) is perhaps more accurately determined with permanent-section technique, the quick recognition of metastatic carcinoma may permit further immediate therapeutic or diagnostic procedures. This is especially true with papillary thyroid carcinoma, in which the primary lesion so often is occult (Fig. 3, a and b). Demonstration of granulomatous inflammation in a node will necessitate handling of the material in such a way as to facilitate additional studies by culture or by inoculation into animals. Because of the frequency with which the latter procedure is required, we have found it an excellent rule in cases of indeterminate cervical adenopathy to have the node bisected in the operating room and one-half placed in a sterile wide-mouthed bottle. Then cultures or animal inoculations can be made
I i, I
I
Fresh-Frozen Sections in Head and Neck Surgery
947
from this as required. Immediate examination of frozen sections is thus an all-important step in a logical and time-conserving sequence of diagnostic procedures. A tumor diagnosed preoperatively as an enlarged cervical node may prove, on immediate section, to be an unsuspected neoplasm or cyst. Thus carotid-body tumor, tumor of glomus vagale, schwannoma, or cyst of the branchial cleft all have been responsible, on occasion, for a preoperative diagnosis of "indeterminate cervical adenopathy." Examination of fresh-frozen sections can establish the correct diagnosis immediately. THYROID AND PARATHYROID GLANDS
Fresh-frozen sections have an important use in surgical procedures on the thyroid gland, particularly in the management of so-called nodular goiter. Distinction between thyroid carcinoma and benign nodules can be made with certainty in almost all cases, allowing the proper surgical procedure to be instituted immediately. Initial diagnosis may be established by examination of a metastatically involved cervical lymph node or by means of an excisional biopsy of the primary lesion. Further surgical treatment after the diagnosis of carcinoma, depending on the exact subtype of tumor, may include total lobectomy or thyroidectomy with or without dissection of regional nodes. Identification of the various types of thyroiditis, including the rarely encountered Riedel's struma, is accomplished readily with fresh-frozen sections. Since both Riedel's and granulomatous thyroiditis may be mistaken for carcinoma on gross examination, the use of fresh-frozen section technique is mandatory. Hashimoto's thyroiditis is less likely to resemble carcinoma but sometimes is confused grossly with lymphosarcoma. Parathyroid surgery is best accomplished with the aid of fresh-frozen sections. Identification of the four parathyroid glands is a necessary part of the surgical procedure, and this can be accomplished readily by sectioning a small biopsy specimen from each gland. Although the combination of size and color usually identifies a parathyroid gland as such, sometimes small lymph nodes, thymic tissue, fatty nodules, or small thyroid adenomas are mistaken for parathyroid tissue on gross examination. The size of a given parathyroid tumor is a factor in its identification. A large tumor requires only a section to identify it as a parathyroid adenoma. Identification of a slightly enlarged parathyroid gland as adenoma or not depends on the determination of its weight combined with examination of a histologic section to establish the presence or absence of fatty stroma. Identification of a nodule composed of large water-clear cells should alert the pathologist and the surgeon to the possiblity of a diffuse primary wasserhelle-cell hyperplasia in which all four glands are involved. The operation in such cases entails removal
948
EDGAR
G.
HARRISON, JR., LEWIS
B.
WOOLNER
of all parathyroid tissue, preserving only 100 to 200 mg. of vascularized parenchyma. The rarely encountered parathyroid carcinoma is identified largely by its invasion of adjacent structures. Surgical removal of such a lesion should be as wide as possible to prevent local recurrence. PAROTID GLANDS
Immediate identification of a given parotid-gland neoplasm at operation provides useful guidance to proper surgical management. For most indeterminate lesions of the parotid, a superficial parotidectomy is carried out initially, and is followed by examination of fresh-frozen sections of the tumor for its identification. Further procedures depend on the exact subtype of tumor present. In general, mixed tumors are treated by superficial parotidectomy with preservation of the facial nerve. Total parotidectomy with preservation of the facial nerve may be the treatment of choice for slow-growing carcinoma (such as the acinic cell type) or low-grade mucoepidermoid tumors. Invasion of nerve by adenoid cystic carcinoma (cylindroma) may be demonstrated readily in freshfrozen sections, and this may dictate extirpation. The more anaplastic carcinomas may require sacrifice of the facial nerve with dissection of regional nodes. Comparable variation in the extent of resectional procedures is indicated for other tumors of the salivary and lacrimal glands. MOUTH, LARYNX, AND UPPER PART OF RESPIRATORY TRACT
Fresh-frozen sections are especially useful for diagnosing a given lesion of the mouth, pharynx, or larynx as inflammatory or neoplastic. In addition to infections by acid-fast organisms, fungus diseases such as blastomycosis or histoplasmosis may be responsible for chronic ulcerative lesions of the mouth, pharynx, or larynx. As outlined in reference to cervical lymph nodes, the demonstration of granulomatous rather than carcinomatous tissue in a given biopsy requires special procedures for identification of the pathogens. Similarly, demonstration of a polymorphonuclear infiltration with or without the presence of so-called ray fungi in lesions of the tongue or mouth may be followed by immediate anaerobic culture of biopsy material, which can provide an accurate diagnosis of actinomycosis (Fig. 4, a). Immediate microscopic demonstration of the depth and extent of a given carcinoma of mucous membranes (Fig. 4, b) is useful in any site, but special mention may be due its application in treatment of laryngeal lesions following laryngofissure. In treating small tumors of the larynx, microscopic proof of an in situ or early infiltrative squamous carcinoma
Fresh-Frozen Sections in Head and Neck Surgery
949
Fig. 4. Inflammatory or neoplastic lesions of the mouth and upper part of the respiratory tract. a, Actinomycosis which grossly may simulate tumor. Note sulfur granule and suppurative reaction (hematoxylin and eosin; X165). b, Tongue deeply infiltrated with squamous cell carcinoma.
confined to one vocal cord may suggest treatment by conservative measures such as cautery or removal of the single involved cord. Contrariwise, the demonstration of more extensive, infiltrative carcinoma present bilaterally may indicate the necessity for laryngectomy. In all laryngeal cancers, whether early or advanced, overtreatment or undertreatment can be avoided best by generous use of fresh-frozen sections.
950
EDGAR
G.
HARRISON, JR., LEWIS
B.
WOOLNER
SUMMARY
Study of fresh-frozen sections can provide-at the surgical stage when needed-guidance in obtaining and handling of biopsy material, identification of the nature of a lesion, and precise definition of its extent. These advantages are demonstrable in dealing with various kinds of lesions at numerous specific sites in the head and neck. In showing immediately what surgery is necessary and how much of it, such study provides obvious benefits to the patient.
THE PURPOSE of this paper is to illustrate the value of using fresh-frozen sections as guides to proper surgical treatment of lesions of the head and neck. The advantages to the surgeon of immediate microscopic examination of tissue include such rather obvious features as identification and classification of malignant neoplasms, confirmation of the adequacy of excision of tumors, and guidance in the obtaining and subsequent proper handling of biopsy material. The advantages to the patient may include a reduction in the number of surgical procedures, a saving of hospital time and expense, or an actual alteration in the extent or type of operation performed for diagnosis or treatment. TECHNIQUE
A number of methods and a variety of microtomes are currently available for the preparation of fresh-frozen sections. The newer cryostats can provide a satisfactory permanent section stained with hematoxylin and eosin in five to seven minutes. For more than four decades, excellent fresh-frozen sections have been obtained in our laboratory by using the simple and inexpensive Spencer freezing microtome combined with a polychrome methylene blue stain. After a reasonable period of training, a technician using this method can produce beautifully detailed histologic preparations in one to two minutes. With the exception of calcified tissue or bone which cannot be cut and certain cartilaginous tumors which stain poorly with methylene blue, almost any tumor or tissue can be identified accurately by an experienced pathologist using the polychrome stain. Soft regions usually are present in bone tumors which allow sampling for diagnosis by frozen-section techniques. In practice, cases that are difficult to diagnose from frozen sections usually are found to be equally difficult on examination of permanent paraffin sections. The value of fresh-frozen section technique in head and neck 943
944
EDGAR
G.
HARRISON, JR., LEWIS
B.
WOOLNER
Fig.!. Pigmented lesions of the skin that are readily identified by frozen section. a, Seborrheic keratosis. b, Blue nevus. c, Malignant melanoma.
surgery can be illustrated best by a brief discussion of its use in the treatment of lesions in a number of specific sites. SKIN AND MUCOUS MEMBRANES
Immediate identification of a resected lesion as benign or malignant is a welcome aid to the surgeon using fresh-frozen sections as a guide to treatment. Although gross appearances of lesions on the skin or mucous membranes are usually fairly characteristic, proper management must include· microscopic examination to establish their true nature. Confusion may arise if gross examination alone is depended on for identification, since pigmented basal cell epithelioma, pigmented seborrheic keratosis, pigmented sclerosing hemangioma, or certain benign pigmented moles may simulate a malignant melanoma (Fig. 1, a, b and c).
Fresh-Frozen Sections in Head and Neck Surgery
945
Fig. 2. Indistinct tumor borders. a, Morphea-like basal cell carcinoma of malar region. b, Ulcerative basal cell carcinoma which invaded the orbit.
Also a keratoacanthoma may be confused with a rapidly growing squamous cell epithelioma, or a small inflammatory ulcerated area in leukoplakia of the lip may be mistaken for an early ulcerative squamous carcinoma. In all such instances, immediate information on the exact nature of the lesion is important in determining the extent of operation and particularly the amount of adjacent uninvolved tissue to be removed. Another advantage lies in the exact classification of malignant neoplasms. In the case of large, obviously malignant neoplasms, a biopsy specimen can be taken and examined immediately prior to definitive surgical treatment. Immediate determination of the adequacy of cancer-free margins also is helpful. In many cases gross examination cannot determine the border of a tumor, and microscopic study of multiple sections from the margin of the resected specimen is required. This is especially true in treatment of infiltrative basal cell epitheliomas in the region of the nose or orbit, where tumor cells may extend far beyond the grossly defined margins (Fig. 2, a and b). The limits of in situ squamous epitheliomas associated with leukoplakia likewise are difficult to define grossly, and immediate microscopic delineation of borders is extremely useful. Examination of the margins of surgically excised tissues for residual carcinoma is a major factor in the prevention of recurrent cancer; and this application of the method is, in itself, ample justification for use of the fresh-frozen technique.
946
EDGAR
G.
HARRISON, JR., LEWIS
B.
WOOLNER
Fig. 3. Cervical adenopathy. a, Metastatic papillary adenocarcinoma from an occult primary lesion in the thyroid gland. Surgical resection of thyroid gland can be accomplished following diagnosis from examination of frozen section of metastatically involved lymph node. b, Hodgkin's disease.
In situations where the surgeon is required only to identify a suspected primary lesion or to obtain suitable material for culture or other diagnostic procedures, fresh-frozen sections are valuable for determining whether or not a representative specimen has been obtained in the biopsy procedure. CERVICAL LYMPH NODES
Fresh-frozen sections of enlarged cervical lymph nodes may demonstrate, among other things, primary lymphoma, metastatic carcinoma, granuloma, or nonspecific lymphadenitis or "hyperplastic" lymph nodes. Although the diagnosis of primary lymphoma (especially its exact histologic classification) is perhaps more accurately determined with permanent-section technique, the quick recognition of metastatic carcinoma may permit further immediate therapeutic or diagnostic procedures. This is especially true with papillary thyroid carcinoma, in which the primary lesion so often is occult (Fig. 3, a and b). Demonstration of granulomatous inflammation in a node will necessitate handling of the material in such a way as to facilitate additional studies by culture or by inoculation into animals. Because of the frequency with which the latter procedure is required, we have found it an excellent rule in cases of indeterminate cervical adenopathy to have the node bisected in the operating room and one-half placed in a sterile wide-mouthed bottle. Then cultures or animal inoculations can be made
I i, I
I
Fresh-Frozen Sections in Head and Neck Surgery
947
from this as required. Immediate examination of frozen sections is thus an all-important step in a logical and time-conserving sequence of diagnostic procedures. A tumor diagnosed preoperatively as an enlarged cervical node may prove, on immediate section, to be an unsuspected neoplasm or cyst. Thus carotid-body tumor, tumor of glomus vagale, schwannoma, or cyst of the branchial cleft all have been responsible, on occasion, for a preoperative diagnosis of "indeterminate cervical adenopathy." Examination of fresh-frozen sections can establish the correct diagnosis immediately. THYROID AND PARATHYROID GLANDS
Fresh-frozen sections have an important use in surgical procedures on the thyroid gland, particularly in the management of so-called nodular goiter. Distinction between thyroid carcinoma and benign nodules can be made with certainty in almost all cases, allowing the proper surgical procedure to be instituted immediately. Initial diagnosis may be established by examination of a metastatically involved cervical lymph node or by means of an excisional biopsy of the primary lesion. Further surgical treatment after the diagnosis of carcinoma, depending on the exact subtype of tumor, may include total lobectomy or thyroidectomy with or without dissection of regional nodes. Identification of the various types of thyroiditis, including the rarely encountered Riedel's struma, is accomplished readily with fresh-frozen sections. Since both Riedel's and granulomatous thyroiditis may be mistaken for carcinoma on gross examination, the use of fresh-frozen section technique is mandatory. Hashimoto's thyroiditis is less likely to resemble carcinoma but sometimes is confused grossly with lymphosarcoma. Parathyroid surgery is best accomplished with the aid of fresh-frozen sections. Identification of the four parathyroid glands is a necessary part of the surgical procedure, and this can be accomplished readily by sectioning a small biopsy specimen from each gland. Although the combination of size and color usually identifies a parathyroid gland as such, sometimes small lymph nodes, thymic tissue, fatty nodules, or small thyroid adenomas are mistaken for parathyroid tissue on gross examination. The size of a given parathyroid tumor is a factor in its identification. A large tumor requires only a section to identify it as a parathyroid adenoma. Identification of a slightly enlarged parathyroid gland as adenoma or not depends on the determination of its weight combined with examination of a histologic section to establish the presence or absence of fatty stroma. Identification of a nodule composed of large water-clear cells should alert the pathologist and the surgeon to the possiblity of a diffuse primary wasserhelle-cell hyperplasia in which all four glands are involved. The operation in such cases entails removal
948
EDGAR
G.
HARRISON, JR., LEWIS
B.
WOOLNER
of all parathyroid tissue, preserving only 100 to 200 mg. of vascularized parenchyma. The rarely encountered parathyroid carcinoma is identified largely by its invasion of adjacent structures. Surgical removal of such a lesion should be as wide as possible to prevent local recurrence. PAROTID GLANDS
Immediate identification of a given parotid-gland neoplasm at operation provides useful guidance to proper surgical management. For most indeterminate lesions of the parotid, a superficial parotidectomy is carried out initially, and is followed by examination of fresh-frozen sections of the tumor for its identification. Further procedures depend on the exact subtype of tumor present. In general, mixed tumors are treated by superficial parotidectomy with preservation of the facial nerve. Total parotidectomy with preservation of the facial nerve may be the treatment of choice for slow-growing carcinoma (such as the acinic cell type) or low-grade mucoepidermoid tumors. Invasion of nerve by adenoid cystic carcinoma (cylindroma) may be demonstrated readily in freshfrozen sections, and this may dictate extirpation. The more anaplastic carcinomas may require sacrifice of the facial nerve with dissection of regional nodes. Comparable variation in the extent of resectional procedures is indicated for other tumors of the salivary and lacrimal glands. MOUTH, LARYNX, AND UPPER PART OF RESPIRATORY TRACT
Fresh-frozen sections are especially useful for diagnosing a given lesion of the mouth, pharynx, or larynx as inflammatory or neoplastic. In addition to infections by acid-fast organisms, fungus diseases such as blastomycosis or histoplasmosis may be responsible for chronic ulcerative lesions of the mouth, pharynx, or larynx. As outlined in reference to cervical lymph nodes, the demonstration of granulomatous rather than carcinomatous tissue in a given biopsy requires special procedures for identification of the pathogens. Similarly, demonstration of a polymorphonuclear infiltration with or without the presence of so-called ray fungi in lesions of the tongue or mouth may be followed by immediate anaerobic culture of biopsy material, which can provide an accurate diagnosis of actinomycosis (Fig. 4, a). Immediate microscopic demonstration of the depth and extent of a given carcinoma of mucous membranes (Fig. 4, b) is useful in any site, but special mention may be due its application in treatment of laryngeal lesions following laryngofissure. In treating small tumors of the larynx, microscopic proof of an in situ or early infiltrative squamous carcinoma
Fresh-Frozen Sections in Head and Neck Surgery
949
Fig. 4. Inflammatory or neoplastic lesions of the mouth and upper part of the respiratory tract. a, Actinomycosis which grossly may simulate tumor. Note sulfur granule and suppurative reaction (hematoxylin and eosin; X165). b, Tongue deeply infiltrated with squamous cell carcinoma.
confined to one vocal cord may suggest treatment by conservative measures such as cautery or removal of the single involved cord. Contrariwise, the demonstration of more extensive, infiltrative carcinoma present bilaterally may indicate the necessity for laryngectomy. In all laryngeal cancers, whether early or advanced, overtreatment or undertreatment can be avoided best by generous use of fresh-frozen sections.
950
EDGAR
G.
HARRISON, JR., LEWIS
B.
WOOLNER
SUMMARY
Study of fresh-frozen sections can provide-at the surgical stage when needed-guidance in obtaining and handling of biopsy material, identification of the nature of a lesion, and precise definition of its extent. These advantages are demonstrable in dealing with various kinds of lesions at numerous specific sites in the head and neck. In showing immediately what surgery is necessary and how much of it, such study provides obvious benefits to the patient.