Short communications & case reports

An immunohistochemical study of a carcinoma of the parotid gland exhibiting both ductal and acinic cell differentiation John A. Smith, M.D., Ph.D., Michael J. Warhol, M.D., and Gilbert L. Brodsky, M.D., Boston, Mass.

DEPARTMENT OF PATHOLOGY, BRIGHAM AND WOMEN’S HOSPITAL AND HARVARD MEDICAL SCHOOL

A 76-year-old man underwent a subtotal parotidectomy for removal of a 3 cm. multicystic mass. The tumor was a salivary gland carcinoma, with both infiltrating and intraductaliintra-acinar components, exhibiting three histologic patterns: cribriform, papillary, and comedo-like. lmmunohistochemical stain for keratin by the immunoperoxidase technique was strongly reactive in the vast majority of the tumor cells, indicating ductal differentiation of the tumor. Ultrastructural studies indicated primarily ductal differentiation of the tumor cells, with additional areas of acinous and myoepithelial differentiation.

F ewer than 3 percent of patients with parotid gland tumors have primary adenocarcinoma of the salivary gland.’ In a small percentage of these there is a histologic: pattern resembling breast carcinoma, which has been classified as “salivary duct carcino- ma*“2. 3 Kleinsasser, Klein, and HubneT originally described the histologic characteristics of this tumor in five patients; two of these were later classified as “tubular carcinoma.“5 Subsequently, nine additional cases have been reported.2*3 The purpose of this article is to describe the clinical and pathologic findings in a Ipatient with an unusual salivary gland carcinoma.

For this study we employed both ultrastructural and immunocytochemical techniques to define this neoplasm precisely. The peroxidase-antiperoxidase (“immunoperoxidase”) technique has become an excellent tool for the histologic localization of cellu- lar antigens and their identification in certain neo- plasms.6 Studies on the localization of keratin in normal7 and neoplastic* tissues have determined that in the salivary glands keratin is a marker for ductal but not acinar cells. Therefore, we used this method to supplement conventional histologic and electron microscopic methods to describe this lesion.

CASEREPORT

A 76-year-old white male psychologist was admitted with a right parotid mass which had been present for 4 years but had increased in size during the preceding 4 to 6 months. The patient had no pain, facial nerve palsy, or palpable adenopathy. He underwent a subtotal superficial and total deep parotidectomy with preservation of the facial nerve. Postoperatively, he received radiation therapy (6,400 rads over 6 weeks). The patient is working and well, with no evidence of recurrent disease 15 months after surgery and radiation therapy.

Pathologic findings

The resected specimen consisted of an ovoid, soft, multilobulated 3 cm mass and adjacent normal-appearing, yellow salivary gland tissue with total dimensions of 5.5 by 3.0 by 1 .O cm. On sectioning, the mass was multicystic and gray-white. The cysts were partially confluent, varying in diameter between 0.1 and 0.5 cm and containing thick, cloudy, brown fluid. Between the cysts were solid, nonlob- ulated, yellow-tan regions. The tumor was poorly demar- cated from normal parotid tissue.

Microscopically, the specimen consisted of an unencap- sulated tumor infiltrating, the adjacent parotid. The tumor showed three distinct architectural patterns: cribriform (Fig. l), papillary (Fig. 2), and comedo-like (Fig. 3). The tumor was present at the resection margin and focally

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Fig. 1. Cribriform area in salivary carcinoma. (Hematoxylin and eosin stain. Magnification, x400.)

Fig. 2. Papillary area in salivary carcinoma. (Hematoxylin and eosin stain. Magnification, x400.)

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Fig. 3’. Comedo-like area in salivary carcinoma. The necrotic debris consists of both amorphous material and degenerating cells. (Hematoxylin and eosin stain. Magnification, x 100.)

Fig. 4. A, Normal parotid gland adjacent to tumor, stained for keratin. Dense cytoplasmic staining of the ductal epithelium, without staining of acinar cells or stroma. (PAP stain for keratin [ 1:lOO dilution] counterstained with hematoxylin. Magnification, X1,000.) B, Salivary carcinoma, stained for keratin. Dense cytoplasmic staining of the tumor cells. (PAP stain for keratin [ 1:lOO dilution] counterstained with hematoxylin. Magnification, X250.)

270 Smith, Warhol, and Brodsky Oral Surg. March, 1983

Fig. 5. Electron micrograph of a portion of the salivary carcinoma. Epithelial cells of the ductal type have irregular, interdigitated cell borders and prominent intraluminal microvilli. Cells of the acinar type have characteristic cytoplasmic granules. (Uranyl acetate stain. Magnification, X2,000.)

infiltrated small endothelium-lined channels. The tumor cells were moderately large and columnar, cuboidal, or polygonal with moderately distinct cell borders. The nuclei were pleomorphic, hyperchromatic, and round to oval with prominent, usually solitary, nucleoli; mitoses were rare. The cytoplasm of the majority of cells was eosinophilic and nongranular. A few cells, however, contained eosinophilic granules which were PAS positive and variably sensitive to diastase digestion. Many of the cells lining the spaces in cribriform areas had either apical “blebs” or a prominent microvillus border. The mucicarmine stain was negative.

The procedure for the immunoperoxidase stain for keratin has been described previously.’ The normal sali- vary gland tissue adjacent to the neoplasm was strongly stained in striated and intercalated duct cells but was uniformly nonstaining for serous acinar cells; myoepithe-

lial cells were also stained (Fig. 4, A). These findings are identical to those previously described for salivary glands.’ The tumor cells stained prominently for keratin in a diffuse pattern throughout the cytoplasm (Fig. 4, B). Such stain- ing was present throughout the entire tumor, regardless of the architectural pattern. In contrast, immunoperoxidase staining for keratin on three pure acinic cell tumors, used as controls, was uniformly negative throughout the neo- plastic cells.

Ultrastructurally, the predominant cell type was ductal and had irregular, complex borders with interdigitating membranes linked by desmosomes with tonofilaments (Fig. 5). The cells formed numerous lumina lined with microvilli, resulting in a cribriform pattern. The cytoplasm of the cells contained abundant rough endoplasmic reticu- lum, polyribosomes, mitochondria, and Golgi apparatuses.

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Fig. 16. Electron micrograph of a myoepithelial tumor cell with cytoplasmic filaments (arrowhe&) between epithelial tumor cells with microvilli and basement membrane. (Uranyl acetate stain. Magnifica- tion, X6,000.)

Occasional cells contained cytoplasmic membrane-bound granules. Myoepithelial cells were seen in larger neoplastic “ducts” in their characteristic position adjacent to the basement membrane (Fig. 6). In areas, the tumor cells exhibited acinar differentiation (Fig. 7); these cells had clear cytoplasim containing zymogen granules.

DISCUSSION

This case has the light microscopic features char- acteristic of a salivary duct carcinoma of the parotid gland. This salivary gland tumor was so named because of its histologic resemblance to ductal carci- noma of the breast and prostate.24 Three distinct histologic patterns-cribriform, papillary, and come- do-like-characterize these tumors. Thirteen cases

of salivary duct carcinoma have been published.24 The patients have been nine men and four women, whose ages ranged from 53 to 76 years with an average of 62 years. The tumor usually presents as a rapidly growing, painless mass, with or without facial nerve paralysis. The parotid gland was involved in all cases except one, which was of palatal minor salivary gland origin.’ The tumor is more aggressive than the more common types of adenocarcinoma and has a high rate of metastasis and tumor-related death.2s3 Fayemi and TokerZ and Chen and Hafez noted the histologic similarity of these tumors to infiltrating ductal breast carcinomas. The latter authors stressed the coexistence of the three architectural patterns (cribriform, papillary, and comedo-like) and the

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March. 1983

Fig. 7. Electron micrograph of an area of acinar differentiation with a tumor cell containing zymogen granules (arrowheads) and a prominent Golgi apparatus. (Uranyl acetate stain. Magnification, ~6,000.)

presence of intraductal growth as features common to both the mammary and salivary gland neoplasms3 Similarity to prostatic carcinoma, raising the possi- bility of metastasis in the differential diagnosis of salivary duct carcinoma, was also noted; one of Fayemi and Toker’s patients later developed a pros- tatic carcinomae3

The ultrastructural findings in this case are simi- lar to those described by Kleinsasser and co- workers,4 who recommended the name epithelial- myoepithelial carcinoma of intercalated ducts for this neoplasm. Chen and Hafez suggested the brief- er term salivary duct carcinoma.

Our case differed from the cases in previous ultrastructural studies in that, in addition to ductal and myoepithelial differentiation (Figs. 5 and 6),

acinar differentiation as indicated by the presence of zymogen granules (Fig. 7) was observed.

The differential diagnosis of salivary gland carci- nomas with a prominent ductal component includes several primary neoplasms, notably adenoid cystic carcinoma, acinic cell tumor, mucoepidermoid tumor, and metastatic adenocarcinoma. The com- bined immunohistochemistry and electron micro- scopic studies indicates that our case represents a tumor exhibiting both ductal and acinar differentia- tion. In areas, this case resembled the papillocystic variant of acinic cell tumor.g However, the extensive cribriform pattern of necrosis is a feature more typical of salivary duct carcinoma. The immunohis- tochemical finding of intracellular keratin is further support for the predominantly ductal differentiation

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of the tumor. The finding of both myoepithelial cells and zymogen granules ultrastructurally reflects the capacity of the ductal epithelium to differentiate along a variety of cell lines. Such multipotential differentiation is reflected in another type of salivary gland neoplasm-the mucoepidermoid carcinoma. The more common forms of adenocarcinoma lack the triad of histologic patterns seen in this tumor and usually are mucin-positive.‘”

Previous reports suggest that carcinomas with a salivary duct histology have a worse prognosis than other salivary gland malignancies. Long-term follow- up on our ca.se is not available.

The authors thank Dr. Geraldine S. Pinkus, in whose laboratory the immunohistochemical studies were con- ducted, and Ms. Ann Benoit for her skillful secretarial assistance.

REFERENCES

1. Thackray, A. C., and Lucas, R. B.: Tumors of the Major Salivary Glands. In Atlas of Tumor Pathology, Fascicle 10, Second Series, Bethesda, Md., 1974, Armed Forces Institute of Pathology.

2. Fayemi, A. 0.. and Toker, C.: Salivary Duct Carcinoma, Arch. Otol.aryngol. 99: 366-368, 1974.

3. Chen, K. T. K., and Hafez, G. R.: Infiltrating Salivary Duct Carcinoma: A Clinicopathologic Study of Five Cases, Arch. Otolaryngol. 107: 37-39, 198 1.

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4.

5.

6.

7.

8.

9.

IO.

Kleinsasser, O., Klein, H. J., and Hubner, G.: Speichelgang- carcinome: Ein den Milchgancarcinomen der Briistdruse analoge Gruppe von Speildrusentumoren, Arch. Klin. Exp. Ohr. Nas. Kehlkopfbeilkd. 192: 100-105, 1968. Donath, K., Seifert, G., and Schmitz, R.: Zu,r Diagnose und Ultrastruktur des tubularen Speichelgangcarcinome: Epithe- lialmyoepitheliales Schaltstiickcarcinom, Virchow’s Arch. Pathol. Anat. 356: 16-31, 1972. Mesa-Tejada, R., Pascal, R. R., and Fenoglio, C. M.: Immu- noperoxidase: A Sensitive lmmunohistochemical Technique as a “Special Stain” in the Diagnostic Pathology Laboratory, Hum. Pathol. 8: 313-320, 1977. Schlegel, R., Banks-Schlegel, S., and Pinkus, G. S.: Immuno- histochemical Localization of Keratin in Normal Human Tissues, Lab. Invest. 42: 91-96, 1980. Schlegel, R., Banks-Schlegel, S., McLeod, J. A., and Pinkus, G. S.: Immunoperoxidase Localization of Keratin in Human Neoplasms, Am. J. Pathol. 101: 41-48, 1980. Abrams, A. M., Cornyn, J., Scofield, H. H., and Hansen, L. S.: Acinic Cell Adenocarcinoma of the Major Salivary Glands: A Clinical-Pathologic Study of 77 Cases, Cancer 18: 1145-l 162, 1965. Blanck, C., Eneroth, C.-M., and Jakobsson, P. A.: Mucus- Producing Adenopapillary (Non-epidermoid) Carcinoma of the Parotid Gland, Cancer 28: 676-685, 1971.

Reprint requests to: Dr. Michael J. Warhol Department of Pathology Brigham and Women’s Hospital 75 Francis St. Boston. Mass. 02115