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The parotid gland is the best known salivary gland, located just below the ear at the angle of the jaw.  Salivary glands, however, are present in the submucosa of numerous organs such as esophagus, larynx, and lung.   Thus, conditions affecting the major salivary glands (parotid, submandibular, and sublingual) also affect these other minor salivary glands.  In general, the likelihood that a tumor of the salivary glands is malignant is inversely proportional to the size of the gland.  Thus, minor salivary glands more frequently give rise to malignant tumors. Because most of the major salivary glands can be felt, any mass lesion is ammenable to a fine needle aspiration.  The pathologist will insert a small needle into the mass, aspirate some tissue, and smear it on a slide.  After staining it, a diagnosis can often be rendered, sparing the patient an invasive surgical procedure.

Basic Anatomy
Chronic Sclerosing Sialadenitis (Kuttner's Tumor)
Sjogren's Syndrome and Benign Lymphoepithelial Lesion

Atlas of Salivary Gland Tumors
Acinic Cell Carcinoma
Adenocarcinoma, Not Otherwise Specified (NOS)
Adenoid Cystic Carcinoma

Basaloid Tumors (Basal Cell Adenoma and Basal Cell Carcinoma)
Epithelial-Myoepithelial Tumors
Hyalinizing Clear Cell Carcinoma of the Salivary Glands
Mucoepidermoid Carcinoma
Myoepithelial Carcinoma of the Salivary Glands
Pleomorphic Adenoma
Polymorphous Low Grade Adenocarcinoma of the Salivary Glands
Salivary Duct Carcinoma
Warthin's Tumor


Histopathological Features and Variants  
Special Stains/
Electron Microscopy
Differential Diagnosis  
Commonly Used Terms  
Internet Links  

Phenotypic composition of salivary gland tumors: an application of principle component analysis to tissue microarray data.

Iwafuchi H, Mori N, Takahashi T, Yatabe Y.

Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan.
Mod Pathol. 2004 Jul;17(7):803-10. Abstract quote  

The tissue organization of the salivary gland is complex, and a large number of salivary gland tumor entities with a broad morphologic spectrum are listed, creating tumor classification schema for the salivary glands that are difficult to understand.

In the present study, we attempted to examine how the anatomical components of the salivary gland are associated with morphological subtypes of tumors.

We selected a panel of 12 molecules, which labeled one or some of the components, with all of the markers covering every component of the salivary glands. Using tissue microarray, expression profiles of these molecules were examined in four representative spots from each of 88 salivary gland tumors. The resulting large data matrix was analyzed using principle component analysis (PCA). We considered the first three eigenvectors to be significant; as the eigenvalues were more than 1.0 and the cumulative proportion achieved was 67%. Comparison with expression patterns in normal tissue suggested that the three components represented myoepithelial differentiation, and luminal and basal cell phenotypes. Then, we compared the PCA results with individual morphologic subtypes.

Individual subtypes were clustered among the three dimensions of the components. This implies that salivary gland tumors may be well characterized by using only three components.

Endocrine Mucin-Producing Sweat Gland Carcinoma: Twelve New Cases Suggest That It Is a Precursor of Some Invasive Mucinous Carcinomas.

Zembowicz A, Garcia CF, Tannous ZS, Mihm MC, Koerner F, Pilch BZ.

From the Departments of *Pathology and double daggerDermatology, Massachusetts General Hospital, Boston, MA; and daggerMassachusetts Eye and Ear Infirmary, Boston, MA.

Am J Surg Pathol. 2005 Oct;29(10):1330-1339. Abstract quote  

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is an underrecognized low-grade carcinoma with predilection to the eyelid. Only 4 cases of this entity have been described in the literature.

Here, we describe 12 cases of EMPSGC. The lesions were twice as frequent in females than males with an average age of 70 years (range, 48-84 years). Clinically, they presented as a slowly growing cyst or swelling. The most common site of occurrence was the lower eyelid (8 cases). Two lesions occurred on the upper eyelid and 2 on the cheek. Histologically, they were well-circumscribed, typically multinodular tumors with solid or partially cystic nodules, frequently showing areas of papillary architecture. Focal cribriform arrangements were also present. The nodules were formed by uniform small- to medium-sized oval to polygonal epithelial cells with lightly eosinophilic to bluish cytoplasm. The nuclei were bland with diffusely stippled chromatin and inconspicuous nucleoli. Intracytoplasmic and extracellular mucin was usually present. Mitotic activity was present but never brisk. All tumors examined immunohistochemically expressed at least one neuroendocrine marker, synaptophysin or chromogranin. CD57 and neuron specific enolase, secondary markers of neuroendocrine differentiation, were expressed in most cases.

All tumors tested expressed estrogen and progesterone receptors, cytokeratin 7, low molecular cytokeratin Cam5.2, and epithelial membrane antigen and were negative for cytokeratin 20 and S-100 protein. Calponin, smooth muscle actin, and p63 immunohistochemical stains did not disclose myoepithelial cells around larger tumor nests in most cases, supporting the notion that EMPSGC is an invasive carcinoma. In 10 cases, cystic areas lined by benign epithelium indistinguishable from eccrine ducts were present. In some foci, the benign ductal epithelium was undermined or replaced by carcinoma in situ with similar cytologic features to the solid or papillary areas of EMPSGC. Myoepithelial cells were preserved in the areas of in situ carcinoma. In 6 cases, EMPSGC was associated with invasive mucinous carcinoma. In situ carcinoma and mucinous carcinoma also expressed neuroendocrine markers. Clinical follow-up showed no recurrences or metastases, consistent with low-grade carcinoma.

The series provides histologic evidence for a multistage progression of noninvasive sweat gland neuroendocrine carcinoma to EMPSGC and then to mucinous carcinoma of the eyelid. Although the data from this series support the notion that the prognosis of EMPSGC and mucinous carcinoma is good, longer follow-up is needed for better understanding of their pathogenesis and clinical behavior.

Osteoclast-type Giant Cell Neoplasm of Salivary Gland. A Microdissection-based Comparative Genotyping Assay and Literature Review: Extraskeletal "Giant Cell Tumor of Bone" or Osteoclast-type Giant Cell "Carcinoma"?

Tse LL, Finkelstein SD, Siegler RW, Barnes L.

*Department of Pathology, Queen Elizabeth Hospital, Hong Kong, China; the daggerDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA; and the double daggerKimball Medical Center, Lakewood, NJ.

Am J Surg Pathol. 2004 Jul;28(7):953-961. Abstract quote  

Primary salivary gland tumors resembling giant cell tumor of bone are very rare and have unsettled histogenesis. Both mesenchymal and epithelial origins have been suggested.

We review 14 cases in the English-language literature and report another case, the first of which to be studied by microdissection-based microsatellite analysis. One-half of the tumors have been associated with a carcinoma, usually salivary duct carcinoma and carcinoma ex pleomorphic adenoma. Significant differences between this tumor and giant cell tumor of bone were observed.

Unlike giant cell tumor of bone, in which the nuclei of the mononuclear and giant cells are similar, those of salivary gland show obvious differences between the nuclei of mononuclear cells and osteoclastic giant cells. In addition and in contrast to giant cell tumor of bone, the mononuclear cells of giant cell tumor of salivary gland express epithelial markers (epithelial membrane antigen, EMA; carcinoembryonic antigen, CEA) and androgen receptor. Genotypically, the microsatellite pattern of the giant cell component is more akin to the carcinomatous component and does not resemble giant cell tumor of bone. Biologically, giant cell tumor of salivary gland tends to be more aggressive than giant cell tumor of bone.

We conclude that giant cell tumor of salivary gland is an unusual carcinoma that is not related to giant cell tumor of bone.
Salivary Heterotopia, Cysts, and the Parathyroid Gland
Branchial Pouch Derivatives and Remnants

J. Aidan Carney, M.D., Ph.D., F.R.C.P.I.

From the Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, U.S.A.

Am J Surg Pathol 2000;24:837-845 Abstract quote

Five cases of periparathyroid salivary heterotopia associated with cysts were studied.

The specimens were obtained from three men and two women age 36 to 62 years who underwent surgery for primary hyperparathyroidism (four patients) and thyroid nodule (one patient). The heterotopia–cyst combination occurred with normal and abnormal parathyroid glands (four inferior and one of unknown location).

Review of histologic slides of all parathyroid glands excised from 258 patients during a 1-year period at the Mayo Clinic revealed two similar salivary gland–cyst units. Seven more cases featured one or more periparathyroid cysts, five with other nonsalivary-type epithelial accompaniments. One of the latter additionally had a focus of parathyroid cells in the cyst wall, and associated thyroid parenchyma with C cells, and cartilage.


Hybrid Carcinomas of the Salivary Glands: Report of Nine Cases with a Clinicopathologic, Immunohistochemical, and p53 Gene Alteration Analysis.

Nagao T, Sugano I, Ishida Y, Asoh A, Munakata S, Yamazaki K, Konno A, Iwaya K, Shimizu T, Serizawa H, Ebihara Y.

Department of Surgical Pathology, Tokyo Medical University Hospital (TN, KI, TS, HS, YE), Tokyo, Japan.

Mod Pathol 2002 Jul;15(7):724-33 Abstract quote

Hybrid carcinomas of the salivary gland are a recently defined and rare tumor entity, consisting of two histologically distinct types of carcinoma within the same topographic area.

In this study, we examined nine such cases, which mainly arose in the parotid gland (seven cases), with an additional one each from submandibular and lacrimal glands, and analyzed their clinicopathologic profiles, including immunohistochemical features and p53 gene alterations. The prevalence of hybrid carcinomas was 0.4% among the 1863 cases of parotid gland tumors in our series. The nine patients comprised five men and four women, ranging in age from 40 to 81 years (mean, 62 y). Tumor size ranged from 2 to 10 cm (mean, 4.2 cm). Of the seven patients who were followed up, two were alive with disease and five were alive with no evidence of disease, although the follow-up period was short. Three cases had cervical lymph nodal metastases.

The combinations of carcinoma components in our hybrid carcinomas were as follows: epithelial-myoepithelial carcinoma and basal cell adenocarcinoma in two cases, epithelial-myoepithelial carcinoma and squamous cell carcinoma in one case, salivary duct carcinoma and adenoid cystic carcinoma in two cases, myoepithelial carcinoma and salivary duct carcinoma in one, acinic cell carcinoma and salivary duct carcinoma in one, and squamous cell carcinoma and salivary duct carcinoma in two. Although the proportion of each carcinoma component in a tumor mass varied from case to case, the minor component always represented >/= 10% of the area. Differences in cellular composition were studied by immunohistochemistry and electron microscopy. The Ki-67-labeling index apparently differed between the two carcinoma elements in five cases. Diffusely positive p53 immunoreactivity was observed in four cases, restricted to the more aggressive component in each pair. Furthermore, p53 gene alteration analysis of these p53-positive cases revealed that all and three cases demonstrated loss of heterozygosity at p53 microsatellite loci and p53 gene point mutations, respectively, which were detected only in the p53-immunoreactive carcinoma component.

Therefore, there is the possibility that such molecular-genetic events take an integral part for inducing the transformation from histologically lower to higher grade tumor during the hybrid carcinoma genesis of the salivary glands.


Keratocystoma of the parotid gland: a report of two cases of an unusual pathologic entity.

Nagao T, Serizawa H, Iwaya K, Shimizu T, Sugano I, Ishida Y, Yamazaki K, Shimizu M, Itoh T, Konno A, Ebihara Y.

Department of Surgical Pathology, Tokyo Medical University Hospital (TN, HS, KI, TS, YE), Tokyo.

Mod Pathol 2002 Sep;15(9):1005-10 Abstract quote

Benign salivary gland tumors composed of purely squamous cells are quite unusual and are not included in the World Health Organization classification. We have seen two benign parotid gland tumors characterized by multicystic spaces with stratified squamous linings and focal solid epithelial nests.

Seifert et al. recently described such a case as a choristoma; we, however, herein propose a new designation, keratocystoma, for this unique tumor group, because of its distinctive histological features. These tumors occurred in men aged 18 and 38 years with enlarging parotid gland tumors. Both had largely similar gross and histological features, with some variations. The epithelium lining of the cysts showed apparent keratinization through a parakeratotic or orthokeratotic pathway without forming a granular cell layer. Stratification of the epithelium was always regularly oriented from the outer basal to the inner keratotic cell layer. Focally, the outer layer had bud-like protrusions. In some areas, solid squamous cell islands surrounded by basement membrane were enclosed within the collagenous stroma. These cystic and solid structures were randomly distributed, showing no definite lobular architecture. All of the tumor cells had uniform, bland nuclei and abundant eosinophilic cytoplasm. Scattered mitotic figures were observed, limited to the outer epithelial layer, and showed no abnormal patterns. Transformation from the parotid ductal epithelium to the tumor cells is evident. Foci of foreign-body reactions against keratin materials were present.

Immunoreactivities for cytokeratins reconfirmed the nature of squamous differentiation of the tumor cells. Ki-67-positive cells were confined along the outer basal layer of the tumor epithelium. Tests for alpha-smooth muscle actin and S-100 protein were completely negative. Both patients had no evidence of recurrence 3 and 2 years after subtotal parotidectomy, respectively, without any additional therapy.

We believe that this lesion represents a benign cystic neoplasm rather than a malignant tumor or pseudoneoplastic metaplastic condition. It is important to recognize that this peculiar benign tumor does originate from the salivary gland.

Clonal Nature of Sclerosing Polycystic Adenosis of Salivary Glands Demonstrated by Using the Polymorphism of the Human Androgen Receptor (HUMARA) Locus as a Marker.

Skalova A, Gnepp DR, Simpson RH, Lewis JE, Janssen D, Sima R, Vanecek T, Palma SD, Michal M.

*Department of Pathology, Medical Faculty Hospital, Charles University, Plzen, Czech Republic daggerDepartment of Pathology, Brown University School of Medicine, Rhode Island Hospital, Providence, RI double daggerDepartment of Histopathology, Royal Devon and Exeter Hospital, Exeter section signDepartment of Pathology, Mayo Clinic, Rochester, MN paragraph signDepartment of Pathology, University of Kiel, Germany **Department of Pathology, Molecular Biology and Genetic Laboratory daggerdaggerDepartment of Histopathology, Royal County Hospital, University of Surrey, Guildford, UK.


Am J Surg Pathol. 2006 Aug;30(8):939-944. Abstract quote

Sclerosing polycystic adenosis (SPA) is a recently described, rare lesion of the salivary glands that bears a resemblance to epithelial proliferative lesions of the breast. The true nature of the lesion is unknown, but up to now it has been generally believed to represent a pseudoneoplastic sclerosing and inflammatory process. However, local recurrence developed in about one-third of the cases. Superimposed dysplastic changes ranging from low-grade dysplasia to carcinoma in situ were described in SPA. Although no metastases-related and/or disease-related patient deaths were documented, these clinical and histopathologic features raise the possibility that SPA might represent a neoplastic lesion. Polymorphism of the human androgen receptor locus is most frequently used to assess whether the pattern of X-chromosome inactivation is random or nonrandom, the latter strongly indicating clonality.

In this study, the assay was applied to tissue from 12 examples of SPA. Three cases (males) were noninformative and 3 cases (females) could not be analyzed owing to poor quality of DNA, but all the remaining 6 lesions satisfied the criteria for monoclonality.

We therefore conclude that the findings in the present study are further supporting evidence that SPA is a neoplasm, and not just a reactive process.

Sclerosing Polycystic Adenosis of the Salivary Gland: A Report of 16 Cases.

Gnepp DR, Wang LJ, Brandwein-Gensler M, Slootweg P, Gill M, Hille J.

From *Brown University School of Medicine, Rhode Island Hospital, Providence, RI; daggerMontefiore Medical Center, Moses Division, Albert Einstein College of Medicine, Bronx, NY; double daggerDepartment of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands; section signUniversity of the Western Cape/National Health Laboratory Services, Cape Town, South Africa; and parallelWeil Cornell Medical Center, New York, NY.

Am J Surg Pathol. 2006 Feb;30(2):154-164. Abstract quote

Sclerosing polycystic adenosis is a recently described, extremely rare, reactive, sclerosing, inflammatory process somewhat similar to fibrocystic changes and adenosis tumor of the breast.

To date, there have been 22 cases described in the literature. Because of the infrequency of this lesion, we describe our combined experience with 16 cases, 1 of which has been previously reported. Thirteen tumors arose in the parotid gland, two involved the submandibular gland, and one arose in the buccal mucosa. There were 9 men and 7 women.

Patients ranged in age from 9 to 75 years. Fourteen patients presented with a primary mass. Two were incidental findings in patients with a mixed tumor and an oncocytoma. Tumors ranged in size from 0.3 to 6 cm in greatest dimension. They are typically well circumscribed and are composed of densely sclerotic lobules with prominent cystic change. Hyperplasia of ductal and acinar elements and areas of apocrine-like metaplasia are frequent.

Foci with mild ductal epithelial atypia were frequent with >50% of cases demonstrating at least focal areas of duct epithelial hyperplasia with atypia. Follow-up ranged from 1.5 to 40 years. One tumor recurred twice; no patient has developed metastases or died of disease.

Sebaceous lymphadenocarcinoma of salivary glands.

Croitoru CM, Mooney JE, Luna MA.

Ann Diagn Pathol. 2003 Aug;7(4):236-9. Abstract quote

Primary sebaceous neoplasms of the salivary glands are extremely rare occurrences; furthermore, sebaceous lymphadenocarcinoma has only been reported in three patients.

We report a case of sebaceous lymphadenocarcinoma arising in a lymphadenoma of the parotid gland. The patient was a 55-year-old man who presented with a parotid mass of 3 years' duration.

Histologically, the lesion consisted of a sebaceous lymphadenoma with transition to a sebaceous carcinoma. The cytologic touch-preparation at the time of frozen section showed clusters of benign sebaceous cells in a rich lymphocytic background together with tridimensional clusters of malignant epithelial cells, strongly raising the suspicion of a malignant neoplasm arising in a benign sebaceous lesion.

Malignant transformation of the sebaceous lymphadenoma, although rare, should be considered in enlarging, locally invasive parotid lesions, considering that clinical behavior and prognosis will be determined by the nature of the malignant component.

Small cell carcinoma of the major salivary glands: clinicopathologic study with emphasis on cytokeratin 20 immunoreactivity and clinical outcome.

Nagao T, Gaffey TA, Olsen KD, Serizawa H, Lewis JE.

Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Am J Surg Pathol. 2004 Jun;28(6):762-70. Abstract quote

Small cell carcinomas arising in salivary glands, extremely rare high-grade malignant tumors, are subclassified into neuroendocrine and ductal types. The neuroendocrine type may be segregated further into Merkel cell and pulmonary varieties according to cytokeratin 20 immunoreactivity. Whether subclassification of this tumor group has any biologic or clinical significance is not known.

We examined 15 cases (11 men, 4 women; mean age, 66.5 years) of small cell carcinoma of major salivary glands from a single institution and analyzed their clinicopathologic profiles, including immunohistochemical features and prognostic factors. Three fourths of small cell carcinomas showed cytokeratin 20-positive immunostaining, often with a paranuclear dotlike pattern of reactivity. All tumors were immunoreactive for at least 2 of 6 neuroendocrine markers examined, and 6 tumors were also positive for neurofilament, with a paranuclear dotlike pattern. Postoperatively, 9 patients developed metastatic disease, and 10 patients died of disease 2 to 45 months (mean, 15.9 months) after diagnosis. By log-rank analysis, overall survival was reduced significantly for patients with a primary tumor larger than 3 cm in diameter (P = 0.032), negative immunostain reaction for cytokeratin 20 (P = 0.012), and decreased immunoreactivity for neuroendocrine markers (P = 0.034).

These results indicate that small cell carcinoma of major salivary glands is a highly aggressive tumor, although the prognosis may be better than for extrasalivary neoplasms. Our data also suggest that most salivary gland small cell carcinomas exhibit neuroendocrine differentiation.

Immunohistochemical expression of cytokeratin 20 can be used to classify salivary small cell carcinomas into Merkel cell and pulmonary types and may have prognostic significance.



Immunohistochemical expression of cytokeratins 7 and 20 in malignant salivary gland tumors.

Nikitakis NG, Tosios KI, Papanikolaou VS, Rivera H, Papanicolaou SI, Ioffe OB.

Department of Diagnostic Sciences and Pathology, University of Maryland, Baltimore, MD 21201, USA.
Mod Pathol. 2004 Apr;17(4):407-15. Abstract quote

On the basis of the heterogeneity of cytokeratins 7 and 20 expression in malignant epithelial tumors, the cytokeratin 7/20 immunophenotype has served as a useful diagnostic tool for discrimination of primary and/or metastatic carcinomas of unknown origin. However, the expression pattern of these cytokeratins in malignant salivary gland tumors has not been thoroughly studied.

Our study material was composed of 84 malignant tumors of primary major or minor salivary gland origin. Nine histologic types of carcinoma were represented, including mucoepidermoid (26 cases), adenoid cystic (25), polymorphous low grade (11), salivary duct (8), acinic cell (4), ex mixed tumor (3), not otherwise specified (3), clear cell (2), and basal cell (2). In all, 13 cases of primary skin or mucosal squamous cell carcinoma with secondary salivary gland involvement were also examined. Immunoreactivity for cytokeratin 7 was evident in all malignant salivary gland tumors; the staining pattern was diffuse and strong in 62 cases, and focal and strong in 22 cases. In contrast, 78 cases were negative for cytokeratin 20, whereas only six cases (two mucoepidermoid, one adenoid cystic, and three salivary duct) displayed focal weak positivity.

Overall, 92.9% of malignant salivary gland tumors were characterized by a cytokeratin 7 positive/20 negative immunoprofile, the remaining 7.1% of cases being positive for both cytokeratins. The latter phenotype was more common in salivary duct carcinomas (P< or =0.05). On the other hand, most squamous cell carcinomas (69%) were negative for both cytokeratins, while the remaining cases (31%) were negative for cytokeratin 20 and focally weakly positive for cytokeratin 7.

We suggest that assessment of cytokeratin 7/20 immunoprofile may facilitate the differential diagnosis of (a) primary malignant salivary gland tumors from metastatic tumors, (b) metastatic salivary gland tumors, (c) primary salivary gland tumors, especially mucoepidermoid carcinomas, from squamous cell carcinomas, and (d) salivary duct carcinomas from other malignant salivary gland tumors.
Expression of Androgen, Estrogen, and Progesterone Receptors in Salivary Gland Tumors
Frequent Expression of Androgen Receptor in a Subset of Malignant Salivary Gland Tumors

Selim M. Nasser, MD,1 William C. Faquin, MD, PhD,1 and Yogeshwar Dayal, MD

Am J Clin Pathol 2003;119:801-806 Abstract quote

The expression of sex hormone receptors in some tumors suggests a role for these receptors in tumor pathogenesis and therapy. Previous studies of the expression of estrogen and progesterone receptors in salivary gland tumors have reported conflicting results.

We evaluated the immunohistochemical expression of androgen, estrogen, and progesterone receptors (AR, ER, and PR) in a series of 78 formalin-fixed, paraffin-embedded salivary gland tumors.

Immunoreactivity for AR was seen in 14 of 14 carcinoma ex pleomorphic adenomas, 6 of 6 salivary duct carcinomas, and 2 of 2 basal cell adenocarcinomas but in only 2 of 10 acinic cell carcinomas, mucoepidermoid carcinomas, and adenoid cystic carcinomas each. AR expression was distributed evenly between the sexes. ER and PR were expressed in only a few cases of salivary gland tumors.

All 26 benign salivary gland tumors were negative for AR, ER, and PR. The uniform expression of AR exclusively in a subset of malignant salivary gland tumors suggests a possible role for AR in the histogenesis and possibly in the clinical management of these malignant salivary gland tumors.


The myoepithelial immunophenotype in 135 benign and malignant salivary gland tumors other than pleomorphic adenoma.

Prasad AR, Savera AT, Gown AM, Zarbo RJ.

Henry Ford Hospital, Detroit, MI 48202, USA.

Arch Pathol Lab Med 1999 Sep;123(9):801-6 Abstact quote

BACKGROUND: We have previously studied the immunoreactivity of 3 novel smooth muscle-specific proteins, alpha-smooth muscle actin, smooth muscle myosin heavy chains, and calponin, to assess myoepithelial differentiation in pleomorphic adenomas.

OBJECTIVE: To further expand our knowledge of myoepithelial differentiation in other benign and malignant salivary gland tumors.

DESIGN: Formalin-fixed paraffin sections of 135 salivary gland tumors with associated normal glands were stained with monoclonal antibodies using the avidin-biotin complex immunoperoxidase method and enzymatic and microwave heat-induced epitope retrieval.

RESULTS: In adenoid cystic carcinomas and epithelial-myoepithelial carcinomas, all 3 markers exclusively highlighted the myoepithelial cell components and the epithelial cells were entirely negative. No immunostaining was detected in canalicular adenomas, oncocytomas, Warthin tumors, acinic cell carcinomas, mucoepidermoid carcinomas, squamous cell carcinomas, and polymorphous low-grade adenocarcinomas. Salivary duct carcinomas and adenocarcinomas, not otherwise specified had a distinctive pattern of uniform periductal staining of reactive myofibroblastic cells, and in salivary duct carcinomas some ducts retained a peripheral immunoreactive myoepithelial cell layer.

CONCLUSION: Immunoreactivity for these 3 smooth muscle-specific proteins confirms the known neoplastic myoepithelial component of adenoid cystic carcinomas and epithelial-myoepithelial carcinomas. The consistently positive staining pattern in adenoid cystic carcinomas may be diagnostically useful in discriminating histologically similar but consistently negative polymorphous low-grade adenocarcinomas. Periductal linear staining in adenocarcinoma, not otherwise specified and salivary duct carcinomas is distinctive and appears to represent a tight cuff of myofibroblasts associated with the infiltrating glands.


CLEAR CELL CARCINOMAS Mucoepidermoid carcinoma
Acinic cell carcinoma
Sebaceous carcinoma
Epithelial-myoepithelial carcinoma
Hyalinizing clear cell carcinoma
Clear cell myoepithelial carcinoma
Myoepithelial carcinomas

Primary Salivary Clear Cell Tumors-A Diagnostic Approach.

Wang B, Brandwein M, Gordon R, Robinson R, Urken M, Zarbo RJ.

Lillian and Henry M. Stratton-Hans Popper Department of Pathology (Drs Wang and Brandwein) and the Department of Otolaryngology, Head and Neck Surgery (Dr Urken), The Mount Sinai School of Medicine, New York, NY; the Department of Pathology, The University of Iowa Hospital and Clinics, Iowa City (Dr Robinson); and the Department of Pathology, Henry Ford Hospital, Detroit, Mich (Dr Zarbo).

Arch Pathol Lab Med 2002 Jun;126(6):676-685 Abstract quote

Context.-Primary salivary clear cell tumors comprise an uncommonly encountered subgroup of salivary neoplasia. We hypothesize that clear cell carcinoma does not represent a "monomorphic" variant of epithelial-myoepithelial carcinoma, but is distinct in terms of histogenesis and tumor biology.

Objectives.-To compare the clinicopathologic features of 20 cases of salivary primary clear cell tumors, including 12 clear cell carcinomas (CCCs), 7 epithelial-myoepithelial carcinomas (EMECs), and 1 clear cell myoepithelial carcinoma (CCMEC); to investigate their interrelationship with regard to myoepithelial differentiation; and to offer a diagnostic approach for distinguishing between these entities.

Design.-Retrospective and prospective identification and review of patients diagnosed with primary salivary clear cell neoplasia and review of the English language literature. Setting.-Three academic tertiary-care hospitals.

Patients.-We identified 12 patients with CCC, 7 with EMEC, and 1 with CCMEC. Patients included 11 men and 9 women, aged 30 to 88 years (median 72.5 years). Main Outcomes Measures.-Immunohistochemical reactivity for S100, muscle-specific actin, and calponin; ultrastructural examination when feasible; review of patient charts; and telephone interviews to establish clinical outcome.

Results.-Clear cell carcinoma has a predilection for intraoral sites, whereas EMEC has a predilection for the parotid. All 3 of the tumor types studied have a propensity for locoregional recurrence, which can manifest decades after initial surgery. There were no mortalities among patients with CCC, even after pulmonary metastasis in 2 patients, confirming the indolent nature of this group of clear cell tumors. A meta-analysis of reported cases of CCC, EMEC, and CCMEC confirmed that EMEC and CCMEC have a much greater propensity for locoregional recurrence than CCC, despite the predilection of both for a more surgically accessible site (parotid). We found no definitive evidence of myoepithelial differentiation in CCC, indicating that it is probably morphogenetically distinct from EMEC and CCMEC, both tumors with diagnostically requisite myoepithelial differentiation.

Conclusions.-The initial treatment of choice for CCC, CCMEC, and EMEC is surgical resection with negative margins. Locoregional recurrence should be treated aggressively, as it is still consistent with long disease-free intervals. The lack of myoepithelial differentiation in CCC is consistent with the concept that this tumor is histomorphogenically distinct from EMEC and that it is not merely a monomorphic variant.


Homologous carcinomas of the breasts, skin, and salivary glands. A histologic and immunohistochemical comparison of ductal mammary carcinoma, ductal sweat gland carcinoma, and salivary duct carcinoma.

Wick MR, Ockner DM, Mills SE, Ritter JH, Swanson PE.

Division of Surgical Pathology, Washington University Medical Center, St Louis, MO 63110, USA.

Am J Clin Pathol 1998 Jan;109(1):75-84 Abstract quote

Morphologic mimicry among human malignant neoplasms is a well-known phenomenon in surgical pathology; both undifferentiated and "committed" neoplasms may exhibit this trait. One particularly common group of histologic simulants includes ductal carcinomas of the breasts, the cutaneous appendages, and the salivary glands.

One hundred three tumors in this structural cluster were analyzed microscopically and immunohistologically to codify points of potential pathologic similarity and difference. All the lesions were typified by irregularly permeative clusters and cords of atypical polygonal cells with variable luminal differentiation. A proportion of primary neoplasms in each site demonstrated in situ ductal components; in the absence of the latter elements, however, it was not possible to make topography-related morphologic distinctions among them.

Immunostains for gross cystic disease fluid protein-15 (GCDFP-15), carcinoembryonic antigen, S100 protein, c-erbB-2 oncoprotein, estrogen receptor protein, and progesterone receptor protein also showed largely overlapping phenotypes in each of the three tumor categories, with selected exceptions.

These differences were elucidated through paired chi 2 analysis and included a statistically significant infrequency of GCDFP-15 in eccrine sweat gland carcinomas, a paucity of carcinoembryonic antigen in breast cancers, and an absence of estrogen receptor protein in salivary duct carcinomas. Such findings may be useful in predefined differential diagnostic settings involving the distinction between primary and metastatic ductal cancers of the breasts, skin, and salivary glands. Nevertheless, because of the striking homologies between such tumors at structural and protein-synthetic levels of comparison, it is mandatory that all available clinicopathologic information be used in this context.



Neutron versus photon irradiation for unresectable salivary gland tumors: final report of an RTOG-MRC randomized clinical trial.

Radiation Therapy Oncology Group. Medical Research Council.

Laramore GE, Krall JM, Griffin TW, Duncan W, Richter MP, Saroja KR, Maor MH, Davis LW. Department of Radiation Oncology, University of Washington Medical Center, Seattle 98195.

Int J Radiat Oncol Biol Phys 1993 Sep 30;27(2):235-40 Abstract quote

PURPOSE: To compare the efficacy of fast neutron radiotherapy versus conventional photon and/or electron radiotherapy for unresectable, malignant salivary gland tumors a randomized clinical trial comparing was sponsored by the Radiation Therapy Oncology Group in the United States and the Medical Research Council in Great Britain.

METHODS AND MATERIALS: Eligibility criteria included either inoperable primary or recurrent major or minor salivary gland tumors. Patients were stratified by surgical status (primary vs. recurrent), tumor size (less than or greater than 5 cm), and histology (squamous or malignant mixed versus other). After a total of 32 patients were entered onto this study, it appeared that the group receiving fast neutron radiotherapy had a significantly improved local/regional control rate and also a borderline improvement in survival and the study was stopped earlier than planned for ethical reasons. Twenty-five patients were study-eligible and analyzable.

RESULTS: Ten-year follow-up data for this study is presented. On an actuarial basis, there continues to be a statistically-significant p = 0.009) but there is no improvement in overall survival (15% vs. 25%, p = n.s.). Patterns of failure are analyzed and it is shown that distant metastases account for the majority of failures on the neutron arm and local/regional failures account for the majority of failures on the photon arm. Long-term, treatment-related morbidity is analyzed and while the incidence of morbidity graded "severe" was greater on the neutron arm, there was no significant difference in "life-threatening" complications. This work is placed in the context of other series of malignant salivary gland tumors treated with definitive radiotherapy.

CONCLUSIONS: Fast neutron radiotherapy appears to be the treatment-of-choice for patients with inoperable primary of recurrent malignant salivary gland tumors.

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Learn the basic disease classifications of cancers, infections, and inflammation

Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate

Got Path?
Recent teaching cases and lectures presented in conferences

Internet Links

Pathologists Who Make A Difference
Search for a Physician Specialist

Last Updated August 9, 2006

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