SALIVARY and PAROTID

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Polymorphous low grade adenocarcinoma: a clinicopathologic study of 164 cases.

Castle JT, Thompson LD, Frommelt RA, Wenig BM, Kessler HP.

Cancer. 1999 Jul 15;86(2):207-19.

BACKGROUND: Polymorphous low grade adenocarcinomas (PLGA) are minor salivary gland neoplasms with a predilection for intraoral sites.

METHODS: One hundred sixty-four cases of PLGA diagnosed between 1970-1994 were retrieved from the files of the Armed Forces Institute of Pathology, Washington, DC. Histologic features were reviewed, immunohistochemical studies and prognostic markers were performed, and patient follow-up was obtained. The data were analyzed statistically.

RESULTS: The patients included 109 women and 55 men, ages 23-94 years (average, 57.6 years). The patients usually presented clinically with a palatal mass that ranged in size from 0.4-6 cm (average, 2.2 cm). The tumors were infiltrative and characterized by a polymorphous growth pattern, with individual tumors demonstrating multiple patterns, including solid, ductotubular, cribriform, trabecular, and single file growth. Neurotropism was identified frequently. The neoplastic cells were isomorphic with vesicular nuclei. Mitotic activity was inconspicuous. At an average of 115.4 months after presentation, approximately 97.6% of all patients were either alive or had died without evidence of recurrent disease after treatment with surgical excision only. Four patients had evidence of disease at last follow-up; three had died with evidence of tumor, and one patient was alive with tumor.

CONCLUSIONS: PLGA is a neoplasm of minor salivary gland origin that must be separated from adenoid cystic carcinoma and benign mixed tumor for therapeutic and prognostic considerations. Conservative but complete surgical excision is the treatment of choice for these slow-growing tumors with a low proliferation index; adjuvant therapy does not appear to alter the prognosis.

PMID: 10421256

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Polymorphous low grade adenocarcinoma.

Thompson LD

Pathol Case Rev 2004;9:259-263.

Polymorphous low-grade adenocarcinomas are minor salivary gland neoplasms with a predilection for intraoral sites. Women are affected twice as frequently as men, and generally present in the fifth to sixth decade of life with a painless ihaoral mass. The palatal mass is, on average, about 2 cm in greatest dimension. The tumors are submucosal, identified below an intact mucosa as a well-circumscribed although unencapsulated mass. The tumor is characterized by a polymorphous growth pattern, with individual tumors demonstrating multiple patterns, including solid, ductal-tubular, cribriform, trabecular, and single-file growth. Neurotropism is common, frequently forming a central nidus around which a "targetoid" pattern is formed. The neoplastic cells are isomorphic, containing round to oval vesicular nuclei with small nucleoli. Mitotic activity and necrosis are inconspicuous. There is frequently a slate gray-blue stroma separating the tumor cells. Immunohistochemical analysis demonstrates reactivity with cytokeratin, vimentin, S-100 protein, CD117, glial fibrillary acidic protein, and actin. Bcl-2 is overexpressed and there is generally a low proliferation index as determined by Ki-67 reactions. The tumor must be separated from pleomorphic adenoma (benign mixed tumor) and adenoid cystic carcinoma. Complete surgical excision will yield a more than 95% 10-year survival, although persistence or recurrence can emerge often in about 10% of patients more than 10 years later.

PMID: n/a

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Lymphadenoma of the salivary gland: clinicopathological and immunohistochemical analysis of 33 tumors.

Seethala RR, Thompson LD, Gnepp DR, Barnes EL, Skalova A, Montone K, Kane S, Lewis JS Jr, Solomon LW, Simpson RH, Khan A, Prasad ML..

Mod Pathol. 2011 Sep 2. doi: 10.1038/modpathol.2011.135. [Epub ahead of print]

Lymphadenomas (LADs) are rare salivary gland tumors. Their clinicopathologic characteristics and etiopathogenesis are poorly understood. We examined 33 LADs in 31 patients (17 women and 14 men) aged 11-79 years (median 65 years). There were 22 sebaceous LADs in 21 patients (9 women and 12 men) and 11 non-sebaceous LADs in 10 patients (8 women and 2 men). Two patients had synchronous double tumors. Twenty-six tumors (79%) arose in parotid, three in the neck, and two each in submandibular gland and oral cavity. Extraparotid tumors were seen in 2 of 21 (10%) patients with sebaceous and 4 of 10 (40%) patients with non-sebaceous LADs. Seven of twenty-three (30%) patients had immunosuppressive therapy for unrelated diseases. The tumors were well circumscribed, encapsulated (n=28, 84%) painless masses, varying in size from 0.6 to 6 cm (median 2.2). The cut surfaces were gray-tan to yellow, homogeneous and multicystic (n=24, 72%). The epithelial cells were basaloid, squamous and glandular, forming solid nests, cords, tubules, and cysts. Sebaceous differentiation was restricted to sebaceous lymphadenoma. The epithelial cells expressed basal cell markers (p63, 34BE12, and/or CK5/6, 18/18, 100%) and the luminal glandular cells expressed CK7 (12/12, 100%). Myoepithelial cells were absent (n=10/16, 63%) or focal. The lymphoid stroma was reactive, with germinal centers in 28 (84%). There was no evidence of HPV (0/11), EBV (0/7), and HHV-8 (0/8). Malignant transformation to sebaceous and basal cell adenocarcinoma was seen in one patient each. None of the 11 patients with follow-up (1-8 years) recurred. In summary, sebaceous and non-sebaceous LADs are benign, encapsulated, solid and cystic tumors affecting older adults. Non-sebaceous LADs affect women and extraparotid sites more frequently than sebaceous LADs. Altered immune status may have a role in their etiopathogenesis. Multiple synchronous tumors, origin in buccal mucosa, and malignant transformation may rarely occur.

PMID: 21892186

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Parotid Gland Solitary Fibrous Tumor: A Case Report and Clinicopathologic Review of 22 Cases from the Literature.

Bauer JL, Miklos AZ, Thompson LD

Head Neck Pathol. 2011 Oct 16. [Epub ahead of print].

Solitary fibrous tumors (SFTs) are rare tumors in the head and neck, and even more so in the parotid gland. The mass-like clinical presentation and histologic features result in frequent misclassification, resulting in inappropriate clinical management. There are only a few reported cases in the English literature. Twenty-one patients with parotid gland solitary fibrous tumor were compiled from the English literature (Medline 1960-2011) and integrated with this case report. The patients included 11 males and 11 females, aged 11-79 years (mean, 51.2 years), who presented with a parotid gland painless mass gradually increasing in size or with compression symptoms, with a mean duration of symptoms of 24.7 months. The mean tumor size was 4.5 cm. Grossly, all tumors were described as well-circumscribed to encapsulated, firm, homogenous white to tan masses. Seven patients had a preoperative fine needle aspiration performed, with the majority interpreted to represent pleomorphic adenoma or cementifying fibroma. Histologically, the tumors were well circumscribed, although many tumors showed focally entrapped normal salivary gland acini and ducts at the edge. The tumors were cellular, arranged in haphazard short interlacing fascicles of spindled to epithelioid cells. The spindled cells showed tapering cytoplasm with monotonous, round to oval nuclei with coarse nuclear chromatin distribution. Keloid-like to wiry collagen was present between the neoplastic cells. Mitoses were identified in most cases, while necrosis was absent. Isolated, patulous vessels were present, but a well developed "hemangiopericytoma-like" vascular pattern was not seen. Three tumors were classified as malignant, showing marked nuclear pleomorphism and increased mitoses. When immunohistochemistry was performed, all tumors showed strong and diffuse vimentin, with a majority showing CD34, bcl-2 and CD99 immunoreactivity; all cases tested were negative for S100 protein, cytokeratin, EMA, CAM5.2, smooth muscle actin, muscle specific actin, desmin, MYOD1, myogenin, CD117, GFAP, CD31, FVIII-RAg, collagen IV, p63, p53, calponin, caldesmon, CD56, NFP, and ALK-1. The principle differential diagnoses include pleomorphic adenoma, myoepithelioma, nodular fasciitis, schwannoma, fibromatosis coli, spindle cell "sarcomatoid" carcinoma, and spindle cell melanoma. All patients were managed with surgery, while two patients also received radiation therapy. Metastatic disease was identified in one patient immediately after excision. All patients with follow-up were alive without evidence of disease (n = 18), but the average follow-up is only 1.9 years. One patient is alive with disease at 12 months. Parotid gland SFT is a rare tumor, usually presenting in middle aged adults as a slowly growing mass. Characteristic histologic appearance with CD34 and bcl-2 immunoreactivity support the diagnosis. Surgery is the treatment of choice to yield a good outcome.

PMID: 22002440

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Polymorphous low grade adenocarcinoma.

Thompson LD

Pathol Case Rev 2004;9:259-263.

Polymorphous low-grade adenocarcinomas are minor salivary gland neoplasms with a predilection for intraoral sites. Women are affected twice as frequently as men, and generally present in the fifth to sixth decade of life with a painless ihaoral mass. The palatal mass is, on average, about 2 cm in greatest dimension. The tumors are submucosal, identified below an intact mucosa as a well-circumscribed although unencapsulated mass. The tumor is characterized by a polymorphous growth pattern, with individual tumors demonstrating multiple patterns, including solid, ductal-tubular, cribriform, trabecular, and single-file growth. Neurotropism is common, frequently forming a central nidus around which a "targetoid" pattern is formed. The neoplastic cells are isomorphic, containing round to oval vesicular nuclei with small nucleoli. Mitotic activity and necrosis are inconspicuous. There is frequently a slate gray-blue stroma separating the tumor cells. Immunohistochemical analysis demonstrates reactivity with cytokeratin, vimentin, S-100 protein, CD117, glial fibrillary acidic protein, and actin. Bcl-2 is overexpressed and there is generally a low proliferation index as determined by Ki-67 reactions. The tumor must be separated from pleomorphic adenoma (benign mixed tumor) and adenoid cystic carcinoma. Complete surgical excision will yield a more than 95% 10-year survival, although persistence or recurrence can emerge often in about 10% of patients more than 10 years later.

PMID: n/a

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Kaposi sarcoma of major salivary gland origin: A clinicopathologic series of six cases.

Castle JT, Thompson LD.

Cancer. 2000 Jan 1;88(1):15-23.

BACKGROUND: Kaposi sarcoma (KS), one of the defining tumors of acquired immune deficiency syndrome (AIDS), is rarely identified in the major salivary glands. To the authors' knowledge, no previous published series has evaluated the clinicopathologic aspects of this tumor in major salivary glands.

METHODS: Six cases of salivary gland KS, diagnosed between 1970 and 1998, were retrieved from the files of the Oral and Maxillofacial Pathology Registry of the Armed Forces Institute of Pathology. Histologic features were reviewed and special stains, immunohistochemical studies, and in situ hybridization were performed (n = 4). Patient follow-up data were obtained.

RESULTS: The patients included 6 men ages 20-73 years (average, 53.0 years). Patients presented clinically with a mass in the submandibular (n = 4) or parotid (n = 2) gland region. Symptoms were present for a mean of 13.7 months. The tumors measured 1-4 cm (average, 2.5 cm) in greatest dimension. Histologically, the tumors exhibited the usual features of KS: a spindle cell vascular proliferation arranged in fasciculated bundles, variable nuclear pleomorphism, mitotic figures, extravasated erythrocytes, and hyaline globules. Five patients were serologically positive for human immunodeficiency virus (HIV) (three homosexual males, one infected by a contaminated blood transfusion, and one with an unknown risk factor). Human herpesvirus-8 (HHV-8) was present in all cases tested (n = 4). Patients were treated with surgical excision (n = 6), followed by chemotherapy (n = 1) for the single patient with other foci of KS (rectal). Three patients died of AIDS-related infectious complications and one of congestive heart failure, whereas the remaining patients are alive with AIDS but free of salivary gland KS.

CONCLUSIONS: Salivary gland enlargement is frequently identified in HIV positive or AIDS patients. Although rare, it is important to consider KS in the differential diagnosis of other AIDS-related salivary gland manifestations (infections and tumors). Copyright 2000 American Cancer Society.

PMID: 10618601

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Oncocytomas of the submandibular gland. A series of 22 cases and a review of the literature.

Thompson LD, Wenig BM, Ellis GL.

Cancer. 1996 Dec 1;78(11):2281-7.

BACKGROUND: Oncocytomas are benign salivary gland neoplasms that represent approximately 1.5% of all salivary gland tumors. Oncocytomas of the submandibular gland, however, are decidedly uncommon.

METHODS: Twenty-two cases of submandibular gland oncocytomas from the files of the Oral and Otolaryngic Tumor Registries of the Armed Forces Institute of Pathology were reviewed, and analysis of the histologic criteria, histochemical and immunohistochemical reactions, and ultrastructural and clinical follow-up data was performed.

RESULTS: The patients included 11 females and 11 males, age 21-88 years, with a mean age at presentation of 58.7 years. Clinically, the tumors were generally asymptomatic masses in the submandibular gland that increased in size over a period ranging from several weeks to 20 years and were occasionally associated with pain (n = 9). The tumors ranged in greatest dimension from 0.7 to 7 cm and were circumscribed to encapsulated. Histologically, the tumors were characterized by large epithelial cells with eosinophilic, granular cytoplasm. The cytoplasm stained positively with stains used to demonstrate mitochondria (phosphotungstic acid-hematoxylin, Novelli, Cresylecht violet V, and Kluver-Barrera Luxol fast blue stains). Immunohistochemical reactions demonstrated an epithelial origin (keratin and epithelial membrane antigen), whereas markers for myoepithelial derivation (S-100 protein, actin, and glial fibrillary acidic protein) were not identified. At the time this study was conducted, all patients with submandibular oncocytomas were either alive without evidence of disease or had died without evidence of recurrent disease, with surgical resection the only treatment.

CONCLUSIONS: Submandibular gland oncocytomas are rare, benign tumors. The tumor cells are filled with mitochondria, which are easily demonstrated by histochemical reactions. Complete surgical resection is adequate therapy.

PMID: 8940996

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Salivary gland acinic cell carcinoma.

Thompson LD.

Ear Nose Throat J. 2010 Nov;89(11):530-2.

FIRST PARAGRAPH: Acinic cell carcinoma (AcCC) is a malignant epithelial salivary gland neoplasm that demonstrates serous acinar cell differentiation with cytoplasmic zymogen secretory granules. While serous-type cells tend to predominate, ductal cells are also part of this neoplasm. There are a few cases that are thought to be related to radiation exposure. AcCC accounts for about 6% of all salivary gland tumors and 10 to 12% of all malignant salivary gland tumors. Patients present at a wide range of ages (mean: 40s). Children are also affected, as AcCC is the second most common neoplasm in the pediatric age group after mucoepidermoid carcinoma. Overall, females are more affected than males by a ratio of 3:2.

PMID: 21086276

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Necrotizing sialometaplasia.

Penner CR, Thompson LD.

Ear Nose Throat J. 2003 Jul;82(7):493-4.

FIRST PARAGRAPH: Necrotizing sialometaplasia is a benign, self-limited, reactive inflammatory process that involves salivary glands. It occurs in middle-aged patients; men are affected slightly more often than women. Patients may experience an antecedent event (e.g., surgery, radiation, or trauma) up to 3 weeks before necrotizing sialometaplasia appears clinically, but many are asymptomatic. A submucosal nodular swelling will give way to an ulcerative, crater-like lesion that usually measures less than 3 cm in its greatest dimension.

PMID: 12955830

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Canalicular adenoma.

Penner CR, Thompson L.

Ear Nose Throat J. 2005 Mar;84(3):132.

FIRST PARAGRAPH: Canalicular adenomas are benign neoplasms with a unique predilection for the upper lip (~80% of cases). They account for 1% of all salivary gland neoplasms. Their incidence peaks during the seventh decade of life; they are distinctly uncommon in patients younger than 50 years of age. The female-to-male predominance is approximately 2:1.

PMID: 15871577

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Mucoepidermoid carcinoma.

Thompson LD

Ear Nose Throat J. 2005 Dec;84(12):762-3.

FIRST PARAGRAPH: Mucoepidermoid carcinoma (MEC) is the most common primary salivary gland malignancy, accounting for approximately 25% of all malignancies. More than half of these cases involve the major salivary glands, primarily the parotid glands. MEC can also involve a variety of other sites that have minor mucoserous glands. Women are more commonly affected than men (3:2), and the mean age at onset is in the 5th decade of life. MEC is also the most common salivary gland malignancy in children.

PMID: 16408550

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Epithelial-myoepithelial carcinoma.

Folk GS, Thompson LD.

Ear Nose Throat J. 2006 Apr;85(4):214, 216.

FIRST PARAGRAPH: Epithelial-myoepithelial carcinoma (EMC) is an uncommon salivary gland malignancy, representing 1% of all salivary gland tumors. Women are more frequently affected (2:1). The incidence of EMC peaks between the ages of 50 and 60 years, although the age range is broad. The parotid gland is most frequently affected (60%), but both major and minor salivary glands can be involved. Patients typically present with a painless, slowly growing mass; occasionally there is rapid growth, pain, or facial weakness.

PMID: 16696350

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Hemangioma of the parotid.

Thompson LD.

Ear Nose Throat J. 2002 Nov;81(11):769.

FIRST PARAGRAPH: Hemangiomas are benign tumors of endothelial cell origin (benign hemangioendotheliomas). They are the most common salivary gland tumor in children younger than 1 year of age, accounting for 90% of cases. Hemangiomas in adults are uncommon. The characteristic features of hemangiomas are the rapid enlargement of a unilateral (usually on the left), compressible, bluish mass shortly after birth, particularly in girls. Hemangiomas are not associated with any syndrome.

PMID: 12472029

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Polymorphous low grade adenocarcinoma.

Thompson LDR

Pathol Case Rev 2004;9:259-263

PMID: 0

Papillary cystadenoma lymphomatosum (Warthin tumor).

Rizzi MD, Thompson LD.

Ear Nose Throat J. 2003 Dec;82(12):920-2.

FIRST PARAGRAPH: Papillary cystadenoma lymphomatosum (Warthin tumor, adenolymphoma) is a benign salivary gland tumor that occurs almost exclusively in the parotid gland. It represents 5 to 6% of all salivary gland tumors, and it is the second most common benign parotid neoplasm. Men are affected more often than women, usually in the fifth to seventh decades of life, although this gender proportion is changing. Warthin tumor is associated with smoking. The most common clinical manifestation is a painless, slowly growing mass in the inferior pole of the superficial lobe of the parotid gland, usually at the level of the mandibular angle. Multifocality occurs in up to 14% of cases; when two salivary gland neoplasms are present synchronously, Warthin tumor is the most common second tumor.

PMID: 14702874

Salivary gland lymphoepithelial cysts.

Varnholt H, Thompson L, Pantanowitz L

Ear Nose Throat J. 2007 May;86(5):265.

FIRST PARAGRAPH: Lymphoepithelial cysts are benign, slowly growing unilocular or multilocular lesions that may appear in the head and neck. Among the reported head and neck sites are the salivary glands (typically the parotid gland) and the oral cavity (usually the floor of the mouth). These cysts are usually seen in adults and only occasionally in children. They range in size from 0.5 to 5.0 cm, and they can cause considerable cosmetic deformity and physical discomfort.

PMID: 17580800

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