Subsets of Salivary Duct Carcinoma Defined by Morphologic Evidence of Pleomorphic Adenoma, PLAG1 or HMGA2 Rearrangements, and Common Genetic Alterations

Chiosea SI, Thompson LD, Weinreb I, Bauman JE, Mahaffey AM, Miller C, Ferris RL, Gooding WE.
Cancer. 2016 Oct 15;122(20):3136-3144. doi: 10.1002/cncr.30179. Epub 2016 Jul 5.
BACKGROUND: The authors hypothesized that histogenetic classification of salivary duct carcinoma (SDC) could account for de novo tumors and those with morphologic or molecular evidence (pleomorphic adenoma gene 1 [PLAG1], high-mobility group AT hook 2 [HMGA2] rearrangement, amplification) of pleomorphic adenoma (PA).
METHODS: SDCs (n = 66) were reviewed for morphologic evidence of PA. PLAG1 and HMGA2 alterations were detected by fluorescence in situ hybridization (FISH). PLAG1-positive tumors were tested by FISH for fibroblast growth factor receptor 1 (FGFR1) rearrangement. Thirty-nine tumors were analyzed using a commercial panel for mutations and copy number variations in 50 cancer-related genes.
RESULTS: On the basis of combined morphologic and molecular evidence of PA, 4 subsets of SDC emerged: 1) carcinomas with morphologic evidence of PA but intact PLAG1 and HMGA2 (n = 22); 2) carcinomas with PLAG1 alteration (n = 18) or 3) HMGA2 alteration (n = 12); and 4) de novo carcinomas, without morphologic or molecular evidence of PA (n = 14). The median disease-free survival was 37 months (95% confidence interval, 28.4-45.6 months). Disease-free survival and other clinicopathologic parameters did not differ for the subsets defined above. Combined Harvey rat sarcoma viral oncogene homolog/phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit α (HRAS/PIK3CA) mutations were observed predominantly in de novo carcinomas (5 of 8 vs 2 of 31 tumors; P = .035). Erb-B2 receptor tyrosine kinase 2 (ERBB2) copy number gain was not observed in de novo carcinomas (0 of 8 vs 12 of 31 tumors; P = .08). Tumor protein 53 (TP53) mutations were more common in SDC ex pleomorphic adenomas than in de novo carcinomas (17 of 31 vs 1 of 8 tumors; P = .033).
CONCLUSIONS: The genetic profile of SDC varies with the absence or presence of pre-existing PA and its cytogenetic signature. Most de novo SDCs harbor combined HRAS/PIK3CA mutations and no ERBB2 amplification.
PubMed ID: 27379604
Article Size: <1 MB

Salivary duct carcinoma and the concept of early carcinoma ex pleomorphic adenoma

Griffith CC, Thompson LD, Assaad A, Purgina BM, Lai C, Bauman JE, Weinreb I, Seethala RR, Chiosea SI.
Histopathology. 2014 Dec;65(6):854-60.
AIMS: The data on the histological type of carcinomatous component and the extent of extracapsular invasion for salivary carcinomas ex pleomorphic adenoma (PA) are conflicting. We aimed to determine the prognostic value of extracapsular invasion in salivary duct carcinomas (SDC) ex PA.
METHODS AND RESULTS: A total of 117 patients with SDC were identified retrospectively; 44 cases involving major salivary glands had pre-existing PA (44 of 117, 37%). The morphological spectrum of SDC ex PA was characterized. The primary endpoint was overall survival (OS). Most SDC ex PA were widely invasive at presentation (27 of 44; 61%). Five patients with intracapsular SDC ex PA experienced no disease progression. The assessment of extracapsular invasion was precluded in eight cases (e.g. positive margins of resection). The rate of lymph node involvement was similar in cases with extracapsular invasion of ?2 mm (two of three) and >7 mm (22 of 26). Only pT correlated with OS [116 months, 95% confidence interval (CI) 22-210 months for pT1 versus 20 months (95% CI 6-34) for pT4; P = 0.013].
CONCLUSIONS: Intracapsular SDC ex PA are potentially indolent. SDC ex PA with extracapsular invasion of ?2 mm are rare, and appear to be clinically aggressive. Several histological parameters preclude assessment of extracapsular invasion.
PubMed ID: 24804831
Article Size: <1 MB

Salivary Duct Carcinoma: The Predominance of Apocrine Morphology, Prevalence of Histologic Variants, and Androgen Receptor Expression

Williams L, Thompson LD, Seethala RR, Weinreb I, Assaad AM, Tuluc M, Ud Din N, Purgina B, Lai C, Griffith CC, Chiosea SI.
Am J Surg Pathol. 2015 May;39(5):705-13.
Salivary duct carcinoma (SDC) is a prototypic aggressive salivary gland carcinoma. Our aim is to determine the prevalence of histologic variants (micropapillary, basal-like) and androgen receptor (AR) expression in a large multi-institutional series of SDC. AR status was determined by immunohistochemistry (IHC). Most SDCs were characterized by an apocrine phenotype and AR expression. Cases with a nonapocrine phenotype and AR-negative status were studied by additional IHC and fluorescence in situ hybridization for ETV6 or MYB/NFIB. The diagnosis of SDC was confirmed in 187 of 199 (94%) cases. Variant morphologies were identified in 12 cases: micropapillary (n=6), sarcomatoid (n=3), mucinous (n=2), and basal-like (n=1). AR IHC was performed in 183 cases, of which 179 (97.8%) showed AR expression. On the basis of morphologic appearance and results of additional studies, 12 cases were reclassified as squamous cell carcinoma (SCC) (n=4), epithelial-myoepithelial carcinoma with high-grade transformation (HGT) (n=2), myoepithelial carcinoma (n=2), mammary analogue secretory carcinoma, high grade (ETV6 translocated; n=1), adenoid cystic carcinoma with HGT (n=1), acinic cell carcinoma with HGT (n=1), and adenosquamous carcinoma (n=1). AR-negative SDC is extremely rare, and the majority of such cases are more accurately classified as other entities. HGTs of other salivary carcinomas and squamous cell carcinoma are the most common mimics of SDC. SDCs with variant morphologies still show at least a minor component of conventional apocrine appearance. Thus, apocrine morphology defines SDC.
PubMed ID: 25871467
Article Size: 1 MB

Molecular Characterization of Apocrine Salivary Duct Carcinoma

Chiosea SI, Williams L, Griffith CC, Thompson LD, Weinreb I, Bauman JE, Luvison A, Roy S, Seethala RR, Nikiforova MN.
Am J Surg Pathol. 2015 Jun;39(6):744-52.
Contemporary classification and treatment of salivary duct carcinoma (SDC) require its thorough molecular characterization. Thirty apocrine SDCs were analyzed by the Ion Ampliseq Cancer HotSpot panel v2 for mutations in 50 cancer-related genes. Mutational findings were corroborated by immunohistochemistry (eg, TP53, BRAF, ?-catenin, estrogen, and androgen receptors) or Sanger sequencing/SNaPshot polymerase chain reaction. ERBB2 (HER2), PTEN, FGFR1, CDKN2A/P16, CMET, EGFR, MDM2, and PIK3CA copy number changes were studied by fluorescence in situ hybridization. TP53 mutations (15/27, 56%), PTEN loss (11/29, 38%, including 2 cases with PTEN mutation), PIK3CA hotspot mutations (10/30, 33%), HRAS hotspot mutations (10/29; 34%), and ERBB2 amplification (9/29, 31%, including 1 case with mutation) represented the 5 most common abnormalities. There was no correlation between genetic changes and clinicopathologic parameters. There was substantial overlap between genetic changes: 8 of 9 cases with ERBB2 amplification also harbored a PIK3CA, HRAS, and TP53 mutation and/or PTEN loss. Six of 10 cases with PIK3CA mutation also had an HRAS mutation. These findings provide a molecular rationale for dual targeting of mitogen-activated protein kinase and phosphoinositide 3-kinase pathways in SDC. FGFR1 amplification (3/29, 10%) represents a new potential target. On the basis of studies of breast carcinomas, the efficacy of anti-ERBB2 therapy will likely be decreased in SDC with ERBB2 amplification co-occurring with PIK3CA mutation or PTEN loss. Therefore, isolated ERBB2 testing is insufficient for theranostic stratification of apocrine SDC. On the basis of the prevalence and type of genetic changes, apocrine SDC appears to resemble one subtype of breast carcinoma-‘luminal androgen receptor positive/molecular apocrine.’
PubMed ID: 25723113
Article Size: <1 MB

Salivary duct carcinoma.

Thompson LD.
Ear Nose Throat J. 2012 Sep;91(9):356-9.
FIRST PARAGRAPH: Salivary duct carcinoma is a high-grade adenocarcinoma that resembles breast ductal carcinoma. It is believed to be derived from intra- and interlobular excretory ducts. Salivary duct carcinoma may arise de novo or as a relatively common malignant component of a carcinoma ex pleomorphic adenoma. It accounts for about 9% of all malignant salivary gland tumors. Although there is a wide age range at presentation, most patients present in the seventh decade of life; men are affected much more frequently than women (4:1).
PubMed ID: 22996706
Article Size: <1 MB

Epithelial-Myoepithelial Carcinoma: Frequent Morphologic and Molecular Evidence of Preexisting Pleomorphic Adenoma, Common HRAS Mutations in PLAG1-intact and HMGA2-intact Cases, and Occasional TP53, FBXW7, and SMARCB1 Alterations in High-grade Cases.

El Hallani S, Udager AM, Bell D, Fonseca I, Thompson LDR, Assaad A, Agaimy A, Luvison AM, Miller C, Seethala RR, Chiosea S.
Am J Surg Pathol. 2018 Jan;42(1):18-27.
We hypothesized that there is a relationship between the preexisting pleomorphic adenoma [PA]), histologic grade of epithelial-myoepithelial carcinomas (EMCAs), and genetic alterations. EMCAs (n=39) were analyzed for morphologic and molecular evidence of preexisting PA (PLAG1, HMGA2 status by fluorescence in situ hybridization, FISH, and FGFR1-PLAG1 fusion by next-generation sequencing, NGS). Twenty-three EMCAs were further analyzed by NGS for mutations and copy number variation in 50 cancer-related genes. On the basis of combined morphologic and molecular evidence of PA, the following subsets of EMCA emerged: (a) EMCAs with morphologic evidence of preexisting PA, but intact PLAG1 and HMGA2 (12/39, 31%), (b) Carcinomas with PLAG1 alterations (9/39, 23%), or (c) HMGA2 alterations (10/39, 26%), and (d) de novo carcinomas, without morphologic or molecular evidence of PA (8/39, 21%). Twelve high-grade EMCAs (12/39, 31%) occurred across all subsets. The median disease-free survival was 80 months (95% confidence interval, 77-84 mo). Disease-free survival and other clinicopathologic parameters did not differ by the above defined subsets. HRAS mutations were more common in EMCAs with intact PLAG1 and HMGA2 (7/9 vs. 1/14, P<0.001). Other genetic abnormalities (TP53 [n=2], FBXW7 [n=1], SMARCB1 deletion [n=1]) were seen only in high-grade EMCAs with intact PLAG1 and HMGA2. We conclude that most EMCAs arose ex PA (31/39, 80%) and the genetic profile of EMCA varies with the absence or presence of preexisting PA and its cytogenetic signature. Progression to higher grade EMCA with intact PLAG1 and HMGA2 correlates with the presence of TP53, FBXW7 mutations, or SMARCB1 deletion.
PubMed ID: 29135520
Article Size: 1.2 MB

Definitive treatment of androgen receptor–positive salivary duct carcinoma with androgen deprivation therapy and external beam radiotherapy.

Soper MS, Iganej S, Thompson LD.
Head Neck. 2014 Jan;36(1):E4-7.
BACKGROUND: Salivary duct carcinoma (SDC) is an aggressive malignancy with high recurrence rates. Standard management includes surgical resection followed by adjuvant radiation. Androgen receptor positivity has been described to be present in 40% to 90% of SDCs, and a recent case series showed a benefit to androgen deprivation therapy (ADT) in recurrent or metastatic disease.
METHODS AND RESULTS: We present the case of an 87-year-old woman with a locally advanced androgen receptor-positive parotid SDC treated definitively with ADT and external beam radiotherapy, a regimen modeled after the treatment of prostate cancer. She had a complete response on positron emission tomography (PET)/CT scan and had no evidence of disease 24 months after the completion of treatment.
CONCLUSION: To our knowledge, this case report is the first to describe the use of ADT plus radiation to definitively treat SDC. This regimen could be considered in patients with androgen receptor-positive SDCs who are considered unresectable or who refuse surgery.
PubMed ID: 23720164
Article Size: <1 MB

Novel PRKD Gene Rearrangements and Variant Fusions in Cribriform Adenocarcinoma of Salivary Gland Origin

Weinreb I, Zhang L, Tirunagari LM, Sung YS, Chen CL, Perez-Ordonez B, Clarke BA, Skalova A, Chiosea SI, Seethala RR, Waggott D, Boutros PC, How C, Liu FF, Irish JC, Goldstein DP, Gilbert R, Ud Din N, Assaad A, Hornick JL, Thompson LD, Antonescu CR.
Genes Chromosomes Cancer. 2014 Oct;53(10):845-56.
Polymorphous low-grade adenocarcinoma (PLGA) and cribriform adenocarcinoma of minor salivary gland (CAMSG) are low-grade carcinomas arising most often in oral cavity and oropharynx, respectively. Controversy exists as to whether these tumors represent separate entities or variants of one spectrum, as they appear to have significant overlap, but also clinicopathologic differences. As many salivary carcinomas harbor recurrent translocations, paired-end RNA sequencing and FusionSeq data analysis was applied for novel fusion discovery on two CAMSGs and two PLGAs. Validated rearrangements were then screened by fluorescence in situ hybridization (FISH) in 60 cases. Histologic classification was performed without knowledge of fusion status and included: 21 CAMSG, 18 classic PLGA, and 21 with ‘mixed/indeterminate’ features. The RNAseq of 2 CAMSGs showed ARID1A-PRKD1 and DDX3X-PRKD1 fusions, respectively, while no fusion candidates were identified in two PLGAs. FISH for PRKD1 rearrangements identified 11 additional cases (22%), two more showing ARID1A-PRKD1 fusions. As PRKD2 and PRKD3 share similar functions with PRKD1 in the diacylglycerol and protein kinase C signal transduction pathway, we expanded the investigation for these genes by FISH. Six additional cases each showed PRKD2 and PRKD3 rearrangements. Of the 26 (43%) fusion-positive tumors, there were 16 (80%) CAMSGs and 9 (45%) indeterminate cases. A PRKD2 rearrangement was detected in one PLGA (6%). We describe novel and recurrent gene rearrangements in PRKD1-3 primarily in CAMSG, suggesting a possible pathogenetic dichotomy from ‘classic’ PLGA. However, the presence of similar genetic findings in half of the indeterminate cases and a single PLGA suggests a possible shared pathogenesis for these tumor types.
PubMed ID: 24942367
Article Size: <1 MB

Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands

Weinreb I, Piscuoglio S, Martelotto LG, Waggott D, Ng CK, Perez-Ordonez B, Harding NJ, Alfaro J, Chu KC, Viale A, Fusco N, da Cruz Paula A, Marchio C, Sakr RA, Lim R, Thompson LD, Chiosea SI, Seethala RR, Skalova A, Stelow EB, Fonseca I, Assaad A, How C, Wang J, de Borja R, Chan-Seng-Yue M, Howlett CJ, Nichols AC, Wen YH, Katabi N, Buchner N, Mullen L, Kislinger T, Wouters BG, Liu FF, Norton L, McPherson JD, Rubin BP, Clarke BA, Weigelt B, Boutros PC, Reis-Filho JS.
Nat Genet. 2014;Nov;(46(11):1166-9.
Polymorphous low-grade adenocarcinoma (PLGA) is the second most frequent type of malignant tumor of the minor salivary glands. We identified PRKD1 hotspot mutations encoding p.Glu710Asp in 72.9% of PLGAs but not in other salivary gland tumors. Functional studies demonstrated that this kinase-activating alteration likely constitutes a driver of PLGA.
PubMed ID: 25240283
Article Size: 1 MB

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.
PubMed ID: 10421256
Article Size: 2 MB

Polymorphous low grade adenocarcinoma.

Thompson LDR.
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.
PubMed ID: n/a
Article Size: 4.9 MB

Clinicopathologic and Immunophenotypic Characterization of 25 Cases of Acinic Cell Carcinoma with High-Grade Transformation

Thompson LD, Aslam MN, Stall JN, Udager AM, Chiosea S, McHugh JB
Head Neck Pathol. 2016 Jun;10(2):152-60.
Acinic cell carcinoma (AiCC) with high-grade transformation is a rare variant of AiCC composed of both a conventional low-grade (LG) AiCC and a separate highgrade (HG) component. We describe here, the clinicopathologic and immunohistochemical features of 25 cases diagnosed between 1990 and 2015. Available tissue was analyzed and compared with a cohort of pure LG AiCC for the morphologic and immunophenotypic profile. Incidence was higher in females (1.8:1) than males with an overall mean age at presentation of 63.2 years. All tumors occurred in the parotid gland including 76 % with facial nerve trunk and branches involvement. Most patients were treated with extensive resection and adjuvant therapy. Local recurrence or distant metastasis occurred in most patients, with 72.7 % dead with disease (mean 2.9 years) and 3 patients alive with disease (mean 2.4 years). The majority of the tumors were composed of a LG microcystic AiCC and a HG component consisting of invasive lobules of undifferentiated cells with predominantly solid, cribriform, and glandular patterns. Acinic differentiation was still present in HG areas but aggressive features such as perineural invasion (76 %), lymphovascular invasion (62 %), positive margins (72 %), high mitotic rate, atypical mitoses and/or comedonecrosis (86 %) were easily identified. Compared to the pure LG AiCC, the cases with HG transformation showed significantly increased expression of cyclin-D1, p53 and Ki-67. Most HG areas of AiCC expressed membranous b-catenin (92 %) and were negative for p63 (three cases were focally positive), S100, SMA, androgen, and estrogen receptors. DOG1 expression was present in all LG AiCC tested with retained expression in 91 % of cases with HG transformation, supporting acinic differentiation in the HG foci. Recognition of AiCC with high-grade transformation is imperative as more aggressive clinical management is warranted.
PubMed ID: 26245749
Article Size: 6 MB

Salivary acinic cell carcinoma: reappraisal and update

Vander Poorten V, Triantafyllou A, Thompson LD, Bishop J, Hauben E, Hunt J, Skalova A, Stenman G, Takes RP, Gnepp DR, Hellquist H, Wenig B, Bell D, Rinaldo A, Ferlito A.
Eur Arch Otorhinolaryngol. 2016 Nov;273(11):3511-3531.
Epidemiologic and clinicopathologic features, therapeutic strategies, and prognosis for acinic cell carcinoma of the major and minor salivary glands are critically reviewed. We explore histopathologic, histochemical, electron microscopic and immunohistochemical aspects and discuss histologic grading, histogenesis, animal models, and genetic events. In the context of possible diagnostic difficulties, the relationship to mammary analog secretory carcinoma is probed and a classification is suggested. Areas of controversy or uncertainty, which may benefit from further investigations, are also highlighted.
PubMed ID: 26685679
Article Size: 5.22 MB

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.
PubMed ID: 21086276
Article Size: <1 MB

Diagnostic Approach to Fine Needle Aspirations of Cystic Lesions of the Salivary Gland

Pantanowitz L , Thompson LDR, Rossi ED.
Head Neck Pathol. 2018 Mar 9. doi: 10.1007/s12105-018-0904-8. [Epub ahead of print]
Fine needle aspiration (FNA) has diagnostic and therapeutic value in the management of salivary gland cysts. Rendering an accurate diagnosis from an aspirated salivary gland cyst is challenging because of the broad differential diagnosis, possibility of sampling error, frequent hypocellularity of specimens, morphologic heterogeneity, and overlapping cytomorphology of many cystic entities. To date, there have been no comprehensive review articles providing a practical diagnostic approach to FNA of cystic lesions of salivary glands. This article reviews the cytopathology of salivary gland cysts employing 2017 World Health Organization terminology, addresses the accuracy of FNA, and presents The Milan System approach for reporting in cystic salivary gland cases. The utility of separating FNA specimens from salivary gland cysts, based upon the presence of mucin and admixed lymphocytes in cyst fluid is demonstrated. A reliable approach to interpreting FNA specimens from patients with cystic salivary gland lesions is essential to accurately determine which of these patients may require subsequent surgery.
PubMed ID: 29524082
Article Size: 3.5 MB

Incisional or core biopsies of salivary gland tumours: how far should we go?

Nelson BL, Thompson LDR.
Diagnostic Pathology Volume 18:9 September 2012 pages 358-365.
Trends in the evaluation of salivary gland masses have changed as imaging studies have improved and sampling techniques have evolved over the past several decades. Whether clinically palpable or detected by imaging studies, salivary gland masses have been readily evaluated by fine needle aspiration. More recently, imaging guided core-needle biopsy has been employed with mixed results. The literature on these techniques is reviewed and analyzed with particular attention to tissue adequacy and diagnostic accuracy. Comparison is made using selected case presentations to highlight the advantages and disadvantages of establishing a diagnosis when core-needle biopsy is utilized. Core-needle biopsy of salivary gland tumours may be a useful first diagnostic approach as long as the limitations of the procedure are well understood and managed.
PubMed ID: n/a
Article Size: <1 MB

Canalicular Adenoma: A Clinicopathologic and Immunohistochemical Analysis of 67 Cases with a Review of the Literature

Thompson LD, Bauer JL, Chiosea S, McHugh JB, Seethala RR, Miettinen M, Müller S.
Head Neck Pathol. 2015 Jun;9(2):181-95.
There is a lack of a comprehensive immunohistochemical (IHC) analysis of canalicular adenoma (CanAd), especially when combined with a description of the unique histologic features. Given the usual small biopsies, IHC may be useful in distinguishing CanAd from other tumors in the differential diagnosis. Retrospective. The patients included 54 females and 13 males (4.2:1), aged 43-90 years, with a mean age at presentation of 69.9 years. Clinical presentation was generally a mass (n = 61) slowly increasing in size (mean 38.5 months), affecting the upper lip (n = 46), buccal mucosa (n = 17) or palate (n = 4), involving the right (n = 29), left (n = 24) or midline (n = 9), without any major salivary gland tumors. The tumors ranged in size from 0.2 to 3 cm (mean 1.2 cm). Most tumors were multilobular or bosselated (76 %), often surrounded by a capsule. Histologically, the tumors were characterized by cystic spaces, tumor cords with beading, tubule formation, and by the presence of luminal squamous balls (n = 41). The cells were cuboidal to columnar with stippled chromatin. Mitoses were inconspicuous. A myxoid stroma (n = 64), sclerosis (n = 42), luminal hemorrhage (n = 51), and luminal microliths (calcifications) (n = 33) were characteristic. Nine (13.4 %) were multifocal. CanAd showed the following characteristic immunohistochemistry findings: CK-pan and S100 protein (strong, diffuse reaction); peripheral or luminal GFAP reaction; CK5/6 and p16 luminal squamous ball reaction; SOX10 nuclear reaction; cytoplasmic p63 reaction. CanAd are unique minor salivary gland tumors showing a distinct architecture and phenotype. They predilect to older women, with the majority multilobulated and affecting the upper lip, multifocal in 13 %; no major salivary gland tumors were identified. S100 protein, CK-pan, GFAP and SOX10 are positive, with luminal squamous balls highlighted by CK5/6 or p16.
PubMed ID: 25141970
Article Size: 4.5 MB

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.
PubMed ID: 15871577
Article Size: <1 MB

Evaluation of PAX2 and PAX8 Expression in Salivary Gland Neoplasms.

Butler RT, Alderman MA, Thompson LD, McHugh JB.
Head Neck Pathol. 2015 Mar;9(1):47-50.
PAX2 and PAX8 are transcription factors involved in embryogenesis that have been utilized as immunohistochemical indicators of tumor origin. Specifically, PAX2 is a marker of neoplasms of renal and müllerian origin, while PAX8 is expressed by renal, müllerian, and thyroid tumors. While studies examining these transcription factors in a variety of tumors have been published, data regarding their expression in salivary gland neoplasms are limited. The goal of this study was to assess expression of PAX2 and PAX8 in a large cohort of salivary gland tumors. Utilizing tissue microarrays, samples of normal salivary glands (n = 68) and benign and malignant salivary gland neoplasms (n = 442) were evaluated for nuclear immunoreactivity with PAX2 and PAX8. No expression was observed with either marker in the normal salivary glands, and PAX8 was negative in all neoplasms. Focal expression of PAX2 was observed in one example each of oncocytoma and acinic cell carcinoma. These results indicate that evaluation of PAX2 and/or PAX8 expression would be valuable in differentiating primary salivary gland tumors from metastases known to express PAX2 and/or PAX8.
PubMed ID: 24771139
Article Size: <1 MB

Oncocytic Lipoadenoma of the Salivary Gland: A Clinicopathologic Analysis of 7 Cases and Review of the Literature

Lau SK, Thompson LD.
Head Neck Pathol. 2015 Mar;9(1):39-46.
Oncocytic lipoadenoma is an exceedingly uncommon neoplasm of the salivary gland composed of oncocytic epithelium and adipose tissue. Retrospective. Seven cases of oncocytic lipoadenoma were analyzed in order to further characterize the clinical and pathologic features of this rare tumor. The patients included six males and one female who ranged from 40 to 83 years of age (mean 62 years) at presentation. All tumors arose in the parotid gland. Grossly, the tumors were solitary, well circumscribed and had light brown to yellow cut surfaces. Histologically, the tumors were composed of an admixed population of oncocytes and adipocytes in varying proportions, with the lipomatous component ranging from 5 to 70 %. Other common features included the presence of serous acini, ductal elements, sebaceous glands, and a patchy chronic inflammation. Clinical follow up information, available in all cases, with a duration of 3-148 months (mean 57 months), showed no evidence of tumor recurrence. Due to its rarity, oncocytic lipoadenoma can pose problems in diagnosis, although the distinctive morphologic features of this neoplasm allow for separation from more commonly recognized oncocytic neoplasms of the salivary glands.
PubMed ID: 24737102
Article Size: 2.2 MB

Papillary Cystadenoma of Minor Salivary Glands: Report of 11 Cases and Review of the English Literature.Cases and Review of the English Literature.

Tjioe KC, de Lima HG, Thompson LD, Lara VS, Damante JH, de Oliveira-Santos C.
Head Neck Pathol. 2015 Sep;9(3):354-9.
Papillary cystadenoma is a rare, benign salivary gland tumor which is well-circumscribed, containing cystic cavities with intraluminal papillary projections. Only 19 cases arising within minor salivary glands (MnSG) from the oral cavity sites have been reported in the English literature (PubMed 1958-2014). We report 11 new cases of MnSG papillary cystadenomas in conjunction with a review of the literature. Demographic information, clinical and histologic features, treatment and prognosis are compiled and discussed for all 30 cases reported in the English literature.
PubMed ID: 25547059
Article Size: 1.2 MB

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. 2012 Jan;25(1):26-35.
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.
PubMed ID: 21892186
Article Size: 1 MB

Cervical Lymph Node Metastasis in High-Grade Transformation of Head and Neck Adenoid Cystic Carcinoma: A Collective International Review.

Hellquist H, Skálová A, Barnes L, Cardesa A, Thompson LD, Triantafyllou A, Williams MD, Devaney KO, Gnepp DR,, Bishop JA, Wenig BM, Suárez C,, Rodrigo JP,, Coca-Pelaz A, Strojan P, Shah JP, Hamoir M, Bradley PJ,, Silver CE, Slootweg PJ, Vander Poorten V,, Teymoortash A, Medina JE, Robbins KT, Pitman KT, Kowalski LP, de Bree R, Mendenhall WM, Eloy JA, Takes RP, Rinaldo A, Ferlito A.
Adv Ther. 2016 Mar;33(3):357-68.
Adenoid cystic carcinoma (AdCC) is among the most common malignant tumors of the salivary glands. It is characterized by a prolonged clinical course, with frequent local recurrences, late onset of metastases and fatal outcome. High-grade transformation (HGT) is an uncommon phenomenon among salivary carcinomas and is associated with increased tumor aggressiveness. In AdCC with high-grade transformation (AdCC-HGT), the clinical course deviates from the natural history of AdCC. It tends to be accelerated, with a high propensity for lymph node metastasis. In order to shed light on this rare event and, in particular, on treatment implications, we undertook this review: searching for all published cases of AdCC-HGT. We conclude that it is mandatory to perform elective neck dissection in patients with AdCC-HGT, due to the high risk of lymph node metastases associated with transformation.
PubMed ID: 26895332
Article Size: 3 MB

Adenoid cystic carcinoma of the head and neck — An update

Coca-Pelaz A, Rodrigo JP, Bradley PJ, Vander Poorten V, Triantafyllou A, Hunt JL, Strojan P, Rinaldo A, Haigentz M Jr, Takes RP, Mondin V, Teymoortash A, Thompson LDR, Ferlito A.
Oral Oncol. 2015 Jul;51(7):652-661.
This article provides an update on the current understanding of adenoid cystic carcinoma of the head and neck, including a review of its epidemiology, clinical behavior, pathology, molecular biology, diagnostic workup, treatment and prognosis. Adenoid cystic carcinoma is an uncommon salivary gland tumor that may arise in a wide variety of anatomical sites in the head and neck, often with an advanced stage at diagnosis. The clinical course is characterized by very late recurrences; consequently, clinical follow-up should extend at least >15 years. The optimal treatment is generally considered to be surgery with postoperative radiotherapy to optimize local disease control. Much effort has been invested into understanding the tumor’s molecular biological processes, aiming to identify patients at high risk of recurrence, in hopes that they could benefit from other, still unproven treatment modalities such as chemotherapy or biological therapy.
PubMed ID: 25943783
Article Size: 2.6 MB

Parotid Gland Nodular Fasciitis: A Clinicopathologic Series of 12 Cases with a Review of 18 Cases from the Literature.

Gibson TC, Bishop JA, Thompson LD.
Head Neck Pathol. 2015 Sep;9(3):334-44.
Nodular fasciitis (NF), very uncommon in the parotid gland, is a benign myofibroblastic proliferation that may be mistaken for other neoplastic proliferations. 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. Cases within the files of the authors’ institutions (retrospective) confined to the parotid gland were compared to cases reported in the English literature (Medline 1966–2014). The patients included five females and seven males, aged 11–70 years (mean 45.2 years). All patients presented with a mass lesion, present on average 1.9 months, without a documented history of trauma. The lesions were 0.7–5.2 cm (mean 2.2 cm). Seven patients had fine needle aspiration. The majority of the lesions were circumscribed (n = 9), composed of spindle-shaped to stellate myofibroblasts (MF) arranged in a storiform growth pattern, juxtaposed to hypocellular myxoid tissue-culture-like areas with extravasation of erythrocytes. Dense, keloid-like collagen (n = 7) and occasional giant cells were seen (n = 6). Mitotic figures (without atypical forms) were readily identifiable (mean 4/10 HPFs). By immunohistochemical staining, the MF were reactive with vimentin, actins, and calponin, while the histiocytes were reactive with CD68. All patients had surgical excision. One patient developed local recurrence (12 months later). All were alive and disease free at last follow-up, with a mean 133 months of follow-up. The principle differential diagnoses include fibrosarcoma, fibromatosis, pleomorphic adenoma, myoepithelioma, neurofibroma, schwannoma, solitary fibrous tumor, leiomyoma, fibrous histiocytoma and myxoma. NF of the parotid gland occurs in middle-aged patients who present with a mass (mean 2.2 cm) in the parotid gland of short duration (1.9 months). FNA misinterpretation frequently leads to excision. Separation from myoepithelial and mesenchymal lesions affecting the parotid gland results in appropriate management.
PubMed ID: 25472697
Article Size: 3.7 MB

Functional Histology of Salivary Gland Pleomorphic Adenoma: An Appraisal.

Triantafyllou A, Thompson LD, Devaney KO, Bell D, Hunt JL, Rinaldo A, Vander Poorten V, Ferlito A.
Head Neck Pathol. 2015 Sep;9(3):387-404.
The complex microstructure of salivary gland pleomorphic adenoma is examined in relation to function. Events related to secretion of macromolecules and absorption, responses to the altered microenvironment and controversies concerning epithelial-mesenchymal transition versus modified myoepithelial differentiation are explored. Their effects on tumor cell phenotypes and arrangements are emphasized. Heterotopic differentiation and attempts at organogenesis are also considered. The approach allows interpreting microstructure independently of histogenetic perceptions, envisaging the tumor cells as a continuum, endorsing luminal structures as the principal components, and defining pleomorphic adenoma as a benign epithelial tumour characterized by variable epithelial-mesenchymal transition, secretion/differentiation and metaplasia.
PubMed ID: 25380577
Article Size: 10.5 MB

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. 2012 Mar;6(1):21-31.
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.
PubMed ID: 22002440
Article Size: 1 MB

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.
PubMed ID: 10618601
Article Size: 1 MB

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.
PubMed ID: 8940996
Article Size: <1 MB

Mucocele: Retention and extravasation types.

Thompson LD.
Ear Nose Throat J. 2013 Mar;92(3):106-8.
FIRST PARAGRAPHS: The extravasation type is the most common mucocele, more common in children and young adults, with a peak in the second decade of life. The most common non-neoplastic lesion of salivary gland tissue is the mucocele (also called sialocele and ptyalocele). A mucocele is defined as the pooling of mucin in a cystic cavity. Two types of mucoceles are recognized: (1) the retention type, in which the mucin pooling is confined within a dilated excretory duct or cyst, and (2) the extravasation type, in which mucin is spilled into the connective tissues from a ruptured or traumatized salivary gland duct.
PubMed ID: 23532645
Article Size: <1 MB

Secretory carcinoma.

Thompson LD.
Ear Nose Throat J. 2016 Dec;95(12):474-476.
FIRST PARAGRAPH: Secretory carcinoma, first described as mammary analogue secretory carcinoma (MASC), is a recently described, distinctive malignant salivary gland tumor that is quite similar to secretory breast carcinoma, defined by the t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 fusion product. The vast majority of these tumors used to be included in the acinic cell carcinoma category.
PubMed ID: 27929593
Article Size: <1 MB

Salivary gland adenoid cystic carcinoma.

Thompson LD.
Ear Nose Throat J. 2015 Jul;94(7):262-4.

Tumors are poorly circumscribed with an infiltrative border, including extracapsular extension beyond the salivary gland.

FIRST PARAGRAPH: Adenoid cystic carcinoma (ACC) is a malignant epithelial salivary gland tumor with myoepithelial and ductal differentiation. Salivary gland tumors account for only about 5% of all head and neck carcinomas, with ACC the fourth most common salivary gland malignancy. ACC has a 3:2 female-to-male ratio. Patients tend to be adults, with a peak clinical presentation in the sixth decade. The tumors are found most frequently in the parotid gland but are also found in the palate, tongue, lip, and other sites in the upper aerodigestive tract and the rest of the body.

PubMed ID: 26214665
Article Size: <1 MB

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.
PubMed ID: 16408550
Article Size: <1 MB

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.
PubMed ID: 16696350
Article Size: <1 MB

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.
PubMed ID: 12472029
Article Size: <1 MB

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.
PubMed ID: 14702874
Article Size: <1 MB

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.
PubMed ID: 17580800
Article Size: <1 MB

Invited Review: An update on salivary gland pathology.

Müller S, Thompson LD.
Head Neck Pathol. 2013 Jul;7 Suppl 1:1-2.
FIRST PARAGRAPH: Over the past few decades, salivary gland tumor pathology has evolved. This includes recognition of newly defined entities as well as reclassification of other salivary gland tumors [1]. The development of genetic tests have shown that some salivary gland tumors have genetic abnormalities which are specific to a histologic type such as MECT1/ MAML2 gene fusion in mucoepidermoid carcinoma and PLAG1 or HMGA2 gene translocation in pleomorphic adenoma. Immunohistochemical studies have aided in both the diagnosis and prognosis of salivary gland tumors. High Ki67 is correlated with poor overall survival in mucoepidermoid carcinoma, acinic cell carcinoma and adenoid cystic carcinoma. High MUC1 in mucoepidermoid carcinoma is associated with higher grade and high recurrence while MUC4 is associated with a lower grade tumor and longer disease free survival. The finding of androgen receptors in salivary duct carcinoma has led to new therapies as these tumors are shown to be responsive to androgen deprivation therapy. Newly described salivary gland entities in the past 20 years include both benign (sclerosing polycystic adenosis, sialolipoma) and malignant (cribriform adenocarcinoma of the tongue, mammary analogue secretory carcinoma) tumors [2]. Newly recognized histologic variants of well-known salivary gland tumors have been reported, to include salivary-duct carcinoma, acinic cell carcinoma and epi-myoepithelial carcinoma.
PubMed ID: 23821215
Article Size: <1 MB