Warthin-like mucoepidermoid carcinoma of the parotid gland: Clinicopathological observation and literature review.

Warthin tumor (WT)-like mucoepidermoid carcinoma resembles the histologic pattern of WT and pathologists unaware of this possibility may misdiagnose it as WT with squamous and mucous epithelium metaplasia or WT malignant transfer into mucoepidermoid carcinoma. The present study reported a case of a 41-year-old Chinese female with a solitary mass in the left parotid gland. In this case, microscopic observation revealed prominent lymph node stroma and multiple cystic structures similar to those seen in WT. However, it lacked the two layers of oncocytic epithelial tissue characteristic of WT. Furthermore, fluorescence in situ hybridization detected MAML2 rearrangement in the case. Considering the histological findings, this case was diagnosed as WT-like mucoepidermoid carcinoma. The present case report provides pathological and clinical features to differentiate it from WT malignant transition into mucoepidermoid carcinoma, WT with squamous and mucous epithelium metaplasia and non-sebaceous lymphadenoma-like mucoepidermoid carcinoma. In conclusion, WT-like mucoepidermoid carcinoma as a special subtype of mucoepidermoid carcinoma has special histological characteristics, which required further observations and more case reports to clearly define this variant.

The molecular landscape of breast mucoepidermoid carcinoma.

Mucoepidermoid carcinoma (MEC) of the breast is an extremely rare salivary gland-type tumor characterized by epidermoid, basaloid, intermediate, and/or mucinous cells arranged in solid and cystic patterns. Despite their triple-negative phenotype, breast MECs are generally considered low-risk malignancies but their biology is largely unexplored; therefore, guidelines for clinical management are lacking. Here, we sought to characterize the molecular landscape of breast MECs. Thirteen cases were histologically reviewed, characterized for tumor-infiltrating lymphocytes (TILs), and were subjected to immunohistochemistry for programmed death-ligand 1 (PD-L1, clone 22C3), EGFR, and amphiregulin (AREG). Rearrangements in MAML2 and EWSR1 were investigated by fluorescent in situ hybridization. Targeted next-generation sequencing of 161 genes was performed on eight cases. Most MECs had low histological grade (n = 10, 77%), with the presence of TILs (n = 9/12; 75%) and PD-L1 combined positive score ranging from 10 to 20 (n = 4/6; 67%). All cases showed EGFR and AREG overexpression and were fusion negative. Enrichment of genetic alterations was observed in PI3K/AKT/mTOR and cell cycle regulation pathways, while only one case harbored TP53 mutations. This is the first study providing extensive molecular data on breast MECs and the largest collection of cases available to date in the literature. Breast MECs lack TP53 mutations found in high-grade forms of triple-negative breast cancers and MAML2 or EWSR1 rearrangements pathognomonic of salivary MECs. Triple-negativity and PD-L1 positivity suggest a window of opportunity for immunotherapy in these patients. The EGFR/AREG axis activation, coupled with the mutational patterns in PI3K/AKT/mTOR and cell cycle pathways warrants caution in considering MECs as low-risk neoplasms.

Molecular Profiling of Salivary Oncocytic Mucoepidermoid Carcinomas Helps to Resolve Differential Diagnostic Dilemma With Low-grade Oncocytic Lesions.

Oncocytic mucoepidermoid carcinoma (OMEC) is a rare but diagnostically challenging variant of mucoepidermoid carcinoma (MEC). OMEC is notable for differential diagnostic considerations that are raised as a result of overlap with other benign and low-grade oncocytic salivary gland tumors. Diffuse and strong immunoreactivity of p63 protein may be useful in distinguishing OMEC from its mimics. However, focal p63 staining can be present in benign oncytomas. Presence of mucin-containing cells, mucinous cystic formation, and foci of extravasated mucin are considered a hallmark of MEC. True mucocytes may be, however, very few and hardly discernable in OMECs. Recent evidence has shown that most MECs harbor gene fusions involving MAML2. A retrospective review of archived pathology files and the authors' own files was conducted to search for "low-grade/uncertain oncocytic tumor," "oncocytoma," and "oncocytic carcinoma" in the period from 1996 to 2019. The tumors with IHC positivity for p63 and/or p40, and S100 negativity, irrespective of mucicarmine staining, were tested by next-generation sequencing using fusion-detecting panels to detect MAML2 gene rearrangements. Two index cases from consultation practice (A.S. and A.A.) of purely oncocytic low-grade neoplasms without discernible mucinous cells showed a CRTC1-MAML2 fusion using next-generation sequencing, and were reclassified as OMEC. In total, 22 cases of oncocytic tumors, retrieved from the authors' files, and from the Salivary Gland Tumor Registry, harbored the MAML2 gene rearrangements. Presence of mucocytes, the patterns of p63 and SOX10 immunopositivity, and mucicarmine staining were inconsistent findings. Distinguishing OMEC devoid of true mucinous cells from oncocytoma can be very challenging, but it is critical for proper clinical management. Diffuse and strong positivity for p63 and visualization of hidden mucocytes by mucicarmine staining may be misleading and does not always suffice for correct diagnosis. Our experience suggests that ancillary studies for the detection of MAML2 rearrangement may provide useful evidence in difficult cases.

Pathologic grading of mucoepidermoid carcinomas of the salivary gland and its effect on clinicopathologic follow-up: an institutional experience.

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor. Differences inprognosis can be noted owing to the tumor grade determined using multiple grading schemes (2-tier: low- and high-grade vs. 3-tier: low-, intermediate-, and high-grade). We studied clinicopathologic features of MEC using a 3-tier grading system and retrospectively categorized cytologic diagnoses as per the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC).A total of 69 cases of MEC were identified, and most were seen in the parotid gland. Aggressive clinical behavior was seen in high-grade MEC compared with intermediate- and low-grade MEC. By fluorescence in situ hybridization (FISH) analysis, MAML2 rearrangements were seen in 78% of cases.The MSRSGC subcategorized the majority (63.8%) of MEC as salivary gland neoplasm of uncertain malignant potential, suspicious for malignancy, or malignant. Clustering intermediate- with low-grade cases did not significantly impact the clinical behavior. Both high-grade and oncocytic MEC can be MAML2 FISH negative.

Warthin-like Mucoepidermoid Carcinoma of the Parotid Gland: Unusual Morphology and Diagnostic Pitfalls.

BACKGROUND: Warthin-like mucoepidermoid carcinoma is a newly recognized rare entity and could be misdiagnosed as a benign Warthin tumor. We report such a case of a 36-year-old male who presented with a left parotid gland mass. CASE REPORT: Fine-needle aspiration showed features suggestive of Warthin tumor. Following parotidectomy, grossly there was a 1.6 cm well-circumscribed multilobular mass with focal areas of cystic change. Microscopically, at low magnification it had histological features resembling Warthin tumor, while lining with squamoid cells with scattered mucocytes demonstrating mild cytologic atypia was observed at high magnification. Immunohistochemically, the tumor cells were positive for p40, p63, cytokeratin 5/6, cytokeratin 7, and cancer antigen 125, but negative for discovered on GIST-1 (DOG1). Mucicarmine stain highlighted intracellular mucin within mucocytes. Rearrangement of mastermind like transcriptional coactivator 2 (MAML2) (11q21) gene was shown to be present in tumor cells by fluorescence in situ hybridization, supporting the diagnosis of a low-grade Warthin-like mucoepidermoid carcinoma. The patient was disease-free 12 months after surgery. CONCLUSION: Warthin-like mucoepidermoid carcinoma has not been widely recognized and can be misdiagnosed as Warthin tumor. Testing for MAML2 rearrangement provides essential support for diagnosis in difficult cases.

[Report of a mucoepidermoid breast carcinoma: Presentation of a rare entity]. / À propos d'un cas de carcinome muco-épidermoïde du sein : présentation d'une entité rare.

Salivary gland-like tumours are described in the breast but remain very rare and difficult to diagnose in this location. Only 37 cases of mucoepidermoid carcinoma have been described in the literature. We report the challenging diagnosis of a mucoepidermoid carcinoma sampled by core biopsy in a 51-year-old woman.

[Diagnostic and prognostic implications of MAML2 gene translocation in primary pulmonary mucoepidermoid carcinoma].

Objective: To investigate MAML2 gene-translocation in primary pulmonary mucoepidermoid carcinoma (PMEC) and pulmanary adenosquamous carcinoma, and the optimal diagnostic immunohistiochemical (IHC) panel in distinguishing PMEC from adenosqumous carcinoma. Methods: Twenty-four cases of PMEC and 44 adenosqumous carcinoma diagnosed in the Guangdong General Hospital were tested for MAML2 translocation by fluorescent in-situ hybridization (FISH) using tissue array. An IHC panel including TTF1, Napsin A, CK5/6, p63, p40 and Ki-67 was performed on the cohort. The clinical data for all cases were collected and all PMEC patients had follow-up information. Results: The patients' age ranged form 6 to 73 years, with a median age of 32 years. The male to female ratio was 1.4∶1.0. MAML2 translocation was found in 16/24 (66.7%) cases of PMEC whereas all 44 cases adenosqumous carcinoma were negative for translocation. All the cases of the PMEC were negative for TTF1 and Napsin A but positive for CK5/6, p63 and p40 in the intermediate cells and epidermal-like cells. In most PMEC cases, the Ki-67 expression index was lower than 10%. In contrast, most cases of adenosqumous carcinomas expressed TTF1 and Napsin A in the adenomatous component and CK5/6, p63 and p40 in the squamous component, which expression pattern was different from that of PMEC. Based on IHC staining, 2 cases of highly invasive ALK-positive adenocarcinoma mimicing PMEC were also found in the study. Conclusions: MAML2 gene translocation can be detected in about two-third of PMEC. Translocation of MAML2 gene and lower morphology grading are associated with good prognosis. The combined use of IHC antibodies panel is helpful to distinguish PMEC from the adenosqumous carcinoma and adenocarcinoma mimicing PMEC.

Expression of α-smooth muscle actin in benign and malignant salivary gland tumors: An immunohistochemical study.

BACKGROUND AND OBJECTIVES: Myoepithelial cells (ME) are known to contribute in the patterning of salivary gland neoplasms (SGN) and possess cytoplasmic smooth muscle actin (SMA) revealed by alpha SMA (α-SMA). The present study aimed to assess the expression of α-SMA in selected benign and malignant SGN (pleomorphic adenoma [PA], mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (ACC), and polymorphous low-grade adenocarcinoma (PLGA). MATERIALS AND METHODS: The intensity and pattern of expression of α-SMA were studied in 25 cases of SGN's ACC (n = 7), MEC (n = 8), PA (n = 8), and PLGA (n = 2), and correlated with the histological patterns. RESULTS: Maximum expression of α-SMA in the epithelial compartment was seen in ACC, followed by PA, whereas MEC and PLGA showed completely negative staining. The connective tissue expression was mild in ACC and MEC. The myxoid stroma of PA with "melting" pattern was weakly positive for α-SMA. The stroma in PLGA showed complete negativity. In ACC, α-SMA-positive cells were lining the cribriform spaces, small islands, and dispersed within large islands. Small nests showed complete positivity for α-SMA. INTERPRETATION AND CONCLUSION: In ACC, α-SMA expression supports the involvement of ME in epithelial organization explaining the histological patterns seen. In PA, the expression correlates with the predominantly secretory nature of ME. The absence of epithelial positivity in MEC and PLGA suggest that ME has less role to play in their histogenesis. The weak stromal positivity observed in MEC and ACC may be attributed to the positive immunoreactivity of myofibroblasts playing a role in modulating the course of SGN's.

"Pancreatic Mucoepidermoid Carcinoma" Is not a Pancreatic Counterpart of CRTC1/3-MAML2 Fusion Gene-related Mucoepidermoid Carcinoma of the Salivary Gland, and May More Appropriately be Termed Pancreatic Adenosquamous Carcinoma With Mucoepidermoid Carcinoma-like Features.

"Mucoepidermoid carcinoma (MEC)" has been accepted as a synonym for pancreatic adenosquamous carcinoma (ASC). Pancreatic ASC can show salivary gland-type MEC-like morphology. CRTC1/3-MAML2 fusion gene is a characteristic molecular feature of MEC of the salivary gland. We conducted this study to clarify whether the pancreatic ASC with salivary gland-type MEC-like morphology (Pan-MEC) is a pancreatic counterpart of salivary gland-type MEC (Sal-MEC). We retrospectively analyzed 37 pancreatic ASCs including 16 Pan-MECs and 21 tumors without MEC-like features (ASC-NOS [not otherwise specified]), and we investigated (1) clinicopathologic features, (2) the presence of CRTC1/3-MAML2 fusion gene by reverse transcription polymerase chain reaction, (3) the presence of rearrangement of MAML2 gene by fluorescence in situ hybridization, and (4) mucin core proteins by immunohistochemistry. We also compared 16 Pan-MECs with 20 Sal-MECs by immunohistochemistry for mucin core protein. There were no significant differences of any clinicopathologic characteristics and survival analysis between the Pan-MECs and ASCs-NOS. Of note, the pancreatic ASCs (including Pan-MEC and ASC-NOS) were significantly more aggressive than conventional pancreatic ductal adenocarcinoma. In addition, all Pan-MECs were histologically high-grade. CRTC1/3-MAML2 fusion gene and MAML2 gene rearrangement were not detected in any ASCs including Pan-MECs. There were significant differences of MUC5AC and MUC6 between the Pan-MECs and Sal-MECs, but no significant differences of mucin core protein between the Pan-MECs and pancreatic ASCs-NOS. Pan-MEC is histologically and biologically high-grade and unrelated to CRTC1/3-MAML2 fusion gene, unlike Sal-MEC which is related to CRTC1/3-MAML2 fusion gene. Pan-MEC is not a pancreatic counterpart of CRTC1/3-MAML2 fusion gene-related Sal-MEC.

Mucoepidermoid carcinoma with extensive spindled morphology and melanocytic marker expression.

Mucoepidermoid carcinoma (MEC) is the most common malignant neoplasm of the salivary gland. Albeit common, histologic variants have rarely been noted in MEC. Here, we report a 49-year-old man with a sublingual gland tumor. Histologically, the tumor was composed of spindle cells arranged in interlacing fascicules or globular nests. A few bland small glands containing mucous cells were also scattered. The spindle tumor cells completely lacked immunoreactivity for cytokeratin, and exhibited immunoreactivity for vimentin, S-100, HMB-45, Melan A, and SOX10. The tumor was initially suspected to be clear cell sarcoma, malignant melanoma, or perivascular epithelioid cell tumor with a few entrapped nonneoplastic duct epitheliums. However, reverse-transcription polymerase chain reaction revealed the CRTC3-MAML2 fusion gene product diagnostic of MEC. In fact, a very minor component of the epithelial cells was reminiscent of conventional MEC, whereas major spindled tumor cells possessed markedly altered differentiation. This is the first case report of MEC with extensive spindled morphology and melanocytic marker expression.

Reevaluation of MAML2 fusion-negative mucoepidermoid carcinoma: a subgroup being actually hyalinizing clear cell carcinoma of the salivary gland with EWSR1 translocation.

Hyalinizing clear cell carcinoma (HCCC) is a rare salivary gland tumor with a specific EWSR1-ATF1 fusion gene and can have mucin production. Mucoepidermoid carcinoma (MEC) with a clear cell component is its morphologic mimic. Using MAML2 fluorescence in situ hybridization (FISH), a total of 49 MEC cases were separated into MAML2 fusion-positive (32 cases) and MAML2 fusion-negative groups (17 cases). This study used EWSR1 FISH to investigate MAML2 fusion-negative cases to identify previously unrecognized HCCC. Among 17 MAML2 fusion-negative cases, 3 had rearrangement of the EWSR1 gene and were reclassified as HCCC. Including 5 previously diagnosed HCCC cases, these 8 HCCC cases had a male-to-female ratio of 1:7, and most (7/8) tumors arose from oral minor salivary glands in the oral cavity (tongue base and palate). EWSR1-ATF1 fusion was confirmed by FISH in all 8 HCCC cases. The histologic features between genetically confirmed HCCC and MEC were compared. HCCC was significantly associated with minor salivary gland involvement, a discrepancy between low-grade cytology and intermediate- to high-grade histology using the MEC grading system, and absence of both epidermoid cells with abundant cytoplasm and goblet cells lining cysts or forming clusters. Clear cells and a hyalinized stroma were not specific for HCCC. HCCC may be erroneously classified as MEC because clear cells may be a minor histologic component and mucin production is not uncommon. Previously diagnosed MEC cases should be reevaluated, especially those arising from minor salivary glands or without MAML2 fusion. Careful histologic evaluation with supporting molecular testing can facilitate pathologic diagnoses.

SOX10-positive salivary gland tumors: a growing list, including mammary analogue secretory carcinoma of the salivary gland, sialoblastoma, low-grade salivary duct carcinoma, basal cell adenoma/adenocarcinoma, and a subgroup of mucoepidermoid carcinoma.

Transcription factor SRY-related HMG-box 10 (SOX10) is an important marker for melanocytic, schwannian, myoepithelial, and some salivary gland tumors. The aim of this study was to investigate SOX10 expression more thoroughly in the salivary gland neoplasms, including mammary analogue secretory carcinoma and hyalinizing clear cell carcinoma harboring specific genetic rearrangements. A new rabbit monoclonal anti-SOX10 antibody (clone EP268) was used to examine SOX10 expression in 14 different types of salivary gland tumors. We found that acinic cell carcinoma (AciCC), adenoid cystic carcinoma, mammary analogue secretory carcinoma (MASC), epithelial-myoepithelial carcinoma, low-grade salivary duct carcinoma, sialoblastoma, basal cell adenocarcinoma, basal cell adenoma, and pleomorphic adenoma were SOX10 positive. Salivary duct carcinoma, lymphoepithelial carcinoma, hyalinizing clear cell carcinoma, and oncocytoma were SOX10 negative. Earlier, mucoepidermoid carcinoma (MEC) was considered a SOX10-negative tumor. This study identified a subgroup of SOX10-positive MEC cases with characteristic polygonal epithelial cells, pale-to-eosinophilic cytoplasm, and colloid-like dense eosinophilic material. Our data show SOX10 expression can be observed in salivary gland tumors with either one of the 4 cell types: acinic cells, cuboidal ductal cells with low-grade cytologic features, basaloid cells, and myoepithelial cells. In this article we thoroughly evaluated SOX10 expression in salivary gland tumors. SOX10 is useful in the differential diagnosis between myoepithelial carcinoma with clear cell features and hyalinizing clear cell carcinoma. It can also be used to discriminate low-grade salivary duct carcinoma from high-grade ones. Pathologists should be cautious with the interpretation of SOX10 positivity in salivary gland tumors, and correlation with histologic feature is mandatory.

[Salivary gland-type lung tumor: An update]. / Tumeurs de type glandes salivaires du poumon.

"Salivary gland-type" tumors arising from the bronchi and lung are rare but not exceptional entities. They are mostly represented by malignant entities such as cystic adenoid carcinoma, mucoepidermoid carcinoma and epithelial/myoepithelial carcinoma. Benign tumors are rare, mainly encompassing pleomorphic adenomas, which are to differentiate from mucous gland adenomas, another entity arising specifically from the peri-bronchial glands. These tumours develop in the proximal bronchi and are not associated with smoke abuse. Their main treatment is surgery. It is important to differentiate them from other broncho-pulmonary tumours as they do not share the same prognosis and therapeutic. This article will review the WHO 2015 classification of these tumours as well as recent updates from the literature to help define diagnosis criteria for these uncommon entities.

Expression of SOX10 in Salivary Gland Oncocytic Neoplasms: A Review and a Comparative Analysis with Other Immunohistochemical Markers.

OBJECTIVES: We evaluated SOX10 (SRY-related HMG-box 10) in differentiating acinic cell carcinoma (AciCC) from other salivary gland neoplasms with oncocytic features on fine-needle aspiration cell blocks (FNA CB) and compared its performance to DOG1 (discovered on gastrointestinal stromal tumor 1). MATERIAL AND METHODS: 35 FNA CB of oncocytic salivary gland neoplasms, i.e. 13 cases of AciCC, 16 of Warthin tumor (WT), 3 of mucoepidermoid carcinoma (MEC) and 3 of oncocytoma (ONC), and 75 salivary gland resections, i.e. 26 AciCC, 7 WT, 36 MEC, 3 ONC, 2 mammary analog secretory carcinomas (MASC) and 1 papillary cystadenoma were stained for SOX10 and DOG1. RESULTS: None of the benign oncocytic neoplasms were immunoreactive for SOX10 on CB or resection, similar to DOG1. On CB, 61.5 and 77% of AciCC were positive for SOX10 and DOG1, respectively. All surgically resected AciCC cases were positive for SOX10 and DOG1; other malignant oncocytic lesions such as MEC and MASC demonstrated variable SOX10 and DOG1 staining. CONCLUSION: The use of SOX10 may increase the diagnostic accuracy of oncocytic lesions on FNA. In this context, SOX10 is equivalent to DOG1 in ruling out benign lesions such as WT and ONC; however, negative results for SOX10 as well as DOG1 do not favor a benign diagnosis since MEC is often negative for both markers.

Warthin-like Mucoepidermoid Carcinoma: A Combined Study of Fluorescence In Situ Hybridization and Whole-slide Imaging.

There has been some debate as to whether a subset of metaplastic Warthin tumors (mWTs) harbor the mucoepidermoid carcinoma (MEC)-associated CRTC1-MAML2 fusion. We analyzed 15 tumors originally diagnosed as mWT (mWT-like tumors), 2 of which had concurrent MECs. We looked for the CRTC1/3-MAML2 fusion transcripts and performed immunohistochemistry for p63 and fluorescence in situ hybridization (FISH) for the MAML2 split. To localize MAML2 split-positive cells at the cellular level, whole tumor tissue sections were digitalized (whole-slide imaging [WSI]). The CRTC1-MAML2, but not CRTC3-MAML2 was detected in 5/15 mWT-like tumors. FISH-WSI results showed that all epithelial cells harbored the MAML2 split in fusion-positive mWT-like tumors and were totally negative in fusion-negative mWT-like tumors. A review of the hematoxylin and eosin-stained slides showed that morphology of the "metaplastic" epithelium was virtually indistinguishable between fusion-positive and fusion-negative tumors. However, oncocytic bilayered tumor epithelium, characteristic to typical WT, was always found somewhere in the fusion-negative tumors but not in the fusion-positive tumors. This distinguishing histologic finding enabled 5 pathologists to easily differentiate the 2 tumor groups with 100% accuracy. The age and sex distribution of fusion-positive mWT-like tumor cases was similar to that of fusion-positive MEC cases and significantly different from those of fusion-negative mWT-like tumor and typical WT cases. In addition, only fusion-positive mWT-like tumors possessed concurrent low-grade MECs. In conclusion, a subset of mWT-like tumors were positive for the CRTC1-MAML2 fusion and had many features that are more in accord with MEC than with WT. The term Warthin-like MEC should be considered for fusion-positive mWT-like tumors.

Adenoid cystic carcinoma of the right main bronchus showing squamous differentiation and mimicking mucoepidermoid carcinoma: a case report.

Complete dissection of tracheobronchial adenoid cystic carcinoma (TACC) by surgery alone is sometimes difficult and has a greater propensity than tracheobronchial mucoepidermoid carcinoma (TMEC) for its surgical margin to become positive. In addition, TACC is more likely to present distant metastases than TMEC. Considering these facts, TACC and TMEC should be differentiated based on histopathological examination of biopsy specimens. Herein, we present a case of 54-year-old woman with a tumor in the right main bronchus, whose biopsy specimen was difficult to diagnose as TACC or TMEC. The specimen from the rounded protrusion of the tumor showed squamous differentiation, along with the presence of glandular and basaloid cells, making morphological examination alone ineffective in rendering a definite diagnosis. Thus, the addition of immunohistochemical analysis, αSMA and CD43 expression in basaloid cells and c-kit expression in glandular cells, was useful for accurately diagnosing TACC in this case. The squamous component was considered to be neoplastic because of its increased expression of cyclin D1 and overexpression of p16. The surgically resected specimen contained typical morphology of ACC, and the diagnosis of TACC was definitely confirmed.

Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid gland in a male patient: a case report and literature review.

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) was first described by Chan et al in 1991. It is characterized by nest or strands of epidermoid tumor cells with squamous differentiation, rare mucous cells, prominent sclerotic stroma, eosinophilic and lymphoplasmacytic infiltration, and a background of chronic lymphocytic thyroiditis in the non-neoplastic thyroid gland. It is important to recognize SMECE of thyroid and differentiate it from squamous cell carcinoma or other neoplasms with squamous differentiation/metaplasia. In published cases, the SMECE of thyroid gland predominantly occurs in women. We report a case of SMECE of thyroid in a 45-year-old male patient. All cases in male patients were Caucasian described in English literature, and our case is the first one in Asian.

An unsuspected diagnosis of mucoepidermoid carcinoma of lung.

A 40-year-old man with dry cough for 5 years, no history of smoking, and a right lung mass, underwent a radiologically-guided core needle biopsy. The initial histopathological diagnosis was adenocarcinoma of the lung. After lobectomy, the final pathology was mucoepidermoid carcinoma. The initial biopsies sampled only a mucinous component of the tumor, leading to a diagnosis of adenocarcinoma. The possibility of mucoepidermoid carcinoma could be suspected on the basis of clinical history and radiologic evidence. This unusual case highlights the importance of adequate multidisciplinary review of patients who increasingly receive pathologic diagnoses based on ever smaller tissue samples.

Histopathologic, immunophenotypic and cytogenetic features of pulmonary mucoepidermoid carcinoma.

Pulmonary mucoepidermoid carcinoma is an uncommon but distinctive manifestation of mucoepidermoid carcinoma. Pulmonary mucoepidermoid carcinoma occurs in adults and children and can cause diagnostic problems, especially in small biopsies. Few studies have characterized the histologic and immunophenotypic features of pulmonary mucoepidermoid carcinoma. t(11;19)(q21;p13) is considered disease-defining for mucoepidermoid carcinoma; its significance in pulmonary mucoepidermoid carcinoma warrants further study. Forty three pulmonary mucoepidermoid carcinomas were re-reviewed and graded according to the Brandwein grading system for mucoepidermoid carcinoma. Four cases were excluded because of a split opinion between pathology report and re-review. These cases were negative for MAML2 rearrangement by FISH. TTF-1, napsin A, p40 and p63 immunostains were scored: 0 (negative), 1 (1-25% tumor cells), 2 (26-50%), 3 (51-75%) or 4 (>75%). FISH to detect MAML2 rearrangement used a MAML2-11q21 break-apart probe. Thirty nine pulmonary mucoepidermoid carcinoma (4 low, 30 intermediate, 5 high grade) contained mucous, epidermoid and intermediate cells and lacked keratinization and in situ carcinoma of the overlying epithelium. All cases with available gross description (n=22) had a central/endo- or peribronchial location. All 25 cases tested for immunohistochemistry were positive (scores 1-4) for p63; 23 also expressed p40. In six cases, the p63 score was higher than p40. TTF-1 and napsin were uniformly negative in all 25 cases. MAML2 rearrangement was identified by FISH in each of the 24 cases tested (3 low, 19 intermediate, 2 high grade). Clinical history was available in 29 patients (15 men) (median age, 48 years) with follow-up in 24 (median, 8.4 years). Five patients died of unrelated causes; one developed metastatic pulmonary mucoepidermoid carcinoma. In conclusion, features helpful in distinguishing pulmonary mucoepidermoid carcinoma from other lung cancers include its central/endo- or peribronchial location together with the presence of mucous cells, p63 expression, lack of keratinization and MAML2 rearrangement. TTF-1 and napsin are typically not expressed.

Toll-like receptor 9 expression in mucoepidermoid salivary gland carcinoma may associate with good prognosis.

BACKGROUND: Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. Although several biomarkers have been evaluated, histological grade remains the most valuable prognostic marker. Toll-like receptor 9 (TLR9) is an immune receptor recognizing microbial DNA. Its expression associates with prognosis or cancer properties in several cancers. This study examined the role of TLR9 in MEC. METHODS: Sixty patients with salivary gland MEC were collected from two Finnish university hospitals, and tumor samples were stained for TLR9. Salivary gland high-grade MEC cell line (UT-MUC-1) was cultured to assess TLR9 and MMP-13 expression. The function of TLR9 was studied in vitro using traditional Matrigel(®) invasion assay and novel human myoma organotypic model. RESULTS: Cancer-specific survival was related with tumor grade (P = 0.01), and there were no deaths in patients with low-grade MEC. TLR9 was expressed in 56 of 60 (93%) tumors. High TLR9 expression indicated better survival in the patient series (P = 0.002) and showed a trend for association with lower disease stage (P = 0.06) and higher differentiation grade (P = 0.068). In multivariate analysis, TLR9 expression was prognostically insignificant due to heavy correlation to disease stage and higher gradus. Treating UT-MUC-1 cells with TLR9 ligand CpG in vitro induced MMP-13 expression and invasion in Matrigel(®) invasion assay, whereas decreased invasion was seen in myoma organotypic model. CONCLUSION: Functional TLR9 is present in salivary MEC, and high level of expression may indicate good prognosis. However, more studies are needed to evaluate biological consequences of TLR9 interaction in tumor cells.