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.

KRAS codon 12 mutations characterize a subset of de novo proliferating "metaplastic" Warthin tumors.

Warthin tumor (WT; synonym: cystadenolymphoma) represents one of the most frequent salivary gland tumors with a frequency equaling or even outnumbering that of pleomorphic adenomas in some series. Histologically, the tumor displays tall columnar oncocytic cells, arranged into two cell-thick layers lining variably cystic glands within an organoid lymphoid stroma. Tumors with exuberant squamous metaplasia in response to FNA-induced or other types of tissue injury/infarction have been referred to as "metaplastic WTs." However, the same terminology was used for tumors with variable mucinous cell and solid or stratified epidermoid proliferations (occasionally mimicking mucoepidermoid carcinoma), although the "metaplasia concept" has never been proven for the latter. We herein investigated 22 WTs showing prominent mucoepidermoid-like or solid oncocytoma-like proliferations without prior FNA or histological evidence of infarction/ trauma using the TruSight Tumor 15 gene panel and KRAS pyrosequencing. As a control, we tested 11 conventional WTs. No statistically significant differences were observed between the two subcohorts regarding patient's age and tumor size. Six of 22 (27%) proliferating/ metaplastic WTs revealed oncogenic KRAS mutations clustering at codon 12 (exon 2), while all conventional tumors lacked these mutations. Our findings are in line with a neoplastic nature of the epidermoid/ mucoepidermoid proliferations in non-injured "metaplastic" Warthin tumors. We propose the descriptive term "de novo proliferating Warthin tumor" for this variant to distinguish it from infarcted/inflamed genuine metaplastic Warthin tumor.

Warthin-like mucoepidermoid carcinoma of the parotid gland: a clinicopathological analysis of two cases.

Mucoepidermoid carcinoma (MEC) is the most common malignant tumour of the salivary gland, primarily involving the parotid gland. Here, the cases of two patients, aged 47 and 67 years, respectively, who underwent surgery for pathologically confirmed Warthin-like MEC of the parotid gland between January 2019 and December 2019 in Anyang Tumour Hospital, are described. In each case, the tumour consisted of epithelial and lymphoid cell components, covered with two or more layers of epithelium, with visible scattered mucous cells, and lymphoid stroma with a large number of lymphocytes and germinal centres formed. Most importantly, the tumours lacked the well-organized, bilayered oncocytic epithelial structure that is characteristic of Warthin's tumour. Mastermind like transcriptional coactivator 2 (MAML2) gene rearrangements were identified in the tumour cells using break-apart fluorescence in situ hybridization (FISH) probes, confirming the diagnosis of Warthin-like MEC. Post-operatively, patients have remained disease free for 31 and 27 months, respectively. Warthin-like MEC of the parotid gland is rare and is often misdiagnosed as metaplastic Warthin's tumour. Diagnosis depends mainly on the unique clinicopathologic features together with FISH analyses.

Primary Warthin's-like adenocarcinoma of the lung: A clinicopathological, immunohistochemical, and molecular analysis of three cases.

Three cases of primary pulmonary adenocarcinoma with prominent lymphoid stroma and papillary features mimicking Warthin's tumor are presented. The patients are two women and one man ages 52, 62, and 74 years respectively. Clinically, the patients presented with non-specific symptoms of cough, dyspnea, and chest pain. Imaging showed the presence of an intrapulmonary mass in the right lower, right upper and left lower lobe. All patients underwent lobectomy. Histologically, the tumors were characterized by the presence of and oncocytic papillary growth pattern embedded in a lymphoid rich background. Immunohistochemical stains for TTF-1, keratin 7, and beta-catenin were positive in the epithelial component, while CD20 showed strong positive staining in the lymphoid component. In addition, CD4 and CD8 also showed positive staining in a ratio of 3-4:1, EBER was negative. Kras mutations with wild type EGFR were identified in one case. Clinical follow-up ranging from 8 to 24 months was obtained showing that all patients are alive without recurrence. The cases herein presented represent an unusual histological variant of primary lung adenocarcinoma, which closely mimics Warthin's tumor.

Cutaneous Lymphadenoma Is a Distinct Trichoblastoma-like Lymphoepithelial Tumor With Diffuse Androgen Receptor Immunoreactivity, Notch1 Ligand in Reed-Sternberg-like Cells, and Common EGFR Somatic Mutations.

The term "cutaneous lymphadenoma" was coined in this journal for an unusual lymphoepithelial cutaneous adnexal neoplasm, possibly with immature pilosebaceous differentiation. Some authors further proposed that cutaneous lymphadenoma was an adamantinoid trichoblastoma. However, although a hair follicle differentiation is widely accepted, the fact that this is a lymphoepithelial tumor is not appropriately explained by the trichoblastoma hypothesis. Our goal was to further clarify the phenotypic and genotypic features of cutaneous lymphadenoma in a series of 11 cases. Histologically, a lobular architecture surrounded by a dense fibrous stroma was present in all cases. The lobules were composed of epithelial cells admixtured with small lymphocytes and isolated or clustered large Reed-Sternberg-like (RS-L) cells. The epithelial cells were diffusely positive for the hair follicle stem cell markers CK15, PHLDA1, and for androgen receptor. No immunostaining for markers of sebaceous differentiation was found. Intraepithelial lymphocytes were predominantly CD3+, CD4+, FoxP3+ T cells. RS-L cells showed both strong Jagged-1 and Notch1 cytoplasmic immunostaining. Androgen-regulated NKX3.1 nuclear immunostaining was present in a subset of large intralobular cells in all cases. Double immunostaining showed coexpression of NKX3.1 and CD30 in a subset of RS-L cells. No immunostaining for lymphocytic or epithelial markers was present in RS-L cells. EGFR, PIK3CA, and FGFR3 somatic mutations were found by next-generation sequencing in 56% of the cases. We consider that cutaneous lymphadenoma is a distinct benign lymphoepithelial tumor with androgen receptor and hair follicle bulge stem cell marker expression, RS-L cell-derived Notch1 ligand, and common EGFR gene mutations.

Expressions of CXCL12, CXCL10 and CCL18 in Warthin tumors characterized pathologically by having a lymphoid stroma with germinal centers.

The Warthin tumor is a benign neoplasm of the salivary glands, histologically, the tumor has an oncocytic epithelial component forming uniform rows of cells surrounded by cystic spaces associated with a lymphoid stroma often showing the presence of germinal centers. The lymphoid stroma is a representative microscopic finding. If this lymphocytic accumulation is active, some sort of transmitter should exist between the Warthin tumor cells and lymphocytes. C-X-C motif chemokine ligand (CXCL12) 12, CXCL10 and C-C motif chemokine ligand 18 (CCL18) are a chemoattractant for lymphocytes in vivo. There is no report on the relationship between these chemokines and Warthin tumors. In this study, we investigated these chemokines expressions in 20 Warthin tumors using immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). For comparison, we also enrolled samples of pleomorphic adenoma, which is another benign salivary gland tumor type without prominent lymphocytic infiltration. All Warthin tumors were immunopositive for CXCL12 and CXCL10, and these reactivities were diffuse. Meanwhile, the majority of pleomorphic adenomas were immunonegative for CXCL12 (95%), CXCL10 (80%) and CCL18 (85%). Warthin tumor and pleomorphic adenoma cases were significantly different in these immunostaining expressions (CXCL12, p<0.001; CXCL10, p<0.001; CCL18, p=0.024). We examined CXCL12, CXCL10 and CCL18 mRNA expressions of 3 representative Warthin tumor samples, each having these chemokines immunopositive areas detected by RT-PCR. Finding CXCL12 and CXCL10 expressions indicate that these chemokines may play a part in the formation of a lymphoid stroma within Warthin tumors. In regards to this phenomenon, the participation of CCL18 might be restrictive compared to CXCL12 and CXCL10.

The significance of mucinous metaplasia in Warthin tumor: a frequent occurrence and potential pitfall.

Mucinous metaplasia in Warthin tumor (WT) is a recognized phenomenon. Nevertheless, its presence can create a diagnostic challenge in the distinction from the newly proposed variant of mucoepidermoid carcinoma (MEC), Warthin-like MEC. In this study, we evaluated the significance and diagnostic relevance of mucinous metaplasia in WTs. A total of 30 WTs diagnosed based on resection specimens formed the basis of this retrospective study. Mucicarmine staining was performed to identify mucinous metaplasia, and fluorescence in situ hybridization (FISH) analysis was used to detect MAML2 gene rearrangement. After review, one MAML2 rearranged case was reclassified as Warthin-like MEC as the classic bilayered epithelium in WT was not identified. The diagnosis of WT was confirmed in the remaining 29 cases. Mucinous metaplasia was encountered in 24 WTs (83%), with 14% (4/29) having an abundant amount. We found that mucinous metaplasia correlated with tumor size (p < 0.05). Age and sex distribution were similar in WT cases with or without mucinous metaplasia. In addition, neither the presence of squamous metaplasia nor the time interval between fine-needle aspiration and surgery was related to mucinous metaplasia (p > 0.05). The MAML2 FISH analyses performed in 18 WTs with variable amounts of mucinous metaplasia were negative for rearrangement. In conclusion, mucinous metaplasia is fairly common in WTs and shows a significant correlation with tumor size. Therefore, caution should be taken to avoid overinterpretation of WT with mucinous metaplasia as MEC in cases showing the classic bilayered oncocytic lining epithelium.

MAML2 rearrangement as a useful diagnostic marker discriminating between Warthin tumour and Warthin-like mucoepidermoid carcinoma.

Warthin tumour is the second most common benign neoplasm of salivary glands. Despite its relatively characteristic histology, it may sometimes mimic other lesions. Here, we report two female non-smoker patients diagnosed with low-grade mucoepidermoid carcinoma with oncocytic epithelium and prominent lymphoid (Warthin-like) stroma and with molecularly confirmed MAML2 rearrangement. In addition, we screened a consecutive series of 114 Warthin tumour cases by means of MAML2 break apart fluorescence in situ hybridization to assess its value in differential diagnosis. MAML2 rearrangement was detected in both mucoepidermoid carcinoma cases, while all Warthin tumours were negative. Taking into account the literature data, Warthin-like mucoepidermoid carcinomas are more frequently observed in women, while a slight male predominance and smoking history are typical for Warthin tumour. In addition, the patients with Warthin-like mucoepidermoid carcinoma were significantly younger than those with Warthin tumour. To conclude, Warthin-like mucoepidermoid carcinoma may usually be suspected based on histology, while the diagnosis can be confirmed by means of molecular assays such as FISH. The investigation of MAML2 status is particularly advised when Warthin tumour is considered in a young, non-smoking, female patient.

Cytological features of warthin-like papillary thyroid carcinoma: A case report with review of previous cytology cases.

Warthin-like papillary thyroid carcinoma (WLPTC) is a rare morphological variant of papillary thyroid carcinoma which mimics various benign and malignant lesions on thyroid aspiration cytology. As correct cytological diagnosis is the cornerstone for appropriate patient management, awareness of the salient cytomorphological characteristics of this tumor is essential. Here, we present cytological features of a case of WLPTC along with discussion of the common differential diagnoses and a brief review of the literature to ascertain the most consistent cytological findings of WLPTC. The present case also harboured BRAFV600E mutation which is the commonest molecular alteration seen in WLPTC.

Immunohistochemical Staining of Histological Fragments Derived from Salivary Gland Tumour Fine-Needle Biopsy Aspirates.

OBJECTIVES: The aim of this study was to describe a method for analysing histological fragments derived from fine- needle aspirate biopsy (FNAB) of salivary gland tumours (SGTs), and to evaluate the use of immunohistochemistry (IHC) on them. STUDY DESIGN: We reviewed all 509 FNAB pathology reports taken from SGTs at Helsinki University Hospital, Finland, between 1999 and 2009. In 51% of the cases (n = 209) "histo-fragments" had been obtained and 31 had been further analysed by IHC. Of these, 25 (81%) were available for review. We evaluated the benefit of IHC by relating its added value to the preoperative cytological diagnosis and its accuracy compared with the postoperative histological diagnosis. RESULTS: Most of the samples analysed by IHC were assigned a malignant diagnosis, with 12 different types of malignancy represented. IHC was advantageous in 76% of the cases. In the 108 studies using IHC in this series, antibodies to 36 different antigens were used. CONCLUSION: Analysis of histo-fragments in FNABs using IHC can be valuable in specific differential diagnostics and raises diagnostic accuracy in SGTs.

Genetic polymorphisms in UDP-glucuronosyltransferase 1A6 and 1A7 and the risk for benign Warthin's tumors of the parotid gland.

BACKGROUND: Warthin's tumors of the parotid gland are associated with smoking, whereas pleomorphic adenomas are not. Genetic polymorphisms in biotransformation enzymes, involved in detoxification of toxins and carcinogens in cigarette smoke, might modify the corresponding enzyme activity and influence detoxifying capacity. We hypothesize that these genetic polymorphisms may influence the individual risk for Warthin's tumor, but not for pleomorphic adenomas. METHODS: Blood from 146 patients with benign parotid gland tumors and 437 controls were investigated for polymorphisms in several biotransformation enzymes. Based on these polymorphisms, patients and controls were divided according to predicted enzyme activity (low, intermediate, and high). RESULTS: Prevalence of predicted intermediate and high activity UGT1A7 and UGT1A6 genotypes was significantly higher in the patients with Warthin's tumors, but not in patients with pleomorphic adenomas, compared with healthy controls. CONCLUSION: Predicted intermediate and high activity UGT1A7 and UGT1A6 genotypes are associated with an increased risk for Warthin's tumor. © 2015 Wiley Periodicals, Inc. Head Neck 38: E717-E723, 2016.

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.

Occult oncocytic papillary thyroid carcinoma with lymphoid stroma (Warthin-like tumor): report of a case with concomitant mutations of BRAF V600E and V600K.

Warthin-Like tumor of the thyroid is a recently described rare variant of papillary thyroid cancer. The distinct histological feature of this variant is papillary architecture lining oncocytic epithelial cells with nuclear characteristics of papillary carcinoma, accompanied by prominent lymphocytic infiltration in the papillary stalks. Here, we present a case of occult Warthin-like papillary thyroid carcinoma, 0.5-cm in maximum dimension, underwent left thyroid lobectomy in a 65 years old Chinese woman. In this case, there was no extrathyroid extension, vascular invasion and lymphatic metastasis, as well as no complication of lymphocytic thyroiditis. Immunohistochemistry staining revealed that the tumor cells were positive for Leu-M1, HBME-1, 34ßE12, and MIB-1 labeling index was low. RET/PTC expression was absent in tumor cells. Furthermore, activated point mutations of BRAF V600E and V600K were concurrently detected by DNA sequencing. Further studies are needed to elucidate the prevalence and role of BRAF(V600K) mutation in papillary thyroid carcinoma, and long-term follow-up for the patient is needed to clarify the biological behavior of this variant with dual BRAF mutations.

99mTcO4- accumulation in scintigraphy and expression of Na+/I- symporter in salivary gland tumors.

OBJECTIVE: Warthin's tumors and oncocytomas show exceptionally good (99m)TcO4(-) (Tc) accumulation images in Tc scintigraphy. However, the mechanism of Tc accumulation in these tumors remains unclear. Sodium-iodide symporter (NIS) is a plasma membrane protein expressed in the thyroid, lactating breast, stomach and salivary glands; it facilitates uptake of I(-) and Tc. We hypothesized that Warthin's tumor cells and oncocytomas may also express NIS, which would promote uptake of Tc. We examined NIS localization and the mechanism of Tc accumulation in various salivary gland tissues. METHODS: Immunohistological localization of NIS was performed for 19 tumors from 18 patients who underwent preoperative Tc scintigraphy. Expression of mRNA for NIS in the normal salivary gland, Warthin's tumors and pleomorphic adenomas was analyzed by real-time PCR. RESULTS: In normal salivary glands, striated duct cells were strongly immunostained by anti-NIS antibodies. In Warthin's tumors, eosinophilic epithelial cells exhibited positive immunostaining, but their staining was varied among the cases. Furthermore, all Tc-positive specimens were NIS-positive, and all Tc-negative specimens were NIS-negative. Real-time PCR showed that NIS mRNA expression was detectable in normal salivary glands and Warthin's tumor cells. The expression was significantly higher in normal salivary glands compared with Warthin's tumor cells and pleomorphic adenoma. CONCLUSION: Tc-positive salivary glands expressed NIS. Our findings suggest that Tc accumulation in Warthin's tumors and oncocytomas is due to poorer Tc excretory function compared with normal salivary gland tissues, in addition to active uptake of (99m)TcO4(-) via NIS.

Genomic alterations in Warthin tumors of the parotid gland.

Despite the fact that Warthin tumors are the second most common type of benign salivary gland tumors, information regarding genetic alterations is extremely limited, and the tumorigenesis of these tumors has not been elucidated. The present results of the largest series of 30 tumors analyzed by comparative genomic hybridization (CGH) to date confirmed previous genetic findings and identified significant new candidate regions. The most commonly observed alterations were deletions of the short arm of chromosome 8, followed by deletions on 9p. Further representative changes were deletions on 16p and 22q with the minimal overlapping region at 16p12p13.1 and 22q12.1q12.3. Moreover, we indicated two different patterns of chromosomal aberrations. One group harbors deletions on 8p partly apparent with deletions on 9q, 11q 15q, 16p and 22. The second group shows gains on 22, partly apparent with gains on 1p and 20q and deletions on 9p. This leads to the assumption that Warthin tumors, in particular those with a high number of alterations, can be divided into two different genetic groups based on the pattern of numerical chromosomal aberrations. Further studies should address whether these subgroups also reflect a different clinical presentation.

CRTC1-MAML2 and CRTC3-MAML2 fusions were not detected in metaplastic Warthin tumor and metaplastic pleomorphic adenoma of salivary glands.

The recurrent translocations t(11;19) and t(11;15) resulting in CRTC1-MAML2 or CRTC3-MAML2 fusion oncogenes, respectively, are identified in a large proportion of mucoepidermoid carcinomas (MECs) of the salivary gland and have impact on prognosis. However, there are conflicting data on the specificity of this translocation, in particular, on its putative occurrence in Warthin tumor (WT) of the parotid gland as reported in few previous cases. It was speculated that extensive squamous metaplasia could explain the presence of t(11;19) translocation in a subset of WTs. We evaluated 76 salivary gland tumors, including 16 cases of metaplastic WT and 8 cases of pleomorphic adenoma (PA) with squamous and/or mucinous metaplasia, extensive enough morphologically to mimic MEC. Detection of CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts and MAML2 gene break was performed using nested reverse transcription-polymerase chain reaction and fluorescence in situ hybridization (FISH), respectively. None of 16 analyzed metaplastic WTs showed positivity for fusion transcripts CRTC1-MAML2 or CRTC3-MAML2, and none showed rearrangement of the MAML2 gene by FISH. Similarly, we did not detect these transcripts or break of MAML2 gene in any case of PA with extensive squamous/mucinous metaplasia. For comparison, 40 cases of low-grade MEC were also evaluated. CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts were detected in 17 and 5 cases, respectively. The FISH method using break-apart probe demonstrated the MAML2 gene rearrangement in 25 cases of low-grade MEC. In contrast to low-grade MEC, neither metaplastic WTs nor metaplastic PAs harbored translocations t(11;19) and anticipated t(11;15) resulting in CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts, respectively, and/or MAML2 gene rearrangement.

MT1 melatonin receptor expression in Warthin's tumor.

We contribute the first immunohistochemical study of MT1 melatonin receptor in Warthin's tumor and normal parotid gland. All 14 Warthin's tumors studied showed intense cytoplasmic positivity for MT1 receptor in all cylindrical epithelial cells lining spaces and a less intense positivity in basal cells. The lymphoid component accompanying the tumor was always negative for MT1 receptor. The parotid structure surrounding the tumor showed intense cytoplasmic positivity in all cells lining excretory ducts (lobar and lobulillar), with a lesser and focal positivity in cells of the acinar component. The biological activity of MT1 receptor in epithelial cells lining parotid excretory ducts may resemble its activity in Warthin's tumor cells. Hence, we propose Warthin's tumor as a useful positive control in immunohistochemical studies of MT1 melatonin receptor.

Human α-defensin (DEFA) gene expression helps to characterise benign and malignant salivary gland tumours.

BACKGROUND: Because of the infrequence of salivary gland tumours and their complex histopathological diagnosis it is still difficult to exactly predict their clinical course by means of recurrence, malignant progression and metastasis. In order to define new proliferation associated genes, purpose of this study was to investigate the expression of human α-defensins (DEFA) 1/3 and 4 in different tumour entities of the salivary glands with respect to malignancy. METHODS: Tissue of salivary glands (n=10), pleomorphic adenomas (n=10), cystadenolymphomas (n=10), adenocarcinomas (n=10), adenoidcystic carcinomas (n=10), and mucoepidermoid carcinomas (n=10) was obtained during routine surgical procedures. RNA was extracted according to standard protocols. Transcript levels of DEFA 1/3 and 4 were analyzed by quantitative realtime PCR and compared with healthy salivary gland tissue. Additionally, the proteins encoded by DEFA 1/3 and DEFA 4 were visualized in paraffin-embedded tissue sections by immunohistochemical staining. RESULTS: Human α-defensins are traceable in healthy as well as in pathological altered salivary gland tissue. In comparison with healthy tissue, the gene expression of DEFA 1/3 and 4 was significantly (p<0.05) increased in all tumours - except for a significant decrease of DEFA 4 gene expression in pleomorphic adenomas and a similar transcript level for DEFA 1/3 compared to healthy salivary glands. CONCLUSIONS: A decreased gene expression of DEFA 1/3 and 4 might protect pleomorphic adenomas from malignant transformation into adenocarcinomas. A similar expression pattern of DEFA-1/3 and -4 in cystadenolymphomas and inflamed salivary glands underlines a potential importance of immunological reactions during the formation of Warthin's tumour.

Immunohistochemical expression of CK7, CK5/6, CK19, and p63 in Warthin tumor.

Our study included a number of 24 cases with Warthin tumor, diagnosed between 2007-2011, which were analyzed in terms of clinical, histopathological and immunohistochemistry point of view, using CK7, CK5/6, CK19, and p63 antibodies. Warthin tumor is most often a tumor with a slow evolution, painless, usually affecting males (M/F 3.2/1) in the seventh decade of life. Histopathologically, it is distinguished the predominance of the typical forms of the tumor, with a balanced ratio epithelium/stroma. The immunostaining for CK7 showed positivity in all the investigated cases both in the columnar luminal cells and basal cells. The immunostaining for CK5/6 was positive in all the investigated cases in bilayer epithelial basal cells, both in the structure of the cysts and the papillae. In the case of the immunostaining for p63 we noticed limited nuclear positivity in the basal cells, while the columnar cells' nucleus were negative. The immunohistochemical study of the bilayer epithelial component of Warthin tumor showed different immunstaining of the two types of epithelia, the oncocytary columnar and the basal on, similar to those found in the salivary gland ducts.

MAML2 rearrangement in Warthin's tumour: a fluorescent in situ hybridisation study of metaplastic variants.

BACKGROUND: Warthin's tumour (WT) is a common benign lesion of the major salivary glands. The nature of WT remains controversial, with particular regard to the presence of clonal chromosomal abnormalities, including the t(11;19) translocation involving the CRTC1 and MAML2 genes, that have been identified in both WT and mucoepidermoid carcinoma. In this study, we focused our attention on metaplastic WT variants, and we conducted a fluorescent in situ hybridisation (FISH) analysis for the presence of MAML2 gene rearrangement. METHODS: Dual-colour FISH analysis was performed on paraffin-embedded sections of eight WTs showing metaplastic changes (five with squamous metaplasia, two with mucinous metaplasia and one with both) using a MAML2 break-apart probe. RESULTS: Presence of split signals indicative of gene rearrangement was identified in a subset of cells in areas of squamous metaplasia in two samples of WT. No rearrangement was observed in the oncocytic epithelium, in lymphocytes and in areas of mucinous metaplasia. CONCLUSIONS: The presence of a small subpopulation of cells carrying MAML2 rearrangement in areas of squamous metaplasia within WT could predispose these lesions to malignant transformation in mucoepidermoid carcinoma and could represent a molecular link between the two entities.