<b><i>Background:</i></b> Mucoepidermoid carcinoma (MEC) showing Warthin’s tumor (WT)-like features is a low-grade malignancy which should be differentiated from WT. Morphological features may be distinctly different in each case, causing diagnostic difficulties. <b><i>Case Presentation:</i></b> Three cases were presented and discussed with their morphologies. All cases that presented with a mass in the parotid gland went to parotidectomy, and all had preoperative fine-needle aspirations (FNAs). Case 1 was a 16-year-old female; FNA was suggestive of WT and initially interpreted as WT histologically. Case 2 was a 27-year-old male; FNA was interpreted as noninformative due to the presence of cyst fluid only. Case 3 was a 53-year-old male and cytologically was found to be suspicious for MEC which contained squamous and goblet cells on a mucoid background. On histopathological examination, case 2 and case 3 were morphologically consistent with low-grade MEC with WT-like features. Prominent lymphoid stroma and the cystic pattern were the characters of these tumors. Case 1 had the classical WT appearance with some mucinous and squamous metaplasia which could only be interpreted as MEC after the detection of MAML2 rearrangement by FISH. The other 2 showed either focal or relatively diffuse usual low-grade MEC findings, and case 3 was also confirmed by MAML2 rearrangement. <b><i>Conclusion:</i></b> Cytological and histopathological features revealed a spectrum. Differentiating WT-like MECs from ordinary WTs may be challenging. On the one end of the spectrum, they may look very much like WT, and on the other end, even though usual MEC features are present, still, WT-like appearance may pose diagnostic difficulty. Showing MAML2 rearrangement in these cases is very helpful. The presence of mucinous and squamous cells in an otherwise WT-like looking tumor should be alarming for MEC, and if possible, each case should be analyzed for MAML2 rearrangement.

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BACKGROUND: The significance of DNA mismatch repair (MMR) deficiency in ampullary cancers (ACs) has not been established. METHODS: In total, 127 ACs with invasive carcinomas measuring ≥3 mmthat had adequate tissue were analyzed immunohistochemically. RESULTS: MMR loss was detected in 18% of ACs (higher than in colorectal cancers). Twelve tumors with MLH1-PMS2 loss were negative for BRAF V600E mutation, suggesting a Lynch syndrome association. MMR-deficient tumors (n = 23), comparedwith MMR-intact tumors (n = 104), showed a striking male predominance (male:female ratio, 4.7). Although the deficient tumors had slightly larger invasion size (2.7 vs 2.1 cm), they also had more expansile growth and less invasiveness, including less perineural invasion, and they ultimately had lower tumor (T) classification and less lymph node metastasis (30% vs 53%; P = .04). More important, patients who had MMR-deficient tumors had better clinical outcomes, with a 5-year overall survival rate of 68% versus 45% (P = .03), which was even more pronounced in those who had higher Tclassification (5-year overall survival, 69% vs 34%; P = .04). MMR deficiencyhad a statistically significant association with medullary phenotype, pushing-border invasion, and tumor-infiltrating immune cells, and it occurred more frequently in ampullary-duodenal type tumors. Programed cell death-ligand 1 (PD-L1) levels analyzed in the 22 MMR-deficient ACs revealed that all medullary carcinomas were positive. Nonmedullary MMR-deficient carcinomas expressed PD-L1 in 33% of tumors cells according to the criteria for a combined positive score ≥1, but all were negative according to the tumor proportion score≥1 method. CONCLUSIONS: In ACs, MMR deficiency is even more frequent (18%) than in colon cancer and often has a Lynch-suggestive profile, thus routine testing is warranted. Male gender, pushing-border infiltration, ampullary-duodenal origin, medullary histology, and tumor-related inflammation have a significantly higher association with MMR deficiency. MMR-deficient tumors have less aggressive behavior. PD-L1 expression is common in medullary-phenotype ACs, thus immunotherapy should be considered at least for this group.

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Objective: Soft tissue tumors comprise a small proportion of a pathologist's routine practice. Although morphology and immunohistochemistry are quite helpful for diagnosing these tumors, many require molecular tests. Fluorescence in-situ hybridization has been the most commonly used method for the detection of specific genomic alteration, but next generation sequencing (NGS) could be more informative in many ways.Here we present our targeted NGS experience on soft tissue tumors with a series of 20 cases. Material and Method:The Laboratory Information System (LIS) was screened for soft tissue tumors that had been sequenced by NGS (between January 2018 -February 2021). 20 consecutive cases were included in the study. All cases were sequenced using a commercial targeted sequencing panel designed for soft tissue tumors. Results:We were able to run a reliable sequencing study for 16 (80%) of the cases but 4 (20%) of them failed in quality tests. We have found pathogenic alterations in 12 (60%) of the cases. The most common alterations were EWSR1 fusions, FLI1 being the most common partner. NGS results drastically changed the initial diagnosis, and thus the treatment modalities, in 3 cases (15%): the case with ETV6-NTRK3 fusion, the case with FUS-TFCP2 fusion, and the case of rhabdomyosarcoma (RMS) that was favored to be of the alveolar subtype and turned out to lack FOXO1 fusions. Conclusion:A targeted NGS panel is robust and very informative. It not only allows pathologists to further specify and/or confirm their diagnosis but it could also play an important role in predicting the outcome.