We report at unique, previously unreported pancreatic tumor occurring in a 60-year-old woman who was preoperative diagnosed on cytoaspiration as having clear cell carcinoma. The resected tumor consisted of a population of large epithelioid cells with clear or eosinophilic, granular cytoplasm, rich in glycogen, with nuclear pleomorphism and no mitotic activity. In spite of the epithelioid appearance, the tumor cells were negative for epithelial (CAM 5.2, KL1, AE1-AE3), endocrine (neuron-specific enolase [NSE], chromogranin A), and acinar (lipase, amylase) markers and positive for actin and melanogenesis-related marker HMB 45. Ultrastructurally, the neoplastic cells showed membrane-bound granules; no evidence of either epithelial or melanocytic differentiation was present. These morphophenotypic features have never been reported in a pancreatic tumor and overlap those of clear cell "sugar" tumor of the lung. The same morphophenotypic features are observed in a family of lesions characterized by the presence of the perivascular epithelioid cell that also includes lymphangiomyomatosis and angiomyolipoma. The present case may be considered a novel member of this family of lesions. We propose this new entity be named clear cell "sugar" tumor of the pancreas.

Background Evaluation of programmed cell death ligand 1 (PD‐L1) expression can be made on both resection specimens and diagnostic biopsies; however, more than 30% of patients with advanced non–small cell lung cancer (NSCLC) do not have adequate histologic material to perform PD‐L1 assays and require additional biopsies. In addition, in our practice, more than 16% of cases have cytological smears as the only available material. Our aim was to validate the PD‐L1 immunocytochemistry assay on cytological smears and compare its accuracy with the results obtained from tissue cores and whole tumor sections using the clinically relevant cutoff of 50%. Method We compared the PD‐L1 staining results of cytological smears to those from tissue cores or whole sections in 50 and 53 NSCLC cases, respectively, using the SP263 assay after scanning hematoxylin and eosin slides. Results We found an overall agreement of 90.6% between cytological smears and whole sections; specifically, we found absolute concordance between smears with PD‐L1 expressed in <10% and ≥50% of cells and whole sections with PD‐L1 expressed in <50% and ≥50% of cells, respectively. In addition, slightly lower diagnostic accuracy was found for the cytological smears in comparison with the tissue cores, but the difference was not statistically significant. We found excellent intraobserver and good interobserver agreement in the evaluation of PD‐L1 on smears. Conclusion Immunocytochemistry on cytological smears is a reliable method for determination of PD‐L1 at the 50% cutoff when positive cells are <10% or ≥50%; for cases showing PD‐L1 expression in 10% to 49% of cells, additional tissue sampling may be necessary.

Epithelial to mesenchymal transition has been suggested as a relevant contributor to pulmonary fibrosis, but how and where this complex process is triggered in idiopathic pulmonary fibrosis is not fully understood. Beta-tubulin-III (Tubβ3), ZEB1, and β-catenin are partially under the negative control of miR-200, a family of micro-RNAs playing a major role in epithelial to mesenchymal transition, that are reduced in experimental lung fibrosis and idiopathic pulmonary fibrosis. We wonder whether in situ expression of these proteins is increased in idiopathic pulmonary fibrosis, to better understand the significance of miR-200 feedback loop and epithelial to mesenchymal transition. We investigated the immunohistochemical and immunofluorescent expression and precise location of ZEB1, Tubβ3, and β-catenin in tissue samples from 34 idiopathic pulmonary fibrosis cases and 21 controls (5 normal lungs and 16 other interstitial lung diseases). In 100% idiopathic pulmonary fibrosis samples, the three proteins were concurrently expressed in fibroblastic foci, as well in damaged epithelial cells overlying these lesions and in pericytes within neo-angiogenesis areas. These results were also confirmed by immunofluorescence assay. In controls the abnormal expression of the three proteins was absent or limited. This is the first study that relates concurrent expression of Tubβ3, ZEB1, and β-catenin to abnormal epithelial and myofibroblast differentiation in idiopathic pulmonary fibrosis, providing indirect but robust evidence of miR-200 deregulation and epithelial to mesenchymal transition activation in idiopathic pulmonary fibrosis. The abnormal expression and localization of these proteins in bronchiolar fibro-proliferative lesions are unique for idiopathic pulmonary fibrosis, and might represent a disease-specific marker in challenging lung biopsies.

ALK translocation may be found in lung pure squamous cell carcinomas. Our data suggest the opportunity to test ALK rearrangements on biopsy samples harboring squamous cell cancer differentiation.

The immunohistochemical characterization of carcinomas arising in IPF patients shows striking divergence from that in non-IPF smokers. The prevalence of rare entities showing bronchiole-related markers is in line with the hypothesis that these tumours arise from transformed small airways in honeycomb lung areas where abnormal bronchiolar proliferation takes place.