Tumor-infiltrating lymphocytes play an important role in cell-mediated immune destruction of cancer cells and tumor growth control. We investigated the heterogeneity of immune cell infiltrates between primary non-small cell lung carcinomas (NSCLC) and corresponding metastases. Formalin-fixed, paraffin-embedded primary tumors and corresponding metastases from 34 NSCLC patients were analyzed by immunohistochemistry for CD4, CD8, CD11c, CD68, CD163 and PD-L1. The percentage of positively stained cells within the stroma and tumor cell clusters was recorded and compared between primary tumors and metastases. We found significantly fewer CD4(+) and CD8(+) T cells within tumor cell clusters as compared with the stromal compartment, both in primary tumors and corresponding metastases. CD8(+) T cell counts were significantly lower in metastatic lesions than in the corresponding primary tumors, both in the stroma and the tumor cell islets. Of note, the CD8/CD4 ratio was significantly reduced in metastatic lesions compared with the corresponding primary tumors in tumor cell islets, but not in the stroma. We noted significantly fewer CD11c(+) cells and CD68(+) as well as CD163(+) macrophages in tumor cell islets compared with the tumor stroma, but no difference between primary and metastatic lesions. Furthermore, the CD8/CD68 ratio was higher in primary tumors than in the corresponding metastases. We demonstrate a differential pattern of immune cell infiltration in matched primary and metastatic NSCLC lesions, with a significantly lower density of CD8(+) T cells in metastatic lesions compared with the primary tumors. The lower CD8/CD4 and CD8/CD68 ratios observed in metastases indicate a rather tolerogenic and tumor-promoting microenvironment at the metastatic site.
Carcinoma showing thymus-like elements (CASTLE) is a rare tumor, most commonly found in the thyroid gland. Here we report a case of CASTLE tumor localized to the parotid gland, recognized in retrospect after a late manifestation of symptomatic pleural carcinomatosis. The original tumor in the parotid gland was treated by surgery followed by radiotherapy. Ten years later, a metastatic disease with recurrent pleural effusions occurred. Pleural carcinomatosis was strongly positive for CD5, CD117, and p63 as was the original tumor of the parotid, which allowed the diagnosis of a CASTLE tumor. Additionally, the pleural tumor expressed high levels of programmed death ligand 1 (PD-L1), and the patient underwent treatment with the monoclonal PD-L1 inhibitor pembrolizumab achieving a partial remission. To the best of our knowledge, this is the first patient with a metastatic CASTLE tumor treated with a PD-L1 inhibitor.
The supporting elements of the human organ of Corti express a number of cytokeratins, and it is obvious that the presence of cytokeratins provides mechanical stability to the framework of the entire organ of Corti. In the basal part of the outer hair cells and in the apical part of the Deiters cells, there is a significant expression of actin. In the human outer hair cells, the system of subsurface cisterns is not only restricted to the lateral cell wall but is also continuous to the basal region where the hair cells are closely attached to the supporting Deiters cells. In contrast to the well-known organization of the subsurface cisterns and pillar structures at the lateral outer hair cell wall of rodents, the pillars at the base of human outer hair cells can form channels. These channels allow a direct communication between the lumen of the subsurface cisterns and the intercellular space which separates outer hair cells and Deiters cells. At the apical part of the Deiters cells, a condensation of microfilaments is present which displays morphological similarities to actin fibers. These well-organized structural configurations between outer hair cells and Deiters cells imply that this region has special contractile properties. The human outer hair cells are therefore firmly stabilized not merely apically but also at the cell base, a situation which would permit a mainly isometric contraction under in vivo physiological conditions.
Denys-Drash syndrome (DDS) consists of the triad of nephropathy, male pseudohermaphroditism, and Wilms tumor caused by mutations within exons 8 or 9 of the Wilms tumor suppressor gene 1. Early onset nephrotic syndrome progresses to end-stage renal failure. The characteristic histological lesion is diffuse mesangial sclerosis. Here, we report on a boy with DDS who presented early with diffuse mesangial sclerosis, but subsequently also developed immune complex glomerulonephritis with a membranoproliferative pattern (MPGN-pattern GN) in his native kidneys. Four years after renal transplantation, immune complex glomerulonephritis with an MPGN pattern recurred in the renal graft resulting in proteinuria and progressive renal insufficiency.
About 15 years ago, the Swiss Society of Pathology has developed and implemented a board examination in anatomical pathology. We describe herein the contents covered by this 2-day exam (autopsy pathology, cytology, histopathology, molecular pathology, and basic knowledge about mechanisms of disease) and its exact modalities, sketch a brief history of the exam, and finish with a concise discussion about the possible objectives and
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