Primary Peritoneal Carcinosarcoma in a Breast Cancer Patient Harboring a Germline BRCA2 Pathogenic Variant: Case Report

Malignant mixed müllerian tumor (MMMT) is a rare neoplasm, consisting of carcinomatous (epithelial) and sarcomatous (mesenchymal) components that most commonly arise in the endometrium and more infrequently in the ovaries, fallopian tube, cervix, and vagina. Primary peritoneal carcinosarcoma (PPCS) is an extremely rare extragenital presentation of MMMT. Although the occurrence of breast cancer and epithelial ovarian carcinoma in association with BRCA pathogenic variants is firmly established, the etiologic role of these genes in the development of other tumor types is less well known. Here, we present a rare case of PPCS in a 42-year-old Brazilian woman with a BRCA2 pathogenic variant, c.2808_2811del (NM_000059.3). The patient developed metastatic breast cancer at the age of 37 and underwent a risk-reducing bilateral salpingo-oophorectomy 2 years later. She was then diagnosed with PPCS 3 years after the risk-reducing surgery. She underwent treatment with surgery, chemotherapy, and targeted therapy but passed away almost 5 years after the second primary tumor diagnosis. To our knowledge, this is the first case of peritoneal carcinosarcoma described in a BRCA2 pathogenic variant carrier, and its report leads to a better understanding of the disease’s molecular features and possible therapeutic approaches

Immune profiling of uveal melanoma identifies a potential signature associated with response to immunotherapy

© BMJ Publishing Group Limited 2020. Background To date, no systemic therapy, including immunotherapy, exists to improve clinical outcomes in metastatic uveal melanoma (UM) patients. To understand the role of immune infiltrates in the genesis, metastasis, and response to treatment for UM, we systematically characterized immune profiles of UM primary and metastatic tumors, as well as samples from UM patients treated with immunotherapies. Methods Relevant immune markers (CD3, CD8, FoxP3, CD68, PD-1, and PD-L1) were analyzed by immunohistochemistry on 27 primary and 31 metastatic tumors from 47 patients with UM. Immune gene expression profiling was conducted by NanoString analysis on pre-treatment and post-treatment tumors from patients (n=6) receiving immune checkpoint blockade or 4-1BB and OX40 dual costimulation. The immune signature of UM tumors responding to immunotherapy was further characterized by Ingenuity Pathways Analysis and validated in The Cancer Genome Atlas data set. Results Both primary and metastatic UM tumors showed detectable infiltrating lymphocytes. Compared with primary tumors, treatment-naïve metastatic UM showed significantly higher levels of CD3+, CD8+, FoxP3+ T cells, and CD68+ macrophages. Notably, levels of PD-1+ infiltrates and PD-L1+ tumor cells were low to absent in primary and metastatic UM tumors. No metastatic organ-specific differences were seen in immune infiltrates. Our NanoString analysis revealed significant differences in a set of immune markers between responders and non-responders. A group of genes relevant to the interferon-γsignature was differentially up-expressed in the pre-treatment tumors of responders. Among these genes, suppressor of cytokine signaling 1 was identified as a marker potentially contributing to the response to immunotherapy. A panel of genes that encoded pro-inflammatory cytokines and molecules were expressed significantly higher in pre-treatment tumors of non-responders compared with responders. Conclusion Our study provides critical insight into immune profiles of UM primary and metastatic tumors, which suggests a baseline tumor immune signature predictive of response and resistance to immunotherapy in UM

Learning reflectance confocal microscopy of melanocytic skin lesions through histopathologic transversal sections.

Histopathologic interpretation of dermoscopic and reflectance confocal microscopy (RCM) features of cutaneous melanoma was timidly carried out using perpendicular histologic sections, which does not mimic the same plane of the image achieved at both techniques (horizontal plane). The aim of this study was to describe the transverse histologic sections research technique and correlate main dermoscopic features characteristic of cutaneous melanoma (atypical network, irregular globules and pseudopods) with RCM and histopathology in perpendicular and transverse sections in order to offer a more precise interpretation of in vivo detectable features. Four melanomas and 2 nevi with different dermoscopic clues have been studied. Lesion areas that showed characteristic dermoscopic features were imaged by dermoscopy and confocal microscopy and directly correlated with histopathology in perpendicular and transverse sections. We presented the possibility to perform transverse sections as a new approach to understand RCM features. Atypical network showed different aspects in the 2 melanomas: in one case it was characterized by pleomorphic malignant melanocytes with tendency to form aggregates, whereas in the other elongated dendritic cells crowded around dermal papillae, some of them forming bridges that resembled the mitochondrial aspect at confocal and histopathology transversal sections. Pigment globules in melanomas and nevi differed for the presence of large atypical cells in the former, and pseudopods showed up as elongated nests protruded toward the periphery of the lesion. Transverse histologic research sections have a consistent dermoscopic and confocal correlate, and it may represent an help in confocal feature interpretation and an advance in improving melanoma diagnosis and knowledge of the biology of melanocytic lesions

Gastric Pouch Mixed Adenoneuroendocrine Carcinoma With a Mixed Adenocarcinoma Component After Roux-en-Y Gastric Bypass

The Roux-en-Y gastric bypass is one of the most common procedures currently performed for surgical treatment of patients with severe obesity. Gastric cancer after bariatric surgery is not common, with most of them arising in the excluded stomach. Gastric mixed adenoneuroendocrine carcinomas are a rare type of stomach malignancy, composed of both adenocarcinoma and neuroendocrine tumor-cell components, with the latter comprising at least 30% of the whole neoplasm. In this article, we report a unique case of a mixed adenoneuroendocrine carcinoma with a mixed adenocarcinoma (tubular and poorly cohesive) component arising in the gastric pouch of a patient who underwent previous Roux-en-Y gastric bypass for glycemic control. Since stomach cancer is not usual in patients who have formerly undergone bariatric surgery and symptoms tend to be nonspecific, such diagnosis is often rendered at an advanced stage. Full assessment of these patients when presenting such vague symptoms is critical for an early cancer diagnosis

Summary of dermoscopic features, reflectance confocal microscopy and histopathologic aspects.

<p>Summary of dermoscopic features, reflectance confocal microscopy and histopathologic aspects.</p

Superficial spreading melanoma <i>in situ</i>.

<p>This lesion shows on dermoscopy (A) a slightly pigmented network (white circle corresponds to the punch area). RCM mosaic image (B, 1×1 mm) at the level of the DEJ shows irregular and dishomogeneous dermal papillae with dendritic cells (white arrows). RCM individual image (C, 0,5×0,5 mm) at the level of the DEJ shows dendritic cells forming “bridges” called mitochondria-like structures (white arrow). Perpendicular section (D) shows disarrangement of the rete ridge and the increased number of atypical melanocytes. Transverse section (E, HE staining) shows atypical melanocytes protruding into the dermal papillae forming bridges (black arrows). Transverse section (F, Melan-A staining) shows cells positive for Melan-A protruding into the dermal papillae (white arrows).</p

Superficial spreading melanoma <i>in situ</i>.

<p>This lesion shows on dermoscopy (A) a broadened pigmented network (white circle corresponds to the punch area). RCM mosaic images (B and D, 1×1 mm) at the level of the DEJ show demarcated and non-demarcated rings separated by loosely thick interpappilary spaces (white arrows) and some plump bright cells and bright dots are visible within dermal papillae (arrowheads). Perpendicular section (C) shows disarrangement of the rete ridge and the increased number of atypical melanocytes in the epidermis. Transverse section (E) shows predominance of atypical melanocytes, isolated or in nests, enlarging the interpapillary spaces (black arrow).</p

Superficial spreading melanoma, Breslow thickness 0,79 mm.

<p>This lesion shows on dermoscopy (A) pseudopods (white circle corresponds to the punch area). RCM mosaic image (B, 3×3 mm) at the level of the DEJ shows compact aggregates of atypical cells distributed in a linear arrangement toward the periphery with a dense nest at the extremity (the area inside the dashed square is represented in figure C). RCM individual image (C, 0,5×0,5 mm) at the level of the DEJ shows a pseudopod in detail, characterized by elongated, dense and bright peripheral aggregate. Perpendicular section (D) shows nests of atypical melanocytes distributed contiguously toward the periphery along the DEJ. Transverse section (E) shows nests of atypical cells arranged in a linear manner throughout the periphery of the lesion (black arrows).</p