The Vulvar Immunohistochemical Panel (VIP) Project:Molecular Profiles of Vulvar Squamous Cell Carcinoma

Introduction: The study's aim was to investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC). Methodology: A series of 101 patients surgically treated at our center from 2016 to 2020 were retrospectively enrolled: 53 node-negative (Group A) and 48 node-positive (Group B). A total of 146 samples, 101 from primary tumor (T) and 45 from nodal metastases (N), were investigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF, and CD31. The reactions were evaluated on qualitative and semi-quantitative scales. Generalized Linear Model (GLM) and cluster analysis were performed in R statistical environment. A distance plot compared the IHC panel of T with the correspondent N. Results: In Group A: p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs. 6.2%, p = 0.04). In Group B: PD-L1 positivity and high EGFR expression were found, respectively, in 77.1% and 97.9% patients (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups: tumoral immune infiltration (CD3 expression) was mainly moderate/intense (80% vs. 95%); VEGF showed strong/moderate-diffuse expression in 13.9% of T samples; CD31, related to tumoral microvessel density (MVD), showed no difference between groups; a mutated p53 and over-expressed PD-L1 showed significant association with nodal metastasis, with Odds Ratios (OR) of 4.26 (CI 95% = 1.14-15.87, p = 0.03) and 2.68 (CI 95% = 1.0-7.19, p < 0.05), respectively; since all mismatch repair proteins (MMR) showed a retained expression and ER, PR, and HER2/neu were negative, they were excluded from further analysis. The cluster analysis identified three and four sub-groups of molecular profiles, respectively, in Group A and B, with no difference in prognosis. The molecular signature of each N and corresponding T diverged significantly in 18/41 (43.9%) cases. Conclusions: Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expressio

Correction to: Correlation of somatostatin receptor PET/CT imaging features and immunohistochemistry in neuroendocrine tumors of the lung: a retrospective observational study

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Identification of spatially-resolved markers of malignant transformation in Intraductal Papillary Mucinous Neoplasms

The existing Intraductal Papillary Mucinous Neoplasm (IPMN) risk stratification relies on clinical and histological factors, resulting in inaccuracies and leading to suboptimal treatment. This is due to the lack of appropriate molecular markers that can guide patients toward the best therapeutic options. Here, we assess and confirm subtype-specific markers for IPMN across two independent cohorts of patients using two Spatial Transcriptomics (ST) technologies. Specifically, we identify HOXB3 and ZNF117 as markers for Low-Grade Dysplasia, SPDEF and gastric neck cell markers in borderline cases, and NKX6-2 and gastric isthmus cell markers in High-Grade-Dysplasia Gastric IPMN, highlighting the role of TNFα and MYC activation in IPMN progression and the role of NKX6-2 in the specific Gastric IPMN progression. In conclusion, our work provides a step forward in understanding the gene expression landscapes of IPMN and the critical transcriptional networks related to PDAC progression

Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data

There is a need to develop and validate biomarkers for treatment response and survival in tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS) stratifies patients into complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response after neoadjuvant chemotherapy (NACT). Our aim was to review current evidence to determine whether the CRS is prognostic in women with tubo-ovarian HGSC treated with NACT.This article is freely available via Open Access. Click on the Publisher URL to access the full-text via the publisher's site

Neuroendocrine neoplasm update: toward universal nomenclature

Neuroendocrine neoplasia is described in almost every tissue, either in the pure endocrine organs, the nerve structures or in the so-called diffuse neuroendocrine system. The current nomenclature contains time-honored widely accepted definitions; however, it is different according to anatomical sites. Diverse definitions may generate confusion and non-standard patient management. The International Agency for Research on Cancer \u2013 World Health Organization (IARC-WHO) proposed a framework for universal classification of neuroendocrine neoplasia. Evidence indicates that neuroendocrine cancer is composed by cells with a distinctive phenotype characterized by the expression of general and specific neuroendocrine markers. The neuroendocrine phenotype is indicated as descriptor of a unique cancer category, now recommended for all organs as Neuroendocrine Neoplasm. Evidence indicates that neuroendocrine neoplasia may be well or poorly differentiated, with diverse incidence and prevalence in different organs. It is proposed that the well differentiated neoplasm is universally defined neuroendocrine tumor (NET), and the poorly differentiated neoplasm neuroendocrine carcinoma (NEC). Evidence indicates that a cancer grading tool based on a proliferation measure by mitotic count, Ki67 % and/or necrosis assessment is useful to predict NET patient behavior. It is proposed to utilize this tool for grading NET universally, with site-specific cut-offs to be defined. It is also acknowledged that significant biological site-specific differences exist. It is recommended that current pathology reports contain this classification together with the current traditional classifiers. This IARC-WHO common classification framework for neuroendocrine neoplasm aims at uniformizing nomenclature toward different organs and at fostering the definition of a similar site-specific gene signature

Congenital aggressive variant of Langerhans cells histiocytosis with CD56+/E-Cadherin- phenotype

In children &lt;2 years of age, cutaneous involvement is the most frequent presentation of Langerhans cell histiocytosis (LCH). Cutaneous LCH can be localized or associated with dissemination and organ dysfunction. The clinical Course is variable, ranging from spontaneous regression to a fatal Outcome. We describe a female newborn presenting with congenital Cutaneous lesions who rapidly developed pulmonary infiltrates and Multiple osteolytic lesions. Skin biopsy showed a dermal infiltrate of medium to large cells morphologically and phenotypically consistent with LCH. The clinical Course was rapidly fatal in spite of chemotherapy. No strict correlation between morphology and prognosis has been documented in LCH, but, in our case, distinct morphological and immunohistochemical features (CD56 expression and no E-Cadherin expression) may have contributed to an aggressive clinical Course. Pediatr Blood Cancer 2009;53:1107-1110. (C) 2009 Wiley-Liss, Inc

The New World Health Organization Classification for Pancreatic Neuroendocrine Neoplasia

Based on the 2010 version, the 2017 World Health Organization (WHO 2017) classification is for pancreatic neuroendocrine neoplasms (PanNEN). The WHO 2017 classification introduces the novel well-differentiated neuroendocrine tumor of high grade (NET G3). A sharp distinction between NET and poorly differentiated neuroendocrine carcinoma (NEC) is emphasized to highlight substantial biological differences. Further changes comprise the definition of mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN), to accommodate all grades of both neoplasm components, and the abolition of preneoplastic lesions given their rarity in the pancreas. The 2017 American Joint Cancer Committee classification (AJCC 2017) adopts such a classification for all digestive sites

Pathology of gastrointestinal disorders

Nonneoplastic and neoplastic proliferative lesions of endocrine cells of the gastrointestinal tract are detailed. A multistep continuum from hyperplasia, dysplasia to neoplasia is identified for histamine-producing enterochromaffin-like (ECL) cells of the gastric corpus. Most gastric neuroendocrine tumors (NETs) are silent and composed by ECL cells, the second most frequent neuroendocrine neoplasms being the high-grade neuroendocrine carcinoma (NEC). In the duodenum, preneoplastic lesions are similarly described for gastrin (G) and somatostatin (D) cells. G-cell NETs are the most frequent neuroendocrine tumors of the duodenum, either functioning or nonfunctioning, followed by D-cell NETs and gangliocytic paraganglioma (GCP). No systematic definition of nonneoplastic lesions exists for endocrine cells of the ileum, appendix, and colon-rectum. The most frequent ileal NETs are serotonin-producing enterochromaffin (EC)-cell NETs (classic carcinoid), associating with functional syndrome only in presence of liver metastases. Neoplasms are usually larger in the colon as compared with the small lesions observed in the rectum. High-grade NECs are observed in the colon and rectum-sigmoid, often associate with nonendocrine neoplastic components, and fare an aggressive course with poor outcome and short survival