Unraveling the Mysteries of Perineural Invasion in Benign and Malignant Conditions.

Perineural invasion (PNI) is defined as the dissemination of neoplastic cells within the perineural space. PNI can be a strong indicator of malignancy and is linked to poor prognosis and adverse outcomes in various malignant neoplasms; nevertheless, it can also be seen in benign pathologic conditions. In this review article, we discuss various signaling pathways and neurotrophic factors implicated in the development and progression of PNI. We also describe the methodology, benefits, and limitations of different in vitro, ex vivo, and in vivo models of PNI. The spectrum of presentation for PNI can range from diffuse spread within large nerves ("named" nerves) all the way through localized spread into unnamed microscopic nerves. Therefore, the clinical significance of PNI is related to its extent rather than its mere presence or absence. In this article, we discuss the guidelines for the identification and quantification of PNI in different malignant neoplasms based on the College of American Pathologists (CAP) and World Health Organization (WHO) recommendations. We also describe benign pathologic conditions and neoplasms demonstrating PNI and potential mimics of PNI. Finally, we explore avenues for the future development of targeted therapy options via modulation of signaling pathways involved in PNI.

Fluid Overload-Associated Large B-Cell Lymphoma: A Case Report and Review of Literature.

Fluid overload-associated large B-cell lymphoma (FO-LBCL) is a new entity described in the fifth edition of the World Health Organization (WHO) Classification of Hematolymphoid Tumors (WHO-HAEM5). It refers to malignant lymphoma present with symptoms of serous effusions in body cavities (pleural, peritoneal, and/or pericardial) in the absence of an identifiable tumor mass. We present a case of an 82-year-old man with a history of atrial fibrillation and atrial flutter, status post-ablation, essential hypertension (HTN), hyperlipidemia (HLD), and diabetes mellitus (DM) type 2 who was referred to our hospital for shortness of breath due to recurrent pleural effusion. Right video-assisted thoracoscopy with right pleural biopsy was performed. Histopathological examination of the pleural biopsy revealed dense fibrous tissue, chronic inflammation, lymphoid aggregates, and granulation tissue, with no evidence of lymphoma. Cytology of the right pleural fluid revealed large lymphoid cells, which were positive for CD45, CD20, PAX-5, MUM-1, BCL2, BCL6, and MYC protein. They were negative for CD3, CD10, CD138, and HHV-8 by immunohistochemistry (IHC). Epstein-Barr virus (EBV) was negative by in situ hybridization (ISH). Due to the absence of any evidence of lymphoma elsewhere, a diagnosis of fluid overload-associated large B-cell lymphoma (FO-LBCL) was made. We provide a synopsis of the main clinicopathological features of FO-LBCL and the two main differential diagnoses, primary effusion lymphoma (PEL) and diffuse large B-cell lymphoma (DLBCL).

Squamous cell carcinoma arising in a Zenker diverticulum.

Squamous cell carcinoma (SCC) arising in a Zenker diverticulum (ZD) is an extremely rare entity. Approximately 50 cases have been reported worldwide. We report a case of a 74-year-old man who presented to our institution with chronic regurgitation, dysphagia and halitosis. The patient was initially seen in 2015 at which point he reported a 10-year history of these symptoms and was diagnosed with ZD. A barium swallow was done revealing a large posterior esophageal diverticulum with significant residual contrast within the diverticulum lumen. Given these findings, he was taken for open surgical excision where a SCC was identified. Although it is extremely rare for a SCC to occur in a ZD, patients with ZD must undergo regular surveillance endoscopy of the esophagus and the diverticulum itself to identify any suspicious mass or lesion arising in within.

ROS1 altered breast cancers - a distinctive molecular subtype of PR- metastatic breast cancers: Expanding the scope of targeted therapeutics.

BACKGROUND: Breast cancer, one of the leading causes of cancer-related mortality in women worldwide, exhibits wide-ranging histo-morphologic, clinical and molecular diversity. OBJECTIVE: This study compares the genetic alterations of breast tumors with the histo-morphological, hormone receptor status and metastatic "organotropism". MATERIALS AND METHODS: Twenty-two cases of primary invasive breast carcinoma with local/distant metastasis were retrieved from the pathology archives. The status of estrogen and progesterone receptors by immunohistochemistry was recorded along with other pertinent case data. Next generation sequencing was performed on formalin-fixed paraffin embedded blocks of tumor. RESULTS: The mean age of the study subjects was 57.9 ± 13.3 years. TP53 mutation was the most common gene alteration in this study and was seen in 40.9% cases. ROS1 gene was mutated in 44.4% PR negative breast cancers while being wild type in the twelve PR positive tumors. (p = 0.021).STRING interaction network constructed with ROS1 and PR revealed a significantly higher number of interactions in this network than expected (p-value 0.000973). CONCLUSION: This study highlights the significantly higher incidence of ROS1 gene alterations in metastatic PR- breast cancers, with STRING network analysis revealing higher nodal interaction in the nodal network comprised of PR and ROS1 exclusive of ER.