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* Context.--Neoadjuvant systemic therapy refers to the use of systemic agent(s) for malignancy prior to surgical treatment and has recently emerged as an option for most breast cancer patients eligible for adjuvant systemic therapy. Consequently, treated breast carcinomas have become routine specimens in pathology practices. A standard protocol has not yet been universally adopted for the evaluation and reporting of these specimens. The American Joint Committee on Cancer staging system recognizes the challenges in staging breast carcinomas after neoadjuvant treatment and provides important data points but does not currently provide detailed guidance in estimating the residual tumor burden in the breast and lymph nodes. The Residual Cancer Burden system is the only Web-based system that quantifies treatment response as a continuous variable using residual tumor burden in the breast and the lymph nodes. Objective.--To provide clarifications and guidance for evaluation and reporting of postneoadjuvant breast specimens, discuss issues with the current staging and reporting systems, and provide specific suggestions for future modifications to the American Joint Committee on Cancer system and the Residual Cancer Burden calculator. Data Sources.--English-language literature on the subject and the data from the I-SPy 2, a multicenter, adaptive randomization phase 2 neoadjuvant platform trial for early-stage, high-risk breast cancer patients. Conclusions.--This article highlights challenges in the pathologic evaluation and reporting of treated breast carcinomas and provides recommendations and clarifications for pathologists and clinicians. It also provides specific recommendations for staging and discusses future directions. doi: 10.5858/arpa.2022-0021-EP, Neoadjuvant systemic therapy (NST) in the treatment of breast cancer involves the administration of chemotherapy (NCT) or endocrine therapy prior to definitive surgery. Initially, NCT was implemented as a standard [...]

Pheochromocytomas are neural crest-derived tumors that arise from inherited or sporadic mutations in at least six independent genes. The proteins encoded by these multiple genes regulate distinct functions. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD). A transcription profile of reduced oxidoreductase is detected in all three of these tumor types, together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The oxidoreductase defect, not previously detected in VHL-null tumors, is explained by suppression of the SDHB protein, a component of mitochondrial complex II. The decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function and loss-of-function analyses show that the link between hypoxia signals (via VHL) and mitochondrial signals (via SDH) is mediated by HIF1alpha. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1alpha activity in tumors.

Background/Aims: Hyalinizing trabecular tumors are rare neoplasms of the thyroid gland often mistaken for thyroid carcinoma on fine-needle aspiration. We review the distinguishing characteristics of hyalinizing trabecular tumors and their management. Methods: We present the case of a patient diagnosed with papillary thyroid carcinoma on fine-needle aspiration as well as a review of the literature. Results: Intraoperative findings were felt to be inconsistent with papillary thyroid carcinoma and only a thyroid lobectomy was performed pending the results from pathologic evaluation, which confirmed a benign process and a diagnosis of hyalinizing trabecular tumor. Due to the diagnostic difficulty in distinguishing hyalinizing trabecular tumors from thyroid carcinomas on fine-needle aspiration, many patients receive overtreatment for what is primarily a benign disease. Conclusions: Recognition of hyalinizing trabecular tumors as a possible benign etiology of a thyroid mass can facilitate appropriate management. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]