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Morphologic Feature Guiding Discovery of Driver Genetic Alteration in Rare Entity
17:47|Adenoid Ameloblastoma is a very rare benign odontogenic tumor characterized microscopically by epithelium resembling conventional ameloblastoma, with additional duct-like structures, epithelial whorls, and cribriform architecture. Dentinoid deposits, clusters of clear cells, and ghost-cell keratinization may also be present.These tumors do not harbor BRAF or KRAS mutations and their molecular basis appears distinct from conventional ameloblastoma but remains unknown. Dr. Carolina Cavalieri Gomes from the Universidade Federal de Minas Gerais in Brazil, discusses her team’s discovery of CTNNB1 (beta-catenin) exon 3 mutations in 4 of 9 primary cases and 2 additional recurrences. While the occasional presence of ghost cells keratinization was the feature that led the team to initially investigate beta-catinin, this feature was present in only 2/6. Furthermore, nuclear beta-catenin immunoexpression (IHC) was found in 7 of 8 tested samples including some with wild type CTNNB1. The findings support the classification of adenoid ameloblastoma as a separate entity, and not as a subtype of ameloblastoma. The use of beta-catenin IHC could help in establishing the diagnosis in challenging cases.
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Risk Stratification for SLNB in Melanoma
25:54|Although prophylactic lymph node dissections do not improve survival, the prognostic implications of a positive sentinel node and the benefits of removing nodal metastases for loco-regional disease control remain important. There is a strong interest in novel approaches that can improve patients’ selection for sentinel lymphnode biopsies(SLNB) given that 85% of these procedures are negative and non-therapeutic. The host discusses with Dr. Alexander Meves his recent review in Modern Pathology on the role of gene expression profiling in this setting when combined with clinicopathologic parameters.Flat urothelial lesions of the urinary bladder: Who is in who is out?
29:59|Flat lesions of the urothelium with histologic features that falls short of the threshold for urothelial carcinoma in situ (CIS) remains a challenging problem in diagnostic surgical pathology. Among these are flat urothelial hyperplasia, urothelial dysplasia, and atypia of unknown significance; lesions that have struggled under evolving classifications, changing criteria, and limited clinical actionability, all confounded by the recognized lack of diagnostic reproducibility. In this episode of ModPath Chat, Dr. Gladell Paner discusses with the host his recently published “Controversies in Pathology” article in Modern Pathology on the pros and cons of keeping the previous terminology of this group of lesions.Radio-Resistant Prostate Carcinoma: “Cribriform” morphologies and DNA Damage Response and Repair defects
17:54|Locally recurrent prostate cancer from 53 patients that failed radiation therapy and underwent salvage radical prostatectomy was analyzed for clinicopathological and genomic characteristics. Most radiorecurrent tumors were enriched in cribriform morphologies (invasive cribrifom PCa and intraductal carcinoma with cribriform pattern) and demonstrated potentially targetable genomic alterations (defects in DDR genes: TP53, BRCA2, PALB2, ATR etc.). The guest, Dr. Rajal Shah of UTSW, discusses how understanding this phenotypic and genotypic diversity of radiorecurrent PCa is critically important for future management of such patients.The Stanford Experience in Implementation of the Molecular Classification of Endometrial carcinomas (EC)
17:58|Establishing an efficient and standardized workflow for performing molecular classification on ECs, and reporting both the molecular and histologic findings in an integrative manner, is imperative. Dr. Brooke Howitt discusses with the host her institution’s effort to implement rapid and routine molecular classification on all ECs diagnosed at Stanford.Expanding the clinico-pathological spectrum of SDH Deficient RCC
21:19|Most succinate dehydrogenase (SDH)-deficient RCCs demonstrate classic morphology characterized by bland eosinophilic cells with intracytoplasmic inclusions. Increasingly, “variant” morphologic features are recognized. Drs. Anthony Gill and Talia Fuchs discuss with the host their findings in a recent publication in Modern pathology where features such as high-grade nuclear features, necrosis, papillary, solid, and tubular architecture are present. These features appear to be associated with more aggressive behavior emphasizing the need for a low threshold for performing SDHB immunohistochemistry in any difficult to classify renal tumor; particularly if occurring at a younger age.High Risk and Selected Benign Breast Lesions on Core Biopsy: Excision Vs Surveillance?
22:01|The vast majority of image-detected breast abnormalities are currently diagnosed by percutaneous core needle biopsy (CNB). While management of frankly malignant lesions diagnosed by CNB is now well-defined, there is less consensus on the optimal management of high-risk and selected benign lesions diagnosed by CNB. In this episode, Dr. Benjamin Calhoun from University of North Carolina in Chapel Hill eloquently discusses the evidence for and against immediate excision of such lesions.