Selective disruption of protein-protein interactions by small molecules is important for probing the structure and dynamic aspects of cellular network. It can also provide new therapeutic targets. β-Catenin of the canonical Wnt signaling pathway uses the same positively charged groove to bind with T-cell factor (Tcf), cadherin, and adenomatous polysis coli (APC). The extravagant formation of β-catenin/Tcf interactions drives the initiation and progression of many cancers and fibroses, while β-catenin/cadherin and β-catenin/APC interactions are essential for cell-cell adhesion and β-catenin degradation. In this study, a selective binding site that can differentiate β-catenin/Tcf, β-catenin/cadherin, and β-catenin/APC interactions was identified by alanine scanning and biochemical assays. A new peptidomimetic strategy that incorporates SiteMap and multiple-copy simultaneous search was used to design selective small-molecule inhibitors for β-catenin/Tcf interactions. A potent inhibitor was discovered to bind with β-catenin and completely disrupt β-catenin/Tcf interactions. It also exhibits dual selectivity for β-catenin/Tcf over β-catenin/cadherin and β-catenin/APC interactions in both biochemical and cell-based assays. This study provides a proof of concept for designing selective inhibitors for β-catenin/Tcf interactions.

Objectives Carcinosarcomas of the salivary gland are rare neoplasms and have been described arising de novo or in association with pleomorphic adenoma (PA). PLAG1 and HMGA2 translocations are known to occur in PAs and carcinomas ex PA but are mutually exclusive. Methods We report a case of a carcinosarcoma in the parotid gland of a 77-year-old man with unusual anaplastic sarcomatoid giant cell morphology. Results Microscopically, a small separate PA was found adjacent to the carcinosarcoma. By conventional notion, the PA and carcinosarcoma would be considered related, as carcinosarcomas are well known to arise from PAs (carcinosarcoma ex PA). However, fluorescence in situ hybridization (FISH) assay demonstrated PLAG1 translocation in the carcinosarcoma and HMGA2 translocation in the separate PA. Conclusions These findings support that the carcinosarcoma likely originated from another PA with a PLAG1 translocation or de novo but not from the coexisting PA harboring a different translocation. To our knowledge, the case is the first to demonstrate PLAG1 translocation by FISH in a sarcomatous component of any parotid gland tumor, which may help better classify these tumors. In addition, multiple PAs are commonly found in the salivary gland, and to our knowledge, our case is the first to demonstrate that the same parotid gland can host PAs and PA-related tumors with different translocations.

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Objectives To develop a structured, introductory curriculum in scientific writing and publishing for residents in anatomic pathology. Methods We assessed the need for this curriculum by using an online questionnaire sent to anatomic pathology residents in our program and tailored content to address areas of least familiarity. The curriculum consisted of 4 virtual lectures delivered by select experts in the field. Curriculum evaluation was assessed through a postcurriculum questionnaire. Results In total, 27 of 31 (87%) residents responded to the initial questionnaire. The major educational need was identified in the following topics: “responsibilities of a corresponding author”; “selecting a journal for publication”; “editor’s approach to evaluating a manuscript”; “correspondence with editors and reviewers”; and “open access, cost and increasing exposure to manuscript.” Eight residents participated in at least 3 of 4 lectures and completed the pre- and postcurriculum survey. The postcurriculum survey demonstrated statistically significant interval increases in familiarity with 7 of 18 topics, and the leading increases were noted in topics of most significant educational need. Conclusions Development of novel curricula is vital to the ever-changing landscape of pathology resident education. This study proposes a generalizable algorithmic approach to assessing new areas of educational need and effectively addressing them through targeted curricula.

Keratin granulomas in the peritoneum are a rare finding with multiple etiologies and can be especially challenging for both the pathologist and the surgeon when these lesions are grossly visible. We report a case of a unique frozen section diagnostic scenario of evaluation of keratin granulomas in the peritoneum of a 47-year-old woman in the setting of multiple potential culprits: endometrial endometrioid adenocarcinoma following fertility sparing treatment, and a concurrent dermoid cyst. We discuss the various etiologies of keratin granulomas in the peritoneum, mechanism of their formation, diagnostic significance, as well as implications of fertility sparing treatments. To the best of our knowledge, this is the only case of keratin granulomas in the peritoneum with multiple distinct potential pathologic culprits as well the only case following fertility sparing treatment.