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<p class="ql-align-justify">Sections show an infiltrating poorly differentiated adenocarcinoma (Grade 3) composed of irregular nests, solid sheets, and scattered discohesive malignant epithelial cells with marked nuclear pleomorphism, hyperchromasia, prominent nucleoli, frequent mitoses, and focal necrosis within a desmoplastic stroma.</p><p class="ql-align-justify">Immunostaining was done with appropriate positive and negative controls and revealed:</p><p class="ql-align-justify">infiltrating lymphocytes.</p><p class="ql-align-justify"><strong>HER2/neu: </strong>Negative score 0</p><p class="ql-align-justify"><strong>MLH1</strong>: Intact, nuclear expression in >90% of tumor cells. </p><p><strong>PMS2: </strong>Intact, nuclear expression in >90% of tumor cells. </p><p><strong>MSH2: </strong>Intact, nuclear expression in >90% of tumor cells.</p><p class="ql-align-justify"><strong>MSH6:</strong> Intact, nuclear expression in >90% of tumor cells.</p>
<p class="ql-align-justify">Referred block for immunostaining of endoscopic biopsy from polypoidal mass located at the gastroesophageal junction.</p>
<p class="ql-align-justify">Received one paraffin block, coded 3304-2026, for Immunostaining (MSI and Her2 new).</p>
<p><strong><em><u>Referred paraffin block of gastroesophageal junction polypoidal mass, endoscopic biopsy:</u></em></strong></p><ul><li><strong>Poorly differentiated adenocarcinoma, grade 3.</strong></li><li><strong>HER2/neu</strong> <strong>negative score 0</strong></li><li><strong>Mismatch Repair (MMR) Status: Proficient (pMMR), See Comment.</strong></li></ul><h6><br></h6><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><strong>Comment:</strong></p><h5 class="ql-align-justify">Immunohistochemical studies demonstrate retained nuclear expression of the mismatch repair proteins, consistent with proficient mismatch repair (pMMR) status, indicating no evidence of mismatch repair deficiency (dMMR). Accordingly, this tumor is not expected to exhibit the microsatellite instability-high (MSI-H) phenotype attributable to loss of MMR protein expression, although molecular MSI testing may be considered in selected clinical scenarios if clinically indicated. HER2 immunohistochemistry is negative (score 0) according to the current CAP/ASCO HER2 testing guidelines for gastroesophageal adenocarcinoma, indicating absent HER2 overexpression and no eligibility for HER2-directed therapy based on immunohistochemistry alone. Correlation with the overall clinicopathologic findings and multidisciplinary evaluation is recommended. Additional predictive biomarker testing, including PD-L1 combined positive score (CPS) and, where clinically appropriate, CLDN18.2 expression and next-generation sequencing (NGS) for actionable genomic alterations, should be considered in accordance with current NCCN/CAP/ASCO recommendations for patients with advanced or metastatic gastroesophageal adenocarcinoma.</h5>
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