BRAFV600E immunohistochemistry can reliably substitute BRAF molecular testing in the Lynch syndrome screening algorithm in colorectal cancer.

AIMS: The Lynch syndrome (LS) screening algorithm requires BRAF testing as a fundamental step to distinguish sporadic from LS-associated colorectal carcinomas (CRC). BRAF testing by immunohistochemistry (IHC) has shown variable results in the literature. Our aim was to analyse concordance between BRAFV600E IHC and BRAF molecular analysis in a large, mono-institutional CRC whole-slide, case series with laboratory validation. METHODS AND RESULTS: MisMatch repair (MMR) protein (hMLH1, hPMS2, hMSH2, and hMSH6) and BRAFV600E IHC were performed on all unselected cases of surgically resected CRCs (2018-2023). An in-house validation study for BRAFV600E IHC was performed in order to obtain optimal IHC stains. BRAFVV600E IHC was considered negative (score 0), positive (scores 2-3), and equivocal (score 1). Interobserver differences in BRAFV600E IHC scoring were noted in the first 150 cases prospectively collected. Nine-hundred and ninety CRCs cases (830 proficient (p)MMR/160 deficient (d)MMR) were included and all cases performed BRAFV600E IHC (BRAFV600E IHC-positive 13.5% of all series; 66.3% dMMR cases; 3.4% pMMR cases), while 333 also went to BRAF mutation analysis. Optimal agreement in IHC scoring between pathologists (P < 0.0001) was seen; concordance between BRAFV600E IHC and BRAF molecular analysis was extremely high (sensitivity 99.1%, specificity 99.5%; PPV 99.1%, and NPV 99.5%). Discordant cases were reevaluated; 1 score 3 + IHC/wildtype case was an interpretation error and one score 0 IHC/mutated case was related to heterogenous BRAFV600E IHC expression. Among the 12 IHC-equivocal score 1+ cases (which require BRAF molecular analysis), three were BRAF-mutated and nine BRAF-wildtype. CONCLUSION: BRAFV600E IHC can be used as a reliable surrogate of molecular testing after stringent in-house validation.

Radiomic and clinical model for predicting atypical ductal hyperplasia upgrades and potentially reduce unnecessary surgical treatments.

OBJECTIVE: To identify patients with atypical ductal hyperplasia (ADH) at low risk of upgrading to carcinoma. This study aims to assess the performance of radiomics combined with clinical factors to predict occult breast cancer among women diagnosed with ADH. METHODS: This study retrospectively included microcalcification clusters of patients who underwent Mx and VABB with a diagnosis of ADH at a tertiary center from January 2015 to May 2023. Clinical and radiological data (age, cluster size, BI-RADS classification, mammographic density, breast cancer history, residual microcalcifications) were collected. Surgical outcomes were used to determine upgrade. Four logistic regression models were developed to predict the risk of upgrade. The performance was evaluated using the area under the receiver operating characteristic curve (AUC) and performance scores. RESULTS: A total of 143 patients with 153 clusters were included. Twelve radiomic features and six clinical factors were selected for model development. The sample was split into 107 training and 46 test cases. Clinical features achieved an AUC of 0.72 (0.60-0.84), radiomic features an AUC of 0.73 (0.61-0.85). Radiomic features with "cluster size" and "age" improved the AUC to 0.79 (0.67-0.91). The best model, incorporating all data, achieved an AUC of 0.82 (0.71-0.92), a specificity of 0.89 (0.75, 0.97), and NPV of 0.92 (0.78-0.98). CONCLUSION: This study demonstrates the potential of radiomic as a valuable tool for reducing unnecessary treatments for patient classified as "low risk of ADH upgrade". Combining radiomic information with clinical data improved the accuracy of risk prediction.

A Rare Case of Breast Metastasis from a Primary Lung Tumor: Case Report.

Breast metastasis originating from a primary lung tumor is exceedingly rare and can present challenges in distinguishing it from primary breast cancer. This case report discusses the management of a 64-year-old woman who initially presented with a nodule in her left breast. A biopsy revealed an infiltrating ductal carcinoma. Despite negative BRCA genetic testing, her significant family history of cancer and the presence of a newly detected right breast lesion led to a bilateral mastectomy. Post-operative imaging identified multiple hypodense nodules and a spiculated pulmonary nodule, necessitating further investigation. An endoscopic lung biopsy confirmed a primary pulmonary carcinoma with histological features similar to the breast carcinoma, suggesting the lung as the primary source. This case highlights the complexity of differentiating breast metastasis originating from a lung tumor and primary breast cancer. It underscores the importance of comprehensive diagnostic evaluations and the consideration of extramammary origins in metastatic cases. The findings emphasize the role of multidisciplinary teams in managing such rare and challenging cases and highlight the necessity for thorough and repeated assessments in atypical breast cancer presentations.