Chen, Longwen

Abstract Lynch syndrome (LS) markedly increases risks of colorectal and endometrial cancers. Early detection biomarkers for LS cancers could reduce the needs for invasive screening and surgical prophylaxis. To validate a panel of methylated DNA markers (MDM) previously identified in sporadic colorectal cancer and endometrial cancer for discrimination of these cancers in LS. In a case–control design, previously identified MDMs for the detection of colorectal cancer and endometrial cancer were assayed by qMSP on tissue-extracted DNA. Results were normalized to ACTB values within each sample. Least absolute shrinkage and selection operator models to classify colorectal cancer and endometrial cancer were trained on sporadic cases and controls and then applied to classify colorectal cancer and endometrial cancer, in those with LS, and cross-validated. We identified colorectal cancer cases (23 with LS, 48 sporadic), colorectal controls (32 LS, 48 sporadic), endometrial cancer cases (30 LS, 48 sporadic), and endometrial controls (29 LS, 37 sporadic). A 3-MDM panel (LASS4, LRRC4, and PPP2R5C) classified LS-CRC from LS controls with an AUC of 0.92 (0.84–0.99); results were similar for sporadic colorectal cancer. A 6-MDM panel (SFMBT2, MPZ, CYTH2, DIDO1, chr10.4479, and EMX2OS) discriminated LS-EC from LS controls with an AUC of 0.92 (0.83–1.0); the AUC for sporadic endometrial cancer versus sporadic controls was nominally higher, 0.99 (0.96–1.0). MDMs previously identified in sporadic endometrial cancer and colorectal cancer discriminate between endometrial cancer and benign endometrium and colorectal cancer and benign colorectum in LS. This supports the inclusion of patients with LS within future prospective clinical trials evaluating endometrial cancer and colorectal cancer MDMs and may provide a new avenue for cancer screening or surveillance in this high-risk population. Prevention Relevance: Lynch syndrome (LS) markedly increases risks of colorectal and endometrial cancers. Early detection biomarkers for LS cancers could reduce the needs for invasive screening and surgery. Methylated DNA markers previously identified in sporadic endometrial cancer and colorectal cancer discriminate between benign and cancer tissue in LS.

AbstractWe describe an exceedingly rare cytology case of a NUTM1‐rearranged sarcoma involving pleural fluid. A 48‐year‐old female presented with progressive abdominal pain. Computed tomography (CT) scan of the abdomen revealed a 5.6 cm soft tissue mass in the right hemi‐abdomen. Needle core biopsy of the mass showed a small round cell tumor. Extensive work‐up including next generation sequencing (NGS) demonstrated a NUTM1:MXI1 rearranged sarcoma. The patient was first treated with ifosfamide, carboplatin, and etoposide (ICE) chemotherapy. She responded initially and then progressed with multiple masses in the abdomen and pleural effusion. The cytology of the pleural effusion showed clusters and single small round blue cells. Some of them displayed rhabdoid morphology. Immunostains of NUT antibody on cell block demonstrated strong positivity of NUT. NUTM1‐rearranged sarcoma is an emerging class of mesenchymal neoplasm and the cytomorphology of this neoplasm in liquid‐based cytology (LBC) is yet to be described. We herein reported the first cytology case of NUTM1‐rearranged sarcoma in pleural fluid.

BACKGROUNDThe Milan System for Reporting Salivary Gland Cytopathology is a tiered classification scheme that includes 6 diagnostic categories. Neoplasm, which is 1 of the 6 proposed categories, consists of benign neoplasm and neoplasm of uncertain malignant potential (NUMP). NUMP is reserved for a salivary gland neoplasm without clear distinction between benign and malignant. The objective of this study was to assess the risk of malignancy (ROM) of NUMP.METHODSA retrospective analysis was conducted on 656 salivary gland fine‐needle aspiration specimens from 2010 to 2016. Cases that qualified as NUMP and had follow‐up surgical resections were reviewed and reclassified into basaloid neoplasm (BN) and salivary gland neoplasm with predominant oncocytic cell (SGNOC) groups. The ROM for each group was calculated. Fifty‐four salivary gland fine‐needle aspirations of NUMP that had surgical follow‐up were identified, which included 29 BNs and 25 SGNOCs.RESULTSHistologic follow‐up for the BN group identified 14 cellular pleomorphic adenomas, 5 basal cell adenomas, 2 benign cystadenomas, 3 adenoid cystic carcinomas, 3 epithelial and myoepithelial carcinomas, 1 basal cell adenocarcinoma, and 1 myoepithelial carcinoma. Histologic follow‐up for the SGNOC group revealed 7 nodular oncocytoses, 6 Warthin tumors, 5 oncocytomas, 1 sebaceous adenoma, 1 mucinous cystadenoma, 2 acinic cell carcinomas, 2 mucoepidermoid carcinomas, and 1 mammary analog secretory carcinoma. The ROM was calculated at 24.1% for the NUMP category overall (27.6% for BNs and 20.0% for SGNOCs).CONCLUSIONSThe ROM of the SGNOC group is similar to that of the BN group but lower than the ROM (35%) proposed by the Milan system. Cancer Cytopathol 2018. © 2018 American Cancer Society.