Homologous Recombination Deficiency in Patients With Pancreatic Ductal Adenocarcinoma and Response to Chemotherapy.

PURPOSE: Mutations or copy number abnormalities of genes involved in homologous recombination (HR) occur in pancreatic ductal adenocarcinoma (PDAC). DNA-based measures of HR deficiency (HRD) have been developed and may help identify tumors with better response to DNA-damaging agents. This study aimed to describe the HR pathway mutations and HRD status and determine their association with treatment response and outcome in patients with PDAC. PATIENTS AND METHODS: We performed a retrospective analysis of tumor samples from patients treated at Indiana University for locally advanced or metastatic PDAC. Patients were included if they received gemcitabine plus nanoparticle albumin-bound paclitaxel (control) or fluorouracil, oxaliplatin, leucovorin, and irinotecan (FOLFIRINOX) and had adequate follow-up to assess survival and response to therapy. Tumor analysis generated a three-biomarker HRD score and mutation data for 44 genes. RESULTS: Ninety-one samples met inclusion criteria, and 78 samples (formalin-fixed paraffin-embedded, n = 15; fine-needle aspiration, n = 63) generated mutation data. HRD analysis was successful for 57 samples (HRD score: median, 18; range, 5 to 61); the primary cause of failure was low tumor cellularity. Six BRCA1/2 mutations were detected, four with HRD scores in the top decile (P = .011). There was no statistically significant correlation between HRD score and radiographic response (odds ratio per interquartile range, 1.40; P = .32 adjusted for treatment) in either treatment group. In patients treated with FOLFIRINOX, HRD score dichotomized at the median was not associated with progression-free survival (median, 5.3 v 9.4 months for low v high HRD score, respectively; P = .083) or overall survival (median, 11.9 v 10.7 months for low v high HRD score, respectively; P = .76). CONCLUSION: Mutations in DNA repair genes occur in PDAC, and HRD scores can be generated in the majority of patients. The HRD score was not significantly associated with higher response rate or prolonged survival in patients treated with FOLFIRINOX.

Fine-Needle Aspiration Cytology of Noninvasive Follicular Variant of Papillary Thyroid Carcinoma Is Cytomorphologically Distinct From the Invasive Counterpart.

OBJECTIVES: To review a series of noninvasive encapsulated follicular variant of papillary thyroid carcinomas (FVPTCs) in an attempt to further define the role of cytopathology in the diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features and invasive FVPTC. METHODS: Surgical pathology cases diagnosed as FVPTC with correlating thyroid fine-needle aspiration (FNA) were identified and divided into two FVPTC groups: noninvasive and invasive. Cytologic diagnoses were compared between them. RESULTS: We identified 23 cases that met the criteria for noninvasive FVPTC and 27 cases that were typical infiltrative FVPTC (n = 16) or encapsulated FVPTC with either capsular and/or lymphovascular invasion (n = 11). Of the noninvasive FVPTC cases, there were four benign lesions, 14 follicular lesions of undetermined significance (FLUS), four follicular neoplasms (FNs), one suspicious case, and no papillary thyroid carcinomas (PTCs). In the invasive FVPTC group, there were no benign cases, four FLUS, three FNs, 12 suspicious cases, and eight PTCs. CONCLUSIONS: There is a distinction in the cytologic diagnosis between noninvasive and invasive FVPTC. The invasive subtype was diagnosed by FNA as suspicious for PTC or PTC in nearly 75% of cases, while only one (4%) case for the noninvasive subtype was diagnosed as suspicious for PTC (P < .05).

Pathological complete response with anti-PD-1 therapy in a patient with microsatellite instable high, BRAF mutant metastatic colon cancer: a case report and review of literature.

IMPORTANCE: Mismatch repair (MMR) and BRAF mutation status are established independent prognostic factors for colorectal cancer (CRC). MMR deficient tumors are considered to have better prognosis whereas BRAF mutation is associated with poor prognosis. Studies evaluating the combined effect of BRAF and MMR status suggest MSI-high and BRAF mutant patients have a poorer prognosis as compared to MSI-high and BRAF wild type patients. Emerging evidence suggests MMR status predicts the immune response to anti-PD-1 therapy in CRC patients; however little is known about combined MMR and BRAF mutation status in this context. Therefore, it is important to identify whether there is a differential response to anti-PD-1 therapy based on BRAF status in the subset of MSI-high CRC patients. OBSERVATIONS: We report the first case of MSI-high, BRAF mutant metastatic CRC that had an excellent response (pathologic complete response) to anti-PD-1 therapy. We take this opportunity to review the similar cases in literature and discuss combined MMR and BRAF status as a potential biomarker for anti-PD-1 therapy. CONCLUSION AND RELEVANCE: The case presented illustrates that anti-PD-1 therapy can be effectively used to treat CRC patients with MSI-high and BRAF mutant status which is usually considered a poor prognostic category as opposed to MSI-high and BRAF wild type tumors. Future studies with anti-PD-1 therapy distinguishing these molecular subgroups will improve our knowledge of whether BRAF status can add to MMR status as a predictive biomarker for anti-PD-1 therapy in patients with metastatic CRC.

Endoscopic ultrasound-guided fine-needle aspiration of the pancreas: a retrospective study of 1000 cases.

INTRODUCTION: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) has emerged as a superior method for the diagnosis of pancreatic tumors. Very few large studies have been published. We retrospectively examined 1000 cases to determine the sensitivity and specificity of EUS-guided FNA for solid and cystic lesions. MATERIALS AND METHODS: EUS-guided FNA was performed in 1000 patients. Air-dried aspirates were reviewed immediately to ensure adequacy, and ethanol-fixed aspirates were reviewed the following day. The rendered diagnoses were placed into various categories and compared to subsequent histologic and clinical follow-up data. RESULTS: Of the 1000 cases, 579 were solid lesions. The FNA diagnoses of the solid lesions were benign (B) 229 (39.5%), atypia (A) 22 (3.8%), suspicious (S) 27 (4.7%), malignant (M) 260 (44.9%), tumor (T) 1 (0.2%), and nondiagnostic (ND) 40 (6.9%). The sensitivity, specificity, positive predictive value, and negative predictive value for solid lesions were 97%, 97%, 99%, and 94%, respectively. There were 421 cystic lesions. The FNAs of the cystic lesions were classified as follows: B 342 (81.2%), A 5 (1.2%), S 4 (1%), M 7 (1.7%), T 46 (10.9%), and ND 17 (4.0%). The sensitivity, specificity, positive predictive value, and negative predictive value to identify mucinous tumors and malignancy for cystic lesions were 46%, 98%, 94%, and 87%, respectively. CONCLUSIONS: At our institution, EUS-guided FNA of solid pancreatic lesions is both sensitive and specific for the diagnosis of both primary and metastatic tumors. For cystic lesions, FNA is not as sensitive, but its specificity remains high.