Mucinous adenocarcinoma of the prostatic urethra following a remote history of primary brachytherapy for prostate cancer.

Secondary malignancies are a known, albeit uncommon, complication of radiation for prostate cancer, either in the form of external beam radiotherapy or seed-implant brachytherapy. Of these secondary malignancies, mucinous adenocarcinoma of the prostatic urothelium is an extremely rare clinical entity that has only once been reported in the literature. We report the case of an 80-year-old gentleman who initially underwent low-dose brachytherapy for low-risk prostate cancer 18 years ago. He subsequently developed recurrent gross hematuria and obstructive voiding symptoms. He underwent cystoscopy and transurethral resection of a large tumor from within the prostate. Final pathology of the tumor revealed a mucinous adenocarcinoma. Further immunostaining revealed this is likely to have originated from the prostatic urothelium. Given his age, comorbidities, and no clear data demonstrating that aggressive extirpative surgery provides a clinical benefit, we elected to undergo surveillance. Clinicians should be aware of mucinous adenocarcinoma of the prostatic urethra as an extremely rare, radiation-induced malignancy. Once a diagnosis is made, extirpative surgery is an option for localized disease, although prognosis remains poor.

Factors Impacting the Performance Characteristics of Bile Duct Brushings: A Clinico-Cytopathologic Analysis of 253 Patients.

CONTEXT: - Literature on factors impacting bile duct brushings (BDBs) performance characteristics remain limited. OBJECTIVE: - To capture the current state of daily practice with BDB sign-out. DESIGN: - Two hundred fifty-three of 444 BDBs signed out by more than 7 cytopathologists, with histopathologic and/or clinical follow-up of at least 18 months, were examined. RESULTS: - One hundred thirty-five of 253 BDBs (53%) had histologically confirmed malignancies, 22 (9%) had cancer-related deaths, and 96 (38%) were benign. Cytologic diagnoses in the 444 BDBs were nondiagnostic (11 [2.5%]), negative (284 [64%]), atypical (62 [13.9%]), suspicious (34 [7.7%]), and malignant (53 [11.9%]). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of malignancy detection were 35%, 100%, 100%, 58%, and 66%, respectively. When atypical, suspicious, and malignant (ASM) categories were combined, sensitivity increased (58%), specificity and PPV dropped (97%), and accuracy increased (73%). Carcinoma type (bile-duct versus pancreatic-ductal) had no effect on accuracy ( P = .60) or diagnostic class ( P = .84), nor did time of performance (first 7.5 versus latter 7.5 years, P = .13). Interestingly, ThinPrep + cell block (n = 41) had higher sensitivity (61%) and lower specificity (80%) than ThinPrep only (versus 51% and 100%, respectively). Sensitivity and specificity were higher (47% and 100%) in nonstented than stented specimens (59% and 97%). Relative risk of malignancy for "suspicious" (2.30) and "atypical" (2.28) categories was lower but not very different from that of "malignant" category (2.41). CONCLUSIONS: - Bile duct brushings had fairly low sensitivity but high specificity and PPV with no false positives. Sensitivity almost doubled and specificity dipped minimally when ASM categories were combined, highlighting the need for better classification criteria for atypical/suspicious cases. Higher specificity, PPV, NPV, and accuracy but lower sensitivity in stented BDBs suggest that they be called malignant only when evidence is overwhelmingly convincing.

Mutational Landscapes of Smoking-Related Cancers in Caucasians and African Americans: Precision Oncology Perspectives at Wake Forest Baptist Comprehensive Cancer Center.

Background: Cancers related to tobacco use and African-American ancestry are under-characterized by genomics. This gap in precision oncology research represents a major challenge in the health disparities in the United States. Methods: The Precision Oncology trial at the Wake Forest Baptist Comprehensive Cancer Center enrolled 431 cancer patients from March 2015 to May 2016. The composition of these patients consists of a high representation of tobacco-related cancers (e.g., lung, colorectal, and bladder) and African-American ancestry (13.5%). Tumors were sequenced to identify mutations to gain insight into genetic alterations associated with smoking and/or African-American ancestry. Results: Tobacco-related cancers exhibit a high mutational load. These tumors are characterized by high-frequency mutations in TP53, DNA damage repair genes (BRCA2 and ATM), and chromatin remodeling genes (the lysine methyltransferases KMT2D or MLL2, and KMT2C or MLL3). These tobacco-related cancers also exhibit augmented tumor heterogeneities. Smoking related genetic mutations were validated by The Cancer Genome Atlas dataset that includes 2,821 cases with known smoking status. The Wake Forest and The Cancer Genome Atlas cohorts (431 and 7,991 cases, respectively) revealed a significantly increased mutation rate in the TP53 gene in the African-American subgroup studied. Both cohorts also revealed 5 genes (e.g. CDK8) significantly amplified in the African-American population. Conclusions: These results provide strong evidence that tobacco is a major cause of genomic instability and heterogeneity in cancer. TP53 mutations and key oncogene amplifications emerge as key factors contributing to cancer outcome disparities among different racial/ethnic groups.