Carcinomas with neuroendocrine (NE) differentiation have been associated with poor outcome in different organs. The purpose of this study was to evaluate the presence and significance of NE expression in a series of 46 undifferentiated endometrial carcinomas diagnosed between 1988 and 2005. NE expression was studied by immunohistochemistry including synaptophysin, chromogranin, and/or CD56. The patients' age ranged from 30 to 84 years (mean 55). Staging information was available for 45 cases and according to the International Federation of Gynecology and Obstetrics system they were distributed as follows: stage I (9 cases), stage II (2 cases), stage III (9 cases), and stage IV (25 cases). NE expression was present in 19/46 (41%) cases; however, it was diffuse in only 9% of the tumors. The median survival for patients without NE expression was 7 months (95% confidence interval 4-10 mo) and for patients with NE expression was 12 months (95% confidence interval 6-27 mo). The survival curves do not differ significantly (P=0.49). NE expression is common in undifferentiated carcinoma of the endometrium, as it was found in 41% of our cases. In most cases, NE expression is only focally present (< or =10% of the cells). There is no difference in overall survival in patients with or without NE expression.

Melanocytic lesions in certain locations (eg, genital, breast, acral) may have histologic and clinical features simulating melanoma. Here we describe a group of lesions from the lower distal extremity and analyze their histologic features and possible relation to dysplastic nevi (DN) and melanomas. One hundred fifteen melanocytic lesions from the ankle were retrieved from January 1990 to August 2006 from the files of M. D. Anderson Cancer Center and were classified as benign melanocytic nevi (BN; n=17), DN (n=35), melanomas (MM; n=52), and melanocytic nevi of the ankle with atypical features (MNAAF; ie, cases that did not readily fit in any of the previous categories, n=11). Data analyzed included clinical (age and sex) and histologic features (circumscription, symmetry, cohesiveness of nests, suprabasal melanocytes, confluence, single-cell proliferation, nuclear chromasia, size, and nucleolar features). Follow-up was collected for all MNAAF. MNAAF differ from the other types of lesions in regard to sex incidence (73% in women). The median age of those patients MNAAF was 47 years (range 29 to 76 y). All MNAAF showed moderate-severe architectural disorder whereas 78% showed only mild-moderate cytologic atypia. No MNAAF cases had recurred after follow-up (4 mo to 13 y). This study highlights a group of melanocytic lesions located on the ankle that share histologic features with acral nevi, DN, and melanoma. These lesions are more predominant in females and have moderate to severe architectural atypia but only mild-moderate cytologic atypia. After complete excision, follow-up data indicate an apparently benign outcome. Pathologists should be aware of this type of lesions to avoid overdiagnosis of melanoma.

BackgroundCaseating granulomas are often associated with a mycobacterial infection (TB) and are thought to be exceedingly rare in cutaneous leishmaniasis (CL). However, no large series has accurately documented the incidence of caseating granulomas in CL.MethodsA multiregional cohort consisting of 317 patients with CL [Syria (157), Pakistan (66), Lebanon (47), Saudi Arabia (43), Ethiopia (2) and Iran (2)] was reviewed. Clinical [age, sex, disease duration, lesion type and geographic and anatomic location] and microscopic data [presence of and type of granuloma, Ridley's parasitic index (PI) and pattern (RP)] were documented. Presence of microorganisms was evaluated using special stains (GMS, PAS, AFB and Gram) and polymerase chain reaction (PCR) for TB and CL. All cases included in this study were confirmed as CL by PCR followed by restriction fragment length polymorphism analysis for molecular speciation and were negative for other organisms by all other studies performed. Categorical and continuous factors were compared for granuloma types using Chi-square, t-test or Mann-Whitney test as appropriate.ResultsGranulomas were identified in 195 (61.5%) cases of CL and these were divided to 49 caseating (25.2%), 9 suppurative (4.6%) and 137 tuberculoid without necrosis (70.2%). Caseating and tuberculoid granuloma groups were significantly different in terms of the geographical source, with more cases harboring caseating granulomas in Saudi Arabia (p<0.0001). Histologically, both groups were also different in the distribution of their RP (p<0.0001) with a doubling RP3 in caseating granulomas (31% vs. 15%) as opposed to doubling of RP5 in tuberculoid granuloma group (38% vs. 19%). Time needed to achieve healing (RP5) was notably shorter in tuberculoid vs. caseating group (4.0 vs. 6.2 months). Parasitic Index, CL species and other considered variables did not differ for the granuloma type groups.ConclusionIn our multiregional large cohort, a notable 18.2% of all CL cases harbored caseating granulomas therefore; CL should be considered part of the differential diagnosis for cases with caseating granulomas in endemic regions, especially considering that the regions included in our cohort are also endemic for TB. Of note, cases of CL with caseating granulomas also showed a slower healing process, with no association with specific species, which may be due to worse host immune response in such cases or to a more aggressive leishmania strains.

Increased BRAF mutation with age along with the lack of a UVR magnitude-BRAF mutation association suggests that duration of exposure rather than UVR exposure dose is the more likely link to acquiring the mutation.