Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a hereditary cancer syndrome where affected individuals are predisposed to the development of multiple leiomyomas of the skin and uterus and aggressive forms of kidney cancer. Affected individuals harbor a germline heterozygous loss-of-function mutation of fumarate hydratase (FH) gene. Uterine leiomyomas are present in up to 77 percent of women with this syndrome. Previous studies have shown that inactivation of the FH gene is unusual for non-syndromic leiomyomas. Therefore, it might be possible to distinguish two genetic groups of smooth muscle tumors: the most common group of sporadic uterine leiomyomas without FH gene inactivation and the more unusual group of HLRCC leiomyomas in patients that harbor a germline mutation of FH, although the exact prevalence of hereditary HLRCC is unknown. We reviewed the clinical, morphological and genotypical features of uterine leiomyomas in 19 HLRCC patients with FH germline mutations. Patients with HLRCC syndrome were younger in age compared with regular leiomyomata. DNA was extracted by microdissection and analysis of LOH at 1q43 was performed. Uterine leiomyomas in HLRCC have young age onset and are multiple with size ranging from 1 to 8 cm. Histopathologically, HLRCC leiomyomas frequently had increased cellularity, multinucleated cells and atypia. All cases showed tumor nuclei with large orangiophillic, nucleoi surrounded by a perinucleolar halo similar to the changes found in HLRCC renal cell cancer. Occasional mitoses were found in three cases; however the tumors did not fulfill the criteria for malignancy. Our study also showed that LOH at 1q43 was frequent in HLRCC leiomyomas (8/10 cases), similarly to what it has been previously found in renal cell carcinomas from HLRCC patients. LOH is considered to be the second hit that inactivates the FH gene. We conclude that uterine leiomyomas associated with HLRCC syndrome have characteristic morphologic features. Both, uterine leiomyomas and renal cell carcinoma share some morphological nuclear changes and genotypical features in HLRCC patients. The specific morphological features of the uterine leiomyomas that we describe, may help to identify patients that may be part of the hereditary syndrome.

For several years, the lack of consensus on definition, nomenclature, natural history, and biology of serrated polyps (SPs) of the colon has created considerable confusion among pathologists. According to the latest WHO classification, the family of SPs comprises hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs). The term SSA/P with dysplasia has replaced the category of mixed hyperplastic/adenomatous polyps (MPs). The present study aimed to evaluate the reproducibility of the diagnosis of SPs based on currently available diagnostic criteria and interactive consensus development. In an initial round, H&E slides of 70 cases of SPs were circulated among participating pathologists across Europe. This round was followed by a consensus discussion on diagnostic criteria. A second round was performed on the same 70 cases using the revised criteria and definitions according to the recent WHO classification. Data were evaluated for inter-observer agreement using Kappa statistics. In the initial round, for the total of 70 cases, a fair overall kappa value of 0.318 was reached, while in the second round overall kappa value improved to moderate (kappa = 0.557; p < 0.001). Overall kappa values for each diagnostic category also significantly improved in the final round, reaching 0.977 for HP, 0.912 for SSA/P, and 0.845 for TSA (p < 0.001). The diagnostic reproducibility of SPs improves when strictly defined, standardized diagnostic criteria adopted by consensus are applied.

Favorable prognosis in completely resected NSCLC is determined by a B-cell-mediated immune response. It can be differently scored by a 50-gene expression profile or by CD20 immunostaining. That prognosis information not reflected by traditional classifications may become a new tool for determining individualized adjuvant therapies.

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