Multifocal mantle cell lymphoma in situ in the setting of a composite lymphoma.

OBJECTIVES: Mantle cell lymphoma in situ (MCLIS) consists of immunophenotypically defined but histologically inapparent neoplastic cells restricted to narrow mantle zones, without expansion or invasion beyond the mantle zone. We report a unique case of MCLIS associated with a much more manifest nodal marginal zone lymphoma (MZL) in an inguinal lymph node, porta hepatis lymph node, and bone marrow. METHODS: Biopsies from all three locations were evaluated using standard H&E-stained sections, immunohistochemistry, flow cytometry, metaphase cytogenetics, and/or fluorescence in situ hybridization (FISH). RESULTS: This case is unique for three reasons. First, the histologically covert mantle cell lymphoma was multifocal, detected in all three locations using one or more of flow cytometry, immunohistochemistry, cytogenetics, and FISH. Second, the MCLIS was always accompanied by a more histologically dominant MZL. Third, where evaluable, it did not grow in an appreciable mantle zone distribution, presumably due to destruction of the normal nodal architecture by the neoplastic MZL cells and the resulting absence of recognizable follicles and mantle zones. CONCLUSIONS: This unique case provides new insight into the pathogenesis of MCLIS.

Morphologic, patient and interpreter profiles of high-risk human papillomavirus-positive vs.-negative cases of atypical squamous cells of undetermined significance.

OBJECTIVE: To define the morphologic and patient profiles, if any, that distinguish high-risk human papillomavirus (HR-HPV)-positive atypical squamous cells of undetermined significance (ASCUS) from HR-HPV-negative ASCUS and to compare individual and laboratory reporting rates with the national averages. STUDY DESIGN: One hundred fifty liquid-based cervicovaginal preparations (ThinPrep, Cytyc Corporation, Boxborough, Massachusetts, U.S.A.) with a diagnosis of ASCUS and a reflex HR-HPV test were assessed for the following features: background patient information, cell morphology, cell patterns and interpreter profiles. Fisher's Exact test (2-tailed) was used to calculate the exact probability of obtaining results by chance. RESULTS: The median age of the HR-HPV-positive patients was approximately 11 years younger than the HPV-negative group, and pregnant patients were also more apt to be HPV positive. Atypical cells in greater numbers and in groups as opposed to single cells correlated more often with HR-HPV-positive individuals. Koilocytelike changes and parakeratosis were more frequently associated with HR-HPV, but the presence of Trichomonas was usually a negative predictor. CONCLUSION: In cases diagnosed as ASCUS, there are certain cytologic features and patient types that are more likely to be associated with HR-HPV positivity. This could be used in everyday practice to further fine tune the diagnosis of ASCUS. Monitoring individual and laboratory ASCUS rates with HR-HPV positivity can be an important quality improvement indicator.

Expression of cytokeratin markers, ER-alpha, PR, HER-2/neu, and EGFR in pure ductal carcinoma in situ (DCIS) and DCIS with co-existing invasive ductal carcinoma (IDC) of the breast.

Previously, we showed that pure ductal carcinoma in situ (DCIS) of the breast can be divided into 3 subtypes (luminal, basal/stem, and null) based on the expression of 5 cytokeratin (CK) markers: CK5/6, CK14, CK17 (stem/basal), and CK8, CK18 (luminal). The distributions of CK subtypes were associated with nuclear grade and differential expression of estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), HER-2/neu, and epidermal growth factor receptor (EGFR). In this study, we further explore the expression patterns of CK markers, ER-alpha, PR, HER-2/neu, and EGFR by immunohistochemical (IHC) analysis of 99 cases of pure DCIS and 96 cases of DCIS with co-existing invasive ductal carcinoma (DCIS/IDC). We show that between high-grade DCIS and DCIS/IDC, there are differential expression patterns for ER-alpha, PR, and EGFR in corresponding CK subtypes, suggesting that at least some pure DCIS is molecularly distinct from DCIS/IDC. In most cases there is a high degree of co-expression of these markers between DCIS and the co-existing IDC, suggesting that DCIS is frequently a precursor lesion for co-existing IDC. The rate of discordant expression of these markers is low and is more frequently associated with high-grade carcinoma, suggesting that other molecular pathways also may also be present. There are significant differences in the expression of these molecular markers between high-grade and non-high-grade carcinomas, supporting the view that high-grade and non-high-grade carcinomas of the breast are molecularly distinct entities.