No abstract

In-depth study of cell cycle proteins and human papillomavirus (HPV) genotyping can provide useful information about the malignant potential of precursor lesions of cervical carcinoma (CC). Immunostaining of cell cycle-related proteins (p16, cyclin D1, Ki-67, p53, and ProEx C) was evaluated using tissue microarrays, and HPV genotypes were identified in 144 cervical tissue specimens encompassing normal or benign epithelial lesions, low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively), and CC. In addition, 14 cases with atypical immature metaplasia (AIM) were included to compare their immunohistochemical features with those of well-established precursor lesions. Expression of p16, Ki-67, and ProEx C was most associated with the severity of dysplasia. Positive expression of p16, Ki-67, and ProEx C and negative expression of p53 seem to be related to HPV-16 infection. AIM cases show an immunohistochemical pattern more similar to LSIL than to HSIL. Immunohistochemical assessment of cell cycle proteins may help to distinguish normal and benign conditions of the cervix from precursor lesions of CC.

Serrated adenocarcinoma (SAC) is a recently recognized colorectal cancer (CRC) subtype accounting for 7.5 to 8.7% of CRCs. It has been shown that SAC has a poorer prognosis and has different molecular and immunohistochemical features compared with conventional carcinoma (CC) but, to date, only one previous study has analyzed its mRNA expression profile by microarray. Using a different microarray platform, we have studied the molecular signature of 11 SACs and compared it with that of 15 matched CC with the aim of discerning the functions which characterize SAC biology and validating, at the mRNA and protein level, the most differentially expressed genes which were also tested using a validation set of 70 SACs and 70 CCs to assess their diagnostic and prognostic values. Microarray data showed a higher representation of morphogenesis-, hypoxia-, cytoskeleton-and vesicle transport-related functions and also an overexpression of fascin1 (actin-bundling protein associated with invasion) and the antiapoptotic gene hippocalcin in SAC all of which were validated both by quantitative real-time PCR (qPCR) and immunohistochemistry. Fascin1 expression was statistically associated with KRAS mutation with 88.6% sensitivity and 85.7% specificity for SAC diagnosis and the positivity of fascin1 or hippocalcin was highly suggestive of SAC diagnosis (sensitivity 5 100%). Evaluation of these markers in CRCs showing histological and molecular characteristics of high-level microsatellite instability (MSI-H) also helped to distinguish SACs from MSI-H CRCs. Molecular profiling demonstrates that SAC shows activation of distinct signaling pathways and that immunohistochemical fascin1 and hippocalcin expression can be reliably used for its differentiation from other CRC subtypes.

Molecular characterization has been extensively studied in serrated polyps but very little is known in serrated adenocarcinomas (SACs). We analyzed the incidence of KRAS, BRAF and PIK3CA mutations, microsatellite instability (MSI) status and loss of the DNA repair proteins MLH1, MSH2, MSH6 and MGMT in a series of 89 SAC, 81 matched conventional carcinomas (CC) and 13 sporadic colorectal cancer showing histological and molecular features of high-level MSI (sMSI-H). Our results demonstrate that KRAS are more prevalent than BRAF mutations in SAC (42.7% vs. 25.8%; p 5 0.011) being the KRAS-mutated cases even more abundant in SAC displaying adjacent serrated adenomas (51%). G12D and E545K are the most common KRAS and PIK3CA mutations found in SAC, respectively. SAC show higher frequency of MGMT loss compared to CC (50.6% vs. 25.3%; p 5 0.001) especially in distal colon/rectum (60.0% vs. 21.6%; p 5 0.0009). SAC differ from sMSI-H in terms of KRAS and BRAF mutation prevalence, MSI status and MLH1 expression (p 5 0.0003, p < 0.0001, p < 0.0001, p < 0.001, respectively). SACs are more often KRAS-mutated and microsatellite stable and display different molecular and immunohistochemical characteristics compared to CC and sMSI-H.KRAS and BRAF are key mediators in the RAS-mitogen activated protein kinase (MAPK) signalling pathway of transduction signals and several components of this route are regarded as promising targets of anticancer drugs. 1,2 Activating KRAS mutations are present in about 37-50% of all colorectal cancers (CRC) 3,4 and most (90%) are found in codons 12 and 13 of exon 1. 5 On the other hand, BRAF activating mutations have been identified in about 13% of CRC 6 and a single activating point mutation at the V600E locus accounts for 80% of BRAF mutations in CRC. 7 This mutation has high sensitivity and specificity for the serrated polyp pathway and is rarely, if ever, found in the conventional adenoma-carcinoma sequence 8,9 and is strongly associated with sporadic microsatellite instability (sMSI) and DNA methylation abnormalities. 8,10 However, it has been recently demonstrated that KRAS mutations are also frequent in the serrated polyp pathway. 11 The PIK3K/AKT pathway regulates various cellular processes including proliferation, growth, apoptosis and cytoskeletal rearrangement 12 and is considered to play an important role in colorectal carcinogenesis either through RAS mutation or

These findings suggest that DLBCLs with HL features constitute a distinctive subgroup of aggressive lymphomas whose neoplastic growth and peculiar characteristics could be facilitated by a particular microenvironment found in the mediastinum.

Compared to CC, SAC displayed more HG-TB, HG-CyPs and fewer PLI at the invasive margins and this may account for its poorer clinical outcome. TB, CyPs, TGP and PLI are useful histological prognostic aids in SAC.

Fourteen cases of granulomatous mastitis (GM) studied by fine‐needle aspiration (FNA) are reviewed and nine cytologic features (necrosis, neutrophil granulocytes, foamy cells, plasma cells, granulomas, epitheloid cells, multinucleated giant cells of foreign body type and Langhans' type, duct cells, and the presence of acid‐fast bacilli) are reappraised in a semiquantitative manner. The main objective of this study was to find out if one or more of these features would permit the various granulomatous entities identified in surgical pathology to be separated cytologically. The results suggest that FNA does not permit the various granulomatous lesions identified in surgical pathology to be differentiated, since in this series different entities share a common cytologic pattern. Only the presence of acid fast bacilli in smears would enable a tuberculous etiology to be diagnosed. The opinion is put forward that the term GM should be avoided in the cytologic report and substituted by the noncommitted term “granulomatous lesion of the breast.” Diagn. Cytopathol. 17:108–114, 1997. © 1997 Wiley‐Liss, Inc.

To date, we have studied 89 palpable lesions of the scrotum, testicle, and epididymis using fine-needle aspiration cytology (FNAC). Cystic lesions (48.3%) and inflammatory pathology (25.8%) were the most frequent findings. Tumors accounted for 11.2% of results, with a slight predominance of the malignant varieties. In this article, we describe the cytopathology of the main entities and discuss the principal problems of differential diagnosis, especially among inflammatory processes, seminomas, and embryonal carcinomas. The cytopathological pattern of the neoplasias is highly characteristic, and this permits their diagnosis with great precision. FNAC is essentially nontraumatic and easy to carry out, but it requires considerable practice in its execution and in the interpretation of the aspirates. We believe FNAC to be the technique of choice for the study of the pathology of the scrotal content, and we think that it should be employed on the patient's very first visit. The main advantage of FNAC is avoiding delays in diagnosis.