Medullary Carcinoma of the Penis: A Distinctive HPV-related Neoplasm: A Report of 12 Cases.

A third to half of penile invasive squamous cell carcinomas are human papillomavirus (HPV) related. Warty (condylomatous), warty-basaloid, and basaloid carcinomas are the most common subtypes associated with HPV. Less frequent are clear cell and lymphoepithelioma-like carcinomas. Here we report a novel penile tumor associated with HPV. Twelve cases were selected from 1010 penile carcinomas, part of an international HPV detection study conducted at the Institut Català d'Oncologia, Barcelona, Spain. Immunostaining with p16 was performed on all cases, and HPV-mRNA detection was also performed. En bloc full tumor staining was the utilized criteria for positivity of p16. For HPV-DNA detection, whole-tissue section polymerase chain reaction analysis was performed by SPF10-DEIA-LiPA25 (version 1). The patients' ages ranged from 42 to 92 years (average, 71 y). The tumor was most commonly located in the glans. A characteristic microscopic finding was the presence of a moderate to dense tumor-associated inflammatory cell infiltrate composed of neutrophils, lymphocytes, plasma cells, or eosinophils. Tumors grew in large solid sheets, nests, or had a trabecular pattern. Cells were large and poorly differentiated or anaplastic. Keratinization was minimal or absent. Nuclei were large with prominent nucleoli. Mitoses were numerous. Tumor necrosis was common. Deep invasion of the corpora cavernosa was frequent. p16 and HPV-DNA were positive in all cases, whereas mRNA detection was positive in 9 cases only. The prevalent genotype was HPV16 (9 cases, 75%). Other genotypes were HPVs 58, 33, and 66. Medullary carcinomas of the penis are morphologically distinctive HPV-related high-grade neoplasms affecting older individuals. More studies are necessary to delineate the epidemiological, clinical, and molecular features of this unusual penile neoplasm.

Gastrointestinal cancers accompanied by a dense lymphoid component: an overview with special reference to gastric and colonic medullary and lymphoepithelioma-like carcinomas.

This review highlights the difference between so-called medullary carcinoma and lymphoepithelioma-like carcinoma with reference to the gastrointestinal tract. The two terms have been applied synonymously in the gastrointestinal tract, with the majority of carcinomas associated with lymphocytes being termed medullary carcinomas. True medullary carcinomas are disposed in syncytial sheets and have well defined peripheral margins; the preponderance of inflammation is peri-tumoural. These tumours are also associated with microsatellite instability (MSI). Lymphoepithelioma-like carcinomas tend not to have continuous sheets of tumour but are instead made up of small clusters and aggregates of tumour that are broken up by large numbers of intra-tumoural lymphocytes. These tumours may be associated with Epstein-Barr virus (EBV). Occasional cases may be associated with epigenetic silencing of MLH-1. In conclusion, carcinomas associated with dense lymphoid stroma maybe associated with either MSI or EBV. There are some morphological features that favour either type and in the stomach MSI and EBV are mutually exclusive.

No evidence of human papillomavirus DNA in breast carcinoma in Tunisian patients.

The aim of this study was to evaluate the prevalence of broad range of anogenital HPVs in a series of 123 Tunisian breast carcinoma cases. PCR assays were performed to amplify regions within the L1, E1, E6 and E7 open reading frames of a broad range of anogenital HPVs and specific types HPV16, 18, 31 and 33. In addition, we performed an in situ hybridization analysis using HPV biotinylated DNA probes for the detection of broad spectrum of anogenital HPV types, high-risk HPV types (16 and 18), intermediate-risk HPV types (31 and 33) and low-risk HPV types (6 and 11). None of the 123 breast carcinoma samples showed PCR amplification of HPV DNA using the broad spectrum consensus primer-pairs E1-350L/E1-547R and GP5+/GP6+ primers. Furthermore, neither high risk nor low-risk HPV types were detected in any of these cases. Moreover, using in situ hybridization for the detection of HPVs, we failed to detect a positive signal in neoplastic cells in any case. Our results suggest that anogenital papillomaviruses are unlikely to play a role in the development of breast carcinomas in Tunisian patients.

Undifferentiated gastric carcinoma with lymphoid stroma (lymphoepithelioma-like carcinoma/medullary carcinoma).

Undifferentiated gastric carcinoma with lymphoid stroma is a histological type of gastric cancer with favourable prognosis, microscopically characterised by nests of neoplastic epithelial cells intermingled with a dense lymphoid proliferation. Various studies have shown a close relationship between undifferentiated gastric carcinoma with lymphoid stroma and Epstein-Barr virus infection; the presence of viral DNA in tumour cell nuclei has been demonstrated using polymerase chain reaction and Epstein-Barr virus-encoded small RNA in neoplastic cell nuclei have been found using in situ hybridization. We describe two cases of undifferentiated gastric carcinoma with lymphoid stroma, one infiltrating the submucosa of the gastric body and the other invading the muscularis propria of the antrum. No lymph node neoplastic invasion was documented in either case. Epstein-Barr virus was detected in the neoplastic cell nuclei in both cases with in situ hybridization.

[Detection of Epstein-Barr virus in breast cancers with lymphoid stroma]. / Détection du virus d'Epstein-Barr dans les cancers du sein à stroma lymphoïde.

OBJECTIVE: the purpose of our work is to detect Epstein-Barr virus (EBV) in 2 types of breast cancer: medullary carcinoma and high grade invasive ductal carcinoma with lymphoid stroma. PATIENTS AND METHODS: we proceeded to a retrospective study of 18 medullary carcinoma and 18 high grade invasive ductal carcinoma with lymphoid stroma. The detection of the virus was carried out by immunohistochemistry with anti-LMP2 antibody and by hybridization in situ by oligonucleotides EBER1 and EBER1. LMP1 as well as hybridization in situ were positive in 5 tumors (3 medullary carcinoma and 2 high grade invasive ductal carcinoma with lymphoid stroma). RESULTS: positivity was observed in tumor cells and neither in epithelial non tumoral ones nor in lymphoid cells. DISCUSSION AND CONCLUSIONS: during numerous years, correlations between the replication of EBV and the appearance of a malignant phenotype were limited to nasopharyngeal carcinoma and to lymphoid cells. A controversy regarding the association of EBV with breast cancers has recently been reported in the literature. This cancer being very frequent, the involvement of EBV even in a small proportion of breast cancers could have important implications. Our results suggest a possible implication of EBV in these tumours but other studies are necessary.

Absence of Epstein-Barr virus in medullary carcinoma of the breast as demonstrated by immunophenotyping, in situ hybridization and polymerase chain reaction.

Medullary carcinoma of the breast is an epithelial malignant proliferation that shares many characteristics (macroscopic, microscopic, epidemiologic, and prognostic) with lymphoepithelioma-like carcinomas of various sites. The authors hypothesized that they could also share the same etiologic agent, the Epstein-Barr virus (EBV). Epstein-Barr virus, a virus of the herpesvirus family, is to be associated with lymphoepithelioma-like carcinomas of the nasopharynx, stomach, lung, thymus, and salivary gland. Therefore, the authors looked for the virus in a series of 10 medullary carcinomas of the breast. Using immunohistochemistry, in situ hybridization and polymerase chain reaction, this investigation failed to show evidence of EBV. Similar negative results have been reported in lymphoepithelioma-like carcinomas arising in the skin and in the uterine cervix, which like the breast do not originate in the foregut. These results suggest that the pathogenesis of these tumors is not unique, implicating probably different etiopathogenic entities.

Epstein-Barr virus association with early cancers found together with gastric medullary carcinomas demonstrating lymphoid infiltration.

Seven early gastric cancers obtained from patients also demonstrating Epstein-Barr virus (EBV)-positive gastric medullary carcinoma with lymphoid infiltration were investigated using a combined polymerase chain reaction (PCR) and in situ hybridization (ISH) approach. Sharing the same background mucosa as gastric medullary cancers, they comprised four intramucosal carcinomas, predominantly well-differentiated adenocarcinomas, and three submucosal carcinomas, histologically showing mixtures of well and poorly differentiated adenocarcinoma. In the three cases of submucosal carcinoma, the presence of EBV was proven by means of both PCR and ISH. However, not all cancer cells were positive for EBV on the basis of ISH examination, in contrast to the large series of gastric carcinoma with lymphoid infiltration previously investigated. All four mucosal carcinomas were EBV-negative. Lymphocyte-determined membrane antigen (LYDMA) monoclonality, performed by PCR, and latent membrane protein-1 (LMP-1) and Epstein-Barr virus (EBNA2) expression, assessed immunohistochemically, were negative in all seven cases. The results suggest that EBV becomes associated with gastric medullary carcinoma with lymphoid infiltration (GMCL) at a relatively early stage of the disease, shortly after the tumour has initially progressed to an invasive form, and plays some role in the manifestation as GMCL.