New Clinicopathologic Scenarios of EBV+ Inflammatory Follicular Dendritic Cell Sarcoma: Report of 9 Extrahepatosplenic Cases.

EBV+ inflammatory follicular dendritic cell (FDC) sarcoma is an indolent malignant neoplasm of spindled FDCs with a rich lymphoplasmacytic infiltrate and a consistent association with Epstein-Barr virus (EBV). It occurs exclusively in the liver and spleen, with the exception of a few colonic examples. In this study, we report 9 extrahepatosplenic cases, including 4 occurring in previously undescribed sites, but all apparently anatomically related to the aerodigestive tract. The cases included 5 gastrointestinal tumors all presenting as colonic pedunculated polyps, 2 presenting as mesocolon mass, and 2 involving the palatine or nasopharyngeal tonsils. One patient with a colonic tumor was complicated by paraneoplastic pemphigus. The patients had a median age of 58 years, with female predominance (female:male=7:2). A favorable outcome was observed in 7 patients. Histologically, EBV+ inflammatory FDC sarcomas arising from these anatomic sites were similar to their hepatosplenic counterparts. Spindled to oval neoplastic cells with ill-defined cell borders were dispersed or formed loose whorled fascicles in a dense lymphoplasmacytic background. They had vesicular nuclei with distinct nucleoli and typically exhibited a range of nuclear atypia in the same case. The neoplastic cells showed variable expression of FDC markers and were labeled for Epstein-Barr virus-encoded RNA on in situ hybridization. These 9 cases thus broaden the clinicopathologic scenarios of EBV+ inflammatory FDC sarcoma. Recognition of the potential existence of this tumor type in extrahepatosplenic sites permits a correct diagnosis to be made.

[The prevalence of human papillomaviruses in patients with colon polyps].

INTRODUCTION: Potential role of HPV infection in pathogenesis of colon polyps and cancer remains undetermined. The aim of the study was to investigate the prevalence of DNA of HPV- 6, -11, -16 and -18 in the biopsies from colon polyps. MATERIAL AND METHODS: We investigated the biopsies from 24 patients (23 from colon polyps and I from colon cancer) of Department of Gastroenterology Medical University of Warsaw using Real time PCR HPV-6/11. Real-TM (Sacace Biotechnologies) was performed on termocycler Smart Cycler Dx. RESULTS: We didn't detect oncogenic HPV16 and HPV18 in any of the investigated specimens, HPV-11 was present in 11 patients including all patients with adenoma tubule-villosum. We detect HPV6 in 5 samples from polyps and 1 from colon cancer. CONCLUSIONS: HPV 6 and HPV 11 could play a role in pathogenesis some colon polyps but the final conclusions demand further investigations. Oncogenic HPV 16 and 18 probably don't play any role in colon polyps pathogenesis.

Demonstration of Herpes Simplex Virus, Cytomegalovirus, and Epstein-Barr Virus in Colorectal Cancer.

BACKGROUND: The present study sought to investigate molecular evidence for association between the presence of herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) in CRC and colorectal polyp by using the PCR method in Iran. METHODS: In this analytical case-control study, we selected 15 patients with CRC, 20 patients with colorectal polyp, and 35 patients without malignancy as controls. After DNA extraction, PCR was used to determine HSV, CMV, and EBV genome by specific primers. Statistical analysis was performed using χ2 tests. RESULTS: Our findings demonstrated that there is no direct molecular evidence to support the association between HSV, CMV, and EBV and human colorectal malignancies. CONCLUSION: The results from this study do not exclude a possible oncogenic role of these viruses in neoplastic development of colon cells.

Detection of human papillomavirus infection by molecular tests and its relation to colonic polyps and colorectal cancer.

OBJECTIVES: To prospectively examine the association between human papilloma virus (HPV) colonization of the colonic mucosa and the development of colorectal polyps (CRPs), and colorectal cancer (CRC) in Saudi Arabia. METHODS: A case control study was performed between January 2013 and December 2014. All eligible patients underwent standard diagnostic colonoscopy. Patients with polyps or colorectal cancer were considered cases, while those with any other endoscopic findings were controls. Biopsy samples from polyps and tumors, and/or from normal colonic mucosa were acquired. Human papilloma virus colonization was detected using a hybrid capture technique of samples taken from both normal tissue, and CRPs and CRC. The association between HPV and CRPs/CRC was evaluated. RESULTS: A total of 132 patients were recruited. The mean age was 53 (± 15.9) years. Sixty patients had endoscopically detectable CRPs/CRC, and 72 had either inflammation or normal endoscopic evaluations. Only 4 (0.8%) of the 132 samples that were collected and analyzed were positive for the HPV gene. Statistical analysis did not identify any significant association between HPV colonization and the presence of CRPs/CRC. The only significant predictor of detecting CRPs/CRC on colonoscopy was symptomatic presentation (odds ratio=11.072, 95% confidence interval 4.7-26.2, p less than 0.001). CONCLUSION: Human papilloma virus colonic colonization is rare in Saudi Arabia. An association between HPV colonization and CRP/CRC development could not be identified in this cohort of patients.

Human JC polyomavirus in normal colorectal mucosa, hyperplastic polyps, sporadic adenomas, and adenocarcinomas in Portugal.

John Cunningham virus (JCV) infects chronically human populations worldwide and probably might confer a higher risk for colorectal cancer (CRC). The prevalence of JCV DNA has been determined in normal colon mucosa and compared it with different degrees of colorectal lesions, as well as viral presence in the urine of the individuals in the study. JCV DNA was detected by a nested-PCR approach targeting the JCV small-t antigen in 100 healthy controls, and 100 patients undergoing biopsy for diagnosis of colorectal disorders. JCV DNA was detected in 40% of normal mucosa from controls and patients. JCV DNA presence in urine was also similar in controls and patients (37-41% range). JCV DNA detection in normal mucosa and urine reflects the infected population in Portugal. However, in cases with colorectal tumor lesions, JCV DNA was detected in 90% cases, independently of histological type or grade, and this increase was significantly higher with respect to its normal surrounding mucosa. This higher detection of JCV DNA in tumor lesions with respect to its own normal mucosa suggested that a selection for virus containing cells has occurred at some early stage in tumor initiation or progression. JCV may have a specific tropism for colon epithelial cells with some inherent predisposition that makes them more prone to oncogenic transformation, with selection of infected cells. Several p53 polymorphisms in intron 2, common to both groups, were more frequently detected in colorectal pathology cases. A novel p53 mutation in the 3' untranslated region (exon 11) was identified in 10 patients.

P16/CDKN2A and Ki-67 enhance the detection of anal intraepithelial neoplasia and condyloma and correlate with human papillomavirus detection by polymerase chain reaction.

The classification of anal intraepithelial neoplasia (AIN) in mucosal biopsies is subject to considerable interobserver variability. Previous studies have shown that Ki-67 and p16/CDKN2A immunostains aid detection of dysplasia in biopsy samples from the uterine cervix. The aim of this study was to determine whether Ki-67 and p16/CDKN2A immunolabeling enhanced diagnostic accuracy in the assessment of anal mucosal biopsies from patients with suspected human papillomavirus (HPV) infection. The study consisted of 75 cases that were originally interpreted to represent normal anal transitional zone (n=15), fibroepithelial polyp (n=10), condyloma accuminatum (n=10), low-grade AIN (AIN1, n=20), and high-grade AIN (n=20), including 10 cases each of AIN2 and AIN3. The histologic features of all cases were re-reviewed and categorized based upon consensus agreement, which resulted in reclassification of 16 cases. Thus, the final study group consisted of 17 samples of normal anal transition zone, 14 fibroepithelial polyps, 6 condylomata accuminata, and 38 cases of AIN (11 AIN1, 16 AIN2, and 11 AIN3). Each case was tested for the presence of HPV DNA by a SPF10 polymerase chain reaction and LiPA25 genotyping assay and immunostained for Ki-67 and p16/CDKN2A. A positive Ki-67 result was defined as the presence of a cluster of at least 2 strongly stained epithelial nuclei in the upper two-thirds of the epithelial thickness. A positive result for p16/CDKN2A was defined as diffuse moderate-to-strong cytoplasmic and nuclear staining. None of the anal transition zone samples or fibroepithelial polyps showed Ki-67 or p16/CDKN2A staining. All condylomata and samples of AIN contained HPV DNA and showed positive Ki-67 labeling. All cases of high-grade AIN showed positive p16/CDKN2A staining. We conclude that Ki-67 labeling detects anal HPV-related changes with a high degree of sensitivity and specificity, whereas increased p16/CDKN2A staining is strongly associated with high-grade squamous neoplasia. These results indicate that a combination of these markers may aid interpretation of anal mucosal biopsy samples.

[The occurrence of human papillomavirus--HPV in the biopsies from colon polyps and cancer]. / Wystepowanie wirusów brodawczaka ludzkiego--Hpv w wycinkach z polipów i raka jelita grubego.

Human papillomaviruses (HPV) infection can be associated with benign (warts) and malignant (precancer and cancer) genital, perianal and oral lesions. The role of HPV in the pathogenesis of colonorectal cancer and adenomas is still undetermined. We investigated the occurrence of nononcogenic HPV 6/11 and oncogenic 16/18 DNA in colon cancer, polyps and normal tissue using PCR. HPV 16/18 were detected more frequently in colon cancers (67%) and adenomas (56%) than in normal colon mucosa (28%). In case of HPV 6/11 the differences were not significant. The results suggest the possible role of HPV 16/18 in pathogenesis of colon cancers and polyps.

Multinucleate epithelial change in colorectal hyperplastic polyps: a review of 27 cases.

AIM: To document the histological features of multinucleated epithelial giant cells (MEGs) in colorectal hyperplastic polyps and determine a possible aetiological agent. METHODS: Hyperplastic polyps were assessed for MEGs during the routine reporting at a private laboratory and public hospital laboratory. The histological features and clinical data were assessed, and immunohistochemical stains were performed to assess for viral infection (cytomegalovirus (CMV) and herpes simplex virus (HSV) 1 and 2) and to assist in the assessment of dysplasia (Ki-67, beta-catenin and p53). Ultrastructural examination was performed in one case. RESULTS: MEGs were identified in 27 polyps (24 patients). There was active inflammation in the polyps in nearly all cases (n = 24) and most showed changes in adjacent non-hyperplastic bowel mucosa such as focal basal cryptitis and apoptosis of crypt epithelium (16 patients). Immunohistochemistry for CMV, HSV and p53 was negative in all cases. The MEGs showed nuclear positivity for the proliferative marker Ki-67 and membranous positivity for beta-catenin. Ultrastructural studies failed to reveal viral particles. CONCLUSIONS: All the polyps containing MEGs showed active inflammation and apoptosis, and in most there was also focal inflammation and apoptosis in the adjacent mucosa. Inflammation in conjunction with the increased epithelial proliferation characteristics of hyperplastic polyps could be the mechanism for the MEG formation. In this series, all the polyps were associated with sodium phosphate bowel preparation (NaP) and the pro-inflammatory properties of NaP may be a stimulus for the induction of giant cells.

Specific localisation of human cytomegalovirus nucleic acids and proteins in human colorectal cancer.

BACKGROUND: Colorectal cancer is the second most frequent cause of death from cancer in the USA, and most tumours arise sporadically with no clear cause or genetic predisposition. Human cytomegalovirus is a beta-herpesvirus that is endemic in the human population and can cause life-threatening disease in immunosuppressed adults. In vitro, human cytomegalovirus can transform cells and dysregulate many cellular pathways relevant to colon adenocarcinoma pathogenesis, especially those affecting the cell cycle, mutagenesis, apoptosis, angiogenesis, and cyclo-oxygenase-2 (COX-2) expression. We aimed to assess whether gene products of human cytomegalovirus could be detected in colorectal cancers. METHODS: We obtained formalin-fixed, paraffin-embedded pathological specimens of colorectal polyps, adenocarcinomas, and adjacent normal mucosa from 29 patients. To detect human cytomegalovirus proteins and nucleic acids, we used immunohistochemistry with two different monoclonal antibodies, in-situ hybridisation, and PCR with DNA sequencing. FINDINGS: Human cytomegalovirus proteins IE1-72 and pp65 were detected in a tumour cell-specific pattern in 14 (82%) of 17 and seven (78%) of nine colorectal polyps, respectively, and 12 (80%) of 15 and 11 (92%) of 12 adenocarcinomas, respectively, but not in adjacent non-neoplastic colon biopsy samples from the same patients (none of seven and none of two, respectively). Human cytomegalovirus infection of colon-cancer cells (Caco-2) in vitro resulted in specific induction of Bcl-2 and cyclo-oxygenase-2 proteins, both of which are thought to contribute to progression of colon cancer. INTERPRETATION: Human cytomegalovirus nucleic acids and proteins can be found that specifically localise to neoplastic cells in human colorectal polyps and adenocarcinomas, and virus infection can induce important oncogenic pathways in colon-cancer cells.

Heterogeneity of TT virus related sequences isolated from human tumour biopsy specimens.

TT viruses have recently been reported in serum samples from varying percentages of human blood donors and in patients with chronic liver disease. However, no association with human pathology has yet been reported. In a pilot study we analysed 162 biopsy specimens from various human cancers and from colon polyps for the presence of TT virus related sequences by polymerase chain reaction using three sets of nested primers for TT virus detection. All gels were subjected to Southern blot hybridisation, and DNA from hybridising bands was cloned and sequenced. A total of 54.3% of tumour specimens contained identifiable TT virus related sequences. Specimens from hypopharynx, larynx, endometrial, ovarian and bladder cancers were 14-35% positive and gastrointestinal cancers (oesophagus, stomach, colon, rectum) and colon polyps 57-100% positive. Lung cancers (68.4%), mammary cancers (50%), multiple myelomas (85.7%) and human leukaemias (53.3%) also revealed a high prevalence of TT virus related sequences. Since normal control tissues were not available for the tumour biopsy specimens tested, these data do not permit conclusions concerning a possible causal relationship between the virus infections and carcinogenesis. Another aspect, however, deserves attention: the heterogeneity of TT virus clones obtained from the specimens tested here was striking: 66 novel sequences, probably belonging to new types were identified. Only 16 clones corresponded by more than 97% of their sequences to established prototypes. Even individual tumours commonly contained sequences substantially diverging in nucleic acid composition. Up to five different types were identified within an individual tumour. The high variability of these virus types suggests that additional primer combinations within the highly conserved region of the genome would detect a still higher rate of positive tumours.

Squamous cell carcinoma in situ arising in inflammatory cloacogenic polyps: report of two cases with PCR analysis for HPV DNA.

Inflammatory cloacogenic polyp (ICP) is regarded as part of the spectrum of pathological changes encountered in mucosal prolapse syndrome (MPS)/solitary rectal ulcer. We present the clinicopathological features of two females with squamous cell carcinoma in situ arising in their ICPs. Human papillomavirus (HPV) type 16 was demonstrated in the areas of squamous carcinoma in situ in both polyps by polymerase chain reaction. These cases highlight the need for close scrutiny of the squamous components of these lesions.