Granulomatous inflammatory pseudotumor of the spleen: association with Epstein-Barr virus.

A 74-year-old woman with a clinical history of invasive ductal carcinoma of the breast was found to have a splenic mass during a routine radiographic survey. Splenectomy revealed a 3-cm well-demarcated lesion, which on histopathologic examination consisted of heterogeneous inflammatory cells. A striking feature of the lesion was the presence of innumerable well-formed non-necrotizing granulomas. Immunohistochemical studies confirmed the lesion to be composed mainly of mixed T and B lymphocytes, histiocytes, and plasma cells. No spindle cell component was evident on light microscopic examination or by immunohistochemical staining for smooth muscle actin, anaplastic lymphoma kinase, or follicular dendritic cell markers CD21 and CD35. Interestingly, Epstein-Barr virus-encoded RNA and latent membrane protein were detected by in situ hybridization and immunohistochemistry in numerous lymphohistiocytic cells within the lesion, but not in surrounding uninvolved splenic tissue. To our knowledge, this case represents a rare example of splenic inflammatory pseudotumor with exuberant granulomatous reaction in association with Epstein-Barr viral infection.

Detection of human papillomavirus-related squamous cell carcinoma cytologically and by in situ hybridization in fine-needle aspiration biopsies of cervical metastasis: a tool for identifying the site of an occult head and neck primary.

BACKGROUND: Fine-needle aspiration (FNA) biopsy often is the first diagnostic procedure performed in patients with head and neck masses. When squamous cell carcinoma (SCC) is diagnosed, proper management and improved prognosis depends on identification of the primary tumor. Recent studies have indicated that human papillomavirus (HPV) infection is associated closely with oropharyngeal SCC and that these tumors have a distinct nonkeratinizing morphology. In this study, the authors explored the value of identifying HPV-related tumors in neck metastases to determine the origin of occult primary head and neck squamous cell carcinoma (HNSCC). METHODS: Thirty FNA biopsies of neck metastases from patients with HNSCC were recovered from the authors' files from 2004 to 2005. The primary sites included 13 oropharynx, 13 oral cavity, and 4 larynx/hypopharynx. All patients had corresponding tissue samples from the neck mass and the primary carcinoma. The FNA specimens and corresponding tissue samples were classified as either nonkeratinizing SCC (NKSCC) or keratinizing SCC (KSCC). In situ hybridization for HPV (HPV-ISH) was performed using ethanol-fixed, Papanicolaou-stained smears. A positive signal was defined as dark blue or black nuclear dots. Corresponding formalin-fixed, paraffin-embedded tissue sections also were processed for HPV-ISH. RESULTS: Twenty of the 30 FNA specimens were KSCC, and 10 were NKSCC. Eight of the 10 NKSCCs originated in the oropharynx, and 2 had nonoropharyngeal origin. HPV was detected in 7 of 10 NKSCCs. Ten of 30 (33%) FNA biopsies were positive for HPV, and 9 of those biopsies were metastatic from the oropharynx. Nonkeratinzing morphology or HPV-positive ISH in FNA samples significantly predicted oropharyngeal origin (P < .0069 and P < .0004, respectively). CONCLUSIONS: NKSCC in metastatic cervical lymph nodes predicted positive HPV-ISH and was strongly suggestive of an oropharyngeal primary tumor.

Histologic identification of human papillomavirus (HPV)-related squamous cell carcinoma in cervical lymph nodes: a reliable predictor of the site of an occult head and neck primary carcinoma.

OBJECTIVE: Patients with head and neck squamous cell carcinoma (SCC) often present with cervical lymph node metastasis. Occasionally the primary tumor site remains unknown even after thorough investigation. Management of such cases is problematic and may result in over-treatment and consequent increased morbidity. High risk HPV has been advocated recently as an important etiologic factor for a subset of head and neck SCC. These are believed to have a special predilection for the oropharyngeal tonsils and are characterized by nonkeratinizing basaloid morphology, and a strong reactivity to p16 immunostain. Identifying HPV-related SCC in the lymph nodes may thus provide a means for localizing the primary tumor site. DESIGN: Ninety-three cases of SCC metastatic to the neck from known primary tumors were classified morphologically into conventional keratinizing SCC (KSCC) and non-keratinizing SCC (NKCa). In situ hybridization (ISH) for high risk HPV as well as immunostaining for p16 were performed on all metastsatic and primary tumors. RESULTS: Of the 93 cases of metastatic carcinomas 32 were oropharyngeal, 35 oral, and 26 arose in the laryx/hypopharynx. Twenty-three cases were found to be HPV+ by ISH, of which 22/23 had oropharyngeal origin (P < 0.0001), with 95.7% sensitivity and 85.7% specificity. Twenty-one of these HPV+ oropharyngeal tumors were NKCa (P < 0.0001). The remaining case showed overlapping NKCa/KSCC hybrid morphology. All NKCa were HPV+ and stained diffusely and strongly with p16 antibodies. CONCLUSION: We have demonstrated that HPV status of the lymph node metastasis can be assessed not only by ISH and p16 immunoreactivity but also histomorphologically. In addition, a positive microscopic identification of HPV-related carcinoma is a reliable predictor of oropharyngeal origin.

Expression of mucins, SIMA, villin, and CDX2 in small-intestinal adenocarcinoma.

Expression of gastrointestinal biomarkers MUC1, MUC2, MUC5AC, small-intestinal mucin antigen (SIMA), villin, and CDX2 has been studied in colorectal adenocarcinoma (CRC). Little is known, however, about their expression in small-intestinal adenocarcinoma (SIA). We immunohistochemically compared 30 SIAs with 48 CRCs for the expression of these biomarkers. The results showed that all 6 proteins were variably expressed in SIA, but the frequencies of expression were significantly lower than those for CRC with the exception of MUC1. Specifically, positive staining for MUC1, MUC2, MUC5AC, SIMA, villin, and CDX2 was observed in 16 (53%), 17 (57%), 12 (40%), 15 (50%), 20 (67%), and 18 (60%) of SIAs and 25 (52%), 43 (90%), 39 (81%), 45 (94%), 47 (98%), and 47 (98%) of CRCs, respectively. In addition, SIAs more frequently exhibited a focal staining pattern for MUC2, MUC5AC, SIMA, and villin, whereas more diffuse immunoreactivity was evident in CRCs. Focal staining for MUC1 and diffuse staining for CDX2 were common for SIAs and CRCs. Furthermore, poorly differentiated SIAs tended to express MUC1 more frequently when compared with well- and moderately differentiated SIAs. These observations further support the notion that SIA is immunophenotypically distinct from CRC despite their morphologic similarity.

Immunohistochemical investigation of tumorigenic pathways in small intestinal adenocarcinoma: a comparison with colorectal adenocarcinoma.

Small intestinal adenocarcinoma is an uncommon neoplasm morphologically similar to or indistinguishable from colorectal adenocarcinoma. Although much has been learned about genetic pathways critical to colorectal tumorigenesis, little is known about molecular alterations involved in the development of small intestinal adenocarcinoma. In this study, we immunohistochemically compared non-ampullary small intestinal adenocarcinomas with sporadic colorectal adenocarcinomas for the expression of several proteins known to serve pivotal roles in colorectal tumorigenesis. These included adenomatous polyposis coli and beta-catenin involved in the Wnt signaling pathway, and DNA mismatch repair enzymes hMLH1, hMSH2 and hMSH6 involved in the microsatellite instability pathway. The expression of two important tumor suppressors, p53 and RB, was also examined. The results show that complete loss of adenomatous polyposis coli immunoreactivity, presumably resulting from its gene mutations, was observed in eight of 26 (31%) small intestinal adenocarcinomas and 36 of 51 (71%) colorectal adenocarcinomas (P = 0.0008). Nuclear localization of beta-catenin, an indirect evidence of deregulated Wnt signaling pathway, was observed in 5 (19%) small intestinal adenocarcinomas and 36 (71%) colorectal adenocarcinomas (P<0.0001). Total lack of nuclear staining for one or more of the DNA mismatch repair enzymes occurred in a similar low frequency in both small intestinal and colorectal adenocarcinomas, seen in two of 25 (8%) and 10 of 47 (21%) cases, respectively (P = 0.1958). The frequencies of aberrant p53 and RB expression were also similar between small intestinal and colorectal adenocarcinomas. These observations indicate that defects in the Wnt and microsatellite instability pathways occur in over 90% of colorectal adenocarcinomas, but in only 40% of small intestinal adenocarcinomas. Small intestinal tumorigenesis appears to follow a distinct, yet unidentified, molecular pathway(s) from its colorectal counterpart despite their morphologic similarity.