Faculty Bibliography

BACKGROUND:For viral load (VL) analysis of hepatitis C virus (HCV) by Real Time PCR, approved collection tubes were lavender top (LTT) and plasma processing (PPT) tubes, that differ in that PPTs include plasma separator. Using a Real Time PCR method, we investigated how the results correlated for the two tube types. METHODS:The plasma fractions of blood samples from each of 202 patients were collected in LTT and PPT tubes at the same time and were assayed for HCV VL by the Abbott m2000 Real Time PCR System; the results were analyzed statistically. RESULTS:=0.006, alpha=0.05) using the paired t-test and confirmed by the Chi Square and McNemars tests. CONCLUSIONS:VLs in LTTs are significantly higher and more sensitive than in PPTs, suggesting the necessity of standardization of collection tubes for HCV VLs.

Iron pill gastritis has been shown to be associated with superficial gastric erosion and deposition of iron in lamina propria and gastric antral glands. However, iron absorption in gastric parietal and chief cells is rare. We present a case of a 62-year-old man with iron deficiency anemia. His past medical history is significant for Billroth II surgery. His medications include ferrous sulphate 325mg. Esophagogastroduodenoscopy showed diffuse circumferential abnormal mucosa at the gastro-jejunal anastomosis. The mucosa was erythematous and violaceous. Biopsy showed reactive gastropathy with iron deposits predominantly in macrophages, parietal cells, and chief cells. These findings were confirmed by iron stain and later by electron micrography of the gastric mucosa that showed iron deposits in mitochondria and cytoplasm of the parietal and chief cells.

Carcinosarcoma of the anus is rare and has yet to be reportedly associated with the keratinocyte-specific Human Papilloma Virus (HPV). We describe a case of anal carcinosarcoma with HPV infection in both the epithelial and mesenchymal components of the tumor by immunohistochemistry, chromogenic in-situ hybridization (CISH) and further supported by electron microscopy (EM). Microscopic examination of the tumor showed nests of poorly-differentiated invasive squamous cell carcinoma with basaloid features intermixed with a hypercellular, atypical spindle cell proliferation. Immunohistochemistry demonstrated that the epithelial component was positive for AE1/AE3, p63, CK5/6 and p16, whilst the mesenchymal component was positive for smooth muscle actin, vimentin, and focally positive for desmin and p16, consistent with carcinosarcoma. The tumor was negative for GATA-3, CK7 and CK20. CISH demonstrated that the tumor was positive for high risk HPV (subtype 16/18) in both tumor components. EM further supported the presence of intracellular virus particles (~50 nm) that is compatible with HPV infection. Infection of both epithelial and mesenchymal tumor components by HPV has not been previously observed in the gastrointestinal tract. This finding may represent initial epithelial HPV infection with subsequent divergent tumoral differentiation and suggests the presence of viral replication in both biphasic tumor components.

We recently demonstrated that anti-SSA/52kD-Ro antibodies (Abs) from patients with autoimmune-diseases and QTc prolongation directly target and inhibit HERG-K channel at the extracellular pore region (E-pore) where homology with SSA/52kD-Ro antigen was demonstrated. We tested the hypothesis that immunization of guinea-pigs with a peptide corresponding to the E-pore region (E-pore peptide) will generate pathogenic inhibitory Abs and cause QTc prolongation. Guinea-pigs were immunized with a 31-amino-acid peptide corresponding to E-pore region of HERG. At days 10 to 62 post-immunization, ECGs were recorded and blood drawn for the detection of E-pore peptide Abs. Sera from patients with autoimmune-diseases was evaluated for reactivity to E-pore peptide by ELISA and histology was performed on hearts using Masson's trichrome. HERG channel inhibition was assessed by electrophysiology and by computational modelling of Human ventricular action potential (AP). ELISA results revealed the presence of high-titers of E-pore peptide Abs and significant QTc prolongation post-immunization. High reactivity to E-pore peptide was found using anti-SSA/Ro Ab positive-sera from patients with QTc prolongation. Histology data showed no evidence of fibrosis in immunized hearts. Simulations of simultaneous inhibition of repolarizing currents by anti-SSA/Ro Ab positive-sera showed predominance of HERG channel in controlling AP duration and QT-interval. The results are first to demonstrate that inhibitory Abs to HERG E-pore region induced QTc prolongation in immunized guinea-pigs by targeting HERG channel independently from fibrosis. The reactivity of anti-SSA/Ro Ab positive-sera from patients with connective tissue diseases with the E-pore peptide opens novel pharmacotherapy avenues in the diagnosis and management of autoimmune-associated QTc prolongation

BACKGROUND: The human papilloma virus (HPV) is a carcinogen known for its strong association with cervical cancers and cervical lesions. It is also known to be associated with a variety of squamous cell carcinomas in other areas, such as the penis, vulva, anus and head and neck. However, the association with urothelial carcinoma remains controversial. Here, we report a case of urothelial carcinoma with squamous differentiation associated with HPV-6/HPV-11. CASE PRESENTATION: This is a case of a 70 year old man who presented with nocturia and pressure during urination. During the TURP procedure for what was clinically thought to be benign prostate hyperplasia with pathologic diagnosis as prostate carcinoma, a 2 cm papillary mass was found in the distal penile urethra. The papillary mass was found to be a high grade urothelial carcinoma positive for GATA 3 expression, with focal areas of squamous differentiation. The areas with squamous differentiation demonstrated koilocytic differentiation, which were positive for strong p16 expression. The tumor was found to harbor low risk HPV 6/11 by in situ hybridization. CONCLUSIONS: This study case demonstrates HPV infection with a low risk subtype (HPV 6/11) associated with an urothelial carcinoma with squamous differentiation and condylomatous features.

Large cell neuroendocrine carcinoma of the prostate (LCNEC), de novo in particular, is an extremely rare entity that has only been described in the literature in case reports. Historically, the majority of the cases of LCNEC reported in the literature represent typical prostatic adenocarcinomas that transformed after long standing androgen deprivation therapy (ADT). These cases were admixed with histological areas of usual adenocarcinoma and showed hybrid features of both neuroendocrine and usual adenocarcinoma. Here we present a case of an LCNEC without admixed areas of usual prostatic adenocarcinoma arising de novo in a patient without prior history of hormonal therapy. The tumor also shows morphologic evidence of neuroendocrine differentiation; composed of large sheets and nests of cells with moderate amphophilic cytoplasm with peripheral palisading, and vesicular clumpy chromatin with prominent nucleoli. The carcinoma's prostatic origin is indicated by positive immunohistochemical staining for PSA, PAP, PSMA, racemase, and Nkx3.1. Diffusely positive staining for chromogranin and synaptophysin, as well as the presence of secretory granules in the cytoplasm of the tumor cells demonstrated by electron microscopy supports the NE differentiation. NE prostate cancer usually does not express AR and is refractory to ADT therapy while AR and ERG are positive in this case. In summary, we report a de novo LCNEC of the prostate with review of literature, in particular, clinical implications.

Spindle cell carcinoma (SpCC) is a unique variant of squamous cell carcinoma (SCC). SpCC confined to the nasal cavity is extremely rare, with only one case having been previously reported. We present a case report of nasal cavity SpCC and review the literature on this rare entity. A 29-year-old male presented with intermittent epistaxis from the left nasal cavity. On physical examination, the patient had an ulcerated mass in the left nasal vestibule and a biopsy showed a proliferation of spindle and epitheliod cells. The patient underwent wide local excision of the mass via a lateral alotomy approach and reconstruction with a composite conchal bowl skin and cartilage graft. Histologically, the mass had dyplastic squamous epithelium and spindle-shaped cells admixed with epitheliod cells. Immunohistochemistry was only positive for pancytokeratin AE1/AE3 and vimentin. Six months after surgery, the patient continues to have no evidence of disease. On literature review, only one previous case of SpCC confined to the nasal cavity was identified. We present a rare case of nasal cavity SpCC. No definite treatment protocol exists for this unique entity, but we believe that this tumor should primarily be treated with aggressive, wide local excision. Adjuvant radiation and/or chemotherapy have also been used anecdotally.