Major Discrepancies of HCV Viral Loads Determined by Real Time Polymerase Chain Reaction Caused by Use of Collection Tubes that Differ Only with the Presence or Absence of Serum Separator.

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: VLs for 103 samples for both tubes were negative. Positive results were obtained for another 79 tube pairs, including six with VLs for LTTs but values below linearity for the corresponding PPTs. For the 73 samples for which quantitative results were obtained for both tube types, VLs were statistically higher in LTTs (means 1,817,821.8 in LTTs and 1,083,669.1 in PPTs, p=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.

Mitochondrial Iron Accumulation in Parietal and Chief Cells in Iron Pill Gastritis Following Billroth II Gastrectomy: Case Report Including Electron Microscopic Examination.

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.

Induction of autoimmune response to the extracellular loop of the HERG channel pore induces QTc prolongation in guinea-pigs.

KEY POINTS: Channelopathies of autoimmune origin are novel and are associated with corrected QT (QTc) prolongation and complex ventricular arrhythmias. We have recently demonstrated that anti-SSA/Ro antibodies from patients with autoimmune diseases and with QTc prolongation on the ECG target the human ether-à-go-go-related gene (HERG) K+ channel by inhibiting the corresponding current, IKr , at the pore region. Immunization of guinea-pigs with a peptide (E-pore peptide) corresponding to the extracellular loop region connecting the S5 and S6 segments of the HERG channel induces high titres of antibodies that inhibit IKr , lengthen the action potential and cause QTc prolongation on the surface ECG. In addition, anti-SSA/Ro-positive sera from patients with connective tissue diseases showed high reactivity to the E-pore peptide. The translational impact is the development of a peptide-based approach for the diagnosis and treatment of autoimmune-associated long QT syndrome. ABSTRACT: We recently demonstrated that anti-SSA/52 kDa Ro antibodies (Abs) from patients with autoimmune diseases and corrected QT (QTc) prolongation directly target and inhibit the human ether-à-go-go-related gene (HERG) K+ channel at the extracellular pore (E-pore) region, where homology with SSA/52 kDa 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 the E-pore region of HERG. On days 10-62 after immunization, ECGs were recorded and blood was sampled for the detection of E-pore peptide Abs. Serum samples from patients with autoimmune diseases were evaluated for reactivity to E-pore peptide by enzyme-linked immunosorbent assay (ELISA), and histology was performed on hearts using Masson's Trichrome. Inhibition of the HERG channel was assessed by electrophysiology and by computational modelling of the human ventricular action potential. The ELISA results revealed the presence of high titres of E-pore peptide Abs and significant QTc prolongation after immunization. High reactivity to E-pore peptide was found using anti-SSA/Ro Ab-positive sera from patients with QTc prolongation. Histological data showed no evidence of fibrosis in immunized hearts. Simulations of simultaneous inhibition of repolarizing currents by anti-SSA/Ro Ab-positive sera showed the predominance of the HERG channel in controlling action potential duration and the QT interval. These results are the first to demonstrate that inhibitory Abs to the HERG E-pore region induce QTc prolongation in immunized guinea-pigs by targeting the 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 pharmacotherapeutic avenues in the diagnosis and management of autoimmune-associated QTc prolongation.

Papillary urothelial carcinoma with squamous differentiation in association with human papilloma virus: case report and literature review.

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.

A rare case of anal carcinosarcoma with human papilloma virus infection in both biphasic tumor elements: An immunohistochemical, molecular and ultrastructural study.

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.

Metastatic Small Cell Carcinoma of the Lung: An Unusual Cause of Acute Fulminant Hepatic Failure.

For patients with acute fulminant liver failure, imaging and histopathologic studies are indicated to reveal the underlying etiology, and metastatic small cell carcinoma should be included in the clinical differential diagnosis when appropriate.

Can Serum Free Light Chains Be Used for the Early Diagnosis of Monoclonal Immunoglobulin-Secreting B-Cell and Plasma-Cell Diseases?

Patients who are undergoing multiple myeloma screening with serum protein electrophoresis and immunofixation, especially those with renal failure, also should receive serum free light chain testing to increase specificity and reduce false-negatives.

De novo large cell neuroendocrine carcinoma of the prostate, case report and literature review.

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.

Urethral adenocarcinoma associated with intestinal-type metaplasia, case report and literature review.

The presence of glandular epithelium in urinary tract biopsies poses a diagnostic challenge. Intestinal metaplasia of the urethra may be seen in many congenital, iatrogenic, and reactive conditions, as well as in association with malignant conditions such as urethral adenocarcinoma. We present a case of a 61 year-old woman presenting with microscopic hematuria. Successive biopsies showed glandular epithelium with focal atypia in close association with inflammation, but no overt malignancy. Only on surgical resection was the associated high grade adenocarcinoma revealed. When intestinal-type mucosa is present within a urinary tract biopsy, associated malignancy may be present only focally. Thorough sampling and consideration of the differential diagnosis is imperative.

Spindle cell carcinoma of the nasal cavity.

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.

Bilateral tubulocystic renal cell carcinomas in diabetic end-stage renal disease: first case report with cytogenetic and ultrastructural studies.

Tubulocystic renal cell carcinoma (TC-RCC) is a rare renal tumor composed of well-differentiated tubules and cysts lined by neoplastic cells with eosinophilic cytoplasm and prominent nucleoli. The origin of the tumor cells is still controversial. TC-RCC typically arises unilaterally. Involvement of both kidneys by multifocal TC-RCC has not been reported. In this study we report the first case of bilateral and multifocal TC-RCC. Immunohistochemical, cytogenetic and ultrastructural studies suggest TC-RCC is closely related to papillary RCC.

Extranodal Rosai-Dorfman disease arising in the right atrium: a case report with literature review.

Rosai-Dorfman disease is a rare, benign histiocytic proliferative disorder that commonly affects the lymph nodes. Although extranodal involvement has been reported in diverse sites, manifestation in the cardiovascular system is extremely uncommon. Specifically, the involvement of the heart by Rosai-Dorfman disease is an extraordinarily infrequent event. Here, the authors present a case of Rosai-Dorfman disease arising in the right atrium in a symptomatic 61-year-old man who initially presented with pleuritic chest pain and was found to have a large, lobulated, and circumscribed right atrial mass. The lesion exhibited an exuberant histiocytic and chronic fibroinflammatory process with focal emperipolesis within histiocytes. Immunohistochemical studies demonstrated strong S100 positivity in CD68+ CD1a- histiocytes. Although rare, Rosai-Dorfman disease should be considered in the differential diagnosis of a right atrial mass.

Metastatic balloon cell malignant melanoma: a case report and literature review.

A case of metastatic balloon cell malignant melanoma (BCMM) is presented. The balloon melanoma cells (BMC) were absent in the shave biopsy of the primary lesion and present as a minor component in the wide and deep excision. A subsequent right neck lymph node metastasis showed complete replacement of the lymph node by large, foamy cells. Though the tumor was amelanocytic and Fontana-Masson stain failed to reveal melanin, it stained positively for S-100, HMB-45, and Melan-A. Ultrastructurally, the foamy cells were characterized by cytoplasmic vacuolization and a lack of melanosomes. The differential diagnosis of metastatic balloon cell malignant melanoma is broad, and clinicopathologic correlation may play a critical role in achieving the correct diagnosis.

Planum sphenoidale meningioma leading to visual disturbance.

A 60-year-old male presented with complaints of dizziness, which worsened with fatigue and a sense his balance was 'off'. Initial physical examination was negative and the laboratory testing was unremarkable. Within weeks, the patient developed bilateral visual field deficits. MRI revealed an extra-axial mass which extended into the pituitary fossa and caused compression of the pituitary gland. The pituitary stalk was displaced posteriorly and the optic chiasm was compressed with displacement superiorly and posteriorly. The patient underwent a surgical resection. Diabetes insipidus developed postoperatively requiring a vasopressin drip. He also developed hypopituitarism after the resection with hypothyroidism, hypoadrenalism and hypogonadism. The patient requires testosterone, levothyroxine and hydrocortisone replacement and has mild residual bitemporal hemianopsia.

Novel PRKAR1A gene mutations in Carney Complex.

Carney complex is a syndrome that may include cardiac and mucocutaneous myxomas, spotting skin pigmentation, and endocrine lesions. Many patients with Carney complex have been shown to have a stop codon mutation in the PRKAR1A gene in the 17q22-24 region. Here we present the case of a 57 year-old man with multiple skin lesions and cardiac myxomas. Histology of the skin lesions showed lentigenous melanocytic hyperplasia and cutaneous myxomas, confirming the diagnosis of Carney complex. Lesional and control normal tissue from the patient were identified and sequenced for the PRKAR1A gene. A germline missense mutation was identified at exon 1A. This is the first report of this mutation, and one of the few reported missense mutation associated with Carney complex. This finding strengthens the argument that there are alternative ways in which the protein kinase A 1-alpha subunit plays a role in tumorigenesis.

Utility of desmin and a Masson's trichrome method to detect early acute myocardial infarction in autopsy tissues.

Detection of early acute myocardial ischemia/infarction prior to neutrophilic infiltration in autopsy myocardium poses a diagnostic dilemma to the surgical pathologist. Morphological changes can be subtle or not identified at all on the hematoxylin and eosin stain. To evaluate the Masson's trichrome stain and immunohistochemical stains, desmin and myoglobin, in detecting acute myocardial ischemia/infarction in autopsy myocardium. We reviewed the autopsy files of the New York Harbor Healthcare System and retrieved 25 cases of early acute myocardial infarction. Three autopsy hearts of non-cardiac related deaths were used as controls. Sections from grossly suspected early acute myocardial infaction areas were stained by a Masson's trichrome stain technique and with desmin by a standard immnunohistochemical method. The ischemic zone surrounding myocardial infarction and the acute infarct itself in 23/25(92%) were detected by desmin depletion, and in all cases with Masson's trichrome color changes. No change in staining for desmin or Masson's trichrome were seen in the three controls. Desmin and Masson's trichrome together are valuable tools when faced with the problem of postmortem detection of early myocardial infarction/ischemia.

Multiple myeloma involving skin and pulmonary parenchyma after autologous stem cell transplantation.

Pulmonary involvement and skin involvement are rare complications of plasma cell neoplasms. Here we describe what may be the first reported case of a patient with relapse in both of these sites following autologous peripheral blood stem cell transplantation.

Pancreatic carcinoma with multilineage (acinar, neuroendocrine, and ductal) differentiation.

The preponderance of pancreatic tumors is adenocarcinoma of the ductal type; carcinomas with multiple lineage differentiation are extremely rare. We report an unusual case of pancreatic carcinoma with combined acinar and neuroendocrine differentiation and minor ductal component with concurrent acinar-ductal metaplasia (ADM), an early lesion implicated in ductal carcinogenesis. The patient is a 56-year-old man with vague complaints of dull left upper quadrant pain with radiation across the mid-portion of his abdomen. A computer tomography scan revealed an irregular enlargement of the distal 3.2 cm of the pancreatic body. A distal pancreatectomy was then performed. Histologic examination revealed a pancreatic carcinoma with cellular features of eosinophilic granular cytoplasm and salt-pepper nuclei. The acinar differentiation of the carcinoma was confirmed by positivity on periodic acid-Schiff stain resistant to diastase digestion (dPAS), positivity for antitrypsin on immunohistochemistry (IHC), and presence of zymogen granules on electron microscopy (EM). The neuroendocrine differentiation was evident by positive synaptophysin and chromogranin stain on IHC and neuroendocrine granules on EM. The ductal component was only visible by PAS stain and immunostains for CEA and CK19A and accompanied by a number of the acinar-ductal metaplasia lesions adjacent to the main tumor. Thus, the histological, histochemical, immunohistochemical and electron-microscopic evidence all suggested that the pancreatic carcinoma underwent trilineage differentiation.

Iron medication-induced gastric mucosal injury.

Severe gastrointestinal erosion, ulcer, necrosis and strictures after an acute iron overdose are well described. However, gastric mucosal injury in patients receiving therapeutic iron has received only scant recognition despite its wide use. We report a case of iron medication-induced gastric mucosal injury in a 76-year-old male who presented with iron deficiency anemia and had been taking ferrous sulfate tablet for 4 years. Esophagogastroduodenoscopy (EGD) revealed a pale, villous appearing flat lesion along the lesser curvature of gastric body. Histopathologic examination of EGD biopsies of the flat lesion showed brown crystalline materials deposited in the lamina propria of gastric mucosa, which was accompanied with fibrosis, chronic inflammation, and foreign body reaction. The crystalline materials were covered and admixed with gastric epithelium. Prussian blue iron stain confirmed that the brown crystalline materials were iron. The iron and hemosiderin accumulation was also seen in cytoplasm of epithelial cells and lumen of fundic gastric glands. The recognition and reporting by pathologists of iron-induced changes in EGD biopsies will alert clinicians to this underrecognized but easily correctable complication by alternative forms of iron therapy, such as liquid preparation.

Case report: Paenibacillus thiaminolyticus: a new cause of human infection, inducing bacteremia in a patient on hemodialysis.

Paenibacilli are gram-positive, aerobic bacteria that are related to Bacilli but differ in the DNA encoding their 16S rRNA. Until recently, these organisms were not known to cause human disease. There are now several reports of human infection caused by a few members of this genus, most commonly by P. alvei. We report a human infection in a patient with a permacath for chronic hemodialysis who was found to have bacteremia caused by P. thiaminolyticus, which is an environmental bacterium that has never been found to cause human disease. We identified this bacterium by biochemical tests, cloning, sequencing the genomic DNA encoding its 16S rRNA, growth characteristics, and electron microscopic studies. This constitutes the first report of a human infection caused by this organism.