Unusual skin manifestations in an elderly man.

A 77-year-old man presented with a 2-month history of a widespread scaly erythematous patches affecting his trunk and limbs. This case report discusses the differential diagnosis in a patient with unusual lumps. It explores the common pitfalls in examining such cases and provides key learning points.

HPV persistence and its oncogenic role in prostate tumors.

HPV has carcinogenic effects at several anatomical sites in women and men. Whether the presence of HPV in the genitourinary tract of men is associated with a higher prostate cancer risk has been a matter of research for a long-time and the results are still not fully conclusive. Similarly, the question of the reservoir of HPV infection in men is not clearly resolved. HPV DNA presence and types were evaluated by means of polymerase chain reaction in the tissue of 146 patients with benign prostate hyperplasia and prostate cancer. HPV-specific antibodies were analyzed by enzyme-linked immunosorbent assay in the sera of all patients and 172 controls. In addition, 256 biopsies taken from non-tumorous tissues were analyzed. No statistically significant differences were observed in HPV DNA prevalence between patients with benign prostate hyperplasia (2%) and patients with prostatic cancer (2%; P = 1.000). The seropositivity rates did not differ significantly between groups of subjects except for antibodies against HPV 6 VLPs which were found more often in prostate cancer patients (adjusted P = 0.018). Similarly, no difference in the seroprevalence rates for HPV 16 E6 and/or E7 oncoproteins between groups of patients and healthy controls was detected. The overall HPV prevalence in 256 healthy tissue samples was 4%. The results indicate that HPV infection is not associated with prostate oncogenesis in men. However, they imply that multiple tissues of the male genitourinary tract may be important reservoirs for the transmission of some HPV types.

Ectopic spleen presenting as a slowly enlarging lung nodule in the right lower lobe following gastric pull up operation.

This is a case report of an elderly man who was investigated at our respiratory clinic for slowly enlarging right lower lobe lung nodule on the background of oesophageal cancer diagnosed more than 11 years ago with gastric pull up. CT guided biopsy confirms the diagnosis of intrathoracic ectopic spleen.

Phosphoprotein associated with glycosphingolipid-enriched microdomains/Csk-binding protein: a protein that matters.

Engagement of plasma membrane receptors is followed by an assembly of a multimolecular complex of signaling molecules organized by scaffolding or adaptor proteins. PAG is a recently characterized transmembrane adaptor protein associated with lipid rafts, which is involved in the regulation of Src-kinases, monomeric Ras protein, and interactions with the cytoskeleton. The review provides up-to-date information about the protein that attracts increasing attention in current biomedical research.

Expression of transmembrane adaptor protein PAG/Cbp in diffuse large B-cell lymphoma: immunohistochemical study of 73 cases.

PAG/Cbp is a transmembrane adaptor protein involved in proximal immune signaling. It is expressed in reactive germinal centers (GC) of secondary lymphatic follicles and related malignant lymphomas. We studied PAG/Cbp expression in GC-like and non-GC-like diffuse large B-cell lymphoma (DLBCL) subtypes. Seventy-three cases of DLBCL identified among 155 malignant lymphomas were classified as GC-like DLBCL (CD10+ or CD10-, bcl-6+, and MUM1-) and non-GC-like DLBCL (CD10-, MUM1+ or CD10-, bcl-6+, MUM1+). PAG/Cbp was detected by monoclonal antibody MEM-255 following routine immunohistochemical procedures. Thirty-five of 40 GC-like DLBCLs (88%) and 20 of 33 non-GC-like DLBCL cases (61%) expressed PAG/Cbp. Four of 12 bcl-6-negative non-GC-like DLBCL cases (33%) were PAG/Cbp positive, and only 4 of 20 bcl-6-positive non-GC-like DLBCL cases (25%) were PAG/CBP negative. All 37 FL and all 5 Burkitt's lymphomas (BL) expressed PAG/Cbp, whereas all 6 mantle cell lymphomas (MCL) and 4 of 5 chronic lymphocytic leukemias (CLL/SLL) were PAG/Cbp negative. PAG/Cbp is a reliable GC marker. Its expression correlates with GC-like DLBC phenotype in a significant majority of cases. It is typically absent in MCL and SLL/CLL.

Expression pattern of adaptor protein PAG: correlation between secondary lymphatic follicle and histogenetically related malignant lymphomas.

Transmembrane adaptor protein PAG, also known as Csk-binding protein (Cbp), which binds and activates the cytoplasmic tyrosine kinase Csk, the major negative regulator of Src-family kinases, was found to be expressed in germinal centers of lymphoid follicles as well as in follicular, but not mantle cell lymphomas. Expression of PAG may reflect its role in regulation of proliferation and differentiation of germinal center B-cells. From the routine histopathology point of view, PAG might be a new positive marker of follicular lymphoma and a negative marker of mantle cell lymphoma.

Renal epithelioid angiomyolipoma--a close mimic of renal cell carcinoma. Report of a case and review of the literature.

The epithelioid variant of angiomyolipoma (EAML) is a rare tumor of unpredictable behavior that is composed of epithelioid, spindle, and giant cells and contains no or only a minimal amount of lipomatous tissue. The picture can lead to an erroneous diagnosis of renal cell carcinoma or sarcoma. We report on a case of EAML in the kidney of a 47-year-old female without any signs of tuberous sclerosis and review the literature. Grossly, a well-demarcated, spheroid, largely hemorrhagic tumor measuring 4.2 cm in diameter occupied the central third of the kidney. Histologically, it was solid, highly cellular, with occasional microcysts, composed of medium to large epithelioid cells with clear or oxyphilic cytoplasm, short spindle cells, and numerous giant multinucleated cells. After extensive sampling, adult-appearing fat tissue was found to present as rare foci of microscopic dimensions. Immunohistochemically, the tumor cells showed positive reactions with antibodies against HMB-45, melan A, CD-68, muscle-specific actin, and, rarely, smooth muscle actin. Cytokeratins and epithelial membrane antigen were negative. The EAML is a variant growing in a carcinoma-like pattern that can lead to an erroneous diagnosis of renal cell carcinoma. An extensive sampling and HMB-45 and CD-68 positivity combined with cytokeratin negativity are of paramount importance for the correct diagnosis. As a sporadic renal tumor it followed a benign course in most of the reported cases.

The development of peripheral T-cell lymphoma after successful treatment for diffuse large B-cell lymphoma in a patient with suspected adult onset immunodeficiency: more questions than answers?

We present the case of a 60-year-old woman who developed peripheral T-cell lymphoma following successful treatment for high-grade B-cell non-Hodgkin's lymphoma. We consider the possible aetiology of this unusual occurrence. We hypothesise that this case represents one of the undiagnosed adult-onset immunodeficiency, in which the pathogenesis of the patient's T-cell lymphoma may have been in part iatrogenic, namely related to previous immunotherapy with rituximab. We feel this case highlights the importance of rebiopsy in patients with recurrent lymphadenopathy and a history of haematological malignancy and hence acts as an important aide memoir in the investigation of such cases.

EBV+ diffuse large B-cell lymphoma arising within atrial myxoma. An example of a distinct primary cardiac EBV+ DLBCL of immunocompetent patients.

Cardiac myxoma and diffuse large B-cell lymphoma are uncommon tumors, yet four composite tumors have been reported since 2009. We are reporting on the fifth case providing detailed immunohistochemical and FISH analyses. The lymphoma was present as superficially located nests of large cells with patchy necrosis in the background of a typical atrial myxoma. It displayed features of DLBCL with non-germinal center phenotype, expressed EBER, LMP1, EBNA2 and shared the following features with the previously reported cases: B-cell lineage, high-grade cytology, high proliferation rate, EBV infection in latency type 3 with one tested case and an excellent outcome. The lymphomas arising within myxoma may follow a pathogenic pathway driven by EBV, whose transformation potential is unleashed in the cytokine-rich milieu of a myxoma, presumably accentuating age-related decline of adaptive immunity known as immune senescence. DLBCL arising within atrial myxoma grouped together with EBV+ DLBCL associated with valve prosthesis and with an atrial thrombus differs in the immunocompetent patients from primary cardiac DLBCL, not otherwise specified, in clinical presentation, pathological features and a course of the disease. Distinction between these groups may have important therapeutic consequences.

Pure epithelioid PEComas (so-called epithelioid angiomyolipoma) of the kidney: A clinicopathologic study of 41 cases: detailed assessment of morphology and risk stratification.

Epithelioid angiomyolipomas (perivascular epithelioid cell tumors) of the kidney are defined as potentially malignant mesenchymal lesions that are closely related to classic angiomyolipoma. Although approximately 120 cases are published, mostly as case reports with variably used diagnostic criteria, the pathologic prognostic predictors of outcome are unknown. We analyzed the clinicopathologic parameters in a large series of 41 cases of pure epithelioid angiomyolipomas of the kidney, which we designate as pure (monotypic) epithelioid PEComas to contrast them from classic angiomyolipomas that are regarded by some as PEComas. We use the terminology "pure" to separate these cases from those that may have variable epithelioid components. The mean age of the patients was 40.7 years (range, 14 to 68 y). The male-to-female ratio was 1:1. Seventy-nine percent of patients were symptomatic at presentation with metastatic disease at onset in 12 cases. Follow-up and/or disease progression information were available for 33 of 41 cases (mean, 44.5 mo and median, 24.5 mo; range, 4 to 240); 9 patients had a history of associated tuberous sclerosis. Recurrence and metastasis were seen in 17% and 49% of patients; 33% of patients died of disease. Lymph node involvement was seen in 24% of patients; the liver (63%), lung (25%), and mesentery (18.8%) were the most common metastatic sites. Clinicopathologic parameters associated with disease progression (recurrence, metastasis, or death due to disease) in univariate analysis included associated tuberous sclerosis complex or concurrent angiomyolipoma (any metastasis, P=0.046), necrosis (metastasis at diagnosis, P=0.012), tumor size >7 cm (progression, P=0.021), extrarenal extension and/or renal vein involvement (progression, P=0.023), and carcinoma-like growth pattern (progression, P=0.040) (the 5 adverse prognostic parameters for pure epithelioid PEComas). Tumors with <2 adverse prognostic parameters (13 cases) were considered to be low risk for progression tumor, with 15% having disease progression. Tumors with 2 to 3 adverse prognostic parameters (14 cases) were considered to be "intermediate risk," with 64% having disease progression. Tumors with more than 4 or more adverse prognostic parameters (6 cases) were considered to be high risk, with all patients having disease progression. Of tumors with 3 or more adverse prognostic parameters, 80% had disease progression. An exact logistic regression analytic model showed that only carcinoma-like growth pattern and extrarenal extension and/or renal vein involvement were significant predictors of outcome (P=0.009 and 0.033, respectively). Our data of a large series with uniform definitional criteria confirm the malignant potential for pure epithelioid PEComas and provide adverse prognostic parameters for risk stratification in these patients.

Haemangioma of the parathyroid gland. Does it really exist?

We are reporting a case of a capillary haemangioma-like proliferation arising within a parathyroid gland adenoma, associated with primary hyperparathyroidism. The vessel proliferation bearing a close resemblance to a capillary haemangioma consisted of tightly packed capillaries, endothelial buds and occasional small caliber muscle-containing vessels. The observation expands the spectrum of tumour-associated vascular proliferations by adding an exuberant haemangioma-like pattern to its extreme end. These are a heterogeneous group of lesions reportedly induced by aberrant production of angiogenic factors. We investigated expression of VEGF, pKDR, FGF2, HIF1alpha and HIF2alpha and only VEGF gave a strong positive reaction in the adenoma cells entrapped in the vascular meshwork. Although this does not constitute a proof that aberrant VEGF production was a causative agent, unexpected supportive evidence for its pathogenic role emerged from a failure to detect chromogranin A. Chromogranin A is a precursor of several regulatory proteins, including vasostatin I, a multilevel suppressor of VEGF. The production of vasostatin I may have been reduced in a chromogranin A-negative adenoma which could lead to a loss of its opposing effect on VEGF-regulated processes. The only two other published cases of haemangioma of the parathyroid gland were reported in patients diagnosed with primary parathyroid hyperplasia with hyperparathyroidism, a pathophysiologic condition similar to our case. Therefore we raise the question whether these tumours could also represent a reactive phenomenon.

Human papillomavirus infection of the epididymis and ductus deferens: an evaluation by nested polymerase chain reaction.

CONTEXT: Human papillomaviruses (HPVs) play an important role in the etiology of squamous cell carcinoma of the uterine cervix. The possible role of the male urogenital tract as a reservoir of HPV infection is not fully understood. We inferred from our previous observation of HPV-31 in epididymal tissue in a case of chronic epididymitis that HPV might be commonly present in cases of epididymitis caused by sexually transmitted pathogens. OBJECTIVE: To assess the presence of HPV in the epididymis and ductus deferens in nontuberculous epididymitis. DESIGN: Epididymal samples obtained from 17 patients and epididymal and ductus deferens samples from 5 patients surgically treated for nontuberculous epididymitis were analyzed by nested polymerase chain reaction for the presence of HPV DNA. In positive samples, the HPV type was determined by DNA sequencing. SETTING: Tertiary-care academic hospital and national reference laboratory for papillomaviruses. RESULTS: Low-risk HPV type 6 and high-risk HPV types 16, 33, 35, 55, and 73 were detected in 7 patients (31%). Neither koilocytes nor dysplastic changes were found in the epididymis and ductus deferens. CONCLUSION: Low-risk and high-risk HPV types were detected in the epididymis and ductus deferens of patients with nontuberculous epididymitis. The infection was not accompanied by koilocytic atypia or dysplasia. Our findings support the hypothesis that the male urogenital tract serves as a reservoir of HPV infection.