David Ramos

Low levels of WWOX protein immunoexpression correlate with tumour grade and a less favourable outcome in patients with urinary bladder tumours

Aims:  To correlate the immunohistochemical detection of WWOX with histological measures and disease progression within the whole spectrum of urothelial bladder neoplasms.

Hepatoid adenocarcinoma of the urinary bladder

Abstract A new case of hepatoid adenocarcinoma was diagnosed in fragments obtained at transurethral resection (TUR) from a 71-year-old man who had complained of haematuria. The tumour was composed of trabeculae and small solid nests of polygonal atypical cells simulating hepatocarcinoma, together with glandular areas of an otherwise typical adenocarcinoma. Immunohistochemistry showed cytoplasmic reactivity to AFP, AAT, albumin and CAM 5.2. Membrane reactivity was seen in EMA immunostaining, and there was also positivity to polyclonal CEA following a canalicular pattern. Immunoperoxidase studies of hepatocyte growth factor (HGF) and its receptor, c-met, were positive. Their expression may be related to the aggressive behaviour of this tumour.

The density and type of MECA-79-positive high endothelial venules correlate with lymphocytic infiltration and tumour regression in primary cutaneous melanoma

Tumour‐infiltrating lymphocytes have prognostic value in malignant melanoma. High endothelial venules (HEVs) are specialized vessels present in lymph nodes and tertiary lymphoid organs. CCL19, CCL21 and CCR7 regulate lymphocyte migration through HEVs. The aim of our study was to correlate HEV density in cutaneous primary and metastatic malignant melanomas with clinicopathological parameters, and with CCL19, CCL21 and CCR7 mRNA expression.

Inflammatory fibroid polyp of the small bowel with a mutation in exon 12 of PDGFRα

Inflammatory fibroid polyp (IFP) is a benign reactive uncommon submucosal lesion of the gastrointestinal tract, the small intestine being the most common site of origin. Histologically, IFPs are characterized by spindle cells, a heavy inflammatory infiltrate including eosinophils and onion-sheet-like formation of lesional cells around blood vessels. We present a case report of an IFP harboring an activation mutation in the PDGFRα gene. The lesion was positive for CD34, PDGFRα, and p-PDGFRα immunostaining but was negative for c-KIT and desmin. After a sequencing analysis of KIT and PDGFRα, a mutation consisting of an in-frame deletion of codons 567-571 and a missense mutation in codon 566 (S566R) of PDGFRα was observed. This mutation could activate key cellular pathways with involvement in the pathogenesis of this entity. We concluded that more studies are necessary in order to clarify if this finding is a biologically distinct behavior or, on the contrary, represents a specific feature of the IFP.

CCL27–CCR10 and CXCL12–CXCR4 chemokine ligand-receptor mRNA expression ratio: new predictive factors of tumor progression in cutaneous malignant melanoma

CXCR4, CCR7 and CCR10 chemokine receptors are known to be involved in melanoma metastasis. Our goal was to compare the relative intratumoral mRNA expression of these receptors with that of their corresponding chemokine ligands, CXCL12, CCL19, CCL21, and CCL27 across the full spectrum of human melanoma progression: thin and thick primary melanomas, as well as “in transit”, lymph node, and distant metastases. Expression was quantified by real-time RT-PCR in 103 melanoma samples: 51 primary tumors and 52 metastases. Particular emphasis was focused on chemokine ligand-receptor expression ratios. Immunohistochemistry was performed to identify the cell types expressing these molecules. CXCL12–CXCR4 and CCL27–CCR10 ratios were higher in thin than in thick primary melanomas, and all four chemokine-receptor ratios were higher in primary tumors than in melanoma metastases. CCL27–CCR10 and CXCL12–CXCR4 expression ratios in primary tumors were inversely associated with the development of distant metastases, and improved the predictive value of tumor thickness for distant metastasis, which is important since chemokine ligand-receptor ratios are not affected by the endogenous gene employed for normalizing mRNA expression. Both receptor and ligand immunolabeling were detected in neoplastic cells suggesting autocrine mechanisms. Our results support the concept that low CCL27/CCR10 and CXCL12/CXCR4 intratumoral mRNA ratios are associated with melanoma progression, and in combination with Breslow thickness, are the best predictive factors for the development of distant metastases in primary cutaneous melanoma.

Ultrastructural and immunohistochemical characterization of the so-called giant multinucleate cells in cutaneous collagenomas

Ultrastructural and immunohistochemical characterization of the so‐called giant multinucleate cells in cutaneous collagenomas

Warty Carcinoma Arising in Condyloma Acuminatum of Urinary Bladder A Case Report

We describe the case of a 62-year-old man with chronic irritation of the urinary bladder resulting in dysuria and hypogastric pain. Three neoplasms measuring 0.5, 1, and 1.5 cm, respectively, were observed by cystoscopy and removed by transurethral resection (TUR). Histologic examination showed a complex folding of squamous hyperplastic epithelium around a connective tissue core. The superficial epithelium contained numerous koilocytes. The double polymerase chain reaction (PCR) detected DNA of type 11 human papillomavirus (HPV). The diagnosis was condyloma acuminatum of bladder. Three months later the patient presented with fever, and a new cytoscopy demonstrated an ulcerated, exophytic 4.5 cm mass. Histopathology showed a squamous carcinoma with papillomatous structure, pronounced viral koilocytosis, and irregular invasive deep margin. HPV type 11 was found with double PCR. The diagnosis was warty carcinoma arising in condyloma acuminatum. To the best of our knowledge, this is the first case of warty carcinoma of the urinary bladder described in the literature. We discuss the relationship between the infection by HPV and the development of condyloma acuminatum, its evolution toward a well-differentiated squamous carcinoma, and its distinction from verrucous carcinoma.

Papel de las quimiocinas en la progresión del melanoma

Metastasis is the main cause of death from melanoma. Chemokines are low molecular weight chemotactic cytokines that facilitate cellular migration. Thus, cells that express receptors for a given chemokine are attracted to the site of its production. As certain chemokines are found in abundance in organs that are common targets of metastasis and receptors for these chemokines are expressed by tumor cells, it was hypothesized that chemokine gradients might selectively facilitate metastasis to these organs. A later finding that these chemokines were produced by tumor cells, with evidence of autocrine effects, obliged the modification of that hypothesis. Many chemokines are also known to have opposing effects according to the type of cell they are acting on (tumor, inflammatory/immune, or endothelial cells), their functional status, or interactions with other molecules. The expression of chemokines and their receptors by melanoma cells enhances tumor progression by altering their microenvironment, stimulating angiogenesis, and inhibiting the immune response.

Poorly Differentiated Adenocarcinomas of Prostate Versus High-Grade Urothelial Carcinoma of the Bladder: A Diagnostic Dilemma With Immunohistochemical Evaluation of 2 Cases

The differential diagnosis between carcinoma of the urinary bladder and adenocarcinoma of the prostate can be difficult, especially in the poorly differentiated forms infiltrating the neighboring organs. In this article, the authors report 2 cases that pose a diagnostic dilemma to the pathologist. The first is an infiltration of the bladder by a poorly differentiated adenocarcinoma of the prostate, which was clinically suspected as a papillary urothelial neoplasm. The second is a collision tumor composed of prostatic adenocarcinoma and urothelial carcinoma observed on a core needle biopsy of the prostate. In both cases, a large panel of immunohistochemical markers were used and demonstrated positivity for prostate-specific antigen and alpha methyl racemase in the prostatic carcinomas and immunoreactivity for CK7, CK20, Ag 34βE12, and p53 in the urothelial carcinoma. The differentiating histological and immunohistochemical findings are discussed.

Analysis of cribriform Gleason grade 3 in prostatic carcinoma. A histopathological and immunohistochemical study of 32 cases

1. Adey GS, Vargas SO, Retik AB et al. Fibroepithelial polyps causing ureteropelvic junction obstruction in children. J. Urol. 2003; 169; 1834–1836. 2. Maizels M, Stephens FD. Valves of the ureter as a cause of primary obstruction of the ureter: anatomic, embryonic and clinical aspects. J. Urol. 1980; 123; 742–747. 3. Huang WY, Olumi AF, Rosen S. Urothelial mucosal malformation: a rare cause for ureteropelvic junction obstruction. Pediatr. Dev. Pathol. 2006; 9; 72–74. 4. Murakumo M, Nonomura K, Yamashita T et al. Structural changes of collagen components and diminution of nerves in congenital ureteropelvic junction abstruction. J. Urol. 1997; 157; 1963–1968. 5. Chiou YY, Shieh CC, Cheng HL et al. Intrinsic expression of Th2 cytokines in urothelium of congenital ureteropelvic junction obstruction. Kidney Int. 2005; 67; 638–646.