Large Congenital Cutaneous Mastocytoma Presenting With Recurrent Persistent Blistering: A Case Report.

Congenital cutaneous mastocytoma is an uncommon disorder characterized by abnormal proliferation of mast cells. It typically presents as a single, small, yellowish-brown plaque, and its diagnosis is generally facilitated by distinctive clinical features, including a positive Darrier's sign. This report presents a case of an unusually large, solitary congenital mastocytoma encompassing nearly the entire circumference of the calf, observed in a newborn boy of Bangladeshi origin. Measuring 13x6 cm, the lesion formed large bullae and subsequent erosions. The perplexing clinical appearance prompted a skin biopsy, revealing monomorphic CD117 (c-KIT) positive infiltration without significant cell pleomorphism, confirming the diagnosis of cutaneous mastocytoma. The patient underwent management with potent and very potent topical steroids, oral antihistamines, and non-adhesive dressings, remaining under long-term follow-up with secondary care dermatology. In reporting this case, our objective is to augment the existing scientific literature by providing additional evidence that cutaneous mastocytomas can display a spectrum of clinical presentations, as illustrated in this case.

Zoonotic acquisition of cutaneous Sporothrix braziliensis infection in the UK.

A veterinarian presented with multiple erythematous tender nodules over his right hand and arm. One month prior to the appearance of the lesions, he had treated a cat imported from Brazil who had ulcerated pustular cutaneous lesions. Despite antibiotic treatment there had been no improvement in his symptoms.Biopsies from the patient were sent for histology, bacterial and fungal culture. Periodic acid-Schiff (PAS) stains showed a PAS positive oval yeast-like micro-organism with surrounding necrosis. Fungal cultures resembling Sporothrix species grew after 18 days with typical appearances seen on direct microscopy; this was confirmed as Sporothrix brasiliensis on 18S PCR. The patient was treated with oral itraconazole.This is a unique case of cutaneous S. brasiliensis acquired from an infected imported cat. S. brasiliensis is a rare pathogen in the UK. This case has clinical relevance due to its unusual aetiology and in raising awareness of rarer infections associated with importation of pets and global travel. Clinicians should be aware of sporotrichosis as a differential diagnosis for cutaneous and extracutaneous infection in patients with a high risk of exposure, as well as the use of appropriate diagnostic tests.

The SWI/SNF complex in eosinophilic and non eosinophilic chronic rhinosinusitis.

INTRODUCTION: Chronic rhinosinusitis (CRS) can be classified as eosinophilic (eCRS) or non-eosinophilic (neCRS) based on infiltration type. The SWI/SNF complex may be involved in the pathophysiology of CRS. AIM: To assess the expression of the SWI/SNF complex in both CRS groups; to correlate blood eosinophil count (BEC), and histopathology eosinophil count (HPEC) with the SWI/SNF expression level in eCRS and neCRS. MATERIALS AND METHODS: The study population consisted of 96 patients (68 eCRS, 28 neCRS). Immunohistochemical staining was performed on sinonasal mucosa for assessment of SWI/SNF protein expression. Type of tissue infiltration was assessed in samples obtained from examined groups (HPEC). The diagnostic value of eCRS was 10 cells/HPF (high power field). Complete blood count was analysed in order to calculate BEC. RESULTS: BEC and HPEC correlated negatively with all the SWI/SNF subunits. HPEC and BEC correlated positively with clinical findings (L-M and SNOT-22), while SWI/SNF correlated negatively with clinical findings (L-M and SNOT-22). CONCLUSIONS: The SWI/SNF was observed in both eCRS and neCRS, with lower expression in former. The meaning of its negative correlation with BEC, HPEC and clinical findings in eCRS group remains to be understood.

Succinate Dehydrogenase-Deficient Renal Cancer Featuring Fructose-1,6-Biphosphatase Loss, Pyruvate Kinase M2 Overexpression, and SWI/SNF Chromatin Remodeling Complex Aberrations: A Rare Case Report.

Succinate dehydrogenase (SDH)-deficient renal cancer is a rare renal cancer subtype recently accepted by the World Health Organization as a unique subtype of renal cell carcinoma (RCC). Here we report a case of 17-year-old man. The detailed evaluation indicated occurrence of the SDHB-deficient RCC. The genetic testing revealed no germline mutation in SDH genes. Immunohistochemistry showed SDHB deficiency, overexpression of pyruvate kinase M2 and dramatic downregulation of fructose-1,6-bisphosphatase metabolic enzymes, and unaltered levels of phosphorylated AMP-activated protein kinase and mammalian target of rapamycin. Strong upregulation of INI1 and BRG1 and overexpression of BAF180, subunits of SWI/SNF ATP-dependent chromatin remodeling complex, were also found. The identified tumor pathologically did not resemble clear cell renal cell carcinoma (ccRCC), but some metabolic alterations are common for both cancer types. Thus, we postulate that the phenotypical differences between ccRCC and SDHB-deficient RCC may be related to distinct molecular and metabolic alterations. IMPLICATIONS FOR PRACTICE: Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare renal tumor occurring even in young patients. Until now, in all described and genetically tested cases, mutations and deletions in SDH genes have been found. This article describes SDHB-deficient RCC without any germline mutations in SDH genes. Therefore, genetic analysis for germline mutations in SDH genes in SDH-deficient RCC, especially in young individuals, should be strongly recommended, although as of now it is not obligatory. This knowledge will allow improvement of patient monitoring including both disease recurrence and new cancer appearance.

Evaluation of the role of downregulation of SNF5/INI1 core subunit of SWI/SNF complex in clear cell renal cell carcinoma development.

Clear cell renal cell carcinoma (ccRCC) is characterized by stabilization of hypoxia-inducible factor (HIF1), and mutations in von Hippel-Lindau (VHL) gene. Additionally, in about 40% of ccRCC cases the mutation in PBRM1 (POLYBROMO1) gene coding for a non-core subunit of SWI/SNF chromatin remodeling complex was found suggesting potential impairment of this complex function in ccRCC. In this study we assessed the extent to which the core SWI/SNF complex subunit - INI1 (hSNF5/SMARCB1) is affected in ccRCC and whether it has any consequences on the development of this type of cancer. The evaluation of INI1 protein level in samples from 50 patients with diagnosed ccRCC, including three displaying rhabdoid features, showed the INI1 positive staining in rhabdoid cells while the conventional ccRCC cells exhibited reduced INI1 level. This indicated the rhabdoid component of ccRCC as distinct from other known rhabdoid tumors. The reduced INI1 protein level observed in all conventional ccRCC cases used in this study correlated with decreased SMARCB1 gene expression at the transcript level. Consistently, the overexpression of INI1 protein in A498 ccRCC cell line resulted in the elevation of endogenous SMARCB1 transcript level indicating that the INI1-dependent regulatory feedback loop controlling expression of this gene is affected in ccRCC Moreover, the set of INI1 target genes including i.e. CXCL12/CXCR7/CXCR4 chemokine axis was identified to be affected in ccRCC. In summary, we demonstrated that the inactivation of INI1 may be of high importance for ccRCC development and aggressiveness.

Downregulation of PTPRH (Sap-1) in colorectal tumors.

Tyrosine phosphorylation is one of the basic mechanisms for signal transduction in the cell. Receptors exhibiting tyrosine kinase activity are widely involved in carcinogenesis and are negatively regulated by receptor protein tyrosine phosphatases (RPTP). Genes encoding different RPTPs are affected by aberrant epigenetic regulation in cancer. PTPRH (SAP-1) has been previously described to be overexpressed in colorectal cancer (CRC) and classified as an oncogenic factor. Previous microarray-based mRNA expression comparison of colorectal adenomas (AD), CRC and normal mucosa samples (NM) demonstrated that PTPRH tumor expression is the most reduced of all RPTP genes. qRT-PCR validation revealed gene downregulation for CRC (7.6-fold-change; P<0.0001) and AD (3.4-fold-change; P<0.0001) compared to NM. This was confirmed by immunohistochemical staining of tumor and NM sections as pronounced decrease of protein expression was observed in CRCs compared to the corresponding normal tissue. DNA methylation of two PTPRH promoter fragments was analyzed by pyrosequencing in a group of CRC, and AD patients as well as NM samples and CRC cell lines. The mean DNA methylation levels of these two regions were significantly higher in CRC than in NM. Both regions were highly methylated in SW480 and HCT116 cell lines contrary to unmethylated HT29 and COLO205. Cell lines with highly methylated promoters notably showed lower PTPRH expression levels, lower RNA II polymerase concentrations and higher levels of H3K27 trimethylation in the promoter and gene body, measured by chromatin immunoprecipitation. Cells were cultured with 5-aza-deoxycitidine and an increase in PTPRH expression was observed in SW480 and HCT116, whereas this was unchanged in the unmethylated cell lines. The results indicate that PTPRH is downregulated in colorectal tumors and its expression is epigenetically regulated via DNA methylation and chromatin modifications.

Expression changes of cell-cell adhesion-related genes in colorectal tumors.

Epithelial tissues achieve a highly organized structure due to cell-cell junction complexes. Carcinogenesis is accompanied by changes in cell interactions and tissue morphology, which appear in the early stages of benign tumors and progress along with invasive potential. The aim of the present study was to analyze the changes in expression levels of genes encoding intercellular junction proteins that have been previously identified to be differentially expressed in colorectal tumors compared with normal mucosa samples (fold change, >2.5) in genome-wide expression profiling. The expression of 20 selected genes was assessed using quantitative reverse transcription polymerase chain reaction in 26 colorectal cancer, 42 adenoma and 24 normal mucosa samples. Between these tissue types, differences were observed in the mRNA levels of genes encoding adherens junction proteins (upregulation of CDH3 and CDH11, and downregulation of CDH19 and PTPRF), tight junction proteins (upregulation of CLDN1 and CLDN2, and downregulation of CLDN5, CLDN8, CLDN23, CLDN15, JAM2 and CGN) and desmosomes (upregulation of DSC3 and DSG3, and downregulation of DSC2), in addition to a decrease in the expression of certain other genes involved in intercellular connections: PCDHB14, PCDH7, MUPCDH and NEO1. The differences between tissue types were statistically significant, and separate clustering of normal adenoma and carcinoma samples was observed in a hierarchical clustering analysis. These results indicate that the morphological changes in neoplastic colon tissue that occur during the 'adenoma-carcinoma sequence' are accompanied by specific changes in the expression of multiple genes encoding the majority of cell-cell junction complexes. The particular differential expression patterns appear to be consistent among patients with cancer and adenoma, in addition to normal mucosa samples.

FISH and array CGH characterization of de novo derivative Y chromosome (Yq duplication and partial Yp deletion) in an azoospermic male.

This study presents a 28-year-old infertile male who was referred to the cytogenetic laboratory for chromosomal analysis after 4 years of regular unprotected intercourse in whom non-obstructive azoospermia was revealed. Standard cytogenetic G-banding was performed on metaphase spreads and a de-novo karyotype 46,X,der(Y)(q11.22;p11.3) was identified. This analysis was followed by flourescence in-situ hybridization(FISH) and array comparative genomic hybridization (aCGH). Finally, the patient's karyotype was identified as 46,X,der(Y)(qter→q11.221::p11.31→qter).ish der(Y) (qter+,pter-,SHOX+,SRY+,Ycen+,DYZ3+;DYZ1+,qter+).arrYq11.221q12(14,448,863-59,288,511) x2, Yp11.32p11.31(104,062-266,388) x0. It is proposed that de-novo derivative monocentric Y chromosome with duplicated region Y qter→q11.221::p11.31→qter with partial deletion of Yp PAR1 region most probably can perturb the conjugation of sex chromosomes during first meiotic division of spermatogenic arrested differentiation (development).

Epigenetic-Mediated Downregulation of µ-Protocadherin in Colorectal Tumours.

Carcinogenesis involves altered cellular interaction and tissue morphology that partly arise from aberrant expression of cadherins. Mucin-like protocadherin is implicated in intercellular adhesion and its expression was found decreased in colorectal cancer (CRC). This study has compared MUPCDH (CDHR5) expression in three key types of colorectal tissue samples, for normal mucosa, adenoma, and carcinoma. A gradual decrease of mRNA levels and protein expression was observed in progressive stages of colorectal carcinogenesis which are consistent with reports of increasing MUPCDH 5' promoter region DNA methylation. High MUPCDH methylation was also observed in HCT116 and SW480 CRC cell lines that revealed low gene expression levels compared to COLO205 and HT29 cell lines which lack DNA methylation at the MUPCDH locus. Furthermore, HCT116 and SW480 showed lower levels of RNA polymerase II and histone H3 lysine 4 trimethylation (H3K4me3) as well as higher levels of H3K27 trimethylation at the MUPCDH promoter. MUPCDH expression was however restored in HCT116 and SW480 cells in the presence of 5-Aza-2'-deoxycytidine (DNA methyltransferase inhibitor). Results indicate that µ-protocadherin downregulation occurs during early stages of tumourigenesis and progression into the adenoma-carcinoma sequence. Epigenetic mechanisms are involved in this silencing.

An incidentally diagnosed prostatic ductal adenocarcinoma.

Ductal adenocarcinoma of the prostate was initially described in 1967 by Melicow and Patcher. It was given the erroneous name endometrioid carcinoma, however, further studies confirmed the prostatic origin of this tumor. Currently DAP is classified as a histological variant of prostatic carcinoma. Compared with "classic" acinar carcinoma of the prostate, DAP is a rare histological finding. It's prevalence in prostatectomy and biopsy specimens varies from less than 1% for pure ductal adenocarcinoma up to 5% for mixed DAP. Because of its typical periurethral location, the tumor usually manifests itself clinically with urinary obstruction, urinary urgency, urinary frequency and hematuria. DAP is associated with more aggressive natural history and worse prognosis than pure AA - patients presented at more advanced stage, with poorly differentiated and distant disease. DAP has a tendency to spread to regional lymph nodes, axial skeleton, and visceral organs. We report a case of a 90-year old man who presented to our clinic with acute urinary retention and gross hematuria. He underwent suprapubic transvesical adenomectomy to diminish the urinary obstruction. The pathological examination of the specimens revealed a dominant focus of DAP, which was located near the intraprostatic urethra and a coexisting, smaller component of "classic" acinar adenocarcinoma.

Renal function after nephron-sparing surgery for renal tumors.

Nephron sparing surgery (NSS) is a technique more frequently utilized in the case of surgical treatment of kidney tumor. The aim of the study is to assess renal function in patients treated with NSS for renal tumors. Twenty patients, after NSS performed for renal tumor, were included in the study. In each patient dynamic renal scintigraphy was performed before surgical treatment (test No. 1) and after a mean interval of 12 months after surgical procedure (test No. 2). In each test renographic curves were evaluated. Creatinine levels and GFR rates were also assessed. Mean GFR was 84 ml/min/1.73 m(2) before surgery, and 79 ml/min/1.73 m(2) after surgical procedure. Mean change of GFR value after the surgical procedure was -5.1 (p >0.058). On renography significant deterioration of renal function was observed in the operated kidneys of 4 patients (20%) after NSS, insignificant deterioration - in four patients (20%) and improvement of renal function of operated kidney was found in one patient. In 12 patients (60%) no change was observed. The relative percentage GFR-share of operated kidney decreased by the average value of 3.8% (p >0.005). Multifactorial analysis did not identify significant effect of potential risk factors on the function of the kidney subjected to NSS. Preliminary results of this study confirm that deterioration of renal function after NSS is a rare event.

Mucinous tubular and spindle cell carcinoma.

A case of a 30-year-old female patient diagnosed with mucinous tubular and spindle cell carcinoma (MT&SCC) of her left kidney of the basis of an abdominal ultrasound scan performed when nonspecific pain is presented. The histopathology report revealed a classic type of MT&SCC. Photographs of histopathological samples are shown. Nephrectomy was applied as sole treatment. A follow-up of six years confirmed surgery to be a sufficient approach. The discussion presents a review of up to date world literature concerning the histopathological features, prognosis, and treatment of MT&SCC.

Urinary incontinence after radical prostatectomy - experience of the last 100 cases.

Radical prostatectomy (RP) is a recognized treatment method of organ-confined prostate cancer. Among post-surgery complications, urinary incontinence is a major one. The aim of this study was to determine the incontinence rate after RP and to analyze factors that might affect it. Between March 2007 and December 2008, 132 RP's were performed at Warsaw Cancer Center. A questionnaire to assess the condition before and after RP was developed by the authors and sent to all treated patients. The questionnaire focused on health status information, function in urinary domain, rate of returning to "normal" activity level as before RP and satisfaction from the treatment. The median age of patients was 62 years. Out of 132 patients 102 subjects (77.2%) responded to the questionnaire. Of all responders, 35 patients (34.3%) reported total urinary continence after RP. After RP 35(34.3%) patients reported total urinary continence and in 55(53.9%) patients urinary incontinence of medium degree was present. In 12 (11.8%) patients significant urinary incontinence developed. The most common cause of urine dripping (82% of patients with any degree of urinary incontinence) was associated with abdominal muscle pressure. No statistically significant association between urinary incontinence and adjuvant radiotherapy after RP or the surgeon performing the RP was found (>0.79, >0.803). Radical prostatectomy carries a certain risk of complications. We observed an 88.2% rate of significant (total and moderate degree) urinary continence. The adjuvant radiotherapy and surgeons, who performed the RP, did not affect the rate of incontinence.

Variation in breast cancer hormone receptor and HER2 levels by etiologic factors: a population-based analysis.

Evidence suggests that breast cancer hormone receptor status varies by etiologic factors, but studies have been inconsistent. In a population-based case-control study in Poland that included 2,386 cases and 2,502 controls, we assessed ER-alpha and PR status of tumors based on clinical records according to etiologic exposure data collected via interview. For 842 cancers, we evaluated ER-alpha, ER-beta, PR and HER2 levels by semiquantitative microscopic scoring of immunostained tissue microarrays and a quantitative immunofluorescence method, automated quantitative analysis (AQUAtrade mark). We related marker levels in tumors to etiologic factors, using standard regression models and novel statistical methods, permitting adjustment for both correlated tumor features and exposures. Results obtained with different assays were generally consistent. Receptor levels varied most significantly with body mass index (BMI), a factor that was inversely related to risk among premenopausal women and directly related to risk among postmenopausal women with larger tumors. After adjustment for correlated markers, exposures and pathologic characteristics, PR and HER2 AQUA levels were inversely related to BMI among premenopausal women (p-trend = 0.01, both comparisons), whereas among postmenopausal women, PR levels were associated directly with BMI (p-trend = 0.002). Among postmenopausal women, analyses demonstrated that BMI was related to an interaction of PR and HER2: odds ratio (OR) = 0.86 (95% CI = 0.69-1.07) for low PR and HER2 expression vs. OR = 1.78 (95% CI = 1.25-2.55) for high expression (p-heterogeneity = 0.001). PR and HER2 levels in breast cancer vary by BMI, suggesting a heterogeneous etiology for tumors related to these markers.

Differences in risk factors for breast cancer molecular subtypes in a population-based study.

Analysis of gene expression data suggests that breast cancers are divisible into molecular subtypes which have distinct clinical features. This study evaluates whether pathologic features and etiologic associations differ among molecular subtypes. We evaluated 804 women with invasive breast cancers and 2,502 controls participating in a Polish Breast Cancer Study. Immunohistochemical stains for estrogen receptor alpha, progesterone receptor, human epidermal growth factor receptors (HER2 and HER1), and cytokeratin 5 were used to classify cases into five molecular subtypes: luminal A, luminal B, HER2-expresing, basal-like, and unclassified. Relative risks were estimated using adjusted odds ratios and 95% confidence intervals. We observed that compared with the predominant luminal A tumors (69%), other subtypes were associated with unfavorable clinical features at diagnosis, especially HER2-expressing (8%) and basal-like (12%) tumors. Increasing body mass index significantly reduced the risk of luminal A tumors among premenopausal women (odds ratios, 0.71; 95% confidence intervals, 0.57-0.88 per five-unit increase), whereas it did not reduce risk for basal-like tumors (1.18; 0.86-1.64; P(heterogeneity) = 0.003). On the other hand, reduced risk associated with increasing age at menarche was stronger for basal-like (0.78; 0.68-0.89 per 2-year increase) than luminal A tumors (0.90; 0.95-1.08; P(heterogeneity) = 0.0009). Although family history increased risk for all subtypes (except for unclassified tumors), the magnitude of the relative risk was highest for basal-like tumors. Results from this study have shown that breast cancer risk factors may vary by molecular subtypes identified in expression studies, suggesting etiologic, in addition to clinical, heterogeneity of breast cancer.