CD56 and smooth muscle actin immunoreactivity in basal cell carcinomas: Are they indicators of differentiation or do they hold a diagnostic use?

BACKGROUND: Basal cell carcinoma (BCC) is the most common cutaneous malignancy and may show various differentiations. The possible pluripotent stem cell lineage of BCCs, whose origins are controversial today, is thought to be the main reason for the different morphologies. The aim of the study is to evaluate the expression of some neuroendocrine and smooth muscle markers of differentiation in BCCs and investigate the relationship between histopathologic subtypes and recurrence. METHODS: A total of 128 cases diagnosed as BCC in our center were included. Immunohistochemical studies of CD56, synaptophysin, chromogranin-A, smooth muscle actin (SMA), desmin, caldesmon, and Ki67 were applied. RESULTS: CD56, chromogranin-A, and synaptophysin immunoreactivity were detected in 77.3%, 13.3%, and 0.8% of the cases, respectively. 78.1% showed SMA positivity while no tumor expressed desmin or caldesmon. A correlation between histopathologic recurrence risk groups and CD56 expression was found (p < 0.05). CONCLUSIONS: CD56 and SMA immunoreactivity is present in the majority of BCCs. However, the available findings do not support neuroendocrine or smooth muscle differentiation. CD56 antigen can be used for prognostic purposes in detecting high recurrence risk tumors. After the investigation of the expression rates of these two antigens in different cutaneous tumors, it may be appropriate to use them for diagnostic purposes in BCCs.

Birt-Hogg-Dubé Syndrome: Diagnostic Journey of Three Cases from Skin to Gene.

Birt-Hogg-Dube syndrome (BHDS) is a rare disorder characterized by the triad of cutaneous lesions, renal tumors, lung cysts and inactivation of the gene folliculin (FLCN). Here, we present three female patients diagnosed with BHDS. First case a 55-year-old female had flesh moles histopathology compatible with angiofibroma, multiple cysts in the lung and kidneys, FLCN gene mutations ('c.1285dupC [p.His429Profs*]' 11th exon and 'c.653G>A [p.Arg258His]' 7th exon). The second case a 76-year-old female had trichodiscoma on her skin, multiple cysts in the lung, spontaneous pneumothorax, FLCN gene mutation 'c.1285dupC (p.His429Profs*27) 11th exon' and, her son had renal carcinoma history under 50 years of age. Our third case, also the daughter of case 2, had dermal papules histopathology compatible with trichodiscoma, spontaneous pneumothorax, FLCN gene mutation 'c.1285dupC (p.His429Profs*27) 11th exon' and, parotid oncocytoma. Through our cases, we document the first case of two mutations ('c.1285dupC [p.His429Profs*]' 11th exon and 'c.653G>A [p.Arg258His]' 7th exon) in the same FLCN gene and the 11th known case of parotid oncocytoma associated with BHDS in the light of the literature.

Maspin expression in gastrointestinal stromal tumors.

BACKGROUND: To investigate the role of maspin expression in the progression of gastrointestinal stromal tumors, and its value as a prognostic indicator. METHODS: In the study 54 patients with GIST diagnosis were included in Uludag University of Faculty of Medicine, Department of Pathology between 1997-2007. The expression of maspin in 54 cases of gastrointestinal stromal tumor was detected by immunohistochemistry and compared with the clinicopathologic tumor parameters. RESULTS: The positive expression rates for maspin in the GISTs were 66.6% (36 of 54 cases). Maspin overexpression was detected in 9 of 29 high risk tumors (31%) and was significantly higher in very low/low (78.6%) and intermediate-risk tumors (63.6%) than high-risk tumors. CONCLUSIONS: Maspin expression might be an important factor in tumor progression and patient prognosis in GIST. In the future, larger series may be studied to examine the prognostic significance of maspin in GISTs and, of course, maspin expression may be studied in different mesenchymal tumors.

Cutaneous heterotopic bronchogenic tissue in the scapular area.

Cutaneous bronchogenic anomalies are very rare lesions, and most of them present as cysts and/or sinus tracts in the subcutaneous layer. We report a 15-year-old boy who presented with a crusted and papillomatous plaque over the right scapular region. Histopathological examination of this plaque revealed pseudostratified ciliated columnar epithelium with papillary invaginations that included mucinous material. The lesion had no cyst or sinus formation and was bordered with smooth muscle bundles in stroma.

Miliary osteoma cutis of the face: treatment with the needle microincision-extirpation method.

Multiple miliary osteoma cutis of the face represents primary extra-skeletal bone formation that arises within the skin of the face. Multiple miliary osteoma cutis of the face is a rare complication of chronic inflammatory acne vulgaris and has invasive and non-invasive treatment alternatives different from acne vulgaris. Invasive techniques should be simple, easy, and inexpensive, with minimal risk of scarring and pigmentation. We used a needle microincision-extirpation technique in a patient with multiple miliary osteoma cutis unresponsive to non-invasive treatment modalities. Skin overlying the papules was incised with a needle and then the calcificated papules were extirpated by using a small curettage device. Lesions were left to secondary healing. Results were quite good and cosmetically acceptable.

Periampullary carcinomas.

BACKGROUND/AIMS: The purpose of this study was to determine predictors of survival after resection for periampullary neoplasms. METHODOLOGY: In this study, we reevaluated our 17 cases of this type tumor which we had reported as periampullar site tumors, in advanced stages with undetermined localization, in our pathology department of the Uludag University faculty of medicine. RESULTS: Six of our cases were female, and 11 were male with a mean age of 60.6 years (range 31-77). Their main complaints were loss of weight, anorexia, jaundice and fatigue. Physical and endoscopic examination of these patients revealed periampullary mass and Whipple operations were performed on all of them. Histopathologic examinations of these tumors revealed adenocarcinoma in 15, small cell (neuroendocrin) carcinoma in two. All were in the advanced stages. Eight of them were alive and free of disease after 1.5- to 20-month follow-ups, while ten died because of disease. CONCLUSIONS: Periampullary carcinoma is a problem with increasing clinical significance. Tumor size, tumor type and differentiation, lymph node status appears to be prognostic markers.

A Mimicker of Gallbladder Carcinoma: Cystic Gastric Heterotopia with Intestinal Metaplasia.

Heterotopic gastric mucosa in the gallbladder is an unusual entity and is usually clinically silent. We report a 75-year-old female patient who presented with intermittent upper abdomial pain radiating to the back. Abdominal imaging studies showed a sessile polypoid lesion and a gallstone in the gallbladder. Gallbladder carcinoma was suspected and cholecystectomy performed. Intraoperative frozen section examination suggested mucinous tumor, suspicious for malignancy. However, the permanent sections revealed aberrant gastric tissue consisted of gastric pyloric and fundic glands of heterotopic gastric mucosa with intestinal metaplasia in the gallbladder.

The biochemical and histological analysis of subcutaneous calcitonin and intramedullary methylprednisolone on bone repair after bone marrow ablation: an experimental comparative study in rats.

BACKGROUND: Although, glucocorticoid (GC) and calcitonin-induced changes in bone repair have been studied previously, the exact effects of these on fracture healing remain controversial. Hence, the purpose of this experimental study is to determine biochemical and histological effects of locally administrated GC and systemically administrated calcitonin on the kinetics of healing response after bone marrow ablation in rats. METHODS: After having undergone marrow ablation, a steroid-treated group of rats (n = 24) received a single dose of intramedullary methylprednisolone (2 mg/kg), a calcitonin-treated group (n = 24) received intermittently administrated subcutaneous salmon calcitonin (16 IU/kg), and a control group (n = 24) received intramedullary saline (25 µl). RESULTS: Blood samples taken on days 1, 3, 7, 9, and 15 after ablation showed an increase in serum calcium, alkaline phosphatase (ALP), and phosphate levels in the Calcitonin and Control groups. Levels of calcium and ALP peaked on day 7 after ablation. However, an increase in phosphate levels indicated a biphasic reaction that peaked on the third and ninth day after ablation. Hypercalcemia was not observed in Steroid group because of the inhibition of osteoclastic bone resorption. In that group, the serum levels of ALP and phosphate were lower than baseline levels. The levels of urinary calcium excretion peaked 3 to 7 days after marrow ablation in the control group and 7 to 9 days after that procedure in the steroid group. Histologic evaluation showed that the rats in the control group demonstrated the expected healing period according to the histological grades and that a delay in healing occurred in the calcitonin group after day 9 because of the inhibition of osteoclastic bone resorption. All rats in the steroid group exhibited a decrease and delayed healing response. CONCLUSION: Total serum calcium, phosphate, and ALP levels increased after bilateral tibial bone marrow ablation and urine calcium and hydroxyproline excretion also increased as a factor of bone resorption. Subcutaneously administrated salmon calcitonin did not affect biochemical changes after marrow ablation. Single-dose intramedullary methylprednisolone inhibited extra-tibial bone resorption induced by cytokines after bone marrow ablation.

A case of epidermodysplasia verruciformis associated with squamous cell carcinoma and Bowen's disease: a therapeutic challenge.

Epidermodysplasia verruciformis (EV) is a very rare and chronic disease characterized by a susceptibility to cutaneous infections by a group of phylogenetically related human papillomavirus (HPV) types. We present here a 52-year-old man previously diagnosed and treated as squamous cell carcinoma but also found to have epidermodysplasia verruciformis lesions in association with Bowen's disease. The patient was effectively treated with a combination of interferon therapy (6 million units, twice a week) and topical imiquimod for Bowen's disease (five times a week). We conclude that topical imiquimod is very effective in the treatment of Bowen's disease and may be combined with systemic interferon therapy in rare cases with multiple vivid presentations of HPV infections.

Adipo-R1 and adipo-R2 expression in colorectal adenomas and carcinomas.

BACKGROUND: Human adiponectin (ApN), a 30 kDa glycoprotein of 244-amino acids which is predominantly produced by adipocytes, exerts its effects via two receptors, namely adiponectin receptor-1 (adipo-R1) and adiponectin receptor-2 (adipo-R2) with differential binding affinity to globular adiponectin. Adiponectin receptor expression has been studied in several cancer tissues. However, there are no studies of colorectal adenomas which are considered to be precursors for colorectal carcinoma (CRC). OBJECTIVES: In the present study, the expression of adipo-R1 and adipo-R2 was investigated immunohistochemically in colorectal adenomas and colorectal carcinoma tissues in an attempt to determine associations with these tumors. MATERIALS AND METHODS: The study enrolled 50 CRC patients with tumor resection and 82 patients who were diagnosed with adenomatous polyps, classified as negative for neoplasia, low-grade dysplasia (L-GD) or high- grade dysplasia (H-GD). RESULTS: Expression of both adipo-R1 and adipo-R2 was found to be significantly lower in the CRCs than in colorectal adenomas (tubular and tubulovillous, p=0.009 and p<0.001, respectively). Adipo-R1 and adipo-R2 expression was also significantly lower in the CRC group when compared with the groups of patients with low grade dysplasia, high-grade dysplasia or no neoplasia (p=0.012 and p<0.001, respectively). In addition, it was observed that adipo-R2 expression was generally positive in the non-neoplastic group irrespective of the adipo-R2 expression. In the L-GD, H-GD and CRC groups, the adipo-R2 result was positive whenever adipo-R1 result was positive but some patients with negative adipo-R1 had positive adipo-R2 (p<0.001, p=0.004, p<0.001, respectively). CONCLUSIONS: This study indicated that ApN may play a role in the progression of colorectal adenomatous polyps to carcinoma through actions on adipo-R1 and adipo-R2 receptors.

Flow Cytometric Analysis of T, B, and NK Cells Antigens in Patients with Mycosis Fungoides.

We retrospectively analyzed the clinicopathological correlation and prognostic value of cell surface antigens expressed by peripheral blood mononuclear cells in patients with mycosis fungoides (MF). 121 consecutive MF patients were included in this study. All patients had peripheral blood flow cytometry as part of their first visit. TNMB and histopathological staging of the cases were retrospectively performed in accordance with International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC) criteria at the time of flow cytometry sampling. To determine prognostic value of cell surface antigens, cases were divided into two groups as stable and progressive disease. 17 flow cytometric analyses of 17 parapsoriasis (PP) and 11 analyses of 11 benign erythrodermic patients were included as control groups. Fluorescent labeled monoclonal antibodies were used to detect cell surface antigens: T cells (CD3(+), CD4(+), CD8(+), TCRαß(+), TCRγδ(+), CD7(+), CD4(+)CD7(+), CD4(+)CD7(-), and CD71(+)), B cells (HLA-DR(+), CD19(+), and HLA-DR(+)CD19(+)), NKT cells (CD3(+)CD16(+)CD56(+)), and NK cells (CD3(-)CD16(+)CD56(+)). The mean value of all cell surface antigens was not statistically significant between parapsoriasis and MF groups. Along with an increase in cases of MF stage statistically significant difference was found between the mean values of cell surface antigens. Flow cytometric analysis of peripheral blood cell surface antigens in patients with mycosis fungoides may contribute to predicting disease stage and progression.

Ursodeoxycholic acid and atorvastatin in the treatment of nonalcoholic steatohepatitis.

BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is a serious disorder with the potential to gradually progress to cirrhosis. It is generally associated with obesity, diabetes and hyperlipidemia. Currently, there is no established therapy for NASH. The aim of the present study was to evaluate the effectiveness of atorvastatin and ursodeoxycholic acid (UDCA) in the treatment of NASH. METHODS: This prospective study included 44 adult patients (24 men, 20 women) with a mean age of 48.90+/-7.69 years and mean body mass index (BMI) of 29.40+/-3.82. Ten patients had a history of diabetes. Serological markers for viral hepatitis were negative in all patients and there was no history of alcohol or drug abuse. Patients who had autoimmune hepatitis were excluded from the study. Liver biopsy was performed before therapy to confirm the diagnosis. Among NASH patients, 17 normolipidemic cases received UDCA 13 to 15 mg/kg/day (group 1), while hyperlipidemic cases (n=27) received atorvastatin 10 mg/day (group 2) for six months. The BMI, serum lipids, liver function tests and liver density, assessed by computerized tomography, were evaluated before and after the treatment period. The BMI, serum aminotransferase levels, histological parameters (steatosis, inflammation, fibrosis scores) and liver densities were not statistically different between the groups at the beginning of therapy. RESULTS: The BMI, serum glucose, and triglyceride levels did not change in either group after the treatment period. In group 1, serum alanine aminotransferase (ALT) and gamma-glutamyl-transferase (GGT) levels reduced significantly, and in group 2, serum cholesterol, aspartate aminotransferase, ALT, alkaline phosphatase and GGT levels reduced significantly. Liver densities increased only in group 2, probably as a result of diminishing fat content of liver. The normalization of transaminases was also more prevalent in group 2. Liver steatosis was closely correlated with liver density, but inflammation and fibrosis were not. CONCLUSIONS: The use of atorvastatin in NASH patients with hyperlipidemia was found to be both effective and safe. The benefit of statin and UDCA therapy in normolipidemic patients with NASH requires confirmation with further placebo-controlled trials.

Small cell carcinoma of the urinary bladder. A clinicopathologic study of five cases.

AIMS AND BACKGROUND: Small cell carcinoma of the bladder (SCCB) is a rare entity characterized clinically by an aggressive behavior with a high incidence of systemic metastases. We report the clinicopathologic findings of five cases. METHODS: We reviewed five consecutive patients with SCCB treated at our institute. In each case the following clinical data were recorded: age, sex, presenting symptoms, endoscopically determined location of the tumor, clinical staging, node involvement (if any), site of metastases (if any), treatment, follow-up and outcome. RESULTS: There were four male and one female patients, age range 42 to 68 years, mean 57.6 years. The clinical presentation was not different from conventional transitional cell carcinoma, with hematuria being the most frequent complaint (four cases). Microscopic examination revealed oat cells in three cases and an intermediate variant in one. At the time of diagnosis the tumors were staged as T3bN2M0, T2N2M0, T4N0M0, T3aN0M0, and T2N0M0. Primary therapy consisted of radical cystectomy alone (one case), transurethral resection (TUR) alone (one case), TUR with chemotherapy (two cases), or TUR with chemotherapy and radiotherapy (one case). Four patients died of progressive disease, with survival from the time of diagnosis ranging from 7 to 16 months (mean, 12.2 months). One patient died of myocardial infarction (unrelated to the primary disease) one month after diagnosis. CONCLUSION: Our study indicates that primary small cell carcinoma of the urinary bladder is as aggressive as its pulmonary counterpart and the overall prognosis of this tumor is very poor.

Eyelid Basal cell carcinoma in a healthy child.

Basal cell carcinoma is rare in children and usually is associated with genetic or immune predisposing factors. A 14-year-old otherwise healthy boy who had an eyelid basal cell carcinoma is presented. The tumor was in the subcilliary area in the lateral part of the lower eyelid, was ulceronodular with some pigmentation, and had grown over the past 6 months. The patient's medical history was unremarkable. Systemic and immunologic studies did not find any abnormality that could present a predisposition to skin cancer. The tumor was excised and the resulting eyelid defect was repaired with a semicircular flap. During a follow-up period of 44 months, the patient did not develop any recurrence, de novo tumor, or extraocular disease of any significance.

Association of adiponectin receptor (Adipo-R1/-R2) expression and colorectal cancer.

INTRODUCTION: Human adiponectin (ApN) is a 30 kDa glycoprotein of 244-amino acids which is extensively produced by adipocytes. ApN acts via two receptors, namely adiponectin receptor-1 (Adipo-R1) and adiponectin receptor-2 (Adipo-R2). Studies have shown the presence of Adipo-R1 and Adipo-R2 expression immunohistochemically in human colorectal cancers (CRCs). However, only a few studies exist which investigated effects of adiponectin receptor expression on CRC characteristics. OBJECTIVES: In the present study, we aimed to explore Adipo-R1/-R2 expression in human colorectal cancers and any association with clinicopathological characteristics and survival. MATERIALS AND METHODS: The study enrolled 58 colorectal cancer patients with tumor resection and a control group of 30 subjects with normal colon mucosa. RESULTS: Positivity for Adipo-R1/-R2 expression was significantly more common in the control group in comparison to the patient group (both p<0.001). There was no significant association between Adipo-R1/-R2 expression and clinicopathological characteristics including age, sex tumor location, pTNM stage, Duke's stage, metastasis, histological differentiation, perineural invasion, venous invasion sex, lymphatic invasion, cancer-related mortality, tumor size and recurrence. Adipo- R1/-R2 positivity was also not significantly linked to progression-free or overall survival [p values (0.871, 0.758 ) and (0.274, 0.232), respectively]. CONCLUSIONS: Although significantly reduced Adipo-R1/-R2 expression was found in colorectal cancer patients, it had no influence on survival.

Multiple warty dyskeratomas: case report.

Warty dyskeratoma is a rare tumor that presents mainly as an isolated papule or nodule on the scalp, face or neck in the adults. Warty dyskeratoma frequently arises as a single lesion with a central keratotic plug on the skin of middle-aged or elderly people. Multiple warty dyskeratomas are very rare cutaneous lesions which are mostly seen on the scalp. We herein report a multiple warty dyskeratoma in a female patient.

Lack of prognostic significance of SOCS-1 expression in colorectal adenocarcinomas.

INTRODUCTION: Recent studies have indicated that down-regulation of the suppressor of cytokine signaling-1 (SOCS-1) gene results in tumor formation and that SOCS-1 acts as a tumor suppressor gene. SOCS-1 has been also suggested to function as a tumor suppressor with colorectal cancer. OBJECTIVES: In the present study, we aimed to determine the association of SOCS-1 expression in colorectal cancer tissues with clinicopathologic characteristics immunohistochemically and also to identify its prognostic significance. MATERIALS AND METHODS: SOCS-1 expression was studied immunohistochemically in 67 patients diagnosed with resected colorectal carcinomas and 30 control subjects. RESULTS: SOCS-1 expression was found in 46.3% of tumor tissues and 46.7% of the control group. Statistical analyses did not establish any significant association between SOCS-1 expression and clinicopathologic characteristics. Also, no significant association with SOCS-1 expression was found using progression-free survival and overall survival analyses (p=0.326 and p=0.360, respectively). CONCLUSIONS: Our results show that SOCS-1 has no prognostic significance in colorectal cancer.

Lack of any prognostic relationship between adiponectin receptor (Adipo R1/R2) expression for early/advanced stage gastric cancer.

INTRODUCTION: Adiponectin (ApN) is a complement C1q-related protein, mainly secreted from adipose tissue, that signals through ApN receptor 1 (Adipo-R1) and ApN receptor 2 (Adipo-R2). Low serum ApN concentrations are associated with obesity-related malignancies. However, there are very few studies on any prognostic role of ApN receptors in gastric cancer. OBJECTIVES: The aim of this study is to investigate the relationship between AdipoR1/R2 expression and early/advanced stage gastric cancer in terms of clinicopathologic characteristics and survival. MATERIALS AND METHODS: Eighteen patients with early and 39 with advanced stage gastric cancer who underwent surgical gastric resection were included in this study. RESULTS: Adipo-R1 expression was low in 2 of the 18 patients with early stage gastric cancer (11.1%), while 4 had low Adipo-R2 expression (22.2%). In those with advanced stage gastric cancer, 7 of 39 had low Adipo-R1 expression (17.9%) and 16 had low Adipo-R2 expression (41%). Adipo-R2 expression was significantly higher (p=0.011) in moderately differentiated tumors when compared to well-differentiated tumors. While there was nearly a statistically significant relationship between TNM stage (T, tumor size; N, regional lymph node; M, whether distant metastases exist) and Adipo-R2 expression (p=0.054), there was no relationship between Adipo-R1/-R2 expression with tumor stage and survival. CONCLUSION: Adipo-R1/-R2 expression has no prognostic significance of in early/advanced stage gastric cancer.

A retrospective multicenter evaluation of cutaneous melanomas in Turkey.

BACKGROUND: We defined melanoma distribution in a large series of Turkish patients and evaluated the prognostic parameters of melanomas. MATERIALS AND METHODS: A total of 1574 patients' data was retrospectively collected at 18 centers in Turkey. Demographic characteristics were questioned and noted. Prognostic parametres were evaluated based on sentinel lymph node involvement. RESULTS: Mean age was 56.7 (4-99) years. While 844 (53.6%) cases were male, 730 (46.4%) cases were female. One thousand four hundred forty-seven (92%) cases were invasive melanoma and 127 (8%) cases were in-situ melanoma. The most common histopathological form was the superficial spreading melanoma (SSM) which was found in 549 patients (37.9%). It was followed by nodular melanoma in 379 (26.2%), acral lentiginous melanoma (ALM) in 191 (13.2%) and lentigo maligna melanoma in 132 (9.1%), respectively. On univariate analysis, lymphovascular invasion (p<0.001), tumor thickness (p<0.001), histopathological subtype (p<0.001), Clark level (p=0.001), ulceration (p<0.001), ≥6/mm2 mitosis (p=0.005), satellite formation (p=0.001) and gender (p=0.03) were found to be associated with sentinel lymph node positivity. Regression was associated with sentinel lymph node negativity (p=0.017). According to multivariate analysis, lymphovascular invasion and tumor thickness were significant independent predictive factors of SLN positivity. Patient age, tumor localization, precursor lesions, lymphocytic infiltration and neurotropism were not related with sentinel lymph node involvement. CONCLUSIONS: In this retrospective analysis, it was found that the prevalence of SSM is at a lower rate while the prevalence of ALM is at a higher rate when compared to western countries. According to Breslow index; most of the melanoma lesions' thickness were greater than 2 mm, corresponding Clark IV. Vascular invasion and tumor thickness are the most important factors for sentinel lymph node involvement.