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Cancer is a group of diseases characterized by DNA injury, and genetic and environmental factors are important in the etiology of the cancers. It is well known that there are association variabilities in DNA repairment and sensitivity against the cancer. The aim of this study is to look for some important gene polymorphisms associated with DNA repair in cases with B cell non-Hodgkin's lymphoma (B-NHL). Ninety-four cases with NHL and 96 healthy controls were included in this study. ERCC2 (Lys751Gln), XPC (Gln939Lys), ERCC5 (Asp1104His), and XRCC3 (Thr241Met) gene polymorphisms were studied by using Tm Shift Real-Time PCR Technology. ERCC5 Asp1104His polymorphism showed a protective effect against the B-NHL in individuals carrying this mutant allele (p = 0.009), and differences were more prominent in males (p = 0.001). When the patient and control groups were divided according to their smoking habit, the mutant allele of the XPC gene showed a protective effect in the nonsmoker group (p = 0.040). The mutant allele G of ERCC5 (CG) polymorphism was found to be protective against lymphoma (p = 0.010). There were no differences among cases with B-NHL and controls for ERCC2 codon 751, XPC codon 939, and XRCC3 codon 241 gene polymorphisms. DNA repair gene polymorphisms can affect the risk of lymphoma, and it will be useful to detect the DNA repair gene polymorphisms in cases with lymphoma in studies covering a higher number of cases.

Objectives: Although Hodgkin's lymphoma (HL) is one of the most curable cancers in adult patients, new targets have to be defined in cases resistant to traditional chemotherapy. The preferentially expressed antigen of melanoma (PRAME) is a cancer testis antigen and its expression is very scarce or absent in normal tissues. For this reason PRAME is a promising candidate for tumor immunotherapy. The aim of this study is to understand the correlation of PRAME expression with prognostic factors in HL, to determine the utility of PRAME as a targeted molecule for immunotherapy and to compare real-time polymerase chain reaction (real-time PCR) and immunohistochemistry (IHC) for the detection of PRAME., Methods: In 82 patients, PRAME was studied using real-time PCR and IHC. Data analyses were performed using statistical methods such as t test, Mann-Whitney U test, χ 2 test, Kaplan-Meier method, log-rank test and Cox regression analysis., Results: PRAME was detected in 15 (18.3%) patients using IHC and in 8 (9.8%) patients using real-time PCR. A correlation was found between PRAME positivity and higher International Prognostic Score (p = 0.039). PRAME positivity detected using real-time PCR was found to be correlated with shorter disease-free survival (DFS) and overall survival (OS, p = 0.0005)., Discussion: The demonstration of PRAME especially in histiocytes and Reed-Sternberg cells may provide guidance for immunotherapy. Although PRAME positivity increases the risk for death (3.56), independent risk factors that affected DFS and OS occurred in advanced age and high-risk groups., Conclusion: Although real-time PCR is sensitive in the detection of PRAME, IHC can be another useful method. Despite the need for studies conducted on larger patient samples, PRAME expression is considered as a poor prognostic parameter in HL.

Hypertrophic osteoarthropathy (HOA) is a condition characterized by arthralgia/arthritis, clubbing, and periosteal reaction. Primary form of HOA is observed at early ages of life and is hereditary in nature. Secondary HOA is more frequently seen in clinical setting and occurs as a result of various disorders including inflammatory and malignant diseases. Regression in HOA may be seen after the treatment of underlying condition. In this report, we presented a case of HOA coexisted with myelofibrosis and reviewed the current literature., (Copyright © 2014 Elsevier Editora Ltda. All rights reserved.)

Objective: To study the role of immuno-histochemistry and T-cell receptor (TCR) gamma gene rearrangement analysis in the diagnosis of mycosis fungoides (MF)., Methods: The study design was retrospective, and 73 cases were selected from the archive of the Pathology Department, School of Medicine, Cukurova University, Adana, Turkey, between January 2004 and December 2009. Thirty-nine MF cases with classical histomorphology, 16 cases with suspicious histomorphology for MF as the inconclusive group, and 18 cases with benign inflammatory dermatoses as the control group were involved in the study. The slides were evaluated for the presence or absence of the histopathological criteria for MF. Immunohistochemically, CD3, CD4, and CD8 were performed in all cases, and their counts and CD4/CD8 ratio were noted. Presence clonal TCR gamma gene rearrangement was evaluated by polymerase chain reaction (PCR)., Results: The histopathological parameters suggestive of MF were epidermotropism (p=0.000), presence of Pautrier microabscess (p=0.004), and atypical lymphocyte (p=0.000). Immunohistochemically, CD4 percentage (p=0.006) and CD4/CD8 ratio (p=0.010) were statistically significant parameters with univariate analysis. Clonality was present in 76.9% of MF cases and 37.5% in the inconclusive group. Four of 6 clonality positive cases in the inconclusive group were diagnosed as MF in rebiopsies. The CD8 percentage was not statistically different between the 3 groups., Conclusion: In suspicious cases, CD4/CD8 ratio and TCR gamma gene rearrangement can support histopathology in early MF.

Extramedullary plasmacytomas are rare malignancies. Most cases (80%) are seen in the head and neck region, where they represent 1% of all head and neck malignancies. We report a case of an extramedullary plasmacytoma of the tongue that was treated successfully with three-dimensional conformal radiotherapy. The patient was a 50-year-old woman who was admitted to our hospital with bilateral pain and ulceration on the sides of her tongue. Findings on magnetic resonance imaging and positron-emission tomography did not demonstrate any mass within the tongue or any lymphatic or distant metastasis. A tissue biopsy identified a plasma cell neoplasm. The patient was treated with a total dose of 50 Gy delivered in 2-Gy daily fractions. After 54 months of post-treatment follow-up, she exhibited no sign of systemic myeloma or local recurrence. This case is presented not only for the rarity of the tumor type, but also for its unusual location.

Rituximab (the chimeric anti-CD20 antibody) is widely used in the treatment of CD20 positive non-Hodgkin's lymphoma (NHL). The response rate at relapse after repeated use in prior CD20 positive responders is lower than 50%. Several mechanisms can be responsible for rituximab resistance. CD20 negative relapses which transformed from CD20 positive aggressive and indolent forms of lymphoma can be the one of the reason of secondary resistance to rituximab. The authors report a case with combination of aggressive and indolent form of lymphoma who relapsed after 7 months from the last dose of rituximab therapy. CD20 transformed negative from positive in her relapsed disease. Patients with CD20 positive B cell NHL must rebiopsy after first line rituximab therapy if their disease relapsed or progressed.

Primary lymphoma of the breast is very rare especially in a male patient. Treatment alternatives include surgery, chemotherapy, immunotherapy and radiation. It is still controversial which combination is the best. Here, we report a male patient who presented with a left breast mass. The excisional biopsy was applied, and pathological assessment revealed marginal zone lymphoma. Both conventional computed tomography and 18)F-Fluorodeoxyglucose positron emission tomography/computed tomography were used for staging. The clinical stage was IIE for Ann Arbor staging and so local radiation following chemo immunotherapy was planned. Left-sided primary breast lymphoma in a male patient is a very rare entity. Treatment modalities are still controversial. Some authors believe that primary breast lymphomas have poor prognosis, and they must be treated aggressively with combined treatment modalities. Another important point is that 18)F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET)/CT could be used for staging of disease and assessing treatment response in a patient with primary breast marginal zone lymphoma.

Background: Diffuse large B cell lymphoma (DLBCL) is the most common subtype of Non-Hodgkins lymphomas (NHL). The outcome of these patients shows a wide variation. We evaluated the effect of six biologic parameters including Cyclooxygenase-2 (Cox-2), Survivin, Epstein Barr Virus (EBV), Vascular Endothelial Growth Factor-A (VEGF-A), Vascular Endothelial Growth Factor-C (VEGF-C), Thrombospondin-1 (TSP-1) and clinical parameters., Patients and Methods: A follow up study was conducted and 88 cases with DLBCL were included in the study. The data of 72 patients were eligible for the survival analyses. Immunohistochemistry was used to detect these parameters., Results: The ratio of positive cases for Cox-2, VEGF-A, Survivin, VEGF-C, EBV, TSP-1 were 71.6%, 64.8%, 60.2%, 36.4%, 21.6%, 14.8%, respectively. Survivin (+) cases showed higher LDH levels and VEGF-A (+) cases showed higher beta 2 microglobulin (B2M) levels compared with (-) cases. Mean survival rates were found to be significantly shorter in cases expressing VEGF-A, VEGF-C, EBV and Survivin than cases not expressing these. EBV expression (HR: 3.78; 95%CI: 1.47-9.74; p=0.006), VEGF-C expression (HR: 3.22; 95%CI: 1.07-9.68; p=0.037) and extranodal involvement (HR: 3.02; 95%CI: 1.01-8.97; p=0.047) were found to be independent risk factors for prognosis according to the Cox regression analysis., Comment: Lymphangiogenesis (VEGF-C) and EBV related viral lymphomagenesis have been found to be related with prognosis in DLBCL patients.

Castleman disease (CD) is an uncommon lymphoproliferative disorder with a unique histopathology. Generally diagnosis is not difficult for an experienced pathologist. However, not usually, some histopathological entities or tissue reactions may mimic CD. Here CD-like reaction due to toxic substance ingestion has been presented.

Background and Aim: EBV is an important virus in the pathogenesis of NHL. VEGF-A is the essential factor in tumor angiogenesis. There is evidence of cross talk between angiogenesis and viral carcinogenesis. The viral latent protein LMP1, may play a role by inducing expression of angiogenic factors In this study EBV-LMP1 and VEGF-A expressions have been studied in cases with NHL and prognostic significance of these has been evaluated., Patients and Methods: One hundred seventy-seven cases (60 had low grade lymphoma (LGL), 117 had aggressive lymphoma (AL)) with NHL have been included in this analysis. Immunohistochemistry has been used for the detection of EBV and VEGF-A., Results: EBV was found in 25 cases (14%); 5 of 60 cases with LGL while 20 of 117 cases with AL had EBV positivity; (OR: 2.3, 95% CI: 0.8-6.3, p=0.113). VEGF-A expression was found in 108 cases (61%); 30 of 60 cases with LGL and 78 of 117 cases with AL showed VEGF-A expression. There was an association between VEGF-A and aggressive histology (OR: 2.0, 95% CI: 1.1-3.8, p=0.031). EBV positivity was associated with VEGF-A expression in diffuse large B cell lymphoma (DLBCL) (0.045). Mean Survival rates were shorter in EBV (+) and/or VEGF-A (+) cases., Comment: Highly significant association between VEGF-A and EBV expression and survival rate, suggests an association between angiogenesis and viral lymphomagenesis. Targeting both the angiogenesis and EBV may be important in the therapy of cases with NHL expressing EBV and/or VEGF-A.

Objective: In systemic sclerosis (SSC), certain abnormalities can occur in fibroblasts, endothelial cells, and immune system cells. Severe pathological changes such as visceral fibrosis and obliteration of the lumen of arteries may develop due to functional alterations of these cells. Because the vascular abnormality is a central mechanism of sclerosis, the aim of this study was to further investigate the impaired vascularity in the gingival tissues of SSC patients by means of immunohistochemistry using vascular endothelial growth factor A (VEGF-A), VEGF-C, and CD34 staining., Study Design: Thirteen SSC patients and 11 systemically healthy controls who had moderate gingivitis were included in the study. Gingival biopsies were obtained from the interdental papilla, and VEGF-A, VEGF-C, and CD34 analyses were done by using immunohistochemical methods., Results: Patients with scleroderma had higher levels of inflammatory infiltrate (P = .041) and microvessel density (P = .003) in their gingival biopsy samples. In contrast, when compared with the controls, the expressions of VEGF-A and VEGF-C were significantly lower in scleroderma patients (P = .033 and P = .015, respectively)., Conclusion: These findings may reflect the defective vascularity and the pronounced histological inflammation of the gingival tissues in systemic scleroderma and may provide a novel target for treatment methods for the gingival involvement in these patients.

Survivin (S) is a member of inhibitor of apoptosis family (IAP) and is expressed in the majority of malignant tumors but undetectable in normal differentiated adult tissues. S is an encouraging target for cancer therapy. TSP-1 is a multifunctional protein regulating cell growth, motility and apoptosis in both physiological and pathological conditions. The role of TSP-1 in cancer progression remains controversial. We aimed to determine the pathogenetic and prognostic role of TSP-1 and S in non-Hodgkin's lymphomas (NHL). S and TSP-1 expressions were looked for in 177 cases with NHL. S was found to be positive in 94 of the cases (53%). TSP-1 was found to be positive in 31 of the cases (17.5%). There was a strong association between S and TSP-1 and also aggressive histology with S and TSP-1. The overall survival (OS) times were longer in cases without S expression than cases with S expression (p=0.0514). Although the OS was shorter in TSP-1 expressing cases as compared with TSP-1 (-) cases, difference was not significant (p=0.2428). In conclusion, S and TSP-1 expressions were detected in 53 and 17.5% of the cases with NHL, and are associated with aggressive histology and shorter OS.

Nitric oxide synthases are isoenzymes that catalyse the synthesis of nitric oxide (NO). NO plays both pathological and physiological roles depending on its rate of synthesis and concentration in cellular source and microenvironment. Apoptosis is an important biological factor in lymphomas. This study evaluates expression of inducible nitric oxide synthase (iNOS) in human lymphomas and its relation with apoptosis. This study comprised 46 cases of B-cell lymphoma. The lymphomas were classified as 3 mantle cell, 5 marginal zone, 4 follicular, 2 Burkitt, 25 diffuse large cell, 2 anaplastic large cell, 3 lymphoblastic, 2 lymphoplasmacytic according to WHO classification of lymphoid neoplasms. Hematoxylin eosin slides of the cases were reviewed and immunoperoxidase technique was performed iNOS and Caspase monoclonal antibodies to selected sections of each case. Antigen staining was carried out with iNOS and Caspase proteins and Ultravision Polyvalent, HRP-AEC kit (Neomarkers-Biogen USA). For the evaluation of iNOS and Caspase, tumor areas with a high density of expression were chosen. Positive stained cells were counted in 5 different areas at a magnification x 40 by an Olympus B x 51 microscope in each case. The iNOS and Caspase expressions were independently recorded by four pathologists and the results were averaged. All of the cases were positive for the iNOS and Caspase. But there is not a statistically important relation between lymphoma grade and iNOS activity. We could not find a correlation between iNOS and patients age. This study reveals the capacity of B-cell neoplasms to express iNOS in situ. In conclusion, our study revealed that there is a positive relation between iNOS expression and apoptosis (p = 0.032 spearman correlation).

Intracranial chondromas usually arise from the base of the skull. They rarely originate from the convexity dura and falx. Here we describe two cases of intracranial chondroma located at the convexity dura and falx, discuss the genesis, radiologic, histologic features and review the literature.

The kidney is frequently affected in patients with sickle cell syndrome, i.e., homozygous and heterozygous patients, with a consequently large spectrum of renal abnormalities that may range from minimal functional changes to chronic renal failure. Here, we present a 13-year-old boy with sickle cell anemia (SCA) (HbSS) who was referred to our unit with nephrotic syndrome. Renal biopsy revealed AA type amyloidosis on the basis of light microscopic findings, indicating Congo red staining and immunohistochemistry. He had neither a family history of familial Mediterranean fever (FMF) nor any complaint of recurrent abdominal pain, arthritis, and fever, but frequent painful vaso-occlusive crises. The patient was found to have no MEFV gene (Mediterranean feVer) mutations either. Painful episodic attacks might provoke recurrent acute inflammation, leading to repeated stimulation of acute phase responses and cause secondary amyloidosis. To our knowledge, this boy is the first case of SCA complicated by renal amyloidosis observed in childhood.

Bilateral testicular tumors are a rare complication of congenital adrenal hyperplasia. It can be extremely difficult to distinguish histologically between Leydig cell tumors and adrenocortical rest hyperplasia, which may lead in some cases to unnecessary orchidectomy. A 7-yr-old boy was admitted because of precocious puberty and enlargement of testicles. Hormonal studies established the diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Testicular biopsy revealed interlacing strands, cords, and rests of cells resembling interstitial (Leydig) cells but with no Reinke crystalloids. Here we report a case of testicular adrenal rest hyperplasia in congenital adrenal hyperplasia and discuss the pathological and clinical features and origin of this rare lesion by using immunohistochemical evaluation.

The diagnosis of cutaneous leishmaniasis (CL) may depend on the detection of the parasite in histologic sections, the growth of the promastigotes in culture, or the identification of parasite by other techniques. We performed polymerase chain reaction (PCR) on paraffin-embedded biopsies to determine the validity of this technique for diagnosis of CL. PCR was used to detect the parasite using 2 different DNA extraction methods. PCR was positive in all 20 cases when the Leishmania parasite was detected by light microscopy. Twenty-seven of 34 cases that were negative microscopically for the parasite were positive using PCR. The first extraction method of DNA identified leishmanial DNA in 41 of 54 cases (75.9%); the second extraction of DNA was positive in 47 of 54 cases (87%). PCR was negative in all of the nonleishmaniasis cases. The PCR-based method appears to be a useful diagnostic approach for identification of suspected cases of CL.

Malignant ectomesenchymoma is a rare tumor reported in head-neck, abdomen and perineal regions. It consists of mesenchymal and neuroectodermal elements. In this tumor group, neoplastic cells are differentiated into neuronal cells. It also has at least one malignant mesenchymal element, generally rhabdomyosarcoma. In this report we present a neonate with ectomesenchymoma.

Objective: Within soft-tissue sarcoma, primitive neuroectodermal tumors have been shown to cover a wide spectrum of small round cell sarcomas, including Ewing's sarcomas (ES) and primitive neuroectodermal tumors (PNET). The role of the stem cell factor/kit pathway has been investigated in different human tumors especially in chronic myelocytic leukemia and gastrointestinal stromal tumor and an autocrine loop has been assumed in small cell lung carcinoma, and recently in ES and PNET. Our aim is to investigate the c-kit expression in ES and PNET and also to assessed if c-kit has any role in disease process., Methods: We thoroughly searched the archives of the Department of Pathology, Faculty of Medicine, Cukurova University Turkey, between 2000 and 2004; and found 14 ES and 14 PNET paraffin embedded tissues. We carried out the detection of the c-kit expression by immunohistochemical staining., Results: The patient's median age was 23.7 +/-14.6 (12 male and 16 female). Five were diagnosed as metastatic disease whereas 23 were diagnosed as non-metastatic disease at admission. The mean follow up period was 38.9 +/- 22.3 months. The main localization of the disease was lower extremity (32.1%), and others were as follows: head and neck 25%, thorax and abdomen 14.3%, pelvic and upper extremity 7.1% (11 were localized skeletal and 17 were extraskeletal). According to treatment modalities, 10 were treated with surgery alone, 11 with surgery and chemotherapy, and 7 with surgery, radiation therapy and also with chemotherapy. The primary tumor was lower than 5 cm in its dimension in 21 patients. While in 5 patients, tumor was more than 5 cm but did not exceed 10 cm, it was >10 cm in 2 patients. The c-kit expression was positive in 7 patients both cytoplasmic and membranously, whereas 8 patients were positive cytoplasmically. In 5 PNET patients, c-kit expression were stained immunohistochemically in over 50% and in 3 of ES patients. There was no significant correlation between c-kit expression and gender, localization, metastatic status, treatment modalities and tumor. Although in survival analysis, patients treated with surgery alone lived longer, while >50% of patients treated with c-kit expression lived for a shorter period., Conclusion: We suggest that therapy with tyrosine kinase inhibitor for PNET and ES patients may be an alternative in addition to standard therapy modalities, especially in patients non-responsive to standard therapy.

The case of a 21-yr-old woman admitted with a two-week history of icterus, fever, multiple peripheral lymphadenopathy and pruritic eruption is presented. A full evaluation including computed tomography, endoscopic retrograde cholangiography, liver, skin and lymph node biopsies and biochemical tests confirmed the diagnosis of multicentric Castleman's disease (angiofollicular lymph node hyperplasia). All symptoms improved within four weeks of commencing prednisone therapy. Castleman's disease should be considered in the differental daignosis of cholestatic hepatitis and bullous pemphigoid.