Oner Dogan

Coexistence of chronic neutrophilic leukemia with multiple myeloma

A case report of simultaneous presentation of chronic neutrophilic leukemia and multiple myeloma (IgG kappa) in a 71-year-old male is described. The patient showed mature neutrophilic leukocytosis, hepatosplenomegaly, high neutrophil alkaline phosphatase score, hyperuricemia, neutrophils with toxic granulation and Döhle bodies, absence of Philadelphia chromosome and of the bcr-abl fusion gene. Moreover, a monoclonal IgG kappa paraproteinemia (36.93   g   l m 1 ) was detected. Bence-Jones proteinuria was 3.84   g   l m 1. The bone marrow was grossly hypercellular with marked myeloid hyperplasia and aggregates of plasma cells. The patient died of severe bronchopneumonia after the transformation of chronic neutrophilic leukemia to acute myelomonocytic leukemia, 1.5 years following diagnosis.

c-erbB-2 Gene Amplification in Nasopharyngeal Carcinoma

Abstract Amplification of the c-erbB-2 gene has been associated with poor prognosis in different types of cancer. However, there are no data on the c-erbB-2 expression levels in nasopharyngeal cancer. In this study, amplification of the gene has been investigated in the tumor tissue of patients with nasopharyngeal cancer by competitive polymerase chain reaction c-erbB-2 amplification was observed in 43.3% of the patients. The increase in the gene copy number correlated with the T stage. No correlation was found with lymph node involvement, histologic grade, differentiation, presence of metastases, or age and sex. We conclude that c-erbB-2 amplification may contribute to the pathogenesis of nasopharyngeal cancer. Our report is the first study investigating the expression of the c-erbB-2 gene in nasopharyngeal cancer at the DNA level.

Immunohistochemical detection of p53 protein in rhabdomyosarcoma: association with clinicopathological features and outcome.

PURPOSE Alteration in the p53 tumor suppressor gene is the most common tumor specific genetic change identified in most major cancer types including rhabdomyosarcomas. To investigate the overexpression of p53 and its relation to clinical features and outcome in patients with rhabdomyosarcoma (RMS), an immunocytochemical study was performed. METHODS Formalin-fixed paraffin embedded tissue sections obtained from 42 cases of RMS were immunostained with a mouse monoclonal antibody p53-D07. Staining was assessed by evaluating the percentage of p53 immunopositive cancer cell nuclei. RESULTS Nuclear accumulation of p53 protein was detected in 8 of 42 (19%) samples. Clinical analyses of patients demonstrated no correlation between positive staining and age, sex, histological subtype, stage and overall survival. This analysis, however, was limited by the small number of patients who demonstrated p53 immunostaining. Nonetheless, a statistically significant association was observed between p53 expression and adverse outcome. Nuclear p53 expression was associated with disease progression or recurrence (p <0.001) and with a worse event free survival (p = 0.0015). CONCLUSION The nuclear p53 immunoreaction rate is low in RMS, but p53 expression appears to correlate with poor prognosis.

Clinical significance of P16INK4A and retinoblastoma proteins in non-small-cell lung carcinoma

This study was performed to determine the frequency of expression loss of p16 and pRb; their relations with each other, tumour histology, tumour stage, nodal status, and survival in formalin fixed, paraffin embedded tumour tissues of patients with non-small-cell lung carcinoma (NSCLC). P16 and/or pRb expression loss is observed in 72 (75.8%) out of 95 patients, and 70 (73.7%) of them showed inverse correlation (P<0.05). Thirty-six (37.9%) of the p16 positive cases usually showed weak or moderate immunohistochemical staining. Loss of p16 expression was found to be significantly greater in squamous cell carcinoma than in adenocarcinoma cases, whilst no relation was observed with other clinical parameters. Immunohistochemical reactivity for pRb was generally moderate or strong. PRb expression loss was observed in 15.8% of the cases, and no relation was found between pRb loss and age, sex, tumour histology, tumour stage, or nodal status. PRb negative squamous cell carcinoma cases had significantly shorter survival independent of nodal status. These results suggest that disruption of p16/pRb pathway is frequently involved in NSCLC, and pRb expression loss in cases with squamous cell carcinoma may predict clinical outcome.

Systemic Rituximab Immunotherapy in the Management of Primary Ocular Adnexal Lymphoma: Single Institution Experience

Abstract Purpose: To evaluate the efficacy of systemic rituximab immunotherapy in the management of primary ocular adnexal lymphomas (OAL). Materials and methods: Clinical records of 10 consecutive patients (11 eyes) with biopsy-proven OAL managed with systemic anti-CD20 monoclonal antibody (rituximab; 375 mg/m2 intravenously once every three weeks for 6–8 cycles) between June 2008–March 2013 were evaluated retrospectively. Orbital magnetic resonance imaging and positron emission tomography were performed to evaluate any orbital and systemic involvement, respectively. Clinical response was classified as complete or partial. Results: The age of patients ranged between 27–85 (median, 55) years. Nine patients (90%) presented with unilateral and one (10%) with bilateral conjunctival involvement. Orbit was affected in 4 patients (40%), one of which had also choroidal involvement (10%). None of the patients had systemic involvement at initial presentation. All patients received an average of 7 cycles (range, 6–8) of systemic immunotherapy. After a median follow-up of 31 months (range, 10–61 months), complete response without recurrence could be achieved in 4 eyes (36%) with rituximab monotherapy. No systemic or ocular side effects were observed in any patient. Additional radiotherapy was required in 6 patients (7 eyes; 64%) with partial response or recurrence. Conclusions: Complete regression of primary OALs without recurrence was observed in about one-third of eyes after systemic rituximab monotherapy. Adjunctive radiotherapy was required in remaining two-thirds of the cases to achieve complete response. Thus, considering the balance between high rate of local control and potential ocular complications of radiotherapy, systemic rituximab can be considered as a first-line therapeutic option in the management of primary OAL.

T-Cell Lymphoblastic Lymphoma Presenting with a Breast Mass

Lymphomas secondarily involving the breast are uncommon, although they do represent the largest group of tumors metastatic to breast. A 20-year-old female with lymphoblastic lymphoma (LBL) presented here with 3 month history of weight loss, night sweats, fatigue and a mass in her left breast. Her physical examination revealed a left breast mass, lympadenopathy, bilateral pleural effusion and hepatomegaly. WBC count was 17,710/mm3 and LDH was mildly elevated. Breast ultrasound showed a 1.7 cm mass in the inner lower quadrant of left breast. Biopsy of the breast mass showed diffuse infiltration with small, round atypical cells which did not stain with CD20, CD43, CD34, cytokeratine and were positive for CD3. She was diagnosed as leukemic phase of a precursor T-cell LBL and treated with 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), intrathecal methotrexate and cranial radiotherapy, achieving a complete response. She then was started on maintenance therapy. Four months later she returned with CNS involvement and was started on induction treatment. She had a very aggressive course of disease and died only 12 months after diagnosis. Breast involvement is very rarely seen in precursor T-cell LBL/ALL and in this patient occurred secondarily as part of widespread disease.

Genetic heterogeneity within the HLA region in three distinct clinical subgroups of myasthenia gravis.

This study aims to investigate genetic susceptibility to early-onset and late-onset anti-acetylcholine receptor antibody positive myasthenia gravis (EOMG and LOMG) and anti-muscle specific kinase antibody positive MG (MuSK-MG) at genome-wide level in a single population. Using a custom-designed array and imputing additional variants and the classical HLA alleles in 398 patients, we detected distinct associations. In EOMG, rs113519545 in the HLA class I region (OR=5.71 [3.77-8.66], P=2.24×10(-16)), HLA-B*08:01 (OR=7.04 [3.95-12.52], P=3.34×10(-11)) and HLA-C*07:01 (OR=2.74 [1.97-3.81], P=2.07(-9)), in LOMG, rs111256513 in the HLA class II region (OR=2.22 [1.59-3.09], P=2.48×10(-6)) and in MuSK-MG, an intronic variant within HLA-DQB1 (rs68081734, OR=5.86, P=2.25×10(-14)) and HLA-DQB1*05:02 (OR=8.56, P=6.88×10(-13)) revealed the most significant associations for genome-wide significance. Differential genetic susceptibility within the HLA to EOMG, LOMG and MuSK-MG has been established in a population from Turkey.

Chronic lymphocytic leukemia and multiple myeloma in the same patient: case report.

We hereby report the occurrence of a non-secreting multiple myeloma (MM) during the course of chronic lymphocytic leukemia (CLL). A 73-year-old patient developed a non-secreting MM 7 years after the diagnosis of CD5 (+) B cell CLL. He received intermittent chlorambucil and prednisolone therapy. The occurrence of tumors in the frontal bone led to resection of the tissue and histopathologic examination revealed neoplastic plasma cell islands within the CLL infiltration. There was no immunoglobulin or light chain accumulation in the serum. Clonal relationship between these diseases has been shown by comparing the isotypes and idiotype of both the heavy and light chains. In our case, the MM was of non-secreting type and thus we could not establish any relation between the 2 disorders. Such a case has not been reported until now in the literature. CLL and MM in the same patient is a rare occurence and investigation of the transformation event at the molecular level will contribute to our understanding of B-cell ontogenesis.

Treatment of aggressive non-Hodgkin's lymphoma with dose-intensified epirubicin in combination of cyclophosphamide, vincristine, and prednisone (CEOP-100): A phase II study

Epirubicin is an agent with a lower incidence of cardiotoxicity and myelotoxicity compared with doxorubicin; and it is active in patients with non-Hodgkin’s lymphoma (NHL). Our aim was to define the therapeutic efficacy and toxicity of dose-intensified epirubicin in combination with cyclophosphamide, vincristine, and prednisone (CEOP) in patients with diffuse large-cell NHL. Previously untreated patients aged between 15 and 75 years, with at least one measurable lesion, adequate liver, renal, cardiac functions, and no central nervous system involvement were included in the study. The planned chemotherapy regimen CEOP consisted of cyclophosphamide 750 mg/m2, epirubicin 100 mg/m2, and vincristine 1.4 mg/m2 intravenously on day 1 and 100 mg prednisone taken orally on days 1 to 5. Courses were repeated every 21 days. Patients with stage I and II received four cycles of chemotherapy followed by involved-field radiotherapy, and patients with stage III and IV received six cycles of chemotherapy followed by radiotherapy to bulky lymph node sites. Seventy-five patients were enrolled in the study. The complete response rate was 83.8%, and 72 patients were assessable for toxicity. The most common toxicity was myelosuppression; 13.9% of the patients had grade III-IV neutropenia. Severe mucositis, diarrhea, and emesis were uncommon (<10%). At a median follow-up period of 41 months, the 5-year progression-free survival and overall survival rates were 63.5% and 65.3%, respectively. Increasing the dose intensity of epirubicin can yield a similar complete response rate compared with the regimens used in NHL without significantly increasing the toxicity rate associated with chemotherapy. The role of dose-intensive epirubicin should be investigated further in future randomized trials.

Prognostic value of proliferating cell nuclear antigen immunostaining in pediatric rhabdomyosarcomas

Background : The levels of proliferating cell nuclear antigen (PCNA) are almost negligible in long‐term quiescent cells and increase dramatically during the cell cycle. Recently, the monoclonal antibodies to PCNA have been used to demonstrate the proliferative component of paraffin‐embedded tumor tissues. It has been shown to be available as a simple histological marker of proliferative activity and the PCNA labeling index has been correlated with the prognosis of several malignant neoplasms.