JAK2V617F mutation in a patient with B-cell chronic lymphocytic leukemia and prefibrotic primary myelofibrosis

Uvod Sekundarni maligniteti, naročito solidni tumori, česti su kod bolesnika s hroničnom limfocitnom leukemijom (HLL), ali retko se sreće udruženost mijeloproliferativnih neoplazmi i HLL. Prikaz bolesnika Prikazujemo muškarca starog 67 godina sa B ćelijskom HLL kod koga se nakon devet godina razvila primarna mijelofibroza (PMF). Bolesnik je lečen alkilišućim agensima i analozima purina, što može biti predisponirajući faktor za razvoj mijeloproliferativnog oboljenja. JAK2V617F mutacija nije otkrivena prilikom postavljanja dijagnoze HLL, ali je utvrđena posle devet godina, kada se razvila PMF, što ukazuje na to da su B ćelijska HLL i PMF neoplazme koje potiču od različitih ćelijskih klonova. Zaključak Patogenetski mehanizmi udruženosti mijeloproliferativne i limfoproliferativne neoplazme kod bolesnika nisu razjašnjeni. Potrebna su dalja istraživanja radi utvrđivanja da li ove maligne bolesti potiču od dva različita ćelijska klona ili nastaju od iste pluripotentne matične ćelije hematopoeze.Introduction Secondary malignancies, particularly solid tumors, are common in patients with chronic lymphocytic leukemia (CLL), but association of myeloproliferative neoplasms and chronic lymphocytic leukemia in the same patient is very rare. Case Outline We report of a 67-year-old man with B-cell chronic lymphoid leukemia (B-CLL) who developed primary myelofibrosis (PMF) nine years after initial diagnosis. Patient received alkylation agents and purine analogue, which can be a predisposing factor for the development of myeloproliferative neoplasms. JAK2V617F mutation was not present initially at the time of CLL diagnosis, but was found after nine years when PMF occurred, which indicates that B-CLL and PMF represent two separate clonal origin neoplasms. Conclusion Pathogenic mechanisms for the development of myeloproliferative and lymphoproliferative neoplasms in the same patient are unknown. Further research is needed to determine whether these malignancies originate from two different cell clones or arise from the same pluripotent hematopoietic stem cell

Double-hit primary unilateral adrenal lymphoma with good outcome

Introduction. Primary adrenal non-Hodgkin’s lymphoma (NHL) is a rare neoplasm with poor prognosis. On the other side, double-hit lymphomas with BCL2 and MYC translocation are characterized by advanced disease stage, extranodal and central nervous system involvements at presentation or disease progression. Case report. We reported a 73-year-old male patient with double-hit primary adrenal lymphoma and preserved adrenal function, showing a favorable clinical course. Computed tomography of abdomen showed a 9 7 cm mass of the left adrenal gland. Laparatomy with left adrenalectomy was done and histological examination revealed diagnosis of a diffuse large B-cell NHL (DLBCL), non-GCB subtype. The patient was treated with 6 cycles of R-CHOP chemotherapy with reduced doses of doxorubicin because of the decreased left verticle ejection fraction. The patient was followed up regularly for 20 months with no evidence of tumor recurrence despite the inherently poor prognostic profile and double-hit phenotype of the disease. Conclusion. R-CHOP chemotherapy in combination with adrenalectomy can be an effective first-line regimen for primary adrenal DLBCL, despite the inherently poor prognostic profile (non-GCB subtype, bulky disease, elevated lactate dehydrogenase and double-hit phenotype of the disease)

Significance of fine-needle aspiration biopsy of peripheral lymph nodes upon the initial presentation of patients with lymphadenopathy of unknown etiology

Fine-needle aspiration biopsy is safe, simple, cost-effective and efficient technique providing rapid information and, therefore, directing further approach to a patient. Its findings are especially beneficial for verification of lymphoid origin of the enlarged growth, diagnostics and differentiation of metastatic, infectious, reactive and lymphomatous conditions; determination of the extent of tumor; detection of recurrence; monitoring of the course of disease; obtaining of material for special studies such as microbiological cultures, immunological or genetic studies as well as electron microscopy; in addition, for encouragement of patient in case of benign nature of the disease. At the Institute of Hematology, in three-year period, a total of 193 fine-needle aspiration biopsies were performed in 172 patients with the enlarged peripheral lymph nodes. Technically, aspiration biopsy was successful in 175/193 attempted interventions (91%). Punctates were analyzed by cytomorphology and subsequently compared with histopathological findings. In indistinguishable cases, additional immunocytochemical streptavidin-biotin peroxidase staining was carried out. In our studies, immunocytochemical analysis was performed in 63 out of 81 patients (78%), and diagnostic accuracy was 93.6% what was compatible with the results of other authors. It significantly corrected the earlier cytomorphological-histological congruence that used to be 83%. Immunocytochemistry has contributed to diagnostic value of cytological analysis of punctate, before all, in view of its higher diagnostic accuracy, which, according to majority of authors, is about 90%

JAK2V617F mutation in a patient with B-cell chronic lymphocytic leukemia and prefibrotic primary myelofibrosis

Introduction. Secondary malignancies, particularly solid tumors, are common in patients with chronic lymphocytic leukemia (CLL), but association of myeloproliferative neoplasms and chronic lymphocytic leukemia in the same patient is very rare. Case Outline. We report of a 67-year-old man with B-cell chronic lymphoid leukemia (B-CLL) who developed primary myelofibrosis (PMF) nine years after initial diagnosis. Patient received alkylation agents and purine analogue, which can be a predisposing factor for the development of myeloproliferative neoplasms. JAK2V617F mutation was not present initially at the time of CLL diagnosis, but was found after nine years when PMF occurred, which indicates that B-CLL and PMF represent two separate clonal origin neoplasms. Conclusion. Pathogenic mechanisms for the development of myeloproliferative and lymphoproliferative neoplasms in the same patient are unknown. Further research is needed to determine whether these malignancies originate from two different cell clones or arise from the same pluripotent hematopoietic stem cell. [Projekat Ministarstva nauke Republike Srbije, br. III 41004

Diffuse large cell lymphoma and colon adenocarcinoma in patient with Waldenström’s macroglobulinaemia

Introduction. Waldenström’s macroglobulinaemia is a rare B cell lymphoproliferative disorder characterized by lymphoplasmocyte bone marrow infiltration and monoclonal IgM gammopathy. In the majority of cases, Waldenström’s macroglobulinaemia is a chronic disease with variable course. Therapy consists of alkylating agents, purine analogs and antiCD20 monoclonal antibody. In the literature, there have been descriptions of rare cases of progression of Waldenström’s macroglobulinaemia to aggressive lymphoma, as well as secondary carcinoma in the patients after treatment of macroglobulinaemia. Case Outline. A 63-year-old patient was diagnosed with serum monoclonal IgM kappa gammopathy (Waldenström’s macroglobulinaemia). Chemotherapy was applied and a good clinical and haematological response had been achieved. Ten years later, the patient was diagnosed with colon adenocarcinoma as a secondary malignancy, and operated on. Within one month, the patient rapidly developed a large neck tumour mass. Tumour biopsy revealed the diagnosis of diffuse large B cell lymphoma with the expression of monoclonal lambda chain, which more likely pointed out to coexistence of two different B cell lymphoproliferative disorders, rather than the transformation of Waldenström’s macroglobulinaemia to aggressive lymphoma. The patient was treated with chemotherapy following R-CHOP protocol, and clinical remission was achieved. Seven months later, despite the successful treatment of lymphoproliferative disorder, dissemination of adenocarcinoma led to the lethal outcome. Conclusion. The patient was diagnosed with a rare occurrence of three neoplastic diseases: Waldenström’s macroglobulinaemia, colon adenocarcinoma and diffuse large B cell lymphoma. The possible mechanisms of the combined appearance of lymphoproliferative and other malignant diseases include the previous treatment with alkylating agents, genetic, immunomodulatory and environmental factors

Atypical hodgkin and reed-sternberg cells in peripheral blood of a patient with advanced stage of Hodgkin's disease - a case report

The occurrence of abnormal Hodgkin's and Reed-Sternberg cells in the peripheral blood in a patient suffering from Hodgkin's disease has been noticed exceptionally rare in a previous period, and especially rare in last ten years primarily due to successfull treatment of this disease. The presence of atypical mononuclear cells in peripheral blood which cytomorphologically resembled Reed-Sternberg cells was registered in 8 patients till 1966. During the last decade, the presence of atypical mononuclear cells in the peripheral blood was used for their isolation cultivation, and detailed immunophenotypic and genetic analysis. The analysis of mononuclear cells in rare patients with Hodgkin's disease was established that they belong to the B-lymphoid cells with expression of CD30 and CD15 antigens. The examination of presence of Hodgkin's cells in the peripheral blood of patients with Hodgkin's disease is important for patients with advanced stage of the disease in which autologous stem cell transplantation and high dose chmeotherapy is planned. The authors present a 33-year-old patient, who noticed enlarged neck lymph nodes in September 2000, high temperature and loss in weight. On physical examination enlarged neck lymph nodes 5x8 cm and hepatosplenomegaly were found. There was anemia and thrombo-cytopenia, and normal WBC count with 24% of lymphoid elements in differential formula. On histologic examination of lymph nodes Hodgkin¢s disease, type nodular sclerosis with mixed cellularity was found. Histology of bone marrow showed nodal lymphomatous infiltration. Immunohistochemistry with monoclonal antibodies of concentrate of peripheral blood cells showed expression of CD30+ and CD15+, immunophenotypically and morphologically matching Reed-Sternberg cells. Cytogentic analysis of mononuclear cells of the bone marrow showed normal karyotype. The patient was in clinical stage IV/V of the disease and chemotherapy with 9 cycles of ABVD+Mp protocol was applied. He is still in remission

Hemangioma of the spleen

Although the most frequent benign tumors of the spleen, hemangiomas are very rare, much rarer than hemangiomas of the liver. They manifest as localized (either single or multiple) or diffuse lesions, vary from solid to cystic, histologically from capillary to cavernous. Usually, they are small in size (1-3 cm), rarely larger and very rarely of large size. A 67-year old woman admitted to Institute of Hematology, CCS, for investigation of the left upper abdominal pain, loss of appetite, loss in weight and malaise. As the investigation showed a number of hypoechogenic lesions within the enlarged, diffusely non-homogenic spleen, splenectomy was indicated. The spleen weighing 2600 grams was removed, in which the number of lesions histologically corresponded to hemangioma of the spleen. Postoperative recovery was uneventful. The patient has remained symptom free more than two years after surgery

Immunohistochemical study of pathological alterations of peritoneum in patients with terminal renal insufficiency and on peritoneal dialysis

Background/Aim. During peritoneal dialysis (PD) an exchange of substances between blood and dialysate takes place through specific histological structures of peritoneum. Peritoneal double-layered serous membrane has, so far, mostly been studied with electron microscopy on experimental animals. The aim of this study was to assess integrity of peritoneal tissue in end-stage renal disease (ESRD) and PD patients using standard light microscopy and immunohistochemical methods. Methods. Peritoneal tissue biopsies were performed on 25 persons: 8 healthy donors during nephrectomy, 9 ESRD patients upon insertion of PD catheter, and 8 PD patients upon removal of the catheter for medical indications. The samples were fixed and prepared routinely for immunocytochemical staining by standardized streptavidin biotin AEC method using a LSAB2® HRP kit (Dako®, Denmark) for collagen IV and analyzed by light microscopy. Results. We observed mesothelial detachment from lamina propria, duplicated basement membrane and much thicker blood vessel walls in ESRD and PD patients, compared to healthy subjects. Differences in histological structure, emphasized with immunostaining, indicated pathological alterations of peritoneal tissue in the renal patients. Conclusions. Imunohistochemistry can be used in studying histological alterations of peritoneal tissue in ESRD and PD patients. This method may indicate possible problems in filtration and secretion processes in this tissue