Tatjana Terzic

Immunochemotherapy for Bcl-2 and MUM-negative aggressive primary cutaneous B-cell non-Hodgkin’s lymphoma

The case of a 44-year-old man with a primary cutaneous large B-cell non-Hodgkin’s lymphoma of the scalp is reported. His mother died of gastric lymphoma and his sib brother is in a 20-year remission of T-cell lymphoma. The patient presented with a 16-year history of occipital and parietal alopecia and a recently worsening scalp rash. The histopathology and immunohistochemistry performed in April 2006 indicated a bcl-6+, MUM− and bcl-2−, primary cutaneous follicle center B-cell non-Hodgkin’s lymphoma, with an aggressive transformation to a diffuse large B-cell lymphoma. Bone marrow biopsy and CT chest, abdomen, and pelvis were negative for systemic lymphoma. The patient had an excellent clinical and histological resolution following 8 cycles of rituximab and CHOP protocol immunochemotherapy, and remains in complete remission until now. The protracted indolent phase of the disease, the familial history of lymphoma, the histological aggressive features and the patient’s excellent response to immunochemotherapy all contribute to a very unusual manifestation of this disease.

Alveolar Granulocytic Sarcoma of the Mandible in a Patient with HIV

Background: Granulocytic sarcoma (chloroma) occurs primarily in patients with acute myelogenous leukemia although it can also appear in connection with other myeloproliferative disorders. Case Report: We present the case of a 52-year-old human immunodeficiency virus (HIV)-positive female patient with a CD4+ count of 321 cells/ml, who developed an alveolar granulocytic sarcoma of the mandible. Pathological analysis of the tumor mass showed an infiltrate of immature cells which were positive for CD13, CD33, CD15, CD11b, and CD64, and negative for CD34, CD117, and HLA-DR. The patient achieved complete remission following a 1-week course of chemotherapy, however, 7 months later she developed a second granulocytic sarcoma in the left soleus muscle. The absolute CD4+ count had now reduced to 3 cells/ml with an inversion in the Th/Ts index (0.01), and she died of gram-negative sepsis 1 month later. Conclusions: Granulocytic sarcoma is extremely rare in patients with HIV. The case is discussed with reference to the literature.

Fatal Sulfasalazine-Induced Eosinophilic Myocarditis in a Patient with Periodic Fever Syndrome

Objective: The aim of this paper is to report the first case of drug-induced eosinophilic myocarditis (EM) in a patient with hereditary periodic fever syndrome (PFS). Case: A 28-year-old man with hyper-IgD syndrome, one of the PFS, developed a sulfasalazine-induced systemic hypersensitivity reaction complicated by EM. Thirteen days after sulfasalazine introduction, which had been given for arthritis, the patient developed fever, facial/neck edema, rash and cardiogenic shock, and died within 8 h. The autopsy revealed hemophagocytosis, while acute heart failure caused by necrotizing EM was established as the cause of death. Conclusion: This was a case of drug-induced EM in a patient with PFS that had an atypical presentation, rapid evolution and poor outcome.

Transformation of primary myelofibrosis with 20q- in Philadelphia-positive acute lymphoblastic leukemia: case report and review of literature.

A 56-year-old male with chronic idiopathic myelofibrosis and cytogenetic finding of 20q- after a period of 10 months developed acute Philadelphia-positive lymphoblastic leukemia. Immunophenotyping of peripheral blood by flow cytometry showed HLA-DR, CD34, CD19, CD22, CD10, CD33, and CD11b positivity. Cytogenetic analysis revealed the presence of 20q- and Philadelphia chromosome t(9;22)(q34:q11) at the time of disease transformation to ALL. The JAK2V617F mutation was not found. This is a very rare case of simultaneous presence of two cytogenetics abnormalities and evolution of primary idiopathic myelofibrosis to Philadelphia-positive acute lymphoblastic leukemia.

Composite Carcinoma of the Stomach Associated with Sarcoid-Like Granulomas

Composite glandular/exocrine-endocrine carcinoma of the gastrointestinal tract is a special tumor type composed of common adenocarcinoma and the neuroendocrine component comprising at least one-third of the whole tumor area. These tumors are rare in the stomach and mostly published as case reports. We describe a further case of a 36-year-old man being unique in that it was associated with extensive formation of sarcoid-like granulomas. Tumor consisted of, predominantly poorly differentiated, intestinal-type adenocarcinoma and poorly differentiated neuroendocrine, small cell carcinoma. The adenocarcinomatous and neuroendocrine areas were separated, but closely juxtaposed with focal areas showing gradual transition from one to another. Perigastric lymph node metastases corresponded either to neuroendocrine or adenocarcinomatous component. On immunohistochemistry, the exocrine part was positive for cytokeratin 7, whereas superficial well-differentiated parts showed positivity with cytokeratin 20 as well. The neuroendocrine component was negative with those two types of cytokeratin. Both adenocarcinomatous and neuroendocrine tumor portions showed carcinoembryonic antigen (CEA) immunoexpression. Neuroendocrine markers (chromogranin A, synaptophysin and neuron-specific enolase) were diffusely positive in the neuroendocrine component, and found only in the scattered cells within the neoplastic glands of the adenocarcinoma. Entire gastric mucosa and all perigastric lymph nodes were extensively affected by noncaseating, sarcoid-like granulomas. The absence of any clinical manifestations combined with the negative results of chest radiograph and laboratory test for the serum angiotensin converting enzyme argued against the possibility of systemic sarcoidosis.

Favourable prognostic factors in therapy related acute myeloid leukaemia.

INTRODUCTION Therapy related acute myeloid leukaemia (t-AML) is a distinct clinical entity recognized by the World Health Organization classification occurring after chemotherapy and/or radiation treatment administered for a previous disease. T-AML is characterised by pancytopenia, three-lineage myelodysplasia, high frequency of unfavourable cytogenetics and short survival. OBJECTIVE The aim of this study was to analyse clinical, cytogenetic, and cytological characteristics of t-AML and their impact on survival. METHODS Seventeen patients with t-AML (8 male and 9 female; median age 59 years) were identified among 730 consecutive patients with acute myeloid leukaemia. The degree of three-lineage dysplasia as well as haematological, cytological and cytogenetic analyses, were assessed by standard methods. RESULTS The patients survived a median of 62.5 days with the 10% probability of survival during two years. Prognostically favourable factors were a higher percentage of dysplastic granulocytic cells, age less than 60 years, and presence of prognostically favourable karyotype inv(16), t(15;17), t(8;21). CONCLUSION The stated prognostic factors that include age, cytogenetics findings and granulocytic dysplasia analysis could contribute to adequate risk stratification of t-AML, though fuller results would require additional analyses.

A9.7 Cholesterol crystals induce neutrophil extracellular traps formation

Background and Objectives Besides phagocytosis as mechanism to combat pathogens, neutrophils are able to eject DNA decorated with microbicidal proteins (neutrophil extracellular traps-NETs), that can immobilize and kill microorganisms extracellularly. Procoagulative properties of NETs have already been shown, however, a role of NETs formation in atherosclerotic disease has not been described so far. The process of chromatin release is referred to as NETosis. The aim of this study was to assess if cholesterol crystals are able to induce NETosis in vivo and in vitro. Materials and Methods Polymorphonuclear cells-PMNs were isolated from blood obtained from healthy volunteers after informed consent. Isolated PMNs as well as whole blood were co/cultured with cholesterol crystals. After the treatment, cytospins were prepared and stained for DNA and neutrophil elastase. Extracelullar DNA was quantified by fluorometry. For in vivo experiments, cholesterol crystals were injected into murine air pouches. After 24h, air pouches were lavaged with PBS. After centrifugation cells were used for cytospins and supernatants for cytokines determination. Tophus-like aggregates were isolated and characterised by immune histochemistry and immunobloting. In addition, human autopsy specimens obtained from subject died of cardiac diseases were assessed for presence of NET markers. Results Cholesterol induced dose dependent NETosis in isolated PMNs as well as in whole blood samples. The maximal applied concentration of cholesterol crystals induced 236.5% higher DNA release when compared to control. Cholesterol crystal injected in air pouches induced tophus-like aggregates composed of aggregated NETs attached to the cholesterol crystals. These structures were highly positive for citrullinated histones, markers of NET formation. NET markers were also found in atherosclerotic blood vessels in zones surrounding necrotic core of atheromatous plaque, which is rich in cholesterol crystals Discussion This study showed for the first time ability of cholesterol crystals to induce NETosis in vitro, as well as in vivo. These data may explain prompt thrombus formation in atherosclerotic disease after rupture of fibrous cap of an atheromatous plaque containing huge amount of cholesterol crystals, which will be the subject of our future research.