Association of pre-treatment bone marrow morphology and achievement of BCR-ABL1 transcript milestones in CML.

Chronic myeloid leukemia (CML) is characterized by the fusion gene BCR-ABL1 which encodes aberrantly functioning tyrosine kinase. Treatment with tyrosine kinase inhibitors (TKI) is a landmark of CML management and the main goal is to achieve major molecular response (MMR) which is defined as BCR-ABL1IS ≤ 0.1 % at 12 months of therapy. The aim of this study is to analyze histologic features of bone marrow (BM) in CML patients at the time of diagnosis and compare it to the level of BCR-ABL1IS transcript at 3 (BCR-ABL1IS ≤10 % early molecular response; EMR) and 12 months (MMR) as well as to so called molecularly undetectable leukemia (MUL) to see weather bone marrow morphology can be of value in predicting achievement molecular response milestones. Thirty-two bone marrow biopsies of CML patients, prior TKI therapy, were re-evaluated and CD34 immunohistochemistry was performed to examine microvessel density (MVD) and microvessel area (MVA) and subsequently compared it to the level of BCR-ABL1IS transcript. This study showed statistically significant association between BM hypercellularity and EMR (p = 0.048) and MUL (p = 0.034), peri-trabecular adipocyte distribution and EMR and MUL (p = 0.027 and p = 0.011, respectively), MMR and bone marrow fibrosis (p = 0.029), loose megakaryocyte clustering and EMR and MUL (p = 0.004 and p = 0.018, respectively), absence of naked nuclei and MUL (p = 0.033) but there was no statistically significant association with vascular parameters. These results suggest that some bone marrow morphologic features prior TKI therapy might be indicators of favorable molecular response.

JAK2-v617F mutation is associated with clinical and laboratory features of myeloproliferative neoplasms.

The aim of this study is to investigate the differences of clinical and laboratory parameters between patients with JAK2-V617F positive myeloproliferative neoplasms (MPNs) and JAK2 wild type MPNs. DNA was isolated from peripheral blood granulocytes of 106 patients treated at Rijeka University Hospital Center: 41 with polycythemia vera (PV), 43 with essential thrombocythemia (ET), 9 with primary myelofibrosis (PMF) and 13 with myeloproliferative neoplasm--unclassifiable (MPN-u). The JAK2-V617F mutation was detected using allele specific PCR. Laboratory and clinical parameters were obtained from patient's medical records. The JAK2-V617F mutation was detected in 69% (73/106) patients with MPNs. The results revealed significantly different prevalence of JAK2-V617F mutation, between MPNs entities: 88% in PV 58% in ET, 56% in PMF and 54% in MPNs-unclassified disorders. The JAK2-V617F mutation significantly correlated with higher leukocyte count and alkaline phosphatase co re in ET group and with higher platelets count, leukocyte alkaline phosphatase score and serum lactate dehydrogenase in PV group. Vascular events were associated with elevated platelets count in whole MPNs group, with higher platelets and leukocyte count in ET and with splenomegaly in PVpatients. Clinical and laboratory data revealed significant contribution ofJAK2-V617F mutation to the development of clinical phenotype in patients with distinct subgroups of MPNs.

Gastrointestinal stromal tumors characteristics in Croatian Northern Adriatic region.

BACKGROUND/AIMS: Gastrointestinal stromal tumors (GISTs) have fairly recently been identified as a new type of tumor, thanks to advances in immunohistochemistry. Aim of our work was to investigate and describe GISTs in our hospital in a 10-year period. METHODOLOGY: Records of patients treated for GIST were analyzed and data describing demographics, comorbidities, primary tumor site, initial symptoms, immunohistochemical characteristics, method of detection and grade of malignancy were shown for each patient. RESULTS: A total of 31 patients were analyzed. There was 54.8% of women and 46.7% of men with GIST. The mean age was 61.9±12.8 years. Predominant symptoms and signs were abdominal pain and anemia, bloody stool or melena, even though a significant portion of patients did not have any, or only mild symptoms. Stomach was the most frequent location of the tumor. CD117 was positive in all but two biopsy specimens. CONCLUSIONS: We observed approximately the same incidence of GISTs as in other published data. However, we reported less asymptomatic cases at the time of diagnosis. Also, we reported more women diagnosed with GIST in our population. Even though many tumors were diagnosed by other methods, immunohistochemistry remains the definitive diagnostic method.

Aggressive multifocal form of epithelioid hemangioendothelioma--case report.

Epithelioid hemangioendothelioma (EHE) is a rare tumor of the vascular origin. It was first described in its pulmonary form by Dail and Leibow in 1975 and named "intravascular bronchioalveolar tumor" (IVBAT). Since then, reports of occurrences of the tumor have been made for number of locations, but most often tumor can be found in soft tissues, liver, lungs, bone and skin. It is considered to be a low or borderline malignant tumor with, usually, slow progression, but aggressive forms have been described. We here report a case of a 46-year old female patient with multifocal malignant tumor spreading to lungs, liver, spleen and with synchronous involvement of lumbal vertebrae, illiac bones and central nervous system dissemination. To the best of the authors knowledge, no case of malignant EHE with multiorgan involvement of this proportions and synchronous central nervous system and bone involvement in one patient has been reported to this date in English-speaking literature.