Does Double Mean Trouble? Coexistence of Myeloproliferative and Lymphoproliferative Neoplasms.

Background: The occurrence of myeloproliferative neoplasms (MPNs) that evolve into each other is well-described, as is this occurrence of lymphoproliferative neoplasms (LPNs). However, less is known about rare MPN/LPN coexistence, and the aim of our study was to analyze charachteristics of these patients after long term follow-up. Methods: Fourteen patients with MPN/LPN coexistence were diagnosed and treated according to guidelines at a single university center across two decades. Results: The overall median age was 53 years (22-69). MPNs patients with subsequent LPNs had a shorter period of second malignancy development and a more aggressive course of LPN, which can cause fatal outcomes. Polycythemia vera and chronic lymphocytic leukemia were most commonly associated (36%). The JAK2V617F mutation had 2/3 and cytogenetic abnormalities occurred in 1/3 of patients. MPN/LPN coexistence cases had significantly higher thrombotic potential (42.8%) and a higher third malignancy accruement frequency (21.4%) versus those without such malignancies. Conclusions: Considering the younger ages at MPN diagnosis, it is recommended to check regularly for blood lymphocytosis or lymphadenopathy occurrences and organomegaly progression faster than expected for MPN, with the aim of timely LPN diagnoses. The presence of molecular-cytogenetic abnormalities in a majority of patients indicate possible genetic instability and increased risk of development of multiple neoplasms, thus elevating thrombotic risk.

The Revised International Staging System Compared to the Classical International Staging System Better Discriminates Risk Groups among Transplant-Ineligible Multiple Myeloma Patients.

BACKGROUND: The Revised International Staging System (R-ISS) has recently been introduced as a comprehensive prognostic score for multiple myeloma (MM). Validation of the R-ISS in patients treated outside of clinical trials is the focus of current investigations. The aim of this study was to test the prognostic role of the R-ISS in MM patients ineligible for autologous stem cell transplantation. PATIENTS AND METHODS: A total of 102 newly diagnosed MM patients were analyzed. All patients were initially treated with thalidomide-based combinations. RESULTS: An overall response rate was achieved in 77.4% patients. Both the International Staging System (ISS) and the R-ISS influenced the event-free survival and the overall survival (OS). However, the ISS was unable to discriminate patients in stages ISS1 and ISS2 regarding OS. On the contrary, the R-ISS clearly differentiated risk categories regarding OS and provided an improved discriminative power of 6.3% compared to the ISS. Furthermore, among the parameters that were significant in univariate analysis (presence of renal impairment, anemia, platelet count < 130 × 109/l, and R-ISS), the multivariate model pointed to the R-ISS (p = 0.001) as the most important parameter influencing OS. CONCLUSION: The R-ISS represents a useful tool for risk stratification of transplant-ineligible MM patients and should be considered as a prognostic index in daily clinical practice.

Primary Intestinal Hodgkin Lymphoma Mimicking Intraabdominal Abscess in a Renal Transplant Recipient: A Case Report.

INTRODUCTION: Post-transplant lymphoproliferative disease (PTLD) comprises a variety of lymphoid and plasma cell disorders arising in patients with a solid organ transplant. Monomorphic lymphomas represent the most significant part of this wide spectrum, with the overall risk rising with the aggressiveness of lymphoid proliferation in comparison to the general population. The development of Hodgkin lymphoma is very rare in transplant recipients, comprising less than 6% of all monomorphic PTLD, while cases of primary intestinal Hodgkin lymphoma in these circumstances are anecdotal. CASE REPORT: We describe an exceptional case of intestinal Hodgkin lymphoma mimicking an intra-abdominal abscess that developed in a transplant recipient 19 years after kidney transplantation. By presenting this case, we wish to emphasize the importance of suitable diagnostic pathways in transplant recipients experiencing prolonged fever episodes or masses of unknown origin, thus raising the awareness of possible PTLD development in such patients. CONCLUSION: The lack of information about transplant recipients with Hodgkin PTLD regarding the site of involvement and type of treatment suggests the necessity of conducting larger international studies aimed at providing further insight into this particular group of patients.

Prognostic value of lymphocyte/monocyte ratio in advanced Hodgkin lymphoma: correlation with International Prognostic Score and tumor associated macrophages.

We studied the prognostic significance of the absolute lymphocyte/monocyte count ratio (ALC/AMC), its contribution to the prognostic value of the International Prognostic Score (IPS), and evaluated if ALC/AMC could serve as a proxy for the frequency of CD68 + tumor-associated macrophages (TAMs) in 101 patients with advanced Hodgkin lymphoma (HL). The receiver operating characteristic (ROC) curve identified best cut-off values of 2.0 for ALC/AMC and 25% for CD68 + TAM. Patients with ALC/AMC < 2, IPS > 2 and > 25% CD68 + TAM had an inferior overall survival (OS) and event-free survival (EFS). Spearman's test also uncovered a significant correlation between the ALC/AMC and TAM. Multivariate analysis identified ALC/AMC < 2, IPS > 2 and > 25% CD68 + TAM as poor prognostic factors of OS and EFS. After evaluating ALC/AMC and IPS, we stratified patients into three progressively-worse-outcome groups (low-risk: 0 risk factors; intermediate: 1 risk factor; high: 2 risk factors). Our study encourages the combination of ALC/AMC with IPS, for refining risk prediction in advanced HL patients.

Myeloid sarcoma of the skin in a patient with myelodysplastic syndrome.

We report the case of a 76-year-old woman who presented with asymptomatic extensive erythematous. Firm plaques were noted over the right cheek. Complete blood count was normal, as was a peripheral smear. An excision biopsy taken from the cheek showed infiltration of the dermis and hypodermis with atypical cells which were strongly positive for human leukocyte antigen (HLA-DR) and lysozyme and were moderately myeloperoxidase (MPO) enzyme. The results of immunohistochemical staining for CD34, CD117, CD3, CD4, CD8, CD20, CD23, CD56, and ALK-1 were negative. Bone marrow analysis indicated myelodysplastic syndrome RAEB 1 while cytogenetic finding showed tetrasomy 8. It was recommended that the patient undergo local radiotherapy of skin lesions, but she refused and was lost to follow-up.

Diagnostic challenges during pretreatment long-term follow-up in a patient with FIP1L1-PDGFRA-positive eosinophilia.

Obtaining a precise characterization of eosinophilia is crucial, as successful treatment relies on the underlying etiology of the disease. Platelet-derived growth factor receptor alpha-related disorders were first specified in 2008 as a distinct group of clonal eosinophilic disorders with exceptional responsiveness to imatinib. We herein present the case of a man with myeloid neoplasm and eosinophilia in whom a definitive diagnosis could not be adequately made based on histopathological features who was ultimately diagnosed only after extensive molecular analyses and successfully treated with imatinib. In addition, we discuss the diagnostic and therapeutic approaches to treating patients presenting with eosinophilia.

Pretreatment risk factors for overall survival in patients with gastrointestinal and non-gastrointestinal mucosa associated lymphoid tissue lymphomas.

PURPOSE: The aim of this 10-year retrospective study was to investigate prognostic clinical and laboratory factors significant for the outcome of patients with mucosa associated lymphoid tissue (MALT) lymphoma. METHODS: The study involved 87 patients diagnosed with MALT lymphoma: 37 (42.5%) with gastrointestinal (GI) and 50 (57.5%) with non-GI localization. The following pretreatment laboratory parameters were analyzed: hemoglobin, serum albumin and lactate dehydrogenase (LDH) level, beta2-microglobulin (bgr;2-M) and bacteriological (H.pylori) status. Estimated clinical features were: stage of disease, ECOG performance status (PS), tumor mass, number of extranodal localizations, presence of B symptomatology, splenomegaly and enlarged lymph nodes. Diagnosis of MALT lymphoma was based on histopathological analysis of tissue samples, obtained by endoscopy or surgery. RESULTS: The median disease-free survival (DFS) was 36 months and the 5-year overall survival (OS) was 64%. OS rate of patients with non-GI localization was higher compared with patients with GI localization (p=0.001). Multivariate analysis showed hypoalbuminemia to be the most significant parameter associated with poor OS (p<0.001) for both patient groups. The most significant prognostic factor for poor OS in patients with GI localization was LDH level (p=0.031), while hypoalbuminemia was the most significant prognostic factor for poor OS in the group with non-GI disease localization (p=0.001). CONCLUSION: Proper therapeutic approach for MALT lymphoma patients could be planned taking into consideration poor prognostic parameters, i.e. hypoalbuminemia and elevated LDH for GI patients and hypoalbuminemia for non- GI lymphoma patients.

Contribution of comorbidities and grade of bone marrow fibrosis to the prognosis of survival in patients with primary myelofibrosis.

The widely used current International Prognostic Scoring System (IPSS) for primary myelofibrosis (PMF) is based on clinical parameters. The objective of this study was to identify additional prognostic factors at the time of diagnosis, which could have an impact on the future treatment of patients with PMF. We conducted a study of 131 consecutive PMF patients with median follow-up of 44 months. Data on baseline demographics, clinical and laboratory parameters, IPSS, grade of bone marrow fibrosis (MF), as well as influence of concomitant comorbidities were analyzed in terms of survival. Comorbidity was assessed using the Adult Comorbidity Evaluation-27 (ACE-27) score and the hematopoietic cell transplantation comorbidity index. An improved prognostic model of survival was obtained by deploying the MF and ACE-27 to the IPSS. A multivariable regression analyses confirmed the statistical significance of IPSS (P<0.001, HR 3.754, 95% CI 2.130-6.615), MF>1 (P=0.001, HR 2.694, 95% CI 1.466-4.951) and ACE-27 (P<0.001, HR 4.141, 95% CI 2.322-7.386) in predicting the survival of patients with PMF. When the IPSS was modified with MF and ACE-27, the final prognostic model for overall survival was stratified as low (score 0-1), intermediate (score 2-3) and high risk (score 4-6) with median survival of not reached, 115 and 22 months, respectively (P<0.001). Our findings indicate that the combination of histological changes, comorbidity assessment and clinical parameters at the time of diagnosis allows better discrimination of patients in survival prognostic groups and helps to identify high-risk patients for a poor outcome.

The emergence of non-secretory multiple myeloma during the non-cytotoxic treatment of essential thrombocythemia: a case report.

INTRODUCTION: The emergence of multiple myeloma as a second malignancy in patients with essential thrombocythemia is extremely rare. Several cases have been published so far, pointing out the impact of a cytotoxic effect during treatment of essential thrombocythemia on the development of multiple myeloma. CASE PRESENTATION: We report the case of a 52-year-old Caucasian man who presented to our hospital because of leukocytosis, a slightly decreased hemoglobin level and thrombocytosis. After a complete hematological work-up, essential thrombocythemia was diagnosed. The patient was included in a multicenter clinical study, treated with anagrelide and his platelet counts were maintained in the normal range for more than 3 years. A sudden drop in his hemoglobin level with normal leukocyte and platelet count occurred at the same time as a back pain. Magnetic resonance imaging of his spine revealed the existence of a pathological fracture of Th4, the collapse of the upper edge of Th7 and osteolytic lesions of multiple thoracic vertebrae. Repeated hematological examinations, including bone biopsy with immunohistochemistry, disclosed diagnosis of multiple myeloma of the non-secretory type. CONCLUSIONS: To the best of our knowledge this is the first published case in which multiple myeloma developed during the treatment of essential thrombocythemia with the non-cytotoxic drug anagrelide. Our attempts to find a common origin for the coexistence of multiple myeloma and essential thrombocythemia have not confirmed the genetic basis of their appearance. Further studies are needed to determine the biological impact of this coexistence.

Unusual presentation of gastric plasmablastic lymphoma in HIV-negative patient.

Plasmablastic lymphoma (PBL) has initially been described as a rapidly progressive and almost invariably fatal diffuse large-cell lymphoma with plasmablastic features, exclusively involving the jaw and oral mucosa in HIV-positive patients. Although its clinical features may help in differential diagnosis, an extra-oral localization in a patient without HIV makes it more difficult to suspect clinically. We describe a very rare case of gastric PBL primarily involving stomach in a middle age man without an HIV infection. A biopsy was performed and its findings revealed a diffuse, monomorphous proliferation of the tumor cells with features of immunoblasts, MUM-1, EMA, and lambda light chains positive. Serology was negative for the human immunodeficiency virus (HIV), HBsAg, and hepatitis C virus infection. The patient started treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy, but unfortunately died before the second cycle was given. To our knowledge, this is the second case of gastric PBL presented in HIV-negative patients. The findings in this case suggest that PBL should be included in the differential diagnosis of gastrointestinal tumors.

The prognostic relevance of tumor associated macrophages in advanced stage classical Hodgkin lymphoma.

Although the treatment of Hodgkin lymphoma (HL) has been improved, distinguishing reliable prognostic biomarkers could better stratify patients for more effective treatment. We analyzed the prognostic relevance of CD68+ tumor-associated macrophages (TAMs) by immunohistochemical analysis at diagnosis and standard clinical parameters in 52 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)-treated patients with advanced stage classical HL (cHL). Patients with >25% CD68+ TAMs compared to those with ≤25% had worse 5-year overall survival (45% vs. 77%, log-rank p = 0.019) and showed a trend toward shorter 5-year event-free survival (51% vs. 71%, log-rank p = 0.19). Additionally, no significant correlation with selected clinical features was found. Significantly shorter 5-year overall survival was associated with International Prognostic Score (IPS) >2, bulky disease, elevated erythrocyte sedimentation rate (log-rank test, p = 0.003, p = 0.049, p = 0.007, respectively). In multivariate analysis, increased CD68+TAMs, IPS >2, and bulky disease were identified as independent prognostic factors for overall survival (Cox multivariate model, p = 0.006, p = 0.007, p = 0.013, respectively). Tumor-associated macrophages represent a potential prognostic biomarker which could contribute to better risk stratification of patients with cHL.

Simultaneous presentation of hairy cell leukemia and metastatic signet ring carcinoma of the stomach diagnosed by bone marrow biopsy.

Hairy cell leukemia (HCL) is a rare chronic B-cell disorder with an increased risk of second tumors. The relative risk of second cancers reported in various series of HCL patients ranged from 0.95 to 4.33, but simultaneous presentation of HCL and other epithelial malignancies is very rare. To our knowledge, we present the first case of the coexistence of signet ring carcinoma of the stomach and HCL. We report a case of the simultaneous presentation of HCL and metastasis of the primary signet ring cell carcinoma of the stomach to the bone marrow and skin. A bone marrow biopsy was performed on a patient with pancytopenia. A histologic examination with immunostaining of the bone marrow specimen showed the presence of signet ring carcinoma cells in addition to HCL. As a consequence, our patient underwent further diagnostic procedures including endo-gastro-duodenoscopy with biopsy of gastric tumor mass, which established the diagnosis of gastric signet ring cell carcinoma.

Multimodality imaging in the assessment of cardiac lymphoma presented as new-onset atrial fibrillation.

Cardiac involvement by non-Hodgkin's lymphoma is not uncommon, however rarely diagnosed during life due to nonspecific clinical presentation. We report a case of secondary cardiac lymphoma in patient who presented with new-onset atrial fibrillation. Cardiac lymphoma was in a form of bulky right atrial mass, infiltrating the atrial septum and cavo-atrial junction with concomitant mild pericardial effusion. In the present case, we illustrate complementary role of transthoracic, transesophageal echocardiography and multislice CT scan with three-dimensional reconstruction, in detection and evaluation of secondary cardiac tumor. Usefulness of echocardiography to follow up the effects of chemotherapy is also shown.

T-cell large granular lymphocytic (T-LGL) leukemia: a single institution experience.

BACKGROUND: T-cell large granular lymphocytic (T-LGL) leukemia is a rare lymphoproliferative disease which usually affects elderly people. The clinical course of T-LGL leukemia is generally indolent, with lymphocytosis and splenomegaly in 20-50% patients, hepatomegaly in 5-20% of patients, and less commonly, lymphadenopathy. T-LGL leukemia is associated with immunological abnormalities: rheumatoid factor with or without rheumatoid arthritis (RA), Coombs positive hemolytic anemia, idiopathic thrombocytopenic purpura (ITP), pure red cell aplasia (PRCA), positive anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), hypogammaglobulinemia, and polyclonal hypergammaglobulinemia. Aim To compare clinical and laboratory features of T-LGL leukemia patients and their responses to different chemotherapy regimens. METHODS: Six patients (3 males and 3 females) with T-LGL leukemia were analyzed. The diagnosis was based on accepted morphologic criteria, immunophenotype, and polymerase chain reaction (PCR) detection of T-cell receptor (TCR) gene rearrangements. RESULTS: All patients exhibited lymphocytosis, mainly with unusual morphologies, splenomegaly, and elevated serum lactate dehydrogenase (LDH). Three patients were treated with a Fludarabine-Cyclophosphamide (FC) combination as initial therapy while three patients received CHOP. Two patients received more than one treatment regimen. One patient died due to T-LGL leukemia in first year after diagnosis, one patient died 4 years after diagnosis, two patients interrupted their treatment, and two patients are still alive. CONCLUSIONS: Further prospective studies are needed for establishing a gold standard therapy for T-LGL leukemia.

[Prognostic significance of cellular vascular endothelial growth factor (VEGF) expression in the course of chronic myeloid leukaemia]. / Prognosticki znacaj vaskularnog endotelnog faktora rasta u razvoju hronicne mijeloidne leukemije.

INTRODUCTION: Increased angiogenesis in bone marrow is one of the characteristics of chronic myeloid leukaemia (CML), a clonal myeloproliferative disorder that expresses a chimeric bcr/abl protein. Vascular endothelial growth factor (VEGF) is one of the most potent and a specific regulator of angiogenesis which principally targets endothelial cells and regulates several of their functions, including mitogenesis, permeability and migration. The impact of elevated VEGF expression on the course of chronic myeloid leukaemia is unknown. OBJECTIVE: The aim of this study was the follow-up of VEGF expression during the course of CML. METHODS: We studied VEGF expression of 85 CML patients (median age 50 years, range 16-75 years). At the commencement of the study, 29 patients were in chronic phase (CP), 25 in an accelerated phase (AP), and 31 in the blast crisis (BC). The temporal expression (percentage positivity per 1000 analysed cells) VEGF proteins over the course of CML were studied using the immunohistochemical technique utilizing relevant monoclonal antibodies. It was correlated with the laboratory (Hb, WBC and platelet counts, and the percentage of blasts) and clinical parameters (organomegaly, duration of CP, AP, and BC) of disease progression. RESULTS: The expression ofVEGF protein was most pronounced in AP (ANOVA, p=0.033). The level of VEGF expression correlated inversely with the degree of splenomegaly (Pearson, r=-0.400, p=0.011). High expression of VEGF correlated with a shorter overall survival (log rank, p=0.042). CONCLUSION: Immunohistochemically confirmed significance of the expression of VEGF in dependence of the CML stage could be of clinical importance in deciding on the timing therapy. These data suggest that VEGF plays a role in the biology of CML and that VEGF inhibitors should be investigated in CML.