Publications (46)

  • Anamarija Morovic · Igor Aurer · Snjezana Dotlic · [...] · Marin Nola
    [Show abstract] [Hide abstract] ABSTRACT: Extranodal NK/T cell lymphoma, nasal type, is an Epstein-Barr virus-associated lymphoma that most commonly involves the nasal cavity and upper respiratory tract. Lung involvement by NK/T cell lymphoma is rare and seldom reported in the literature. We describe the unusual case of a 41-year-old male with NK cell lymphoma, nasal type, who presented with massive secondary lung involvement 2.5 years after the detection of a retroperitoneal mass. The diagnosis was made by open lung biopsy. Despite aggressive treatment, the patient died shortly after the initiation of therapy. Lung involvement by NK/T cell lymphoma occurs most commonly as part of widely disseminated disease and carries a poor prognosis for the patient. Novel agents and innovative therapies need to be developed for this aggressive lymphoma.
    Article · Jun 2010 · Journal of Hematopathology
  • [Show abstract] [Hide abstract] ABSTRACT: Anaplastic large cell lymphoma (ALCL) is a highly malignant neoplasm characterized by pleomorphic appearance, different immunophenotypes and variable sites of involvement. Expression of myeloid-associated markers in anaplastic large cell lymphomas may mislead the medical team and result in delay of diagnosis due to unusual phenotype. It is important to diagnose this type of tumors and distinguish it from myeloid neoplasms (extramedullary myeloid cell tumors and histiocytic tumors) since therapy and prognosis are significantly different. A 16-year-old female patient presented with fever, lymphadenopathy, and high white blood cell count. Diagnosing a CD13+ ALCL with leukemic presentation with additional cytogenetic abnormality (duplication 5q35) was a significant diagnostic challenge. This combination of features, unusual for lymphoma, should be considered in differential diagnosis of myeloid neoplasms and fatal infections. Diagn. Cytopathol. 2010.
    Article · Feb 2010 · Diagnostic Cytopathology
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    Ivana Ilić · Zdravko Mitrović · Igor Aurer · [...] · Marin Nola
    [Show abstract] [Hide abstract] ABSTRACT: The influence of the germinal-center B-cell (GCB) and the non-GCB phenotypes of diffuse large B-cell lymphoma (DLBCL) on the outcome of 92 patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like chemotherapy, with or without rituximab was determined in this study. The differentiation between the GCB and non-GCB types was arrived at by immunohistochemistry using previously published criteria. Thirty-nine patients had the GCB and 53 had the non-GCB type of DLBCL. Forty-nine patients were treated with rituximab and chemotherapy; 43 were treated with chemotherapy alone. The GCB and non-GCB group did not differ in their international prognostic index factors and score, presence of bulky disease, or frequency of rituximab treatment. Median follow-up of the surviving patients was carried out for 37 months. There was no difference between the GCB and non-GCB groups in both overall response rates (67 vs. 70%, respectively) and estimated rates of 3-year event-free (46 vs. 49%, respectively) and overall (54 vs. 56%, respectively) survival. In addition, no differences of the outcomes were observed between the subgroups treated with or without rituximab. The patients of this study with immunohistochemically determined GCB-type DLBCL did not have an improved prognosis, irrespective of whether they had received rituximab or not.
    Full-text Article · Jul 2009 · International journal of hematology
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    Zdravko Mitrovic · Ivana Ilic · Marin Nola · [...] · Boris Labar
    [Show abstract] [Hide abstract] ABSTRACT: CD43 is a transmembrane glycoprotein expressed in different hematopoietic cells, including some subsets of B lymphocytes. About a quarter of diffuse large B-cell lymphomas (DLBCLs) express CD43, but its prognostic significance is unknown. We analyzed the prognostic effect of immunohistochemically determined CD43 expression in 119 patients with newly diagnosed DLBCL. All were treated with CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone)-like chemotherapy, 57 without and 62 with rituximab. A total of 31 DLBCL cases (26%) expressed CD43. Patients with CD43+ and CD43- lymphomas did not differ regarding sex, International Prognostic Index (IPI) factors and score, rituximab treatment, presence of bulky disease, or germinal center subtype. Median follow-up was 45 months. Patients with CD43+ DLBCL had significantly lower complete response rates (59% vs. 80%; P = .019), 2-year event-free survival (EFS) rates (34% vs. 64%; P = .003), and overall survival (OS) rates (45% vs. 76%; P = .002). The prognostic significance of CD43 expression was retained in multivariate analysis (relative risk [RR] 2.04; P = .013 for EFS; RR 2.17; P = .016 for OS). In subgroup analysis, the effect of CD43 expression was significant in patients treated with rituximab and those with low IPI, whereas it was not reached in patients treated without rituximab. The effect was not observed in patients with high IPI. These results indicate that CD43 expression is an important independent adverse prognostic factor in DLBCL.
    Full-text Article · May 2009 · Clinical Lymphoma & Myeloma
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    [Show abstract] [Hide abstract] ABSTRACT: Basal cell carcinoma (BCC) is the most common cutaneous malignancy and the most common human malignancy in general. Out of all basal cell carcinomas, giant basal cell carcinoma represents less than 1%. Only 10% of all basal cell carcinomas are located on the trunk and majority is located on the head and neck. We describe a patient with a exophytic giant basal cell carcinoma of the back size 8.5 x 8 x 6 cm, infiltrating skin 1.5 cm. Two years after the lesion has occurred, diagnosis was made by pathohistological analysis. The patent was treated surgically, by excision. Review of the literature that refers to giant basal cell carcinoma was carried out.
    Full-text Article · Apr 2009 · Collegium antropologicum
  • Conference Paper · Mar 2009
  • M. Nola · S. Dotlić
    Article · Jan 2009
  • M. Nola · S. Dotlić
    Article · Jan 2009
  • [Show abstract] [Hide abstract] ABSTRACT: Although non-melanoma skin cancers are the most predominant malignancies in the Caucasian population and hemophilia A is one of the most frequent hereditary bleeding disorders, medical literature data about the management of non-melanoma skin cancers in patients with hemophilia are surprisingly scarce. In this case report we describe the treatment of a patient with multiple recurrent non-melanoma skin cancers and severe hemophilia A. The management of such patients could be very challenging, with possible significant bleeding complications, and requires a multidisciplinary approach.
    Article · Jan 2009 · Tumori
  • I Aurer · Z Mitrović · D Nemet · [...] · B Labar
    [Show abstract] [Hide abstract] ABSTRACT: We report the outcomes of 45 patients with relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) treated with a combination of ifosfamide, carboplatinum and etoposide (ICE) and 28 patients treated with a combination of ifosfamide, methotrexate and etoposide (IMVP) during two 5-year periods. The response rate (RR) to ICE was 47%, 2-year overall survival (OS) 31% and 2-year event-free survival (EFS) 22%. These results were similar to those obtained with IMVP (RR 39%, 2-year OS 23%, 2-year EFS 13%; p=0.355 for RR, 0.275 for OS, 0.668 for EFS). Higher IPI scores and refractoriness to treatment were negative prognostic factors, immunophenotype (B vs. T) had no influence on prognosis. Changing from IMVP to ICE does not substantially improve the outcome of patients with relapsed or refractory aggressive NHL. Patients with relapsed/refractory aggressive B-NHL do not have a superior outcome in comparison to those with T-NHL if treated with chemotherapy alone.
    Article · Nov 2008 · Journal of chemotherapy (Florence, Italy)
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    Ana Borovecki · Petra Korać · Marin Nola · [...] · Mara Dominis
    [Show abstract] [Hide abstract] ABSTRACT: To define prognostic significance of B-cell differentiation genes encoding proteins and BCL2 and BCL6 gene abnormalities in diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern. In 53 patients with diffuse large B-cell lymphoma and 20 patients with follicular lymphoma grade 3 with >75% follicular growth pattern the following was performed: 1) determination of protein expression of BCL6, CD10, MUM1/IRF4, CD138, and BCL2 by immunohistochemistry; 2) subclassification into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) groups according to the results of protein expression; 3) detection of t(14;18)(q32;q21)/IgH-BCL2 and BCL6 abnormalities by fluorescent in situ hybridization in diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern as well as in GCB and ABC groups; and 4) assessment of the influence of the analyzed characteristics and clinical prognostic factors on overall survival. Only BCL6 expression was more frequently found in follicular lymphoma grade 3 with >75% follicular growth pattern than in diffuse large B-cell lymphoma (P=0.030). There were no differences in BCL2 and BCL6 gene abnormalities between diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern. Diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern patients were equally distributed in GCB and ABC groups. t(14;18)(q32;q21) was more frequently recorded in GCB group, and t(14;18)(q32;q21) with BCL2 additional signals or only BCL2 and IgH additional signals in ABC group (P=0.004). The GCB and ABC groups showed no difference in BCL6 gene abnormalities. There was no overall survival difference between the diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern patients, however, GCB group had longer overall survival than ABC group (P=0.047). Multivariate analysis showed that BCL6, CD10, and BCL2 expression, BCL2 and BCL6 abnormalities, and International Prognostic Index were not significantly related to overall survival. Diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern patients have very similar characteristics and their prognosis is more influenced by protein expression of B-cell differentiation stage genes than by tumor cells growth pattern, BCL2 and BCL6 abnormalities, and International Prognostic Index.
    Full-text Article · Oct 2008 · Croatian Medical Journal
  • Iva Brcić · Boris Labar · Melita Perić-Balja · [...] · Marin Nola
    [Show abstract] [Hide abstract] ABSTRACT: Precursor lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL) is a malignant neoplasm of precursor lymphocytes of T- or B-cell phenotype. We describe the unusual features of an ALL/LBL in an adolescent man in whom the disease presented with involvement of lymph nodes, but without bone marrow and peripheral blood involvement. Immunohistochemical studies revealed that the tumor cells were positive for CD3, CD34 class II, CD10, CD79a and CD99 but negative for TdT. Even though TdT was negative, he received ALL-therapy and is now in remission.
    Article · Jun 2008 · International Journal of Hematology
  • Mirela M Dabić · Marin Nola · Ivana Tomicić · [...] · Stanko Jukić
    [Show abstract] [Hide abstract] ABSTRACT: This study was designed to determine the possible impact of status of human papillomavirus (HPV) infection (no infection, single, multiple infections) on the survival of patients with cervical adenocarcinoma, to correlate the HPV status with other clinicopathologic parameters, and to examine clinical, histological and flow cytometric parameters as predictors of survival in cervical adenocarcinoma. The clinical data of 51 patients with adenocarcinoma of the cervix who were treated at the Department of Gynecology and Obstetrics, Zagreb University School of Medicine, from 1978 to 2004 were analysed: age at presentation, menstrual status, clinical stage, relapse, survival. Exact histologic subtype, architectural grade and nuclear grade were determined. DNA flow cytometry was performed to determine DNA ploidy and proliferative index. Polymerase chain reaction (SPF primers), followed by reverse hybridisation for genotyping, was used to determine the HPV status. The status of HPV infection had no impact on patient survival, and could not be correlated with any of the analysed clinicopathologic parameters. Univariate analysis showed significant association between patient survival and clinical stage (p=0.002) and architectural grade (p=0.033). Multivariate analysis confirmed both parameters as significantly associated with survival. Menstrual status, nuclear grade, DNA ploidy and proliferative activity had no impact on patient survival. Clinical stage and architectural grade are significant predictors for survival of patients with cervical adenocarcinoma. Status of HPV infection, flow cytometric parameters, nuclear grade and menstrual status do not predict patient survival.
    Article · Feb 2008 · Acta Obstetricia Et Gynecologica Scandinavica
  • N. Nola · A. Lukenda · M. Nola · [...] · T. Orešić
    [Show abstract] [Hide abstract] ABSTRACT: Aims. The aim of the study was to determine cellular ploidy of invasive ductal breast carcinoma with neuroendocrine (NE) differentiation and its share in certain phases of the cell cycle. It was also aimed at assessing the relationship of the cell cycle profile with other clinical and histopathological features. Methods. The study was carried out in 80 patients with invasive ductal breast cancer, and classified as breast carcinoma with NE differentiation according to their histopathological parameters. The patients underwent treatment at the University Hospital for Tumors, Zagreb, Croatia during the period January 1 to December 31, 1992. Data about patients' age, estrogen and progesterone receptor concentration, cancer size, and treatment modality were retrospectively collected from their case histories. Paraffin blocks were used for immunohistochemical and histochemical analysis and flow cytometric analysis of the tumor cell cycle. Neuroendocrine tumor diagnosis was made using Grimelius and immunohistochemical staining including neuron-specific enolase (NSE), chromogranin A and synaptophysin. Results. Analysis by flow cytometry detected 27 tumors (33.8%) with DNA diploidy showing proliferative activity lower than 20%, and 53 tumors (66.2%) with DNA aneuploidy, tetraploidy and/or DNA diploidy with proliferative activity over 20%. Progesterone receptor concentration in DNA-diploid tumors was significantly higher that in DNA-aneuploid, tetraploid tumors and tumors with proliferative activity of ≥20% (p<0.001). Concentration of estrogen receptors, age, histological grade, tumor size, Grimelius staining and immnohistochemical markers did not significantly differ between the groups. Conclusion. Data collected in our study show a higher mean concentration of progesterone receptors in the group of diploid tumors and tumors with low proliferative activity. In consideration with the above criterium, other pathological and clinical parameters did not show any significant difference relative to both tumor ploidy and its proliferative activity. For final conclusion on the clinical significance of neuroendocrine differentiation in breast cancer further studies that would include monitoring of the course and outcome of the disease are required.
    Article · Jan 2008 · Libri Oncologici
  • [Show abstract] [Hide abstract] ABSTRACT: A 17-year-old Croatian boy with Nijmegen breakage syndrome (NBS) who developed diffuse large B-cell non-Hodgkin lymphoma is presented. The majority of the patients with this rare autosomal recessive disease are of Slavic origin and, in most of them, the disease is caused by NBS1 mutation 657del5, as was found in our patient. Nijmegen breakage syndrome is characterized by microcephaly, growth retardation, abnormal facial appearance, spontaneous chromosomal rearrangements, immunodeficiency, and a high predisposition to cancer development, predominantly lymphoma. Because of increased sensitivity to radiation therapy and chemotherapy, the treatment of malignancies in patients with NBS can be difficult. To our knowledge, our patient is the first with NBS reported in the literature who was successfully treated for diffuse large B-cell lymphoma with the anti-CD20 monoclonal antibody rituximab in addition to a modified dose of CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy. He has been in complete remission for 3 years after finishing the treatment.
    Article · Dec 2007 · Clinical Lymphoma & Myeloma
  • Article · Sep 2007 · Leukemia Research
  • Z. Mitrovic · I. Aurer · M. Nola · [...] · B. Labar
    Article · Sep 2007 · Leukemia Research
  • [Show abstract] [Hide abstract] ABSTRACT: Hairy cell leukemia is a chronic B-cell lymphoproliferative disorder characterized by clonal proliferation of hairy cells. Treatments of choice are purine analogues, particularly cladribine. We treated thirty patients with cladribine either by continuous 7-day infusion at a daily dose of 0.1 mg/kg or by 2-h infusion for 5 consecutive days at a daily dose of 0.14 mg/kg. Remission was achieved in 90% of the patients. After a median follow-up of 44 months overall survival is 93% and time to treatment failure more than 6 years. Two patients did not respond, one patient died of infection shortly after the treatment. Side-effects resulted mainly from hematological toxicity, 23% of the patients had neutropenic fever while 20% required platelets or packed red cell transfusions. Our results show that cladribine is safe and effective in the treatment of hairy cell leukemia. There were no significant differences in toxicity and response between 7-day continuous infusion and 5-day intermittent infusions of the drug.
    Article · Mar 2007 · Lijec̆nic̆ki vjesnik
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    Full-text Article · Mar 2007 · Croatian Medical Journal
  • [Show abstract] [Hide abstract] ABSTRACT: Primary cardiac lymphomas (PCL) are rare cardiac neoplasms that carry an ominous prognosis. They occur more frequently in immunocompromised patients. We report on an immunocompetent 67-year-old who presented with dyspnea and dysphagia. Echocardiographic evidence of impending cardiac tamponade and obstruction of the inferior vena cava (IVC) with the tumor was seen. The deteriorating hemodynamics of our patient prompted an urgent surgical intervention. Pathohistological diagnosis showed diffuse large B-cell lymphoma of centroblastic subtype. Chemotherapy remains the standard treatment of PCL, with surgery reserved for relieving life-threatening complications of the neoplasm.
    Article · Jul 2006 · Journal of Cardiac Surgery