Marin Nola

University Hospital Centre Zagreb, Zagrabia, Grad Zagreb, Croatia

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Publications (36)43.77 Total impact

  • [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. © 2009 Wiley-Liss, Inc.
    Diagnostic Cytopathology 01/2010; 38(2):141 - 146. · 1.49 Impact Factor
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    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.
    Journal of Hematopathology 01/2010; 3(1):19-22.
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    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.
    International journal of hematology 07/2009; 90(1):74-80. · 1.17 Impact Factor
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    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.
    Clinical Lymphoma & Myeloma 05/2009; 9(2):133-7. · 1.13 Impact Factor
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    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.
    Collegium antropologicum 04/2009; 33(1):315-8. · 0.61 Impact Factor
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    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.
    Journal of chemotherapy (Florence, Italy) 11/2008; 20(5):640-4. · 0.83 Impact Factor
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    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.
    Croatian Medical Journal 10/2008; 49(5):625-35. · 1.25 Impact Factor
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    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.
    International Journal of Hematology 06/2008; 88(2):189-91. · 1.68 Impact Factor
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    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.
    Acta Obstetricia Et Gynecologica Scandinavica 02/2008; 87(3):366-72. · 1.85 Impact Factor
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    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.
    Clinical Lymphoma & Myeloma 12/2007; 7(9):590-3. · 1.13 Impact Factor
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    Croatian Medical Journal 03/2007; 48(1):4-8. · 1.25 Impact Factor
  • Leukemia Research - LEUK RES. 01/2007; 31.
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    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.
    Lijec̆nic̆ki vjesnik 01/2007; 129(3-4):80-3.
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    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.
    Journal of Cardiac Surgery 01/2006; 21(4):414-6. · 1.35 Impact Factor
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    ABSTRACT: To investigate prognostic significance of several clinicopathologic parameters in patients with adenocarcinoma of the uterine cervix. We retrospectively studied 36 patients treated at the Department of Gynecology and Obstetrics, Zagreb University School of Medicine, Croatia, in the period from 1978-1998. Cox proportional hazard analysis was performed to examine the prognostic significance of menstrual status, clinical stage, architectural grade, nuclear grade, DNA ploidy, proliferative activity, and mode of therapy. The 5-year survival for this group of patients was 75%. The following parameters proved to be statistically significant in a univariate analysis: clinical stage (P=0.042), architectural grade (P=0.009), and nuclear grade (P=0.002). In the multivariate analysis, the nuclear grade (P=0.007) turned out to be the only statistically significant parameter. According to the nuclear grade, the five-year survival was 80% in the prognostically favorable and only 30% in the unfavorable group of patients. Our data showed that in patients with adenocarcinoma of the uterine cervix the nuclear grade, clinical stage, and architectural grade of the tumor represent the most important prognostic parameters. The analysis of DNA ploidy and proliferative activity had no prognostic significance.
    Croatian Medical Journal 07/2005; 46(3):397-403. · 1.25 Impact Factor
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    ABSTRACT: To determine whether the students enrolled in the computer-based teaching program would take the final examination in pathology earlier than those who studied according to the previous traditional program. The study included all medical students enrolled in the pathology course at the Zagreb University School of Medicine, Zagreb, Croatia, between 1995/96 and 2000/01 academic years. In the fall of 1998, computer-based teaching program from the University of Kansas was implemented at the Zagreb University School of Medicine, with 48 of the class of 225 students (20%) randomly enrolled in the program. The remaining 80% of students of the same class were enrolled in the traditional teaching program used at the Zagreb University School of Medicine. We compared the success of these two groups of students at the final pathology examination in the first term. Following this initial observational period, all students in the next two years (1999/00 and 2000/01), were enrolled in the computer-based teaching program. Pass rates of these students at the final examination taken in the first term were compared with the pass rates of students who studied according to the traditional teaching program during the period from 1995 to 1998. In 1998, 58.3% of students from the computer-based teaching program group chose to take the final examination in the first term, compared with only 32.2% of students from the traditional teaching program group (chi(2) (1)=10.97, P<0.001). Students in the computer based program had better final examination mean scores (-/+ standard deviation) than students in the traditional program (81.9-/+9.8 and 73.3-/+14.2, respectively; t=2.908, P=0.005). Upon the implementation of the computer-based teaching program for the entire class in 1999 and 2000, the number of students taking the final examination in the first term increased more than we expected on the basis of the data from the academic years 1995 to 1998 (chi(2) (5)=39.60, P<0.001). The computer-based program introduced at the Zagreb University School of Medicine in 1998 had a positive effect on medical students, as evidenced by the fact that more students chose to take the final pathology examination in the first term and more of them passed the examination in the first attempt than those in the traditional teaching program.
    Croatian Medical Journal 06/2005; 46(3):343-7. · 1.25 Impact Factor
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    ABSTRACT: To investigate the prognostic significance of several clinicopathologic parameters in patients with invasive squamous cell carcinoma of the vulva. We retrospectively studied 43 patients with invasive squamous cell carcinoma of the vulva treated with radical vulvectomy at the Department of Gynecology and Obstetrics at Zagreb University School of Medicine, Croatia, in the period from 1978-1996. At the time of analysis, follow-up information was obtained for all patients, 18 (41.9%) of whom have died and 25 (58.1%) who were alive at the time of the last contact. The mean follow-up time of surviving patients was 121 months (range, 6-216 months). Cox proportional hazard analysis was performed to examine the prognostic significance of age, menstrual status, clinical stage, diameter and localization of the tumor, histological grade, nuclear grade, depth of tumor invasion, presence of vascular space invasion, tumor growth pattern, presence of lymph node metastasis, DNA ploidy, proliferative activity, and mode of therapy. The overall 5-year survival for this group of patients was 62.3%. The results of univariate statistical analysis confirmed that statistically significant prognostic parameters included the age of patients (P=0.038), clinical stage (P=0.001), nuclear grade (P=0.002), the depth of tumor invasion (P<0.001), and presence of lymph node metastasis (P=0.001). On the other hand, the results of multivariate statistical analysis showed that only the depth of tumor invasion (P<0.001) can be considered independent, statistically significant prognostic parameter. Our data suggest that the depth of tumor invasion represents the most important prognostic parameter in the group of patients with invasive squamous vulvar carcinoma. Clinical significance of DNA ploidy and proliferative activity was not found.
    Croatian Medical Journal 06/2005; 46(3):436-42. · 1.25 Impact Factor
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    ABSTRACT: BACKGROUND Epidermal growth factor receptor (EGFR) overexpression and amplification are important prognostic factors in many solid tumors and anti-EGFR antibody-based therapy is now available as a promising therapeutic modality. There is little information in the literature regarding the biologic role of EGFR in thymomas that are characterized by variable clinical presentations, histologic heterogeneity, and unpredictable behavior.METHODS Protein expression and gene amplification of EGFR were investigated in 32 thymomas (9 World Health Organization [WHO] type A, 5 type AB, 7 type B2, 7 type B3, 4 type C) using immunohistochemistry and fluorescence in situ hybridization (FISH). FISH analysis included assessment of the average number of copies of the EGFR gene per cell, the average ratio of the EGFR gene to chromosome 7 copy numbers, and ploidy.RESULTSThe results of FISH analysis showed statistically significant correlation with WHO histologic type, invasion, advanced clinical stage, but not with tumor size and outcome. Thymomas associated with myasthenia gravis more frequently showed hyperploidy when compared with sporadic tumors, but there was no difference in EGFR gene amplification. EGFR protein expression assessed by immunohistochemistry did not correlate with any studied clinicopathologic variables. There was poor correlation between the protein expression and gene amplification, only 7 of 23 specimens (30%).CONCLUSIONS The potential role of EGFR in the pathogenesis of advanced-stage thymomas indicated that evolving anti-EGFR antibody therapy may be considered as a treatment option. Cancer 2005. © 2005 American Cancer Society.
    Cancer 01/2005; 103(3):630 - 636. · 5.20 Impact Factor
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    ABSTRACT: The cause of non-Hodgkin lymphoma is still unclear. By knowing the signs of B-cell lymphomas, dentists can play an important role in the early detection of the disease. We describe a 63-year-old man with non-Hodgkin’s lymphoma developed at the ginigiva near the inflamed root. After therapy, the patient has remained systemically healthy. This case illustrates the need for cooperative diagnostic referrals between physicians and dentists.
    Oral Oncology Extra. 01/2005;
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    ABSTRACT: To classify ocular lymphomas in patients treated at the Zagreb University Hospital Center according to the new classification of the World Health Organization (WHO) and to determine factors with prognostic significance. From 1986 to 2003, histological diagnosis of ocular lymphoma was made in 24 patients. The median age of patients was 62 years, with 2:1 female predominance. The patients underwent staging procedures and clinical evaluations prior to the date of the initial therapy. Histopathologic slides were reviewed and tumors were classified according to the new WHO classification. Additional immunohistochemical studies were performed on 35 available specimens. The antibodies used were CD3, CD5, CD10, CD20, CD43, and bcl-6; and in a few cases cyclin D1, bcl-2, CD23, CD79a, and CD138. The main outcome measures were development of distant recurrence after new presentation with solely ocular adnexal disease, and death attributable to widespread lymphoma. Ocular adnexal lymphomas were found in orbit in 20 patients, in eyelid in two, and conjunctiva in two patients. Twenty patients had lymphoma stage IE, one had IIE, and three had stage IV. Three patients had prior or concurrent systemic disease and 21 patients had primary lymphoma. The main subtypes of non-Hodgkin lymphoma according to the WHO classification were extranodal marginal zone B-cell lymphoma (n=20), diffuse large cell B-cell lymphoma (n=2), mantle cell lymphoma (n=1), and plasmacytoma (n=1). Six lymphomas were CD43 positive and five of them were extranodal marginal zone B-cell lymphomas. Radiotherapy was given to 11 patients, chemotherapy in 8 patients, whereas radiotherapy and chemotherapy were implemented in three patients. Two patients underwent only surgical excision of the tumor. Local relapse was found in three and distant recurrence in four patients. Distant recurrence was found in four patients with stage IE (two of them also had a local relapse). In the group of patients with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (B-EMZL), the estimated 5-year overall survival was 92.9+/-6.6% (mean+/-standard deviation) and the 5-year failure-free survival was 80.1+/-10.3%. Age, sex, side of involvement, anatomic localization of the lesion, clinical stage of disease, and mode of therapy did not have any prognostic significance during the follow-up period (median, 53; range, 9-131 months). Immunohistochemical marker CD43 was the only parameter of prognostic significance (p=0.035). Patients with B-EMZL had almost 14 times higher chance for an unfavorable outcome if the tumor cells expressed CD43 on their surface, than the CD43-negative cases. Most ocular adnexal lymphomas usually have a B-cell immunophenotype, the morphologic and immunohistochemical features of extranodal marginal zone B-cell lymphoma, and a favorable prognosis. Our data suggest that CD43 could be useful to separate the group of patients with extranodal marginal zone B-cell lymphomas with unfavorable prognosis from those that have a good prognosis. CD43 positive ocular lymphomas are associated with a higher rate of subsequent distant recurrence and the rate of lymphoma-related death.
    Croatian Medical Journal 07/2004; 45(3):328-32. · 1.25 Impact Factor

Publication Stats

187 Citations
43.77 Total Impact Points

Institutions

  • 1997–2010
    • University Hospital Centre Zagreb
      • • Department of Obstetrics and Gynecology
      • • Division of Gynecologic and Perinatal Pathology
      Zagrabia, Grad Zagreb, Croatia
  • 2004–2008
    • University of Zagreb
      • Department of Pathology
      Zagreb, Grad Zagreb, Croatia