Diagnosis of Pediatric-Type Follicular Lymphoma in Young Adults (Own Data)

Aim. Pathomorphological, immunophenotypical and clinical characteristics of a new clinico-morphological form of pediatric-type follicular lymphoma (FL) in young adults discovered in 2008 (WHO classification). Background. FL is a heterogeneous disease according to its morphological, immunophenotypical and molecular-genetic characteristics. FL de novo includes transformed FL, FL without t(14;18), FL with diffuse growth associated with del(1p.36) and TNFRSF14 mutation. Pediatric-type FL in young adults is poorly studied; and it is especially interesting because of its clinical diversity and molecular-genetic heterogeneity of FL, in general. Methods. Biopsy materials taken from 5 patients (aged 18–25 years; median age: 22 years; the female/male ratio 3:2) were included in the study; all patients were examined, diagnosed and treated in the Hematology Research Center over the period from 2012 to 2016. Clinical stage I with isolated involvement a palatine tonsil or an inguinal lymph node was diagnosed in 4/5 patients; clinical stage II with involvement of a palatine tonsil and cervical lymph node was diagnosed in 1/5 patients. Morphological, immunophenotypical and FISH tests were performed with paraffin blocks. Results. The morphological pattern was typical for FL 3B (n = 2) and FL 3 with blastoid nucleus morphology (n = 3). Immunophenotypical features demonstrated an intermediate position between FL 3 de novo and transformed FL 3. No BCL-2 rearrangement was detected in any observation. Conclusion. The comparison of our data on characteristics of pediatric-type FL with those published in the literature demonstrated that lack or weak expression (< 30 % of tumor substrate cells) of MUM1 was the key feature of the experimental group of young adults with pediatric-type FL. This, in turn, indicates the absence of IRF4 rearrangements and possible presence of other genetic abnormalities. The clinical, morphological, and immunophenotypical characteristics broaden the FL heterogeneity spectrum in young adults

Stevens-Johnson Syndrome after Treatment of Female Patient with Small Lymphocytic B-Cell Lymphoma, Autoimmune Hemolytic Anemia and Antiphospholipid Antibody Syndrome with Rituximab

Stevens-Johnson syndrome is a severe delayed type systemic allergic reaction which affects the skin and mucous membranes. In adults, Stevens-Johnson syndrome is usually caused by the administration of drugs or a malignant process. The paper presents a case of Stevens-Johnson syndrome after the treatment of a female patient with small lymphocytic B-cell lymphoma, autoimmune hemolytic anemia and antiphospholipid antibody syndrome with rituximab. A rare combination of Stevens-Johnson syndrome and small lymphocytic B-cell lymphoma of small lymphocytes, as well as the development of severe delayed type systemic allergic reaction to introduction of rituximab are of special interest. A detailed medical history and the clinical manifestations of the disease allowed to diagnose Stevens-Johnson syndrome at early stages and prescribe an adequate therapy. As a result of the treatment, the patient’s condition has improved considerably. Symptoms of general toxicity were arrested completely; there was a complete epithelization of erosive defects. Therefore, the presented clinical observation shows that timely diagnosis, complex drug therapy, and comprehensive care can cure the diseases as soon as possible and prevent complications

Effectiveness of the Initial Escalation of Immunochemotherapy in Patients with High Risk MALT-Lymphoma: Pilot Study Results

Background. MALT-lymphoma is usually characterized with an indolent course. The factors underlying the effectiveness of the standard chemotherapy in patients with MALT-lymphomas include MALT-IPI risk group and a high SUVmax according to the results of positron emission tomography (PET). All well-known MALT-lymphoma risk factors indirectly indicate a high risk of transformation to large cell lymphoma. The search for an effective chemotherapy continues. Aim. To evaluate the effectiveness of the R-EPOCH/R-BAC escalated immunochemotherapy for MALT-lymphoma patients with poor prognosis factors. Materials & Methods. In the period of 2016–2017 the study included 5 female MALT-lymphoma patients (the mean age of 41 years), of which 1 patient had an early relapse after surgery and 4 patients were newly diagnosed. Prior to therapy 4 patients were evaluated with PET. The mean SUVmax was 10.04. According to MALT-IPI 2 patients belonged to a high-risk group and 3 belonged to a middle-risk group. All the patients received R-EPOCH/R-BAC regimen therapy. A month after completing the treatment all the patients were again evaluated with PET. Results. In 4 patients with 10–24 months follow-up complete remission was reported, which was confirmed by the results of histology and PET. The treatment of 1 patient was not completed. The immunotherapy was well tolerated by the patients. Hematological toxicity grade 3–4 occurred only after completing R-BAC treatment regimens. No severe infectious complications were reported. Conclusion. MALT-lymphoma patients need to be evaluated in terms of all prognostic factors to identify the high-risk patients for whom escalated therapy is to be used already in the first line treatment. This pilot study of the use of R-EPOCH/R-BAC for treatment of MALT-lymphoma patients with poor prognosis factors yielded positive results and showed its acceptable tolerance

Dermatological Toxicity of Hydroxycarbamide

Hydroxycarbamide is an antitumor agent mainly used for treatment of Ph-negative myeloproliferative disorders and sickle cell disease. The development of skin ulcers is a rare but serious adverse event in long-term antitumor therapy. Hydroxycarbamide-induced ulcers are often multiple and bilateral, and usually occur in the lower legs, although they can occur in other regions of the body. The ulcers are small-sized and shallow with sharp margins and yellow fibrine-covered base. They cause constant severe, difficult to treat pain which is a characteristic sign. The drug withdrawal usually leads to spontaneous healing of ulcers. Regular dermatologic screening must be obligatory for all the patients receiving hydroxycarbamide. The present paper provides a literature review on dermatological toxicity of hydroxycarbamide and a clinical case description

Primary Mediastinal (Thymic) Large B-Cell Lymphoma: Diagnostics of Extramediastinal Lesions and Treatment Opportunities

Background. Current diagnostic methods and the introduction of molecular investigations into clinical practice allow to improve the understanding of classical primary mediastinal (thymic) large B-cell lymphoma (PMBCL). Aim. To investigate clinical characteristics of PMBCL patients with extramediastinal lesions. Materials & Methods. The study was performed from 2007 to 2017 in the National Medical Hematology Research Center and included 157 PMBCL patients. The data of 16 (10.2 %; 4 men and 12 women) patients with extramediastinal lesions were analyzed; the median age was 27 years (range 23–69). Results. The extramediastinal lesions were found in pancreas (6; 37.5 %), kidneys (5; 31.2 %), ovaries (3; 18.7 %), liver (3; 18.7 %), bone marrow (3; 18.7 %), and breasts (2; 12 %); the lesions in stomach, bones, soft tissues, spleen, adrenals, and small pelvis were observed each in a single case. In 15 of 16 cases extramediastinal lesions were accompanied by involvement of superior mediastinum, and only 1 patient had an isolated lesion in thoracic soft tissues without mediastinal involvement. The samples of 8 out of 16 patients were analyzed using PCR. In all samples overexpression of 2 or more genes (JAK2, TRAF1, MAL, PDL1, PDL2) was determined which allowed to confirm, and in some cases to revise the diagnosis of PMBCL. Overall 5-year survival (93 %) of patients with classical PMBCL with thoracic involvement was similar to the cohort with extramediastinal lesions. All unfavourable events (progression/relapse) were identified at an early stage, i.e. within a year after the completion of therapy. Conclusion. PMBCL patients can have not only superior mediastinum involvement, but extramediastinal lesions as well, including bone marrow. The spreading of the disease beyond superior mediastinum should be differentiated from diffuse large B-cell lymphoma using standard evaluation methods, and molecular analysis in some cases

The Comparison of De Novo Grade 3 Follicular Lymphoma and Transformed Grade 3 Follicular Lymphoma: Own Data

Background. Grade 3 follicular lymphoma (FL) is a heterogenetic group of tumors. The selections of patients with similar characteristics of the tumor process is important for classification 3 grade forms of FL and risk stratification, as well as for the development of new therapeutic approaches. Different morphological, immunohistochemical and cytogenetical characteristics of the tumor result in different clinical forms of the disease. Aim. To describe the clinical, morphological, immunohistochemical and cytogenetical characteristics of grade 3 FL and evaluate their prognostic value for R-CHOP-21 chemotherapy. Materials & Methods. We performed retrospective and prospective analysis of morphological, immunohistochemical and genetical characteristics of 93 primary patients with grade 3 FL (21–78 years, median 53 years, women to men — 1:1.4) admitted to National Medical Hematology Research Center from years 2001 to 2016. Morphological and immunohistochemical assessment of the affected lymph nodes and bone marrow biopsy material was performed. Data obtained from the standard cytogenetic and FISH assessment were compared to identify the BCL2 rearrangement. Results. We proposed an algorithm for differential diagnosis of the 2 types of grade 3 FL: de novo FL (n = 22) and transformed FL (n = 21). De novo grade 3 FL had the immunophenotype of CD10– in 19 (86 %) cases, MUM1++ (monomorphically) in 19 (90 %), and BCL-2 in 5 (22 %). It was characterized by the absence of the BCL2 rearrangement (n = 22, 100 %) and bone marrow involvement (n = 14, 67 %) and/or bone marrow involvement (n = 7, 100 %). Third grade FL transformed from grades 1 or 2 had was CD10+ (n = 19, 90 %), MUM1+ (heterogeneously, n = 16, 76 %) or MUM1– (n = 4, 19 %), BCL-2+ (n = 20, 95 %) and had BCL2 rearrangement (n = 19, 90 %). Small cell bone marrow involvement was observed in 71 % of cases, whereas large cell involvement was seen predominantly in de novo FL (p = 0.06). The analysis showed that 5-year relapse-free survival in patients with grade 3 de novo FL after R-CHOP-21 therapy was 87 % compared to 16 % with transformed FL (p = 0.06) for the median 41 months of follow up. Conclusion. We described the morphological, immunohistochemical and cytogenetical characteristics of grade 3 de novo FL and grade 3 FL, transformed from grades 1 or 2. The described variants show different sensitivity to immunochemotherapy

A Case Report of Myeloid Sarcoma in a Child

The diagnosis of myeloid tumors is based on a complex approach and causes significant difficulties especially in young children. Morphologic, immunologic, cytogenetic, molecular and biologic data on myeloid sarcoma are presented based on the literature data and own clinical case. Treatment results of myeloid sarcoma (especially in the high risk group) are unsatisfactory and should be improved

Polycythemia Vera: New Diagnostic Concept and Its Types

Polycythemia vera (PV) is a clonal Ph-negative myeloproliferative disorder characterized by excessive myeloid proliferation of three hematopoietic cell lineages leading to ineffective myelopoiesis. According to WHO classification (2008), hemoglobin and hematocrit values are listed among the major diagnostic criteria. However, in many PV patients the levels may be below the diagnostic level, thus leading to underdiagnosis of PV. At present, three clinical types of the disease are recognized: 1) masked (latent/prodromal), 2) classic (overt), and 3) PV with progression/transformation into myelofibrosis. The masked form is most difficult for diagnosis, being highly heterogeneous with regard to clinical manifestations, laboratory data, medical history, and the course of the disease. It includes early stages, some of them with very high platelet count, imitating essential thrombocythemia, cases with abdominal thrombosis, and latent PV. Bone marrow trephine biopsy appears to be the most reliable method for diagnosis of masked PV. Findings typical for PV are readily visible, including hypercellular bone marrow with three-lineage myeloid proliferation, excess of megakaryocytes with mild to moderate cellular atypia and polymorphism. Gradi ng of reticulin fibrosis has impact on prognosis and reflects the risk of progression into myelofibrosis. In revised edition of WHO classification (2016), the typical bone marrow histopathology will be included among the major criteria for the diagnosis of PV, meaning that bone marrow trephine biops

Modern Aspects of Diagnosis and Treatment of Anaplastic Large Cell Lymphoma in Children (Literature Review)

Anaplastic large cell lymphoma (ALCL) includes different types of the disease that are heterogeneous according to clinical, morphological, immunological, cytogenetic and molecular biological features. The review demonstrates not only main clinical and morphoimmunological characteristics of ALCL, but also presents data about expression and prognostic significance of STAT3, pSTAT3tyr705, and survivin (transcription factor). It demonstrates the value of defining the minimal disseminated disease (the minimal disseminated disease is evaluated using the PCR test before initiation of the treatment, and the minimal residual disease is evaluated during the treatment and after its completion), and clinical and molecular biological prognostic factors are also identified. There is still no a standard therapeutic regimen for pediatric ALCL patients. However, the following therapeutic protocols are considered most effective: NHL-BFM 90/95, CCG5941, SFOP-LM 89/91, UKCCSG, ALCL99-Vinblastine, POG АРО 9315, AIEOP LNH-92/97. Treatment outcomes are presented in this paper. Particular attention is paid to different molecular biological markers that allow further improvement of patients’ stratification in risk groups and possible use of target medications (multikinase inhibitors and monoclonal antibodies) improving the therapy outcomes

Pathomorphological Diagnosis of Splenic Diffuse Red Pulp Small B-Cell Lymphoma

Background. Unclassifiable splenic B-cell lymphoma/leukemia is a rare and poorly studied disorder introduced in the WHO classification of hematopoietic and lymphoid tissue malignancies for the first time in 2008. This type of lymphoma requires differential diagnosing between hairy cell leukemia-variant (HCL-V) and splenic diffuse red pulp small B-cell lymphoma (SDRPL). Aim. To develop criteria for diagnosis of SDRPL by comparison of bone marrow biopsies (BMB) and surgical specimens of the spleen. Methods. In the Department of Morbid Anatomy of the Hematology Research Center, preoperative BMBs and surgical specimens of the spleen (2013–2015) were compared in 71 patients (men/women ratio 1:2.6, age range 44–81, median age 58 years) using morphological and extended immunohistochemical studies. Sanger sequencing and PCR assay were carried out to analyze the mutational status of IgHV and to identify mutations in MAP2K1, NOTCH, BRAF. Results. SDRPL was diagnosed in 5 (7 %) of 71 patients. In 2 groups of patients (with normal and high WBC count), the morphological features of spleen tissue were similar to those of a neoplastic substrate of HCL-V. The immunohistochemical assay demonstrates monomorphic expression of CD20 and DBA.44 and heterogeneous expression of CD11c, TRAP, CD103, CD123 in all cases. In none of the 5 cases, expression of CD25, CD27, Cyclin D1, Annexin-1 was found. In bone marrow (unlike HCL and HCL-V), predominantly interstitial and intravascular scant CD20+ lymphoid infiltration (4 of 5 cases) was found without detectable nucleoli in nuclei of small lymphoid cells. In 1 case, there was a combined lymphoid infiltration: CD20+ microfocal-interstitial infiltration with an intravascular component. No persistent molecular mutations in the spleen tissue specimens were found. Conclusion. SDRPL is diagnosed in 7 % of splenic B-cell lymphomas. It is a rare disorder, whose verification requires an integrated approach taking into account clinical and laboratory data, results of flow cytometry, cytological, morphological, extended IHC and molecular biological studies