pathomorphology

Correlation of the Number of TGFβF1-Expressing Atypical Megakaryocytes with the Degree of Bone Marrow Stroma Fibrosis and Osteosclerosis in Patients with Essential Thrombocythemia and Different Stages of Primary Myelofibrosis

AUTOIMMUNE THROMBOCYTOPENIA , ,

DI Chebotarev, AM Kovrigina, AL Melikyan

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Dmitrii Ilich Chebotarev, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(916)091-27-09; e-mail: chebadmitry@gmail.com

For citation: Chebotarev DI, Kovrigina AM, Melikyan AL. Correlation of the Number of TGFβF1-Expressing Atypical Megakaryocytes with the Degree of Bone Marrow Stroma Fibrosis and Osteosclerosis in Patients with Essential Thrombocythemia and Different Stages of Primary Myelofibrosis. Clinical oncohematology. 2022;15(1):76–84. (In Russ).

DOI: 10.21320/2500-2139-2022-15-1-76-84

ABSTRACT

Background. As morphological pattern of bone marrow (BM) biopsy samples at advanced stages of clonal evolution in essential thrombocythemia (ET) appears similar to that in the development of post-thrombocythemic myelofibrosis and primary myelofibrosis (PMF), the expression of fibrogenesis factors by atypical megakaryocytes (MKC) acquires increased interest.

Aim. To study the expression of the transforming growth factor TGFβF1 by atypical MKC; to relate the number of TGFβF1-positive MKCs with the degree of BM stroma fibrosis and trabecular bone changes in patients with ET and different PMF stages.

Materials & Methods. BM biopsy samples of ET and PMF patients, obtained before cytoreductive therapy, were subjected to histochemical study with Gomori stain and Masson trichrome as well as to CD42b and TGFβF1 antibody immunohistochemical assays. The degree of myelofibrosis and osteosclerosis was estimated by semi-quantitative method in accordance with the European Consensus guidelines. The morphological characteristics of atypical MKC included the comparative evaluation of nuclear-cytoplasmic ratio.

Results. The number of MKCs with high nuclear-cytoplasmic ratio was significantly higher in BM biopsy samples of patients with pre-fibrosis/early PMF (pre-PMF) stage and fibrosis stage of PMF (f-PMF) compared with BM biopsy samples of ET patients. The analysis of TGFβF1 expression showed different numbers of positive MKCs in the study groups. The matching of the number of TGFβF1-positive MKCs with the degree of myelofibrosis and osteosclerosis, with no regard to nosologic entities, revealed significant moderate correlation between these features (r = 0.431, p = 0.001 и r = 0.499, p = 0.001, respectively). In 55 % of pre-PMF patients’ BM biopsy samples, histochemical study with Masson trichrome stain visualized minimal immature osteoid deposits on bone trabeculae. Similar changes were also identified in f-PMF patients’ BM biopsy samples, whereas the ET patients’ samples featured none of them.

Conclusion. The results of the study prove that the pathological clone of MKC with TGFβF1 expression affects myelofibrosis and osteosclerosis processes whose manifestation in BM biopsy samples is associated with the number of TGFβF1-expressing atypical MKCs.

Keywords: primary myelofibrosis, pre-fibrosis and fibrosis stages, essential thrombocythemia, osteosclerosis, TGFβF1, pathomorphology, immunohistochemistry.

Received: August 12, 2021

Accepted: November 30, 2021

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Статистика Plumx английский

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    [Chebotarev DI, Kovrigina AM, Melikyan AL, Kuzmina LA. Comparative characteristics of bone marrow cell composition, stroma, and trabecular bone in allogenic hematopoietic stem cell transplantation in patients with primary myelofibrosis. Russian journal of hematology and transfusiology. 2021;66(1):68–78. doi: 10.35754/0234-5730-2021-66-1-68-78. (In Russ)]
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Overt and Masked Polycythemia Vera Within the Scope of Ph-Negative Myeloproliferative Diseases

AUTOIMMUNE THROMBOCYTOPENIA

ZhV Tratsevskaya, AM Kovrigina, DI Chebotarev, AL Melikyan, AO Abdullaev, AB Sudarikov

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Prof. Alla Mikhailovna Kovrigina, PhD in Biology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-61-12; e-mail: kovrigina.alla@gmail.com

For citation: Tratsevskaya ZhV, Kovrigina AM, Chebotarev DI, et al. Overt and Masked Polycythemia Vera Within the Scope of Ph-negative Myeloproliferative Diseases. Clinical oncohematology. 2020;13(1):58–66 (In Russ).

DOI: 10.21320/2500-2139-2020-13-1-58-66

ABSTRACT

Aim. To study the structure of Ph-negative myeloproliferative diseases (Ph– MPD) and to identify morphological markers for diagnosing masked polycythemia vera (PV).

Materials & Methods. Bone marrow core biopsy samples from the database of pathology department of National Research Center for Hematology within the period from January 2014 to June 2017 provided the basis for analyzing the diagnosed Ph– MPD cases. The trial included the bone marrow core biopsy samples of the patients treated and followed-up not only at the National Research Center for Hematology but also at other medical centers in the Russian Federation in the context of clinical, laboratory and molecular data.

Results. In 1611 Ph– MPD patients PV prevailed corresponding to 40.6 % of all cases. In the PV group the masked form was diagnosed in 29 % of patients. Primary myelofibrosis (PMF) was diagnosed in 26.6 % of all patients including 10 % of cases with pre-fibrosis/early stage. The 3d most frequent disorder was essential thrombocythemia (ET) which corresponded to 16 %. JAK2 driver mutation was identified in all 654 PV patients. In 4 cases out of them exon 12 mutation was detected. A similar mutation was found out in PMF (53 %) and ET (60 %). In 36 % of PMF patients and 27 % of ET patients CALR mutation was detected. MPL mutation was identified in 4 % of PMF cases and was not discovered in ET. Triple negative patients were identified in 7 % of PMF and 13 % of ET cases. The designation of “myeloproliferative disease unclassifiable” can be applied to 16.8 % of cases. The trial deals with morphological criteria for diagnosing masked PV during examination of bone marrow core biopsy samples. In 30 % of patients with masked PV (according to the 2017 WHO classification) and splenomegaly (> 14 cm) portal vein thrombosis was identified.

Conclusion. In the Ph– MPD group PV diagnosis prevailed (40.6 %). The histological analysis of bone marrow core biopsy samples of the patients with the masked PV accounting for 29 % of all PV cases, revealed morphological features typical of overt PV. Histological analysis of bone marrow is a reliable method for diagnosing overt and masked PV. Among morphological characteristics of the bone marrow of patients with masked PV and portal vein thrombosis special attention should be paid to the MF-1 grade of reticulin fibrosis (29 % of cases) and loose clusters of megakaryocytes (71.4 %).

Keywords: Ph-negative myeloproliferative disease/neoplasms, masked polycythemia vera, pathomorphology, bone marrow core biopsy.

Received: September 14, 2019

Accepted: December 12, 2019

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    [Kovrigina AM, Baikov VV. Polycythemia Vera: New Diagnostic Concept and Its Types. Clinical oncohematology. 2016;9(2):115–22. doi: 10.21320/2500-2139-2016-9-2-115-122. (In Russ)]

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

LYMPHOID TUMORS , , , , ,

AM Kovrigina, LV Plastinina, SK Kravchenko, ES Nesterova, TN Obukhova

Hematology Research Center under the Ministry of Health of the Russian Federation, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Alla Mikhailovna Kovrigina, DSci, Professor, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel: +7(495)612-62-12; e-mail: kovrigina.alla@gmail.com

For citation: Kovrigina AM, Plastinina LV, Kravchenko SK, et al. Diagnosis of Pediatric-Type Follicular Lymphoma in Young Adults (Own Data). Clinical oncohematology. 2017;10(1):52–60 (In Russ).

DOI: 10.21320/2500-2139-2017-10-1-52-60

ABSTRACT

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.

Keywords: pediatric-type follicular lymphoma, follicular lymphoma, young adults, pathomorphology, immunohictochemistry, MUM1.

Received: August 14, 2016

Accepted: November 27, 2016

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Principles of Pathomorphological Differential Diagnosis of Myelodysplastic Syndromes

MYELOID TUMORS , , ,

AM Kovrigina1, SA Glinkina1, VV Baikov2

1 Hematology Research Center, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

2 R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022

For correspondence: Alla Mikhailovna Kovrigina, PhD, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-61-12; e-mail: kovrigina.alla@gmail.com

For citation: Kovrigina AM, Glinkina SA, Baikov VV. Principles of Pathomorphological Differential Diagnosis of Myelodysplastic Syndromes. Clinical oncohematology. 2015;8(1):62–8 (In Russ).

ABSTRACT

The article dwells on the diagnosis of myelodysplastic syndromes (MDS) in bone marrow trephine biopsies. The paper describes problems of a complex approach to differential diagnostics of MDS and non-clonal/reactive changes in hematopoiesis. It is emphasized that clinical and laboratory data, as well as data on patient’s medical history should be submitted to a pathologist. The authors substantiate the algorithm for the morphological investigation of a bone marrow trephine bioptate, including evaluation of cellularity, stromal patterns, and morphological signs of dysplasia. The diagnostic value of histochemistry and immunohistochemistry is discussed.

Keywords: myelodysplastic syndrome, bone marrow trephine biopsy, pathomorphology, differential diagnostics.

Received: October 22, 2014

Accepted: November 10, 2014

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