[Expression of transferrin receptor 1 and ß1-integrins correlates with estrogen receptor status and immune infiltration in breast cancer]. / Ekspressiya transferrinovykh retseptorov 1 i ß1-integrinov korreliruet so statusom retseptorov estrogenov i immunnoi infil'tratsiei pri rake molochnoi zhelezy.

Cancer cells can aberrantly express various markers, including transferrin receptor 1 (CD71) and ß1-integrin molecules. Their role in invasion, migration and metastasis has been demonstrated. Determination of their expression in breast cancer (BC) may be an important point to characterize the clinical course of the tumor and prognosis of the disease. OBJECTIVE: To study of transferrin receptor 1 (CD71) expression by primary breast cancer cells in correlation with tumor cell phenotype. MATERIAL AND METHODS: Determination of BC phenotype: immunohistochemical staining method (immunofluorescence). Antibodies to ER (estrogen receptors), KL-1 (pancytokeratin), CD71 (transferrin receptor), CD29 (ß1-integrins). CD45, CD3, CD4, CD8, CD20 infiltration was also evaluated. ZEISS microscope (AXIOSKOP; Germany), method of G.J. Hammerling et al. Statistical processing: IBM-SPSS Statistics v.21. RESULTS: 63% of BC cases had CD71+ phenotype. CD71-mosaic tumors were observed in 14.4%. ß1-integrin expression was monomorphic in 51.6% of cases and mosaic in 38.7%. 85% of ER-positive tumors were CD71-positive with a monomorphic type of reaction; p=0.014. Among ER-negative tumors, CD71-negative reactions were 2-fold more frequent and the monomorphic type was less frequent. ER-positive tumors were CD29-positive in 73%; p=0.031. 45.5% of ER+ tumors were CD29-monomorphic. Among ER-negative tumors, the frequency of CD29-monomorphic tumors was 55%. Significant infiltration by CD3+ cells was predominant in CD71-positive tumors; p=0.016. In the CD29-monomorphic phenotype, CD45+ infiltration was 31.3%, and in the mosaic phenotype, 67.1%. CONCLUSION: BC aberrantly expresses transferrin receptors, ß1-integrins. CD71 expression is associated with ER expression. ER-positive tumors are often monomorphic for CD71. Prominent CD3+ infiltration was present in CD71+ tumors. Expression of ß1-integrins correlated with ER+ status and weak immune infiltration.

[MALT-lymphomas in Sjogren's disease].

AIM: To develop algorithm of early diagnosis of extranodal lymphoma arising in patients with Sjorgen's disease (SD). MATERIAL AND METHODS: SD diagnosis was made in 457 patients treated in Rheumatology Institute clinic in 1999-2004, 38 (8.3%) females aged 19-82 had lymphoproliferative diseases. MALT-lymphomas were diagnosed in 15 (42.2%) patients. All the patients have undergone morphological, immunomorphological investigations of the salivary glands, postoperative material was analysed in some patients. In addition, the following investigations were made: ultrasonography of the salivary glands, lymph nodes, viscera; scintigraphy; trephine biopsy of the bone marrow; myelograms; CT of the chest, abdomena and brain; tests for monoclonal immunoglobulins in the serum and light chains in urine; biopsy of the parotid gland. Clinical, morphological and immunophenotypical characteristics of MALT-lymphomas were assessed by WHO classification. Lymphoma stages were classified according to Ann Arbor. RESULTS: Parotid glands were affected with MALT-lymphoma most frequently. Predominant were extranodal lymphomas of the parotid submandibular, minor salivary glands of the lip and lacrimal glands of stage I E-II E. Extranodal lymphoma with nodal lesion of stage IV occurred less frequently. Untreated long existing MALT-lymphomas of the parotid glands may transform into B-large cell lymphomas deteriorating SD prognosis. The presence of long-term (> 12 months) massive enlargement of parotid/submandibular salivary and lacrimal glands, massive infiltration, monoclonal immunoglobulins in blood serum and their light chains in the urine predict development of MALT-lymphoma in SD. CONCLUSION: In SD, MALT-lymphomas develop primarily in target organs--salivary and lacrimal glands. SD patients with persistent enlargement of the parotid glands need biopsy for early detection of malignant lymphoproliferation.

[Clinico-immunological characteristics of lymphoid tumors in children]. / Kliniko-immunomorfologicheskaia kharakteristika limfoidnykh opukholei u detei.

The clinical and immunological characteristics of lymphoid tumors were compared in 591 children with acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). Comprehensive investigation of a tumor cell by using cytological, morphological, and immunological studies revealed the most significant criteria for differential diagnosis of ALL and NHL in children and showed the specific features of the site of a tumor and the extent of its growth in ALL and NHL in relation to the immunological affiliation of a tumor cell. The predominance of immature forms, such as stem-cell CD34+, pre-pre-B, pre-B and less commonly T-cell forms with almost none peripheral B- and T-cell markers could be immunophenotypically detected in ALL. NHL was, on the contrary, characterized by the prevalence of mature immunological subtypes with peripheral B- and T-cell markers and much less frequently pre-B and pre-T cells and at the same time there was no CD34 antigen in the tumor cells. Anaplastic giant lymphoma was a peculiar type of NHL characterized by the presence of large cells having marked anaplasia and expression on the surface of CD30 antigen. A comprehensive study of lymphoid tumors in children showed that immunophenotyping was of great value, whose results were associated with the specific feature of tumor growth and prognosis, which should be borne in mind while planning antitumor therapy programmes.

[Mantle cell lymphoma]. / Limfoma iz kletok mantii.

Two morphological variants of mantle cell lymphoma are described: classic and blastoid. The former consists of small and medium-size cells, the latter is represented by cells with lympho- and centroblast morphology. An immunohistochemical examination has established a high degree of cyclic D1 expression by these lymphomas.

[MALT gastric lymphoma--principles of morphological diagnosis]. / MALT-limfoma zheludka--osnovy morfologicheskogo diagnoza.

MALT gastric lymphoma presents difficulties for morphological diagnosis as it is represented by neoplastic elements having morphology of mature cells. 75 MALT-lymphomas of the stomach with polymorphous tumour infiltrate are reported. The infiltrate was analyzed by cell composition, cell atypia, the presence of lymphoepithelial lesions (LEL) and lymphoid follicles, blast cells and "blast" LEL. Immunohistochemistry may be necessary for diagnosis when clear-cut morphological characteristics are lacking.

[Diagnosis of chronic lymphoid leukemia (an immunomorphological study)]. / K diagnostike khronicheskogo limfoleikoza (immunomorfologicheskoe issledovanie).

31 cases of chronic lymphoid leukemia (CLL)/lymphoma from small lymphocytes (LSL) was studied immunomorphologically. All cases had B-phenotype and positive expression of markers CD 5, CD 23. Most characteristic for CLL/LSL was pseudofollicular character of tumour growth. Two morphological variants of CLL/LSL having similar phenotype were distinguished: typical variant with roundish conturs of tumour cells and atypical with centrocytoid morphology of tumour cell nuclei.

[Epithelial membrane antigen in lymphosarcoma cells (immunomorphologic study)]. / Epitelial'nyi membrannyi antigen v kletkakh limfosarkom (immunomorfologicheskoe issledovanie).

11 cases of different types of lymphosarcoma of T- and B-nature are studied immunohistochemically by means of antibodies against epithelial membrane antigen (EMA), including new Soviet monoclonal antibodies ICO-25 to this antigen, common leucocytic antigen, vimentin and cytokeratin. The phenomenon of the EMA including ICO-25 binding to the cells of some lymphosarcomas is confirmed. This indicates that the use of only this "epithelial differentiation marker" in not sufficient for the differentiation between lymphosarcoma and poorly differentiated carcinoma. Variability of lymphosarcoma cells staining by vimentin antibodies is shown, other limitations of the immunohistochemical examination of lymphoma are discussed. The conclusion is made of the necessity to use the spectrum of the above antibodies when differentiating between lymphosarcoma and poorly differentiated carcinoma.

[Hodgkin lymphoma with lymphoid predominance: differential diagnosis of nodular lymphoid predominance and classical variant]. / Limfoma Hodzhkina s limfoidnym preobladaniem: differentsial'naia diagnostika noduliarnogo limfoidnogo preobladaniia i klassicheskogo varianta.

A topical problem of differential diagnosis of nodular lymphoid predominance of Hodgkin's lymphoma and classical variant rich in lymphocytes is discussed. Main morphological diagnostic criteria are considered on the basis of the authors' observations and literature data. Immunological characteristics of two variants of Hodgkin's lymphoma with lymphoid predominance are reviewed.

[Argyrophilic proteins of nucleolar organizers regions as markers of malignancy grade of anaplastic large-cell lymphoma and Hodgkin's lymphoma]. / Znachenie argirofil'nykh belkov oblastei iadryshkovykh organizatorov kak markerov stepeni zlokachestvennosti anaplasticheskoi krupnokletochnoi limfomy i limfomy Khodzhkina.

Expression of argyrophilic proteins of nucleolar organizers regions (Ag-NOR-proteins) was studied in tumor cells from 17 patients with a classic variant of anaplastic large-cell lymphoma (ALCL) and 22 patients with Hodgkin's lymphoma (HL). Eight cases of p80+ and nine cases of p80-ALCL were studied. HL was represented by 13 cases with lymphoid depletion by a reticular type and 9 cases with nodular sclerosis with a syncytial growth. Ag-NOR-proteins were identified using histochemical method with silver nitrate. The expression of Ag-NOR-proteins in tumor cells of ALCL and HL appeared intensive, being highest in ALCL cells, in p80+ cells of ALCL there was superexpression. The differences in expression of Ag-NOR-proteins point to different proliferative activity and growth of the above variants of ALCL and HL. The test for Ag-NOR-proteins expression can be recommended as an additional tool in differential diagnosis, determination of malignancy grade, assesssment of prognosis and sensitivity to chemotherapy.

[Aminopeptidases in cells of non-Hodgkin's lymphoma of varying degrees of malignancy and in lymphogranulomatosis]. / Aminopeptidazy v kletkakh nekhodzhkinskikh limfom raznoi stepeni zlokachestvennosti i pri limfogranulematoze.

26 cases of lymphoproliferative diseases were studied: 8 cases of reactive follicular hyperplasia (RFH), 11 cases of non-Hodgkin's malignant lymphomas (NML), 7 cases of lymphogranulomatosis (LGM). Only gamma-glutamyl transpeptidase (GGT) was found in lymphoid cells of B- and T-dependent areas of lymph nodes with reactive changes as well as in tumor cells of NML and LGM. GGT activity was more pronounced in NML of high-grade malignancy (centroblast and immunoblast) as compared to lymphomas of lower grade of malignancy (lymphocytic, centroblast-centrocytic and in Lennert lymphoma). GGT activity in cells of Hodgkin and Berezovsky-Sterberg in some cases of LGM was high, in others low. Significant differences in GGT activity between RFH and follicular centroblast-centrocytic lymphoma were not found. Activity of aminopeptidase M was observed in histiocytes, fibroblasts, vessels and areas of connective tissue growth. Aminopeptidase A activity was observed in vessels only. Activity of dipeptidyl(amino)peptidase IV was observed in some lymphoid cells in RFH, NML and LGM. Thus, GGT activity may be considered as a differential-diagnostic marker in separating NML of high and low degree of malignancy and this may presume a different sensitivity to the therapy.

[Lymphoproliferative diseases of the orbit and appendages of the eye]. / Limfoproliferativnye zabolevaniia orbity i pridatochnogo apparata glaza.

The results are available of clinical, morphological, cytological and immunological investigations of orbital lymphomas and lymphomas of appendages of the eye. Malignant lymphoma was detected in 17 patients and reactive lymphoid hyperplasia in 3 patients. All the malignant lymphomas had B-cell phenotype. By cell composition, MALT-lymphoma is more polymorphic than lymphoma from mantle zone cells and lymphoma from small lymphocytes and centro follicular lymphoma. The conjunctive is affected primarily with lymphoma from marginal zone cells or mantle zone cells. As a rule, this is a primary local lesion. Other variants of orbital lymphoma and lymphoma of the eye appendages develop more often as secondary lesions in systemic disease and are characterized by more aggressive course. The key in differential diagnosis of reactive lymphoid hyperplasia and small cells lymphomas is immunophenotyping, especially at initial stages of the tumor process.

[Nucleolar organizer as a marker of malignancy grade and prognosis of non-Hodgkin's malignant lymphoma]. / Iadryshkovyi organizator kak marker stepeni zlokachestvennosti i prognoza nekhodzhkinskikh zlokachestvennykh limfom.

There were 51 cases of non-Hodgkin's malignant lymphoma (NHL) and 9 cases of reactive follicular hyperplasia among 60 cases of lymphoproliferative conditions. According to the Kiel classification, lymphomas of a low grade of malignancy (17 cases) and lymphomas of a high grade of malignancy (34 cases) were distinguished among NML. Significantly higher activity of the nucleolar organizers (NO) was observed in lymphomas of a high malignancy grade, particularly in lymphomas formed of cells of early differentiation stages, and enhancement of NO activity with development of lymphoma aggression. "Anomalies" of NO activity expression reflecting clinical lymphoma presentation were noted among NML of various malignancy grade. NML with a high NO activity are described as having less favourable prognosis compared to lymphomas with low NO activity. No significant difference in NO activity was found between reactive follicular hyperplasia and follicular centroblast-centrocytic lymphoma. Thus, NO activity can be considered as an additional diagnostic marker of NML grade of malignancy and prognosis.

[Differential diagnosis of B-cell lymphoma rich in T cells and peripheral T-cell lymphomas]. / O differentsial'noi diagnostike B-kletochnoi limfomy, bogatoi T-kletkami, i perifericheskikh T-kletochnykh limfom.

Clinicomorphological analysis of T-cell-rich B-cell lymphoma in a 50-year-old female and literature data revealed objective difficulties in morphological diagnosis using cytological and histological methods. Large number of epithelioid histiocytes and tumor cells polymorphism resembled Lennert's lymphoma (peripheral T-cell lymphoma). Immunohistochemical study confirmed B-cell origin of tumor cells and large number of reactive T-cells. It is suggested that it would be more correctly to use the term "Lennert-like areas" in such cases with subsequent immunohistochemical study.

[Dipeptidyl aminopeptidase-IV as a histochemical marker of differential diagnosis of large cell anaplastic CD30+-lymphoma and Hodgkin's disease]. / Dipeptidilaminopeptidaza-IV kak gistokhimicheskii marker differentsial'noi diagnostiki krupnokletochnoi anaplasticheskoi CD30+-limfomy i limfogranulematoza.

Using histochemical methods, we studied distribution of dipeptidylaminopeptidase-IV (DPP-IV) in tumor cells of 16 patients with non-Hodgkin's malignant lymphomas (NHL) including B-cell NHL (10 cases), pleomorphic T-cell lymphoma (1 case), CD30+ anaplastic large cell lymphoma (ALCL) of T-cell (1 case) and ALCL of null-cell type (4 cases) and of 13 patients with Hodgkin's disease (HD). The results indicate that tumour cells of pleomorphic T-cell NHL and ALCL of T- and null-cell type showed DPP-IV activity. In contrast, no DPP-IV activity was seen in the tumor cells of B-cell NHL (lymphocytic, centroblastic/centrocytic, centroblastic, immunoblastic), in Berezovsky-Reed-Sternberg and Hodgkin's cells of different HD variants. These results demonstrate that difference in DPP-IV activity between tumor cells of ALCL and HD may be diagnostically important for separation of ALCL from HD and moreover may be used in verification of the borderline between HD-like ALCL and ALCL-like HD. It is possible that DPP-IV activity contributes to pathogenesis of ALCL and may determine clinical behaviour of this NHL being involved in autocrine and paracrine regulation of tumor cell growth of ALCL.

[Cytomorphological differentiation diagnosis and evaluation of p53mut, bcl-2, CD95 in peripheral B-cell small cell lymphomas]. / Tsitomorfologicheskaia differentsial'naia dignostika i otsenka p53mut, bcl-2, CD95 pri perifericheskikh B-kletochnykh melkokletochnykh limfomakh.

Basing on the analysis of the cytological evidence, the authors suggest criteria for differential diagnosis of peripheral small-cell B-cell lymphomas including position of the tumor cells in cytological preparations and cell composition of the tumor. A high level of p53mut and bcl-2 expression in centrofollicular lymphomas and lymphomas originating from small lymphocytes may serve an additional criterion in differential diagnosis with reactive changes in the lymph nodes.

[Morphological manifestations of large cell anaplastic Ki1(CD30)-positive lymphoma in children]. / Morfologicheskie proiavleniia krupnokletochnoi anaplazirovannoi Ki1 (CD30)-pozitivnoi limfomy u detei.

Classic morphological and lymphohistiocytic variant were found in 46 and 2 cases, respectively, of 49 LCAL cases studied pathohistologically. One patient had a variant with a predominance of small tumor cells. Ultrastructurally, cells with feature of histiocytic and lymphoid differentiation and undifferentiated cells in various proportions were observed.

[The prolymphocytic-lymphocytic leukemization of T-cell lymphosarcomas]. / Prolimfotsitarno-limfotsitarnaia leikemizatsiia T-kletochnykh limfosarkom.

The paper presents a detailed clinical, hematological, morphological, ultrastructural and immunological characterisation of T-cell lymphosarcoma with prolymphocytic-lymphocytic leukemic transformation (PLLT). In PLLT the proportion of T-cell immunological subvariant of lymphosarcoma came to 15% being detected only in 8 out of 52 examinees. The patients (6 males and 2 females) varied in age from 24 to 76 years (median 49 years) and had the following histological forms of primary tumor tissue: lymphoblastic lymphosarcoma (n = 3), pleiomorphic small cell lymphosarcoma (n = 1), large-cell anaplastic lymphosarcoma (n = 1), prolymphocytic lymphosarcoma. Immunological characteristics of these 8 cases were heterogeneous: in lymphoblastic variant there was immature T-immunological phenotype. In pleomorphic small-cell lymphosarcoma there were also signs of T-cell activation. In large-cell anaplastic lymphosarcoma an immunological phenotype of lymphoid cells from the primary tumor tissue and bone marrow differed in more advanced immunological differentiation of bone marrow tumor cells. In prolymphocytic variant tumor cells had features of T-helpers or T-suppressors. Most of the patients received polychemotherapy according to the schemes for high-grade lymphosarcomas despite PLLT though the latter is not a universal indicator of late tumor progression, more aggressive course of the disease and poor prognosis.

[The clinicoimmunological characteristics of blast transformation in lymphosarcomas]. / Kliniko-immunologicheskaia kharakteristika blastnoi transformatsii limfosarkom.

The authors studied a blast cell immunological phenotype in 50 adults with lymphosarcoma undergoing leukemization following the pattern of acute leukemia. Among the patients there were 12 females and 38 males aged 14-61. Immunological phenotyping of tumor cells was performed using a panel of monoclonal antibodies to T- and B-lymphocyte antigens, to myelomonocytic cells, some nonlinear and activation antigens. T, B and zero variants of blast cells were identified. Occasionally, blast cells carried nonlymphoid antigens and those corresponding to the common lymphosarcoma subvariant. Leukemization in the direction of lymphoblastic leukemia is associated with greater frequency of lymphosarcoma T subvariant (46%). B-cell and zero subvariants occurred in 28% and 20% of the patients, respectively. The number of complete remissions in the group of patients with T-cell subvariant was greater than in the group with B-cell subvariant. The survival in these two groups, however, was almost similar (median up to 8-12 months). Further studies into lymphoblastic leukemization immunophenotyping can help design programs of differentiated polychemotherapy.

[The prolymphocytic-lymphocytic leukemization of B-cell lymphosarcomas]. / Prolimfotsitarno-limfotsitarnaia leikemizatsiia B-kletochnykh limfosarkom.

The paper presents clinical, hematological, morphological and immunological characteristics of B-cell lymphosarcoma with prolymphocytic-lymphocytic type of leukemization in 50 adult patients (9 females and 41 males aged 29-86 years). In B-cell immunological subvariant of prolymphocytic-lymphocytic leukemization changes in the primary tumor always corresponded to prolymphocytic variant of lymphosarcoma. This distinguishes B-cell lymphosarcomas from previously described T-cellular ones in which the type of eventual leukemic changes did not always correspond to the kind of initial tumor. The presence or absence of prolymphocytes with split nuclei in bone marrow puncture samples was neither of clinical nor of prognostic significance. In leukemization of B-cell prolymphocytic lymphosarcoma from the cells with split nuclei or cells with different configuration of the nuclei, immunological phenotype typical for B-cell chronic lymphoid leukemia did not occur. In prolymphocytic lymphosarcoma from cells with round nuclei one-third of patients had immunological phenotype more typical for B-cell chronic lymphoid leukemia. However, among them were patients with aggressive course with predominant extranodal location of tumor and prolymphocytic type of leukemization. Tumor nodes in B-cell prolymphocytic lymphosarcomas, irrespective of leukemization morphological variant, proved rather resistant to therapy. A complete clinicohematological remission according to the international criteria occurred in 2 of 50 patients, only.

[Richter's syndrome: analysis of literature data and original observations]. / Sindrom Rikhtera: analiz dannykh literatury i sobstvennykh nabliudenii.

AIM: Review of literature data and original experience with Richter's syndrome. MATERIALS AND METHODS: 250 patients suffering from malignant lymphoproliferative diseases with blood and bone marrow lymphocytosis were observed. 8 (3.2%) of them developed diffuse large-cell lymphoma (criteria and classification of REAL). RESULTS: 5 of the above 8 patients demonstrated spontaneous regression of lymphocytosis. These cases may illustrate transformation (clonal progression) of one morphological variant of malignant non-Hodgkin's lymphoma into another one, more aggressive. For this rare variant of Richter's syndrome running with regression of lymphocytosis the term Richter-Lortolary syndrome is proposed. Lortolary was the first who revealed a decrease of lymphocytosis in Richter's syndrome. The studies of the genome structure, first of all, of immunoglobulin genes show that in Richter-Lortolary syndrome it is easier, to confirm monoclonality of the two tumors (lymphocytic and large-cell) than to reject it. However, the idea of transformation has not been confirmed morphologically yet. CONCLUSION: Development of diffuse large-cell lymphoma in the course of chronic lymphatic tumor does not always indicate terminal state, later stage of tumor progression and poor prognosis.