[Indeterminate cell histiocytosis - disappearance of skin infiltration following electron beam therapy and an application of 2-chlorodeoxyadenosine: case report]. / Histiocytóza z indeterminovaných bunek - vymizení kozní infiltrace po ozárení elektronovým svazkem a aplikace 2-chlorodeoxyadenozinu: kazuistika.

Indeterminate cell histiocytosis is a rare disease belonging to the group of malignant histiocytic diseases. The disease predominantly affects the skin. The disease appeared in the described patient at the age of 80 years. Morphs began to develop on the skin and rapidly spread over the whole body including the face. Only the hands and feet were left uncovered. The patients skin samples were taken from 2 sites for histological examination. The resulting conclusion was indeterminate cell histiocytosis. The treatment we chose was analogous to the procedures for Langerhans cell histiocytosis. We chose PUVA phototherapy as the first-line treatment. This treatment is frequently efficient for skin forms of Langerhans cell histiocytosis. In the described case, however, PUVA phototherapy did not influence the disease activity at all. As the second-line treatment, we used low-energy electron beam irradiation in the total dose of 36.2 Gy. This treatment had a positive impact, morphs began to diminish and slowly disappear from the skin. But they have not disappeared completely, therefore we assessed the treatment effect of the radiotherapy itself as partial remission of the disease. Within the third-line treatment, we used 2-chlorodeoxyadenosine in a dose of 5 mg/m2/per day, administered via subcutaneous injection over 5 consecutive days in monthly intervals. There were three cycles of this treatment administered overall. The treatment with 2-chlorodeoxyadenosine was tolerated without any adverse effects. The patient aged 82 years was only administered 3 cycles of 2-chlorodeoxyadenosine. When after the 3rd cycle the skin was free from any pathological morphs and only some pigmentation spots remained, we finished the treatment. The skin expressions of indeterminate cell histiocytosis completely disappeared after electron beam irradiation and the following administration of 3 cycles of 2-chlorodeoxyadenosine. The remission was short, however, after 6 months the disease recurred and the treatment is planned to resume. We assume the disease regresses following administration of 2-chlorodeoxyadenosine, but more than 3 treatment cycles will probably be needed to reach a longer-term response.Key words: electron beam irradiation - indeterminate cell histiocytosis - 2-chlorodeoxyadenosine.

Plasmacytoid dendritic cell proliferations and neoplasms involving the bone marrow : Summary of the workshop cases submitted to the 18th Meeting of the European Association for Haematopathology (EAHP) organized by the European Bone Marrow Working Group, Basel 2016.

Two distinct forms of neoplasms derived from plasmacytoid dendritic cells (PDC) exist: mature PDC proliferations associated with myeloid neoplasms and blastic PDC neoplasms (BPDCN). Ten cases of PDC proliferations and neoplasms in the bone marrow have been submitted to the bone marrow workshop held at the 18th EAHP meeting. Based on observations from the submitted cases, scattered PDC (≤1% of cells) and PDC aggregates (≤10 PDC/HPF) reflect the normal bone marrow composition, while in myelodysplastic syndromes (MDS), there is a propensity for larger/more PDC aggregates (1-5% and 35 PDC/HPF). A shared PTPN11 mutation between a mature PDC proliferation and an accompanying MDS provides evidence of clonal relationship in such instances and shows that PDC are a part of the malignant clone. CD123 and CD303 should be considered backbone markers to histopathologically establish the diagnosis of BPDCN, since they are detectable in almost all cases and properly well on biopsies subjected to different fixations. Expression of some T-cell markers (e.g., CD2 and CD7 but not CD3), B-cell markers (e.g., CD79a but not CD19 and CD20), and myeloid markers (e.g., CD33 and CD117 but not myeloperoxidase) can be observed in BPDCN. Genetical data of the summarized cases corroborate the important role of chromosomal losses in BPDCN. Together with five previously reported instances, one additional workshop case with MYC rearrangement proposes that translocations of MYC may be recurrent. The frequent nature of deleterious mutations of IKZF3 and deletions of IKZF1 suggests a role for the Ikaros family proteins in BPDCN.

Clinical outcome, PDGFRß and KIT expression in feline histiocytic disorders: a multicentre study.

Information about histiocytic disease in cats is limited. The aim of this study was to document clinical findings and outcome in feline histiocytic disorders, and characterize the expression of PDGFRß and KIT in order to identify potential treatment targets. Morphologically diagnosed feline histiocytic tumours were reviewed and characterized by immunohistochemistry (IHC). Five cases of feline progressive histiocytosis (FPH), eight histiocytic sarcomas (HS) and two haemophagocytic histiocytic sarcomas (HaeHS) were confirmed. PDGFRß was variably positive in most histiocytic cases, while KIT was negative in all. Clinical presentation, treatment and outcome were also evaluated. Partial responses were recorded in measurable disease with tyrosine kinase inhibitors and lomustine, and radiotherapy achieved long-term control in some cases. Survival times were shortest in HaeHS and disseminated disease. PDGFRß, but not KIT, may represent a therapeutic target in feline histiocytic disorders but more studies are needed to investigate other potential treatment targets.

Dendritic cell sarcoma: a pooled analysis including 462 cases with presentation of our case series.

Dendritic cell tumors are extremely rare and current knowledge on these tumors is limited. The characteristics of three dendritic cell sarcoma subtypes and their optimal treatment approaches are not fully clarified. We aimed to make a systematic review of the literature and enrich the current data with five new cases. Pooled analysis of 462 reported cases revealed that the tumor had no age, gender or racial predilection. Our analysis suggests that the young age, advanced stage, intraabdominal involvement and unfavorable histological features (i.e. large tumor size, absence of lymphoplasmacytic infiltration, coagulative necrosis, high mitotic count) may predict poor prognosis. Subtypes of this tumor have different clinical behaviors with interdigitating dendritic cell sarcoma being the most aggressive form. In general, surgery is the most effective treatment modality and adjuvant radiotherapy has no significant effect on overall survival of patients. The role of chemotherapy for the management of advanced disease is controversial.

CD137 is expressed in follicular dendritic cell tumors and in classical Hodgkin and T-cell lymphomas: diagnostic and therapeutic implications.

CD137 (also known as 4-1BB and TNFRSF9) is a member of the tumor necrosis factor receptor superfamily. Originally identified as a costimulatory molecule expressed by activated T cells and NK cells, CD137 is also expressed by follicular dendritic cells, monocytes, mast cells, granulocytes, and endothelial cells. Anti-CD137 immunotherapy has recently shown promise as a treatment for solid tumors and lymphoid malignancies in preclinical models. We defined the expression of CD137 protein in both normal and neoplastic hematolymphoid tissue. CD137 protein is expressed by follicular dendritic cells in the germinal center and scattered paracortical T cells, but not by normal germinal-center B cells, bone marrow progenitor cells, or maturing thymocytes. CD137 protein is expressed by a select group of hematolymphoid tumors, including classical Hodgkin lymphoma, T-cell and NK/T-cell lymphomas, and follicular dendritic cells neoplasms. CD137 is a novel diagnostic marker of these tumors and suggests a possible target for tumor-directed antibody therapy.

Histiocytic sarcoma - a case with evenly distributed multinucleated giant cells.

Histiocytic sarcoma is an uncommon neoplasm of mature histiocytes with a poor clinical outcome. We report a case of a true histiocytic sarcoma with prominent and evenly distributed multinucleated giant cells that mimics a giant cell tumor of soft tissue. The tumor was located between the appendix, right ovary, and the terminal ileum with severe adhesion. The liver and spleen were not enlarged. Grossly, the tumor appeared grayish white, solid, and soft. Microscopically, polygonal mononuclear tumor cells aggregated to form somewhat epithelioid nests, which occasionally showed coagulative necrosis. Prominent and evenly scattered giant cells were present in all sections. In addition, tumor cell infiltration was noted in regional lymph nodes. The tumor cells were positive for lysozyme, CD68, CD163, and negative for T- and B-cell lineage markers, follicular dendritic cell, megakaryocytic, epithelial, muscular, and melanocytic markers, CD1a and CD30. This case posed great difficulty in clinical and pathological diagnoses. Gross pictures, microscopic findings, and extensive immunostains are important for the differential diagnosis.

Primary central nervous system histiocytic sarcoma with relapse to mediastinum: a case report and review of the literature.

Histiocytic sarcoma is a rare, malignant neoplasm of the lymphohematopoietic system that usually occurs in the skin, lymph node, and intestinal tract. Here we describe a unique case of primary central nervous system histiocytic sarcoma that initially showed an indolent clinical course following local resection and radiotherapy. However, relapse of disease within the mediastinum was noted 3 1/2 years later. Biopsies of the initial brain lesion and subsequent mediastinal recurrence each revealed an identical, diffuse proliferation of histiocytes with expression of CD45, CD68, and CD163 but not pan-cytokeratin, epithelial membrane antigen, CD3, CD15, CD20, CD30, CD43, CD79a, CD138, myeloperoxidase, ALK-1, PAX-5, CAM 5.2, S100, CD1a, or glial fibrillary acidic protein. In the literature, central nervous system histiocytic sarcoma portends a poor prognosis with median survival of 4.5 months. To our knowledge, this case represents the first case of "low-grade" primary central nervous system histiocytic sarcoma with relatively indolent clinical course. A thorough discussion of the differential diagnosis of histiocytic sarcoma and a review of primary central nervous system histiocytic sarcoma are also presented.

Histiocyte disorders.

Histiocyte disorders are characterised by tissue infiltration with cells of monocyte/macrophage lineage, with two disorders, Langerhans' cell histiocytosis (LCH) and haemophagocytic lymphohistiocytosis (HLH) accounting for the overwhelming majority of cases in childhood and, apart from monocyte variants of acute myeloid leukaemia, histiocytic malignancy is very rare. Although both LCH and HLH are considered reactive disorders, the prognosis of these conditions differs greatly, LCH is usually self limiting, with a mortality of 10%, but HLH is usually fatal, with a mortality of over 80% in the absence of bone marrow transplantation. Increased levels of cytokines have been demonstrated in these disorders, and may be responsible for many of the clinical features: it is unclear whether histiocytes themselves, or other immune cells, particularly T lymphocytes, are the abnormal cell population. Due to the rarity of histiocyte disorders, collaborative studies are essential to improve understanding and advance treatment.

[The initial experience of using isolated ultrafiltration of the blood for the correction of severe respiratory failure in hemoblastosis patients]. / Pervyi opyt primeneniia izolirovannoi ul'trafil'tratsii krovi dlia korrektsii tiazheloi dykhatel'noi nedostatochnosti u bol'nykh gemoblastozami.

To correct acute respiratory failure in patients with hemoblastoses and taking into consideration the low efficacy of standard techniques, 8 operations of isolated ultrafiltration combined with low-flow extracorporeal oxygenation in 6 patients were performed. The first results have been analyzed. To attain the maximum positive result, it is recommended that the method may be included earlier in a complex of intensive therapy measures.