Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages.

The histiocytoses are rare disorders characterized by the accumulation of macrophage, dendritic cell, or monocyte-derived cells in various tissues and organs of children and adults. More than 100 different subtypes have been described, with a wide range of clinical manifestations, presentations, and histologies. Since the first classification in 1987, a number of new findings regarding the cellular origins, molecular pathology, and clinical features of histiocytic disorders have been identified. We propose herein a revision of the classification of histiocytoses based on histology, phenotype, molecular alterations, and clinical and imaging characteristics. This revised classification system consists of 5 groups of diseases: (1) Langerhans-related, (2) cutaneous and mucocutaneous, and (3) malignant histiocytoses as well as (4) Rosai-Dorfman disease and (5) hemophagocytic lymphohistiocytosis and macrophage activation syndrome. Herein, we provide guidelines and recommendations for diagnoses of these disorders.

[Reactive and neoplastic histiocytic diseases in the dog]. / Reaktive und neoplastische histiozytäre erkrankungen beim hund.

There are different histiocytic diseases in dogs that are characterized by the proliferation of histiocytic cells (macrophages and myeloid dendritic cells). Histiocytic diseases can be devided into neoplastic (cutaneous histiocytoma complex, histiocytic sarcoma, dendritic cell leukaemia) and reactive forms (reactive histiocytosis, haemophagocytic syndrome). All subtypes of the cutaneous histiocytoma complex (cutaneous histiocytoma, metastatic histiocytoma and Langerhans' cell histiocytosis) are of Langerhans' cell origin. Histiocytoma, which is a solitary tumour of the skin in young dogs, shows spontaneous regression in most cases. Occasionally, metastasis to lymph nodes can be seen (metastatic histiocytoma). Only one dog with Langerhans' cell histiocytosis has been described and was euthanized. Histiocytic sarcoma, which arises from myeloid dendritic cells, can be classified as localised histiocytic sarcoma or disseminated histiocytic sarcoma. Another form of histiocytic sarcoma - haemophagocytic histiocytic sarcoma - is derived from macrophages. Histiocytic sarcoma displays a very aggressive clinical course and has a poor prognosis. Breed predispositions have been reported for the disseminated and haemophagocytic form of histiocytic sarcoma in Bernese mountain dogs, Rottweilers and varoiusretrievers. In contrast, reactive histiocytosis (cutaneous and systemic forms) develops by reactive proliferation of interstitial dendritic cells. In systemic histiocytosis, breed predilections are similar to histiocytic sarcoma. Haemophagocytic syndrome develops as a consequence of proliferation of activated macrophages in different tissues. Prognosis in general is moderate to poor and depends on the origin of the underlying disease process.

Update on the classification of T-cell lymphomas, Hodgkin lymphomas, and histiocytic/dendritic cell neoplasms.

Introduction: The classification of lymphomas is based on the postulated normal counterparts of lymphoid neoplasms and currently constitutes over 100 definite or provisional entities. As this number of entities implies, lymphomas show marked pathological, genetic, and clinical heterogeneity. Recent molecular findings have significantly advanced our understanding of lymphomas. Areas covered: The World Health Organization (WHO) classification of lymphoid neoplasms was updated in 2017. The present review summarizes the new findings that have been gained in the areas of mature T-cell neoplasms, Hodgkin lymphomas, and histiocytic/dendritic cell neoplasms since the publication of the 2017 WHO classification. Expert opinion: Although formal revisions to the WHO classification are published only periodically, our understanding of the pathologic, genetic, and clinical features of lymphoid neoplasms is constantly evolving, particularly in the age of -omics technologies and targeted therapeutics. Even in the relatively short time since the publication of the 2017 WHO classification, many significant findings have been identified in the entities covered in this review.

Histiocytic proliferations in childhood.

Histiocytic disorders occur with increased frequency in children and young adults. The wide spectrum of neoplastic and nonneoplastic diseases characterized by histiocytic proliferation was reflected in the cases submitted to the 2003 Society for Hematopathology and the European Association for Haematopathology Workshop. This review focuses on the entities represented at the workshop. It includes an overview of the classification and immunophenotype of the histiocytic disorders. The clinical and pathologic features of each entity are illustrated with representative cases submitted to the workshop, with an emphasis on recent biologic and genetic insights. In addition, a brief review of the pathologic features of the lysosomal storage disorders is included, with an emphasis on findings relevant to the practicing hematopathologist, exemplified with cases presented at the workshop.

[Histiocytic syndromes in childhood]. / Histiocytární syndromy v detském veku.

The authors submit an account of the new classification of histiocytic diseases in childhood, they mention contemporary views on their aetiology, pathogenesis, advances in diagnosis and therapy. The paper is supplemented by case-histories from the authors' own practice.

[Sarcoma consisting of dendritic reticular cells]. / Sarkoma iz dendriticheskikh retikuliarnykh kletok.

Sarcoma consisting of dendritic reticular cells is one of the histiocytic sarcoma variants. In the case reported sarcoma affected axillary lymph nodes in a 20-year-old male. The tumor was surgically removed but recurred 2 years after radiation and polychemotherapy. The recurrent tumor was also surgically removed. Histology of the primary and recurrent tumors was similar. The tumors were studied electron-microscopically and immunohistochemically.

[Fibrohistiocytic skin tumors]. / Fibrohistiozytäre Tumoren der Haut.

The fibrohistiocytic tumors of the skin are a heterogeneous group of dermal/subcutaneous mesenchymal neoplasms which show fibroblastic, myofibroblastic and histiocytic (macrophage-like) differentiation, often one beside the other in the same tumor. "Fibrohistiocytic" means in this context the morphologic similarity of the cells with fibroblasts and histiocytes. The WHO classification of 2005 includes the following entities as fibrohistiocytic tumors of the skin: BENIGN: 1. Fibrous histiocytoma (FH)/(synonymous: Dermatofibroma. Variants of FH: 1a. cellular fibrous histiocytoma, 1b. atypical (pseudosarcomatous) fibrous histiocytoma, 1c. aneurysmatic fibrous histiocytoma, 1d. epithelioid fibrous histiocytoma; 2. dermatomyofibroma; 3. (juvenile) xanthogranuloma. INTERMEDIATE: 4. plexiform fibrohistiocytic tumor; 5. dermatofibrosarcoma protuberans; 6. atypical Fibroxanthoma. MALIGNANT: 7. malignant fibrous histiocytoma. All these entities are reviewed in this paper with particular attention devoted to differential diagnostic considerations.

Malignant histiocytosis: a reassessment of cases formerly classified as histiocytic neoplasms and review of the literature.

Malignant histiocytosis (MH) and true histiocytic lymphoma (THL) are hematopoietic malignancies of the mononuclear phagocytic system distinguished from each other by clinical presentation and presumed cell of origin. THL present as a localized mass derived from the fixed tissue histiocyte which may or may not disseminate. MH originates from the circulating monocyte or tissue macrophage and is characterized by a syndrome of systemic symptoms, pancytopenia, adenopathy, hepatosplenomegaly, and wasting. The distinction between MH and THL is at times arbitrary and overlap exists between these syndromes. The clinicopathologic studies that defined these entities were performed prior to the development of immunophenotyping and other molecular techniques currently used to ensure proper classification of hematopoietic malignancies. Nine patients from the University of Minnesota originally diagnosed with MH were retrospectively analyzed using a panel of antibodies reactive against T cell, B cell, and myelomonocytic antigens. Only one patient was reclassified as a possible histiocytic malignancy after reevaluation. Similar immunophenotyping studies have also shown cases previously diagnosed as MH or THL express lymphoid antigens, and would now be classified as Ki-1 positive anaplastic large cell lymphoma (ALCL) or some other hematopoietic neoplasm. These results indicate true histiocytic neoplasms are extremely rare, and previous concepts concerning clinical presentation and therapeutic outcome of the entities are inaccurate. In this paper we summarize the results of multiple retrospective analyses of cases previously diagnosed as MH or THL, including our experience at University of Minnesota, to illustrate the overall rarity of these entities. The current literature on malignant histiocytic disorders is reviewed, and the clinical presentation of patients determined to have histiocytic malignancies using contemporary analytical techniques is discussed.

Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases.

Neoplasms of histiocytes and dendritic cells are rare, and their phenotypic and biological definition is incomplete. Seeking to identify antigens detectable in paraffin-embedded sections that might allow a more complete, rational immunophenotypic classification of histiocytic/dendritic cell neoplasms, the International Lymphoma Study Group (ILSG) stained 61 tumours of suspected histiocytic/dendritic cell type with a panel of 15 antibodies including those reactive with histiocytes (CD68, lysozyme (LYS)), Langerhans cells (CD1a), follicular dendritic cells (FDC: CD21, CD35) and S100 protein. This analysis revealed that 57 cases (93%) fit into four major immunophenotypic groups (one histiocytic and three dendritic cell types) utilizing six markers: CD68, LYS, CD1a, S100, CD21, and CD35. The four (7%) unclassified cases were further classifiable into the above four groups using additional morphological and ultrastructural features. The four groups then included: (i) histiocytic sarcoma (n=18) with the following phenotype: CD68 (100%), LYS (94%), CD1a (0%), S100 (33%), CD21/35 (0%). The median age was 46 years. Presentation was predominantly extranodal (72%) with high mortality (58% dead of disease (DOD)). Three had systemic involvement consistent with 'malignant histiocytosis'; (ii) Langerhans cell tumour (LCT) (n=26) which expressed: CD68 (96%), LYS (42%), CD1a (100%), S100 (100%), CD21/35 (0%). There were two morphological variants: cytologically typical (n=17) designated LCT; and cytologically malignant (n=9) designated Langerhans cell sarcoma (LCS). The LCS were often not easily recognized morphologically as LC-derived, but were diagnosed based on CD1a staining. LCT and LCS differed in median age (33 versus 41 years), male:female ratio (3.7:1 versus 1:2), and death rate (31% versus 50% DOD). Four LCT patients had systemic involvement typical of Letterer-Siwe disease; (iii) follicular dendritic cell tumour/sarcoma (FDCT) (n=13) which expressed: CD68 (54%), LYS (8%), CD1a (0%), S100 (16%), FDC markers CD21/35 (100%), EMA (40%). These patients were adults (median age 65 years) with predominantly localized nodal disease (75%) and low mortality (9% DOD); (iv) interdigitating dendritic cell tumour/sarcoma (IDCT) (n=4) which expressed: CD68 (50%), LYS (25%), CD1a (0%), S100 (100%), CD21/35 (0%). The patients were adults (median 71 years) with localized nodal disease (75%) without mortality (0% DOD). In conclusion, definitive immunophenotypic classification of histiocytic and accessory cell neoplasms into four categories was possible in 93% of the cases using six antigens detected in paraffin-embedded sections. Exceptional cases (7%) were resolvable when added morphological and ultrastructural features were considered. We propose a classification combining immunophenotype and morphology with five categories, including Langerhans cell sarcoma. This simplified scheme is practical for everyday diagnostic use and should provide a framework for additional investigation of these unusual neoplasms.

Regressing atypical histiocytosis: report of two cases with progression to high grade T-cell non-Hodgkin's lymphoma.

Two cases of regressing atypical histiocytosis (RAH) are presented. Both patients followed a typical regressing/relapsing course for several years before progression to high-grade neoplasia. In both cases these high-grade tumors were diagnosed as T-cell non-Hodgkin's lymphoma on histopathologic and immunophenotypic grounds, and demonstrated T-cell receptor beta chain (TCR beta) gene rearrangement on Southern blotting. The original cases of RAH were considered to be indolent neoplasms of histiocytic lineage. A single case of a patient with RAH demonstrating TCR beta and gamma gene rearrangements has been described. Our cases lend further weight to the proposition that RAH is a neoplasm of T-cell lineage, and ultimately of aggressive potential. This description accords with current thinking that many of the conditions previously classified as malignant histiocytosis would be better classified as T-cell non-Hodgkin's lymphoma.