Overview of histiocytic and dendritic disorders by the 5th version of WHO Classifi cation of Hematolymphoid Tumours from 2022.

BACKGROUND: Histiocytoses are rare disorders characterized by the accumulation of macrophages, dendritic cells, or monocyte-derived cells in various tissues and organs of children and adults, with a wide range of clinical manifestations, presentations, and histology. The histiocytoses are classified according to the WHO Classification, the last version of which was published in 2022, or according to the Histiocyte Society Classification, with the last version published in 2016. PURPOSE: This text provides an overview of histiocytoses as described in the WHO Classification 2022.

[Histiocytoses: General classification and molecular criteria]. / Classification histologique et altérations moléculaires des histiocytoses.

Histiocytoses are rare and heterogeneous disease sharing histology, characterized by accumulation of histiocytes. They may be inherited or sporadic, and related to the accumulation of endo- or exogenous material in macrophages or to macrophage activation. Recent discoveries have shown that some histiocytoses, such as Langerhans cell histiocytosis or Erdheim-Chester disease, previously considered as idiopathic or inflammatory were clonal myeloid proliferations. This review presents the general classification of histiocytoses, and describes diagnostic and molecular criteria of idiopathic histiocytoses and histiocytic neoplasms.

[Histiocytic diseases in childhood and adolescence]. / Histiozytäre Erkrankung des Kindes- und Jugendalters.

Histiocytic diseases are generally rare with a variable clinical course and variable morphology which often have a peak frequency of occurrence in childhood and adolescence. Histiocytoses are subdivided into Langerhans cell histiocytosis and the so-called non-Langerhans cell histiocytosis, such as juvenile xanthogranuloma, Erdheim-Chester disease and Rosai-Dorfman disease. The most common forms of histiocytosis in childhood are Langerhans cell histiocytosis and juvenile xanthogranuloma. In contrast, forms of histiocytosis which occur more frequently in adulthood, such as Erdheim-Chester disease and Rosai-Dorfman disease are rare in childhood. Some forms of histiocytosis harbor BRAFv600E mutations. In Langerhans cell histiocytosis they have been found in 50-55 % of the cases examined and in Erdheim-Chester disease in up to 100 % of cases. In the remaining forms of histiocytosis (especially juvenile xanthogranuloma and Rosai-Dorfman disease) BRAF mutations could not be detected. A prognostic relevance could not be shown so far; however, in individual cases a mutation analysis of BRAF could provide help in the differential diagnostic considerations or the option of a therapy approach with BRAF inhibitors.

Cytophagic histiocytic panniculitis in a 74-year-old man.

Cytophagic histiocytic panniculitis is a chronic histiocytic disease of the subcutaneous adipose tissue characterised by lobular panniculitis with histiocytes containing blood cell fragments. It is also associated with marked systemic features such as fever, pancytopenia, hepatosplenomegaly, liver abnormalities and coagulopathy. We report a case of cytophagic histiocytic panniculitis in a 74-year-old man successfully treated using combination therapy with prednisolone and cyclosporine A.

Crystal-storing histiocytosis: report of a case, review of the literature (80 cases) and a proposed classification.

We report a case of crystal storing histiocytosis (CSH) of the upper lip and cheek in a 51-year-old woman and review the clinicopathologic features of 80 cases in the literature. These occurred in 41 men and 39 women with a respective mean age of 59 and 61 years (range 17-81 years). Forty-six patients (58%) had localized CSH, and, of these, 16 (35%) occurred in the head and neck, with the most common site being the eye/orbit. The remaining 34 patients (42%) had generalized CSH primarily involving bone marrow, liver, lymph nodes, spleen and/or kidney. Regardless of whether the CSH was localized or generalized, the vast majority of patients (90%) had an underlying lymphoproliferative or plasma cell disorder, especially multiple myeloma, lymphoplasmacytic lymphoma, or monoclonal gammopathy of undetermined significance. In 7 cases (8.8%), the CSH was associated with a variety of benign disorders, often with an inflammatory background, and no evidence of a clonal lymphoproliferative or plasma cell disorder. Treatment and prognosis varied according to the underlying disease. A classification of CSH based on etiology and/or associated disease and chemical composition of the crystal is proposed, rare non-immunoglobulin variants of CSH are discussed, and a differential diagnosis of other potentially confusing lesions is provided.

[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.

Langerhans cell histiocytosis: a review of the current recommendations of the Histiocyte Society.

Langerhans cell histiocytosis is a rare proliferative disorder where pathologic Langerhans cells accumulate in a variety of organs. Historically, the nomenclature regarding this entity has been confusing because the disease had been subcategorized simply based upon the different clinical manifestations. In the following article, we summarize the current recommendation of the Histiocyte Society regarding the classification, evaluation, prognosis, and treatment of Langerhans cell histiocytosis.

Diagnósticos diferenciales de la histiocitosis a células de Langerhans / The differential diagnostics of Langerhans cell histiocytosis

La histiocitosis a células de Langerhans (HCL) debe diferenciarse de las siguientes entidades: eritema tóxico neonatorum (ETN), dermatitis seborreica (DS), foliculitis pustulosa eosinofílica (FPE), incontinencia pigmenti (IP), mastocitosis/urticaria pigmentosa (M/UP), acrodermatitis enteropática (ADE), síndrome de Wiskott-Aldrich (WAS), acropustulosis infantil (API). Además se deben considerar la enfermedad de Rosai- Dorfman (ERD), xantomas diseminados, melanosis pustulosa neonatal (MPN), candidiasis congénita, listeriosis neonatal, herpes simple perinatal y la varicela neonatal. Debido a que los métodos auxiliares de laboratorio no siempre están disponibles o los resultados laboratoriales algunas veces son extemporáneos, y puesto que el médico práctico a menudo necesita tomar decisiones precozmente, es que la epidemiología resulta útil, pues brinda el marco adecuado para ordenar y jerarquizar las sospechas diagnósticas frente a un caso concreto, con un paciente determinado, en un momento específico.

The differential diagnostics of Langerhans cell histiocytosis should include the following disorders: erythema toxicum neonatorum, seborrheic dermatitis, eosinophilic pustular folliculitis, incontinentia pigmenti, mastocytosis / urticaria pigmentosa, acrodermatitis enteropathica, Wiskott-Aldrich syndrome, infantile acropustulosis, Rosai- Dorfman disease, xanthoma disseminatum, neonatal pustular melanosis, congenital candidiasis, perinatal listeriosis, perinatal herpes simplex, neonatal varicella. Since the auxiliary methods of lab are not always available, or lab results are sometimes extemporaneous, the physicians often needs to make quick decisions. The epidemiology is useful because it offers the appropriate mark to prioritize the diagnostic in specific cases.

Aggressive histiocytic disorders that can involve the skin.

Histiocytoses are a heterogeneous group of disorders that are characterized by the proliferation and accumulation of reactive or neoplastic histiocytes. Three classes of histiocytoses have been defined: class I, Langerhans cell disease; class II, non-Langerhans cell histiocytic disease without features of malignancy; and class III, malignant histiocytic disorders. Although the disorders in classes I and II usually have a benign appearance on histology and are commonly non-aggressive and self-healing, some can cause debilitating or even fatal outcomes. Such cases beg the question: what stimulates aggressive behavior of a classically benign disease? New molecular information may now provide insight into the driving force behind many of the aggressive histiocytoses. In this article, we review Langerhans cell disease and seven aggressive histiocytoses that can involve skin, discuss histologic features that may forecast a poor prognosis, and discuss the molecular findings that help to explain the pathophysiology of these aggressive histiocytic disorders.

Síndrome hemofagocítico secundario en pediatría: experiencia clínica en ocho casos / Pediatric secondary hemophagocytic síndrome: clinical report of eight cases

El Síndrome hemofagocítico secundario (SHS) es una entidad poco frecuente caracterizada por activación macrofágica asociada a infecciones, inmunodeficiencias o neoplasia, pudiendo presentarse como un cuadro grave y de alta letalidad. El objetivo de este estudio es describir las características clínicas de un grupo de pacientes con SHS y su evolución en relación a los tratamientos utilizados. Pacientes y Método: Análisis retrospectivo de 8 casos de SHS diagnosticados en 3 años. Resultados: Edad promedio de 6 años. Los diagnósticos de base fueron: Neoplasia (3), Artritis reumatoidea (2), Síndrome de Down (1) y 2 pacientes sin patología asociada. En todos se asoció a infecciones, documentándose agente etiológico en 4 de ellos (adenovirus, Mycoplasma pneumoniae, Streptococo viridans y Pseudomona aeruginosa). Seis pacientes recibieron gammaglobulina EV y Metilprednisolona además de los antibióticos. Fallece 1 paciente. Comentario: La sospecha precoz del SHS y el inicio de tratamiento inmunomodulador se asociaron en esta serie a respuesta favorable y menor mortalidad.

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.

Síndromes histiocíticos en Pediatría: a propósito de un caso / Histiocytic syndromes in pediatry: apropos of a case

Las histiocitosis son un grupo heterogéneo de enfermedades unidas débilmente por características microscópicas y con una terminología que se sobrepone. Muchos de los desórdenes histiocíticos tienen su inicio en la infancia o niñez. Esta revisión se enfocará en estos síndromes histiocíticos de la infancia.