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Nature Reviews. Disease Primers Oct 2021The historic term 'histiocytosis' meaning 'tissue cell' is used as a unifying concept for diseases characterized by pathogenic myeloid cells that share histological... (Review)
Review
The historic term 'histiocytosis' meaning 'tissue cell' is used as a unifying concept for diseases characterized by pathogenic myeloid cells that share histological features with macrophages or dendritic cells. These cells may arise from the embryonic yolk sac, fetal liver or postnatal bone marrow. Prior classification schemes align disease designation with terminal phenotype: for example, Langerhans cell histiocytosis (LCH) shares CD207 antigen with physiological epidermal Langerhans cells. LCH, Erdheim-Chester disease (ECD), juvenile xanthogranuloma (JXG) and Rosai-Dorfman disease (RDD) are all characterized by pathological ERK activation driven by activating somatic mutations in MAPK pathway genes. The title of this Primer (Histiocytic disorders) was chosen to differentiate the above diseases from Langerhans cell sarcoma and malignant histiocytosis, which are hyperproliferative lesions typical of cancer. By comparison LCH, ECD, RDD and JXG share some features of malignant cells including activating MAPK pathway mutations, but are not hyperproliferative. 'Inflammatory myeloproliferative neoplasm' may be a more precise nomenclature. By contrast, haemophagocytic lymphohistiocytosis is associated with macrophage activation and extreme inflammation, and represents a syndrome of immune dysregulation. These diseases affect children and adults in varying proportions depending on which of the entities is involved.
Topics: Erdheim-Chester Disease; Histiocytosis, Langerhans-Cell; Histiocytosis, Sinus; Humans; Inflammation; Xanthogranuloma, Juvenile
PubMed: 34620874
DOI: 10.1038/s41572-021-00307-9 -
Cancers Oct 2022Rosai-Dorfman disease (RDD) is a rare myeloproliferative disorder of histiocytes with a broad spectrum of clinical manifestations and peculiar morphologic features... (Review)
Review
Rosai-Dorfman disease (RDD) is a rare myeloproliferative disorder of histiocytes with a broad spectrum of clinical manifestations and peculiar morphologic features (accumulation of histiocytes with emperipolesis). Typically, the patient with RDD shows bilateral painless, massive cervical lymphadenopathy associated with B symptoms. Approximately 43% of patients presented with extranodal involvement. According to the 2016 revised histiocytosis classification, RDD belongs to the R group, including familial and sporadic form (classical nodal, extranodal, unclassified, or RDD associated with neoplasia or immune disease). Sporadic RDD is often self-limited. Most RDD needs only local therapies. Nevertheless, a small subpopulation of patients may be refractory to conventional therapy and die of the disease. Recent studies consider RDD a clonal neoplastic process, as approximately 1/3 of these patients harbor gene mutations involving the MAPK/ERK pathway, e.g., , , , and, rarely, the mutation. In addition to typical histiocytic markers (S100/fascin/CD68/CD163, etc.), recent studies show that the histiocytes in RDD also express BCL-1 and OCT2, which might be important in pathogenesis. Additionally, the heterozygous germline mutation involving the FAS gene is identified in some RDD patients with an autoimmune lymphoproliferative syndrome type Ia. germline mutation is associated with familial or Faisalabad histiocytosis and H syndrome.
PubMed: 36358690
DOI: 10.3390/cancers14215271 -
Neuro-oncology Sep 2021Histiocytoses are heterogeneous hematopoietic diseases characterized by the accumulation of CD68(+) cells with various admixed inflammatory infiltrates. The... (Review)
Review
Histiocytoses are heterogeneous hematopoietic diseases characterized by the accumulation of CD68(+) cells with various admixed inflammatory infiltrates. The identification of the pivotal role of the mitogen-activated protein kinase (MAPK) pathway has opened new avenues of research and therapeutic approaches. We review the neurologic manifestations of 3 histiocytic disorders with frequent involvement of the brain and spine: Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), and Rosai-Dorfman-Destombes disease (RDD). Central nervous system (CNS) manifestations occur in 10%-25% of LCH cases, with both tumorous or neurodegenerative forms. These subtypes differ by clinical and radiological presentation, pathogenesis, and prognosis. Tumorous or degenerative neurologic involvement occurs in 30%-40% of ECD patients and affects the hypothalamic-pituitary axis, meninges, and brain parenchyma. RDD lesions are typically tumorous with meningeal or parenchymal masses with strong contrast enhancement. Unlike LCH and ECD, neurodegenerative lesions or syndromes have not been described with RDD. Familiarity with principles of evaluation and treatment both shared among and distinct to each of these 3 diseases is critical for effective management. Refractory or disabling neurohistiocytic involvement should prompt the consideration for use of targeted kinase inhibitor therapies.
Topics: Central Nervous System; Erdheim-Chester Disease; Histiocytosis, Langerhans-Cell; Histiocytosis, Sinus; Humans; Prognosis
PubMed: 33993305
DOI: 10.1093/neuonc/noab107 -
Clinical Lymphoma, Myeloma & Leukemia Jan 2021Histiocytic disorders are an exceptionally rare group of diseases with diverse manifestations and a paucity of approved treatments, thereby leading to various challenges... (Review)
Review
Highlights of the Management of Adult Histiocytic Disorders: Langerhans Cell Histiocytosis, Erdheim-Chester Disease, Rosai-Dorfman Disease, and Hemophagocytic Lymphohistiocytosis.
Histiocytic disorders are an exceptionally rare group of diseases with diverse manifestations and a paucity of approved treatments, thereby leading to various challenges in their diagnosis and management. With the discovery of novel molecular targets and the incorporation of targeted agents in the management of various adult histiocytic disorders, their management has become increasingly complex. In an attempt to improve the understanding of the clinical features and management of common adult histiocytic disorders (Langerhans cell histiocytosis, Erdheim-Chester disease, Rosai-Dorfman disease, and hemophagocytic lymphohistiocytosis), we created this document based on existing literature and expert opinion.
Topics: Adult; Drug Therapy, Combination; Erdheim-Chester Disease; Histiocytosis, Langerhans-Cell; Histiocytosis, Sinus; Humans; Lymphohistiocytosis, Hemophagocytic; Treatment Outcome
PubMed: 32943371
DOI: 10.1016/j.clml.2020.08.007 -
Journal of the National Comprehensive... Nov 2021Adult-onset histiocytoses (AOH), primarily Rosai-Dorfman disease (RDD), Erdheim-Chester Disease (ECD), and adult Langerhans cell histiocytosis (ALCH), are a group of... (Review)
Review
Adult-onset histiocytoses (AOH), primarily Rosai-Dorfman disease (RDD), Erdheim-Chester Disease (ECD), and adult Langerhans cell histiocytosis (ALCH), are a group of related histiocytic neoplastic disorders featuring multisystemic manifestations. The disorders are largely incurable, and are essentially chronic neoplastic diseases with a variable prognosis. Prompt diagnosis and treatment is important to prevent debilitating and even life-threatening complications. Survivorship issues abound in AOH, due to their multisystemic manifestations and the sometimes recalcitrant chronic inflammation, which can lead to other debilitating complications such as fatigue, weakness, and pain. Because these disorders are rare, few healthcare professionals are proficient in their management; therefore the aim of these guidelines is to offer guidance on how to manage patients, and how to create survivorship care plans through the efforts of an interdisciplinary team.
Topics: Adult; Erdheim-Chester Disease; Histiocytosis, Langerhans-Cell; Histiocytosis, Sinus; Humans; Neoplasms; Prognosis; Survivorship
PubMed: 34781266
DOI: 10.6004/jnccn.2021.7096 -
Journal of the European Academy of... Aug 2020Reticulohistiocytoses (RH) are rare and clinically heterogeneous histiocytic disorders of dermatological interest. Three clinical entities with superimposable... (Review)
Review
Reticulohistiocytoses (RH) are rare and clinically heterogeneous histiocytic disorders of dermatological interest. Three clinical entities with superimposable histopathological features are currently considered, namely solitary reticulohistiocytoma, diffuse/generalized reticulohistiocytosis and multicentric reticulohistiocytosis. Although in the last decade, RH studies have only minimally progressed, histiocytosis research has advanced considerably: the prognostic and therapeutic importance of the clinical subclassification of histiocytosis patients as well as of the detection of genetic alterations in the genes of the ERK pathway has been highlighted. According to these insights, we previously reported the presence of molecular alteration RH and described a subset of patients with disseminated multisystem involvement lacking arthritis. In the present review, we aim to update and revise the knowledge regarding RH. We first reviewed their histopathological, immunophenotypical and ultrastructural features, discussed their histopathological differential diagnosis with other conditions characterized by infiltrates made of oncocytic or epithelioid cells (with special regard to Destombes-Rosai-Dorfman disease) and finally summarized the molecular landscape of RH. We therefore tried to adjust the clinical subclassification of Langerhans cell histiocytosis to the clinical phenotypes of RH, outlining five clinically different groups of patients. Finally, we reconsidered the clinical workflow to the evaluation of RH patients, in light of the 5 different clinical groups and discussed the different therapeutic approaches and the possible role of target inhibitors.
Topics: Diagnosis, Differential; Epithelioid Cells; Histiocytosis, Langerhans-Cell; Histiocytosis, Non-Langerhans-Cell; Histiocytosis, Sinus; Humans
PubMed: 31955466
DOI: 10.1111/jdv.16214 -
Archives of Pathology & Laboratory... Jan 2022Rosai-Dorfman disease is a rare histiocytic proliferative disorder of unknown pathogenesis that may be diagnostically difficult in extranodal sites. It is commonly an... (Review)
Review
CONTEXT.—
Rosai-Dorfman disease is a rare histiocytic proliferative disorder of unknown pathogenesis that may be diagnostically difficult in extranodal sites. It is commonly an unsuspected diagnosis when arising in bone and soft tissue, especially when it presents without associated lymphadenopathy. Its variable clinical presentation and nonspecific imaging findings make the diagnosis quite challenging, particularly in small biopsies. The problem is compounded by its less-characteristic histomorphologic features in comparison with nodal disease. Awareness of the potential diagnostic pitfalls in Rosai-Dorfman disease of bone and soft tissue should raise the degree of diagnostic accuracy.
OBJECTIVE.—
To review the clinical manifestations, imaging characteristics, and histomorphologic features of Rosai-Dorfman disease of bone and soft tissue along with a brief discussion of its differential diagnosis, pathogenesis, and current management.
DATA SOURCES.—
Thorough review of the literature with focus on clinical manifestations, imaging findings, key histomorphologic features, pathogenesis, and treatment.
CONCLUSIONS.—
The diagnosis of Rosai-Dorfman disease of bone and soft tissue may be quite challenging because of its variable clinical presentation and nonspecific imaging findings. It may be asymptomatic without systemic manifestations or associated lymphadenopathy. The definitive diagnosis relies on histopathologic identification of the characteristic S-100-positive histiocytes demonstrating emperipolesis. Bone and soft tissue lesions tend to have lower numbers of characteristic histiocytes and less conspicuous emperipolesis and often demonstrate areas of fibrosis or storiform spindle cell areas resembling fibrohistiocytic lesions. Awareness of these unusual features is necessary in order to consider Rosai-Dorfman disease in the differential diagnosis when confronting these rare and often misleading lesions.
Topics: Diagnosis, Differential; Emperipolesis; Histiocytes; Histiocytosis, Sinus; Humans; Lymphadenopathy
PubMed: 34965285
DOI: 10.5858/arpa.2021-0116-RA -
Systematic Reviews Jan 2021To review and summarize the clinical features, diagnosis, treatment strategies, and prognosis of spinal Rosai-Dorfman disease (RDD). (Review)
Review
PURPOSE
To review and summarize the clinical features, diagnosis, treatment strategies, and prognosis of spinal Rosai-Dorfman disease (RDD).
METHODS
RDD is also termed as sinus histiocytosis with massive lymphadenopathy. We searched the databases of PubMed, Elsevier ScienceDirect, SpringerLink, and OVID. The keywords were Rosai-Dorfman disease and spine/central nervous system. Research articles and case reports with accessibility to full texts regarding spinal RDD were eligible for the inclusion. A total of 62 articles were included, and they contained 69 cases. We extracted the information of interest and analyzed them using SPSS statistics package.
RESULTS
The average age was 33.1 ± 18.3 years. The ratio of males to females was 1.9/1. Overall, 63 cases presented with spine-related symptoms. A total of 27 cases (39.1%) had multi-organ lesions, and 12 cases had records of massive lymphadenopathy. Among 47 cases who first manifested spine-related symptoms, 93.6% were preoperatively misdiagnosed. The disease had a predilection for cervical spine (38.8%) and thoracic spine (40.3%). 62.9% of lesions were dura-based. Surgery remained the mainstream treatment option (78.8%), with or without adjuvant therapies. Total lesion resection was achieved in 34.8% of cases. The rate of lesion recurrence/progression was 19.5%, which was marginally lower for total resection than for non-total resection.
CONCLUSION
Spinal RDD has no pathognomonic clinical and imaging features. Most cases first present with spine-relevant symptoms. Massive lymphadenopathy is not common, but a tendency for multi-organ involvement should be considered. Spinal RDD has a high recurrence rate; thus, total resection is the treatment of choice. Adjuvant therapies are indicated for multi-organ lesions and residual lesions. A wait and watch strategy is recommended for asymptomatic patients. Herein, a workflow of diagnosis and treatment of the spinal RDD is established.
Topics: Adolescent; Adult; Female; Histiocytosis, Sinus; Humans; Male; Middle Aged; Prognosis; Recurrence; Young Adult
PubMed: 33461611
DOI: 10.1186/s13643-021-01581-0 -
Blood Advances Aug 2023Erdheim-Chester disease (ECD) and Rosai-Dorfman disease (RDD) are rare non-Langerhans cell histiocytoses (non-LCHs), for which therapeutic options are limited. MAPK...
Erdheim-Chester disease (ECD) and Rosai-Dorfman disease (RDD) are rare non-Langerhans cell histiocytoses (non-LCHs), for which therapeutic options are limited. MAPK pathway activation through BRAFV600E mutation or other genomic alterations is a histiocytosis hallmark and correlates with a favorable response to BRAF inhibitors and the MEK inhibitor cobimetinib. However, there has been no systematic evaluation of alternative MEK inhibitors. To assess the efficacy and safety of the MEK inhibitor trametinib, we retrospectively analyzed the outcomes of 26 adult patients (17 with ECD, 5 with ECD/RDD, 3 with RDD, and 1 with ECD/LCH) treated with orally administered trametinib at 4 major US care centers. The most common treatment-related toxicity was rash (27% of patients). In most patients, the disease was effectively managed at low doses (0.5-1.0 mg trametinib daily). The response rate of the 17 evaluable patients was 71% (73% [8/11] without a detectable BRAFV600E achieving response). At a median follow-up of 23 months, treatment effects were durable, with a median time-to-treatment failure of 37 months, whereas the median progression-free and overall survival were not reached (at 3 years, 90.1% of patients were alive). Most patients harbored mutations in BRAF (either classic BRAFV600E or other BRAF alterations) or alterations in other genes involved in the MAPK pathway, eg, MAP2K, NF1, GNAS, or RAS. Most patients required lower than standard doses of trametinib but were responsive to lower doses. Our data suggest that the MEK inhibitor trametinib is an effective treatment for ECD and RDD, including those without the BRAFV600E mutation.
Topics: Adult; Humans; Proto-Oncogene Proteins B-raf; Retrospective Studies; Erdheim-Chester Disease; Histiocytosis, Sinus; Protein Kinase Inhibitors; Mitogen-Activated Protein Kinase Kinases
PubMed: 36857436
DOI: 10.1182/bloodadvances.2022009013 -
Head and Neck Pathology Dec 2019Sinus histiocytosis with massive lymphadenopathy, or Rosai-Dorfman disease, is a rare, benign type of non-Langerhans cell histiocytosis. The radiological findings are...
Sinus histiocytosis with massive lymphadenopathy, or Rosai-Dorfman disease, is a rare, benign type of non-Langerhans cell histiocytosis. The radiological findings are often nonspecific, potentially mimicking malignancies. The diagnosis is ultimately made based on pathology, in which the lymph nodes are characterized by a dilated subcapsular sinus filled with histiocytes that can exhibit emperipolesis. Immunohistochemically, the histiocytes are variably CD68 positive and reliably negative for CD1a. The features of head and neck sinus histiocytosis with massive lymphadenopathy are exemplified in this radiology-pathology correlation sine qua non article.
Topics: Child; Histiocytosis, Sinus; Humans; Male
PubMed: 29855802
DOI: 10.1007/s12105-018-0941-3