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Rosai-Dorfman disease (RDD) is a rare form of non-Langerhans cell histiocytosis. Although 20% of patients with RDD have spontaneous remission, some cases with central nervous system (CNS) involvement require surgery or systemic treatment. We encountered a case of RDD in which hypertrophic pachymeningitis was diffuse, eliminating the need for surgical intervention. A 72-year-old Japanese man was diagnosed with RDD based on pathological lymph node findings. Repeated intravenous methylprednisolone (IVMP) administration resolved and stabilized the hypertrophic pachymeningitis without any sequelae. If surgery or anticancer medications are contraindicated, repeated IVMP may be a good therapeutic option for CNS-associated RDD.

Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder characterized by lymphadenopathy and extra-nodal manifestations. Some patients with RDD require systemic treatment, but there is no consensus on the treatment strategy owing to its extreme rarity. Overexpression of tumor necrosis factor α (TNF-α) has been reported in lesions of patients with RDD and is thought to be involved in its pathogenesis. We herein report the first case of RDD with cutaneous involvement and arthritis that was successfully treated with methotrexate and infliximab. This case highlights the potential efficacy of anti-TNF-α therapy for RDD, offering a novel treatment option for this rare condition.

Rosai-Dorfman-Destombes disease (RDD) is a rare histiocytosis characterized by accumulation of S100 + , CD68 + , and CD1a- histiocytes, with emperipolesis. It occurs predominantly in black adolescents and young adults, but rarely in Japanese children. Recently, oncogenic mutations in mitogen-activated protein kinase (MAPK) pathway genes were reported in 30-50% of patients with RDD, and several studies have described treatment of adult patients with MAPK inhibitors. Here, we present the case of a Japanese boy with refractory RDD without signs of cardiofaciocutaneous (CFC) syndrome who harbored MAP2K1 p.Lys59del and responded to trametinib. The patient had lymph node, nasal cavity, kidney, upper respiratory tract, and intracranial involvement. RDD progressed after multi-agent chemotherapy, but responded to trametinib (0.025 mg/kg). Trametinib did not eliminate the mass lesions, but trametinib plus minimal prednisolone (0.1 mg/kg) resulted in a good outcome for more than 15 months, without significant adverse effects. MAP2K1 p.Lys59del has been described as a germline mutation in a patient with CFC syndrome, but not as a somatic mutation in patients with malignancies. Trametinib may be a promising drug for children with RDD that is refractory to multi-agent chemotherapy. Its long-term efficacy and safety alone and in combination with chemotherapy should be investigated., (© 2024. Japanese Society of Hematology.)

Rosai-Dorfman disease (RDD) is a rare myeloproliferative disorder involving histiocytes, with an incidence of 1:200 000 and approximately 100 new cases diagnosed annually in the USA. The condition presents a diverse range of clinical manifestations, and early recognition and treatment generally result in a favourable prognosis. However, diagnosing RDD poses challenges due to its rarity. The clinical management of RDD lacks a consensus, further complicating its diagnostic and therapeutic approach. We present a case of a man in his late 50s with RDD who experienced worsening cytopenias, including severe neutropenia and respiratory distress, despite an initial positive response to steroids, rituximab and lenalidomide. Genetic testing revealed mutations in POLE, KRAS (G13C), NDE1 and EZH2, suggesting potential new therapeutic targets. Sirolimus was initiated and led to complete radiological remission of the disease. This case adds strength to the growing evidence supporting the efficacy of sirolimus in refractory RDD cases., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Histiocytic neoplasms are diverse clonal haematopoietic disorders, and clinical disease is mediated by tumorous infiltration as well as uncontrolled systemic inflammation. Individual subtypes include Langerhans cell histiocytosis (LCH), Rosai-Dorfman-Destombes disease (RDD) and Erdheim-Chester disease (ECD), and these have been characterized with respect to clinical phenotypes, driver mutations and treatment paradigms. Less is known about patients with mixed histiocytic neoplasms (MXH), that is two or more coexisting disorders. This international collaboration examined patients with biopsy-proven MXH with respect to component disease subtypes, oncogenic driver mutations and responses to conventional (chemotherapeutic or immunosuppressive) versus targeted (BRAF or MEK inhibitor) therapies. Twenty-seven patients were studied with ECD/LCH (19/27), ECD/RDD (6/27), RDD/LCH (1/27) and ECD/RDD/LCH (1/27). Mutations previously undescribed in MXH were identified, including KRAS, MAP2K2, MAPK3, non-V600-BRAF, RAF1 and a BICD2-BRAF fusion. A repeated-measure generalized estimating equation demonstrated that targeted treatment was statistically significantly (1) more likely to result in a complete response (CR), partial response (PR) or stable disease (SD) (odds ratio [OR]: 17.34, 95% CI: 2.19-137.00, p = 0.007), and (2) less likely to result in progression (OR: 0.08, 95% CI: 0.03-0.23, p < 0.0001). Histiocytic neoplasms represent an entity with underappreciated clinical and molecular diversity, poor responsiveness to conventional therapy and exquisite sensitivity to targeted therapy., (© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Cutaneous Rosai Dorfman disease (CRDD) is a rare histiocytic disorder that shows distinctive clinical presentation and prognosis. Sufficient data is currently lacking regarding evidence-based management of CRDD. This systematic review aims to provide a comprehensive overview of CRDD, focusing on treatment approaches and outcomes. PubMed and Scopus databases were searched for studies on CRDD from June 1st, 2013 to May 31st, 2023. Articles describing cases of CRDD confirmed with histological examination were eligible for inclusion. All interventions for CRDD were analyzed. The primary outcome measure was the response of cutaneous lesions to treatment including complete response (CR), partial response (PR), and no response. The secondary outcome measures were mortality rate, relapse rate, and the occurrence of adverse events related to CRDD treatment. Eighty-seven articles describing 118 CRDD cases were included. The mean age was 48.2±16.8 years. The sex ratio (F/M) was 1.53. Nodular (46.6%) erythematous (45.3%) lesions, located on the face (38.1%) were the most prevalent presentations. Associated hematological malignancies were noted in 8 (6.8%) cases. Surgical excision was the most prevalent intervention (51 cases) with CR in 48 cases. Systemic corticosteroids were used in 32 cases with 20 CR/PR, retinoids in 10 cases with 4 CR/PR, thalidomide in 9 cases with 5 CR/PR, methotrexate in 8 cases with 7 CR/PR while observation was decided in 10 cases with 6 CR/PR. Factors independently associated with the absence of response to treatment were facial involvement (OR = 0.76, p = 0.014), and cutaneous lesion size (OR = 1.016, p = 0.03). This systematic review shows distinctive clinical characteristics of CRDD and provides insights into the appropriate management of the disease. It allowed a proposal of a treatment algorithm that should be interpreted in the context of current evidence and would help practitioners in treating this rare disease., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cutaneous Rosai-Dorfman Disease (CRDD), a rare form of Rosai-Dorfman Disease (RDD), lacks established treatment guidelines. In this case report, we detailed a successful case of CRDD management in a 50-year-old woman with facial lesions. Our treatment included 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and low-dose oral corticosteroids. Remarkable improvement was evident after six ALA-PDT courses, and a one-year follow-up confirmed sustained remission. This case highlights the potential of combining ALA-PDT with low-dose corticosteroids as a promising therapeutic strategy for CRDD. Further research is necessary to fully elucidate its mechanisms and effectiveness., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Rosai Dorfman disease (RDD) is a non-Langerhans cell histiocytic neoplasm characterized by sinus histiocytosis with variable emperipolesis. There is a limited understanding of the factors that contribute to disease progression. Traditional management of RDD consists of local therapies (resection, radiation) for localized disease and myelosuppression for systemic disease; targeted medications have also recently been introduced into clinical practice as an additional therapeutic modality. The goals of this study are to compare the impact of targeted therapies to conventional management of RDD and identify trends in laboratory data that may provide insight into disease progression. A retrospective analysis was conducted at a single institution over a 20-year period in 35 adult patients with histopathologic evidence of RDD without confounding secondary malignancies. Clinical data points included laboratory evaluation, molecular diagnostics, imaging, and therapies rendered. Binary data was utilized for statistical analysis and comparison of outcomes by treatment type and utilization of targeted agents. Evaluation of treatment response varied based on anatomic disease sites and baseline imaging modality. To standardize the radiographic analysis, we included PERCIST (if PET was utilized) or RECIST assessments (in the cases of CT or MR imaging). Conventional therapies rendered included local treatment (surgery, radiation, intralesional injections), systemic corticosteroids, immunotherapy, and chemotherapy while targeted agents included only small molecule inhibitors. In this analysis, primary disease was identified in cutaneous, osseous, and CNS structures (17, 11, and 6/35 patients respectively). Management consisted of surgery (12/35 patients), steroid and myelosuppressive therapies (9/35 each), immunotherapy (5/35), and targeted molecular agents (5/35). In evaluating outcomes, the proportion of partial responses was substantially higher in recipients of molecular as compared to conventional therapy (4/5 patients compared to 6/29) while complete responses were more common in the conventional therapy cohort (12/29 compared to 1/5). Lastly, an evaluation of peripheral blood absolute monocytes in all patients who had progressed on therapy identified a significant decrease in pre-progression values as compared to values following therapy re-institution (averages of 0.70 and 0.27 K/µL, respectively; p = 0.0002, 95% CI 0.652-0.2360). Larger-scale studies are needed to further evaluate the relevance of the monocyte trends that were identified in terms of their relationship to disease status. This study is the largest analysis of Rosai Dorfman disease, that we are aware of, from a single institution. In this cohort, the utilization of small molecule inhibitors corresponded to a greater increase in partial responses than conventional therapies, although the opposite effect has been observed in complete responses. This finding can be attributed to the recent introduction of targeted agents and shorter follow-up. We anticipate higher complete response rates with the use of small molecule in ongoing analyses over a longer follow-up period. The recognition of relative monocyte elevation prior to disease progression is an intriguing and to our knowledge, novel finding in the field of Rosai Dorfman disease. Future studies aimed at elucidating the implications of this trend are in progress., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rosai-Dorfman disease(RDD) is a rare benign histiocytic proliferative disorder. Cutaneous Rosai-Dorfman disease(CRDD)is a rare variant of RDD with lesions localized to the skin. We report a case of patients with CRDD who was refractory to methotrexate, thalidomide, cyclosporine, glucocorticoid for local injection and external use, but resolved with fractional laser combined with 5-aminolevulinic acid photodynamic therapy (ALA-PDT). We believe that fractional laser technology combined with ALA-PDT for CRDD is a minimally invasive, effective and satisfactory treatment., Competing Interests: Declaration of Competing Interest None disclosed., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Rosai-Dorfman Disease, otherwise known as sinus histiocytosis with massive lymphadenopathy, is a rare form of non-Langerhans cell histiocytosis with an estimated incidence of 100 cases per year in the United States. Due to its variable presentation and nonspecific clinical findings, it is particularly difficult to diagnose in pediatric patients. We report a case of an 11-month-old male who presented with a 4-day history of a right groin mass. Ultrasound of the groin and pelvis demonstrated, and MRI of the abdomen and pelvis confirmed an inguinal mass with surrounding lymphadenopathy. Pathology confirmed Rosai-Dorfman Disease and the patient improved after starting oral steroid therapy. To the best of our knowledge, this is the first case of Rosai-Dorfman Disease involving the inguinal region in an infant under 1 year of age reported in the literature. In this case report, we discuss the imaging and histology findings as well as provide a brief literature review for this diagnosis., (Copyright Journal of Radiology Case Reports.)

Objectives: Rosai-Dorfman disease (RDD) is one of 3 major types of histiocytosis, along with Erdheim-Chester disease and Langerhans cell histiocytosis. While historically, RDD was considered a benign self-limited condition, current data show MAPK/ERK pathway mutations in 30% to 50% of cases, indicative of a clonal process. Rosai-Dorfman disease was incorporated as a histiocytic neoplasm in the fifth edition of the World Health Organization classification of hematopoietic tumors and the International Consensus Classification., Methods: We discuss the diagnosis of RDD using 2 illustrative cases, interpretative challenges, and a diagnostic algorithm., Results: Rosai-Dorfman disease involves nodal and extranodal sites, including skin, sinuses, salivary gland, orbit, central nervous system, kidney, and bone. In a subset, RDD can coexist with other neoplasms (lymphomas, other histiocytosis) or autoimmune disease. Morphologically, RDD histiocytes are characterized by enlarged round to oval nuclei, distinct nucleoli, and voluminous cytoplasm with engulfment of inflammatory cells (emperipolesis). By immunohistochemistry, they express CD68, CD163 (majority), S100, OCT2, and cyclin D1. Appropriate use of ancillary studies is important to support the diagnosis of RDD while excluding other histiocytic neoplasms and reactive histiocytic proliferations., Conclusions: Management of RDD is dependent on the extent of organ involvement and clinical symptoms. In patients who require therapy, next-generation sequencing is recommended to identify MAPK/ERK pathway mutations for targeted therapy., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Rosai Dorfman disease (RDD) is a rare benign histiocytic proliferative disorder of lymph node sinuses. Langerhans cell histiocytosis (LCH) is a solitary or multisystem clonal proliferation of abnormal dendritic cells (Langerhans cells) with varied presentations. The co-occurrence of these two entities is quite rare., Case Description: A six-year-old boy presented with multiple mass lesions in the neck since two years and a nodular lesion in right upper eyelid for the past 4 months. He was diagnosed with tubercular lymphadenitis 2 years back, and was given a course of anti-tubercular therapy (ATT) elsewhere. No improvement was seen. Fine needle aspiration cytology (FNAC) of the cervical lymph nodes revealed reactive lymphadenitis while lymph node biopsy showed features of RDD. Excision biopsy of the orbital mass showed features of both RDD and LCH. The patient was started on tablet prednisolone. Six months later, complete resolution of lymph node enlargement and remaining orbital mass was noted. Post operative contrast enhanced Magnetic Resonance Imaging of head and neck was normal., Conclusion: The coexistence of RDD and LCH may be a result of divergent differentiation from a common lineage or a de novo phenotypic evolution.

Erdheim-Chester disease (ECD) is a non-Langerhans cell histiocytosis characterised by clonal expansion of histiocytes in various organs. These induce an inflammatory environment, which leads to damage of the affected areas. Recently, a new disease entity was proposed encompassing key features of ECD but also of Rosai-Dorfman-Destombes disease, another histiocytosis. Mitogen-activated protein kinase kinase 1 ( MAP2K1) mutations seem to present a specific genetic lesion for this subtype.Here, we describe a case of this new disease entity with clinical, radiological and genetic findings compatible with ECD but histological findings compatible with Rosai-Dorfman-Destombes disease. In particular, there were intraabdominal and retroperitoneal lesions, which tested positive for a (c.167A>C; p.Q56P) mutation of the MAP2K1 gene. On histological examination, S100-positive, giant histiocytes with focal emperipolesis of haematological cells in addition to infiltration by lymphocytes and granulocytes were seen.As described for this rare variant of ECD, there was also bilateral testicular infiltration. We also describe a manifestation of oligoarthritis in this patient with ECD.The patient was treated with methotrexate and prednisolone. While radiological response to this regime was excellent, arthritis persisted. We added anakinra, which induced a response of the arthritis for more than a year. Due to treatment failure therapy was switched to upadacitinib, which induced a remission of the arthritis as well.This case adds a rare phenotype to an already rare presentation of ECD. The patient responded to immunosuppressive therapy., Competing Interests: Competing interests: JP received travel grants from AbbVie, EuroImmun, CSL-Behring, Galapagos and Janssen-Cilag. MG received travel grants, speaker’s fees or compensation for advisory boards from AbbVie, Eli Lilly, Hexal, Janssen-Cilag, Novartis, Pfizer and Takeda. AH has no competing interests to declare. AR has no competing interests to declare. SH received travel grants from Jannsen-Cilag. LR has no competing interests to declare. MS received compensation for his work as an advisor or consultant by Chugai/ Roche, Hexal/Sandoz, Gilead, AbbVie, Janssen-Cilag and Boehringer/Ingelheim, for his work as a lecturer by Novartis, AbbVie, AstraZeneca, Chugai/Roche and Janssen-Cilag and for his work relating to medical conventions by Chugai/Roche, Boehringer/Ingelheim, Celgene, Medac and UCB., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Rosai-Dorfman disease (RDD) is a rare histiocytic neoplasm with recent studies showing alterations in the MAPK pathway, most commonly in the KRAS and MEK genes in about 40% of patients. Reports on the use of MEK-inhibitor therapy in RDD have been limited to small case studies. There are no approved treatments for this neoplasm, and therefore patients with RDD need efficacious treatments., Objective: To study the outcomes after treatment with cobimetinib based on MAPK pathway alterations in patients with RDD., Design, Setting, and Participants: This retrospective cohort study conducted at 2 tertiary care centers included patients with RDD who underwent treatment with cobimetinib between January 1, 2013, and December 1, 2021. Cobimetinib was administered at a dosage of 20 to 60 mg orally once daily as a single agent for 21 days in a 28-day cycle. Pathology was centrally reviewed. Response assessment was centrally conducted and was based on the established positron emission radiography response criteria used for clinical trials of targeted therapies in histiocytosis., Main Outcomes and Measures: Main outcomes were overall response rate (ORR), progression-free survival (PFS), adverse events (AEs) of cobimetinib in the entire cohort, and ORRs and PFS based on MAPK pathway alterations in patients with RDD., Results: A total of 16 patients (median [range] age at cobimetinib initiation, 57 [31-74] years; 11 [69%] women) were included in the study. The median follow-up duration was 19.0 months (95% CI, 8.4-27.8 months). The ORR was 63% (n = 10), including 5 complete responses and 5 partial responses. Somatic alterations in the KRAS or MEK genes were detected in 8 (50%) patients. Patients with KRAS or MEK alterations had significantly higher ORR (88% vs 38%; P = .03), deeper responses (complete responses among responders: 71% vs 0%; P = .002), and better PFS (at 1 year, 100% vs 29% were free from progression or death, respectively; P < .001) compared with those without such alterations. Grade 2 or higher AEs occurred in 12 (75%) patients, and 9 (56%) required dose reduction or temporary/permanent treatment discontinuation due to AEs., Conclusions and Relevance: In this cohort study, treatment with cobimetinib was associated with positive outcomes in KRAS- or MEK-variant RDD. However, AEs requiring dose modifications were common.

Purpose: To present a patient with Rosai-Dorfman Disease (RDD), a histiocytic proliferative disorder typified by lymphadenopathy with rare ocular manifestations, who developed panuveitis that responded to pegylated interferon., Methods: Descriptive case report of a patient with RDD with multi-organ involvement including ocular manifestations including bilateral panuveitis with choroidal masses., Results: A 54-year-old African American woman with known systemic RDD of the breast, lung, and gastrointestinal tract presented with panuveitis with choroidal masses in both eyes. Her systemic and ocular disease initially responded well to oral and topical steroid therapy. Later, however, her systemic disease progressed with multiple muscular and bony lesions. Systemic therapy was switched to pegylated interferon, a cytokine with antiviral, antitumor and immunomodulatory activity. After 14 months of therapy with pegylated interferon, the patient's systemic and ocular disease stabilized., Conclusion: Rosai-Dorfman disease may be complicated by panuveitis and choroidal masses that may respond to pegylated interferon with stabilization of systemic and ocular manifestations. A multi-disciplinary approach is essential given the unique diagnostic and management challenges of RDD.

What Is Known and Objective: Rosai-Dorfman disease (RDD) is an infrequent entity of unknown aetiology. Currently, there is no clear consensus on the treatment, and nothing has shown definitive safety and efficacy. We describe the case of a woman diagnosed with pulmonary RDD, who responded to thalidomide treatment after failure of four previous lines of systemic chemotherapy., Case Description: We present the case of a 74-year-old woman diagnosed with pulmonary RDD and autoimmune complications. We decided to use thalidomide as a rescue treatment after the failure of corticosteroids and several chemotherapies. Our patient achieved remission of the disease and remained stable for years., What Is New and Conclusion: To the authors' knowledge, this is the first reported case in which thalidomide treatment induced remission in refractory pulmonary RDD. Thalidomide showed a rapid onset of action, with lasting responses, which could make it an exciting option for treating this life-threatening., (© 2021 John Wiley & Sons Ltd.)

We report the case of a patient diagnosed with cutaneous Rosai-Dorfman disease (CRDD) who was treated successfully with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with carbon dioxide (CO 2 ) laser therapy. CRDD is a rare form of Rosai-Dorfman disease that has various clinical presentations and multiple possible therapies with varying efficacies. ALA-PDT combined with CO 2 laser therapy was safe and effective for treating CRDD in the current patient, with no recurrence during the 3 months of follow-up medical examinations. This case suggests that ALA-PDT combined with CO 2 laser can be used to treat patients with CRDD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Non-Langerhans cell histiocytosis, including Erdheim-Chester disease (ECD), Rosai-Dorfman disease (RDD), indeterminate cell histiocytosis (ICH), and unclassified histiocytosis, is a rare disorder lacking a standard treatment strategy. We report our experience using intermediate-dose cytarabine as the first or subsequent therapy in non-Langerhans cell histiocytosis., Results: Nine ECD patients, 5 RDD patients, 1 ICH patient and 1 unclassified histiocytosis patient were enrolled. Intermediate-dose cytarabine therapy was administered as 0.5-1.0 g/m 2 of intravenous cytarabine every 12 h for 3 days every 5 weeks. The median age at cytarabine initiation was 47.5 years (range 18-70 years). The median number of cycles of cytarabine administered was 5.5 (range 2-6). The overall response rate (ORR) was 87.5% in the overall cohort, including 12.5% with complete response and 75.0% with partial response. One patient experienced disease recurrence 19 months after cytarabine therapy. The median follow-up duration for the entire cohort was 15.5 months (range 6-68 months). The estimated 2-year progression-free survival and overall survival rates were 85.6% and 92.3%, respectively. The most common toxicity was haematological adverse events, including grade 4 neutropenia and grade 3-4 thrombocytopenia. No treatment-related deaths occurred., Conclusions: Intermediate-dose cytarabine is an efficient treatment option for non-Langerhans cell histiocytosis patients, especially for those with CNS involvement., (© 2022. The Author(s).)

Objective and Importance: Rosai-Dorfman disease (RDD) is a benign and rare non-Langerhans cell histiocytic proliferative disorder. Laryngeal involvement is an unusual site of extranodal involvement of RDD. Laryngeal RDD can cause life-threatening airway obstruction that requires effective control of the disease. In this study, we report three cases of laryngeal RDD with excellent and durable responses to thalidomide., Clinical Presentation: Patient 1 was a 39-year-old male who presented with a two-year history of nasal obstruction. Patient 2 was a 26-year-old woman who presented complaining of a hoarse voice for one year. Patient 3 was a 24-year-old man who presented with complaints of a hoarse voice and progressing dyspnea for five months. Electronic laryngoscopy revealed submucous nodular lesions in the nasal cavity, nasopharynx, and larynx of the three patients. Biopsy of the lesions showed large histiocytes with abundant pale cytoplasm which were S-100 and CD68 positive consistent with RDD., Intervention: Before thalidomide treatment, patient 1 received chemotherapy and six times surgical excision due to the recurrence of laryngeal lesions. Patient 2 failed steroid treatment. Patient 3 underwent an emergency tracheostomy due to airway obstruction. All three patients then received thalidomide 100 mg/d treatment and achieved satisfactory and durable responses with the longest follow-up of 45 months., Conclusion: Thalidomide may induce long-term remission in laryngeal RDD.

Histiocytic neoplasms are rare hematologic disorders accounting for less than 1% of cancers of the soft tissue and lymph nodes. Clinical presentation and prognosis of these disorders can be highly variable, leading to challenges for diagnosis and optimal management of these patients. Treatment often consists of systemic therapy, and recent studies support use of targeted therapies for patients with these disorders. Observation ("watch and wait") may be sufficient for select patients with mild disease. These NCCN Guidelines for Histiocytic Neoplasms include recommendations for diagnosis and treatment of adults with the most common histiocytic disorders: Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai-Dorfman disease.

Rosai-Dorfman disease (RDD), a rare form of histiocytosis, has been reported to cause choroidal masses and subsequent serous retinal detachments. We present a case of RDD associated with a choroidal mass and retinal detachment that did not respond to corticosteroid treatment and regressed after treatment with photodynamic therapy (PDT). Following treatment, the patient had a successful anatomic and clinical outcome, with no recurrence of serous detachment and 20/25 visual acuity. This is the first report of choroidal RDD successfully treated with PDT. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:568-571.] .

Background: Cutaneous rosai-dorfman(CRDD) is a rare non-langerhans cell histiocytosis with unknown origin. Studies reporting the dermoscopic features of CRDD are limited., Case Presentation: We report a case of a 62-year-old Asian woman with 1-month history of a solitary reddish nodule on her left nose wing which was histolocically diagnosed as CRDD. The lesion underwent spontaneous remission without any intervention.Dermoscopy was utilized for follow-up observation., Results: The dermoscopic features of the CRDD lesion included red-brownish and red-orange background, yellowish follicular keratotic plugs, whitish opaque cotton structures and linear- irregular vessels. These features gradully faded away along with the remission of the lesion., Conclusions: We describe the dynamic dermoscopic changes of the remission process of CRDD. Dermoscopy is potentially useful in the assessment and follow-up of CRDD patients., (Copyright © 2021. Published by Elsevier B.V.)

We report a case of Rosai-Dorfman disease in a 28-year-old Nigerian woman with a 7-year history of painless prominent bilateral neck swelling which waxed and waned over the years. She had two misdiagnosis hence appropriate therapy was not initiated over the years. She was eventually referred for independent opinion and was diagnosed correctly with review of the histology sections and with the use of CD45, S100, CD 68, CD 15, CD 20, synaptophysin and AE1/AE3 immunohistochemistry markers. Classic features on Haematoxylin and eosin stained sections and positivity of the lesional cells for S100 and CD68 were diagnostic of Rosai-Dorfman disease. She was subsequently placed on oral steroids with minimal objective reduction in the neck circumference from 57 to 46 cm. After two months, she was managed with three courses of chemotherapy (cyclophosphamide, doxorubicin hydrochloride, vincristine and prednisolone) which resulted to a significant sustained reduction in her neck circumference to 36 cm. She has been on follow up for about a year without a recurrence., Competing Interests: The Authors declare that no competing interest exists

Langerhans cell histiocytosis, Rosai-Dorfman disease, and juvenile xanthogranuloma may present at birth or any time afterward. Some patients have minimal skin or lymph node involvement, but others present with life-threatening pulmonary, hepatic, bone marrow, or central nervous system lesions. There is often a delay in diagnosis because of confusing overlap with more common neonatal diseases. Many treatment regimens have been applied to these diseases, but those directed at myeloid cells, such as cytarabine and clofarabine or mutation-targeting inhibitors, are gaining favor. This article provides information on the pathophysiology, clinical presentation, evaluation guidelines, and treatment of these uncommon tumors of neonates., Competing Interests: Disclosure Dr. K.L. McClain is on the medical advisory board of the SOBI Corporation and the HistioCure Foundation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Rosai-Dorfman disease is a rare benign histiocytic proliferative disease of unknown cause that, in exceptional cases, presents with lesions confined to the skin. Clinically variable types of lesions such as papules, nodules and plaques have been reported. We present a case of a 27-year-old woman with a 1-year history of erythematous papular and nodular lesions on the malar and right axillary regions, previously misdiagnosed as acne. She reported no fever, malaise or weight loss, while physical examination and laboratory workup were normal. Bacteriological and mycobacteriological cultures were negative. Histopathological findings showed dense infiltration of inflammatory cells involving the entire dermis, consisting of large macrophages with emperipolesis, S100 and CD68 positive, neutrophils, eosinophils, lymphocytes and plasma cells. The patient was treated with oral prednisolone without improvement. Dapsone was subsequently initiated with favourable clinical response. The present article aimed to emphasise the clinical and histological differential diagnosis and share the treatment experience., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Cutaneous Rosai - Dorfman disease (CRDD) is extremely rare variant of idiopathic histiocytic proliferative disorder, which may manifest as a non-specific macules, papules, plaques or nodules ranging in size and colour from yellow - red to red -brown., Case Presentation: A 52-year-old female presented with three gradually enlarging, reddish - brown nodules on the right upper extremity lasting six months. The patients denied fever, weight loss, malaise. Clinical examination and imaging tests showed no sign of lymphadenopathy. A biopsy specimen of a nodule showed a dense dermal polymorphic infiltrate with numerous histiocytes exhibiting emperipolesis phenomenon. Immunohistochemical staining of the histiocytes showed S-100 protein (+), CD68(+), but CD1a (-). Aforementioned findings were consistent with CRDD characteristics. Additionally, a routine serological screening and confirmatory serological tests for syphilis were positive. Syphilis of unknown duration was diagnosed. The IgG antibodies titre against Chlamydia trachomatis was elevated. An isolated sensory impairment over the right trigeminal nerve was found on neurological consultation. Comprehensive gynaecological assessment was carried out because of patient's complaints of bleeding after sexual intercourse and led to diagnosis of cervical cancer. The initial therapy with methotrexate was discontinued after three months due to neutropenia. Further therapy with dapson was ineffective, therefore complete surgical excision was recommended., Conclusions: CRDD is a rare, benign condition especially difficult to diagnose due to lack of general symptoms and lymphadenopathy. Histopathologic examination with immunohistochemical staining, exhibiting characteristic and reproducible findings play a key role in establishing an accurate diagnosis. In the presented case activated histiocytes demonstrated in a lesional skin might be a response to immune dysregulation related to chronic, untreated sexually transmitted infections and cancer.

Background: Rosai-Dorfman disease (RDD) is a rare pathologic entity caused by sinus histiocytosis with massive cervical lymphadenopathy. Isolated spinal involvement is an infrequent presentation of extranodal RDD. The clinical and radiologic appearance of RDD represents a diagnostic challenge. We report 2 patients with paraparesis caused by RDD of the thoracic spine and a PRISMA-style systematic review., Case Description: There were 2 patients with isolated extranodal thoracic spinal RDD without cervical lymphadenopathy. One patient presented with anterior thoracic RDD and a subtotal resection. The small residual disease completely responded to the postoperative course of steroids. The second patient had extradural thoracic spine RDD, which was resected completely. A 6-month postoperative follow-up magnetic resonance imaging (MRI) scan showed local recurrence, which responded to radiation therapy. Five years follow-up of both patients showed normal neurologic functions and no recurrence on MRI scan surveillance., Conclusions: RDD is a rare occurrence and should be considered in the differential diagnosis of extradural or intradural spinal lesions. Gross total resection is recommended, and long-term clinical follow-up with MRI is advised. Residual or recurrent RDD requires steroids or radiation therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Rosai-Dorfman disease (RDD), also called sinus histiocytosis with massive lymphadenopathy, is a rare, benign and self-limited histiocytosis. We present a case of cutaneous Rosai-Dorfman disease (CRDD) on the right cheek that responded well to combination of subtotal resection and ALA-PDT. We believe that the combination of subtotal resection and ALA-PDT treatment for large cutaneous facial Rosai-Dorfman disease patients is a more effective, highly satisfying, and quick therapy worth promoting., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Destombes-Rosai-Dorfman disease (RDD) is a rare multisystemic histiocytosis. Pulmonary involvement during RDD has been poorly described. The goal of this study was to examine the clinical presentations, radiological features, and outcomes of 15 patients with RDD and lung involvement., Methods: The cases of RDD with lung involvement were extracted from the French National Histiocytosis registry. Efficacy of the MEK inhibitor cobimetinib in treating lung disease was evaluated with an 18 fluorodeoxyglucose PET scanner and chest CT scans., Results: Fifteen patients (six women; median age, 40 years at RDD diagnosis) were included. All patients had evidence of systemic disease with extrapulmonary localizations of the disease (lymphadenopathy [n = 12], skin [n = 9], bones [n = 6], retroperitoneal involvement [n = 3], sinuses [n = 3], parotid gland [n = 2], submandibular gland [n = 1], and breast [n = 1]). Presenting symptoms were dominated by dyspnea and dry cough in seven patients. Restrictive physiology was observed in two of five patients. BAL showed lymphocytosis in one of five cases. Eight patients received corticosteroids, all but one with variable immunosuppressive or immunomodulatory therapies. Two patients received cobimetinib for severe lung disease, with dramatic pulmonary metabolic and tumoral responses. Two patients died during follow-up: one of hemoptysis, and the other of an unrelated cerebral tumor., Conclusions: Pulmonary involvement in RDD is rare, proteiform, and sometimes severe. The MEK inhibitor cobimetinib can lead to dramatic responses., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Rosai-Dorfman disease (RDD) is a rare disease which characterized by proliferation and overproduction of histiocytes in the lymph nodes appearing as lymphadenopathy, however, it may also occur in extranodal sites. The occurrence of unusual manifestations of the disease such as the appearance of the mass in an unusual area may increase the probability of misdiagnosis. Herein, we describe a case of RDD in an old woman with an unusual appearance of RDD in the leg that was successfully treated by thalidomide., (© 2019 Wiley Periodicals, Inc.)

Background: Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder of unknown etiology. The skin is the most frequent extranodal site of RDD involvement and may be the only organ involved. While RDD is an indolent self-limited disease, treatment is needed in patients with extensive, persistent or progressive disease, or if cosmetic disfigurement or physical impairment significantly affects the patient. There is no specific treatment for RDD, and multiple therapeutic approaches have been described with variable success rates. Ojective: To demonstrate the clinical efficacy of oral bexarotene for RDD. Materials and methods: Descriptive retrospective case series of three patients with RDD receiving oral bexarotene. Results: Two patients had excellent response and regression of their skin lesions was achieved with long-term therapy. In the other patient, pruritus was promptly controlled while the lesions did not seem to regress and treatment was discontinued after five months. Conclusions: Our case series is the first report in the literature of the use of oral bexarotene as an effective and safe treatment for RDD.

Introduction: Rosai-Dorfman disease (RDD) is a rare usually self-limited non-Langerhans cell histiocytosis of unknown etiology. Nodal and extranodal RDD appear to represent distinct conditions with different molecular alterations and prognosis. They also pose different diagnostic challenges on biopsies and fine-needle aspiration (FNA) cytology. The aim of this study was to report on 3 cases of intra-abdominal RDD and perform an extensive review of the literature on FNA findings of RDD., Materials and Methods: We reviewed FNA specimens from cases diagnosed histologically or cytologically as RDD during the past 10 years. We searched the PubMed and Google Scholar databases for cases of RDD sampled by FNA., Results: We identified 3 cases of intra-abdominal RDD, involving the kidney, periportal lymph node, and pancreas. FNA of the latter was hypocellular with fibrosis and was nondiagnostic. FNA of the first 2 yielded hypercellular smears that were diagnosed as RDD due to the identification of emperipolesis occurring in large uni- or binucleated histiocytes with large nuclei, fine chromatin, and prominent nucleoli in smears and cell-block sections. Immunohistochemistry showed positive staining for S100 and CD68 and negative staining for CD1a. The large histiocytes with emperipolesis were more difficult to identify histologically and their demonstration required immunohistochemical stains., Conclusion: Our experience and an extensive review of the literature suggest that extranodal RDD can be diagnosed on FNA, and that the recognition of histiocytes with emperipolesis may be less challenging cytologically than histologically. The fibrosis frequently seen in extranodal RDD may lead to nondiagnostic aspirates, however., (Copyright © 2019. Published by Elsevier Inc.)