Repeated Intravenous Methylprednisolone May Prevent Deterioration of Hypertrophic Pachymeningitis in Rosai-Dorfman Disease.

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 as Constrictive Pericarditis: An Unusual Childhood Presentation.

Rosai-Dorfman disease (RDD) is a rare, multisystemic, histiocytic disorder that usually presents with painless cervical lymphadenopathy. We describe a case of constrictive effusive pericarditis with congestive cardiac failure in a six-year-old child as an initial presentation of RDD. The child underwent pericardiectomy and was treated with steroids, following which the symptoms resolved entirely. While tuberculosis accounts for the majority of cases presenting with constrictive pericarditis in developing countries, the presentation of RDD can be easily missed if not kept in mind as a possibility. This case report documents the unique presentation of a rare disease.

Trametinib for a child with refractory Rosai-Dorfman-Destombes disease harboring a novel somatic mutation in MAP2K1.

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.

Rosai-Dorfman disease differentiated from a posterior mediastinal tumour: a case report.

Rosai-Dorfman disease presenting solely with intrathoracic lesions is exceptionally rare. Herein, we report the case of a 53-year-old man presenting with a posterior mediastinal tumour. Computed tomography revealed a 7-cm soft tissue shadow in the posterior mediastinum. Positron emission tomography-computed tomography demonstrated a high maximum standardized uptake value of 10.35 in the tumour, with no evidence of lymph node or other organ involvement. Serum marker levels were within the normal range. Thoracoscopic surgery was performed to obtain a biopsy for a definitive diagnosis and treatment planning. Postoperative histological findings revealed a diffuse infiltration of eosinophilic histiocytes, lymphocytes, and plasma cells. Immunohistochemical analysis indicated positivity for S-100 protein, oct-2, and cyclin D1 in these histiocytes. Consequently, the patient was diagnosed with Rosai-Dorfman disease and is currently asymptomatic, undergoing regular monitoring without treatment as an outpatient. The absence of characteristic findings, such as bilateral cervical lymphadenopathy, posed challenges in preoperative diagnosis.

Advancements in the understanding and management of histiocytic neoplasms.

Histiocytic neoplasms are rare diseases involving macrophages, dendritic cells, and monocytes. They include Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), and histiocytic sarcoma. Histiocytic neoplasms are characterized by varied clinical courses and prognoses, necessitating a nuanced understanding of their classification, epidemiology, and clinical manifestations. Genetic studies have revealed somatic mutations, predominantly in the MAPK pathway, suggesting a clonal neoplastic nature. This review covers the current understanding of histiocytic neoplasms, molecular pathophysiology, with a particular focus on mutations in genes such as BRAF, MAP2K1, and the PI3K-AKT signaling pathways, and evolving treatment strategies, especially focusing on LCH, ECD, RDD, and JXG. The treatment landscape has evolved with advancements in targeted therapies. BRAF inhibitors, such as vemurafenib and dabrafenib, have shown efficacy, especially in high-risk LCH cases; however, challenges remain, including relapse post-treatment discontinuation, and adverse effects. MEK inhibitors have also demonstrated effectiveness, and cobimetinib has recently been approved for use in adults. Further research is required to determine the optimal treatment duration and strategies for managing therapy interruptions. Advancements in molecular genetics and targeted therapies have revolutionized the management of histiocytic neoplasms. However, ongoing research is crucial for optimizing patient outcomes.

Case report: Uncommon manifestations of Rosai-Dorfman disease in the liver mimicking HCC.

Rosai-Dorfman-Destombes disease (RDD) is a rare non-Langerhans cell histiocytosis (LCH) disorder characterized by systemic extranodal lesions. Common cases include skin lesions, whereas liver lesions are rare. This study presents a case of a 66-year-old woman with a solitary extranodal liver lesion who underwent successful surgical treatment followed by glucocorticoid therapy. The patient did not experience any symptoms before surgery. The liver lesion was incidentally discovered during a routine ultrasound examination. Enhanced CT scan revealed the lesion with the characteristic of washout, similar to primary hepatic cancer (HCC). CT scans of the head, neck, chest, and abdominal pelvis revealed no lymph node or other organ lesions. After surgery, the liver lesion was diagnosed as RDD, and subsequent whole-body examinations did not reveal any skin lesions. The definitive diagnosis was solid liver RDD in adults. Although there were no typical cases of bilateral cervical lymph node lesions, ultrasound and CT examinations promptly detected liver lesions, leading to the correct diagnosis through surgical resection. The findings from this case indicate that RDD can occur in rare extrasegmental areas, and the imaging characteristics of liver lesions are not specific, indicating the importance of avoiding delayed diagnosis.

Surgical resection of pediatric craniocervical junction Rosai-Dorfman histiocytosis-a case report and literature review.

Rosai-Dorfman disease (RDD) with craniocervical junction involvement is a rare clinical entity. We present herein a case of a pediatric patient with craniocervical junction RDD which was surgically treated. A 10-year-old female with a history of B-cell acute lymphoblastic leukemia (B-ALL) in remission and RDD presented with frontal migraine headaches. She previously had a right posterior chest wall lesion which was biopsy-proven RDD. She was found on imaging to have a dural-based right craniocervical junction lesion. Given her history of B-ALL, after a multidisciplinary discussion, the decision was made to proceed with resection with possible initiation of cobimetinib or clofarabine. The patient underwent a suboccipital craniotomy, C1 laminectomy, and resection of the dural-based lesion. Gross total resection was achieved, and histopathology confirmed the diagnosis of RDD. She was discharged home on postoperative day 4. No recurrence was seen on follow-up imaging at 3 months. We conducted a systematic literature review examining all cases of pediatric intracranial RDD and all cases of craniocervical junction RDD. This represents, to the best of our knowledge, only the second case of pediatric craniocervical junction RDD. Although RDD is often self-limiting, medical treatment is often considered for intracranial disease, but tissue confirmation is necessary. Surgical resection provides histopathologic diagnosis and can sometimes serve as definitive treatment for a particular lesion.

Multiple foci of Rosai-Dorfman disease in colon: a case report.

BACKGROUND: Rosai-Dorfman disease (RDD) is an uncommon proliferative histiocytic disorder involving lymph nodes and various organs. Forty-three percent of RDD cases originate from extranodal sites; however, RDD rarely arises from the colon. CASE PRESENTATION: A 75-year-old man was admitted to our hospital because of intra-abdominal masses that were incidentally detected during surveillance by computed tomography (CT) after treatment for lung cancer. Enhanced CT showed two mass lesions located in the cecum to the appendix (diameter, 40 mm) and around the sigmoid colon (diameter, 24 mm). Positron emission tomography (PET)-CT revealed an apparent uptake of fluorodeoxyglucose. Intraluminal endoscopy did not reveal definite mucosal abnormalities. These findings suggest the presence of malignant neoplasms including gastrointestinal stromal tumors, lung cancer metastasis, and malignant lymphoma. Exploratory laparoscopy and/or tumor excision were planned to obtain a definitive diagnosis. Based on laparoscopic findings, ileocecal resection and sigmoidectomy were simultaneously performed to excise the tumors. Postoperative histopathological examination revealed multiple RDD originating from the mesocolon side of the cecum and the sigmoid colon. The patient did not receive any adjuvant therapy. No recurrence was observed one year after surgery. CONCLUSION: RDD originating from the colon is extremely rare. Tumor extirpation or organ resection is sometimes required to obtain a definitive diagnosis of RDD, and minimally invasive surgery is helpful.

Management of intracranial Rosai-Dorfman disease: An institutional experience.

OBJECTIVE: Rosai-Dorfman disease (RDD) is a rare benign proliferative disorder of histiocytes. The study discusses the intracranial RDD approach, its management, and its outcome. METHODS: It is a retrospective study performed in a tertiary center, the National Institute of Mental Health and Neuroscience, Bangalore, from January 2010 to December 2022. The biopsy-proven patients of RDD were recruited in the present cohort. Demographic and surgical details were collected from the record section, and radiology was collected from the internal storage system. Follow-up assessments were done clinically and telephonically. RESULTS: A total of 25 patients matched the criteria. The mean age was 32 ± 13.4 years, with male predominance. We have included only cranial cases (N=25). Among the intracranial lesions, 5/25 (20 %) patients had multicentric lesions. All the lesions were avidly enhancing on contrast, and 16 (64 %) lesions were hypointense on T2. Perilesional edema (T2/Flair hyperintensities in the surrounding white matter) was seen in 12 (48 %) patients. Gross total resection (GTR) was carried out in six (24 %) cases. Sub-total resection was in 14 (56 %), and biopsy was in five cases (20 %). Nineteen patients received adjuvant therapy, either only steroid (40 %), only low-dose radiotherapy (16 %), only Chemotherapy (4 %), or a combination of both. At follow-up,44 % of patients had stable disease,28 % had primary disease or recurrence growth, and regression in 12 % of cases. CONCLUSION: We demonstrate that surgical resection is an effective therapy for treating isolated intracranial RDD. Adjuvant therapy is an add-on treatment for skull base locations in multicentric locations or surgically inaccessible locations.

Fourth Ventricular Rosai-Dorfman Disease Mimicking Intraventricular Tumor in Young Adult: A Rare Case Report.

Rosai-Dorfman disease (RDD) or sinus histiocytosis with massive lymphadenopathy can present with or without systemic disease. It is a benign histioproliferative disorder characterized by generalized lymphadenopathy, weakness, anemia, and rarely extranodal involvement. While RDD most commonly affects lymph nodes, extranodal involvement of multiple organs has been reported, including the central nervous system (CNS). However, CNS involvement in RDD is rare and is not well characterized. Isolated involvement of the fourth ventricle is even rarer. Such lesions may be mistaken for intraventricular tumors such as ependymoma or medulloblastoma. This report highlights the necessity to consider RDD as a differential diagnosis in case of intraventricular space-occupying lesion.

Lenalidomide and dexamethasone for Rosai-Dorfman disease: a single arm, single center, prospective phase 2 study.

Background: Rosai-Dorfman disease (RDD) is a rare heterogeneous histiocytic disorder lacking standardized first-line treatment. Methods: This single-center, phase 2 prospective study enrolled 13 newly diagnosed and 10 recurrent RDD patients from June 2021 to March 2023 at Peking Union Medical College Hospital (Beijing, China). Lenalidomide 25 mg days 1-21 plus dexamethasone 40 mg days 1, 8, 15, 22 was administered in 28-day cycles, totaling 12 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate (ORR) to lenalidomide and dexamethasone (RD) regimen, toxicity, and overall survival (OS) measured from RD start to death or last follow-up. OS and PFS were estimated according to Kaplan-Meier survival analysis and compared with the log-rank test. For OS and OR rate, 95% confidence limits were obtained using the Clopper-Pearson method, with standard methods used for PFS. p < 0.05 was considered statistically significant. The trial was registered with ClinicalTrials.gov (NCT04924647). Findings: The median age was 44 years (IQR 35-54). All patients had extranodal RDD. MAPK pathway alterations occurred in 6/18 (33%). Elevated IL-6 and TNF-α were found in 39% (n = 9) and 70% (n = 16), respectively. All patients received ≥6 cycles (median 12, range 6-12, IQR 10-12). The ORR was 87% (20/23, 95% CI 66%-97%), 30% (n = 7) complete remission, 57% (n = 13) partial remission). Treatment with RD significantly decreased median serum levels of both IL-6 (from 5.9 (IQR 4.2-8.7) to 2.9 (IQR 2.1-5.9) pg/mL, p = 0.031) and TNF-α (from 12.2 (IQR 8.6-17.9) to 8.3 (IQR 6.1-10.5) pg/mL, p = 0.0012). With a median 26 months follow-up (range 6-28, IQR 16-28), 4 patients relapsed and none died. Two-year OS and PFS were 100.0% (95% CI 85%-100%) and 69.0% (95% CI 51%-94%), respectively. No grade 3-4 adverse events or discontinuations due to adverse events occurred. Twelve patients (n = 12, 52%) had grade 1-2 hematological toxicity. Other toxicities included constipation (n = 2, 9%), glucose intolerance (n = 2, 9%), edema (n = 2, 9%), insomnia (n = 1, 4%), and tremor (n = 1, 4%). Interpretation: Lenalidomide and dexamethasone regimen is an effective and safe regimen for newly diagnosed and recurrent RDD. Funding: National Natural Science Foundation of China, Beijing Natural Science Haidian frontier Foundation Funding, and the National High Level Hospital Clinical Research Funding.

Rosai Dorfman Disease of Nose and Paranasal Sinuses: An Incidental Discovery.

Rosai Dorfman disease is a benign lymphoproliferative disorder. Isolated extranodal involvement is rarely encountered. The causation has not been attributed to any particular factor and the clinical progress of the disease is varied. Treatment options range from observation to medical therapy to surgical excision. Long term follow up is advocated. We report an elderly female with complaints of nasal obstruction who underwent ESS and was diagnosed with this disease on account of histopathology. Follow up period has been uneventful. The case report illustrated here is aimed at highlighting high index of suspicion as well as creating awareness regarding diagnosis and management of a rarely seen pathology.

Extranodal Rosai-Dorfman Disease of Breast Mimicker of Breast Malignancy.

Rosai-Dorfman-Destombes (RDD) disease is also known as sinus histiocytosis with massive lymphadenopathy. It is an uncommon heterogeneous disease of children and young adults. Most of the patients with RDD generally present with painless lymphadenopathy, while extranodal and multisystem manifestation of the disease is unusual. The diagnosis is based on the imaging with clinicopathological correlation. Flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography is useful for the initial staging of the RDD lesions, which have similar appearance and avidity like intermediate and high-grade lymphomas. Here, we present the case of a 55-year-old female presented with left breast mass that turned out to be the extranodal Rosai-Dorfman disease.

Case report: A rare case of isolated sigmoid Rosai-Dorfman disease on contrast-enhanced CT and 18F-FDG PET/CT.

Rosai-Dorfman disease (RDD) is an uncommon histiocytic disorder that occurs in nodal and/or extranodal sites. Extranodal RDD exhibits a wide range of clinical and radiological presentations, frequently leading to misdiagnoses. Involvement of the gastrointestinal (GI) system is uncommon, accounting for less than 1% of the reported cases. Here we present a case of a 54-year-old male who complained of abdominal distention and was diagnosed with RDD affecting the sigmoid colon, manifesting as a sigmoid mass. The patient had a past medical history of liver transplantation due to hepatocellular carcinoma (HC). This report details the multiphase contrast-enhanced computed tomography (CT) and fluorodeoxyglucose (18F-FDG) positron emission tomography (PET-CT) imaging findings of RDD involving the sigmoid colon without lymphadenopathy, and a review of the relevant literature is provided.

Thymic Rosai-Dorfmann disease: a case report.

BACKGROUND: Rosai-Dorfman disease (RDD), known as sinus histiocytosis with massive lymphadenopathy, commonly involves lymph nodes in the neck or mediastinum, although extranodal involvement is observed in approximately 40% of RDD patients. RDD involving only the thymus has rarely been reported. Here, we report a case of RDD originating in the thymus. The lesion was surgically removed, and a cure was finally achieved. There was no recurrence after telephone follow-up for 3 years. CASE PRESENTATION: A 52-year-old male was accidentally found to have a 7 × 6 cm anterior mediastinum lump by chest computed tomography (CT). The mediastinal lesion was resected by surgery, and postoperative pathology revealed RDD originating from the thymus. Regular telephone follow-up after surgery lasted 3 years and showed that the patient remained in good condition without any relevant symptoms. CONCLUSIONS: RDD originating in the thymus cannot be characterized from CT images and is easily misdiagnosed as a traditional mediastinal tumor. This is mainly because there is so little disease in this area that physicians are not aware of it. We report this case with the hope that clinicians will have a better understanding of this disease. According to our follow-up results, surgery is an effective means of treatment.

Cutaneous Rosai-Dorfman disease: a systematic review and reappraisal of its treatment and prognosis.

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.

Cranial Rosai-Dorfman disease: a case report and literature review.

Rosai-Dorfman Disease (RDD) is a rare, benign, idiopathic histiocytic proliferative disorder, with its occurrence in the cranial bones being particularly uncommon and prone to misdiagnosis in preoperative radiological examinations. This article reports a case of RDD in the left temporal bone. The radiological presentation of intraosseous RDD includes osteolytic bone destruction, infrequent periosteal reaction, clearly defined tumor margins, and marked uniform enhancement on contrast-enhanced scans. However, these radiological features lack specificity, highlighting the necessity of histopathological examination for a definitive diagnosis, especially for the rarer extranodal subtypes of RDD. Surgical excision of the lesion can lead to favorable therapeutic outcomes.

Radiotherapeutic outcomes of Rosai-Dorfman disease with falx cerebri and superior sagittal sinus involvement: A rare case report with long-term follow-up.

Key Clinical Message: Intracranial RDD is rare medical event mimicking different diagnoses. Although the surgical resection is the best treatment option, but radiation therapy can also achieves long-term suboptimal outcomes. Abstract: An 83-year-old male with a history of tension-type headaches was evaluated. He was conscious with no focal neurological deficits. His brain MRI revealed an enhancable bifrontal tumor originating from falx cerebri and superior sagittal sinus dura. Due to the patient's preference and decline for gross total resection, she underwent a stereotactic biopsy. The pathology was positive for Rosai-Dorfman diseases. He received definitive targeted radiation with a total dose of 4500 cGy administered in 200 cGy daily fractions. His 4-year follow-up showed regional tumor control with excellent neurological outcome.

Orbital histiocytosis; From A to Z.

PURPOSE: Histiocytosis is one of the most challenging diseases in medical practice. Because of the broad spectrum of clinical manifestations, systemic involvements, unknown etiology, and complex management, different types of histiocytosis are still a big question mark for us. Orbital histiocytosis is characterized by the abnormal proliferation of histiocytes in orbital tissues. It could affect the orbit, eyelid, conjunctiva, and uveal tract. Orbital histiocytosis can cause limited eye movement, proptosis, decreased visual acuity, and epiphora. In this study, we review the novel findings regarding the pathophysiology, diagnosis, and treatment of different types of histiocytosis, focusing on their orbital manifestations. METHOD: This review was performed based on a search of the PubMed, Scopus, and Embase databases or relevant published papers regarding orbital histiocytosis on October 9th, 2023. No time restriction was proposed, and articles were excluded if they were not referenced in English. RESULTS: 391 articles were screened, most of them being case reports. The pathophysiology of histiocytosis is still unclear. However, different mutations are found to be prevalent in most of the patients. The diagnostic path can be different based on various factors such as age, lesion site, type of histiocytosis, and the stage of the disease. Some modalities, such as corticosteroids and surgery, are used widely for treatment. On the other hand, based on some specific etiological factors for each type, alternative treatments have been proposed. CONCLUSION: Significant progress has been made in the detection of somatic molecular changes. Many case studies describe various disease patterns influencing the biological perspectives on different types of histiocytosis. It is necessary to continue investigating and clustering data from a broad range of patients with histiocytosis in children and adults to define the best ways to diagnose and treat these patients.

A rare presentation of Rosai-Dorfman disease as a single dural-based lumbar intradural lesion: A case report.

Central nervous system Rosai Dorfman disease (RDD) is a rare condition and it is just reported in 5% of 600 registered RDD cases. In previously reported patients, the intradural extramedullary spinal lesion is extremely rare. In this article, we aim to report a case of intradural extramedullary Rosai-Dorfman lesion of the lumbar spine which was managed with gross total resection. Lumbar meningioma was the pre-operative diagnosis for this patient, the final correct diagnosis of Rosai-Dorfman disease was made after histological examination. RDD should be considered in the differential diagnosis of single intradural extramedullary lesions of the lumbar spine.