Common progenitor origin for Rosai-Dorfman disease and clear cell sarcoma.

Histiocytic neoplasms (HNs) in adults have been reported to be associated with a high prevalence of coexisting haematological and solid malignancies. While a proportion of coexisting HNs and haematological malignancies share identical genetic alterations, the genetic association between HNs and solid malignancies has scarcely been reported. We report a case of Rosai-Dorfman disease (RDD) complicated by coexisting clear cell sarcoma (CCS). RDD is a rare HN. CCS is an ultrarare soft tissue sarcoma with a poor prognosis. Mutation analysis with whole-exome sequencing revealed six shared somatic alterations including NRAS p.G12S and TP53 c.559+1G>A in both the RDD and CCS tissue. This is the first evidence of a clonal relationship between RDD and solid malignancies using mutational analysis. We hypothesise that neural crest cells, which originate in CCS, are likely the common cells of origin for RDD and CCS. This case helps to unravel the underlying clinicopathological mechanisms of increased association of solid malignancies in HNs. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Rosai-Dorfman-Destombes disease in adults: a single center experience.

Recent advances in Rosai-Dorfman-Destombes disease (RDD), notably molecular testing, targeted therapy, and PET-CT imaging, hold promise for better recognition and improved outcomes. This study presents patients diagnosed and treated in a "real world" setting, where navigating limited resources must be considered. This retrospective single-center review includes 15 adult patients diagnosed with RDD at Vancouver General Hospital between November 2015 and October 2023. The cohort comprised five males and ten females with a median age 53 years (range 19-80 years). All 15 patients had extra-nodal disease; 11 patients exclusively had extra-nodal disease, and four patients also had lymph node involvement. Seven patients had tissue next-generation sequencing, identifying MAP2K1 mutations in four cases and a KRAS p.K117N mutation in one case that was treated with targeted therapy using trametinib. PET-CT was used for disease staging in four cases. Six patients with refractory disease tolerated lenalidomide and dexamethasone without significant toxicity; three patients achieved complete response, and three had partial response. This study highlights RDD's diverse extra-nodal manifestations. Lenalidomide combined with dexamethasone is an effective and well-tolerated treatment option for select patients, especially those with refractory disease. Broad utilization of NGS and PET-CT can positively influence management decisions.

Cutaneous Rosai-Dorfman disease with MAP2K1 mutation, initially mimicking an infection with parasitized histiocytes.

Rarely, Rosai-Dorfman disease (RDD) manifests exclusively in the skin, typically as nodules on the trunk and extremities. Recognition of characteristic histopathologic features enables diagnosis of RDD. A 55-year-old female presented with a 7-year history of cutaneous nodules involving the trunk and extremities. A prior skin biopsy specimen at a different institution had demonstrated a dense dermal lymphohistiocytic infiltrate with histiocytes containing GMS+ forms, favored to represent cryptococcal organisms, with a differential diagnosis including other infections with parasitized histiocytes. Despite antibiotic therapy, lesions persisted. After a presentation to our institution, a biopsy specimen showed a diffuse infiltrate, including histiocytes with voluminous pale cytoplasm with focal emperipolesis of inflammatory cells and S100 immunohistochemical positivity. Clinical and radiologic examinations did not identify significant extracutaneous involvement. A genetic study performed on the biopsy specimen identified a K57Q mutation of MAP2K1. The presence of this mutation correlated with prior reports of MAP2K1 mutation in classic RDD, thereby supporting our histopathologic diagnosis of RDD over an infectious process and further illuminating options for targeted therapies. At 3-year follow-up, the patient has been managed with a course of systemic corticosteroids and excision of bothersome lesions. Consideration of systemic therapy is ongoing.

Synchronous occurrence of primary cutaneous B-cell lymphoma and cutaneous Rosai-Dorfman disease in distinct lesions: A unique association.

Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy (SHML), is a rare subtype of reactive histiocytosis which is seldom associated with Hodgkin's and non-Hodgkin's lymphomas. To date, the coexistence in the same patient of extra nodal SHML and primary cutaneous B-cell lymphoma (PCBCL) has been reported in the literature, as metachronous diagnosis in the anatomical area of the original PCBCL or synchronous occurrence in the same lesions. However, no data have been published as for synchronous occurrence of the two pathological entities in distinct anatomical sites. Herein, we report the first ever described synchronous occurrence of PCBCL and SHML, detected in distinct lesions, affecting the same patient. The complete resolution of the patient's PCBCL after rituximab treatment and the concomitant regression of SHML suggest that this clinically benign reactive histiocytic proliferation, potentially triggered by the lymphoma microenvironment itself, may take place not only in the site of the PCBCL lesion, but also in other distant areas not directly affected by the primary cutaneous lymphoma.

Primary Rosai-Dorfman disease of the central nervous system: A clinical, histological, and molecular appraisal.

Rosai-Dorfman disease (RDD) is characterized by clonal proliferation of S-100 positive histiocytes and variable emperipolesis. It commonly affects cervical lymph nodes. Central nervous system (CNS) involvement is extremely rare. We attempted to evaluate the Cyclin D1 expression and frequency of KRAS and BRAF mutations in the RDD involving the CNS. All patients with histopathologically diagnosed RDD involving CNS were recruited from 2011 to 2022. All cases were subjected to immunohistochemistry for CD68, CD163, S100, CD1a, GFAP, CD207, EMA, ALK, BRAFV600E, IgG4, IgG, and CyclinD1. The real-time polymerase chain reaction (RT-PCR) for hotspot mutation analysis of KRAS (exons 2, 3, and 4) and BRAF (V600E) was conducted on formalin-fixed paraffin-embedded tissue using a commercial kit (EntroGen). A total of seven cases were included. The median age was 31 years, with six men and one woman. It showed spinal cord (n = 4) and intracranial (n = 3) involvement. Histologically, all cases showed histiocyte-rich inflammation with evidence of emperipolesis. These histiocytes were positive for S100, CD68, CD163, and Cyclin D1, whereas negative for CD1a, CD207, and EMA. BRAF V600E was expressed in a single case. None of the control cases (demyelination and infarction) with histiocytic infiltrate showed Cyclin D1 expression. Four RDD cases showed increased IgG4-positive plasma cells (>10/HPF) and IgG4/IgG ratio (>40%). BRAF V600E mutation was detected in one case (14.28%), while none showed KRAS mutation. RDD involving CNS is extremely rare and diagnostically challenging. Nuclear Cyclin D1 expression along with S-100 positivity in the tumor cells is a strong diagnostic clue. BRAF and KRAS mutations are rare in CNS RDD.

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.

Extranodal Rosai-Dorfman Disease: a rare presentation involving anterior chest wall in a middle-aged female.

Rosai-Dorfman Disease is a rare benign disorder involving overproduction of immune cells, causing swollen lymph nodes and, in rare cases, the sternum. The sternal involvement may cause chest pain and masses. Diagnosis is confirmed through clinical examination, biopsy, and imaging. Treatment options may include surgery, radiation, or steroids. In this case study, we present an unusual example of extranodal Rosai-Dorfman Disease involving the sternum, bilateral clavicles and first three ribs, and pectoral muscle with no associated lymphadenopathy or systemic symptoms in a 57-year-old female. The etiology, pathology, immunohistochemistry, imaging findings, and treatment options of this unique disease are discussed.

Orbital masses as a rare presentation of Rosai-Dorfman disease: Clinicopathologic characterization of five cases.

Rosai-Dorfman disease (RDD) is a rare, non-Langerhans cell histiocytosis. Most cases present with marked, non-tender lymphadenopathy due to the proliferation of atypical histiocytes. A minority of cases involves extranodal sites and can present as bone lesions, skin rashes, pulmonary nodules, and rarely orbital masses. Orbital involvement in RDD is rare and may infrequently present as an isolated tumor mass without lymphadenopathy. This study aims to better characterize this uncommon presentation of this rare disease. Five cases of orbital RDD were identified from the last 18 years and the clinical characteristics of each case were compared with histopathological findings. Three men and two women ages 12-36 presented with complaints of eye swelling and/or vision changes. One patient had a history of neurofibromatosis type I and inflammatory pseudotumors while the other four had no signs of systemic disease or other sites of extranodal involvement at the time of presentation. Masses ranged in size from 1.0 cm to 3.5 cm and primarily involved the superior orbit. Resected lesions all displayed characteristic findings of admixed atypical histiocytes, lymphocytes, and plasma cells with a fibrotic background. Emperipolesis was seen in all cases. Immunostaining for S100 and CD68 was diffusely positive in the histiocyte population. Clinical follow-up was obtained for 4 of 5 patients: all four were disease-free at 1 to 15 years after resection. RDD should be considered in the differential for patients with orbital masses, even in the absence of lymphadenopathy or signs of systemic disease.

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.

Characterizing Rosai-Dorfman disease with [18F]FDG PET/CT: a retrospective analysis of a single-center study.

OBJECTIVES: Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytic proliferative disorder. We performed a retrospective study to characterize the clinical and [18F]FDG PET/CT features of RDD. METHODS: We retrospectively recruited 38 RDD patients with [18F]FDG PET/CT scan in our center. [18F]FDG PET/CT features were assessed, and clinical and follow-up data were recorded. RESULTS: In the recruited patients, 20/38 (52.6%) patients had single-system disease, while others (18/38, 47.4%) had disease affecting multiple system. RDD most commonly involved the upper respiratory tract (47.4%), followed by cutaneous/subcutaneous lesion (39.5%), lymph node (36.8%), bone (31.6%), central nervous system (28.9%), and cardiovascular system (13.2%) in the recruited patients. In PET/CT, the RDD lesions were FDG-avid, and the SUVmax of the hottest lesion in an individual patient was positively correlated with C-reactive protein levels (r = 0.418, p = 0.014), and negatively correlated with hemoglobin levels (r = -0.359, p = 0.036). The overall response rate of the first-line treatment was 80.8% in newly diagnosed RDD patients, and for patients with relapsed/progressive RDD, the overall response rate was 72.7%. CONCLUSION: [18F]FDG PET/CT could be a useful tool for evaluating RDD. KEY POINTS: • About half of the patients with Rosai-Dorfman disease had single-system disease, while others had disease affecting multiple system. Rosai-Dorfman disease most commonly involved the upper respiratory tract, followed by cutaneous/subcutaneous lesion, lymph node, bone, central nervous system, and cardiovascular system. • In [18F]FDG PET/CT, Rosai-Dorfman disease was usually hypermetabolic, and the SUVmax of the hottest lesion in an individual patient was positively correlated with C-reactive protein levels. • Rosai-Dorfman disease usually has a high overall response rate after treatment.