Rosai-Dorfman Disease Research Articles

Neurological Manifestations of Histiocytic Disorders.

Histiocytic disorders, including Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LCH), and Rosai-Dorfman disease (RDD), are rare neoplasms that may present with a spectrum of neurologic involvement. Diagnostic delay is common due to heterogeneity in presentation and challenging pathology. Recent advances in the treatment of these diseases targeted towards mutations in the MAP kinase pathway have led to an improved prognosis in these patients with neurologic involvement. It is critical for clinicians to have a high index of suspicion to allow for early targeted treatment and optimize neurologic outcomes. A systematic approach to diagnosis is presented in this article to allow for accurate diagnosis of these rare diseases.

Comparison of neuroimaging features of histiocytic neoplasms with central nervous system involvement: a retrospective study of 121 adult patients

ObjectivesTo compare neuroimaging characteristics of three types of histiocytoses, namely Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), and Rosai-Dorfman disease (RDD), with central nervous system (CNS) involvement.MethodsA total of 121 adult patients with histiocytoses (77 LCH, 37 ECD, and 7 RDD) and CNS involvement were retrospectively included. Histiocytoses were diagnosed based on histopathological findings combined with suggestive clinical and imaging features. Brain and dedicated pituitary MRIs were systematically analyzed for tumorous, vascular, degenerative lesions, sinus, and orbital involvement and for hypothalamic pituitary axis involvement.ResultsEndocrine disorders, including diabetes insipidus and central hypogonadism, were more common in LCH patients than in ECD and RDD patients (p < 0.001). In LCH, tumorous lesions were mostly solitary (85.7%), located in the hypothalamic pituitary region (92.9%), and without peritumoral edema (92.9%), while in ECD and RDD, tumorous lesions were often multiple (ECD: 81.3%, RDD: 85.7%), their distribution was more widespread with meninges mostly involved (ECD: 75%, RDD: 71.4%), and they most likely presented with peritumoral edema (ECD: 50%, RDD: 57.1%; all p ≤ 0.020). Vascular involvement was an exclusive imaging characteristic of ECD (17.2%), which was not observed in LCH or RDD; this was also associated with a higher risk of death (p = 0.013, hazard ratio = 11.09).ConclusionThe typical characteristic of adult CNS-LCH was endocrine disorders with radiological findings limited to the hypothalamic pituitary axis. The pattern of multiple tumorous lesions with predominant involvement of meninges was the main manifestation of CNS-ECD and CNS-RDD, while vascular involvement was pathognomonic for ECD and associated with poor prognosis.Clinical relevance statementInvolvement of the hypothalamic-pituitary axis is the typical imaging characteristic of Langerhans cell histiocytosis. Multiple tumorous lesions, predominantly involving but not limited to meninges, occur in most Erdheim-Chester disease and Rosai-Dorfman disease patients. Vascular involvement occurs only in Erdheim-Chester disease patients.Key Points• The different distribution patterns of brain tumorous lesions can help differentiate among LCH, ECD, and RDD.• Vascular involvement was an exclusive imaging finding of ECD and was associated with high mortality.• Some cases with atypical imaging manifestations were reported to further expand the knowledge on these diseases.

The value of 18F-FDG PET/CT in the systemic evaluation of patients with Rosai–Dorfman disease: a retrospective study and literature review

BackgroundRosai–Dorfman disease (RDD) is a rare form of non-Langerhans cell histiocytic disease. The aim of this study was to review the characteristics of RDD using 18F-FDG PET/CT and determine its efficacy in the disease management.ResultsA total of 28 RDD patients underwent 33 18F-FDG PET/CT scans for systematic assessment and follow-up. The common involved sites included the lymph nodes (17, 60.7%), upper respiratory tract (11, 39.3%), and skin (9, 32.1%). Five patients had more lesions detected in PET/CT images than in CT and/or MRI, including inapparent nodules (n = 5) and bone destruction (n = 3). After thorough treatment evaluation using PET/CT, the treatment strategies of 14 patients (14/16, 87.5%) were changed. Five patients underwent PET/CT twice during follow-up and the SUVs were significantly decreased (15.3 ± 3.4 vs. 4.4 ± 1.0, p = 0.02), which demonstrated disease improvement.Conclusions18F-FDG PET/CT contributed to displaying the holistic characteristics of RDD, in particular during initial assessment, treatment strategy adjustment, or efficacy evaluation, and could compensate for some disadvantages of CT and MRI images.

How I Diagnose Rosai-Dorfman Disease.

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. We discuss the diagnosis of RDD using 2 illustrative cases, interpretative challenges, and a diagnostic algorithm. 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. 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.

Rosai-Dorfman Disease with Nodal and Extranodal Involvements: A Case Report

Rosai-Dorfman disease (RDD) is a rare histiocytic disorder characterized by the proliferation of non-Langerhans cells within the lymph nodes, and occasionally in extranodal sites. We report a case of RDD presenting as a left jugal swelling in a 43-year-old male. Imaging studies revealed a poorly defined lesion infiltrating the subcutaneous and muscular planes, as well as the maxillary bone. Biopsy confirmed the diagnosis of RDD. Treatment included surgical excision, followed by low-dose radiation therapy. The patient remained asymptomatic during a one-year follow-up.

Quantification of linear and nonlinear elasticity by compression optical coherence elastography for determining lymph node status in breast cancer

We report the first application of compression optical coherence elastography (C-OCE) to evaluate both linear and nonlinear elastic properties of lymph nodes (LNs) for assessing their status, which is an important factor for detecting metastasis and staging breast cancer. The reported study involved 27 excised sentinel and axillary LNs from 24 patients with breast cancer, including normal LNs (n = 6), reactive LNs with follicular hyperplasia (n = 7) and sinus histiocytosis (n = 8), and metastatic LNs (n = 6). C-OCE data were compared with co-registered gold-standard histopathology and demonstrated a significantly higher contrast in differentiation of LNs as compared to structural optical coherence tomography imaging. Normal LNs are characterized by low stiffness values in the areas of LN cortex (<200 kPa). C-OCE revealed that abnormal reactive LNs with follicular hyperplasia exhibit moderately increased stiffness (200–300 kPa) in the cortex areas and more pronounced stiffness increase (400–600 kPa) in the areas of sinus histiocytosis. LNs with total metastasis exhibit fairly uniformly distributed highest stiffness values (>600 kPa). Since in terms of the tangent Young’s modulus there remained an appreciable overlap among these types of LNs, we also evaluated their elastic nonlinearity parameters. Complementary usage of both linear and nonlinear elastic parameters enabled very clear differentiation of all four main states of LNs. Thus, C-OCE imaging demonstrates high potential for future intraoperative usage to rapidly determine the LN status during breast-conserving surgery and to assess the extent of the cancer cells propagation in regional lymphatic collectors for preserving benign LNs. This is important for reducing the associated risks and complications (such as lymphedema) from excessive surgical removal of lymphoid structures.

ROSAI DORFMAN DISEASE-A RARE DISEASE, ATYPICALLY PRESENTING AS PALINDROMIC RHEUMATISM

Sinus histiocytosis with massive lymphadenopathy (SHML)(Rosai Dorfman disease) is a rare disorder of unknown etiology, usually associated with lymph node enlargement in various supercial or deep sites. These cases can often be misdiagnosed as lymphoma. The disease affects predominantly the younger age group. It is a benign proliferative histiocytic disorder morphologically characterized by 'emperipolesis'. Extranodal involvement isnot rare (43%).Sites include skin, nasal cavity, para nasal sinuses, eyelids, orbit, bone and central nervous system (1)

Molecular and clinicopathologic characterization of pediatric histiocytoses.

The spectrum of somatic mutations in pediatric histiocytoses and their clinical implications are not fully characterized, especially for non-Langerhans cell histiocytosis (-LCH) subtypes. A cohort of 415 children with histiocytosis from the French histiocytosis registry was reviewed and analyzed for BRAFV600E . Most BRAFWT samples were analyzed by next-generation sequencing (NGS) with a custom panel of genes for histiocytosis and myeloid neoplasia. Of 415 case samples, there were 366 LCH, 1 Erdheim-Chester disease, 21 Rosai-Dorfman disease (RDD), 21 juvenile xanthogranuloma (JXG, mostly with severe presentation), and 6 malignant histiocytosis (MH). BRAFV600E was the most common mutation found in LCH (50.3%, n = 184). Among 105 non-BRAFV600E -mutated LCH case samples, NGS revealed mutations as follows: MAP2K1 (n = 44), BRAF exon 12 deletions (n = 26), and duplications (n = 8), other BRAF V600 codon mutation (n = 4), and non-MAP-kinase pathway genes (n = 5). Wild-type sequences were identified in 17.1% of samples. BRAFV600E was the only variant significantly correlated with critical presentations: organ-risk involvement and neurodegeneration. MAP-kinase pathway mutations were identified in seven RDD (mostly MAP2K1) and three JXG samples, but most samples were wild-type on NGS. Finally, two MH samples had KRAS mutations, and one had a novel BRAFG469R mutation. Rarely, we identified mutations unrelated to MAP-kinase pathway genes. In conclusion, we characterized the mutational spectrum of childhood LCH and clinical correlations of variants and subtypes. Variants responsible for JXG and RDD were not elucidated in more than half of the cases, calling for other sequencing approaches.

Thoracic primary Rosai-Dorfman disease complicated with compression fracture:a case report

Thoracic primary Rosai-Dorfman disease complicated with compression fracture:a case report

The Rosai-Dorfman Syndrome: A Case Report

Sinus histiocytosis, also known as Rosaï Dorfman Syndrome (SRD), is a noncancerous condition that causes the growth of large masses of histiocytes in lymph nodes, primarily in the cervical area. Visceral damage is common, and diagnosis is made through histological examination. The cause of SRD is unknown and can occur at any age, even in children. The condition can sometimes improve spontaneously, but large tumor masses can cause compression and damage, particularly if they involve the retro-orbital or epidural areas. In most cases, it is best to avoid treatment, but therapeutic interventions may be necessary for forms of the disease that pose a direct threat or are progressing. Treatment is not standardized and may involve surgery, corticosteroids, immunosuppressants, and/or alpha interferon, depending on the individual case.&#x0D; We present a case study of a 4-year-old child who had multiple bilateral adenopathies. The diagnosis was verified through a biopsy of the lymph nodes.

Abstract 4536: Investigating the correlation between molecular diagnostics, targeted therapies and treatment outcomes in Rosai Dorfman disease: a single-institution experience

Abstract Introduction: Rosai Dorfman Disease (RDD) is a non-Langerhans cell histiocytic disease whose pathologic features include sinus histiocytosis with variable emperipolesis. Traditional management consists of local therapies (resection, radiation) for limited lesions and myelosuppressive therapies for systemic disease. Recent studies, however, have identified MAP Kinase pathway mutations in RDD, prompting further research into the utility of targeted agents. Methods: A retrospective analysis was conducted at a single institution over a 20-year period (2002-2022) of 40 patients with RDD. Inclusion criteria included age ≥18 and histopathologic evidence of RDD without obscuring secondary malignancies. Clinical data points included biological gender, age at diagnosis, molecular diagnostics, imaging and therapies administered. Binary data was utilized for statistical analysis and comparison of outcomes by treatment type, time to diagnosis and use of targeted agents. Results: In this analysis, 72% of patients were female and 28% male with an average age at diagnosis of 45.8 years, over 50% of whom were diagnosed between 1 and 12 months of presentation. Primary disease was most commonly extranodal (&amp;gt;90%), found in cutaneous, osseous and CNS structures (50%, 36% and 16.6%, respectively). Regarding management, surgery was most common in &amp;gt;36% of patients, followed by steroid and myelosuppressive therapies (25% each), immunotherapy (13.88%) and targeted molecular therapies (11.1%). Disease responses were considered stable if grossly unchanged during serial exam or imaging surveillance, partial if diminished but still present and complete if disease was grossly and radiographically resolved; a partial response or better was observed in &amp;gt;75% of patients. With respect to treatment rendered, stable disease was equally likely between recipients of molecular and conventional (non-molecular) therapy at 25%. Partial responses were higher in molecular therapy recipients (75% as compared to 42%), although complete responses have not yet been observed in this cohort. Patients diagnosed at &amp;lt;1 month from symptom onset had higher rates of disease stability and complete responses compared to those diagnosed at &amp;gt;24 months. Conclusions: To our knowledge, this study is the largest of its kind in adult Rosai Dorfman Disease. Early recognition and utilization of targeted molecular therapies, based on our preliminary data, are associated with higher rates of achieving disease stability and at least a partial response. The current absence of complete responses in patients receiving targeted molecular therapy is likely attributable to the still-emerging use of these agents and interim response assessments not yet being completed. Higher complete response rates in targeted agents relative to conventional therapies are anticipated in ongoing analyses. Citation Format: Samuel B. Reynolds, Sabrina R. Wilcox, Moshe Talpaz, Asra Z. Ahmed. Investigating the correlation between molecular diagnostics, targeted therapies and treatment outcomes in Rosai Dorfman disease: a single-institution experience. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4536.

PU.1 is a useful nuclear marker to distinguish between histiocytosis and histiocyte-rich tumours.

The aim was to test the expression of PU.1 on different types of histiocytoses and to test the utility of PU.1 in confirming or excluding a histiocytic origin in tumour samples with suspicion of histiocytosis. We analysed 66 biopsies of nonmalignant histiocytoses represented by Langerhans-cell histiocytosis (n = 13), Erdheim-Chester disease (ECD) (n = 19), Rosai-Dorfman disease (RDD) (n = 14), mixed ECD-RDD (n = 3), ALK-positive histiocytosis (n = 6), and juvenile xanthogranuloma (n = 11). All cases were positive for PU.1 in reactive and neoplastic histiocytes. In addition, 39 cases of tumours with high-grade cytological atypia were referred to our center as suspicion of malignant histiocytosis/histiocytic sarcoma and only 18 were confirmed. Indeed, more than half of these tumours (21/39) were either undifferentiated malignant tumours with a stroma rich in histiocytes, diffuse large B-cell lymphoma, or high-grade dedifferentiated liposarcoma. PU.1 was useful to distinguish between the negativity of large atypical nuclei and the positivity of stromal reactive histiocytes. PU.1 is expressed by all types of histiocytosis. It distinguishes histiocytosis from histiocyte-rich tumours with an easy interpretation due to its sharp nuclear staining. Its negativity in lesional/tumour cells in histiocyte-like lesions is useful to eliminate a histiocytosis.

Cervical tumefaction in a child at Brazzaville University Hospital, Republic of the Congo

A 8-year-old schoolgirl from West Africa with no previous pathological history was admitted to the haematology department of the Brazzaville University Hospital for the management of cervical adenopathy. The diagnosis of sinus histiocytosis or Destombes-Rosaï-Dorfman disease was retained and the patient was treated with PO corticosteroids (methylprednisolone 32 mg/d then 16 mg/d). Given the rarity and uncertain aetiopathogeny of this syndrome, treatment is poorly codified. It includes corticosteroid therapy, immunomodulators and sometimes chemotherapy, radiotherapy or surgery, indicated in case of clinical manifestations of local organ compression. The disease may regress spontaneously. Its benignity does not justify systematic treatment in the absence of complications.

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

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. 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. 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%. [18F]FDG PET/CT could be a useful tool for evaluating RDD. • 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.

Top Ten Lymphoproliferative Lesions Not to Miss When Evaluating Oral Ulcer Biopsies.

Oral ulcers represent afull thickness lossof the mucosal epithelium leading to exposure of the submucosal connective tissue. These are common and usually self-limited lesions, although they may sometimes result from neoplasms, most commonly squamous cell carcinoma. Lymphoproliferative disorders may be difficult to diagnose in apthous ulcers since they mimic reactive inflammation. This review presents ten rare oral lymphoid proliferations which should not be missed when assessing oral ulcer biopsies. The ten lesions include several with diagnostic cells which look similar to the histiocytes of a reactive inflammatory ulcer, including Rosai-Dorfman disease, reticulohistiocytoma, Langerhans cell histiocytosis, and traumatic ulcerative granuloma. Other lesions, such as EBV-positive mucocutaneous ulcer, extranodal marginal zone lymphoma of mucosal-associated lymphoid tissue, and plasmablastic lymphoma have lymphoid and/or plasma cell differentiation that mimic the reactive lymphocytes and plasma cells foundin reactive ulcers. Two dendritic cell lesions, follicular dendritic cell sarcoma and blastic plasmacytoid dendritic cell neoplasm, both have distinct phenotypes which are required to make an accurate diagnosis. Each of these lesions are diagnosed by evaluating their histology, along with their phenotypic profile, which is sometimes enhanced by pertinent molecular findings.

Bilateral clinoidal Rosai Dorfman disease mimicking meningioma – a rare cause of bilateral blindness

Rosai Dorfman disease is a self-limiting disease usually affecting the lymph nodes. Intracranial lesions are seen in less than 5% of cases. Isolated intracranial RDD without nodal involvement is rare, only 70 cases have been reported to date. Skull base lesions are seen in only 7 cases, petro clival RDD. Clionoidal lesions of RDD have not been reported in the literature, we report a rare case of bilateral Clionoidal lesions of RDD presenting with bilateral blindness in a young male.

Primary diffuse Rosai-Dorfman disease in central airway: a case report and literature review

BackgroundRosai-Dorfman disease (RDD) is a rare benign non-langerhans cell histiocytosis, mainly involving lymph nodes and skin. It is even rarer occurring only in central airway of lung and in diffuse form. Central airway RDD is similar to malignant tumor in imaging by radiological method and in bronchoscopy features. It is difficult to differentiate it from primary airway malignant tumor and to diagnose correctively in time.Case presentationHere we present a rare case of 18-year-old male diagnosed with primary diffuse RDD in central airway. Although the features examined by enhanced chest computed tomography, positron emission tomography/computed tomography, diffusion-weighted imaging of enhanced chest MRI and bronchoscopy indicate to be malignant tumor, the patient was definitely confirmed by multiple transbronchial biopsies and immunohistochemistry. After two transbronchial resections, the patient's symptoms of paroxysmal cough, whistle sound and shortness of breath were significantly reduced, as well as the airway stenosis was significantly improved. After 5 months of follow-up, the patient had no symptoms and the central airway were unobstructed.ConclusionsPrimary diffuse RDD in central airway is characterized by intratracheal neoplasm, which is usually suspected as malignant tumor according to radiological image and bronchoscopy. Pathology and immunohistochemistry are necessary for definite diagnosis. Transbronchial resection is effective and safe for patients with primary diffuse RDD in central airway.

Nasal Presentations of Rosai-Dorfman Disease: Clinical Manifestation and Treatment Outcomes.

There has been a lack of evidence-based management strategies on the nasal presentations of Rosai-Dorfman disease (RDD). We aim to investigate the clinical manifestation, treatment, and outcomes in patients with nasal RDD. We retrospectively reviewed available medical records of patients diagnosed with nasal RDD from 2014 to 2021 at our department. A total of 26 patients were included with a marked female preponderance (2.25:1). The most common symptom and affected sites were nasal congestion (31%) and nasal cavity (73%), respectively. The average times of biopsies was 1.5 times (range: 1-3). The histiocytes were positive about S100 and CD68 and negative for CD1a with common emperipolesis. The mean duration of follow-up was 34months (range, 3-87). One patient with concomitant nasal small B-cell lymphoma achieved complete remission after chemoradiotherapy. Recommended treatments were endoscopic resection (92%) and oral corticosteroids (21%). Surgery was performed to remove the resectable lesion as completely as possible. Corticosteroids induced almost 100% overall remission. Of the relapses, two patients achieved an overall response and one remained in progressive stage after subsequent excision. Two patients only received dissection biopsy that responded to oral corticosteroid administration and combined therapies of lenalidomide and dexamethasone, respectively. Diffuse lesions in nasal cavity and sinuses, and even widely affected nasal skull base, laryngopharynx, orbit, and cavernous sinus, should be considered the possibility of Rosai-Dorfman disease. Characteristic immunohistochemical staining is helpful for the diagnosis. Endoscopic surgical therapy remains the mainstream treatment for patients enduring an unbearable course. Oral corticosteroid administration serves as an adjuvant therapy for first-line treatments.

Successful treatment of non-Langerhans cell histiocytosis with the MEK inhibitor trametinib: a multicenter analysis

AbstractErdheim-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.

Erdheim-Chester Disease Involving the Left Uterine Adnexa: Mimicking an Ovarian Carcinoma Clinically.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis (LCH) that results in multiorgan disease involving the skin, bones, lungs, and kidneys. Female reproductive system manifestation of ECD was rare. Herein, we report a case of ECD involving the left ovary and fallopian tube. A 69-year-old woman presented with abdominal pain for 20 days. Magnetic resonance imaging revealed a solid and cystic mass on the left pelvic cavity. Histological examination revealed ovarian and fallopian tube infiltration by abundant histiocytes, with single small nuclei and foamy cytoplasm, reactive small lymphocytes, and plasma cells. Based on histopathological and immunohistochemical findings of positivity for CD68, CD163, and BRAF V600E and negativity for CD1α and S100, the molecular finding of BRAF V600E mutation, the patient was diagnosed with ECD. Positron emission tomography examination did not reveal any other lesions. The patient recovered well 12 months after surgery without any treatment. ECD involving the left fallopian tube and ovary was rare and needed to be differentiated from LCH, Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), IgG4+-related disease (IgG4+RD), and metastatic signet ring cell carcinoma.