Diagnosis Of Rosai-Dorfman Disease Research Articles

Clinicopathological characteristics of extranodal Rosai-Dorfman disease: A retrospective case series of 25 patients

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis, classically affecting the lymph nodes. Even rarer extranodal disease is diagnostically challenging due to overlapping histologic features with other entities and lack of a universally agreed set of biomarkers. Cyclin D1 immunohistochemistry (IHC) may serve as a useful adjunct in diagnosing extranodal RDD. We present a retrospective case series of patients diagnosed with extranodal RDD between January 2013 and December 2023. IHC staining for cyclin D1 was performed on archived tissue samples. Baseline IHC results for biomarkers supporting the RDD diagnosis were recorded along with patient demographic characteristics, clinical features, and disease outcomes. A total of 25 patients with extranodal RDD were included: 21 women (84 %) and 4 men (16 %). The mean age at diagnosis was 42.6 years. Cutaneous and deep tissue involvement was seen in 5 (20 %) and 20 (80 %) patients, respectively. 11 patients (44 %) had disease localized to the trunk and extremities, and 13 had disease in the head and neck region (52 %), of which 5 occurred in the nose and paranasal tissues. Available follow-up data showed most patients fully recovered (n = 11; 78.6 %). However, 1 patient had disease recurrence, 1 developed blindness, and 1 developed deafness. Cyclin D1 IHC was positive in all samples (100 %), consistent with previous studies. The clinicopathologic findings in this study highlight the spectrum of potential disease sites, possible morbid outcomes related to disease site, and the diagnostic utility of cyclin D1 IHC.

Rosai-Dorfman disease of the cauda equina: illustrative case.

Rosai-Dorfman disease (RDD) is a rare, nonmalignant histiocytosis. It typically occurs in lymph nodes, skin, and soft tissues, but numerous reports of central nervous system involvement exist in the literature. The peripheral nervous system has rarely been involved. In this study, the authors present a case of RDD isolated to the cauda equina. The presentation, management, surgical technique, and adjunctive treatment strategy are described. A 31-year-old female presented with 6 months of progressive left lower-extremity numbness involving the lateral aspect of the foot and weakness of the left toes. Magnetic resonance imaging of the lumbar spine demonstrated a homogeneously enhancing intradural lesion involving the cauda equina at the L2-3 levels. Histopathology after resection revealed a histiocytic infiltrate, positive for CD68 and S100, and emperipolesis consistent with RDD. No adjuvant therapy was administered, and the patient had full remission at the 1-year follow-up. Only five other cases of intradural RDD lesions of the cauda equina have been reported in the literature. RDD of the cauda equina is an especially rare and challenging diagnosis that can mimic other dura-based lesions, such as meningiomas. A definitive diagnosis of RDD relies on pathognomonic histopathological and immunohistochemical findings.

Unusual presentation of extranodal Rosai-Dorfman disease: A scalp lump

Rosai-Dorfman disease (RDD) is a benign and idiopathic proliferative histiocytic disorder that typically manifests with extensive cervical lymphadenopathy, fever, polyclonal gammopathy, and leukocytosis with neutrophilia. However, the purely cutaneous variant of RDD is exceptionally uncommon, occurring in only 3% of all RDD cases. In this abstract, we present a rare case of RDD exhibiting a purely cutaneous form. The patient, a 40-year-old male, presented with a scalp lump. Diagnostic investigations, including histopathological examination, confirmed the diagnosis of RDD. No lymphadenopathy or systemic involvement was detected, highlighting the uniqueness of the cutaneous presentation. The rarity of pure cutaneous RDD underscores the significance of reporting such cases to enhance our understanding of the diverse clinical manifestations of this condition. Awareness of this atypical presentation is crucial for accurate diagnosis and appropriate management, as the treatment approach for purely cutaneous RDD may differ from the more common systemic forms. Through this case report, we aim to contribute to the existing medical literature on RDD, emphasizing the need for careful evaluation of skin lesions to include RDD in the differential diagnosis, even in the absence of lymphadenopathy or systemic symptoms. Further research and documentation of similar cases will undoubt­edly advance our knowledge of this intriguing disease and aid clinicians in providing optimal patient care.

Diagnostic Challenges of Rosai-Dorfman Disease Presenting as Pachymeningitis and Meningiomatosis: A Report of Two Unusual Cases Involving the Spinal Cord

Rosai-Dorfman disease (RDD) is an exceptionally rare medical condition, with spinal cord involvement even more infrequent. It is frequently misidentified as another malignancy or infectious disease. In this report, we present two cases of RDD with spinal cord involvement. Each patient presented with spinal intradural extramedullary masses within the thoracic and cervical levels, respectively. The differential diagnoses remained uncertain, with the potential for pachymeningitis and meningiomatosis due to the shared nature of nonspecific imaging findings and clinical symptoms in both conditions. Given the presence of neurologic symptoms and spinal cord compression, the individual lesions were surgically excised. Subsequent pathological analysis definitively confirmed the diagnosis of RDD. As an adjunctive therapeutic measure, both patients were orally administered prednisolone. Both patients exhibited favorable neurologic improvement. These cases highlight the diagnostic challenges of RDD when solely relying on imaging studies. Surgical intervention, in conjunction with a meticulous pathologic examination, is imperative for a precise diagnosis and guides appropriate treatment strategies. The multifaceted spatial manifestation of this disease further underscores the potential for multifocal occurrences within the central nervous system, providing an avenue for improved comprehension of the underlying mechanisms contributing to its dissemination.

Primary unifocal thymic Rosai-Dorfman disease: an extremely rare challenge in diagnostic practice

Rosai-Dorfman disease (RDD) is currently considered a group of neoplastic diseases of unknown etiology, with monoclonal proliferation of histiocytes, showing unique histopathologic features and varying clinical presentation. Primary thymic RDD is an extremely rare extranodal form of this disorder. In this study, we describe the case of an otherwise healthy 64-year-old Chinese man who presented with an isolated, asymptomatic soft tissue density lesion in the anterior mediastinum detected by computed tomography. Histology of the surgical specimen revealed infiltration of thymic tissue by sheets of large histiocytes with mixed lymphocytes and plasma cells, and background fibrosis. Immunohistochemical staining of the histiocytes was positive for S100, CD68, CD163, OCT2 and cyclin D1, but negative for CD1a and BrafV600E expression, thus supporting a diagnosis of RDD. Primary thymic RDD is extremely rare and may be a diagnostic challenge when presenting as mediastinal lesion.

A case report of Rosai–Dorfman disease of the breast

Abstract Rosai-Dorfman disease (RDD), or sinus histiocytosis with massive lymphadenopathy, is a benign, self-limiting disease. In the majority of cases, there is massive and painless lymphadenopathy in any lymph node group but most commonly in the cervical lymph nodes, associated with constitutional symptoms. Extranodal involvement has been reported to occur in almost every organ system, with or without concomitant nodal disease. The breast is a rare site of presentation of this disease. A 52-year-old female presented with a hard, nodular swelling(3x2cm) in the left breast, with a clinical suspicion of malignancy. Atypical cells were note in fine needle aspiration smears. Histopathology and immunohistochemistry were of critical importance and showed a specific pattern of histiocytosis. A diagnosis of Rosai-Dorfman disease (RDD) was made. RDD of the breast is a rare form of histiocytosis, with fewer than 100 globally published cases. Although the management of this disease is not established yet by guidelines, a follow-up approach should be enough for these patients, and surgery might be overtreatment. Mortality from RDD is very low due to comorbidities. A multidisciplinary team decision is important, and abstinence might significantly benefit these patients.

A Rare Case of Pseudo-Malignant Paranasal Extranodal Rosai-Dorfman Disease.

Rosai-Dorfman disease is a very rare disease characterized by histiocytic accumulation in the head and neck region and lymph node enlargement. We report a rare pseudo-malignant paranasal extranodal Rosai-Dorfman disease. A 69-year-old-man presented nasal bleeding and nasal obstruction. Paranasal mass was detected in the left nasal cavity and computed tomography (CT) findings are the sphenoid sinus, maxillary sinus, and ethmoid sinus were involved with inconstant bone thickening, however, no bone destruction was detected. Magnetic resonance imaging scans show iso-intensity signal in T1-weighed image and T2-weighed image. Positron emission tomography/CT fluorodeoxyglucose (FDG) uptake in posterior ethmoid sinus and sphenoid sinus, bilateral cervical lymph node, clavicle, and sternum. Based on the above results, we considered malignant lymphoma and performed a biopsy. After pathological examination, a diagnosis of Rosai-Dorfman disease was established.

Rosai Dorfman disease : A rare association of sero positive rheumatoid arthritis

Rosai-Dorfman disease (RDD) is a rare self-limiting histiocytic proliferative disorder that mostly presents with cervical lymphadenopathy with constitutional symptoms. It is associated with connective tissue disease in 10% of cases. Here we present a case of 14-year-old boy who presented with a prolonged fever, arthralgia and generalize lymphadenopathy. Eventually the diagnosis of RDD associated with early Rheumatoid arthritis was made.

Rosai-Dorfman Disease With Pure and Multifocal Cutaneous Lesions: A Case Report

A 52‐year‐old woman developed progressive infiltrated purple and hyperpigmented cutaneous lesions in the face, thighs, armpits, chest, and abdomen evolving forone year. Histopathological examination showed large histiocytes exhibiting intact inflammatory cells in their cytoplasm (emperipolesis). Immunohistochemical analyses showed that the histiocyte population was positive for S100 and CD68, but negative for CD1a. Based on the clinical, histopathological, and immunohistochemical findings, we made the diagnosis of Rosai Dorfman disease (RDD). Our patient didn’t manifest any other extra-cutaneous involvement and all the biological and radiological investigations were normal. This form of pure cutaneous RDD (P-CRDD) with multifocal lesions has been rarely reported. RDD is very rare and hardly recognized in the absence of lymphadenopathy. The diagnosis of this entity involves a combination of histology and immunohistochemistry. To date, there is no standard treatment.

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.

A report of Rosai–Dorfman disease with systemic multiple lymphadenopathy and high IgG4 plasma cell infiltration

The Rosai-Dorfman disease (RDD) is a kind of sinus histiocytosis with massive lymphadenopathy and is remarkably rare. RDD is characterized by large histiocytes with emperipolesis. However, the cause of RDD is unknown, and most cases are relieved spontaneously. In rare cases, patients may have onset and remission of lymph nodes and extranodal involvement. This report showed an RDD case in a 67-year-old male patient with systemic superficial lymphadenopathy and high IgG4 plasma cell infiltration. We showed that a possible RDD diagnosis should be kept in mind when encountering a systemic multiple lymphadenopathy and high IgG4 plasma cell infiltration. Also, an overlap between RDD and IgG4-related disease might be present, which might help in clinical recognition of RDD.

Cutaneous Emperipolesis: Rosai–Dorfman Disease – An Uncommon Entity

Rosai–Dorfman disease (RDD) is a rare, benign idiopathic, non-Langerhans cell histiocytosis. The most common presentation is massive bilateral painless lymphadenopathy with fever and weight loss. Approximately 40% of patients with RDD have extranodal involvement. The cutaneous involvement is the most common extranodal manifestation comprising 11% of RDD, but only 3% presents as pure cutaneous disease (CRDD). A 55-year-old male presented with a painless swelling over the neck in the midline of 2 months duration. On examination, a firm nodular lesion measuring 1 cm × 1 cm was located on the midline of the neck. Excision biopsy was done with a differential diagnosis of calcified cyst. Histopathological examination showed emperipolesis, and immunohistochemistry was positive for S 100 and cluster of differentiation (CD) 68 and negative for CD1a confirming a diagnosis of RDD. All systemic, biochemical, and radiological examinations were unremarkable. There was no further local recurrence after 1 year of follow-up.

Rosai Dorfman's Disease with MAP2K1 Mutation Refractory to Chemotherapy with Complete Response to MEK Inhibitor Therapy: A Case Report

Background: Rosai Dorfman's Disease (DRD) is a rare primary histiocytosis, usually benign and self-limited, characterized by significant cervical lymphadenopathy. In 23 to 43% of cases it presents extra-lymph node symptoms. Symptomatic patients are often treated with prednisone and chemotherapy, with varying success rates. Although classically considered non-clonal inflammatory pathologies, NRAS, KRAS and MAP2K1 mutations are described in a fraction of patients with histiocytic disorders. This report will discuss a case of a patient with DRD with MAP2K1 mutation, who responded dramatically to targeted therapy with cobimetinib, after failure in several lines of treatment. Case presentation: A 41-year-old woman was evaluated for massive bilateral cervical adenopathy with 2 months of evolution, associated with fatigue, weight loss (7% in 2 months), chest pain and arthralgias of large joints. Cervical lymph node biopsy was performed, with a diagnosis of Rosai-Dorfman disease. Pet-Scan showed bilateral cervical, supraclavicular and mediastinal lymph node enlargement, with a marked increase in metabolism. She was initially submitted to corticosteroid therapy for up to 8 months, with partial response, but with recrudescence of adenopathies and symptoms in the attempts to reduce prednisone to less than 20 mg/day. She was then sequentially submitted to chemotherapy combinations containing Vinblastine, Methotrexate, 6-Mercaptopurine, Cyclophosphamide and Prednisone, presenting a progressive disease characterized by involvement of the nasopharynx. There was also a failure in response with the use of Lenalidomide. After 19 months of diagnosis, she was treated with 6 cycles of Cladribrine, obtaining a partial response, lost 5 months after completion. Investigation with NGS Panel Target One Pan Cancer (52 Genes) detected MAP2K1 c.607G> mutation. The patient started treatment with the MEK inhibitor Cobimetinib (Cotellic ®) with complete response. The medication was used for 12 months, with a dose reduction between the 7th and 12th month due to cutaneous adverse events. A complete response is maintained one month after cobimetinib discontinuation. Discussion: Due to the disease being rare there is still no well-defined protocol for DRD treatment. As it has mostly benign and self-limited evolution, observation is indicated in oligosymptomatic cases and corticosteroid therapy is the first line of treatment when necessary. Cases that are refractory to traditional therapies, such as the one presented in the report, can be treated with targeted therapies when actionable mutations are identified. The present report supports the idea that genomic analysis can be an important tool in the management of cases of refractory or aggressive DRD.

Radiological features of Rosai–Dorfman disease: case series and review of the literature

To improve the accuracy of diagnosis of Rosai-Dorfman disease (RDD) by summarising the computed tomography (CT) and magnetic resonance imaging (MRI) characteristics. The clinical manifestations, imaging findings, and pathological characteristics of 14 patients with histopathologically confirmed RDD were analysed retrospectively and a literature review was undertaken. Of the 14 patients, nine had multiple lesions and five had single lesions. Eight patients had extranodal lesions, while six had mixed-type lesions. In patients with head and neck lesions, plain CT/MRI revealed irregularly shaped, well-defined, homogeneous, and mainly progressive lesions, with marked homogeneous enhancement on multiphasic contrast-enhanced imaging. One patient had dural lesions, one of which iso-intense to grey matter, with patchy hypo-intensity on T2-weighted imaging, meningeal tail signs, and characteristic crabfoot-like enhancement. Three patients with skeletal system involvement exhibited osteolytic bone destruction without sclerosis at the edges, associated soft-tissue masses, or periosteal reactions. Two patients had well-defined subcutaneous lesions, inhomogeneous density, and progressive parenchymal enhancement on contrast-enhanced CT. One patient had multiple intestinal lesions with inhomogeneous nodular thickening of the blind ascending colon and ileum, with marked and progressive enhancement. RDD involvement is mainly multifocal, primarily in the head and neck regions. Plain CT/MRI revealed well-defined, irregularly shaped lesions with homogeneous density/signal, with marked and progressive enhancement on multiphasic contrast-enhanced imaging; however, histopathology is still required to confirm the diagnosis of RDD.

Not all lymphadenopathy is lymphoma: A case report of Rosai-Dorfman disease

Background: Rosai-Dorfman Disease (RDD) is a rare non-Langerhans cell histiocytic disorder most commonly presenting as bilateral cervical lymphadenopathy in children and young adults. Although a heterogeneous entity with a range of clinical phenotypes, here we describe a presentation at one of the oldest ages found to date in the available literature and its spontaneous resolution in the absence of treatment. Case presentation: A 75-year-old man presented with new-onset right-sided cervical lymphadenopathy and fever, weight loss, fatigue, and anorexia. Physical exam revealed cervical and axillary lymphadenopathy. CT chest/abdomen/pelvis showed extensive adenopathy in the axillary regions, groin, mediastinum, retroperitoneum, splenic hilum, gastrohepatic ligament and porta hepatis, and celiac chains. Left axillary lymph node excisional biopsy revealed sinus histiocytosis with massive lymphadenopathy, consistent with a diagnosis of RDD. Flow cytometry showed mixed polytypic B-cell and T-cell subsets with polyclonal plasma cells. Immunofixation was negative for monoclonal immunoglobulins. On seeing a hematologist one month later, the patient’s symptoms had resolved and he had gained 10+ pounds. Discussion: Rosai-Dorfman Disease is a rare non–Langerhans cell histiocytosis most often seen in children and young adults, although it has been reported up to age 79 years. It typically presents with markedly enlarged, non-tender cervical lymphadenopathy; however, other nodal and extranodal sites can be involved. Due to the rarity of the disease there is a lack of robust data regarding specific treatment modalities, although consensus guidelines were published in 2018 recommending various treatment options, including corticosteroids, chemotherapy, radiation, and surgery. Spontaneous resolution may be observed but can take many months to years. Keywords: sRosai-Dorfman disease; Sinus histiocytosis with massive lymphadenopathy; Non–langerhans cell histiocytosis.

Diagnosis of Rosai-Dorfman Disease by Upper Endoscopic Ultrasound–Guided Fine-Needle Biopsy

Diagnosis of Rosai-Dorfman Disease by Upper Endoscopic Ultrasound–Guided Fine-Needle Biopsy

Differential diagnosis in Rosai-Dorfman disease: A rare case of isolated hepatic presentation mimicking a metastatic tumor with positive 18-FDG uptake.

Rosai-Dorfman disease (RDD) is also called sinus histiocytosis with massive lymphadenopathy, and it is caused by a histiocytic disorder with unclear etiology. It usually involves cervical lymph nodes, but it may also present with extranodal involvement. We report a rare condition of isolated hepatic RDD without nodal involvement, clinically manifested with three-month abdominal pain and tenderness of the right hypochondrium. CT- and PET-CT scans were compatible with a secondary lesion from an unknown primary tumor. Therefore, the patient underwent an atypical liver resection. Immunohistochemistry and histological results were compatible with a diagnosis of RDD. RDD is characterized by phenomena of emperipolesis, histiocytic proliferation and positive immunostaining for CD14, CD68 and S-100 protein. Cases of isolated gastrointestinal localization of RDD are particularly rare, especially in the liver. Instrumental exams might confuse RDD with other malignancies. RDD is a rare entity, which might be misdiagnosed using PET-CT due to its similarities with malignant tumors. An accurate multidisciplinary approach may help to clear diagnostic clues of this uncommon disease.

PULMONARY ROSAI-DORFMAN DISEASE WITH NO LYMPH NODE INVOLVEMENT

TOPIC: Lung Pathology TYPE: Fellow Case Reports INTRODUCTION: Histiocytosis is a disorder when a collection of hematopoietic-derived cells multiply without regulation but is not considered malignant. The most recent classification was laid out by the World Health Organization in 2016 dividing them into multiple groups. Rosai-Dorfman disease typifies the R group and is unique in its presentation ranging from a solitary lesion or multifocal, systemic disease. CASE PRESENTATION: A 74-year-old male of African descent with a past medical history significant for tobacco abuse presented to the emergency department with hemoptysis that started 2 days prior to presentation. Patient was seen as outpatient due to hemoptysis in the past and CT chest showed a 4.2 cm mass in the left lower lobe, no lymphadenopathy; confirmed by another CT Chest in the emergency department. PET/CT at that time showed the mass had increased 18-FDG uptake with SUV 26.4. There was very high suspicion for lung carcinoma and bronchoscopy showed a friable, bleeding, pedunculated mass occupying LLL basal segmental airway. The mass was removed using a snare and forceps and the tumor base was cauterized with argon plasma coagulation. Pathology report of the mass showed proliferation of histocytes with immunostaining positive for S100 and CD68, but negative for CD1a consistent with the diagnosis of Rosai-Dorfman disease. The patient was started on definitive radiation therapy with resolution of his symptoms. DISCUSSION: Rosai-Dorfman disease (RDD) is a rare histiocytosis that is characterized as being multisystemic. First described in 1969 by Rosai and Dorfman, this was described as self-limiting painless lymph node enlargement seen in teenagers and young adults. Our patient presented in his late 70's and was of African descent. Recent publications coming from China with 25 cases of RDD showed that extranodal presentation less common in Asians compared to white/black patients, and the mean age was 45 years old. Pulmonary involvement of RDD usually involves mediastinal lymphadenopathy which our patient did not have; the PET/CT showed the disease was limited to the mass in the left lower lobe. Differentiating RDD with this presentation from malignant lung disease, especially on a patient with significant smoking history, is challenging. Histopathology will give the diagnosis - in RDD S-100 and CD68 are the common positive markers with negative CD1a ruling out Langerhans cell histiocytosis. Treatment with radiation therapy is described for localized disease-causing symptoms, our patient has had a good response with resolution of his symptoms. CONCLUSIONS: RDD is very rare to present in lungs alone with no lymphadenopathy and this presentation is difficult to differentiate from malignancy. Diagnosis is based on tissue sampling with immunohistochemistry staining characterized by (+) S-100 and CD68 with (-) CD1a. Radiation therapy is an effective treatment for symptomatic localized disease. REFERENCE #1: Abla O, Janka G. Histiocytic Disorders Cham: Springer International Publishing AG; 2017:30-33 REFERENCE #2: Ali A, Mackay D. Rosai-Dorfman disease of the lung. Thorax. 2009;64(10):908-909 REFERENCE #3: Kong Y, Kong J, Shi D et al. Cutaneous Rosai-Dorfman disease a clinical and histopathologic study of 25 cases in China. The American journal of surgical pathology. 2007;31(3):341-350 DISCLOSURES: No relevant relationships by Alfredo Iardino, source=Web Response No relevant relationships by Jill Ono, source=Web Response No relevant relationships by Arthur Oliver Romero, source=Web Response No relevant relationships by Ipsita Samanta, source=Web Response

Rosai-Dorfman Disease Displays a Unique Monocyte-Macrophage Phenotype Characterized by Expression of OCT2.

Rosai-Dorfman disease (RDD) is a rare histiocytosis with heterogenous clinical features. In this study, we characterized the histologic and phenotypic features in 33 RDD patients to better define the pathologic diagnosis. Cases included 24 patients with extracutaneous disease ("R" group), and 9 patients with lesions limited to the skin or subcutaneous tissue ("C" group). We identified OCT2 as a novel marker for the monocyte-macrophage phenotype of RDD, expressed in 97% of RDD cases. In contrast, OCT2 expression was seen in 0% of Erdheim-Chester disease cases and 6.7% of Langerhans cell histiocytosis cases. Other markers useful in the diagnosis of RDD included S100 (100%), CD163 (88%), and cyclin D1 (97%). In a subset of cases, RDD showed moderate to strong expression of factor 13a (30%), p16 (64%), and phosphorylated extracellular signal-regulated kinase (45%); RDD was uniformly negative for ZBTB46, CD1a, and langerin. Within the "R group" of RDD, increased expression of factor 13a or phosphorylated extracellular signal-regulated kinase showed a statistically significant association with multifocal disease (P<0.05). Identification of the unique monocyte-macrophage phenotype of RDD with OCT2 expression furthers our understanding of this complex disease and allows for more uniform classification.