Introduction: Rosai-Dorfman disease (RDD) is a rare benign histiocytic proliferation, characterized by a group of clinical symptoms. This report presents a case of extranodal RDD manifesting as a progressively enlarging left maxillary mass in a 42-year-old woman. Surgical exploration and biopsy confirmed the diagnosis of RDD, with characteristic histopathological features including emperipolesis. Treatment involved corticotherapy, resulting in controlled maxillary pain and improvement of the disease after one year. This case underscores the potential for extra-nodal RDD presentations, posing diagnostic challenges and emphasizing the importance of considering RDD in the differential diagnosis of maxillary masses.

A systematic literature review revealed 88 Rosai-Dorfman Disease (RDD) cases affecting the orbit. We present a review of the literature on orbital RDD in addition to two brothers with isolated bilateral extra-nodal orbital RDD cases associated with G-6PD deficiency. The disease manifested as asymmetric extensive orbital and paranasal sinus infiltration, with orbital bone destruction. Orbital mass debulking and steroids improved the condition in both patients. This is the most extensive case series of orbital RDD reported, including clinical manifestation, imaging, pathologic results, management, and outcome. Vigilant follow-up is essential to monitor for potential malignant transformation, systemic manifestations, potential vision loss, or life-threatening recurrences.

Histiocytosis is a group of rare diseases characterized by inflammation and accumulation of cells derived from monocytes and macrophages in different tissues. The symptoms are highly variable, from mild forms with involvement of a single organ to severe multisystem forms that can be life compromising. The diagnosis of histiocytosis is based on the clinic, radiological findings and pathological anatomy. A biopsy of the affected tissue is recommended in all cases as it may have therapeutic implications. During the last decade, some mutations have been identified in the affected tissue that condition activation of the MAPK/ERK and PI3K/AKT pathway, in a variable proportion depending on the type of histiocytosis. In this review we mainly focus on Langerhans Cell Histiocytosis, Erdheim-Chester Disease and Rosai-Dorfman Disease.

Three cases of primary Rosai-Dorfman disease of the thymus and lung are presented. The patients are 3 men between the ages of 42 and 47 years who presented with non-specific symptoms including cough, chest pain, and shortness of breath. Clinically, the patients did not have any other pertinent clinical history. Diagnostic imaging revealed in one patient a cystic anterior mediastinal mass, while in two other patients the imaging was that of an intrapulmonary mass, one in the right upper lobe and the other in the left lower lobe. The three patients undergo surgical resection of the mass. In the cases in which the tumor mass was in the lung, both patients had a lobectomy while in the patient with anterior mediastinal mass, surgical resection via thoracotomy was performed. The intrapulmonary tumors were described as soft and yellowish measuring 2.5 and 3.0 cm in greatest diameter, while the mediastinal mass was described as cystic measuring 4.0 cm in diameter. Histologically, all tumors show similar features in terms of a proliferation of large histiocytes admixed with an inflammatory component composed predominantly of plasma cells. Immunohistochemical stains show positive staining for CD68 and S-100 protein, while negative for keratin, CD1a, and langerin. The cases herein presented highlight the ubiquitous distribution of Rosai-Dorfman disease and the importance of keeping this entity in the differential diagnosis of histiocytic proliferation in the thymus or lung.

Non-Langerhans cell histiocytosis, including Rosai-Dorfman disease (RDD) and xanthogranuloma are rare disorders with occasional overlapping in the histopathological and immunohistochemical (IHC) findings. We report the case of a 53-year-old woman with erythematous-violaceous plaques on the cheeks and edema in the auricular pavilions. A biopsy was performed and the histopathological examination revealed a histiocytic proliferation with emperipolesis characteristic of RDD and lymphoplasmocitic infiltrate. IHC analysis showed S100 and CD68 positivity in the histiocytes but was negative for CD1a, supporting the diagnosis of RDD. Molecular analysis failed to detect BRAF-V600, NRAS or KRAS mutation. We discuss the differential diagnosis of cutaneous non-Langerhans cell histiocytosis. Pathologist must be aware of unusual presentations of RDD and further treatment options must be explored for patients with unresectable lesions and/or resistance to the classical management of RDD.

An 81-year-old man presented with anemia, fatigue, weight loss, and recurrent urinary tract infections and was found to have diffuse large adenopathy and infiltrating renal masses. Surgical excision of a lymph node and histologic evaluation led to the diagnosis of Rosai-Dorfman disease, a rare histioproliferative condition that classically presents with enlarged cervical lymph nodes bilaterally. It also can involve additional nodal chains and/or have extranodal manifestations. The condition can self-resolve or have periods of remission and reactivation.

We report a case of a 49-year-old female diagnosed with extranodal multifocal Rosai-Dorfman disease (RDD) of the breast using mammography and ultrasound. RDD is a rare non-Langerhans cell benign proliferative disorder of histiocytes that usually involves the lymph nodes, but may involve extranodal sites. We review the clinical presentation as well as imaging features of this rare disease on multiple modalities and the importance of recognizing the diagnosis in order to direct treatment.

Rosai-Dorfman Disease (RDD), or sinus histiocytosis with massive lymphadenopathy, is a rare entity characterized by proliferating S100-positive histiocytes. It is most commonly found in lymph nodes with extranodal involvement usually occurring in the head and neck. Pancreatic involvement is extremely rare. The pathology department archives were searched for fine needle aspirations and pancreatic resections showing evidence of RDD. Clinicopathologic features, cytologic smears, cell blocks, immunocytochemical stains and surgical resections were reviewed. Three cases were identified. They were all females, aged 65, 69 and 75, with involvement of the pancreatic tail or head by solid masses of median size 2.3 cm (range 2.1-4.5 cm). Cytologic findings on smears included multiple histiocyte clusters resembling loosely cohesive epithelioid granulomas, singly dispersed histiocytes with moderate to marked nuclear atypia and characteristic emperipolesis. These atypical histiocytes stained positively for CD68, CD163 and S100. Smear background contained variable mixed inflammatory cells, necrotic debris and stromal fragments. The RDD diagnosis was further confirmed on pancreatic resection in two patients and core biopsy in one. The latter patient required three separate procedures before a definitive diagnosis was made. RDD of pancreas is a rare benign inflammatory condition that is diagnostically challenging on cytology. This can cause delays in cytologic diagnosis and/or misdiagnosis. Identification of characteristic cytologic features, primarily histiocytes with emperipolesis, and matching immunocytochemical profile can ensure accurate diagnosis and distinction from mimics.

UNASSIGNED: Rosai-Dorfman disease (RDD) is a rare lympho-histiocytic disorder of indeterminate etiology usually presenting with lymph node involvement, and infrequently with extra-nodal manifestations. The diagnosis of this condition is challenging due to the wide spectrum of disease manifestations.
UNASSIGNED: To elucidate the radiologic features of this disease using multimodality imaging in histopathologically proven cases and to identify characteristic features that would enable its differentiation from its mimics.
UNASSIGNED: We retrospectively evaluated imaging studies of 19 patients with histopathologically confirmed RDD presenting to our institute between January 2004 and March 2016. Imaging modalities included magnetic resonance imaging (MRI), computed tomography, FDG-positron emission tomography (PET) CT, mammography, and ultrasonography.
UNASSIGNED: Lymphadenopathy was the most common imaging feature in our study, seen in 11 (57.8%) cases followed by sino-nasal involvement in 7 (36.8%) cases and intracranial masses in 5 (26.3%) cases. Bilateral homogeneously enhancing cervical lymphadenopathy with avidity on FDG-PET scans was the predominant abnormality on imaging. Sino-nasal involvement manifested as homogeneously enhancing soft-tissue masses occupying the paranasal sinuses. Intracranial disease manifested as sellar/suprasellar masses, dural-based lesions along the cerebral hemispheres and choroid plexus enlargement. Unusual disease manifestations included spinal, osseous, and breast lesions.
UNASSIGNED: Due to the high likelihood of multifocal involvement, the recognition of RDD at one site necessitates screening of other sites for disease. Homogeneously enhancing, FDG-avid lymphadenopathy and sino-nasal masses in association with hypointense extra-nodal lesions on T2-weighted MRI are imaging features which could aid the diagnosis of RDD and facilitate its differentiation from pathologies that present in a similar manner.

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