Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy, is a rare idiopathic condition characterized by painless cervical lymphadenopathy. Accompanying features are fever, leukocytosis, and weight loss. Deposition of histiocytes in other organs has been observed, which is why the diagnosis rests on a thorough imaging and laboratory workup, histopathological examination and immunohistochemistry testing.
Rosai-Dorfman disease is primarily encountered in adolescents, as more than 80% of cases are diagnosed in patients under 20 years of age, and a small, but significant predilection toward male gender is observed  . The clinical presentation is diverse, but the deposition of histiocytes in lymphatic tissues is primarily manifested as massive and painless bilateral cervical lymphadenopathy, which is considered to be the hallmark of the disease  . For this reason, the term sinus histiocytosis with massive lymphadenopathy (SHML) is often used as a synonym  . Fever, weight loss, night sweats, malaise, and pharyngitis are additional symptoms, while enlargement of other lymph nodes (axillary, mediastinal, inguinal, retroperitoneal) is reported in some cases  . Extranodal accumulation of histiocytes was reported in numerous sites, including the genitourinary and gastrointestinal tracts, the lungs, skin, heart, musculoskeletal system, thyroid gland, the orbit and in very rare cases, the central nervous system and the breast  . As a result, a myriad of symptoms can be seen depending on the organ or tissue involved - Headaches and seizures, in addition to constitutional symptoms, are reported when the head and neck area is the site of histiocyte proliferation, whereas solitary or multiple skin lesions of various types (macular, papular, nodular, xanthomatous) or a soft tissue mass may be seen on the face, trunk, extremities or genitalia in the case of skin or soft tissue deposition .
Although signs and symptoms may be numerous and non-specific, the presence of bilateral cervical lymphadenopathy must raise clinical suspicion. However, key findings can only be obtained after a meticulous physical examination and a thorough patient history, which are key step during workup. Laboratory evaluation should follow, and anemia, elevated erythrocyte sedimentation rate and hypergammaglobulinemia are cardinal features of Rosai-Dorfman disease   . Because the differential diagnosis involves numerous conditions of infectious and neoplastic (both lymphoproliferative and metastatic forms) origin or disorders of similar pathophysiological mechanisms (such as Langerhans cell histiocytosis), imaging studies are required in order to assess additional organ involvement. Computed tomography (CT) and magnetic resonance imaging (MRI) are recommended procedures, but depending on signs and symptoms, additional studies may be required (ultrasonography, mammography, scintigraphy, echocardiography, etc). To confirm Rosai-Dorfman disease, a histopathological examination is necessary . A dense infiltrate of large histiocytes containing large nuclei, small nucleoli, and a pink cytoplasm, as well as scattered lymphoid cells (lymphocytes and neutrophils) are main characteristics of this condition . The most important distinguishing feature, however, is emperipolesis, defined as the presence of intact lymphoid cells within histiocytes, and is considered as a pathognomonic feature of Rosai-Dorfman disease . In addition, positive S-100 and CD68 , together with negative CD1a, are key findings on immunohistochemistry testing  .