RDD is a well-defined clinicopathological entity, first described by Destombes in 1965.[6,21] Later in 1969, Juan Rosai and Ronald Dorfman, recognized it as a distinct disease entity comprising sinus histiocytosis and massive lymphadenopathy [9,21] and previously classified by the Working Group of the Histiocyte Society of 1987 as a non-Langerhans cell (LC) histiocytosis.[25] This same society has recently reclassified the histiocytoses based on new insights into the pathological, genetic and molecular features of these disorders.[6] In this new classification, RDD now forms part of the ‘R group’ of histiocytoses, which includes familial RDD, sporadic RDD and other miscellaneous non-cutaneous, non-LC histiocytoses. Cutaneous RDD is classified separately as part of the ‘C group’ of histiocytoses.[26] 20–50% of RDD patients with nodal/cutaneous disease undergo spontaneous remission.[3] The prevalence of the disease is 1:200,000 and is more prevalent in children.[34]
It can affect individuals of any age, but the peak incidence is in the second or third decade. RDD is more common in males and people of African descent.[22-24]
The aetiopathogenesis of RDD is poorly understood. It has been previously perceived to be a reactive, non-neoplastic histiocytic disorder that lacks clonality and was therefore not included in the latest (2017) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Evidence in support of a clonal nature of at least a subset of cases of RDD has recently come to light.[27] Possible infection and immunodeficiency have been suggested as causes of RDD.[5] Association with HHV6, EBV, Klebsiella spp., and CMV has been cited, but no definite etiological link with RDD has been confirmed.[9] Kinase mutations have been recently described in nodal and extranodal (but not cutaneous) RDD, including mutations in ARAF, MAP2K1, NRAS and KRAS.[28]
The presentation of the disease also varies with site of involvement. Commonly it presents with massive cervical lymphadenopathy but our patient has generalized lymphadenopathy over bilateral axillary, inguinal area and even in atypical location like epitrochlear areas with no cervical lymphadenopathy. extranodal involvement has also been documented in around 40% of cases, the most common being skin followed by upper respiratory tract and bone.[10] However, RDD also can occur in a variety of other sites, including the genitourinary system, lower respiratory tract, oral cavity, and soft tissues.[29] Other reported specific sites include brain, spine, liver, kidney, thyroid, breast, parotid gland, orbit, nasal cavity, and lungs.[30]
Rapid on-site evaluation with fine-needle aspiration cytology can be a useful, cost-effective technique for the diagnosis of RDD .[3] Aspiration from the lesion showed proliferation of histiocytes with abundant eosinophilic to vacuolated cytoplasm, vesicular single to multiple nuclei, and lymphophagocytosis or emperipolesis in a reactive inflammatory background (lymphocytes in early-stage and plasma cells in later stages).[5] The lymphocytes inside the histocyte have a halo around them, which is not seen in the tissue section due to fixation artifacts .[9] Less often, neutrophils and RBCs can also be seen.[5] FNA may be sufficient to make the diagnosis in most cases thus preventing unnecessary invasive procedures and helps to rule out common clinical differential diagnosis .[6,7,19]
Histologically, there is an infiltration of the tissue by lymphocytes, histiocytes, and plasma cells. The presence of emperipolesis (histiocytes with engulfed lymphocytes, erythrocytes, and plasma cells) is usually characteristic of Rosai–Dorfman–Destombes disease along with dilated sinusoids .[5,9] The diagnosis can be confirmed by using immunohistochemical (IHC) markers. Characteristically, S100 is always positive along with other markers, like CD68, CD163, α1 anti-chymotrypsin, and α1 anti-trypsin, with negative results for CD1a and Lagerin (CD207).[31]
The differential diagnoses can include reactive lymph node hyperplasia, infectious lymphadenitis, Langerhans cell histiocytosis, non-Hodgkin's lymphoma, and metastatic carcinoma.[11,19]
The rarity of RDD has limited our understanding of the choice of the best treatment.[2] Therapy is unnecessary in most cases. For patients with persistent, worsening, or life-threatening symptoms such as airway obstruction, treatment modalities may include surgery, radiotherapy, and chemotherapy. [1] None of these treatments are reported to dependably attain persistent remission, however .[32] Therapy based on steroids has been widely used as one of the most important drug treatments for RDD.[3] Oral prednisone can have a remarkably favorable response, mainly in patients with lymph node involvement .[33] However, intralesional corticosteroid, as well as oral prednisone, does not always result in resolution of cutaneous lesions .[26]
In our case, the patient received oral corticosteroid after the diagnosis of RDD.