Soft Tissue Rosai-Dorfman Disease Case report

Rosai-Dorfman disease (RDD) is a rare benign proliferative histiocytic disorder characterised by massive lymphadenopathy. While extranodal involvement can occur in generalised RDD, isolated soft tissue RDD (STRDD) is extremely rare. We report a 17-year-old male patient who presented to the maxillofacial outpatient department of the Sultan Qaboos Hospital, Salalah, Oman, in 2015 with a painless cheek mass which had been slowly growing over the previous two months. Routine histopathological examinations and immunohistochemistry confirmed a diagnosis of STRDD. Currently, surgical excision is considered to be the most effective curative treatment for STRDD, as the outcomes of other treatment modalities are still unknown. Despite its rarity, STRDD should be considered in the differential diagnosis of histiocytic soft tissue lesions.

A lso known as sinus histiocytosis with massive lymphadenopathy, Rosai-Dorfman disease (RDD) was first described as a unique clinicopathological entity in 1969. 1 Clinically, it is characterised by massive bilateral painless lymphadenopathy of the head and neck region, with affected patients often presenting with fever, leukocytosis, an elevated erythrocyte sedimentation rate and polyclonal hypergammaglobulinaemia. 2 Isolated soft tissue RDD (STRDD) may occur as part of a generalised process involving the lymph nodes or may involve extranodal sites independent of lymph node status. 3,4The clinical presentation is similar to that of nodal RDD. 5 Nodalbased RDD usually regresses spontaneously, whereas isolated STRDD is indolent in nature and may recur years or even decades later. 6This report describes a case of isolated STRDD which presented initially as a painless nodular cheek mass.The importance of including this rare entity in the differential diagnosis of histiocytic soft tissue lesions is highlighted.

Case Report
A 17-year-old male patient presented to the maxillofacial outpatient department of the Sultan Qaboos Hospital, Salalah, Oman, in 2015 with a firm painless nodular mass in his right cheek which had been progressively increasing in size over the previous two months.In addition, he had mild proptosis of the right eye.There were no significant findings in the patient's medical history or laboratory investigations.On clinical examination, the cheek mass measured 4 cm in diameter and was not associated with any lymph node enlargement.The differential diagnosis was of either a neoplastic or inflammatory soft tissue lesion.An excisional biopsy was performed.
The excised mass was formed of two separate pieces of tissue with a firm whitish cut surface.The larger piece measured 1.7 x 0.8 x 0.3 cm and the smaller one measured 1.5 x 0.7 x 0.4 cm.A microscopic examination revealed fibrocollagenous and adipose lesion was continuous with another mass measuring 3.2 x 3.4 cm in the right infratemporal fossa, with obliteration of the fat planes.The optic nerve and extraocular muscles were in contact with the mass, but the globe was still intact.Clinically, this lesion was considered to be of the same disease as the cheek lesion and no specific treatment or biopsy was attempted.After two years of follow-up, there was no evidence of disease progression in either lesion.

Discussion
While RDD has been reported worldwide, it is more common among patients of African descent. 7Up to 80% of cases occur among individuals in the first two decades of life, although other age groups can also be affected; in addition, RDD tends to occur more frequently among males. 7,8In the largest known study of RDD, 43% of 423 patients had associated extranodal disease along with lymphadenopathy; in comparison, only 3% of patients had no detectable lymphadenopathy. 2 The skin and the paranasal sinuses are the most common sites for extranodal involvement. 9 an extensive review of the literature, Komaragiri et al. identified only 36 STRDD cases reported between 1969 and 2012. 10The current report adds an additional case to the existing literature concerning this rare entity.Two large case series of STRDD have been reported from the USA; the first described 17 cases of STRDD, of which four presented with lymphadenopathy, whereas the second found that only one of 18 patients with STRDD had associated lymph node involvement from a single node. 5,11In both series, STRDD was more common in the trunk and proximal extremities and tended to grow rapidly, although the actual size of the lesion varied.The age of the affected patients also ranged widely and there was a slight female predominance. 5,11Multifocal STRDD is extremely uncommon but recurs more frequently than a solitary lesion. 11,12The rate of recurrence of STRDD after excision has been reported to range from 21.4-54%. 5,11mmunohistochemistry is key to differentiating soft tissue lesions in order to determine the correct diagnosis.Morphologically, STRDD is similar to nodal RDD in exhibiting the diffuse subcutaneous infiltration of large polygonal histiocytes, which in turn demonstrate emperipolesis predominantly of lymphocytes, although sometimes plasma cells, erythrocytes and neutrophils are also affected. 5Infiltration of lymphocytes, plasma cells and neutrophils may also occur, along with the histiocytes.However, mitosis and necrosis are rare. 5While some researchers have tissue with nodular infiltration of lymphocytes, plasma cells, eosinophils, neutrophils and foamy histiocytes.Many of the histiocytes showed ingested lymphocytes, plasma cells, eosinophils or neutrophils in the cytoplasm [Figure 1].No necrosis or mitosis was noted and the histiocytes were immunoreactive to S100 proteins [Figure 2].As a result, a diagnosis of RDD was made.
The patient was subsequently referred to a tertiary hospital in Oman for further examination and management.Additional immunostaining of the mass revealed that the histiocytes were positive for S100 proteins and cluster of differentiation (CD)68, but negative for CD1a, CD30 and CD15.The plasma cells were polyclonal on both kappa and lambda light chain stains.Moreover, even though a few cells were stained by immunoglobulin G (IgG)4, the IgG4:IgG ratio did not increase.These findings confirmed the diagnosis of extranodal RDD, with a final diagnosis of isolated STRDD.The patient was followed up continuously without any active treatment.Five months later, a computed tomography scan of the right eye showed an enhancing lesion in the posteroinferior and lateral aspect of the right orbit measuring 3 x 2 cm.This  reported frequent spindling of the histiocytes, others have claimed this is uncommon. 5,11In cases with histiocyte spindling, STRDD may be confused with a sarcoma. 10In terms of immunohistochemistry, RDD histiocytes are consistently positive for S100 proteins and CD68 and negative for CD1a. 13The microscopic appearance of an inflammatory pseudotumour can resemble STRDD; however, the histiocytes of inflammatory pseudotumours are negative for S100.These lesions may reflect a histological continuum. 14Another differential diagnosis of STRDD is Langerhans cell histiocytosis, in which the histiocytes are positive for both S100 proteins and CD1a. 15he histogenesis of RDD is still unclear, but may be the result of an aberrant immunoresponse. 7he disease has also been associated with lymphoproliferative disorders. 2In cases of Hodgkin's lymphoma, certain cytokines have been found to alter the morphology of histiocytes to that seen in RDD. 16 relationship between polyomavirus infections and intra-abdominal STRDD has also been postulated. 11ue to its rarity, there is as yet no definitive treatment strategy for patients with STRDD; however, surgical excision has been proven effective in preventing disease recurrence. 10Further studies are required to establish evidence-based treatment strategies for this disease and to increase our understanding of its outcomes and natural history.

Conclusion
STRDD is a very rare benign proliferative histiocytic disorder.Morphologically, it may mimic an inflammatory pseudotumour, sarcoma or Langerhans cell histiocytosis.As such, it is important that STRDD be considered in the differential diagnosis of histiocytic soft tissue lesions.

Figure 1 :
Figure 1: Haematoxylin and eosin stain at x400 magnification showing lymphoid aggregates of mixed inflammatory cells including mature lymphocytes, neutrophils and plasma cells.Note the evidence of emperipolesis as shown by the histiocytes engulfing the intact lymphocytes, neutrophils and plasma cells (arrow).