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Rosai and Dorfman first characterised sinus histiocytosis with massive lymphadenopathy in 1969.1 This condition most commonly presents as a massive painless cervical adenopathy in children or young adults of African ancestry. The lymphadenopathy typically has a protracted course, lasting for several years before spontaneously resolving. Complications can include compression of vital organs or associated anaemia or leucopenia. The results of chemotherapy or radiation treatments have generally been disappointing; however, surgical debulking, when necessary, has been effective.
Microscopic examination of the lymph nodes reveals a polymorphous infiltrate composed of plasma cells, other lymphocytes, and histiocytes. The histiocytes often contain phagocytised lymphocytes, a histological finding termed emperipolesis. Since these histiocytes fill and expand lymph node sinuses, the disease was first named morphologically as sinus histiocytosis with massive lymphadenopathy. Extranodal involvement, most commonly in the upper respiratory tract and stomach, displays a histology similar to lymph node infiltrates. Because extranodal infiltrates are often found in the absence of lymphadenopathy, the eponym Rosai-Dorfman disease is now preferred.2
The orbit is a common extranodal site of RDD.3 Four cases of RDD manifesting as an epibulbar conjunctival mass have also been reported.4–7 In two of these cases, both in children, the epibulbar mass was an isolated finding.5,7 We present RDD occurring as an isolated epibulbar mass in two adult patients.
A 71 year old African-American man with a history of hypertension, benign prostatic hyperplasia, asthma, gout, and degenerative joint disease was evaluated for a painless 1.5 cm episcleral mass on the medial aspect of the right eye, adjacent to the limbus (fig 1A). The mass had been growing for 4 months. The patient was examined by an internist, who found no lymphadenopathy, anaemia, or leucopenia. The mass was excised for histopathological diagnosis. Haematoxylin and eosin stained sections of the episcleral nodule revealed a mixed cellular infiltrate, predominantly composed of histiocytes mixed with lymphocytes, including plasma cells and polymorphonuclear leucocytes (fig 1B). The histiocytes exhibited a large, round, vesicular nucleus with abundant pale staining and finely vacuolated cytoplasm. Several of these cells displayed the presence of polymorphonucleocytes, lymphocytes, and plasma cells within the cytoplasm (fig 1B, inset). Several foci of necrosis were noted, without the formation of granulomas (fig 1C). Stains for bacteria, acid fast bacilli, and fungi were negative. On immunohistochemistry, histiocytes stained positive for S-100, CD-68, lysozyme, and α-1-antitrypsin and negative for CD-1a (fig 2). The lymphoid infiltration showed the presence of kappa and lambda immunoglobulin chains.
A 51 year old African-Brazilian man with no medical problems presented with a 5 mm erythematous, subconjunctival mass. The mass was adjacent to the limbus and appeared to be adherent to the underlying tissues (fig 1D). Systemic evaluation was negative and there was no lymphadenopathy. The patient underwent a superficial sclerectomy with excision of the mass, and the lesion was submitted for histopathology. Follow up examination at 4 months showed no signs of recurrence. Haematoxylin and eosin stained sections of the nodule revealed a mixed cellular infiltrate, predominantly composed of histiocytes mixed with lymphocytes, including plasma cells and polymorphonuclear leucocytes. Several of these histiocytes showed emperipolesis, displaying phagocytosed polymorphonucleocytes, lymphocytes, and plasma cells. Stains for bacteria, acid fast bacilli, and fungi were negative.
The cases show that RDD can present as an isolated epibulbar mass in the elderly, as late as the eighth decade. Two previous cases of RDD manifesting as an isolated epibulbar mass in children have been described.5,7 One case of epibulbar and cutaneous RDD in a 40 year old has also been described.6 Although most cases of RDD occur in children or young adults, the disease is known to manifest in the elderly as well. A review of 423 cases of RDD showed a median age at presentation of 20 years (SD 20 years).8 The oldest patient in that series was 74 at the time of presentation. The mean age in cases with ocular involvement was 6 years. Patients with soft tissue lesions are known to be older than patients with nodal or solid organ involvement, with a mean age of 46 years in one series.9
Although clinical features of RDD may vary from benign soft tissue masses or lymphadenopathy to life threatening compression of vital organs, anaemia, or leucopenia, the characteristic histological features are histiocytic infiltration admixed with lymphocytes and other inflammatory cells. One typical feature of this entity has been emperipolesis, with histiocytes displaying phagocytosed lymphocytes and plasma cells. Histiocytes in RDD, Langerhans cell histiocytosis, and other histiocytoses express S-100, a neural tissue specific protein; however, the pathophysiology of this S-100 expression remains obscure. Although positive staining for S-100 strongly suggests RDD, it is not absolutely required to make the diagnosis in the presence of typical histology for RDD.9 CD68 is a monocyte/macrophage marker frequently expressed by histiocytes in all histiocytic disorders and believed to be associated with lysosomal granules. In all histiocytoses other than Langerhans cell histiocytosis, the histiocytes frequently stain positive for lysozyme, indicating that these cells are activated and have strong phagocytic potential. α-1-Antitrypsin is a proteinase inhibitor expressed by monocytes, inhibiting overexpressed proteinases during inflammation. It has been variably expressed in histiocytes in RDD.9 CD-1a is a marker for the Langerhans histiocyte and may be involved in antigen presentation. Staining for CD-1a is negative in RDD. Early reviews of RDD stress the lack of necrosis on histopathology. Despite the lack of documentation in the early literature, small foci of necrosis are sometimes present in RDD. Consistent with our case 1, small foci of necrosis resembling microabcesses were observed in a series of soft tissue RDD.9
Rosai-Dorfman disease should be considered by the clinician and pathologist when evaluating epibulbar masses in children, adults, and the elderly. The diagnosis is made by the pathologist based on the typical histology, including emperipolesis and confirmatory immunohistochemistry. Surgical excision is the treatment of choice. Patients should be managed in conjunction with the internist to evaluate for lymphadenopathy, multiple extranodal lesions, anaemia, and leucopenia.
The authors thank Dr Brian Lee of the Department of Ophthalmology, Southern California Permanente Medical Group, for providing the clinical photograph and history for patient 1, and Dr Brian Platz of the Department of Pathology, Southern California Permanente Medical Group, for submitting histology from case 1 for review to the A Ray Irvine Ocular Pathology Laboratory. Supported in part by National Eye Institute grant EY3040, from the National Institutes of Health, Bethesda, MD, and by a grant from Research to Prevent Blindness, Inc, New York, NY, USA.