1Department of Pathology & Laboratory Medicine, Sultan Qaboos Hospital, Salalah, Oman; 2Department of Pathology, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman *Corresponding Author’s e-mail: rajib562@yahoo.com مرض روزاي-دورفمان املعزول يف األنسجة الرخوة تقرير حالة روبياث �صودري رايب، راجا�صيخاران بيالي، اإبراهيم عدنان �صليمان، اإبراهيم الهدابي abstract: 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. Keywords: Histiocytosis; Rosai-Dorfman Disease; Emperipolesis; S100 Proteins; Case Report; Oman. ملفاوية عقد بوجود ويتميز الهي�صتيو�صايت خاليا ا�صطراب تكاثرو عن ناجت حميد نادر مر�ض هو دورفمان روزاي مر�ض امللخ�ص: مر�ض حدوث جدا النادر من انه ال الليمفية الغقد خارج املعمم روزاي-دورفمان مر�ض حدوث امكانية من وبالرغم �صخمة. اخلارجية العيادات ق�صم اإىل قدم عاما 17 العمر من يبلغ مري�ض عن حالة تقرير هذا الرخوة. الأن�صجة يف املعزول روزاي-دورفمان للوجه والفكني يف م�صت�صفى ال�صلطان قابو�ض، �صاللة، عمان، يف عام 2015 مع كتلة خديه غري موؤملة كانت تنمو ببطء خالل ال�صهرين حاليا، الرخوة. الأن�صجة يف املعزول روزاي-دورفمان ت�صخي�ض الكيميائية واملناعية املر�صية الأن�صجة فحو�صات واأكدت املا�صيني. يعترب ال�صتئ�صال اجلراحي هو العالج الأكرث فعالية لهذا املر�ض حيث اأن نتائج ا�صاليب العالج الأخرى ل تزال غري معروفة. على الرغم من ندرته، ينبغي و�صع مر�ض الروزاي-دورفمان املعزول يف الأن�صجة الرخوة يف الت�صخي�ض التفريقي لأمرا�ض الأن�صجة الرخوة خلاليا الهي�صتيو�صايت. الكلمات املفتاحية: اأمرا�ض الهي�صتيو�صيتوزي�ض؛ مر�ض روزاي-دورفمان؛ اخرتاق اخللية؛ الربوتينات S100؛ تقرير احلالة؛ عمان. Soft Tissue Rosai-Dorfman Disease Case report *Rubyath C. Rajib,1 Rajasekharan Pillai,1 Ibrahim A. Sulaiman,1 Ibrahim Al-Haddabi2 case report Sultan Qaboos University Med J, November 2017, Vol. 17, Iss. 4, pp. e452–454, Epub. 10 Jan 18 Submitted 3 Jun 17 Revision Req. 17 Jul 17; Revision Recd. 8 Aug 17 Accepted 24 Aug 17 doi: 10.18295/squmj.2017.17.04.012 Also 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 lymph- adenopathy 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.3,4 The clinical presentation is similar to that of nodal RDD.5 Nodal- based RDD usually regresses spontaneously, whereas isolated STRDD is indolent in nature and may recur years or even decades later.6 This 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 maxillo- facial 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 Rubyath C. Rajib, Rajasekharan Pillai, Ibrahim A. Sulaiman and Ibrahim Al-Haddabi Case Report | e453 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.7 Up 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.7,8 In 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 lymphadeno- pathy.2 The skin and the paranasal sinuses are the most common sites for extranodal involvement.9 In an extensive review of the literature, Komaragiri et al. identified only 36 STRDD cases reported between 1969 and 2012.10 The 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.5,11 In 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.5,11 Multifocal STRDD is extremely uncommon but recurs more frequently than a solitary lesion.11,12 The rate of recurrence of STRDD after excision has been reported to range from 21.4–54%.5,11 Immunohistochemistry 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 demo- nstrate emperipolesis predominantly of lymphocytes, although sometimes plasma cells, erythrocytes and neutrophils are also affected.5 Infiltration of lymphocytes, plasma cells and neutrophils may also occur, along with the histiocytes. However, mitosis and necrosis are rare.5 While 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 cyto- plasm [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 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). Figure 2: Immunohistochemistry stain at x400 mag- nification showing the S100 protein positivity of large histiocytes (arrow). Soft Tissue Rosai-Dorfman Disease Case report e454 | SQU Medical Journal, November 2017, Volume 17, Issue 4 3. Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy: A pseudolymphomatous benign disorder - Analysis of 34 cases. Cancer 1972; 30:1174–88. doi: 10.1002/ 1097-0142(197211)30:5<1174::AID-CNCR2820300507>3.0. CO;2-S. 4. Wenig BM, Abbondanzo SL, Childers EL, Kapadia SB, Heffner DR. Extranodal sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) of the head and neck. Hum Pathol 1993; 24:483–92. doi: 10.1016/0046- 8177(93)90160-I. 5. Montgomery EA, Meis JM, Frizzera G. Rosai-Dorfman disease of soft tissue. Am J Surg Pathol 1992; 16:122–9. doi: 10.1097/00000478-199202000-00004. 6. Costa AL, Silva NO, Motta MP, Athanazio RA, Athanazio DA, Athanazio PR. Soft tissue Rosai-Dorfman disease of the posterior mediastinum. J Bras Pneumol 2009; 35:717–20. doi: 10.1590/S1806-37132009000700015. 7. Sodhi KS, Suri S, Nijhawan R, Kang M, Gautam V. Rosai- Dorfman disease: Unusual cause of diffuse and massive retroperitoneal lymphadenopathy. Br J Radiol 2005; 78:845–7. doi: 10.1259/bjr/23127241. 8. Potts CA, Bozeman AP, Walker AN, Floyd WE 3rd. Cutaneous Rosai-Dorfman disease of the forearm: Case report. J Hand Surg Am 2008; 33:1409–13. doi: 10.1016/j.jhsa.2008.04.003. 9. Brenn T, Calonje E, Granter SR, Leonard N, Grayson W, Fletcher CD, et al. Cutaneous Rosai-Dorfman disease is a distinct clinical entity. Am J Dermatopathol 2002; 24:385–91. doi: 10.1097/00000372-200210000-00001. 10. Komaragiri M, Sparber LS, Santos-Zabala ML, Dardik M, Chamberlain RS. Extranodal Rosai-Dorfman disease: A rare soft tissue neoplasm masquerading as a sarcoma. World J Surg Oncol 2013; 11:63. doi: 10.1186/1477-7819-11-63. 11. Al-Daraji W, Anandan A, Klassen-Fischer M, Auerbach A, Marwaha JS, Fanburg-Smith JC. Soft tissue Rosai-Dorfman disease: 29 new lesions in 18 patients, with detection of polyomavirus antigen in 3 abdominal cases. Ann Diagn Pathol 2010; 14:309–16. doi: 10.1016/j.anndiagpath.2010.05.006. 12. Young PM, Kransdorf MJ, Temple HT, Mousavi F, Robinson PG. Rosai-Dorfman disease presenting as multiple soft tissue masses. Skeletal Radiol 2005; 34:665–9. doi: 10.1007/s00256- 005-0906-y. 13. Rosai J. Rosai and Ackerman’s Surgical Pathology, 10th ed. New York, USA: Mosby, 2011. Pp. 1771–900. 14. Govender D, Chetty R. Inflammatory pseudotumour and Rosai- Dorfman disease of soft tissue: A histological continuum? J Clin Pathol 1997; 50:79–81. doi: 10.1136/jcp.50.1.79. 15. Lu D, Estalilla OC, Manning JT Jr, Medeiros J. Sinus histio- cytosis with massive lymphadenopathy and malignant lymphoma involving the same lymph node: A report of four cases and review of the literature. Mod Pathol 2000; 13:414–19. doi: 10.1038/modpathol.3880071. 16. Falk S, Stutte HJ, Frizzera G. Hodgkin’s disease and sinus histiocytosis with massive lymphadenopathy-like changes. Histopathology 1991; 19:221–4. doi: 10.1111/j.1365-2559.1991. tb00025.x. reported frequent spindling of the histiocytes, others have claimed this is uncommon.5,11 In cases with histiocyte spindling, STRDD may be confused with a sarcoma.10 In terms of immunohistochemistry, RDD histiocytes are consistently positive for S100 proteins and CD68 and negative for CD1a.13 The microscopic appearance of an inflammatory pseudotumour can resemble STRDD; however, the histiocytes of infla- mmatory pseudotumours are negative for S100. These lesions may reflect a histological continuum.14 Another differential diagnosis of STRDD is Langerhans cell histiocytosis, in which the histiocytes are positive for both S100 proteins and CD1a.15 The histogenesis of RDD is still unclear, but may be the result of an aberrant immunoresponse.7 The disease has also been associated with lympho- proliferative disorders.2 In cases of Hodgkin’s lymphoma, certain cytokines have been found to alter the morphology of histiocytes to that seen in RDD.16 A relationship between polyomavirus infections and intra-abdominal STRDD has also been postulated.11 Due 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.10 Further 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 infla- mmatory pseudotumour, sarcoma or Langerhans cell histiocytosis. As such, it is important that STRDD be considered in the differential diagnosis of histiocytic soft tissue lesions. References 1. Rosai J, Dorfman RF. Sinus histiocytosis with massive lympha- denopathy: A newly recognized benign clinico-pathological entity. Arch Pathol 1969; 87:63–70. 2. Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): Review of the entity. Semin Diagn Pathol 1990; 7:19–73. https://doi.org/10.1002/1097-0142%28197211%2930:5%3C1174::AID-CNCR2820300507%3E3.0.CO%3B2-S https://doi.org/10.1002/1097-0142%28197211%2930:5%3C1174::AID-CNCR2820300507%3E3.0.CO%3B2-S https://doi.org/10.1002/1097-0142%28197211%2930:5%3C1174::AID-CNCR2820300507%3E3.0.CO%3B2-S https://doi.org/10.1016/0046-8177%2893%2990160-I https://doi.org/10.1016/0046-8177%2893%2990160-I https://doi.org/10.1097/00000478-199202000-00004 https://doi.org/10.1590/S1806-37132009000700015 https://doi.org/10.1259/bjr/23127241 https://doi.org/10.1016/j.jhsa.2008.04.003 https://doi.org/10.1097/00000372-200210000-00001 https://doi.org/10.1186/1477-7819-11-63 https://doi.org/10.1016/j.anndiagpath.2010.05.006 https://doi.org/10.1007/s00256-005-0906-y https://doi.org/10.1007/s00256-005-0906-y https://doi.org/10.1136/jcp.50.1.79 https://doi.org/10.1038/modpathol.3880071 https://doi.org/10.1111/j.1365-2559.1991.tb00025.x https://doi.org/10.1111/j.1365-2559.1991.tb00025.x