Treatment of multifocal cutaneous Rosai-Dorfman disease with radiotherapy

Abstract

Rosai-Dorfman disease (RDD) is an exceptionally rare form of non-Langerhans cell histiocytosis which can present either as systemic RDD with or without skin manifestations, or as cutaneous RDD (CRDD) limited to the skin.1Rosai J. Dorfman R.F. Sinus histiocytosis with massive lymphadenopathy: a newly recognized benign clinicopathological entity.Arch Pathol. 1969; 87: 63-70PubMed Google Scholar In the skin, it presents as solitary or grouped papules, nodules, plaques, or a combination thereof.1Rosai J. Dorfman R.F. Sinus histiocytosis with massive lymphadenopathy: a newly recognized benign clinicopathological entity.Arch Pathol. 1969; 87: 63-70PubMed Google Scholar CRDD is more common in middle-aged women and in patients of Asian or Caucasian descent.2Brenn T. Calonje E. Granter S.R. et al.Cutaneous Rosai-Dorfman disease is a distinct clinical entity.Am J Dermatopathol. 2002; 24: 385-391https://doi.org/10.1097/00000372-200210000-00001Crossref PubMed Scopus (189) Google Scholar,3Abla O. Jacobsen E. Picarsic J. et al.Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease.Blood. 2018; 131: 2877-2890https://doi.org/10.1182/blood-2018-03-839753Crossref PubMed Scopus (208) Google Scholar There is a lack of generalized treatment guidelines for CRDD because of the extremely low prevalence and overall poor response to most therapies.3Abla O. Jacobsen E. Picarsic J. et al.Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease.Blood. 2018; 131: 2877-2890https://doi.org/10.1182/blood-2018-03-839753Crossref PubMed Scopus (208) Google Scholar,4Al-Khateeb T.H. Cutaneous Rosai-Dorfman disease of the face: A comprehensive literature review and case report.J Oral Maxillofac Surg. 2016; 74: 528-540https://doi.org/10.1016/j.joms.2015.09.017Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar Here, we present a case of CRDD that showed significant partial response to localized radiotherapy. A 43-year-old African American woman presented with an approximately 2-year history of pruritic papulonodules on the right buttock and left shoulder that had enlarged over time. Treatments prior to dermatology consultation included triamcinolone 0.1% ointment and mupirocin ointment without response, followed by 2 separate courses of 40 mg prednisone taper with only partial improvement followed by recurrence. An excisional biopsy of the left arm papules demonstrated a dermal and subcutaneous infiltrate of large S100-positive histiocytes with emperipolesis on a background of lymphocytes and plasma cells, consistent with RDD. She was referred to dermatology for further evaluation of the buttock lesion. On physical examination, there were clustered pink-violaceous papulonodules and plaques with overlying scale on the right buttock (Fig 1, A). At the site of the previous excisional biopsy on the left arm, there was an atrophic scar surrounded by few remaining pink-violaceous scaly papulonodules. Histopathology of the buttock biopsy similarly showed sheets of feathery histiocytes with emperipolesis, admixed with lymphocytes, plasma cells, and neutrophils, consistent with RDD (Fig 2). The histiocytes were positive for S100, and microbial stains did not reveal any organisms.Fig 2Histopathologic features of cutaneous Rosai-Dorfman disease. A, A dense infiltrate with pale and dark areas filled the biopsy specimen (B), High magnification showed feathery histiocytes displaying emperipolesis of lymphocytes and neutrophils (C), S100 staining confirmed the diagnosis. (A-C, Hematoxylin-eosin stain; original magnifications: A, ×20; B, ×600; and C, ×400.)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Evaluation for systemic disease included computed tomography imaging of the neck, chest, abdomen, and pelvis, which was notable for mild cervical lymphadenopathy with no evidence of organ involvement. Laboratory work-up included a complete blood count, comprehensive metabolic panel, antinuclear antibody, and serum immunoglobulin levels, which were notable for mild leukocytosis (11,400/μL; normal range, 4000-10,000/μL) and a mild elevation in IgG4 (95.2 mg/dL; normal range, 3.9-86.4 mg/dL). Work-up of the leukocytosis revealed a negative V-β analysis on flow cytometry, signifying normal T-cell polyclonality. These findings supported a diagnosis of CRDD without evidence of systemic RDD. After multidisciplinary consultation with radiation oncology and medical oncology, the decision was made to proceed with localized radiotherapy to a dose of 30 Gy in 15 fractions, with the radiation field encompassing a 2-cm margin around the visible disease. The lesions were observed to be thin during the treatment course, and the patient tolerated radiotherapy well with only minor radiodermatitis which self-resolved. At the 2-month follow-up after completion of radiotherapy, she had significant partial resolution of the treated lesions, and only a few residual papules with postinflammatory hyperpigmentation (Fig 1, B). At the 7-month follow-up, there was continued improvement, with just 2 residual pink nodules and postinflammatory hyperpigmentation. While 10% of systemic RDD cases involve skin lesions, purely cutaneous RDD is a rare clinical entity and has notable differences from systemic RDD.3Abla O. Jacobsen E. Picarsic J. et al.Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease.Blood. 2018; 131: 2877-2890https://doi.org/10.1182/blood-2018-03-839753Crossref PubMed Scopus (208) Google Scholar,4Al-Khateeb T.H. Cutaneous Rosai-Dorfman disease of the face: A comprehensive literature review and case report.J Oral Maxillofac Surg. 2016; 74: 528-540https://doi.org/10.1016/j.joms.2015.09.017Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar The age distribution of patients with CRDD is wide, with a mean of 43.5 years, which is significantly higher than the mean age of systemic RDD (20.6 years).2Brenn T. Calonje E. Granter S.R. et al.Cutaneous Rosai-Dorfman disease is a distinct clinical entity.Am J Dermatopathol. 2002; 24: 385-391https://doi.org/10.1097/00000372-200210000-00001Crossref PubMed Scopus (189) Google Scholar,3Abla O. Jacobsen E. Picarsic J. et al.Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease.Blood. 2018; 131: 2877-2890https://doi.org/10.1182/blood-2018-03-839753Crossref PubMed Scopus (208) Google Scholar Furthermore, patients with CRDD lack massive lymphadenopathy, fever, night sweats, and lab abnormalities (commonly elevated erythrocyte sedimentation rate, C-reactive protein, various cytopenias) found in patients with systemic RDD.3Abla O. Jacobsen E. Picarsic J. et al.Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease.Blood. 2018; 131: 2877-2890https://doi.org/10.1182/blood-2018-03-839753Crossref PubMed Scopus (208) Google Scholar,4Al-Khateeb T.H. Cutaneous Rosai-Dorfman disease of the face: A comprehensive literature review and case report.J Oral Maxillofac Surg. 2016; 74: 528-540https://doi.org/10.1016/j.joms.2015.09.017Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar CRDD is a difficult entity to treat. A review reported the overall cure rate for CRDD as 28.6%, when considering all therapeutic modalities.4Al-Khateeb T.H. Cutaneous Rosai-Dorfman disease of the face: A comprehensive literature review and case report.J Oral Maxillofac Surg. 2016; 74: 528-540https://doi.org/10.1016/j.joms.2015.09.017Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar Potential treatments for CRDD include topical steroids, cryotherapy, laser therapy, surgical excision, localized radiotherapy, prednisone, thalidomide, dapsone, methotrexate, isotretinoin, and imatinib.5Fang S. Chen A.J. Facial cutaneous Rosai-Dorfman disease: a case report and literature review.Exp Ther Med. 2015; 9: 1389-1392https://doi.org/10.3892/etm.2015.2260Crossref PubMed Scopus (24) Google Scholar Our case adds further support for the use of localized radiotherapy for treatment of CRDD. Only 2 cases of CRDD treated with radiotherapy have been reported previously, with radiotherapy more often employed for the treatment of RDD lesions of the soft tissue or bone that persist after surgical resection.3Abla O. Jacobsen E. Picarsic J. et al.Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease.Blood. 2018; 131: 2877-2890https://doi.org/10.1182/blood-2018-03-839753Crossref PubMed Scopus (208) Google Scholar,6Annessi G. Giannetti A. Purely cutaneous Rosai-Dorfman disease.Br J Dermatol. 1996; 134: 749-753https://doi.org/10.1046/j.1365-2133.1996.89803.xCrossref PubMed Google Scholar,7Bunick C.G. Leffell D. Bosenberg M. Yahalom J. Choi J.N. Cutaneous Rosai-Dorfman disease of the right ear responsive to radiotherapy.J Am Acad Dermatol. 2012; 67: e225-e226https://doi.org/10.1016/j.jaad.2012.04.025Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Standard dosing guidelines for radiotherapy treatment of CRDD and RDD are not available, but doses generally vary between 20 Gy and 40 Gy.3Abla O. Jacobsen E. Picarsic J. et al.Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease.Blood. 2018; 131: 2877-2890https://doi.org/10.1182/blood-2018-03-839753Crossref PubMed Scopus (208) Google Scholar This range is similar to that for treatment of primary cutaneous lymphomas, for which the dose varies by subtype but generally ranges from 20 to 40 Gy.8Specht L. Dabaja B. Illidge T. Wilson L.D. Hoppe R.T. International Lymphoma Radiation Oncology GroupModern radiation therapy for primary cutaneous lymphomas: field and dose guidelines from the International Lymphoma Radiation Oncology Group.Int J Radiat Oncol Biol Phys. 2015; 92: 32-39https://doi.org/10.1016/j.ijrobp.2015.01.008Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar A case series of 9 patients with various forms of RDD showed sustained response to radiation in 4 patients.9Christopherson K.M. Gunther J.R. Hilal L. et al.Thirty year experience with Rosai Dorfman disease treated with radiation, chemotherapy, and/or surgery.Int J Radiat Oncol Biol Phys. 2018; 102: e432https://doi.org/10.1016/j.ijrobp.2018.07.1256Abstract Full Text Full Text PDF Google Scholar In conclusion, we suggest localized radiotherapy be considered as an effective therapeutic option for CRDD, especially in areas, which may be challenging to resect, or which are cosmetically sensitive. None disclosed.