Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease

Abstract

Rosai-Dorfman-Destombes disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by accumulation of activated histiocytes within affected tissues. RDD, which now belongs to the R group of the 2016 revised histiocytosis classification, is a widely heterogeneous entity with a range of clinical phenotypes occurring in isolation or in association with autoimmune or malignant diseases. Recent studies have found NRAS, KRAS, MAP2K1, and ARAF mutations in lesional tissues, raising the possibility of a clonal origin in some forms of RDD. More than 1000 reports have been published in the English literature; however, there is a lack of consensus regarding approach for the clinical management of RDD. Although in most cases RDD can be observed or treated with local therapies, some patients with refractory or multifocal disease experience morbidity and mortality. Here we provide the first consensus multidisciplinary recommendations for the diagnosis and management of RDD. These recommendations were discussed at the 32nd Histiocyte Society Meeting by an international group of academic clinicians and pathologists with expertise in RDD. We include guidelines for clinical, laboratory, pathologic, and radiographic evaluation of patients with RDD together with treatment recommendations based on clinical experience and review of the literature.

Figure 1.

Summary of the diverse kinase mutations documented in RDD. (A) Pie chart illustrating the known activating kinase mutations in RDD (N = 34). (B) Diagrams of somatic mutations described in KRAS and NRAS. (C) Diagram of somatic mutations uncovered in MAP2K1. (D) Diagram of somatic mutation discovered in ARAF.

Figure 2.

Pathologic and clinical features of RDD. (A-E) Representative images of nodal RDD from tissue biopsies (A-B) and fine-needle aspiration (C-E). (A) Mixed RDD/LCH case with sinus expansion. The large RDD histiocytes display conspicuous emperipolesis with pale cytoplasm, as compared with the intermixed LCH cells with dense eosinophilic cytoplasm and convoluted nuclei (original magnification [OM] ×400; hematoxylin and eosin [H&E] stain). (B) The RDD histiocytes show pale watery-clear cytoplasm, a central round nucleus with a conspicuous nucleolus, and emperipolesis (OM ×1000; H&E stain). Cell block preparation shows clusters of RDD histiocytes (OM ×400; H&E stain) (C), with nuclear and cytoplasmic staining for S100 (OM ×1000) (D) and fascin (OM ×1000) (E); the trafficking intact leukocytes are negative. (F) A child with immunodeficiency and RDD with massive cervical lymphadenopathy. (G) RDD of the skin showing red nodular lesions. (H) Tongue enlargement resulting from oral RDD.

Figure 3.

Radiographic features of RDD. (A) Gadolinium-enhanced coronal T1-weighted magnetic resonance imaging (MRI) demonstrates a dural-based lesion at the base of the right frontal lobe (blue arrow). (B) Patchy enhancing lesions in the brainstem on gadolinium-enhanced axial T1-weighted MRI (green arrow). (C) Gadolinium-enhanced axial T1-weighted MRI demonstrates lesions in the bilateral cavernous sinuses and Meckel’s cave (red asterisks) as well as the left orbit (red arrow), with resulting proptosis. (D) Axial fused [¹⁸F]fluorodeoxyglucose (FDG)–positron emission tomography (PET)/computed tomography (CT) demonstrates a hypermetabolic dural-based paraspinal mass with involvement of the osseous elements of the thoracic spine with foraminal extension. (E) Response to 12 weeks of 1 mg/kg per day of prednisone is demonstrated, with near resolution of hypermetabolism and regression of the tumor. (F) Partly T2-weighted bright-blood image shows an oval mass (black arrow) in the left atrium (LA) arising from the central part of the heart at the atrioventricular junction. LV, left ventricle; RA, right atrium; RV, right ventricle.

Figure 4.

A proposed management algorithm for patients with RDD.