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Clinical features of Rosai-Dorfman disease
Histopathologic and molecular features
The median number of biopsies required to establish a diagnosis was two (range, 1-6). Eleven (18%) patients underwent ≥3 tissue biopsies. Classic histopathologic fea- tures of RDD were enlarged histiocytes demonstrating emperipolesis, expressing CD163 and S100, but not CD1a by immunohistochemistry (Figure 3). However, the pathognomonic RDD histiocytes were infrequently found within the infiltrates in some extranodal lesions, and often were obscured by the inflammatory background or fibro- sis. The inflammation accompanying RDD infiltrates was characterized by secondary lymphoid follicles and abun- dant plasma cells. Due to these features, the histopatholo- gy was most often mistaken as non-specific chronic inflammation, with the diagnosis of RDD only recognized following a repeat tissue biopsy or review at our institu- tion (n=11).
Among the five patients who underwent NGS, one showed a CDC73 truncation in exon 5, and another had a KRAS c.351A>T (K117N) mutation. Interestingly, two of the three patients with RDD/ECD overlap showed the presence of a MEK1 mutation, one on testicular tissue
[MAP2K1 c.157T>C (F53L)] and the other on peripheral blood [MAP2K1 c.167A>C (Q56P)]. No pathogenic muta- tion was detected in the tissue specimen of the remaining two cases. None of these specimens demonstrated the presence of known oncogenic gene fusions on RNA sequencing. BRAF-V600E mutation testing was performed in two cases and both were negative: one by immunohis- tochemistry and one by cell-free DNA polymerase chain reaction.
Treatments and outcome
1. First line treatments
Treatment and initial follow-up data were available for 57 (89%) patients (Table 2 and Figure 6). Of these, eight (14%) patients were initially observed. All of the patients who were observed and with follow-up data (n=3; 38%) eventually required treatment, with a median time to treatment of 30 months. Overall, the most common first- line therapeutic modality was surgical excision in 24 (38%) patients. The duration of response to surgery was variable (median 12 months, range 2-162), with 33% relapse rate. Of the relapses, five (21%) patients under-
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Figure 5. A variety of less common Rosai-Dorfman disease imaging findings. (A) Coronal contrast enhanced head MRI depicting a homogenously enhancing extra- axial intracranial soft tissue mass. Note the lack of dural tail (arrow) characteristic of the more common and similar appearing meningioma. (B) Enhanced axial orbit CT showing large intraconal soft tissue masses (*) and associated exophthalmos. (C) Enhanced coronal CT of the neck showing a soft tissue lesion involving the left parotid (circle) along with soft tissue lesions encasing arteries of the neck (arrowheads). (D & E) Axial CT and FDG PET/CT images of the thorax demonstrating an FDG avid soft tissue lesion in the right atrioventricular groove (oval), encasing the right coronary artery (arrowhead). (F) Delayed enhanced axial CT of the abdomen depicting perinephric (bracket) and renal hilar (arrow) infiltrative soft tissue. (G) Cranial-caudal compression mammogram elucidating a palpable subareolar mass (circle). (H) Fused axial FDG PET/CT demonstrating a focal FDG avid biopsy proven hepatic lesion. ( I) Enhanced reformated CT of the chest demonstrating a soft tis- sue lesion in the lower airway, overriding the carina (square). (J & K) Fused coronal FDG PET/CT and testicular ultrasound demonstrating a hypermetabolic (14.2 SUVmax) testicle (arrow) with multiple corresponding hypoechoic lesions on ultrasound (arrowheads) in a patient with RDD/ECD overlap.
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