Access at https://isn-slidearchive.org/?col=ISN however, MRI-brain continued to demonstrate a persistent lesion with a slight interval decrease from 4.2 to 4.0 cm. Concurrent computed tomography (CT) angiogram showed a lack of hyperostosis of the clivus, arguing against meningioma diagnosis, subsequently prompting the differential diagnosis of neurosarcoidosis versus idiopathic hypertrophic cranial pachymeningitis. He continued to follow up every 6 months since then; however, his clinical symptoms continued to worsen with the development of generalized arthralgia, fatigue, progressive bilateral hearing loss, imbalance, and papilledema resulting in a presumed clinical diagnosis of neurosarcoidosis. He underwent right ventriculoperitoneal shunting and right cochlear implantation with transient resolution of symptoms. After 12 years since the initial presentation, he presented to the emergency department with altered mental status, seizures, and left hemiparesis. MRI-brain showed persistence of the meningeal lesion (Figure 1) with brain parenchymal involvement. Infectious disease evaluation was negative. Given the clinical impression of neurosarcoidosis, a rheumatology evaluation was pursued which demonstrated left perinephric soft tissue thickening on CT-abdomen/pelvis, raising the differential diagnosis of sarcoidosis, lymphoma, Erdheim–Chester disease (ECD), and inflammatory pseudotumor. No other organs were involved by radiology evaluation. Biopsies of both the dural-based mass and the perinephric soft tissue mass were performed. The patient was initiated on empiric treatment with dexamethasone, rituximab, and subsequently cobimetinib, with worsening of neurologic symptoms. He passed away within a week from diagnosis due to massive pulmonary embolism and cardiac arrest (Box 1). Biopsy of dural mass showed extensive involvement by abundant lymphoplasmacytic and histiocytic infiltrates. These histiocytes were characterized by enlarged round to oval nuclei, inconspicuous nucleoli, and abundant pale eosinophilic to foamy cytoplasm; foci of emperipolesis were present (Figure 2). By immunohistochemistry, these histiocytes were positive for CD163, S100, cyclinD1, and were negative for CD1a, SSTR2, BRAF V600E, and ALK. SSTR2 immunostaining highlighted the leptomeninges, which demonstrated reactive changes and showed no evidence of a mass-forming meningothelial lesion. The background lymphocytes were composed of predominantly CD3-positive T-cells admixed with relatively fewer CD20-positive B-cells, and admixed plasma cells showed no increase in IgG4/IgG ratio and were polytypic for kappa and lambda light chains. No distinct granulomas were seen. Histopathologic sections from left perinephric mass showed similar morphologic and immunophenotypic features to the dural mass (Figure 2). Rosai–Dorfman disease. Rosai–Dorfman disease (RDD) is a rare histiocytic disorder characterized by accumulation of histiocytes in nodal and extranodal sites. Historically, it was considered to be a reactive process; contemporary evidence has demonstrated the presence of mitogen-activated protein kinase (MAPK) pathway mutations in nearly one-third of RDD cases, resulting in recognition of RDD as a distinct histiocytic neoplasm by the World Health Organization classification of hematopoietic tumors (5th edition, 2022) 1. The challenging histopathologic feature is the presence of abundant inflammatory infiltrates masquerading the lesional histiocytic cells, often resulting in an under-diagnosis. Intra-cranial RDD accounts for ~5%–10% of all RDD cases 2. For dural-based lesions with extensive irregular pachymeningeal thickening, RDD is a frequent mimic of meningiomas and should be entertained in the differential diagnosis during radiology evaluation in addition to inflammatory disorders (neurosarcoidosis, hypertrophic pachymeningitis, IgG4-related disease) and lymphoid neoplasms 2, 3. By histopathology, cyclinD1 expression in RDD cells is a useful immunohistochemical marker to distinguish from reactive histiocytes which are cyclinD1-negative 1, 3. RDD can be associated with increased IgG4-positive plasma cells; however, a concurrent diagnosis of IgG4-related disease should only be made if other histopathologic criteria (IgG4/IgG ratio >40%) and radiologic criteria are met 1. Further, the presence of emperipolesis characterized by engulfment of inflammatory cells (predominantly lymphocytes and plasma cells, occasionally neutrophils) is not a pathognomonic feature in RDD, as it can be observed in both reactive histiocytes as well as other histiocytic neoplasms including ECD and juvenile xanthogranuloma (JXG) 1. Therefore, distinction from ECD and JXG relies heavily on integration of clinical, radiologic, histopathologic, and molecular data. RDD can be distinguished from ALK-positive histiocytes by absence of ALK expression, and from Langerhans cell histiocytosis (LCH) by absence of CD1a and langerin expression, respectively 1, 2. While most RDDs have a favorable prognosis, the delayed recognition of this diagnosis has led to neurocognitive decline in this patient. Although next generation sequencing (NGS) was considered to identify targetable mutations, the patient's deteriorating clinical status resulted in discontinuity of NGS testing. This case highlights the complexities in recognition of neurohistiocytic tumors and their radiologic mimics, emphasizing the need to increase awareness of these rare histiocytic disorders. Alyssa M. Lee and Aishwarya Ravindran conceptualized and drafted the manuscript. Aishwarya Ravindran made the primary histopathologic diagnosis due to expertise in histiocytic disorders and acquired histopathologic images. Siddhartha Gaddamanugu interpreted the radiologic findings. Kathryn L. Eschbacher participated in the diagnostic discussions, reviewed, and edited the manuscript. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Lee et al. (Sun,) studied this question.