Case 1 -

Extranodal Sinus Histiocytosis (Rosai-Dorfman Disease), Bilateral Dural Involvement Anthony T. Yachnis University of Florida College of Medicine Gainesville, FL

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Click here to view (or print) handout in single page format. (1.95 MB) Note: Any slides will be printed in color. Click here to view (or print) black and white handout. (1.44 MB) Note: Text will be in single page format and any slides will be in 6-per-page format. Clinical History A previously well 35-year-old man presented with new onset tonic clonic seizures. Imaging revealed bilateral, contrast-enhancing masses that were felt to represent meningiomas. There was no family history of neurofibromatosis (types 1 or 2) and the past medical history was unremarkable. The patient underwent a craniotomy with complete excision of the larger, symptomatic, right-sided lesion with a margin of uninvolved dura mater. No intra-operative frozen section was requested. The second (left) lesion was surgically removed at a later time. Case 1 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 1 - Figure 1 T1-weighted MRI showing bilateral contrast-enhancing dural-based masses. Case 1 - Figure 2 Low magnification H&E-stained section showing a cellular lesion attached to the dura mater (lower left). Case 1 - Figure 3 Intermediate magnification H&E-stained section showing a mixed inflammatory infiltrate composed of mature lymphocytes (left), plasma cells (right), and histiocyte-like cells. Case 1 - Figure 4 High magnification H&E-stained section showing a prominent plasma cell infiltrate (right) and atypical histiocyte-like cells with large nuclei and prominent nucleoli. Case 1 - Figure 5 High magnification H&E-stained section showing atypical histiocyte-like cells with large nuclei and prominent nucleoli in a background of mature lymphocytes. Case 1 - Figure 6 High magnification H&E-stained section showing an atypical histiocyte-like cell that contains several engulfed mononuclear cells. Case 1 - Figure 7 Immunohistochemical reaction for S-100 (high magnification) showing strongly reactive histiocytes with engulfed mononuclear cells. Case 1 - Figure 8 Immunohistochemical reaction for CD68 (high magnification) showing positive reactivity of histiocytic cells. Diagnosis Extranodal Sinus Histiocytosis (Rosai-Dorfman Disease), Bilateral Dural Involvement Discussion This case of extranodal sinus histiocytosis (Rosai-Dorfman disease) presented as dural-based intracranial masses, which by imaging studies mimicked bilateral meningiomas. This disorder was originally described in young individuals who presented with massive, painless cervical lymphadenopathy, fever, weight loss, and increased sedimentation rate [1, 2, 3]. Lymph node biopsy of such patients revealed an inflammatory-like mass that contained prominent atypical histiocytes that appeared to be engulfing the other cellular elements. These clinical and pathologic findings comprise the well-described entity of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) [3]. Mass lesions elsewhere in the body with similar histologic characteristics are considered to represent extranodal forms of this disease [4] and intracranial examples are well described [5, 6]. While classic Rosai-Dorfman disease occurs in children and young adults, intracranial disease most commonly occurs in adults, although the age range is wide (5 years to the seventh decade) [5]. About two-thirds of patients who present with CNS symptoms will have involvement of non-CNS sites (esp. salivary gland and skeletal muscle). Primary Rosai-Dorfman disease of the central nervous system most often presents as a dural-based lesion with imaging features consistent with meningioma [6, 7, 8, 9, 10, 11, 12, 13]. A presentation as bilateral lesions (as illustrated in this case) has also been reported [14]. The radiologist and operating neurosurgeon may be so certain of the diagnosis that an intraoperative frozen section is not requested. Spinal [15, 16, 17], suprasellar [18], cavernous sinus [19, 20], and orbital examples [21] of Rosai-Dorfman disease have been described. Only rare cases of true intra-axial brain involvement have ever been documented [22, 23]. Gross inspection and low magnification histologic study of CNS Rosai-Dorfman disease may reveal a dural attachment to a rather well circumscribed mass. The diagnosis of meningioma will quickly be excluded by histologic study, which reveals a mixed inflammatory infiltrate composed of mature lymphocytes, plasma cells, neutrophils and a prominent population of large atypical-appearing histiocytes. The histiocytes present an eosinophilic cytoplasm, often with indistinct cell borders, and round-to-oval vesicular nuclei with prominent nucleoli. The distinctive feature of these cells is the presence of well preserved lymphocytes, plasma cells and red blood cells within their cytoplasm (emperipolesis). Although the latter feature is characteristic of the disease, it may be inconspicuous in some examples. The atypical histiocytes show strong cytoplasmic immunoreactivity for S-100 protein, which provides a marked contrast with negatively reactive "engulfed" cells. These cells are variably reactive for CD68 but are negative for CD1a, thus providing a means to distinguish histiocytes of Rosai-Dorfman type from those of Langerhans cell lineage (CD1a-reactive). The prognosis for central nervous system Rosai-Dorfman disease, as in other sites, is generally good with complete resection and corticosteroid therapy. However, recurrent and even disseminated forms have been reported [17]. The Langerhans cell histiocytoses (LCH) comprise a group of overlapping clinicopathologic disorders that most commonly occur in children [5, 6] and are due to abnormal proliferations of dendritic Langerhans-like cells (CD68 +, S-100 +, CD1a +, CD207/Langerin +) with an inflammatory reaction featuring variable numbers of eosinophils. These disorders may manifest as solitary or localized lesions ("eosinophilic granulomas"), multifocal disease often with bony involvement (Hand-Schuller-Christian disease), a disseminated form occurring in infants and young children (Abt-Letterer-Siwe disease), and even a congenital self-healing disorder (Hashimoto-Pritzker disease). In contrast to CNS Rosai-Dorfman disease, the hypothalamus, pituitary stalk, and neurohypophysis are preferred sites of involvement in the nervous system in LCH. Erdheim-Chester disease is a non-Langerhans cell histiocytosis that can affect the brain and its coverings, is composed of lipid-laden and sometimes multinucleated histiocytes that are typically positive for CD68 but negative for S-100 and CD1a. Hemophagocytic lymphohistiocytosis only affects infants who present with fever, hepatoslenomegaly and cytopenias, with CNS involvement occurring in about three-fourths of cases. Malignant histiocytoses (histiocytic sarcoma) and disseminated xanthomatous disorders may rarely affect the nervous system. The differential diagnosis in this case includes tumors arising in the intracranial compartment that may have a dural attachment [7]. The various forms of meningioma account for the majority of such lesions, and multiple meningiomas may occur in type 2 neurofibromatosis. Tumors of the hemangiopericytoma/solitary fibrous tumor group may present as dural-based tumors. Immunohistochemical staining for CD34 may be useful for this differential diagnosis. Hematologic malignancies such as extramedullary myeloid tumors ("granulocytic sarcomas") or MALT-like lymphomatous processes may sometimes present as dural-based lesions. A bilateral convexity presentation would be highly unusual for nerve sheath tumors. Small blue cell tumors such as rhabdomyosarcoma in children or esthesioneuroblastoma may present as anterior skull base masses, and rare examples of mesenchymal chondrosarcoma and synovial sarcoma can occasionally be encountered in the intracranial compartment. Benign and malignant smooth muscle tumors may present as intracranial masses, with EBV-associated neoplasms occurring in immunocompromised patients. Finally, granulomatous infections or inflammations should be considered and excluded with appropriate special stains (especially acid-fast and GMS preparations). Take Home Points Unusual dural based masses may mimic meningioma on imaging studies Such lesions include neoplastic (benign and malignant) to inflammatory/infectious etiologies Certain entities may present reactive as well as neoplastic characteristics Awareness of these mimics will promote accurate diagnoses and appropriate therapy References: Rosai J, Dorfman R. Sinus histiocytosis with massive lymphadenopathy. 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