Case 1 -
Extranodal Sinus Histiocytosis (Rosai-Dorfman Disease), Bilateral Dural Involvement
Anthony T. Yachnis
University of Florida College of Medicine
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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
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.
Extranodal Sinus Histiocytosis (Rosai-Dorfman Disease), Bilateral Dural Involvement
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
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)
. Mass lesions elsewhere in
the body with similar histologic characteristics are considered to represent extranodal forms of this
disease  and
intracranial examples are well described
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)
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
presentation as bilateral lesions (as illustrated in this case) has also been
reported . The
radiologist and operating neurosurgeon may be so certain of the diagnosis that an intraoperative frozen
section is not requested. Spinal
examples  of Rosai-Dorfman disease have been described. Only rare cases of true intra-axial brain
involvement have ever been documented
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 .
The Langerhans cell histiocytoses (LCH) comprise a group of overlapping clinicopathologic disorders
that most commonly occur in children
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 . 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
- Certain entities may present reactive as well
as neoplastic characteristics
- Awareness of these mimics will promote accurate
diagnoses and appropriate therapy
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