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Stereotactic Interstitial Radiosurgery for Intracranial Rosai-Dorfman DiseaseA Novel Therapeutic Approach

Faycal El Majdoub1, 2, Anna Brunn3, Frank Berthold4, Volker Sturm1, Mohammad Maarouf1

Background: Rosai-Dorfman disease is an idiopathic, histoproliferative disorder characterized by massive painless lymphade-nopathy. The favorable treatment of Rosai-Dorfman disease affecting the central nervous system is surgical resection. Histological and immunohistochemical confirmation is essential for a definitive diagnosis.Case Report: The authors report on a 10-year-old patient with Rosai-Dorfman disease of the central nervous system who presented with increased intracranial pressure. She was treated by stereotactic interstitial irradiation using iodine-125 seeds (interstitial radiosurgery).Result: Stereotactic surgery was performed without complications. The patient recovered well to a normal neurologic status. MR images showed a complete remission 49 months after treatment.Conclusion: The presented case demonstrates the high efficacy and safety of interstitial irradiation for intracranial Rosai-Dorf-man disease. Hence, interstitial radiosurgery could be an appropriate therapeutic option for high-risk resectable intracranial Rosai-Dorfman disease.

Key Words: Rosai-Dorfman disease · Sinus histiocytosis · Intracranial lesion · Stereotactic brachytherapy · Iodine-125 · Interstitial radiosurgery

Strahlenther Onkol 2009;185:109–12DOI 10.1007/s00066-009-1911-1

Stereotaktische interstitielle Radiochirurgie zur Behandlung des intrakraniellen Rosai-Dorfman-Syndroms. Ein neuer therapeutischer Ansatz

Hintergrund: Das Rosai-Dorfman-Syndrom ist eine idiopathische, proliferative Erkrankung, welche durch eine schmerzlose Lymphknotenschwellung charakterisiert ist. Bei Befall des zentralen Nervensystems ist die mikrochirurgische Resektion die Thera-pie der ersten Wahl. Die histologische und immunhistochemische Analyse ist entscheidend für die definitive Diagnose.Fallbericht: Die Autoren berichten über eine 10-jährige Patientin mit erhöhten Hirndruckzeichen und einem zerebralen Ro-sai-Dorfman-Syndrom. Primär wurde eine stereotaktisch geführte interstitielle Brachytherapie mit Jod-125-Seeds durchgeführt.Ergebnis: Die Behandlung konnte ohne Komplikationen durchgeführt werden. Der neurologische Zustand normalisierte sich. MRT-Veraufskontrollen zeigten 49 Monate nach der Behandlung eine komplette Tumorremission.Schlussfolgerung: Der vorliegende Fall veranschaulicht die Effizienz der stereotaktisch geführten interstitiellen Seedbestrah-lung zur Behandlung eines intrakraniellen Rosai-Dorfman-Syndroms und sollte insbesondere bei inoperablen Tumoren als Thera-pieoption berücksichtigt werden.

Schlüsselwörter: Rosai-Dorfman-Syndrom · Sinushistiozytose · Intrakranielle Raumforderung · Stereotaktische Brachy-therapie · Jod 125 · Interstitielle Radiochirurgie

1Department of Stereotactic and Functional Neurosurgery, University of Cologne, Germany,2Department of General Neurosurgery, University of Cologne, Germany,3Department of Neuropathology, University of Cologne, Germany,4Department of Pediatric Oncology and Hematology, University of Cologne, Germany.

Received: May 21, 2008; accepted: October 22, 2008

Case StudyStrahlentherapie und Onkologie

El Majdoub F, et al. Brachytherapy for Intracranial Histiocytosis

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Figures 1a to 1d. Gadolinium-enhanced T1- and T2-weighted MR images show a well-circumscribed, enhancing lesion in the left white matter and basal ganglia (a, b). In the T2-weighted MR image, hypointense foci within the mass are visible (b). Follow-up MR images reveal a complete remis-sion 49 months after stereotactic surgery (c, d).

Abbildungen 1a bis 1d. Präoperative, T1-gewichtete MRT-Aufnahmen mit Gadolinium zeigen eine gut abgrenzbare, Kontrastmittel aufnehmende Läsion im frontalen Marklager und in den Stammganglien links (a). Die Raumforderung ist in der T2-Wichtung hypointens (b). Die MRT-Kontrollen 49 Monate nach stereotaktischer Jod-125-Seed-Katheterimplantation zur interstitiellen Brachytherapie zeigen eine komplette Tumorremission (c, d).

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IntroductionRosai-Dorfman disease, also known as sinus histiocytosis, is a benign histiocytic proliferative disorder with massive lymph-adenopathy [16]. Its classic form occurs in children and ado-lescents causing bilateral painless cervical lymphadenopathy, fever and leukocytosis [4]. An isolated intracranial manifesta-tion without associated lymphadenopathy is extremely rare. We report a first case of Rosai-Dorfman disease of the central nervous system in a child treated by stereotactic interstitial ir-radiation using low-activity iodine-125 seeds.

Case ReportA 10-year-old girl presented with headache, nausea, vomit-ing, weight loss of 3 kg and progressive dizziness that had lasted for 6 weeks. Cranial MR images revealed a gadolin-ium-enhancing, well-circumscribed lesion with a maximal diameter of 2.5 cm and a massive perifocal edema resulting in compression of the left lateral ventricle. The lesion was located in the left white matter and basal ganglia, showing hypointense foci on T2-weighted MR images and a moderate perifocal edema (Figures 1a and 1b). On physical examina-tion, there was no evidence of lymphadenopathy or hepa-tosplenomegaly. Stereotactic biopsy was performed without complications.

Histopathologically, the lesion exhibited multiple nodules of histiocytes with an eosinophilic cytoplasm, which were ac-companied by broad infiltrates of small, mature lymphocytes

and plasma cells (Figure 2a). Immunohistochemistry revealed a positive staining with CD68 and S-100 protein, whereas the CD1a antigen was not expressed by the histiocytes. In addi-tion, the cytoplasm of enlarged histiocytes harbored well-pre-served lymphocytes and plasma cells (emperipolesis; Figure 2b). Between the cellular infiltrates, there was a fibrosis of the connective tissue whereas immunohistochemistry with the antibody against the glial fibrillary acidic protein detected only single reactive hypertrophic astrocytes.

Initially, the tumor was treated with oral dexamethasone (3 × 2 mg/d, days 1–27, then tapering). Follow-up MR images showed a decrease of the perifocal edema, while the tumor was progressive.

Because of the sensitivity of histiocytic lesions to radio-therapy and location in the basal ganglia, the local interdis-ciplinary tumor board consisting of pediatric oncologist, ra-diotherapist, neuropathologist, pediatric radiologist, general neurosurgeon and stereotactic neurosurgeon recommended a stereotactic-guided implantation of low-activity iodine-125 seeds for interstitial irradiation. Stereotactic surgery was per-formed without complications. A tumor surface dose of 50 Gy was applied as temporary implants within 42 days. The surgi-cal approach and technical data are published elsewhere [10]. Postoperatively, the patient’s condition improved to a normal status. Follow-up MR images up to now 49 months after sur-gery revealed a complete remission. An adverse radiation ef-fect was not visible (Figures 1c and 1d).

Figures 2a and 2b. Histopathology of the stereotactic biopsy reveals nodules of histiocytes (arrows, a) with an eosinophilic cytoplasm and phago-cytosed lymphocytes which are well preserved (emperipolesis; arrows, insert in a). Between the histiocytic nodules, there are infiltrates consisting of lymphocytes (arrow, b) and plasma cells (arrowhead, b). Histiocytes are S-100-positive (asterisk, b) and CD68-positive (insert in b). The asterisk in the insert in b indicates further emperipolesis. a) H&E staining, x200; insert x600. b) Anti S-100 protein immunostaining, x400; insert anti CD68 immunostaining, x600.

Abbildungen 2a und 2b. Die histopathologische Aufarbeitung des stereotaktischen Biopsiematerials zeigt knotenförmige Anhäufungen von Histiozyten (Pfeile, a) mit eosinophilem Zytoplasma und phagozytierten Lymphozyten (Emperipolesis; Pfeile, Vergrößerung in a). Zwischen den Histiozyteninseln befinden sich Infiltrate bestehend aus Lymphozyten (Pfeil, b) und Plasmazellen (Pfeilspitze, b). Immunhistochemisch sind die Histiozyten positiv für S-100 (Stern, b) sowie CD68 (Vergrößerung in b). Der Stern in der Vergrößerung in b deutet auf eine weitere Emperipolesis. hin. a) H&E-Färbung, x200; Insert x600. b) Anti-S-100-Protein-Immunfärbung, x400; Anti-CD68-Immunfärbung im Insert, x600.

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DiscussionThis case is the first to demonstrate a complete remission of an isolated intracranial lesion associated with Rosai-Dorfman disease treated with stereotactic interstitial radiosurgery.

In 1969, Rosai & Dorfman reported a first case of sinus histiocytosis [16]. Since then, it has become a well-described entity affecting the cervical region more often than other sites. Extranodal manifestation appears in 25–40% of cases including the skin, bones, respiratory tracts, and central nervous system [4, 11]. Involvement of the central nervous system is rare, and the majority of these lesions imitate meningiomas presenting as well-circumscribed, dural-based lesions, strongly enhancing on T1-weighted MR images after gadolinium administration [6, 8, 9].

Since laboratory results are nonspecific, diagnosis relies on histological and immunochemical analysis of the patho-logic sample. Rosai-Dorfman disease has a distinctive his-tological appearance characterized by an infiltration of lym-phoplasmatic cells and histiocytes displaying emperipolesis (lymphophagocytosis). The histiocytes of Rosai-Dorfman dis-ease are immunopositive for S-100 protein and CD1a-negative distinguishing them from histiocytes found in granulomatous disease [7, 9].

The primary treatment of Rosai-Dorfman disease of the central nervous system has been surgery [3, 14, 17]. Recur-rence after surgery has been reported in 14% of cases [4]. The adjuvant treatment modalities, i.e. radiotherapy, systemic cor-ticosteroid or combinations of these, have been applied with different success [1, 5, 14, 17]. Petzold et al. [14] reported on a resolution of the intracranial mass treated by postoperative fractionated irradiation.

Interstitial brachytherapy is a special application of irra-diation [12, 13, 18]. Its feasibility and efficacy for the treatment of well-delineated gliomas as well as some extracranial solid tu-mors are referred in several publications [2, 10, 15, 18, 19]. The case presented here demonstrates the high efficacy and safety of interstitial brachytherapy for intracranial Rosai-Dorfman disease. Hence, stereotactic interstitial radiosurgery could be an appropriate therapeutic option for high-risk resectable in-tracranial Rosai-Dorfman disease. Due to the radiosensitivity of this tumor, fractionated radiotherapy should be considered for inoperable, large and complex-configurated lesions.

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Address for CorrespondenceMohammad Maarouf, MDAssociate ProfessorDepartment of Stereotactic and Functional NeurosurgeryUniversity of CologneKerpener Straße 6250924 KölnGermanyPhone (+49/221) 478-4759, Fax -5112e-mail: m.maarouf@uni-koeln.de