- Email: [email protected]
Intracranial Rosai–Dorfman disease
Case Reports / Journal of Clinical Neuroscience 32 (2016) 133–136 [4] Sinha GP. Tuberculoma of the ulnar nerve. J Bone Joint Surg Am 1975;57:131. [5] Nucci F, Mastronardi L, Artico M, et al. Tuberculoma of the ulnar nerve: case report. Neurosurgery 1988;22:906–7. [6] Hasa, Prakashvn SA. Tuberculoma of the ulnar nerve. A new Clinical entity. J Int Coll Surg 1964;42:30–4. [7] Ramesh Chandra VV, Prasad BC, et al. Ulnar nerve tuberculoma. J Neurosurg Pediatr 2013;11:100–2.
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[8] Chatterjee D, Lath K, Sharma RK, et al. Ulnar nerve tuberculoma masquerading as a neurofibroma. Neurol India 2015;63:268–70. [9] World Health Organization. Global tuberculosis control. World Health Organization report. Geneva: World Health Organisation; 2011. p. 1–258. [10] Hernandez Pando R. Modelling of cerebral tuberculosis: hope for continuous research in solving the enigma of the Bottom Billion’s Disease. Malays J Med Sci 2011;18:12–5.
http://dx.doi.org/10.1016/j.jocn.2015.12.047
Intracranial Rosai–Dorfman disease Bo Yuan Huang a,1, Miao Zong a,1, Wen Jing Zong b, Yan Hui Sun c,⇑, Hua Zhang c,⇑, Hong Bo Zhang d a
Department of Neurosurgery, Beijing Electric Power Hospital, Capital Medical University, Beijing, China College of Traditional Chinese Medicine, Capital Medical University, Beijing, China Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China d Integrated Traditional and Western Medicine Hospital of Hubei Province, Department of Neurosurgery, Wu Han, China b c
a r t i c l e
i n f o
Article history: Received 14 November 2015 Accepted 29 December 2015
Keywords: Histioproliferative disease Intracranial Rosai–Dorfman disease
a b s t r a c t Rosai–Dorfman disease (RDD) is a rare histioproliferative disorder that only occasionally involves the central nervous system. We present the diagnosis and treatment of five patients with intracranial RDD. The patients were preoperatively misdiagnosed as meningioma or eosinophilic granuloma. All five patients were treated by total or subtotal surgical resection and none of them experienced recurrence. Histopathological examination showed a characteristic emperipolesis, the lymphocytes were engulfed in the S-100 protein and CD68 positive histiocytes, with negative expression of CD1a. Preoperative diagnosis of intracranial RDD is still challenging because the lesion is usually a dural-based lesion that mimics a meningioma. Surgical resection is an effective treatment and radiotherapy, steroid and chemotherapy has not demonstrated reliable therapeutic efficiency. Ó 2016 Elsevier Ltd. All rights reserved.
1. Introduction Sinus histiocytosis with massive lymphadenopathy, also known as Rosai–Dorfman disease (RDD), was first reported by Rosai and Dorfman in 1969 [1]. This histioproliferative disorder is a rare idiopathic disease that is generally characterized by bilateral massive but painless cervical lymphadenopathy. Other concomitant syndromes, such as fever, neutrophilia, elevated sedimentation rate, and polyclonal hypergammaglobulinemia may also be found in the RDD patient. Moreover, the extranodal involvement including the skin, orbit, upper respiratory tract, or bones can also be seen in 43% of patients [2]. Central nervous system (CNS) involvement is extremely rare and is usually associated with the endocranium or skull base. Moreover, it was usually misdiagnosed as meningioma for the neuroimaging displaying as a dura-based lesion. We presented a report of five patients with isolated intracranial RDD. 2. Clinical summary We retrospectively analyzed the medical records of five patients with isolated intracranial RDD who were treated at the Department of Neurosurgery of Beijing Tiantan hospital from January 2009 to February 2015. Clinically, all five patients underwent surgery with total or subtotal resection of the masses. None of the patients underwent radio- or chemotherapy postoperatively. Follow-up after the surgery were performed ranging from 6 months to 36 months, and no recurrences were observed during the follow-up. Clinical data of the five patients are summarized in Table 1. One woman and four
men ranging from 18 to 68 years (mean 38.8 years) were involved in this analysis. Three patients (Patients 1, 3 and 4) (Fig. 1, 3, 4) had a dura-based lesion associated with the superior sagittal sinus located in the cerebral convexity. Interestingly, all three patients came to our hospital with a history of a generalized epileptic seizure. One patient (Fig. 2) had a lesion located in middle and posterior cranial fossa with progressive cephalgia and face numbness. Another patient came to our hospital for painful subcutaneous mass in the right frontal skull (Fig. 5). None of the patients were found to have massive cervical lymphadenopathy nor other extranodal involvement. On examination, the patients demonstrated no unusual results of routine laboratory assays. 2.1. Neuroimaging results Brain MRI showed that all the lesions were extraparenchymal and associated with dura or skull. On T1-weighted MRI the lesions were slightly hyperintense or isointense with distinct borders. T2weighted scanning revealed that the lesions were isointense. There was slight edema surrounding the three lesions which were located in the cerebral convexity (patients 1, 3 and 4) (Fig. 1, 3, 4). All the lesions demonstrated homogeneous and obvious enhancement followed contrast agent administration. Preoperative diagnosis of four patients (patients 1–4) based on the neuroimaging was meningioma and the other patient (patient 5) in whom a skull-based lesion was found, was preoperatively diagnosed as eosinophilic granuloma. 2.2. Pathological findings
⇑ Corresponding authors. Tel.: +86 13436561446. 1
E-mail address: [email protected] (Y.H. Sun). These authors contributed equally to this manuscript.
Pathological examinations of the lesion involving the brain in patient 1, showed large pale histiocytes with vacuolated
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Case Reports / Journal of Clinical Neuroscience 32 (2016) 133–136
Table 1 Clinical characteristics of patients with intracranial Rosai–Dorfman disease Case Case Case Case Case Case
1 2 3 4 5
Gender
Age
Location
Clinical presentation
Preoperative diagnosis
Treatment
Follow-up
Male Male Female Male Male
18 18 50 40 68
Bilateral parietal and occipital lobes Middle and posterior cranial fossa Right parietal lobe Right parietal lobe Right frontal skull
Epileptic seizure Face numbness and leg convulsions Epileptic seizure Epileptic seizure Painful subcutaneous mass
Meningioma Meningioma Meningioma Meningioma Eosinophilic granuloma
Resection Resection Resection Resection Resection
24 months 36 months 12 months 6 months 12 months
Fig. 1. An 18-year-old man (Patient 1). Left: T1-weighted MRI with enhancement showed that the lesion was located in the bilateral parietal and occipital lobes associated with the superior sagittal sinus. There was a mild edema surrounding the mass. The lesion was homogeneously enhanced followed contrast agent administration. Right: T1-weighted MRI with enhancement showed that the lesion was partially removed by surgery.
Fig. 2. An 18-year-old man (Patient 2). Left: T1-weighted MRI with enhancement showed that the lesion was a dumbbell-shaped-mass located in the middle and posterior cranial fossa. There was a slight edema surrounding the mass. The lesion was homogeneously enhanced followed contrast agent administration. Right: T1weighted MRI with enhancement showed that the lesion was partially removed by surgery.
Fig. 4. A 40-year-old man (Patient 4). Left: T1-weighted MRI with enhancement showed that the lesion was located in right parietal lobe associated with the superior sagittal sinus. There was a mild edema surrounding the mass. The lesion was homogeneously enhanced followed contrast agent administration. Right: Postoperative CT scan confirmed that the lesion was totally removed by surgery.
Fig. 5. A 68-year-old man (Patient 5). Left: T1-weighted MRI with enhancement showed that the lesion was a subcutaneous mass, located in the right frontal skull. The lesion invaded through the skull to the dura. The lesion was homogeneously enhanced followed contrast agent administration. Right: Postoperative CT scan confirmed that the lesion was totally removed by surgery.
eosinophilic cytoplasm mixed with scattered plasma cells and mature lymphocytes (Fig. 6A). Emperipolesis, consisting of histiocytes engulfed well-preserved lymphocytes was found in permanent paraffi-embedded tissue (Fig. 6B). The lymphoplasmacytic cells were well-differentiated without nuclear atypia. The histopathology of the other four patients was the same as shown for patient 1. Immunohistochemical staining results of all five patients demonstrated a common immunohistochemistry of strong positivity for CD68 or S-100 protein with negative expression of CD1a. All five patients were pathologically diagnosed as RDD.
Fig. 3. A 50-year-old woman (Patient 3). Left: T1-weighted MRI with enhancement showed that the lesion was located in the right parietal lobe and associated with the superior sagittal sinus. The lesion was homogeneously enhanced followed contrast agent administration. Right: T1-weighted MRI with enhancement showed that the lesion was total removed by surgery.
3. Discussion Rosai–Dorfman disease is a histioproliferative disorder that mainly involved cervical lymphadenopathy. Primary intracranial
Case Reports / Journal of Clinical Neuroscience 32 (2016) 133–136
Fig. 6. Histopathology of Patients 1 and 4 are displayed. (A) Mixed infiltrate composed of large pale histiocytic cells, lymphocytes, and plasma cells can be seen in histology of Patient 1 (Hematoxylin and eosin [H&E] 200). (B) A characteristic emperipolesis, where small lymphocytes or plasma cells are engulfed in histiocyte cytoplasm, can be seen in histology of Patient 4 (H&E 400).
RDD without other body involvement was observed in no more than 5% of all patients with extranodal RDD [3]. Retrospective analysis showed that from 1969, when the disease was first described, to 2014 there have been only 167 incidents of RDD with isolated intracranial involvement [4]. RDD has been reported in all age groups but mainly involves adolescents and young adults which usually present with massive cervical lymphadenopathy [5]. The etiology of RDD remains controversial. Some studies supported that immune-system dysfunctions and autoimmune process caused by viral infection such as Epsteine-Barr virus and human herpes virus type 6 might be attributed to this disease [2,5]. Usually, the intracranial RDD is an extraaxial dura-based lesion with homogenous contrast enhancement that mimics a dura-based meningioma. However, heterogeneous intracranial involvement has also been reported [6–9]. Common symptoms included cephalgia, seizure, weakness of limbs, and cranial nerve deficiency, based on the locations of the lesions. Isolated intracranial RDD could usually invade convexity, parasagittal region, suprasellar region, cavernous sinus, and petroclival region [9–14]. However, extremely rare patients with intraventricular and intraparenchymal lesions have also been reported [15–18]. In our report, the lesions of five patients were all extraaxial which involved convexity (patients 1, 3, 4) (Fig. 1, 3, 4), middle and posterior cranial fossa (patient 2) (Fig. 2), and skull (patient 5) (Fig. 5). As noted above, the intracranial RDD is an uncommon entity and diagnostic neuroimaging usually presents as a dura-based lesion. As a result, the disease, without biopsy, is commonly misdiagnosed as meningioma. T1-weighted MRI showed that the intracranial RDD was usually an isointense or hyperintense mass with distinct borders, and had avid homogenous contrast enhancement. On T2-weighted scanning, the lesions usually presented as isointense [19]. Moreover, an exceptional case was also reported where the lesion could be isointense on T1-weighted but hyperintense on T2-weighted MRI with minimal contrast enhancement [8]. In our report, lesions were slightly hyperintense or isointense on T1-weighted and isointense on T2-weighted MRI. Four patients were preoperatively misdiagnosed as meningioma (patients 1–4), and the other patient (patient 5) was misdiagnosed as eosinophilic granuloma. The differential diagnosis of RDD includes meningioma, histiocytosis X, lymphoproliferative disorders, plasma cell granuloma, and infectious diseases. Both RDD and meningioma is a durabased lesion with homogenous contrast enhancement, and even on microscope levels the two entities can be hardly distinguished. During the surgery of patient 4 who was preoperatively diagnosed as meningioma, we found that the lesion had a distinctly thickened and tough tunic. This was a little different from a meningioma and
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made us suspect the imaging diagnosis. The pathological results substantiated our suspicion. The typical pathological displays of RDD are sheets of multinucleated histiocytes with emperipolesis, a lymphocytic engulfment by the proliferative histiocytes [20]. The histiocytes in RDD display characteristic of antigen presenting cells (positive for S-100 protein) and phagocytic histiocytes (positive for CD 68, ɑ1antitrypsin, lysozymes, MAC – 378 but negative for CD1a). The emperipolesis, however, could be seen in about 70% of RDD patients [21]. Meningioma, which is featured with positive epithelial membrane antigen, can be readily differentiated by the immunohistochemical staining. Plasma cell granuloma, characterizing in a mixed inflammatory infiltrate with polyclonal plasma cells, is usually confused with RDD as it can present as a discrete, dura-based inflammatory mass. However, emperipolesis (Fig. 6B) and expression of S-100 protein is negative in the pathology of plasma cell granuloma. Lymphoproliferative disorders may also be misdiagnosed as RDD because of the histiocytes presenting phagocytic phenomenon and positive S-100 protein. However, the erythryophagocytosis can differentiate the lesion from RDD. Langerhans cell histiocytosis (LCH) may also present as a durabased mass. Furthermore, the S-100 protein-positive histiocytes can also be found in this lesion. However, the LCH can usually be found in pathological examination of characteristic longitudinal nuclear grooves, conspicuous eosinophils, pathognomonic Birbeck granules with the absence of lymphophagocytosis in histiocytes. And the expression of CD1a in LCH is positive. As in our patients, immunological examinations showed the histiocytes were S-100 protein- and CD68-positive with negative expression of CD1a. It is worth noting that the histiocytes in RDD are featured with S100 protein positive expression but negative for CD1a. Accordingly, immunological staining of CD1a is also significant for the diagnosis of RDD. Our immunohistochemical criteria for diagnosis are also helpful for differential diagnosis of RDD. As noted above, both RDD and LCH can present as positive expression of S-100 protein but CD1a, which is reliably expressed on histiocytes of LCH, is negative in RDD [3]. Generally, the treatment for systemic RDD is advised only in patients with symptomatic lesions or masses that have damaged the function of vital organs since this disease is considered to be a benign, non-neoplastic lymphoproliferative disorder [4]. Furthermore, complete spontaneous resolution is reported in about 20% of patients with systemic RDD [22], however, in intracranial RDD, no complete spontaneous resolution has been reported. Accordingly, with regard to the intracranial RDD, surgery is still the first choice of treatment for both diagnostic purposes and rapid improves neurologic symptoms [23,24]. Complete resection should be attempted and when lesions adhere to surrounding critical structures, subtotal resection should also be performed for pathological diagnosis and symptomatic remission. After surgery, most patients can achieve stable disease and thus a wait-and-watch treatment is advised [25]. Moreover, radiotherapy, chemotherapy and corticosteroid therapy had been applied in patients who could not be relieved from neurological symptoms after surgery [26–30]. Both fractionated radiotherapy and stereotactic radiotherapy has been used in intracranial RDD followed surgery, however, results varied and some patients even did not show any improvement [25,31,32]. In other words, although steroid treatment has shown some therapeutic benefit in the treatment of systemic RDD patients with rapid growing lymph node and/or other constitutional symptoms and some intracranial RDD patients [25,28,33], sufficient randomized trials are still needed to standardize its usage. Chemotherapy has also been used in systemic RDD and intracranial RDD. Pulsoni et al. retrospectively analyzed therapeutic outcomes of 12 systemic RDD patients who were treated with anthracyclines, vinca alkaloids, and alkylating agents. Only two
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patients achieved complete relief. Diones Rivera et al. adapted CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisone) regimen to treat two recurrent intracranial RDD patients who underwent recurrence within 2 years of the first subtotal resection surgery. After the second treatment of chemotherapy, they have been free from recurrence for 7 years [30]. Although adjuvant chemotherapy has been recommended after subtotal resection [30,34], there still needs further clinical trials to establish standardized rules. In all our patients, lesions were successfully removed by surgery and no recurrences were observed in the follow-up with a mean of 18 months. 4. Conclusion Isolated intracranial RDD is an exceptional rare disease and the diagnosis for the lesion is still challenging. The histological displays and immunophenotypical characteristics of the disease are still the only reliable basis for diagnosis. Surgical resection was demonstrated an effective treatment and other forms of treatment such as radiotherapy, steroid-therapy and chemotherapy still need studies to clarify the usage and effectiveness. Conflicts of Interest/Disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. References [1] Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy: a newly recognized benign clinicopathological entity. Arch Pathol 1969;87:63–70. [2] Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease): review of the entity. Semin Diagn Pathol 1990;7:19–73. [3] Andriko JA, Morrison A, Colegial CH. Rosai–Dorfman disease isolated to the central nervous system: a report of 11 cases. Mod Pathol 2001;14:172–8. [4] Sandoval-Sus JD, Sandoval-Leon AC, Chapman JR, et al. Rosai–Dorfman disease of the central nervous system: report of 6 cases and review of the literature. Medicine (Baltimore) 2014;93:165–75. [5] Luppi M, Barozzi P, Garber R, et al. Expression of human herpesvirus-6 antigens in benign and malignant Lymphoproliferative diseases. Am J Pathol 1998;153:815–23. [6] Kim M, Provias J, Bernstein M. Rosai–Dorfman disease mimicking multiple meningioma: case report. Neurosurgery 1995;36:1185–7. [7] Simos M, Dimitrios P, Philip T. A new clinical entity mimicking meningioma diagnosed pathologically as Rosai–Dorfman disease. Skull Base Surg 1998;8:87–92. [8] Di Rocco F, Garnett MR, Puget S, et al. Cerebral localization of Rosai–Dorfman disease in a child. Case report. J Neurosurg 2007;107:147–51. [9] Johnston JM, Limbrick DD, Ray WZ, et al. Isolated cerebellar Rosai–Dorfman granuloma mimicking Lhermitte-Duclos disease. Case report. J Neurosurg Pediatr 2009;4:118–20. [10] Toh CH, Chen YL, Wong HF, et al. Rosai–Dorfman disease with dural sinus invasion. Report of two cases. J Neurosurg 2005;102:550–4. http://dx.doi.org/10.1016/j.jocn.2015.12.046
[11] Yetiser S, Cekin E, Tosun F, et al. Rosai–Dorfman disease associated with neurosensorial hearing loss in two siblings. Int J Pediatr Otorhinolaryngol 2004;68:1095–100. [12] Castellano-Sanchez AA, Brat DJ. May 2003: 57-yearold-woman with acute loss of strength in her right upper extremity and slurred speech. Brain Pathol 2003;13:641–2. 645. [13] Ture U, Seker A, Boskurt SU, et al. Giant intracranial Rosai–Dorfman disease. J Clin Neurosci 2004;11:563–6. [14] Gupta DK, Suri A, Mahapatra AK, et al. Rosai–Dorfman disease in a child mimicking bilateral giant petroclival meningiomas: a case report and review of literature. Childs Nerv Syst 2006;22:1194–200. [15] Juric´ G, Jakic´-Razumovic´ J, Rotim K, et al. Extranodal sinus histiocytosis (Rosai– Dorfman disease) of the brain parenchyma. Acta Neurochir (Wien) 2003;145:145–9 [discussion 149]. [16] Gaetani P, Tancioni F, Di Rocco M, et al. Isolated cerebellar involvement in Rosai–Dorfman disease: case report. Neurosurgery 2000;46:479–81. [17] Natarajan S, Post KD, Strauchen J, et al. Primary intracerebral Rosai–Dorfman disease: a case report. J Neurooncol 2000;47:73–7. [18] Morandi X, Godey B, Riffaud L, et al. Isolated Rosai–Dorfman disease of the fourth ventricle. Case illustration. J Neurosurg 2000;92:890. [19] Wu M, Anderson AE, Kahn LB. A report of intracranial Rosai–Dorfman disease with literature review. Ann Diagn Pathol 2001;5:96–102. [20] Tubbs RS, Kelly DR, Mroczek-Musulman EC, et al. Spinal cord compression as a result of Rosai–Dorfman disease of the upper cervical spine in a child. Childs Nerv Syst 2005;21:951–4. [21] Rastogi V, Sharma R, Misra SR, et al. Emperipolesis – a review. J Clin Diagn Res 2014;8:ZM01–2. [22] Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease): review of the entity. Semin Diagn Pathol 1990;7:19–73. [23] Kayali H, Onguru O, Erdogan E, et al. Isolated intracranial Rosai–Dorfman disease mimicking meningioma. Clin Neuropathol 2004;23:204–8. [24] Griffiths SJ, Tang W, Parameswaran R, et al. Isolated intracranial Rosai– Dorfman disease mimicking meningioma in a child. Br J Neurosurg 2004;18:293–7. [25] Cooper SL, Jenrette JM. Rosai–Dorfman disease: management of CNS and systemic involvement. Clin Adv Hematol Oncol 2012;10:199–202. [26] Franco-Paredes C, Martin K. Extranodal Rosai–Dorfman disease involving the meninges. South Med J 2002;95:1101–2. [27] Sato A, Sakurada K, Sonoda Y, et al. Rosai–Dorfman disease presenting with multiple intracranial and intraspinal masses: a case report. No Shinkei Geka 2003;31:1199–204. [28] Hadjipanayis CG, Bejjani G, Wiley C, et al. Intracranial Rosai–Dorfman disease treated with microsurgical resection and stereotactic radiosurgery. Case report. J Neurosurg 2003;98:165–8. [29] Hinduja A, Aguilar LG, Steineke T, et al. Rosai–Dorfman disease manifesting as intracranial and intraorbital lesion. J Neurooncol 2009;92:117–20. [30] Rivera D, Pérez-Castillo M, Fernández B, et al. Long-term follow-up in two cases of intracranial Rosai–Dorfman Disease complicated by incomplete resection and recurrence. Surg Neurol Int 2014;5:30. [31] Hadjipanayis CG, Bejjani G, Wiley C, et al. Intracranial Rosai–Dorfman disease treated with microsurgical resection and stereotactic radiosurgery. Case report. J Neurosurg 2003;98:165–8. [32] Kidd DP, Revesz T, Miller NR. Rosai–Dorfman disease presenting with widespread intracranial and spinal cord involvement. Neurology 2006;67:1551–5. [33] Shaver EG, Rebsamen SL, Yachnis AT, et al. Isolated extranodal intracranial sinus histiocytosis in a 5-year-old boy. Case report. J Neurosurg 1993;79:769–73. [34] Le Guenno G, Galicier L, Uro-Coste E, et al. Successful treatment with azathioprine of relapsing Rosai–Dorfman disease of the central nervous system. J Neurosurg 2012;117:486–9.
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[8] Chatterjee D, Lath K, Sharma RK, et al. Ulnar nerve tuberculoma masquerading as a neurofibroma. Neurol India 2015;63:268–70. [9] World Health Organization. Global tuberculosis control. World Health Organization report. Geneva: World Health Organisation; 2011. p. 1–258. [10] Hernandez Pando R. Modelling of cerebral tuberculosis: hope for continuous research in solving the enigma of the Bottom Billion’s Disease. Malays J Med Sci 2011;18:12–5.
http://dx.doi.org/10.1016/j.jocn.2015.12.047
Intracranial Rosai–Dorfman disease Bo Yuan Huang a,1, Miao Zong a,1, Wen Jing Zong b, Yan Hui Sun c,⇑, Hua Zhang c,⇑, Hong Bo Zhang d a
Department of Neurosurgery, Beijing Electric Power Hospital, Capital Medical University, Beijing, China College of Traditional Chinese Medicine, Capital Medical University, Beijing, China Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China d Integrated Traditional and Western Medicine Hospital of Hubei Province, Department of Neurosurgery, Wu Han, China b c
a r t i c l e
i n f o
Article history: Received 14 November 2015 Accepted 29 December 2015
Keywords: Histioproliferative disease Intracranial Rosai–Dorfman disease
a b s t r a c t Rosai–Dorfman disease (RDD) is a rare histioproliferative disorder that only occasionally involves the central nervous system. We present the diagnosis and treatment of five patients with intracranial RDD. The patients were preoperatively misdiagnosed as meningioma or eosinophilic granuloma. All five patients were treated by total or subtotal surgical resection and none of them experienced recurrence. Histopathological examination showed a characteristic emperipolesis, the lymphocytes were engulfed in the S-100 protein and CD68 positive histiocytes, with negative expression of CD1a. Preoperative diagnosis of intracranial RDD is still challenging because the lesion is usually a dural-based lesion that mimics a meningioma. Surgical resection is an effective treatment and radiotherapy, steroid and chemotherapy has not demonstrated reliable therapeutic efficiency. Ó 2016 Elsevier Ltd. All rights reserved.
1. Introduction Sinus histiocytosis with massive lymphadenopathy, also known as Rosai–Dorfman disease (RDD), was first reported by Rosai and Dorfman in 1969 [1]. This histioproliferative disorder is a rare idiopathic disease that is generally characterized by bilateral massive but painless cervical lymphadenopathy. Other concomitant syndromes, such as fever, neutrophilia, elevated sedimentation rate, and polyclonal hypergammaglobulinemia may also be found in the RDD patient. Moreover, the extranodal involvement including the skin, orbit, upper respiratory tract, or bones can also be seen in 43% of patients [2]. Central nervous system (CNS) involvement is extremely rare and is usually associated with the endocranium or skull base. Moreover, it was usually misdiagnosed as meningioma for the neuroimaging displaying as a dura-based lesion. We presented a report of five patients with isolated intracranial RDD. 2. Clinical summary We retrospectively analyzed the medical records of five patients with isolated intracranial RDD who were treated at the Department of Neurosurgery of Beijing Tiantan hospital from January 2009 to February 2015. Clinically, all five patients underwent surgery with total or subtotal resection of the masses. None of the patients underwent radio- or chemotherapy postoperatively. Follow-up after the surgery were performed ranging from 6 months to 36 months, and no recurrences were observed during the follow-up. Clinical data of the five patients are summarized in Table 1. One woman and four
men ranging from 18 to 68 years (mean 38.8 years) were involved in this analysis. Three patients (Patients 1, 3 and 4) (Fig. 1, 3, 4) had a dura-based lesion associated with the superior sagittal sinus located in the cerebral convexity. Interestingly, all three patients came to our hospital with a history of a generalized epileptic seizure. One patient (Fig. 2) had a lesion located in middle and posterior cranial fossa with progressive cephalgia and face numbness. Another patient came to our hospital for painful subcutaneous mass in the right frontal skull (Fig. 5). None of the patients were found to have massive cervical lymphadenopathy nor other extranodal involvement. On examination, the patients demonstrated no unusual results of routine laboratory assays. 2.1. Neuroimaging results Brain MRI showed that all the lesions were extraparenchymal and associated with dura or skull. On T1-weighted MRI the lesions were slightly hyperintense or isointense with distinct borders. T2weighted scanning revealed that the lesions were isointense. There was slight edema surrounding the three lesions which were located in the cerebral convexity (patients 1, 3 and 4) (Fig. 1, 3, 4). All the lesions demonstrated homogeneous and obvious enhancement followed contrast agent administration. Preoperative diagnosis of four patients (patients 1–4) based on the neuroimaging was meningioma and the other patient (patient 5) in whom a skull-based lesion was found, was preoperatively diagnosed as eosinophilic granuloma. 2.2. Pathological findings
⇑ Corresponding authors. Tel.: +86 13436561446. 1
E-mail address: [email protected] (Y.H. Sun). These authors contributed equally to this manuscript.
Pathological examinations of the lesion involving the brain in patient 1, showed large pale histiocytes with vacuolated
134
Case Reports / Journal of Clinical Neuroscience 32 (2016) 133–136
Table 1 Clinical characteristics of patients with intracranial Rosai–Dorfman disease Case Case Case Case Case Case
1 2 3 4 5
Gender
Age
Location
Clinical presentation
Preoperative diagnosis
Treatment
Follow-up
Male Male Female Male Male
18 18 50 40 68
Bilateral parietal and occipital lobes Middle and posterior cranial fossa Right parietal lobe Right parietal lobe Right frontal skull
Epileptic seizure Face numbness and leg convulsions Epileptic seizure Epileptic seizure Painful subcutaneous mass
Meningioma Meningioma Meningioma Meningioma Eosinophilic granuloma
Resection Resection Resection Resection Resection
24 months 36 months 12 months 6 months 12 months
Fig. 1. An 18-year-old man (Patient 1). Left: T1-weighted MRI with enhancement showed that the lesion was located in the bilateral parietal and occipital lobes associated with the superior sagittal sinus. There was a mild edema surrounding the mass. The lesion was homogeneously enhanced followed contrast agent administration. Right: T1-weighted MRI with enhancement showed that the lesion was partially removed by surgery.
Fig. 2. An 18-year-old man (Patient 2). Left: T1-weighted MRI with enhancement showed that the lesion was a dumbbell-shaped-mass located in the middle and posterior cranial fossa. There was a slight edema surrounding the mass. The lesion was homogeneously enhanced followed contrast agent administration. Right: T1weighted MRI with enhancement showed that the lesion was partially removed by surgery.
Fig. 4. A 40-year-old man (Patient 4). Left: T1-weighted MRI with enhancement showed that the lesion was located in right parietal lobe associated with the superior sagittal sinus. There was a mild edema surrounding the mass. The lesion was homogeneously enhanced followed contrast agent administration. Right: Postoperative CT scan confirmed that the lesion was totally removed by surgery.
Fig. 5. A 68-year-old man (Patient 5). Left: T1-weighted MRI with enhancement showed that the lesion was a subcutaneous mass, located in the right frontal skull. The lesion invaded through the skull to the dura. The lesion was homogeneously enhanced followed contrast agent administration. Right: Postoperative CT scan confirmed that the lesion was totally removed by surgery.
eosinophilic cytoplasm mixed with scattered plasma cells and mature lymphocytes (Fig. 6A). Emperipolesis, consisting of histiocytes engulfed well-preserved lymphocytes was found in permanent paraffi-embedded tissue (Fig. 6B). The lymphoplasmacytic cells were well-differentiated without nuclear atypia. The histopathology of the other four patients was the same as shown for patient 1. Immunohistochemical staining results of all five patients demonstrated a common immunohistochemistry of strong positivity for CD68 or S-100 protein with negative expression of CD1a. All five patients were pathologically diagnosed as RDD.
Fig. 3. A 50-year-old woman (Patient 3). Left: T1-weighted MRI with enhancement showed that the lesion was located in the right parietal lobe and associated with the superior sagittal sinus. The lesion was homogeneously enhanced followed contrast agent administration. Right: T1-weighted MRI with enhancement showed that the lesion was total removed by surgery.
3. Discussion Rosai–Dorfman disease is a histioproliferative disorder that mainly involved cervical lymphadenopathy. Primary intracranial
Case Reports / Journal of Clinical Neuroscience 32 (2016) 133–136
Fig. 6. Histopathology of Patients 1 and 4 are displayed. (A) Mixed infiltrate composed of large pale histiocytic cells, lymphocytes, and plasma cells can be seen in histology of Patient 1 (Hematoxylin and eosin [H&E] 200). (B) A characteristic emperipolesis, where small lymphocytes or plasma cells are engulfed in histiocyte cytoplasm, can be seen in histology of Patient 4 (H&E 400).
RDD without other body involvement was observed in no more than 5% of all patients with extranodal RDD [3]. Retrospective analysis showed that from 1969, when the disease was first described, to 2014 there have been only 167 incidents of RDD with isolated intracranial involvement [4]. RDD has been reported in all age groups but mainly involves adolescents and young adults which usually present with massive cervical lymphadenopathy [5]. The etiology of RDD remains controversial. Some studies supported that immune-system dysfunctions and autoimmune process caused by viral infection such as Epsteine-Barr virus and human herpes virus type 6 might be attributed to this disease [2,5]. Usually, the intracranial RDD is an extraaxial dura-based lesion with homogenous contrast enhancement that mimics a dura-based meningioma. However, heterogeneous intracranial involvement has also been reported [6–9]. Common symptoms included cephalgia, seizure, weakness of limbs, and cranial nerve deficiency, based on the locations of the lesions. Isolated intracranial RDD could usually invade convexity, parasagittal region, suprasellar region, cavernous sinus, and petroclival region [9–14]. However, extremely rare patients with intraventricular and intraparenchymal lesions have also been reported [15–18]. In our report, the lesions of five patients were all extraaxial which involved convexity (patients 1, 3, 4) (Fig. 1, 3, 4), middle and posterior cranial fossa (patient 2) (Fig. 2), and skull (patient 5) (Fig. 5). As noted above, the intracranial RDD is an uncommon entity and diagnostic neuroimaging usually presents as a dura-based lesion. As a result, the disease, without biopsy, is commonly misdiagnosed as meningioma. T1-weighted MRI showed that the intracranial RDD was usually an isointense or hyperintense mass with distinct borders, and had avid homogenous contrast enhancement. On T2-weighted scanning, the lesions usually presented as isointense [19]. Moreover, an exceptional case was also reported where the lesion could be isointense on T1-weighted but hyperintense on T2-weighted MRI with minimal contrast enhancement [8]. In our report, lesions were slightly hyperintense or isointense on T1-weighted and isointense on T2-weighted MRI. Four patients were preoperatively misdiagnosed as meningioma (patients 1–4), and the other patient (patient 5) was misdiagnosed as eosinophilic granuloma. The differential diagnosis of RDD includes meningioma, histiocytosis X, lymphoproliferative disorders, plasma cell granuloma, and infectious diseases. Both RDD and meningioma is a durabased lesion with homogenous contrast enhancement, and even on microscope levels the two entities can be hardly distinguished. During the surgery of patient 4 who was preoperatively diagnosed as meningioma, we found that the lesion had a distinctly thickened and tough tunic. This was a little different from a meningioma and
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made us suspect the imaging diagnosis. The pathological results substantiated our suspicion. The typical pathological displays of RDD are sheets of multinucleated histiocytes with emperipolesis, a lymphocytic engulfment by the proliferative histiocytes [20]. The histiocytes in RDD display characteristic of antigen presenting cells (positive for S-100 protein) and phagocytic histiocytes (positive for CD 68, ɑ1antitrypsin, lysozymes, MAC – 378 but negative for CD1a). The emperipolesis, however, could be seen in about 70% of RDD patients [21]. Meningioma, which is featured with positive epithelial membrane antigen, can be readily differentiated by the immunohistochemical staining. Plasma cell granuloma, characterizing in a mixed inflammatory infiltrate with polyclonal plasma cells, is usually confused with RDD as it can present as a discrete, dura-based inflammatory mass. However, emperipolesis (Fig. 6B) and expression of S-100 protein is negative in the pathology of plasma cell granuloma. Lymphoproliferative disorders may also be misdiagnosed as RDD because of the histiocytes presenting phagocytic phenomenon and positive S-100 protein. However, the erythryophagocytosis can differentiate the lesion from RDD. Langerhans cell histiocytosis (LCH) may also present as a durabased mass. Furthermore, the S-100 protein-positive histiocytes can also be found in this lesion. However, the LCH can usually be found in pathological examination of characteristic longitudinal nuclear grooves, conspicuous eosinophils, pathognomonic Birbeck granules with the absence of lymphophagocytosis in histiocytes. And the expression of CD1a in LCH is positive. As in our patients, immunological examinations showed the histiocytes were S-100 protein- and CD68-positive with negative expression of CD1a. It is worth noting that the histiocytes in RDD are featured with S100 protein positive expression but negative for CD1a. Accordingly, immunological staining of CD1a is also significant for the diagnosis of RDD. Our immunohistochemical criteria for diagnosis are also helpful for differential diagnosis of RDD. As noted above, both RDD and LCH can present as positive expression of S-100 protein but CD1a, which is reliably expressed on histiocytes of LCH, is negative in RDD [3]. Generally, the treatment for systemic RDD is advised only in patients with symptomatic lesions or masses that have damaged the function of vital organs since this disease is considered to be a benign, non-neoplastic lymphoproliferative disorder [4]. Furthermore, complete spontaneous resolution is reported in about 20% of patients with systemic RDD [22], however, in intracranial RDD, no complete spontaneous resolution has been reported. Accordingly, with regard to the intracranial RDD, surgery is still the first choice of treatment for both diagnostic purposes and rapid improves neurologic symptoms [23,24]. Complete resection should be attempted and when lesions adhere to surrounding critical structures, subtotal resection should also be performed for pathological diagnosis and symptomatic remission. After surgery, most patients can achieve stable disease and thus a wait-and-watch treatment is advised [25]. Moreover, radiotherapy, chemotherapy and corticosteroid therapy had been applied in patients who could not be relieved from neurological symptoms after surgery [26–30]. Both fractionated radiotherapy and stereotactic radiotherapy has been used in intracranial RDD followed surgery, however, results varied and some patients even did not show any improvement [25,31,32]. In other words, although steroid treatment has shown some therapeutic benefit in the treatment of systemic RDD patients with rapid growing lymph node and/or other constitutional symptoms and some intracranial RDD patients [25,28,33], sufficient randomized trials are still needed to standardize its usage. Chemotherapy has also been used in systemic RDD and intracranial RDD. Pulsoni et al. retrospectively analyzed therapeutic outcomes of 12 systemic RDD patients who were treated with anthracyclines, vinca alkaloids, and alkylating agents. Only two
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patients achieved complete relief. Diones Rivera et al. adapted CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisone) regimen to treat two recurrent intracranial RDD patients who underwent recurrence within 2 years of the first subtotal resection surgery. After the second treatment of chemotherapy, they have been free from recurrence for 7 years [30]. Although adjuvant chemotherapy has been recommended after subtotal resection [30,34], there still needs further clinical trials to establish standardized rules. In all our patients, lesions were successfully removed by surgery and no recurrences were observed in the follow-up with a mean of 18 months. 4. Conclusion Isolated intracranial RDD is an exceptional rare disease and the diagnosis for the lesion is still challenging. The histological displays and immunophenotypical characteristics of the disease are still the only reliable basis for diagnosis. Surgical resection was demonstrated an effective treatment and other forms of treatment such as radiotherapy, steroid-therapy and chemotherapy still need studies to clarify the usage and effectiveness. Conflicts of Interest/Disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. References [1] Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy: a newly recognized benign clinicopathological entity. Arch Pathol 1969;87:63–70. [2] Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease): review of the entity. Semin Diagn Pathol 1990;7:19–73. [3] Andriko JA, Morrison A, Colegial CH. Rosai–Dorfman disease isolated to the central nervous system: a report of 11 cases. Mod Pathol 2001;14:172–8. [4] Sandoval-Sus JD, Sandoval-Leon AC, Chapman JR, et al. Rosai–Dorfman disease of the central nervous system: report of 6 cases and review of the literature. Medicine (Baltimore) 2014;93:165–75. [5] Luppi M, Barozzi P, Garber R, et al. Expression of human herpesvirus-6 antigens in benign and malignant Lymphoproliferative diseases. Am J Pathol 1998;153:815–23. [6] Kim M, Provias J, Bernstein M. Rosai–Dorfman disease mimicking multiple meningioma: case report. Neurosurgery 1995;36:1185–7. [7] Simos M, Dimitrios P, Philip T. A new clinical entity mimicking meningioma diagnosed pathologically as Rosai–Dorfman disease. Skull Base Surg 1998;8:87–92. [8] Di Rocco F, Garnett MR, Puget S, et al. Cerebral localization of Rosai–Dorfman disease in a child. Case report. J Neurosurg 2007;107:147–51. [9] Johnston JM, Limbrick DD, Ray WZ, et al. Isolated cerebellar Rosai–Dorfman granuloma mimicking Lhermitte-Duclos disease. Case report. J Neurosurg Pediatr 2009;4:118–20. [10] Toh CH, Chen YL, Wong HF, et al. Rosai–Dorfman disease with dural sinus invasion. Report of two cases. J Neurosurg 2005;102:550–4. http://dx.doi.org/10.1016/j.jocn.2015.12.046
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