Case Report
A Singular Case of Intracranial Sinus Histiocytosis without Massive Lymphadenopathy: Isolated Rosai-Dorfman Disease of the Hypothalamus Srinivas Chivukula1
Kenneth Clark2
Geoffrey Murdoch2
1 School of Medicine, University of Pittsburgh School of Medicine,
Pittsburgh, Pennsylvania, United States 2 Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States 3 Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States
Johnathan Engh3
Address for correspondence Johnathan Engh, Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States (e-mail: [email protected]).
J Neurol Surg A 2014;76:244–248.
Abstract
Keywords
► Rosai-Dorfman disease ► hypothalamus ► central nervous system ► sinus histiocytosis with massive lymphadenopathy ► CNS
Background Sinus histiocytosis with massive lymphadenopathy (also known as RosaiDorfman disease [RDD]) is a benign but chronic cervical lymphadenopathy associated with systemic inflammation. Although extranodal manifestations of RDD have been described, isolated central nervous system (CNS) involvement is exceedingly rare. Case Description We present the case of a 66-year-old woman who presented with 3 weeks of intermittent headaches, diplopia, and increasing confusion who was found on work-up to have isolated hypothalamic RDD, evidenced by a dense admixture of large histiocytic cells admixed with numerous small mature lymphocytes and some scattered plasma cells and neutrophils on stereotactic brain biopsy. Over 19 months of follow-up, neurologic examination continues to reveal stable bilateral partial abducens nerve palsies without diplopia, and a new gradual onset short-term memory loss. Interim treatment for the histiocytic lesion consisted of 10 cycles of external-beam radiation therapy along with high-dose steroids. The patient currently experiences minimal functional loss from treatment of her intracranial sinus histiocytosis, with a Karnofsky performance status of 80, and she remains without any disease involvement outside of the CNS. Conclusion Because misdiagnosis of a hypothalamic contrast-enhancing lesion could potentially lead to therapeutic mismanagement and poor outcomes, it is important to consider RDD in the differential diagnosis.
Introduction First described in the 1960s as sinus histiocytosis with massive lymphadenopathy, Rosai-Dorfman disease (RDD) is a fairly rare disease that most typically presents (as the name implies) with massive and painless bilateral cervical lymphadenopathy. It is usually associated with additional clinical parameters, most often including elevated erythrocyte sedi-
received August 12, 2013 accepted February 14, 2014 published online June 27, 2014
mentation rate, anemia, hyperpyrexia, and hypergammaglobulinemia.1 The disease usually follows a benign clinical course, either undergoing spontaneous resolution or maintaining a fairly indolent and protracted course for many years or even decades. The disorder is most frequently noted in adolescents, and extranodal manifestations, especially of the skin and the central nervous system (CNS), are seen in a minority of cases.1 The few reports that have described CNS
© 2015 Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0034-1382780. ISSN 2193-6315.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
244
involvement of RDD have largely documented dural-based lesions, with only rare reported instances of intraparenchymal brain involvement.2 In this report, we describe the case of an elderly female patient with isolated RDD of the hypothalamus. To our knowledge, this is the first report of histologically confirmed intraparenchymal RDD in the absence of nodal involvement.
Case Report A 66-year-old woman presented to a local facility in June 2011 with a 3-week history of intermittent headaches, diplopia, and increasing confusion. The patient’s past medical and surgical history were unremarkable except for diabetes mellitus (DM) type 2, and family history was not remarkable for any brain tumors or inflammatory disorders. The ensuing work-up, including magnetic resonance imaging (MRI), revealed mild hydrocephalus and a hypothalamic mass lesion, and the patient was transferred to our institution for further management. Neurologic examination revealed bilateral partial abducens nerve palsies and mild disorientation but was otherwise normal. Repeat brain MRI with contrast re-demonstrated a homogeneously enhancing hypothalamic mass (2.1 1.9 1.3 cm) abutting the posterior optic chiasm with splaying of the optic tracts; the pituitary stalk was identified at the anterior aspect of the mass (►Fig. 1). A pituitary laboratory panel was negative for any abnormalities. Lumbar puncture was unremarkable including a cytologic analysis that was negative for malignant cells. A systemic metastatic work-up was negative for any mass lesions, and therefore a frame-based stereotactic brain biopsy was performed. A right transfrontal approach was taken at the level of the coronal suture, and core biopsies were obtained without complication.
Chivukula et al.
numerous small mature lymphocytes and some scattered plasma cells and neutrophils (►Fig. 2). Rare histiocytes appeared to engulf intact inflammatory cells (emperipolesis). Subsequent examination of the formalin-fixed tissue again showed a dense histiocytic infiltrate with patchy distribution of small mature lymphocytes and plasma cells. The histiocytic cells demonstrated abundant vacuolated or pale eosinophilic cytoplasm and rare foci of probable emperipolesis (►Fig. 3). The cells were growing in a sheet-like fashion with intersecting collagenous septae; no conclusive granulomas were seen. Special stains for fungal and mycobacterial organisms were negative. Immunohistochemical staining for S100, CD68, CD163, and Fascin showed strong and diffuse expression in virtually all of the lesional histiocytes (►Fig. 2); markers of other histiocytic processes (CD1a and Langerin) were negative. These collective findings indicated a diagnosis of RDD.
Hospital Course The patient’s hospital stay was protracted by the development of diabetes insipidus (DI), secondary hypothyroidism, and delirium. Intraoperative head computed tomography (CT) scan demonstrated no evidence of hemorrhage or acute process. Treatment per standard protocols was initiated for both the DI and the hypothyroidism; in addition, the patient was started on moderate dose steroid therapy for the RDD diagnosis with plans for later taper. Work-up for delirium (including lumbar puncture and head CT primarily to rule out infection, malignancy, and hemorrhage) was unremarkable, and the patient was eventually discharged on postoperative day 14 to rehabilitation; neurologic examination at the time was notable for orientation to person and time but not to place, and for stable bilateral partial abducens nerve palsies.
Pathology
Follow-Up
Intraoperative examination of the biopsy tissue revealed a dense combination of large histiocytic cells admixed with
Over 19 months of follow-up, neurologic examination continues to reveal stable bilateral partial abducens nerve palsies
Fig. 1 Rosai-Dorfman disease in a 66-year-old woman who presented with 3 weeks of intermittent headaches, diplopia, and increasing confusion. (Left) Pretreatment axial and (right) coronal T1-weighted magnetic resonance images obtained after contrast administration, demonstrating a hypothalamic mass abutting the optic apparatus and splaying the optic tracts. Journal of Neurological Surgery—Part A
Vol. 76
No. A3/2014
245
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Isolated Rosai-Dorfman Disease of the Hypothalamus
Isolated Rosai-Dorfman Disease of the Hypothalamus
Chivukula et al.
Fig. 2 Low- and high-power magnification of the intraoperative smear preparation using hematoxylin and eosin. The lesion consists of a dense population of large pale histiocytes admixed with many small mature lymphocytes. Many histiocytes appeared to show emperipolesis (arrow).
Fig. 3 Histologic and immunohistochemical characteristics of the lesion (formalin-fixed, paraffin-embedded). Sections stained with hematoxylin and eosin show a dense population of large histiocytes with ample pale or clear cytoplasm admixed with smaller number of lymphocytes. The cells show no clear granuloma formation or necrosis. Many scattered histiocytes also show emperipolesis (arrow). Immunohistochemical staining for CD68 and CD163 confirm the lineage. S100 shows strong and diffuse staining of the lesional cells. Fascin, a recently described marker of RosaiDorfman disease, is also positive. Immunohistochemical staining for CD1a is negative (not shown). Special stains for fungal and mycobacterial organisms were also negative (not shown).
without diplopia, and a new gradual onset short-term memory loss. Interim treatment for the histiocytic lesion consisted of 10 cycles of external-beam radiation therapy (over 6 months following biopsy) along with high-dose steroids (for a total of 275 days following biopsy); radiographic followup at 6-month intervals showed progressive shrinkage of the contrast-enhancing hypothalamic lesion (►Fig. 4). The patient did experience temporary adrenal dysfunction induced by the high-dose steroid therapy necessitating hormone replacement therapy; this has since resolved. The Journal of Neurological Surgery—Part A
Vol. 76
No. A3/2014
patient is currently residing at home with her husband and currently experiences minimal functional loss from treatment of her intracranial sinus histiocytosis, with a Karnofsky performance status of 80.
Discussion Literature regarding intracranial RDD has thus far been limited to case reports.2 Most have discussed dural-based intracranial masses with CNS RDD; intraparenchymal RDD
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
246
Chivukula et al.
Fig. 4 Posttreatment. (Left) Axial and (right) coronal T1-weighted magnetic resonance images obtained after contrast administration, demonstrating the near resolution of the hypothalamic mass 19 months after the initial presentation.
has been much rarer in comparison.3 Although the vast majority of lesions in CNS RDD are intracranial, dural-based masses within the spinal canal have occurred in a small minority of cases, typically compressing the spinal cord and presenting with paraplegia.4,5 Further, the vast majority of patients with CNS RDD reported to date have been older men with a median age of 39 at the time of presentation.6 In stark contrast to the literature findings, we present in this report the case of a 66-year-old woman with isolated hypothalamic sinus histiocytosis, without massive lymphadenopathy, and pathologically confirmed RDD. To our knowledge, this is the first report of its kind. This report was prompted by the scant availability of data regarding the clinical manifestations of isolated intraparenchymal CNS RDD, to add to the growing body of literature regarding this disease of yet unknown etiology.7 In cases of CNS involvement, presenting symptoms described have included seizures, headaches, focal neurologic deficits such as visual changes, and endocrine abnormalities, depending on the location and extent of mass effect from the lesion.6 It has been noted in prior reports that treatment does not appear to be necessary in most cases; accordingly, no clearly defined role has yet been identified for radiation, surgery, or chemotherapy.8 In the case of our patient, the lesion has been showing continued shrinkage on imaging following 10 cycles of radiation therapy. The differential diagnosis for intraparenchymal RDD can present a clinical challenge because proper diagnosis of this condition ultimately requires histopathologic confirmation. In this particular case, the minute amount of lesional tissue as well as histomorphologic overlap with other histiocyte-rich lesions that can arise in this anatomical region made diagnosis more challenging. The broad differential diagnosis of histiocyte-rich lesions includes RDD, Langerhans cell histiocytosis (LCH), Erdheim-Chester disease, neurosarcoidosis, and a handful of infectious processes. In terms of histomorphology, infectious etiologies such as fungi or mycobacteria
typically result in clear granuloma formation with varying degrees of necrosis. Because these features were not seen on hematoxylin and eosin examination, this possibility was considered unlikely and was essentially ruled out with negative special stains for fungal (Grocott) and mycobacterial (acid-fast stain) organisms. Neurosarcoidosis was also considered unlikely due to the lack of granulomatous morphology as well as the absence of additional CNS sites of involvement. Emperipolesis is a phenomenon that refers to the presence of intact cells within the cytoplasm of phagocytic cells and can be seen in several primary hematopoietic disorders. Although not specific, in the context of this histomorphology it raises a suspicion of RDD where it is a commonly seen feature.9 Ultimately the diagnosis rests on the combination of histomorphology and the immunohistochemical profile of the lesion.10 The strong and diffuse expression of CD68 and CD163 confirms that the lesional cells are of monocyte/macrophage lineage. Additionally, the strong S100 positivity and CD1a negativity is a typical immunostaining profile of RDD, and essentially rules out LCH (S100-positive and CD1a-positive) and Erdheim-Chester disease (S100-negative and CD1a-negative). Fascin is a relatively newer marker of dendritic cells that has also been shown to be positive in RDD.11 Taken together, the histomorphology and immunohistochemical profile of the lesion strongly implicates RDD as the diagnosis. The patient in this case typifies the smooth benign prognostic course that RDD typically carries.12 Because this lesion was in such a deep-seated critical location, surgical excision of the mass was not pursued. Therefore, fractionated radiation therapy was believed to be the next best option because the lesion was too close to the optic complex for radiosurgery to be feasible. Because misdiagnosis of a hypothalamic contrastenhancing lesion could potentially lead to therapeutic mismanagement and poor outcomes, it is important to consider RDD in the differential diagnosis. We presented our successful therapeutic strategy in this report; nonetheless, future Journal of Neurological Surgery—Part A
Vol. 76
No. A3/2014
247
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Isolated Rosai-Dorfman Disease of the Hypothalamus
Isolated Rosai-Dorfman Disease of the Hypothalamus
Chivukula et al.
studies will be helpful to improve our understanding of this uncommon disease.
6 Adeleye AO, Amir G, Fraifeld S, Shoshan Y, Umansky F, Spektor S.
7
References 1 Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive
2
3
4
5
lymphadenopathy (Rosai-Dorfman disease): review of the entity. Semin Diagn Pathol 1990;7(1):19–73 Shuangshoti S Jr, Navalitloha Y, Sukpanichnant S, et al. Central nervous system involvement in Rosai-Dorfman disease: report of a case with a review of the literature. Neuropathology 1999; 19:341–346 Wu M, Anderson AE, Kahn LB. A report of intracranial RosaiDorfman disease with literature review. Ann Diagn Pathol 2001; 5(2):96–102 Andriko JA, Morrison A, Colegial CH, Davis BJ, Jones RV. RosaiDorfman disease isolated to the central nervous system: a report of 11 cases. Mod Pathol 2001;14(3):172–178 Warrier R, Chauhan A, Jewan Y, Bansal S, Craver R. Rosai-Dorfman disease with CNS involvement. Clin Adv Hematol Oncol 2012; 10(3):196–202
Journal of Neurological Surgery—Part A
Vol. 76
No. A3/2014
8
9 10
11
12
Diagnosis and management of Rosai-Dorfman disease involving the central nervous system. Neurol Res 2010;32(6):572–578 Cooper SL, Jenrette JM III. Rosai-Dorfman disease: management of CNS and systemic involvement. Clin Adv Hematol Oncol 2012; 10(3):199–202 Asai A, Matsutani M, Kohno T, et al. Leptomeningeal and orbital benign lymphophagocytic histiocytosis. Case report. J Neurosurg 1988;69(4):610–612 Rosai J. Rosai and Ackerman’s Surgical Pathology. 9th ed. London: UK: Elsevier; 2004 Shi Y, Griffin AC, Zhang PJ, Palmer JN, Gupta P. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): a case report and review of 49 cases with fine needle aspiration cytology. Cytojournal 2011;8:3 Mannan AA, Karak AK. Sinus histiocytosis with massive lymphadenopathy (Rosai Dorfman disease): evidence for a dendritic cell derivation? Indian J Pathol Microbiol 2005;48(3):300–304 Kidd DP, Revesz T, Miller NR. Rosai-Dorfman disease presenting with widespread intracranial and spinal cord involvement. Neurology 2006;67(9):1551–1555
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
248
Copyright of Journal of Neurological Surgery. Part A. Central European Neurosurgery is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
A Singular Case of Intracranial Sinus Histiocytosis without Massive Lymphadenopathy: Isolated Rosai-Dorfman Disease of the Hypothalamus Srinivas Chivukula1
Kenneth Clark2
Geoffrey Murdoch2
1 School of Medicine, University of Pittsburgh School of Medicine,
Pittsburgh, Pennsylvania, United States 2 Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States 3 Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States
Johnathan Engh3
Address for correspondence Johnathan Engh, Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States (e-mail: [email protected]).
J Neurol Surg A 2014;76:244–248.
Abstract
Keywords
► Rosai-Dorfman disease ► hypothalamus ► central nervous system ► sinus histiocytosis with massive lymphadenopathy ► CNS
Background Sinus histiocytosis with massive lymphadenopathy (also known as RosaiDorfman disease [RDD]) is a benign but chronic cervical lymphadenopathy associated with systemic inflammation. Although extranodal manifestations of RDD have been described, isolated central nervous system (CNS) involvement is exceedingly rare. Case Description We present the case of a 66-year-old woman who presented with 3 weeks of intermittent headaches, diplopia, and increasing confusion who was found on work-up to have isolated hypothalamic RDD, evidenced by a dense admixture of large histiocytic cells admixed with numerous small mature lymphocytes and some scattered plasma cells and neutrophils on stereotactic brain biopsy. Over 19 months of follow-up, neurologic examination continues to reveal stable bilateral partial abducens nerve palsies without diplopia, and a new gradual onset short-term memory loss. Interim treatment for the histiocytic lesion consisted of 10 cycles of external-beam radiation therapy along with high-dose steroids. The patient currently experiences minimal functional loss from treatment of her intracranial sinus histiocytosis, with a Karnofsky performance status of 80, and she remains without any disease involvement outside of the CNS. Conclusion Because misdiagnosis of a hypothalamic contrast-enhancing lesion could potentially lead to therapeutic mismanagement and poor outcomes, it is important to consider RDD in the differential diagnosis.
Introduction First described in the 1960s as sinus histiocytosis with massive lymphadenopathy, Rosai-Dorfman disease (RDD) is a fairly rare disease that most typically presents (as the name implies) with massive and painless bilateral cervical lymphadenopathy. It is usually associated with additional clinical parameters, most often including elevated erythrocyte sedi-
received August 12, 2013 accepted February 14, 2014 published online June 27, 2014
mentation rate, anemia, hyperpyrexia, and hypergammaglobulinemia.1 The disease usually follows a benign clinical course, either undergoing spontaneous resolution or maintaining a fairly indolent and protracted course for many years or even decades. The disorder is most frequently noted in adolescents, and extranodal manifestations, especially of the skin and the central nervous system (CNS), are seen in a minority of cases.1 The few reports that have described CNS
© 2015 Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0034-1382780. ISSN 2193-6315.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
244
involvement of RDD have largely documented dural-based lesions, with only rare reported instances of intraparenchymal brain involvement.2 In this report, we describe the case of an elderly female patient with isolated RDD of the hypothalamus. To our knowledge, this is the first report of histologically confirmed intraparenchymal RDD in the absence of nodal involvement.
Case Report A 66-year-old woman presented to a local facility in June 2011 with a 3-week history of intermittent headaches, diplopia, and increasing confusion. The patient’s past medical and surgical history were unremarkable except for diabetes mellitus (DM) type 2, and family history was not remarkable for any brain tumors or inflammatory disorders. The ensuing work-up, including magnetic resonance imaging (MRI), revealed mild hydrocephalus and a hypothalamic mass lesion, and the patient was transferred to our institution for further management. Neurologic examination revealed bilateral partial abducens nerve palsies and mild disorientation but was otherwise normal. Repeat brain MRI with contrast re-demonstrated a homogeneously enhancing hypothalamic mass (2.1 1.9 1.3 cm) abutting the posterior optic chiasm with splaying of the optic tracts; the pituitary stalk was identified at the anterior aspect of the mass (►Fig. 1). A pituitary laboratory panel was negative for any abnormalities. Lumbar puncture was unremarkable including a cytologic analysis that was negative for malignant cells. A systemic metastatic work-up was negative for any mass lesions, and therefore a frame-based stereotactic brain biopsy was performed. A right transfrontal approach was taken at the level of the coronal suture, and core biopsies were obtained without complication.
Chivukula et al.
numerous small mature lymphocytes and some scattered plasma cells and neutrophils (►Fig. 2). Rare histiocytes appeared to engulf intact inflammatory cells (emperipolesis). Subsequent examination of the formalin-fixed tissue again showed a dense histiocytic infiltrate with patchy distribution of small mature lymphocytes and plasma cells. The histiocytic cells demonstrated abundant vacuolated or pale eosinophilic cytoplasm and rare foci of probable emperipolesis (►Fig. 3). The cells were growing in a sheet-like fashion with intersecting collagenous septae; no conclusive granulomas were seen. Special stains for fungal and mycobacterial organisms were negative. Immunohistochemical staining for S100, CD68, CD163, and Fascin showed strong and diffuse expression in virtually all of the lesional histiocytes (►Fig. 2); markers of other histiocytic processes (CD1a and Langerin) were negative. These collective findings indicated a diagnosis of RDD.
Hospital Course The patient’s hospital stay was protracted by the development of diabetes insipidus (DI), secondary hypothyroidism, and delirium. Intraoperative head computed tomography (CT) scan demonstrated no evidence of hemorrhage or acute process. Treatment per standard protocols was initiated for both the DI and the hypothyroidism; in addition, the patient was started on moderate dose steroid therapy for the RDD diagnosis with plans for later taper. Work-up for delirium (including lumbar puncture and head CT primarily to rule out infection, malignancy, and hemorrhage) was unremarkable, and the patient was eventually discharged on postoperative day 14 to rehabilitation; neurologic examination at the time was notable for orientation to person and time but not to place, and for stable bilateral partial abducens nerve palsies.
Pathology
Follow-Up
Intraoperative examination of the biopsy tissue revealed a dense combination of large histiocytic cells admixed with
Over 19 months of follow-up, neurologic examination continues to reveal stable bilateral partial abducens nerve palsies
Fig. 1 Rosai-Dorfman disease in a 66-year-old woman who presented with 3 weeks of intermittent headaches, diplopia, and increasing confusion. (Left) Pretreatment axial and (right) coronal T1-weighted magnetic resonance images obtained after contrast administration, demonstrating a hypothalamic mass abutting the optic apparatus and splaying the optic tracts. Journal of Neurological Surgery—Part A
Vol. 76
No. A3/2014
245
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Isolated Rosai-Dorfman Disease of the Hypothalamus
Isolated Rosai-Dorfman Disease of the Hypothalamus
Chivukula et al.
Fig. 2 Low- and high-power magnification of the intraoperative smear preparation using hematoxylin and eosin. The lesion consists of a dense population of large pale histiocytes admixed with many small mature lymphocytes. Many histiocytes appeared to show emperipolesis (arrow).
Fig. 3 Histologic and immunohistochemical characteristics of the lesion (formalin-fixed, paraffin-embedded). Sections stained with hematoxylin and eosin show a dense population of large histiocytes with ample pale or clear cytoplasm admixed with smaller number of lymphocytes. The cells show no clear granuloma formation or necrosis. Many scattered histiocytes also show emperipolesis (arrow). Immunohistochemical staining for CD68 and CD163 confirm the lineage. S100 shows strong and diffuse staining of the lesional cells. Fascin, a recently described marker of RosaiDorfman disease, is also positive. Immunohistochemical staining for CD1a is negative (not shown). Special stains for fungal and mycobacterial organisms were also negative (not shown).
without diplopia, and a new gradual onset short-term memory loss. Interim treatment for the histiocytic lesion consisted of 10 cycles of external-beam radiation therapy (over 6 months following biopsy) along with high-dose steroids (for a total of 275 days following biopsy); radiographic followup at 6-month intervals showed progressive shrinkage of the contrast-enhancing hypothalamic lesion (►Fig. 4). The patient did experience temporary adrenal dysfunction induced by the high-dose steroid therapy necessitating hormone replacement therapy; this has since resolved. The Journal of Neurological Surgery—Part A
Vol. 76
No. A3/2014
patient is currently residing at home with her husband and currently experiences minimal functional loss from treatment of her intracranial sinus histiocytosis, with a Karnofsky performance status of 80.
Discussion Literature regarding intracranial RDD has thus far been limited to case reports.2 Most have discussed dural-based intracranial masses with CNS RDD; intraparenchymal RDD
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
246
Chivukula et al.
Fig. 4 Posttreatment. (Left) Axial and (right) coronal T1-weighted magnetic resonance images obtained after contrast administration, demonstrating the near resolution of the hypothalamic mass 19 months after the initial presentation.
has been much rarer in comparison.3 Although the vast majority of lesions in CNS RDD are intracranial, dural-based masses within the spinal canal have occurred in a small minority of cases, typically compressing the spinal cord and presenting with paraplegia.4,5 Further, the vast majority of patients with CNS RDD reported to date have been older men with a median age of 39 at the time of presentation.6 In stark contrast to the literature findings, we present in this report the case of a 66-year-old woman with isolated hypothalamic sinus histiocytosis, without massive lymphadenopathy, and pathologically confirmed RDD. To our knowledge, this is the first report of its kind. This report was prompted by the scant availability of data regarding the clinical manifestations of isolated intraparenchymal CNS RDD, to add to the growing body of literature regarding this disease of yet unknown etiology.7 In cases of CNS involvement, presenting symptoms described have included seizures, headaches, focal neurologic deficits such as visual changes, and endocrine abnormalities, depending on the location and extent of mass effect from the lesion.6 It has been noted in prior reports that treatment does not appear to be necessary in most cases; accordingly, no clearly defined role has yet been identified for radiation, surgery, or chemotherapy.8 In the case of our patient, the lesion has been showing continued shrinkage on imaging following 10 cycles of radiation therapy. The differential diagnosis for intraparenchymal RDD can present a clinical challenge because proper diagnosis of this condition ultimately requires histopathologic confirmation. In this particular case, the minute amount of lesional tissue as well as histomorphologic overlap with other histiocyte-rich lesions that can arise in this anatomical region made diagnosis more challenging. The broad differential diagnosis of histiocyte-rich lesions includes RDD, Langerhans cell histiocytosis (LCH), Erdheim-Chester disease, neurosarcoidosis, and a handful of infectious processes. In terms of histomorphology, infectious etiologies such as fungi or mycobacteria
typically result in clear granuloma formation with varying degrees of necrosis. Because these features were not seen on hematoxylin and eosin examination, this possibility was considered unlikely and was essentially ruled out with negative special stains for fungal (Grocott) and mycobacterial (acid-fast stain) organisms. Neurosarcoidosis was also considered unlikely due to the lack of granulomatous morphology as well as the absence of additional CNS sites of involvement. Emperipolesis is a phenomenon that refers to the presence of intact cells within the cytoplasm of phagocytic cells and can be seen in several primary hematopoietic disorders. Although not specific, in the context of this histomorphology it raises a suspicion of RDD where it is a commonly seen feature.9 Ultimately the diagnosis rests on the combination of histomorphology and the immunohistochemical profile of the lesion.10 The strong and diffuse expression of CD68 and CD163 confirms that the lesional cells are of monocyte/macrophage lineage. Additionally, the strong S100 positivity and CD1a negativity is a typical immunostaining profile of RDD, and essentially rules out LCH (S100-positive and CD1a-positive) and Erdheim-Chester disease (S100-negative and CD1a-negative). Fascin is a relatively newer marker of dendritic cells that has also been shown to be positive in RDD.11 Taken together, the histomorphology and immunohistochemical profile of the lesion strongly implicates RDD as the diagnosis. The patient in this case typifies the smooth benign prognostic course that RDD typically carries.12 Because this lesion was in such a deep-seated critical location, surgical excision of the mass was not pursued. Therefore, fractionated radiation therapy was believed to be the next best option because the lesion was too close to the optic complex for radiosurgery to be feasible. Because misdiagnosis of a hypothalamic contrastenhancing lesion could potentially lead to therapeutic mismanagement and poor outcomes, it is important to consider RDD in the differential diagnosis. We presented our successful therapeutic strategy in this report; nonetheless, future Journal of Neurological Surgery—Part A
Vol. 76
No. A3/2014
247
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Isolated Rosai-Dorfman Disease of the Hypothalamus
Isolated Rosai-Dorfman Disease of the Hypothalamus
Chivukula et al.
studies will be helpful to improve our understanding of this uncommon disease.
6 Adeleye AO, Amir G, Fraifeld S, Shoshan Y, Umansky F, Spektor S.
7
References 1 Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive
2
3
4
5
lymphadenopathy (Rosai-Dorfman disease): review of the entity. Semin Diagn Pathol 1990;7(1):19–73 Shuangshoti S Jr, Navalitloha Y, Sukpanichnant S, et al. Central nervous system involvement in Rosai-Dorfman disease: report of a case with a review of the literature. Neuropathology 1999; 19:341–346 Wu M, Anderson AE, Kahn LB. A report of intracranial RosaiDorfman disease with literature review. Ann Diagn Pathol 2001; 5(2):96–102 Andriko JA, Morrison A, Colegial CH, Davis BJ, Jones RV. RosaiDorfman disease isolated to the central nervous system: a report of 11 cases. Mod Pathol 2001;14(3):172–178 Warrier R, Chauhan A, Jewan Y, Bansal S, Craver R. Rosai-Dorfman disease with CNS involvement. Clin Adv Hematol Oncol 2012; 10(3):196–202
Journal of Neurological Surgery—Part A
Vol. 76
No. A3/2014
8
9 10
11
12
Diagnosis and management of Rosai-Dorfman disease involving the central nervous system. Neurol Res 2010;32(6):572–578 Cooper SL, Jenrette JM III. Rosai-Dorfman disease: management of CNS and systemic involvement. Clin Adv Hematol Oncol 2012; 10(3):199–202 Asai A, Matsutani M, Kohno T, et al. Leptomeningeal and orbital benign lymphophagocytic histiocytosis. Case report. J Neurosurg 1988;69(4):610–612 Rosai J. Rosai and Ackerman’s Surgical Pathology. 9th ed. London: UK: Elsevier; 2004 Shi Y, Griffin AC, Zhang PJ, Palmer JN, Gupta P. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): a case report and review of 49 cases with fine needle aspiration cytology. Cytojournal 2011;8:3 Mannan AA, Karak AK. Sinus histiocytosis with massive lymphadenopathy (Rosai Dorfman disease): evidence for a dendritic cell derivation? Indian J Pathol Microbiol 2005;48(3):300–304 Kidd DP, Revesz T, Miller NR. Rosai-Dorfman disease presenting with widespread intracranial and spinal cord involvement. Neurology 2006;67(9):1551–1555
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
248
Copyright of Journal of Neurological Surgery. Part A. Central European Neurosurgery is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
