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Juvenile xanthogranuloma of the cerebellopontine angle: A case report and review of the literature
Otolaryngology Case Reports 12 (2019) 100124
Contents lists available at ScienceDirect
Otolaryngology Case Reports journal homepage: www.elsevier.com/locate/xocr
Juvenile xanthogranuloma of the cerebellopontine angle: A case report and review of the literature
T
Sarah M. Tittmana,∗, Ashley M. Nassiria, Nauman F. Manzoora, Robert J. Yawna, Bret C. Mobleyb, John C. Wellons IIIc, Alejandro Rivasa a
The Otology Group of Vanderbilt, Vanderbilt University Medical Center, 7209 Medical Center East-South Tower, 1215 21st Ave. South, Nashville, TN, 37232-8605, USA Department of Pathology, Microbiology, & Immunology, Vanderbilt University Medical Center, 1161 21st Ave. South, Nashville, TN, 37232-2561, USA c Division of Pediatric Neurosurgery, Monroe Carell Jr. Children's Hospital at Vanderbilt, 2200 Children's Way, 9222 Doctor's Office Tower, Nashville, TN, 37232-9557, USA b
A R T I C LE I N FO
A B S T R A C T
Keywords: Juvenile xanthogranuloma Histiocytosis Cerebellopontine angle
Juvenile xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis, most often presenting with skin lesions of the head, neck, and upper trunk. Intracranial presentations have been previously described, however, due to its rarity, treatment algorithms have not been developed. The current study presents the case of a JXG of the cerebellopontine angle in a 17-month-old male and a review of the current literature with management options.
Introduction Juvenile xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis, and it exists on the spectrum of histiocytic proliferations [1]. JXG is considered a benign, proliferative condition, and it is predominantly a self-limited disease of the skin during childhood. Disseminated disease and central nervous system involvement are extremely rare [2]. Approximately 50% of cases of intracranial JXG present with multiple lesions, and intracranial JXG most commonly involve the ventricular region, sellar region, skull base, dural-cortical region, or are within the brain parenchyma [3]. Presentation of JXG as an isolated cerebellopontine angle (CPA) mass has not previously been described. Case presentation A previously healthy 17-month-old male presented with a 3-month history of left facial paresis and new onset ataxia, vomiting, irritability, and left CN IV palsy. Computed tomography (CT) of the head demonstrated a 5 cm left CPA mass with significant cerebellar and brainstem compression leading to obstructive hydrocephalus. Initial management included systemic steroids and placement of an external ventricular drain. Gadolinium enhanced magnetic resonance (MR) imaging of the brain demonstrated a 5.5× 4.8 × 4.4 cm heterogenous, predominantly T1 iso-to hypointense and T2 hypointense extra-axial mass with moderate contrast enhancement and without restricted diffusion (Fig. 1A-
∗
D). The initial radiographic differential diagnosis included an ependymoma, malignant nerve sheath tumor, metastatic lesion, endolymphatic sac tumor, or a benign mass of unknown origin. In the setting of obstructive hydrocephalus, the patient underwent a retrosigmoid approach to the CPA for diagnosis and resection of the mass. Intraoperatively, the tumor was found to be encasing cranial nerves IV, VII, VIII, and abutting cranial nerves V and VI. Tissue sent for frozen section pathology revealed a neoplastic process with severe atypia; however, no specific features could be discerned. Auditory brainstem response (ABR) waveforms were monitored intraoperatively and indicative of non-serviceable hearing. There was a small portion of tumor extending above the tentorium cerebelli into the middle fossa. The tentorium was partially sectioned from below, and tumor was resected until the middle fossa region was thought to be tumor free. Consequently, a gross total resection of the tumor with intentional sacrifice of cranial nerves IV, VII, and VIII was performed due to complete tumor encasement and concern for malignant process on frozen pathology. This resulted in intracranial decompression, and postoperatively, the patient recovered without complication. Permanent sections of the CPA mass showed a neoplastic proliferation of cells with ovoid-to-reniform nuclei and eosinophilic cytoplasm arranged in sheets (Fig. 2A–B). Tumor cells were immunoreactive for CD68, CD163, and Factor XIIIa, and Ki67 showed a moderate proliferation rate (Fig. 2C and D). The lesional cells were negative for CD1a, S100, ALK1, SMA, GFAP, and synaptophysin, while CD45 labeled infiltrating lymphocytes. PCR assay for BRAF V600E mutation was
Corresponding author. E-mail address: [email protected] (S.M. Tittman).
https://doi.org/10.1016/j.xocr.2019.100124 Received 31 January 2019; Received in revised form 15 April 2019; Accepted 29 May 2019 Available online 30 May 2019 2468-5488/ © 2019 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Otolaryngology Case Reports 12 (2019) 100124
S.M. Tittman, et al.
Fig. 1. MR with gadolinium, (A) axial T2 image revealing a large, hypointense lesion of the left cerebellopontine angle and surrounding mass effect, (B) coronal T2 image revealing significant cerebellar compression, (C) axial T1 + gadolinium reveals a contrast enhancing left cerebellopontine angle lesion with scattered areas of hemorrhage (*), (D) coronal T1 + gadolinium image revealing focal areas of hemorrhage (*) within the tumor.
consistently positive for the macrophage marker Ki-M1P and CD68, while consistently negative for both CD1a and S-100 [1]. Due to its rarity, intraoperative frozen section of this type of mass is unlikely to reveal the diagnosis, as in our case, which can impact intraoperative decision-making. The precise treatment strategy for intracranial JXG is still unclear given the paucity of data. It has been proposed that when feasible, total surgical resection of intracranial lesions may be curative, and aggressive or unresectable cases may require systemic chemotherapy and radiation [3]. After extensive discussion, adjunctive therapy in the form of post-operative vinblastine with pulsed prednisone was elected in this case.
negative. Importantly, no cytomorphologic features concerning for malignancy or sarcoma were identified. Considered together, the features were those of a histiocytic proliferation, and fit best with a juvenile xanthogranuloma family lesion. In light of this diagnosis, adjuvant chemotherapy was recommended and completed. Additionally, the patient underwent early facial reanimation with a combined hypoglossal to facial anastomosis and a masseteric to buccal branch anastomosis for orbital and smile rehabilitation. Post-operative MRI at three months showed no evidence of recurrent disease.
Discussion While a CPA JXG has not previously been described, general imaging features of JXG of the head and neck in the pediatric population have been reported. Ginat et al. showed that head and neck JXG have varied manifestations with typical findings including mild hyperintensity on T1, hypointensity on T2, decreased diffusivity, and homogenous enhancement [4]. Interestingly, in their review of 10 pediatric patients, JXG was never included in the radiographic differential diagnosis. Given the uncommon nature of this disease process, large studies evaluating the non-Langerhans cell histiocytoses are scarce, but analyses of tumor registries have provided additional insight into the histopathologic characteristics. Immunohistochemical stains are
Conclusion Tumors comprised of histiocytes within the juvenile xanthogranuloma family present a significant diagnostic and treatment challenge to physicians due to their rarity, varied presentations, difficult histopathologic diagnosis, and lack of consensus on management. A large JXG of the CPA has not previously been described, and this unique case emphasizes the importance of pursuing treatment through a multidisciplinary approach.
2
Otolaryngology Case Reports 12 (2019) 100124
S.M. Tittman, et al.
Fig 2. (A) Tumor cells arranged in sheets (right half of field) were seen adjacent to a central region of fibrosis and necrosis (left side of field), scale = 200 μm. (B) Tumor cells showed ovoid nuclei, eosinophilic cytoplasm, and discernible cell borders with scattered multinucleated cells observed (arrowheads), scale = 50 μm. (C) CD68 immunohistochemistry was positive, scale = 50 μm (D) Factor XIIIa immunohistochemistry was positive, scale = 50 μm.
Ethical statement
clinicopathologic study of 129 patients from the Kiel pediatric tumor registry. Am J Surg Pathol 2005;29(1):21–8https://doi.org/10.1097/01.pas.0000147395. 01229.06. [2] Pagura L, de Prada I, López-Pino MA, Huertas JG, Villareio F. Isolated intracranial juvenile xanthogranuloma. A report of two cases and review of the literature. Childs Nerv Syst 2015;31:493–8https://doi.org/10.1007/s00381-014-2567-4. [3] Wang B, Jin H, Zhao Y, Ma J. The clinical diagnosis and management options for intracranial juvenile xanthogranuloma in children: based on four cases and another 39 patients in the literature. Acta Neurochir 2016;158:1289–97https://doi.org/10. 1007/s00701-016-2811-7. [4] Ginat DT, Vargas SO, Silvera VM, Volk MS, Degar BA, Robson CD. Imaging features of juvenile xanthogranuloma of the pediatric head and neck. Am J Neuroradiol 2016;37:910–6https://doi.org/10.3174/ajnr.A4644.
All research carried out was in accordance with the Code of Ethics of the World Medical Association. No financial support was provided for this research, and there are no relevant financial disclosures. Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.xocr.2019.100124. References [1] Janssen D, Harms D. Juvenile xanthogranuloma in childhood and adolescence: a
3
Contents lists available at ScienceDirect
Otolaryngology Case Reports journal homepage: www.elsevier.com/locate/xocr
Juvenile xanthogranuloma of the cerebellopontine angle: A case report and review of the literature
T
Sarah M. Tittmana,∗, Ashley M. Nassiria, Nauman F. Manzoora, Robert J. Yawna, Bret C. Mobleyb, John C. Wellons IIIc, Alejandro Rivasa a
The Otology Group of Vanderbilt, Vanderbilt University Medical Center, 7209 Medical Center East-South Tower, 1215 21st Ave. South, Nashville, TN, 37232-8605, USA Department of Pathology, Microbiology, & Immunology, Vanderbilt University Medical Center, 1161 21st Ave. South, Nashville, TN, 37232-2561, USA c Division of Pediatric Neurosurgery, Monroe Carell Jr. Children's Hospital at Vanderbilt, 2200 Children's Way, 9222 Doctor's Office Tower, Nashville, TN, 37232-9557, USA b
A R T I C LE I N FO
A B S T R A C T
Keywords: Juvenile xanthogranuloma Histiocytosis Cerebellopontine angle
Juvenile xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis, most often presenting with skin lesions of the head, neck, and upper trunk. Intracranial presentations have been previously described, however, due to its rarity, treatment algorithms have not been developed. The current study presents the case of a JXG of the cerebellopontine angle in a 17-month-old male and a review of the current literature with management options.
Introduction Juvenile xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis, and it exists on the spectrum of histiocytic proliferations [1]. JXG is considered a benign, proliferative condition, and it is predominantly a self-limited disease of the skin during childhood. Disseminated disease and central nervous system involvement are extremely rare [2]. Approximately 50% of cases of intracranial JXG present with multiple lesions, and intracranial JXG most commonly involve the ventricular region, sellar region, skull base, dural-cortical region, or are within the brain parenchyma [3]. Presentation of JXG as an isolated cerebellopontine angle (CPA) mass has not previously been described. Case presentation A previously healthy 17-month-old male presented with a 3-month history of left facial paresis and new onset ataxia, vomiting, irritability, and left CN IV palsy. Computed tomography (CT) of the head demonstrated a 5 cm left CPA mass with significant cerebellar and brainstem compression leading to obstructive hydrocephalus. Initial management included systemic steroids and placement of an external ventricular drain. Gadolinium enhanced magnetic resonance (MR) imaging of the brain demonstrated a 5.5× 4.8 × 4.4 cm heterogenous, predominantly T1 iso-to hypointense and T2 hypointense extra-axial mass with moderate contrast enhancement and without restricted diffusion (Fig. 1A-
∗
D). The initial radiographic differential diagnosis included an ependymoma, malignant nerve sheath tumor, metastatic lesion, endolymphatic sac tumor, or a benign mass of unknown origin. In the setting of obstructive hydrocephalus, the patient underwent a retrosigmoid approach to the CPA for diagnosis and resection of the mass. Intraoperatively, the tumor was found to be encasing cranial nerves IV, VII, VIII, and abutting cranial nerves V and VI. Tissue sent for frozen section pathology revealed a neoplastic process with severe atypia; however, no specific features could be discerned. Auditory brainstem response (ABR) waveforms were monitored intraoperatively and indicative of non-serviceable hearing. There was a small portion of tumor extending above the tentorium cerebelli into the middle fossa. The tentorium was partially sectioned from below, and tumor was resected until the middle fossa region was thought to be tumor free. Consequently, a gross total resection of the tumor with intentional sacrifice of cranial nerves IV, VII, and VIII was performed due to complete tumor encasement and concern for malignant process on frozen pathology. This resulted in intracranial decompression, and postoperatively, the patient recovered without complication. Permanent sections of the CPA mass showed a neoplastic proliferation of cells with ovoid-to-reniform nuclei and eosinophilic cytoplasm arranged in sheets (Fig. 2A–B). Tumor cells were immunoreactive for CD68, CD163, and Factor XIIIa, and Ki67 showed a moderate proliferation rate (Fig. 2C and D). The lesional cells were negative for CD1a, S100, ALK1, SMA, GFAP, and synaptophysin, while CD45 labeled infiltrating lymphocytes. PCR assay for BRAF V600E mutation was
Corresponding author. E-mail address: [email protected] (S.M. Tittman).
https://doi.org/10.1016/j.xocr.2019.100124 Received 31 January 2019; Received in revised form 15 April 2019; Accepted 29 May 2019 Available online 30 May 2019 2468-5488/ © 2019 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Otolaryngology Case Reports 12 (2019) 100124
S.M. Tittman, et al.
Fig. 1. MR with gadolinium, (A) axial T2 image revealing a large, hypointense lesion of the left cerebellopontine angle and surrounding mass effect, (B) coronal T2 image revealing significant cerebellar compression, (C) axial T1 + gadolinium reveals a contrast enhancing left cerebellopontine angle lesion with scattered areas of hemorrhage (*), (D) coronal T1 + gadolinium image revealing focal areas of hemorrhage (*) within the tumor.
consistently positive for the macrophage marker Ki-M1P and CD68, while consistently negative for both CD1a and S-100 [1]. Due to its rarity, intraoperative frozen section of this type of mass is unlikely to reveal the diagnosis, as in our case, which can impact intraoperative decision-making. The precise treatment strategy for intracranial JXG is still unclear given the paucity of data. It has been proposed that when feasible, total surgical resection of intracranial lesions may be curative, and aggressive or unresectable cases may require systemic chemotherapy and radiation [3]. After extensive discussion, adjunctive therapy in the form of post-operative vinblastine with pulsed prednisone was elected in this case.
negative. Importantly, no cytomorphologic features concerning for malignancy or sarcoma were identified. Considered together, the features were those of a histiocytic proliferation, and fit best with a juvenile xanthogranuloma family lesion. In light of this diagnosis, adjuvant chemotherapy was recommended and completed. Additionally, the patient underwent early facial reanimation with a combined hypoglossal to facial anastomosis and a masseteric to buccal branch anastomosis for orbital and smile rehabilitation. Post-operative MRI at three months showed no evidence of recurrent disease.
Discussion While a CPA JXG has not previously been described, general imaging features of JXG of the head and neck in the pediatric population have been reported. Ginat et al. showed that head and neck JXG have varied manifestations with typical findings including mild hyperintensity on T1, hypointensity on T2, decreased diffusivity, and homogenous enhancement [4]. Interestingly, in their review of 10 pediatric patients, JXG was never included in the radiographic differential diagnosis. Given the uncommon nature of this disease process, large studies evaluating the non-Langerhans cell histiocytoses are scarce, but analyses of tumor registries have provided additional insight into the histopathologic characteristics. Immunohistochemical stains are
Conclusion Tumors comprised of histiocytes within the juvenile xanthogranuloma family present a significant diagnostic and treatment challenge to physicians due to their rarity, varied presentations, difficult histopathologic diagnosis, and lack of consensus on management. A large JXG of the CPA has not previously been described, and this unique case emphasizes the importance of pursuing treatment through a multidisciplinary approach.
2
Otolaryngology Case Reports 12 (2019) 100124
S.M. Tittman, et al.
Fig 2. (A) Tumor cells arranged in sheets (right half of field) were seen adjacent to a central region of fibrosis and necrosis (left side of field), scale = 200 μm. (B) Tumor cells showed ovoid nuclei, eosinophilic cytoplasm, and discernible cell borders with scattered multinucleated cells observed (arrowheads), scale = 50 μm. (C) CD68 immunohistochemistry was positive, scale = 50 μm (D) Factor XIIIa immunohistochemistry was positive, scale = 50 μm.
Ethical statement
clinicopathologic study of 129 patients from the Kiel pediatric tumor registry. Am J Surg Pathol 2005;29(1):21–8https://doi.org/10.1097/01.pas.0000147395. 01229.06. [2] Pagura L, de Prada I, López-Pino MA, Huertas JG, Villareio F. Isolated intracranial juvenile xanthogranuloma. A report of two cases and review of the literature. Childs Nerv Syst 2015;31:493–8https://doi.org/10.1007/s00381-014-2567-4. [3] Wang B, Jin H, Zhao Y, Ma J. The clinical diagnosis and management options for intracranial juvenile xanthogranuloma in children: based on four cases and another 39 patients in the literature. Acta Neurochir 2016;158:1289–97https://doi.org/10. 1007/s00701-016-2811-7. [4] Ginat DT, Vargas SO, Silvera VM, Volk MS, Degar BA, Robson CD. Imaging features of juvenile xanthogranuloma of the pediatric head and neck. Am J Neuroradiol 2016;37:910–6https://doi.org/10.3174/ajnr.A4644.
All research carried out was in accordance with the Code of Ethics of the World Medical Association. No financial support was provided for this research, and there are no relevant financial disclosures. Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.xocr.2019.100124. References [1] Janssen D, Harms D. Juvenile xanthogranuloma in childhood and adolescence: a
3