- Email: [email protected]
Tumor-to-Tumor Metastasis of Hepatocellular Carcinoma to Vestibular Schwannoma
Case Report
Tumor-to-Tumor Metastasis of Hepatocellular Carcinoma to Vestibular Schwannoma Michael J. Yang1, Knarik Arkun2, Carl B. Heilman1
Key words Acoustic neuroma - Collision tumor - Metastatic hepatocellular carcinoma - Tumor-to-tumor metastasis - Vestibular schwannoma -
Abbreviations and Acronyms CNS: Central nervous system CPA: Cerebellopontine angle MRI: Magnetic resonance imaging From the 1Department of Neurosurgery, Tufts Medical Center, and 2Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, Massachusetts, USA To whom correspondence should be addressed: Michael J. Yang, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2019) 128:324-327. https://doi.org/10.1016/j.wneu.2019.05.106
- BACKGROUND:
Intracranial metastasis is a common complication of systemic malignancy. A rare subset of intracranial masses constitutes tumor-totumor metastasis, in which an extracranial neoplasm hematogenously spreads to an existing intracranial lesion.
- CASE
DESCRIPTION: Here we present the unique case of a 59-year-old man with known hepatocellular carcinoma who presented with acute headaches, double vision, vertigo, and gait instability in the context of 2 years of right-sided hearing loss. Head imaging showed a heterogeneous right cerebellopontine angle mass extending into the porus acousticus with adjacent cerebellar edema. Histopathologic analysis after resection found coexisting hepatocellular carcinoma within a vestibular schwannoma.
- CONCLUSIONS:
Tumor-to-tumor metastasis is an important consideration in the diagnostic work-up and treatment of patients with known systemic malignancy who present with a new intracranial lesion. This pathologic entity could be missed if this patient were treated with single-fraction radiosurgery such as Gamma Knife.
Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.
INTRODUCTION Intracranial metastasis is a common complication of systemic neoplasms. Although reports vary widely, there is an approximate 8.5% 9.6% incidence of central nervous system (CNS) metastasis in patients with confirmed systemic cancer.1 Primary lung and breast carcinomas, as well as melanomas, account for up to 80% of CNS metastases; only 4% 6.2% originate from primary gastrointestinal cancers.1,2 A rare subset of CNS metastatic lesions are intracranial tumor-to-tumor metastases, defined as the coexistence of a metastatic neoplasm with a primary CNS tumor in the same lesion. The first case of a tumor-to-tumor metastasis was documented in 1930, with >100 cases published since.3,4 Lung and breast cancers are the most common donor neoplasms, with meningiomas serving as the recipient intracranial lesion in approximately two-thirds of cases.4,5 Fukushima et al6-11 detail that there have been only 7 reported cases of tumor-totumor metastases involving vestibular
324
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schwannomas. However, there are no published cases of tumor-to-tumor metastasis, regardless of recipient intracranial tumor location or type, containing metastatic hepatocellular carcinoma. Here we present a unique case of a tumor-to-tumor metastasis of coexisting vestibular schwannoma and hepatocellular carcinoma. CASE REPORT A 59-year-old male with hepatitis C complicated by hepatocellular carcinoma presented after 3 days of sudden-onset gait instability and severe headache associated with double vision and vertigo. The patient also endorsed a 2-year history of gradual right-sided hearing loss. Physical examination was significant for loss of right-sided hearing with no dysmetria or dysdiadochokinesis; gait testing revealed unsteadiness on pivoting. Strength to confrontation, sensation to light touch, and deep tendon reflexes were intact in all 4 extremities. The patient had no family or personal history of neurofibromatosis type II. Initial computed tomography imaging of the head showed a 3.9 cm 2.9 cm 2.3 cm mass in the right
cerebellopontine angle (CPA) with extension into the porus acusticus, mildly compressing the fourth ventricle. The internal auditory canal was widened by the tumor. Magnetic resonance imaging (MRI) indicated a bilobed extra-axial CPA mass compressing the right cerebellar hemisphere and brachium pontis with surrounding vasogenic edema, displaying avid heterogeneous enhancement with extensive susceptibility artifact (Figure 1A and B). The patient’s hepatocellular carcinoma had been monitored with serial imaging. Initial abdominal computed tomography 17 months before neurosurgical presentation revealed a cirrhotic liver with multiple lesions exhibiting arterial enhancement and venous washout, fulfilling diagnostic imaging criteria for hepatocellular carcinoma. Despite sorafenib therapy and multiple chemoembolization procedures, follow-up abdominal MRI showed a left adrenal mass concerning for metastatic disease in addition to hepatic disease progression in the months before presentation (Figure 2). The patient underwent right suboccipital craniotomy for tumor resection.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.05.106
CASE REPORT MICHAEL J. YANG ET AL.
INTRACRANIAL TUMOR-TO-TUMOR METASTASIS
Figure 1. (A) Axial T2 and (B) axial post-contrast T1 magnetic resonance imaging sequences acquired on presentation showing a bilobed, heterogeneously enhancing, extra-axial mass centered in the right cerebellopontine angle, approximately 4.2 cm 2.8 cm 2.7 cm. The mass extends into and widens the porus acousticus with associated vasogenic edema in the adjacent cerebellar hemisphere and brachium pontis. There is partial effacement of the fourth ventricle. Areas of presumed hepatocellular carcinoma are demarcated with red arrows, with white arrows indicative of schwannoma based on the appearance of the tumor at surgery.
The tumor capsule of the CPA mass, immediately identifiable after opening the dura, had a superficial yellow appearance
similar to that of an acoustic neuroma. Internally, however, there was soft gray material with areas of focal hemorrhage
Figure 2. Post-contrast coronal abdominal magnetic resonance imaging showing multiple nodular liver masses in addition to an approximately 5 cm heterogeneous mass in the left adrenal gland, 2 months before neurosurgical presentation.
WORLD NEUROSURGERY 128: 324-327, AUGUST 2019
more consistent with metastatic carcinoma. Frozen sections identified metastatic carcinoma with no definite schwannoma. There was no observable facial nerve invasion; however, the tumor required microdissection to be separated from the facial nerve at the brainstem, trigeminal nerve, and anterior inferior cerebellar artery. The eighth cranial nerve was sacrificed during tumor resection. A small portion of the tumor capsule adherent to the facial nerve was left behind in order to preserve facial nerve function. This portion of the tumor capsule appeared typical for a schwannoma. Postoperative examination revealed no hearing in the right ear with new House-Brackmann grade II out of VI right facial paresis. The patient tolerated the procedure well. MRI 2 weeks after the procedure visualized gross total resection with a thin rim of residual tumor along the facial nerve as it entered the internal auditory canal (Figure 3). Two months postoperatively, the patient’s gait stability and headache had significantly improved with resolution of his blurry vision and vertigo. Postoperative pathologic examination of the resected tumor identified schwannoma with metastatic hepatocellular carcinoma (Figure 4AeC). Hematoxylineosin stained sections displayed numerous nests of large atypical epithelioid cells with dense eosinophilic cytoplasm, consistent with metastatic carcinoma, encircled by spindle cells. The background spindle cells showed characteristic biphasic population with areas of hypocellularity and hypercellularity, as well as focal hyalinization. Hyalinized vessels with extravasated red blood cells and pigment-laden macrophages, confirming recent and remote hemorrhage, were present. A panel of immunohistochemical stains was performed to confirm the histologic impression. Hepatocyte antibody showed strong cytoplasmic immunopositivity in nests of metastatic carcinoma. The schwannoma component showed strong immunopositive labeling in nuclei and cytoplasm of spindle cells. DISCUSSION There have been multiple proposed classification systems for intracranial lesions
www.journals.elsevier.com/world-neurosurgery
325
CASE REPORT MICHAEL J. YANG ET AL.
INTRACRANIAL TUMOR-TO-TUMOR METASTASIS
Figure 3. Postoperative axial post-contrast T1 magnetic resonance imaging nearly 2 weeks status-post gross total resection of the right cerebellopontine angle mass showing minimal residual enhancement along the lateral right cerebellum and posterior petrous bone with a small amount of residual tumor within the right internal auditory canal (white arrow).
consisting of >1 neoplastic histology. Frassanito et al12 discussed different interactions between coexistent tumor types, specifically distinguishing collision tumors from tumor-to-tumor metastases. Collision tumors exhibit radiologic and histologic continuity with both tumor types being of intracranial origin, whereas tumor-to-tumor metastases constitute single radiologic lesions consisting of 1
extracranial and 1 intracranial tumor type, with 1 tumor in the context of another.12 Separately, Graffeo et al13 described “synchronous tumors” as those with 2grossly distinct tumor types and discrete masses; in contrast, “tumor-to-tumor metastasis” was defined as tumors with a grossly singular pathology with evidence of hematogenous spread of 1 tumor into another. Our case of hepatocellular
Figure 4. (A) Hematoxylin-eosin section shows nests of metastatic hepatocellular carcinoma within schwannoma at low magnification. (B) Immunohistochemistry with hepatocyte antigen decorates malignant cells in nest, confirming hepatic origin of carcinoma, at low magnification. (C) Immunohistochemistry with S-100 highlights benign spindle cells of
326
www.SCIENCEDIRECT.com
carcinoma metastasis to a vestibular schwannoma falls within the tumor-totumor metastasis category of both the Frassanito and Graffeo classification systems. Importantly, it should be considered as distinct from a collision tumor, as hepatocellular carcinoma is extracranial in origin. Intracranial metastasis of hepatocellular carcinoma is rare, with reported incidence rates of 0.2% 2.2%.14-16 However, the presence of an existing benign tumor has been postulated to provide an environment that may protect and, in fact, foster metastatic proliferation.17,18 Although the exact mechanism is unknown, several theories have been proposed for meningiomas harboring metastatic disease: A low metabolic rate provides a noncompetitive metabolic environment,19 increased collagen and lipid content serves as a nutrient-rich setting,20 enhanced vascularity increases the likelihood of malignant cells docking in the tumor itself,21 and the relative paucity of immune surveillance in the benign brain tumor may protect metastatic disease from immune destruction.22,23 Although schwannomas are not typically as well vascularized as meningiomas, these same mechanisms may underlie the metastasis of this patient’s hepatocellular carcinoma to vestibular schwannoma, particularly in the context of the vascularity of the CPA itself. Treatment of patients with suspected tumor-to-tumor metastasis must be approached on an individual basis. Crucial variables to consider are the staging and grading of the patient’s primary systemic
schwannoma between the nests of metastatic carcinoma at low magnification. As in many cerebellopontine angle schwannomas, characteristic Verocay bodies and Antoni A and B regions were present only focally and were not as prominently visualized as in peripheral schwannomas.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.05.106
CASE REPORT MICHAEL J. YANG ET AL.
malignancy and its response to previous chemotherapeutic and/or radiation treatments, as applicable. There are numerous other considerations before offering surgical resection of a suspected intracranial tumor-to-tumor metastasis, including the number and location of additional intracranial metastases and any medical comorbidities that may preclude a patient’s surgical candidacy. Our patient had extensive hepatocellular carcinoma at the time of presentation with ongoing gait instability, headache, and vertigo. He had recently failed sorafenib and showed potential progression of disease on nivolumab, a second-line immunotherapy for hepatocellular carcinoma. The decision was made to recommend operative intervention given his persistent symptoms, the possibility that the CPA mass was an isolated vestibular schwannoma, the presence of only 1 intracranial mass, and the fact he was medically stable aside from his known hepatic and adrenal disease. Adjuvant radiation was pursued after final pathology confirmed the presence of metastatic hepatocellular carcinoma in the right CPA mass. In their review of 46 patients with synchronous CPA tumors, Graffeo et al13 report a 27% overall rate of HouseBrackmann grade III-VI facial nerve dysfunction after CPA tumor resection, regardless of the tumor histopathologic classification. This rate is considerably higher than for isolated vestibular schwannomas, in which only 16% of patients in their own cohort of 267 patients had long-term House-Brackmann grade III-VI facial nerve paralysis.24 Although intraoperative facial nerve monitoring is increasingly used to minimize facial nerve injury, this is an important morbidity to discuss with patients before offering surgical resection. CONCLUSION Here we present a unique case of metastatic hepatocellular carcinoma to a vestibular schwannoma treated surgically with gross total resection. Intracranial tumor-to-tumor metastasis, although rare, is a well-documented phenomenon. It is distinguished from collision tumors in that it contains an extracranial neoplastic component with evidence of
INTRACRANIAL TUMOR-TO-TUMOR METASTASIS
hematogenous spread into an intracranial lesion. In patients with documented systemic cancer, tumor-to-tumor metastasis is important to consider in the evaluation and treatment of new symptomatic intracranial masses. Physicians should be aware of this possibility, particularly if considering radiosurgery for the treatment of an acoustic neuroma in a patient with systemic cancer.
definitions and proposal for classification. Acta Neurochir. 2011;153:1989-1993. 13. Graffeo CS, Perry A, Copeland WR III, et al. Synchronous tumors of the cerebellopontine angle. World Neurosurg. 2017;98:632-643. 14. Lim S, Lee S, Lim JY, et al. Hepatocellular carcinoma specific graded prognostic assessment can predict outcomes for patients with brain metastases from hepatocellular carcinoma. J Neurooncol. 2014;120:199-207. 15. Choi HJ, Cho BC, Sohn JH, et al. Brain metastases from hepatocellular carcinoma: prognostic factors and outcome. J Neurooncol. 2009;91:307-313.
REFERENCES 1. Nayak L, Lee EQ, Wen PY. Epidemiology of brain metastases. Curr Oncol Rep. 2012;14:48-54. 2. Bartelt S, Momm F, Weissenberger C, Lutterbach J. Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy: Prognostic factors and survival. World J Gastroenterol. 2004;10:3345-3348. 3. Fried BM. Inoculation of a meningioma by cancer cells from a bronchiogenic carcinoma. Am J Pathol. 1930;VI:47-52. 4. Richter B, Harinath L, Pu C, Stabingas K. Metastatic spread of systemic neoplasms to central nervous system tumors: review of the literature and case presentation of esophageal carcinoma metastatic to meningioma. Clin Neuropathol. 2017; 36:60-65. 5. Lu J, Khalil M, Hu W, Sutherland G, Clark A. Tumor-to-tumor metastasis: esophageal carcinoma metastatic to an intracranial paraganglioma. J Neurosurg. 2009;110:744-748. 6. Fukushima Y, Ota T, Mukasa A, Uozaki H, Kawai K, Saito N. Tumor-to-tumor metastasis: lung adenocarcinoma metastasizing to vestibular schwannoma suspected on preoperative [18F]fluorodeoxyglucose positron emission tomography imaging. World Neurosurg. 2012;78: 553.e9-553.e13.
16. Jiang X-B, Ke C, Zhang G-H, et al. Brain metastases from hepatocellular carcinoma: clinical features and prognostic factors. BMC Cancer. 2012; 12:49. 17. Lanotte M, Benech F, Panciani PP, Cassoni P, Ducati A. Systemic cancer metastasis in a meningioma: report of two cases and review of the literature. Clin Neurol Neurosurg. 2009;111:87-93. 18. Lua B-K, Lieu A-S, Hwang S-L. Breast carcinoma metastasized to a vestibular schwannoma: a rare case of tumor-to-tumor metastasis and literature review. Kaohsiung J Med Sci. 2012;28:397-399. 19. Crockard A, Barnard R, Isaacson P. Metastasis of carcinoma to hemangioblastoma cerebelli: case report. Neurosurgery. 1988;23:382-384. 20. Fidler IJ. The pathogenesis of cancer metastasis: the “seed and soil” hypothesis revisited. Nat Rev Cancer. 2003;3:453-458. 21. Best PV. Metastatic carcinoma in a meningioma. J Neurosurg. 1963;20:892-894. 22. Jr MSM, Brooks WH, Roszmann T, Bigner DD, Dudka L, Richardson S. Immunobiology of primary intracranial tumours: part 1. Studies of the cellular and humora general immune competence of brain tumour patients. J Neurosurg. 1977;46: 467-476.
7. Chambers P, Davis R, Blanding J, Buck F. Metastases to primary intracranial meningiomas and neurilemomas. Arch Pathol Lab Med. 1980;104: 350-354.
23. Brooks WH, Netsky MG, Normansell DE, Horwitz DA. Depressed cell-mediated immunity in patients with primary intracranial tumors. J Exp Med. 1972;136:1631.
8. LeBlanc R. Metastasis of bronchogenic carcinoma to acoustic neurinoma. Case report. J Neurosurg. 1974;41:614-617.
24. Schmitt WR, Daube JR, Carlson ML, et al. Use of supramaximal stimulation to predict facial nerve outcomes following vestibular schwannoma microsurgery: results from a decade of experience. J Neurosurg. 2013;118:206-212.
9. Tang G, Piao Y, Zhao L, Lu D. Lung adenocarcinoma metastasizing to cerebellopontine angle schwannoma (collision tumor). Acta Neurochirurgica (Wien). 2007;149:87-90. 10. Wallach JB, Edberg S. Metastases of cancer to primary intracranial tumor. AMA Arch Neurol. 1959; 1:191-194. 11. Wong T, Bennington J. Metastasis of a mammary carcinoma to an acoustic neuroma: report of a case. J Neurosurg. 1962;19:1088-1093. 12. Frassanito P, Montano N, Lauretti L, et al. Simultaneously occurring tumours within the same cerebello-pontine angle: refining literature
WORLD NEUROSURGERY 128: 324-327, AUGUST 2019
Conflict of interest statement: The authors report no conflict of interest, and no financial support was given. Received 21 March 2019; accepted 13 May 2019 Citation: World Neurosurg. (2019) 128:324-327. https://doi.org/10.1016/j.wneu.2019.05.106 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.
www.journals.elsevier.com/world-neurosurgery
327
Tumor-to-Tumor Metastasis of Hepatocellular Carcinoma to Vestibular Schwannoma Michael J. Yang1, Knarik Arkun2, Carl B. Heilman1
Key words Acoustic neuroma - Collision tumor - Metastatic hepatocellular carcinoma - Tumor-to-tumor metastasis - Vestibular schwannoma -
Abbreviations and Acronyms CNS: Central nervous system CPA: Cerebellopontine angle MRI: Magnetic resonance imaging From the 1Department of Neurosurgery, Tufts Medical Center, and 2Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, Massachusetts, USA To whom correspondence should be addressed: Michael J. Yang, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2019) 128:324-327. https://doi.org/10.1016/j.wneu.2019.05.106
- BACKGROUND:
Intracranial metastasis is a common complication of systemic malignancy. A rare subset of intracranial masses constitutes tumor-totumor metastasis, in which an extracranial neoplasm hematogenously spreads to an existing intracranial lesion.
- CASE
DESCRIPTION: Here we present the unique case of a 59-year-old man with known hepatocellular carcinoma who presented with acute headaches, double vision, vertigo, and gait instability in the context of 2 years of right-sided hearing loss. Head imaging showed a heterogeneous right cerebellopontine angle mass extending into the porus acousticus with adjacent cerebellar edema. Histopathologic analysis after resection found coexisting hepatocellular carcinoma within a vestibular schwannoma.
- CONCLUSIONS:
Tumor-to-tumor metastasis is an important consideration in the diagnostic work-up and treatment of patients with known systemic malignancy who present with a new intracranial lesion. This pathologic entity could be missed if this patient were treated with single-fraction radiosurgery such as Gamma Knife.
Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.
INTRODUCTION Intracranial metastasis is a common complication of systemic neoplasms. Although reports vary widely, there is an approximate 8.5% 9.6% incidence of central nervous system (CNS) metastasis in patients with confirmed systemic cancer.1 Primary lung and breast carcinomas, as well as melanomas, account for up to 80% of CNS metastases; only 4% 6.2% originate from primary gastrointestinal cancers.1,2 A rare subset of CNS metastatic lesions are intracranial tumor-to-tumor metastases, defined as the coexistence of a metastatic neoplasm with a primary CNS tumor in the same lesion. The first case of a tumor-to-tumor metastasis was documented in 1930, with >100 cases published since.3,4 Lung and breast cancers are the most common donor neoplasms, with meningiomas serving as the recipient intracranial lesion in approximately two-thirds of cases.4,5 Fukushima et al6-11 detail that there have been only 7 reported cases of tumor-totumor metastases involving vestibular
324
www.SCIENCEDIRECT.com
schwannomas. However, there are no published cases of tumor-to-tumor metastasis, regardless of recipient intracranial tumor location or type, containing metastatic hepatocellular carcinoma. Here we present a unique case of a tumor-to-tumor metastasis of coexisting vestibular schwannoma and hepatocellular carcinoma. CASE REPORT A 59-year-old male with hepatitis C complicated by hepatocellular carcinoma presented after 3 days of sudden-onset gait instability and severe headache associated with double vision and vertigo. The patient also endorsed a 2-year history of gradual right-sided hearing loss. Physical examination was significant for loss of right-sided hearing with no dysmetria or dysdiadochokinesis; gait testing revealed unsteadiness on pivoting. Strength to confrontation, sensation to light touch, and deep tendon reflexes were intact in all 4 extremities. The patient had no family or personal history of neurofibromatosis type II. Initial computed tomography imaging of the head showed a 3.9 cm 2.9 cm 2.3 cm mass in the right
cerebellopontine angle (CPA) with extension into the porus acusticus, mildly compressing the fourth ventricle. The internal auditory canal was widened by the tumor. Magnetic resonance imaging (MRI) indicated a bilobed extra-axial CPA mass compressing the right cerebellar hemisphere and brachium pontis with surrounding vasogenic edema, displaying avid heterogeneous enhancement with extensive susceptibility artifact (Figure 1A and B). The patient’s hepatocellular carcinoma had been monitored with serial imaging. Initial abdominal computed tomography 17 months before neurosurgical presentation revealed a cirrhotic liver with multiple lesions exhibiting arterial enhancement and venous washout, fulfilling diagnostic imaging criteria for hepatocellular carcinoma. Despite sorafenib therapy and multiple chemoembolization procedures, follow-up abdominal MRI showed a left adrenal mass concerning for metastatic disease in addition to hepatic disease progression in the months before presentation (Figure 2). The patient underwent right suboccipital craniotomy for tumor resection.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.05.106
CASE REPORT MICHAEL J. YANG ET AL.
INTRACRANIAL TUMOR-TO-TUMOR METASTASIS
Figure 1. (A) Axial T2 and (B) axial post-contrast T1 magnetic resonance imaging sequences acquired on presentation showing a bilobed, heterogeneously enhancing, extra-axial mass centered in the right cerebellopontine angle, approximately 4.2 cm 2.8 cm 2.7 cm. The mass extends into and widens the porus acousticus with associated vasogenic edema in the adjacent cerebellar hemisphere and brachium pontis. There is partial effacement of the fourth ventricle. Areas of presumed hepatocellular carcinoma are demarcated with red arrows, with white arrows indicative of schwannoma based on the appearance of the tumor at surgery.
The tumor capsule of the CPA mass, immediately identifiable after opening the dura, had a superficial yellow appearance
similar to that of an acoustic neuroma. Internally, however, there was soft gray material with areas of focal hemorrhage
Figure 2. Post-contrast coronal abdominal magnetic resonance imaging showing multiple nodular liver masses in addition to an approximately 5 cm heterogeneous mass in the left adrenal gland, 2 months before neurosurgical presentation.
WORLD NEUROSURGERY 128: 324-327, AUGUST 2019
more consistent with metastatic carcinoma. Frozen sections identified metastatic carcinoma with no definite schwannoma. There was no observable facial nerve invasion; however, the tumor required microdissection to be separated from the facial nerve at the brainstem, trigeminal nerve, and anterior inferior cerebellar artery. The eighth cranial nerve was sacrificed during tumor resection. A small portion of the tumor capsule adherent to the facial nerve was left behind in order to preserve facial nerve function. This portion of the tumor capsule appeared typical for a schwannoma. Postoperative examination revealed no hearing in the right ear with new House-Brackmann grade II out of VI right facial paresis. The patient tolerated the procedure well. MRI 2 weeks after the procedure visualized gross total resection with a thin rim of residual tumor along the facial nerve as it entered the internal auditory canal (Figure 3). Two months postoperatively, the patient’s gait stability and headache had significantly improved with resolution of his blurry vision and vertigo. Postoperative pathologic examination of the resected tumor identified schwannoma with metastatic hepatocellular carcinoma (Figure 4AeC). Hematoxylineosin stained sections displayed numerous nests of large atypical epithelioid cells with dense eosinophilic cytoplasm, consistent with metastatic carcinoma, encircled by spindle cells. The background spindle cells showed characteristic biphasic population with areas of hypocellularity and hypercellularity, as well as focal hyalinization. Hyalinized vessels with extravasated red blood cells and pigment-laden macrophages, confirming recent and remote hemorrhage, were present. A panel of immunohistochemical stains was performed to confirm the histologic impression. Hepatocyte antibody showed strong cytoplasmic immunopositivity in nests of metastatic carcinoma. The schwannoma component showed strong immunopositive labeling in nuclei and cytoplasm of spindle cells. DISCUSSION There have been multiple proposed classification systems for intracranial lesions
www.journals.elsevier.com/world-neurosurgery
325
CASE REPORT MICHAEL J. YANG ET AL.
INTRACRANIAL TUMOR-TO-TUMOR METASTASIS
Figure 3. Postoperative axial post-contrast T1 magnetic resonance imaging nearly 2 weeks status-post gross total resection of the right cerebellopontine angle mass showing minimal residual enhancement along the lateral right cerebellum and posterior petrous bone with a small amount of residual tumor within the right internal auditory canal (white arrow).
consisting of >1 neoplastic histology. Frassanito et al12 discussed different interactions between coexistent tumor types, specifically distinguishing collision tumors from tumor-to-tumor metastases. Collision tumors exhibit radiologic and histologic continuity with both tumor types being of intracranial origin, whereas tumor-to-tumor metastases constitute single radiologic lesions consisting of 1
extracranial and 1 intracranial tumor type, with 1 tumor in the context of another.12 Separately, Graffeo et al13 described “synchronous tumors” as those with 2grossly distinct tumor types and discrete masses; in contrast, “tumor-to-tumor metastasis” was defined as tumors with a grossly singular pathology with evidence of hematogenous spread of 1 tumor into another. Our case of hepatocellular
Figure 4. (A) Hematoxylin-eosin section shows nests of metastatic hepatocellular carcinoma within schwannoma at low magnification. (B) Immunohistochemistry with hepatocyte antigen decorates malignant cells in nest, confirming hepatic origin of carcinoma, at low magnification. (C) Immunohistochemistry with S-100 highlights benign spindle cells of
326
www.SCIENCEDIRECT.com
carcinoma metastasis to a vestibular schwannoma falls within the tumor-totumor metastasis category of both the Frassanito and Graffeo classification systems. Importantly, it should be considered as distinct from a collision tumor, as hepatocellular carcinoma is extracranial in origin. Intracranial metastasis of hepatocellular carcinoma is rare, with reported incidence rates of 0.2% 2.2%.14-16 However, the presence of an existing benign tumor has been postulated to provide an environment that may protect and, in fact, foster metastatic proliferation.17,18 Although the exact mechanism is unknown, several theories have been proposed for meningiomas harboring metastatic disease: A low metabolic rate provides a noncompetitive metabolic environment,19 increased collagen and lipid content serves as a nutrient-rich setting,20 enhanced vascularity increases the likelihood of malignant cells docking in the tumor itself,21 and the relative paucity of immune surveillance in the benign brain tumor may protect metastatic disease from immune destruction.22,23 Although schwannomas are not typically as well vascularized as meningiomas, these same mechanisms may underlie the metastasis of this patient’s hepatocellular carcinoma to vestibular schwannoma, particularly in the context of the vascularity of the CPA itself. Treatment of patients with suspected tumor-to-tumor metastasis must be approached on an individual basis. Crucial variables to consider are the staging and grading of the patient’s primary systemic
schwannoma between the nests of metastatic carcinoma at low magnification. As in many cerebellopontine angle schwannomas, characteristic Verocay bodies and Antoni A and B regions were present only focally and were not as prominently visualized as in peripheral schwannomas.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.05.106
CASE REPORT MICHAEL J. YANG ET AL.
malignancy and its response to previous chemotherapeutic and/or radiation treatments, as applicable. There are numerous other considerations before offering surgical resection of a suspected intracranial tumor-to-tumor metastasis, including the number and location of additional intracranial metastases and any medical comorbidities that may preclude a patient’s surgical candidacy. Our patient had extensive hepatocellular carcinoma at the time of presentation with ongoing gait instability, headache, and vertigo. He had recently failed sorafenib and showed potential progression of disease on nivolumab, a second-line immunotherapy for hepatocellular carcinoma. The decision was made to recommend operative intervention given his persistent symptoms, the possibility that the CPA mass was an isolated vestibular schwannoma, the presence of only 1 intracranial mass, and the fact he was medically stable aside from his known hepatic and adrenal disease. Adjuvant radiation was pursued after final pathology confirmed the presence of metastatic hepatocellular carcinoma in the right CPA mass. In their review of 46 patients with synchronous CPA tumors, Graffeo et al13 report a 27% overall rate of HouseBrackmann grade III-VI facial nerve dysfunction after CPA tumor resection, regardless of the tumor histopathologic classification. This rate is considerably higher than for isolated vestibular schwannomas, in which only 16% of patients in their own cohort of 267 patients had long-term House-Brackmann grade III-VI facial nerve paralysis.24 Although intraoperative facial nerve monitoring is increasingly used to minimize facial nerve injury, this is an important morbidity to discuss with patients before offering surgical resection. CONCLUSION Here we present a unique case of metastatic hepatocellular carcinoma to a vestibular schwannoma treated surgically with gross total resection. Intracranial tumor-to-tumor metastasis, although rare, is a well-documented phenomenon. It is distinguished from collision tumors in that it contains an extracranial neoplastic component with evidence of
INTRACRANIAL TUMOR-TO-TUMOR METASTASIS
hematogenous spread into an intracranial lesion. In patients with documented systemic cancer, tumor-to-tumor metastasis is important to consider in the evaluation and treatment of new symptomatic intracranial masses. Physicians should be aware of this possibility, particularly if considering radiosurgery for the treatment of an acoustic neuroma in a patient with systemic cancer.
definitions and proposal for classification. Acta Neurochir. 2011;153:1989-1993. 13. Graffeo CS, Perry A, Copeland WR III, et al. Synchronous tumors of the cerebellopontine angle. World Neurosurg. 2017;98:632-643. 14. Lim S, Lee S, Lim JY, et al. Hepatocellular carcinoma specific graded prognostic assessment can predict outcomes for patients with brain metastases from hepatocellular carcinoma. J Neurooncol. 2014;120:199-207. 15. Choi HJ, Cho BC, Sohn JH, et al. Brain metastases from hepatocellular carcinoma: prognostic factors and outcome. J Neurooncol. 2009;91:307-313.
REFERENCES 1. Nayak L, Lee EQ, Wen PY. Epidemiology of brain metastases. Curr Oncol Rep. 2012;14:48-54. 2. Bartelt S, Momm F, Weissenberger C, Lutterbach J. Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy: Prognostic factors and survival. World J Gastroenterol. 2004;10:3345-3348. 3. Fried BM. Inoculation of a meningioma by cancer cells from a bronchiogenic carcinoma. Am J Pathol. 1930;VI:47-52. 4. Richter B, Harinath L, Pu C, Stabingas K. Metastatic spread of systemic neoplasms to central nervous system tumors: review of the literature and case presentation of esophageal carcinoma metastatic to meningioma. Clin Neuropathol. 2017; 36:60-65. 5. Lu J, Khalil M, Hu W, Sutherland G, Clark A. Tumor-to-tumor metastasis: esophageal carcinoma metastatic to an intracranial paraganglioma. J Neurosurg. 2009;110:744-748. 6. Fukushima Y, Ota T, Mukasa A, Uozaki H, Kawai K, Saito N. Tumor-to-tumor metastasis: lung adenocarcinoma metastasizing to vestibular schwannoma suspected on preoperative [18F]fluorodeoxyglucose positron emission tomography imaging. World Neurosurg. 2012;78: 553.e9-553.e13.
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WORLD NEUROSURGERY 128: 324-327, AUGUST 2019
Conflict of interest statement: The authors report no conflict of interest, and no financial support was given. Received 21 March 2019; accepted 13 May 2019 Citation: World Neurosurg. (2019) 128:324-327. https://doi.org/10.1016/j.wneu.2019.05.106 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.
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