Accepted Manuscript Case Report: A Comparative Report on Intracranial Tumor-to-Tumor Metastasis and Collision Tumors Sohail Syed, David I. Karambizi, Amanda Baker, Darren M. Groh, Steven A. Toms PII: S1878-8750(18)30829-5 DOI: 10.1016/j.wneu.2018.04.109 Reference: WNEU 7945 To appear in: World Neurosurgery Received Date: 10 January 2018 Revised Date: 16 April 2018 Accepted Date: 17 April 2018 Please cite this article as: Syed S, Karambizi DI, Baker A, Groh DM, Toms SA, Case Report: A Comparative Report on Intracranial Tumor-to-Tumor Metastasis and Collision Tumors, World Neurosurgery (2018), doi: 10.1016/j.wneu.2018.04.109. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT Toms 1 Case Report: A Comparative Report on Intracranial Tumor-to-Tumor Metastasis RI PT and Collision Tumors Sohail Syed1, David I. Karambizi5, Amanda Baker4, Darren M. Groh3, SC Steven A. Toms1,2 M AN U Department of Neurosurgery1; Normal Prince Neurosciences Institute2; Department of Neuropathology3; Department of Radiology4; Warren Alpert Medical School of Brown TE D University5; Brown University: 222 Richmond Avenue Providence, RI 02903, USA Corresponding Author: EP Steven A. Toms, MD Rhode Island Hospital AC C 593 Eddy St Providence, RI 02903, USA Tel: (410) 793-9175 Fax: (401) 606-4012 Email: Steven.Toms@lifespan.org ACCEPTED MANUSCRIPT Toms 2 Key words: Collision tumors, Tumor-to-tumor metastasis, Glioblastoma, Meningioma, Perfusion magnetic resonance (MR) imaging, Magnetic resonance (MR) spectroscopy. RI PT Abbreviations used: CT, MRI, FLAIR, GBM, GFAP, TTF, Cho, Cr, NAA , FDG PET, AC C EP TE D M AN U SC NSCLC, MUC16, CA125, wnt ACCEPTED MANUSCRIPT Toms 3 Abstract: AC C EP TE D M AN U SC RI PT Background: The incidence of two distinct tumor types occupying the same anatomical location is rarely observed and may be accounted for by two separate mechanisms: Tumor to tumor metastasis and “collision” tumors where two adjacent tumors invade one another. These rare phenomena arise from distinct mechanisms, which may impact their preoperative recognition, surgical approach, and postoperative care. We will review two cases, highlighting their identification and perioperative management. Case descriptions: In case 1, a 71-year-old patient with history of sphenoid wing meningioma presented with headache, nausea, vomiting and was found to have a mass with meningioma and glioblastoma (GBM) characteristics. In case 2, a 61-year-old male with worsening dysmetria in the setting of unintentional weight loss, presented with multiple masses in the pelvis, abdomen, lung, and brain. The brain masses were classified as meningioma with intra-tumoral metastatic adenocarcinoma foci. Conclusion: Preoperative recognition of collision tumor and tumor-to-tumor metastasis is imperative for surgical planning including selecting regions for tissue biopsy and goals of care. Meticulous evaluation of history and imaging, and thorough pathological analysis allows for effective diagnosis and optimal patient outcomes. ACCEPTED MANUSCRIPT Toms 4 Introduction SC RI PT The anatomical co-localization of distinct tumors is a rare occurrence. Two such phenomena are presented in this report: a tumor-to-tumor metastasis and a collision tumor. These tumor types are often mistakenly used interchangeably in current literature. Collision tumors are generally characterized by the co-localization of two distinct malignancies arising within the same organ and growing into one another [1]. In contrast, a tumor-to-tumor metastasis is a tumor composed of a primary recipient mass into which a hematogenous metastatic donor arrives and establishes a secondary cancer [2]. The low prevalence of these intracranial tumor types is evidenced by the limited volume of reports in clinical publications, with approximately 30 cases reported on collision tumors and fewer than 100 reports on tumor-to-tumor metastasis over the past century [1- 4]. TE D M AN U Given their hyper-vascularization and relatively high incidence intracranially, meningioma are the most commonly implicated intracranial neoplasms in both metastasis and collision tumors [4,5,6]. For a tumor to be classified as a tumor-to-tumor metastasis, the following criteria must be met: 1) the donor metastasis must be partially enclosed by a recipient benign primary neoplasm of the brain 2) the metastatic neoplasm must be shown to originate from a known primary carcinoma [1]. In a tumorto-tumor metastasis mass, the recipient tumor, commonly a meningioma, most frequently receives metastatic foci from donor breast and lung cancer [5,7,8]. There have also been reports on metastatic foci originating from renal cell, prostate and thyroid carcinomas [1,5]. In comparison, a collision tumor is most typically the result of a tumor such as a meningioma forming adjacent to another intracranial tumor such as a schwannoma or pituitary adenoma and a craniopharyngioma [9,10]. The most commonly encountered collision tumor constitutes a meningioma and an astrocytoma [11,12,13]. AC C EP Though both phenomena have been independently described in previous literature, they have seldom been juxtaposed in a single comprehensive, comparative study. The main objectives of this case report are to compare patient presentations, imaging findings, and medical/surgical management of these lesions as well as to discuss the underlying mechanism behind these rare intracranial tumors. Case Summaries Case 1: Collision Tumor Case The first patient is a 71-year-old female with known history of right sphenoid wing meningioma, who presented initially to the emergency department with approximately 1 week of persistent headache, nausea, and dizziness. Physical examination revealed no focal neurological deficits. Patient was initially seen at an outside hospital where non-contrast computed tomography (CT) brain revealed a new right parieto-occipital mass. The patient underwent a magnetic resonance imaging (MRI) of the brain, showing a heterogeneously enhancing mass with cystic ACCEPTED MANUSCRIPT Toms 5 EP TE D M AN U SC RI PT components, as well as possible intraventricular involvement. As per radiology, differential included primary malignancy, lymphoma, and atypical meningioma. Patient was initially taken for stereotactic biopsy from which pathology revealed likely meningioma. Given patient’s severe edema and mass effect, the patient underwent a craniotomy and resection of mass. Intraoperatively, a firm lesion was encountered in the atrium of the lateral ventricle. Surrounding the lateral ventricle was a soft, hypervascular lesion with necrosis. Pathology confirmed both an intraventricular meningioma component as well as a GBM. The patient had a benign post-operative course other than a visual field loss (a left inferior quadrantanopia) and underwent radiation therapy and concomitant temozolomide therapy for the GBM. She did well for the first 9 months postoperatively, before moving out of the region and being lost to follow-up. Case 2 Tumor-to-tumor Metastasis Case The second patient is a 61year-old male, non-smoker, who presented to the emergency department with worsening dysmetria over two weeks as well as a 15lbs unintentional weight loss and poor exercise tolerance. Patient initially presented at an outside hospital where a non-contrast CT brain revealed a right-sided parasagittal mass with edema. CT of the chest, abdomen, and pelvis revealed a spiculated lung mass as well as liver lesions. MRI brain was obtained to further characterize the lesion and revealed a heterogeneously enhancing parasagittal mass with encasement of the sagittal sinus without any occlusion as well as a second remote site of osseous involvement of the left middle skull base was noted. Given history of lung mass, the primary diagnosis was likely metastatic disease. Patient underwent biopsy of his liver lesions, which revealed adenocarcinoma. Given this finding we elected to offer patient surgical resection of his parietal mass. Patient underwent bilaterally craniotomies overlying the affected region for resection. Patient operative course was without complication. Intraoperative pathological specimens revealed meningioma with intra-tumoral metastasis of patient’s adenocarcinoma. The patient underwent chemotherapy for his lung primary lesion and brain radiotherapy. One year postoperatively, he is free of disease. Proposed Mechanisms for Collision Tumors and Tumor-to-Tumor Metastasis AC C The exact mechanisms underlying the rare co-localization of these intracranial tumors have not yet been characterized. However, few potential mechanisms have been proposed to elucidate how collision tumors occur and how malignancies may metastasize to an intracranial mass. The most recently suggested mechanism driving tumor-to-tumor metastasis involves the co-expression of molecular markers MUC16 and mesothelin in meningioma with intratumoral adenocarcinoma [15]. Adenocarcinomas are the most likely metastatic masses to ascend to intracranial meningioma [1,14]. Mesothelin, which is normally found on peritoneal, pericardial, and pleural mesothelium, has increased expression in meningioma. MUC16 or CA125 is a transmembrane, glycoprotein, mucin protein that is markedly found on metastatic adenocarcinoma [15, 16,19]. MUC16 has high affinity for mesothelin. The latter interaction between MUC16 ACCEPTED MANUSCRIPT Toms 6 M AN U SC RI PT and mesothelin is believed to play an integral role in facilitating the migration of metastatic adenocarcinoma to the brain [17,18,19]. It is however important to also note the potential, concurrent role of other metastatic processes such as alterations in expressions of metalloproteinases, e-cadherin levels and increased relative blood flow to meningioma. [20,24,26]. Furthermore, various criteria render meningioma an ideal recipient for tumor metastasis: 1) meningioma are very slow growing tumors, providing ample time for metastasis to develop and spread 2) there is increased potential for hematogenous spread due to hypervascularity 3) meningioma lack immune response to metastasis and hence permits their growth [32]. Therefore, meningiomas are a favorable milieu for metastasis. If one were to refer to Paget’s proposed “soil and seed” hypothesis, meningioma represent a perfect soil or environment for metastases implantation. Briefly put, the seed and soil hypothesis maintains that a metastatic tumor cell may circulate to regions that are physiologically and biologically favorable for its implantation and development. Despite its robust barrier and a less well-characterized lymphatic drainage, the brain is considered an attractive destination (soil) for metastasis (seeds). Further understanding of the role of the perivascular niche and epigenetic mechanisms involved in metastasis will aid in the elucidation of preventative and therapeutic options for patients with brain metastases[40, 41, 31]. AC C EP TE D Though the pathogenesis of collision tumors remains unclear there is a host of proposed postulates enumerating the circumstances that make this tumor type possible. Some studies suggest that collision tumors are incidental and purely a result of statistical chance [21]. Others maintain that a histologically distinct intratumoral neoplasm may arise within a primary tumor secondary to prior surgery, trauma, or radiation therapy [22]. Lastly, an adjacent primary tumor, commonly a meningioma, may induce nearby cells to transform into distinct tumor types [6,23]. Transformations may be facilitated by certain driving genes/genetic changes that predispose brain tissues to tumorigenesis as well as via intracellular cross talk through mechanisms of communication such as exosomes [42]. Though there are a multitude of genetic mutations and effector protein alterations that may drive oncogenesis, some of the wellestablished tumorigenic pathways mutations are found in the wnt signaling and P53 pathways [33]. Genetic mutations in the wingless-related integration site (wnt) protooncogene pathway ranging from alterations in signaling/effector molecules such as APC and B-catenin to downregulation of e-cadherin are shown to play a significant role in tumorigenesis [34,35]. Down regulation of the key tumor suppressor p53 is known to facilitate oncogenesis. Cross talks between p53 and wnt signaling pathways have most recently been proposed [36]. Therefore, it is possible that intracranial tumors may induce tumorigenic mutations or epigenetic alterations in signal transduction pathways in adjacent brain parenchyma, thus facilitating the formation of tumor adjacent to the primary tumor. Continued growth of the adjacent neoplasms eventually coalesces into the collision tumors. Radiologic Considerations There are few reports discussing the radiologic features of co-localizing tumors, which allow for the preoperative identification of these entities to aid in ACCEPTED MANUSCRIPT Toms 7 M AN U SC RI PT planning surgery and therapy. Meningiomas, which are the most implicated tumor types in both tumor-to-tumor metastasis and tumor collisions, generally appear as welldemarcated, intense homogenous contrast enhancing lesions on MRI and CT [32,38]. It has been reported that the presence of heterogeneous enhancement, mushroom pattern and irregular margins may be indicative of harbored metastasis [38]. Furthermore, foci of intense enhancement on a background of moderate enhancement on CT/MRI have been shown to pre-operatively identify tumor-to-tumor metastasis in some patients [39]. However, the reliability of these findings is questionable given that benign meningiomas are known to occasionally contain necrotic tissue and cyst. Therefore, there is no definite correlation between MRI/CT imaging pattern and histological diagnostics [32,38,39]. Ultimately, conventional anatomical imaging modalities such as CT and MRI, cannot always differentiate amongst intracranial masses, thus requiring more precise and valid pre-operative means of tumor type diagnosis. Physiology based neuro-imaging such as dynamic susceptibility weighted enhanced contract perfusion MR and MR spectroscopy represents noninvasive means of specifically characterizing and differentiating tumor types [26]. TE D Perfusion MR imaging relies on regional hemodynamic differentiation based on tumor types microvasculature whereas MR spectroscopy depends on metabolic composition of the tumors. This allows for noninvasive imaging-based differentiation between extra-axial tumors such as meningioma/ metastases and intra-axial tumor masses [26,27]. Due to the hyper-vascularity relative to mucin-filled metastasis, meningioma show a greater T2 intensity drop and therefore greater relative blood volume compared to metastases [27]. In some cases, peak height and percentage of signal recovery intensity derived from perfusion MR can play a crucial in the differentiation of similarly appearing malignant tumors, such as GBM and metastasis [30]. AC C EP Furthermore, with MR spectroscopy disparate tumor types have different metabolites composition. Generally, most tumors, including metastasis, have increased choline (Cho) with decreased creatine (Cr) and N-acetyl-aspartate (NAA). Gliomas possess significantly increased Cho and lipid that correlates with tumor grading [28,29]. Metastases, like high-grade gliomas, tend to have high Cho, however the latter have more lipid formation in comparison. Meningioma and other extra-axial tumors can be differentiated from other tumor types due to very low levels of NAA [29]. Ultimately, even with such excellent imaging modalities, histopathologic diagnosis in conjunction with patient history remains the golden standard for tumor type evaluation. Discussion In the two cases described in this report, preoperative suspicion of collision tumor and tumor-to-tumor metastasis were entertained, facilitating surgical planning. Case one, the meningioma / GBM collision tumor, shows distinct features on MRI suggesting the presence of distinct tumor types. Non-contrasted CT upon emergency room presentation showed a hyperdense lesion with calcified flecks and extensive vasogenic edema suggestive of meningioma or metastasis (Fig. 1A). T2 weighted MRI ACCEPTED MANUSCRIPT Toms 8 RI PT demonstrated a hypointense solid intracentricular lesion capped by a mixed intensity lesion with extensive edema (Fig. 1B). Contrast enhancement illustrated the solidly enhancing central, intraventricular core with a multicystic, enhancing parenchymal lesion (Fig. 1C). Although the patient had undergone biopsy showing meningioma, it was not felt that the brain parenchymal lesion was compatible with meningioma and possibly represented a malignant tumor such as lymphoma, metastasis, or, more likely, GBM and the patient underwent definitive craniotomy and gross total resection of both the intraventricular meningioma and the surrounding GBM (Fig. 1D.). M AN U SC Pathology showed two distinct lesions. The meningioma was WHO Grade 1 transitional type with multiple whorls of tumor cells and no mitoses or other atypical features (Fig. 2A). The parenchymal lesion surrounding the atrium of the lateral ventricle demonstrated hypercellularity, pleomorphism and geographic necrosis consistent with GBM (Fig 2B). When the two tissues were stained for glial fibrillary acidic protein, the meningioma (top of slide) was largely negative while the GBM component at the bottom was strongly positive for GFAP (Fig. 2C). EP TE D In the second case, the patient had both clinical and radiographic clues that the lesion was not a simple parasagittal meningioma. First, the patient had unexplained 15pound weight loss over the past several months. MRI showed bony calvarial erosion and extensive edema consistent with meningioma on FLAIR sequences. However, there were mixed intensity areas within the lesion not consistent with cyst formation typically seen in a meningioma (Fig 3A). Sagittal contrast enhanced MRI shows differential enhancement within the lesion and poorly defined borders (Fig. 3B). Given the clinical suspicion for atypical meningioma or metastasis, a chest, abdomen, and pelvis CT was performed. The axial lung windows demonstrated a mass in the right upper lobe consistent with lung primary (Fig 3C). Given the edema, mass effect, and lack of diagnosis, a decision was made to debulk the lesion to establish diagnosis and improve the existing mass effect on the brain. One year after surgery and radiotherapy, the patient remains disease free. (Fig. 3D). AC C The tumor-to-tumor metastasis pathological examination showed many bland meningothelial cells surrounded by a large cell pleomorphic tumor with many mitotic figures (Fig. 4A). The large cells stained positive for antibody to TTF-1 (Fig. 4B), confirming the suspicions of a lung cancer primary in this patient with abrupt weight loss and a lung lesion. Diagnosis of collision tumor can have significant management implications perioperatively. The nature of diagnostic management may appropriately expand when a previously thought to be CNS primary reveals to involve a metastatic focus. An expanded imaging regimen may require additional CT imaging, FDG PET and scintigraphy may be warranted given associated clinical concerns in the setting of solid malignancy like NSCLC [43]. In cases of hematopoietic malignancies, bone marrow biopsy may be required as well to assess for systemic involvement [44]. Post diagnosis, care must be coordinated with the appropriate hematology and/or oncology teams to ACCEPTED MANUSCRIPT Toms 9 arrange for appropriate work up, management and continued surveillance of the systemic disease/metastatic disease. RI PT Comprehensive and systemic review of 175 cases reported to date on these rare intracranial tumor lesions demonstrates that approximately 1/3 of all such reported cases are collision tumors and about 2/3 are tumor-to-tumor metastasis [2, 3 ,4 5, 8, 10, 13, 49-131] . The most prevalently reported intracranial collision type is the meningioma/astrocytoma combination, constituting a little less than 1/3 or of all reported intracranial collision cases [13, 49-62]. Other comparatively less common but fairly reported collision cases are meningioma/schwannoma and pituitary adenoma/craniopharyngioma combinations [63-78]. The most common intracranial tumor-to-tumor metastases are the breast cancer or lung cancer to meningioma combinations [2, 5, 7, 8, 79-119 ]. The most prevalent donors, which contribute in more than half of all tumor-to-tumor metastasis cases, are lung and breast carcinoma; while the most common recipients are meningioma, comprising more than 3/4 of all recipients [2, 5, 7, 8, 79-131]. Surgical AC C EP TE D M AN U SC planning may be complicated by pathology as well. Highly vascular tumors may benefit from pre-operative angiographic embolization or intraoperative glue/cement based embolization prior to surgical resection [45]. 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ACCEPTED MANUSCRIPT Toms 24 FIGURE LEGENDS SC RI PT Figure 1: 71-year-old female with known history of meningioma who presented with headache and dizziness. Glioblastoma multiforme and meningioma were surgically proven. A-B, Axial unenhanced CT (A), axial T2 weighted (B) images show a large predominantly solid mass containing specks of calcium as well as multiple cystic areas and extensive vasogenic edema. Abnormal signal extends into the splenium of the corpus callosum. Axial contrast-enhanced T1-weighted images (C) show homogenous enhancement of the solid component corresponding to known meningioma as well as ring-enhancement of the cystic components and subependymal enhancement suggestive of a centrally necrotic, invasive glioblastoma multiforme. Postoperative axial contrast-enhanced T1-weighted MR images show a gross total resection of both lesions (D). M AN U Figure 2: Pathology of Case 1 showed two distinct lesions. The meningioma component was WHO Grade 1 transitional type with multiple whorls of tumor (A). The parenchymal lesion surrounding the atrium of the lateral ventricle demonstrated hypocellularity, pleomorphism and geographic necrosis consistent with GBM (B). The meningioma (top of slide) was largely negative while the GBM component at the bottom was strongly positive for GFAP (C). EP TE D Figure 3: 61-year-old male with dysmetria and weight loss. Metastatic adenocarcinoma involving meningioma proven at biopsy. A and B, Axial FLAIR (A) and sagittal contrast-enhanced T1-weighted (B) images show a midline heterogeneously enhancing mass centered on the parieto-occipital sulcus with extensive edema and osseous destruction of the inner table of the calvarium. The mass encases the superior sagittal sinus. An axial unenhanced CT image of the chest (C) demonstrates a spiculated right lower lobe mass consistent with primary lung adenocarcinoma. One year postoperatively, sagittal contrast-enhanced T1-weighted MRI shows that the patient remains free of intracranial disease (D). AC C Figure 4: Case 2 pathological examination showed many meningothelial cells surrounded by a large cell pleomorphic tumor with many mitotic figures (A). The large cells stained positive for antibody to TTF-1 (B), confirming the suspicions of a lung cancer primary. ACCEPTED MANUSCRIPT Table 1. Intracranial Tumor-to-Tumor Metastases Total Cases (67) Total Cases (108) RI PT Intracranial Collision Tumors Case Prevalence Case Prevalence [13] [49-62] [63-70] [71-78] [supplemental] Breast Carcinoma to Meningioma (31) Lung Carcinoma to Meningioma (19) Renal Cell Carcinoma to Hemangioblatoma (13) Others (45) SC Meningioma/Astrocytoma (19) Pituitary Adenoma/Craniopharyngioma (10) Schwannoma/Meningioma (10) Others (28) Contributing Tumor Subtype [5][7][79-104] [2][8] [105-118] [119-130] [supplemental] Contributing Tumor Subtype Donors M AN U Common Contributors Meningioma (39) Pituitary Adenoma (21) Schwannoma (12) Craniopharyngioma (11) Others [supplemental] Breast Carcinoma (34) Lung Carcinoma (24) Renal Cell Carcinoma (21) Prostate Adenocarcinoma (10) Others (21) Recipients Meningioma (81) Hemangioblastoma (15) Others (12) AC C EP TE D Table 1. The top half of the table denotes highest percent prevalence of reported intracranial collision tumors and tumor-to-tumor metastasis cases by tumor type combination. The bottom half shows degree of tumor subtypes involvement in reported intracranial collision tumor cases and donor/recipient percent prevalence in reported tumor-to-tumor metastasis. Note: numbers in parenthesis represents number of cases. ACCEPTED MANUSCRIPT Table 2. Supplemental Content Intracranial Collision Tumors Intracranial Tumor-to-Tumor Metastases Total Cases Total Cases (67) (108) Case Prevalence Case Prevalence Common Cases Breast Carcinoma to Meningioma (31) Lung Carcinoma to Meningioma (19) Renal Cell Carcinoma to Hemangioblatoma (13) Others (28) [3] [10] [131-153] Meningioangiomatosis/Meningioma (2) Pleomorphic Xanthoastrocytoma/Oligodendroglioma (2) Pituitary/Gangliocytoma (2) Meningioma/Pituitary Adenoma (3) Pituitary Adenoma/ Astrocytoma (1) Pituitary Adenoma/Ganglioglioma (2) Pituitary Adenoma/Plasmocytoma (1) Pituitary Adenoma/Chondroma (1) Pituitary Adenoma/Lymphoma (1) Meningioma/Ependymoma (1) Meningioma/Gangliocytoma (1) Meningioma/Introsseous Lipoma (1) Anaplastic Meningioma/Papillary Meningioma (1) Meningioma/CNS lymphoma (1) Meningioma/Hemangiopericytoma (1) Ependymoma/Hemangioblastoma (1) Solitary Fibrous Tumor/astrocytoma (1) Supratentorial Primitive Neuroectodermal Tumor/astrocytoma (1) schwannoma/Atypical Teratoid and Rhabdoid (1) Schwannoma/Neurofibroma (1) Pontine glioma/Cerebellar Pontine Angle Epidermoid tumor (1) Brainstem Squamous Cell Carcinoma/Epidermoid Tumor (1) Others (46) [4] [5][26] [154-192] Renal Cell Carcinoma to Meningioma (7) Breast Carcinoma to Schwannoma (2) Lung Carcinoma to Schwannoma (2) Lung Carcinoma to Astrocytoma (3) Lung Carcinoma to Ependymoma (1) Papillary Thyroid Carcinoma to Anaplastic Meningioma (1) Thyroid carcinoma to Meningioma (1) Cervical Carcinoma to Meningioma (1) Esophageal Carcinoma to Meningioma (1) Prostatic Adenocarcinoma to Meningioma (9) Pituitary Carcinoma to Meningioma (1) Rectal Adenocarcinoma to Meningioma (1) Colorectal Carcinoma to Meningioma (3) Schwannoma to Meningioma (1) Melanoma to Meningioma (3) Melanoma to Schwannoma (1) Leukemia to Meningioma (1) Thyroid Carcinoma Pituitary Adenoma (1) Thyroid Carcinoma and B-Cell Lymphoma to Brain (1) Pancreatic Neuroendocrine Tumor to Hemangioblastoma (1) Breast Carcinoma to Oligodendroglioma (1) Colon Cancer to Oligodendroglioma (1) Melanoma to Central Neurocytoma(1) Contributing Tumor Subtype Contributing Tumor Subtype SC M AN U TE D EP AC C Common Contributors: Meningioma (39) Pituitary Adenoma (21) Schwannoma (12) Craniopharyngioma (11) RI PT Common Cases Meningioma/Astrocytoma (19) Pituitary Adenoma/Craniopharyngioma (10) Schwannoma/Meningioma (10) Donors Common Donors Breast Carcinoma (34) Lung Carcinoma (24) Renal Cell Carcinoma (21) Prostate Adenocarcinoma (9) Others (21) Melanoma (5) Colorectal Carcinoma (5) Thyroid Carcinoma (4) Cervical carcinoma (1) Esophageal Carcinoma (1) Pancreatic Neuroendocrine Tumor(1) Schwannoma (1) Pituitary Carcinoma (1) B-cell Lymphoma (1) Leukemia (1) Recipients Common Recipients Meningioma (81) Hemangioblastoma (15) Others (12) Schwannoma (4) Astrocytoma (3) Oligodendroglioma (2) Ependymoma (1) Pituitary Adenoma (1) Central Neurocytoma (1) ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT Table 2. Supplemental Content AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT Highlights: RI PT SC M AN U TE D - EP - Collision tumors represent two distinct, geographically co-localized tumors growing into one another Tumor-to-tumor metastasis involves the hematogenous spread of a malignant tumor to the parenchyma of an anatomically distant tumor Preoperative identification of these entities aids in surgical planning and successful treatment of these rare tumors AC C -