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Year : 2020  |  Volume : 3  |  Issue : 1  |  Page : 38-41

Collision tumor: Metastatic renal cell carcinoma to cerebellar hemangioblastoma in Von Hippel-Lindau disease

Department of Neurosurgery, Smt NHL Medical College and SVP Hospital, Ahmedabad, Gujarat, India

Date of Submission14-Feb-2020
Date of Acceptance04-Dec-2020
Date of Web Publication2-Jul-2020

Correspondence Address:
Dr. Nirmal L Desai
Department of Neurosurgery, Smt NHL Medical College and SVP Hospital, Ahmedabad - 380 007, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJNO.IJNO_3_20

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A tumor-to-tumor metastasis, also known as collision tumor, is a rare metastatic process in which primary malignant tumor metastasizes to another tumor. Meningioma has been implicated as the most common intracranial neoplasm to harbor metastasis, with donor tumor is the most common lung or breast tumor. Here, we describe the case of metastasis of renal cell carcinoma (RCC) to capillary hemangioblastoma (HAB) of the cerebellum in a patient of Von Hipple-Landau (VHL) disease. Patients with hereditary cancer syndromes may be at increased risk for the development of tumor-to-tumor metastasis. We review the literature about RCC to HAB metastasis and described the pathological and immunohistochemical findings of both the tumor to distinguish the two and to do clinical diagnosis of VHL syndrome.

Keywords: Collision tumor, renal cell carcinoma to hemangioblastoma, Von Hippel-Lindau syndrome

How to cite this article:
Soni TV, Desai NL. Collision tumor: Metastatic renal cell carcinoma to cerebellar hemangioblastoma in Von Hippel-Lindau disease. Int J Neurooncol 2020;3:38-41

How to cite this URL:
Soni TV, Desai NL. Collision tumor: Metastatic renal cell carcinoma to cerebellar hemangioblastoma in Von Hippel-Lindau disease. Int J Neurooncol [serial online] 2020 [cited 2022 Jun 27];3:38-41. Available from: https://www.Internationaljneurooncology.com/text.asp?2020/3/1/38/288790

  Introduction Top

In 1928, Cushing and Bailey introduced the term “hemangioblastoma” (HAB). It is a benign neoplasm that arises almost in the central nervous system (CNS). HABs accounting for 1%–2.5% of all intracranial neoplasms.[1] According to the World Health Organization (WHO), classification of tumors of the CNS and HABs is classified as mesenchymal nonmeningothelial Grade I neoplasm.[2] HABs occur either sporadically or as a manifestation of Von Hippel-Lindau (VHL) syndrome, inherited disorder characterized by tumors or tumor-like lesions developing in several organs. Renal cell carcinoma (RCC) accounts for approximately 9% of all metastases to the brain, have no particular site predilection, occurring in the brain stem and cerebellum as frequently as in any of the cerebral lobes.[3] Renal carcinoma is the cause of death in approximately one third and is present at autopsy in two-thirds of patients affected with VHL disease.[4] Here, we present the rare case of a 55-year-old male patient with VHL disease having metastasis of RCC to left cerebellar HAB.

  Case Report Top

A 55-year-old male patient presented with a positive family history (having renal and pancreatic cyst in sister) having vomiting and imbalance while walking for 15 months. Patient diagnosed of having left cerebellar tumor and bilateral renal mass consistent radiologically with a RCC and pancreatic mass. The patient was advised surgical intervention for cerebellar lesion, but he dined, and he was managed with steroids [Figure 1] and [Figure 2].
Figure 1: Axial contrast-enhanced MRI brain image showing solid cystic lesion with postcontrast enhancement in the posterior fossa. Radiologically, it looks like hemangioblastoma

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Figure 2: Axial contrast-enhanced CT of the abdomen image showing B/L renal lesion possibility of RCC

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The patient's neurological condition remains stable for the next few months, and again he developed difficulty in walking, weakness in the left lower limb, headache, and giddiness [Figure 3]. Clinical examination revealed ataxic gait with swaying to left side dysarthria. Repeat imaging suggestive of increase in size of the cerebellar lesion, development of hydrocephalus, and small new cerebral and cerebellar lesions and upper cervical spinal cord lesion [Figure 3].
Figure 3: CT brain contrast image (a and b) showing cerebellar lesion with contrast enhancement. (c and d) newly developed supra- and infratentorial lesions (e) MRI cervical spine showing the development of upper cervical spinal cord lesion

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The patient was undergone operative intervention in the form of the right ventriculoperitoneal shunt and excision of the left cerebellar lesion. Tumor was a purple red-colored nodule with cystic area. Postoperative stay was uneventful and was discharged on the 4th postoperative day. On the 10th postoperative day, he noticed worsening of left-sided weakness and gait ataxia and disorientation. Post-operative imaging shows near total excision of cerebellar lesion with development of new lesions in both the supratentorial and infratentorial regions. Renal and pancreatic lesions were of same size, but he developed new lesions in both lobes of the liver, bilateral adrenal glands, lungs and pleura possibility of metastasis of primary renal lesion [Figure 4] and [Figure 5].
Figure 4: Postoperative contrast-enhanced MRI brain showing excised cerebellar lesion with newly developed cerebral and cerebellar lesions

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Figure 5: CT chest and abdomen showing renal, pleural, lung, liver lesion possibility of metastasis of renal cell carcinoma

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Histopathological examination shows nodular proliferation of thin-walled capillaries-forming network with a large vessel. Stromal cells show a clear abundant cytoplasm [Figure 6]. One area with large cells with clear-to-eosinophilic cytoplasm and prominent nucleoli was seen [Figure 6]. Histopathological features were the mixed patterns of HAB and RCC. Hence, immunohistochemistry was done.
Figure 6: (a) Histopathological features of hemangioblastoma, (b) Histopathological features of renal cell carcinoma, (c) MIX pattern of both hemangioblastoma and renal cell carcinoma that the pathology cannot be differentiated

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Immunohistochemistry showed that epithelial tumor cell was positive for cytokeratin (CK), EMA, CD10, and PAX8 and was negative for glial fibrillary acidic protein (GFAP), alpha-inhibin, and thyroid-transcription factor-1. HAB-like cells were positive for S-100; some cells were positive for GFAP and negative for CK, EMA, CD10, alpha inhibin, and PAX8 suggestive of capillary HAB WHO Grade I and metastatic clear-cell renal carcinoma WHO Grade 3. The patient was managed conservatively with steroids and discharged after 5 days.

  Discussion Top

VHL is an inherited autosomal-dominant disorder. Eugene Von Hippel, an ophthalmologist, described hereditary hemangioblastoma involving the retina in 1904. In 1926, Arvil Lindau recognized the association between retinal, cerebellar, and visceral hemangioblastomas. The syndrome was later termed VHL disease. VHL revealed the loss of VHL gene on the short arm of chromosome 3 (3p25–26). The prevalence of VHL is between 1:35,000 and 1:53,000. The mean age of the diagnosis of retinal, cerebellar hemangioblastoma, and RCC is 25, 30, and 37 years, respectively.[5] The visceral tumors associated with VHL disease and having metastatic potential include RCCs, pheochromocytomas, and pancreatic neuroendocrine tumors.

Patients with mutant VHL gene are predisposed to develop HAB s of the cerebellum, brain stem and spinal cord, retinal angiomas, renal cysts and tumors, pancreatic cysts and tumors, pheochromocytomas, and epididymal cystadenomas. The diagnosis of VHL in a member of a family with VHL can be made if that individual develops any one of the cardinal manifestations of the disease (except renal cysts, which occur frequently in the normal population). The patient without a family history requires at least two of the cardinal manifestations which must include retinal or CNS involvement. Families that do not meet clinical criteria have been shown to have germ-line mutations.

Patients with HAB of the brain usually present with a longer history of neurological symptoms, followed by a sudden exacerbation. In most patients, the correct diagnosis is made after the appearance of acute signs of raised increased intracranial pressure. They are usually cystic with a solid mural nodule. Histopathologically, the most frequent differential diagnosis of hemangioblastoma is metastatic RCC, which may be associated with VHL.

Renal involvement in VHL is characterized by multiple, bilateral RCC, s and cysts. The youngest reported patient was 16 years old.[6] In VHL, men and women are equally affected with RCC in contrast to the male predominance in sporadic RCC. RCC appears to account for about 50% of deaths in VHL.[7] Usually, RCC in VHL is detected incidentally during computed tomography or ultrasound examination requested for other reasons, or while screening of VHL families. The histopathology of renal tumors is clear-cell carcinoma. Renal cysts may be the cancer-predisposing lesion in VHL-associated RCC. RCC can metastasize to the CNS, but a tumor in the CNS in a patient with VHL is likely to be a HAB, not a RCC metastasis. There is a positive correlation between RCC size and metastasis. RCCs <3 cm in diameter did not metastasize, whereas those >3 cm in diameter metastasized in 27% of patients.[8]

Pamphlett defined the criteria for the diagnosis of tumor-to-tumor metastasis. He established the following criteria: (1) the metastatic nidus must be at least partially enclosed by a rim of histologically distinct primary tumor tissue and (2) the existence of the primary carcinoma must be proven.[9] Fried first described a metastasis to a primary intracranial tumor (lung carcinoma to a meningioma).[10] Meningioma is the most common CNS recipient tumor (83% of metastasis to a CNS tumor), and breast and lung carcinomas are the most common metastatic tumors (79% of metastases to the CNS).[11] HABs associated with VHL disease are slow growing. Consequently, they are available to receive a metastasis for a prolonged period in the presence of other systemic malignancies, suggests that time is an important factor.[11] HAB being a vascular tumors provide an ideal environment for metastatic seeding. The impaired VHL protein disrupts fibronectin matrix assembly, making these tumors vulnerable to metastatic disease.[12]

The histological distinction between primary hemangioblastoma and an RCC metastasis in the cerebellum is often difficult, because both tumors have cells with vacuolated cytoplasm-containing intracytoplasmic glycogen and vascular stroma with associated reticulin fibers. Immunohistochemistry is most useful in differentiation between two pathologies. Antibodies to epithelial markers, such as CK CAM 5.2 and EMA, typically stain RCC but not HAB.[13] In addition, CD10 should be positive in RCC, but not in HAB cells.[14] In contrast, neural tissue markers such as NSE, GFAP, S100, neural cell adhesion molecule (CD56), and Leu-7 (CD57) are more often expressed by HAB cells.[13] Recently, antibodies for inhibin-alpha have been shown to preferentially stain HAB stromal cells, but not RCC cells.[15]

As imaging did not detect metastases to HABs, the diagnosis is based on the histopathological findings. Whenever CNS HABs are removed from patients with VHL disease who are known to have visceral malignancies, complete and detailed histological analyses should be performed on the tumors to determine whether they contain metastatic lesions. Continued follow-up imaging required for patients who undergo complete resection of an RCC metastasis to a HAB and harbor a primary RCC. In patients with VHL disease who have other types of metastases to HABs, decisions regarding the treatment of the primary tumor should be based on the histological characteristics of the tumor, the extent of the disease, and the completeness of resection of the HAB containing the metastasis.

  Conclusion Top

The recognition of tumor-to-tumor metastasis has increased in recent years. Tumor-to-tumor metastasis of RCC to HAB is rare, and its diagnosis is challenging. One should remain alert to distinguish the histological appearance of the two components and undergo immunohistochemical stains that can differentiate between them. The occurrence of metastatic RCC to HAB is a clinical diagnostic of VHL. Screening of the family member can be advised for the early diagnosis and management of family members to prevent undue complications.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Neumann H, Eggert H, Weigel K, Friedburg H, Wiestler O, Schollmeyer P: Haemangioblastomas of the Central Nervous System. J Neurosurg 1989;70:24-30.  Back to cited text no. 1
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol 2016;131:803-20.  Back to cited text no. 2
Gong J, Maia MC, Dizman N, Govindarajan A, Pal SK. Metastasis in renal cell carcinoma: Biology and implications for therapy. Asian J Urol 2016;3:286-92.  Back to cited text no. 3
Cooper JD, Arieff AI. Lindau disease treated by bilateral nephrectomy and hemodialysis. West J Med 1979;130:456-8.  Back to cited text no. 4
Abd Hamid D, Abdullah J, Ariff A, Muhamad M, Madhavan M. Cerebellar hemangioblastoma in a patient with von hippel-lindau disease: A case report. Malays J Med Sci 2000;7:43-8.  Back to cited text no. 5
Neumann HP, Zbar B. Renal cysts, renal cancer and von Hippel-Lindau disease. Kidney Int 1997;51:16-26.  Back to cited text no. 6
Maher ER, Yates JR, Harries R, Benjamin C, Harris R, Moore AT, et al. Clinical features and natural history of von Hippel-Lindau disease. Q J Med 1990;77:1151-63.  Back to cited text no. 7
Duffey BG, Choyke PL, Glenn G, Grubb RL, Venzon D, Linehan WM, et al. The relationship between renal tumor size and metastases in patients with von Hippel-Lindau disease. J Urol 2004;172:63-5.  Back to cited text no. 8
Pamphlett R. Carcinoma metastasis to meningioma. J Neurol Neurosurg Psychiatry 1984;47:561-3.  Back to cited text no. 9
Fried BM. Metastatic inoculation of a meningioma by cancer cells from a bronchogenic carcinoma. Am J Pathol 1930;6:47-52.  Back to cited text no. 10
Caroli E, Salvati M, Giangaspero F, Ferrante L, Santoro A. Intrameningioma metastasis as first clinical manifestation of occult primary breast carcinoma. Neurosurg Rev 2006;29:49-54.  Back to cited text no. 11
Ohh M, Yauch RL, Lonergan KM, Whaley JM, Stemmer-Rachamimov AO, Louis DN, et al. The von Hippel-Lindau tumor suppressor protein is required for proper assembly of an extracellular fibronectin matrix. Mol Cell 1998;1:959-68.  Back to cited text no. 12
Gouldesbrough DR, Bell JE, Gordon A. Use of immunohistochemical methods in the differential diagnosis between primary cerebellar haemangioblastoma and metastatic renal carcinoma. J Clin Pathol 1988;41:861-5.  Back to cited text no. 13
Polydorides AD, Rosenblum MK, Edgar MA. Metastatic renal cell carcinoma to hemangioblastoma in von Hippel-Lindau disease. Arch Pathol Lab Med 2007;131:641-5.  Back to cited text no. 14
Hoang MP, Amirkhan RH. Inhibin alpha distinguishes hemangioblastoma from clear cell renal cell carcinoma. Am J Surg Pathol 2003;27:1152-6.  Back to cited text no. 15


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]


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