Brain Pathology Case of the Month - July 2012


Balloon cell melanoma, metastatic to cerebellum


Metastatic melanoma is one of the most common nervous system metastatic tumor types encountered by pathologists, but this balloon cell variant is exceedingly unusual as a CNS metastasis and can be challenging to diagnose correctly, especially at the time of intraoperative consultation or when the slides from the original cutaneous tumor are not available for direct comparison, both of which were true in this case.

Even in primary cutaneous sites, balloon cell melanoma is one of the rarest variants, with more than 95% of primary cutaneous melanomas fitting into one of the more common, classic subtypes (8). Balloon cell melanoma has been the subject of only sporadic case reports, even as a primary lesion (5, 9). This case illustrates the additional challenges when this rare subtype is encountered as a metastasis, especially to the CNS and especially to the cerebellum, where either metastatic renal cell carcinoma or hemangioblastoma are more likely.

There have been few reports of metastatic balloon cell melanoma and even fewer cases which involve the central nervous system (CNS). One prior report documented two cases balloon cell melanoma arising from the choroid of the eye with associated metastatic disease (6). Balloon cell melanoma has also been reported as a primary lesion of the CNS arising from the leptomeninges (1). We were able to identify only a single prior case report of metastatic balloon cell melanoma to the cerebellum (3).

This case underscores the value in requesting pathology reports, and optimally, the actual glass slides from any known primary lesion on a patient suspected of harboring a metastatic brain tumor. Only after obtaining, and reviewing this patient's actual slides from his original skin lesion was it apparent that the primary cutaneous melanoma had contained a subpopulation of tumor cells with a balloon cell phenotype (Figure 6). By the time of the cerebellar metastasis, the tumor had evolved into a pure balloon cell appearance.

Pathologically, balloon cell melanoma is characterized by nests and sheets of large, abundantly vacuolated cells that result in a "clear-cell" appearance on microscopic analysis (5, 7). Balloon cell melanomas typically label with several or all of the immunohistochemical markers for melanoma, S100, Melan-A and HMB-45. There was strong immunoreactivity for S100 and Melan-A in our case.

The exact nature of the ballooning change remains incompletely understood but was originally thought to represent a degenerative process. Recent studies propose that the balloon cells are, in fact, metabolically active, as they demonstrate abundant ribosomes and RNA on electron microscopy as well as positive immunohistochemical labeling for HMB-45 (an antigen with an established predilection for metabolically active and neoplastic melanocytes) (5). Of note, our case was HMB-45 negative. Balloon cell melanomas possess the same propensity for metastasis as other melanomas and the extent of ballooning does not influence the metastatic potential. Recent theories, therefore, attribute the ballooning change to some sort of aberrancy in the maturation of melanosomes rather than a degenerative change (5).

The incidence of melanoma in the United States is rising (4) and associated morbidity and mortality for CNS metastatic disease are high (10). Chemotherapy and radiotherapy only provide modest clinical benefit, with approaches utilizing a combination of surgery and chemotherapy offering the longest survival advantage (2). As always, correct treatment is predicated on accurate pathological diagnosis.


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  2. Bafaloukos D, Gogas H (2004) The treatment of brain metastases in melanoma patients. Cancer Treat Rev. 30(6):515-20.
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  6. Khalil MK (1983) Balloon cell malignant melanoma of the choroid: ultrastructural studies. Br J Ophthalmol 67(9):579-84.
  7. Magro CM, Crowson AN, Mihm MC (2006) Unusual variants of malignant melanoma. Mod Pathol 19 Suppl 2:S41-70.
  8. Perniciaro C (1997) Dermatopathologic variants of malignant melanoma. Mayo Clin Proc 72(3):273-9.
  9. Peters MS, Su WP (1985) Balloon cell malignant melanoma. J Am Acad Dermatol 13(2 Pt 2):351-4.
  10. Sampson JH, Carter JH Jr, Friedman AH, Seigler HF (1998) Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma. J Neurosurg 88(1):11-20.

Contributed by Marlin Dustin Richardson, MD; Hilary Somerset, MD; B.K. Kleinschmidt-DeMasters, MD; Allen Waziri, MD

International Society of Neuropathology