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Trial balloons of gene expression profiles of calloon cell melanoma predict the future

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By Warren R. Heymann, MD
Jan. 29, 2018

balloon cell melanoma
Satellite metastasis of balloon cell melanoma. Graft scar of melanoma and satellite bluish skin–colored indurated papules with pseudovesiculation (black arrow points to the papule examined with dermoscopy).
Credit: JAAD
The site of balloons is joyous; however, I am always nervous blowing them up, because of a nagging fear that they would explode in my face. Similarly, the histologic site of balloon nevus cells may bring a smile, but is tempered by the concern that the lesion could be a balloon cell melanoma.

Balloon cells are comparatively large, displaying central small basophilic nuclei with a clear, foamy cytoplasm. When balloon cells occupy at least 50% of nevus cells or melanoma, the lesion is called a balloon cell nevus (BCN) or balloon cell melanoma (BCM), respectively. Balloon cells are believed to be altered melanocytes formed by progressive vacuolization due to the enlargement and disintegration of melanosomes. Balloon cells may present with or without abundant pigment. Balloon cells have been observed in acquired nevi, Spitz nevi, blue nevi (common and cellular), combined nevi, halo nevi, dysplastic and nodal nevi. (1) There is no correlation of balloon cells and risk of malignant progression. (2)
Balloon cell nevi do not have distinctive clinical features. They are usually asymptomatic, brown, smooth papules, or polypoid lesions. Most frequently they are found on the head and neck, followed by the trunk and extremities. (3) Dermatoscopy suggests that the balloon cells correlate with either white (4) or yellow globules. (5). Balloon cells may be recognized by non-invasive imaging including optical coherence tomography and reflectance confocal microscopy. (6)

Balloon cell melanomas are rare lesions accounting for only 0.15% of melanomas. Their anatomic distribution mirrors that of BCN. BCM stains positive for S100, HMB-45, Melan-A, NK/1-C3, and MART-1. (7) The main histologic differential diagnoses of BCM include BCN, clear cell sarcoma, metastatic renal cell carcinoma, basal cell carcinoma, squamous cell carcinoma, and dermatofibroma. (8)
We are witnessing a revolution in melanoma diagnostics by the advances in gene expression signatures. Utilizing a gene expression signature evaluating 23 genes that are differentially expressed in malignant melanoma and benign melanocytic nevi by quantitative reverse transcription PCR, Ko et al, evaluated 182 samples including 99 primary cutaneous melanomas with proven distant metastases and 83 melanocytic nevi. They found that the gene expression score differentiated melanoma from nevi with a sensitivity of 93.8% and a specificity of 96.2%. The results of gene expression testing closely correlated with long-term clinical outcomes of patients with melanocytic neoplasms. The authors concluded that the gene signature adds valuable adjunctive information to aid in the accurate diagnosis of melanoma. (9)
Friedman et al, reported 2 women with BCM manifested by the dermatoscopic findings of a white-gray veil and dull yellow globules. Utilizing the gene expression described above, it was demonstrated that gene expression profiling yielded vital information by confirming the diagnosis of BCM, in these histologically borderline cases with minimal cytologic atypia. The authors conclude that a “gene expression profiling test may provide additional useful diagnostic information in cases that are difficult to interpret.” (10) This conservative conclusion belies that fact that in our professional lifetimes, molecular diagnosis will likely supplant classical microscopic diagnosis, with far greater precision. That will be the time to break out the balloons!

1. Huang YY, Vandergriff T. Balloon cell change in common blue nevus. J Cutan Pathol 2017; 44: 407-9.
2. Valdivielso-Ramos M, et al. Balloon-cell variant of the Spitz nevus. J Eur Acad Dermatol 2016; 30: 1621-2.
3. Martinez-Casimiro L, et al. Balloon cell naevus. J Eur Acad Dermatol Venereol 2009; 23: 236-7.
4. Jaimes N, et al. White globules correlate with balloon cell nevi nests. J Am Acad Dermatol 2011; 65: e119-20.
5. Cinotti E, et al. Yellow globules in balloon cell naevus. Australas J Dermatol 2013; 54: 268-70.
6. Oliveira A, Zalaudek I. Balloon cell naevus: New perspectives using high-definition optical coherence tomography with dermoscopic and reflectance confocal microscopy. J Eur Acad Dermatol Venereol 2015; 30: 1624-5.
7. Chavez-Alvarez S, et al. Balloon cell melanoma and its metastasis, a rare entity. Am J Dermatopathol 2017; 39: 404-10.
8. Hattori Y, et al. Balloon cell malignant melanoma in a young female: A case report and review of the literature. Case Rep Oncol 2016; 9: 262-6.
9. Ko JS, et al. Diagnostic distinction of malignant melanoma and benign nevi by a gene expression signature and correlation to clinical outcomes. Cancer Epidemiol Biomarkers Prev 2017; 26: 1107-1113.
10. Friedman BJ, et al. Association of clinical, dermoscopic, and histopathologic findings with gene expression in patients with balloon cell melanoma. JAMA Dermatol 2018; 154: 77-81.

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