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Figure. Ultrasonographic, whole-mount, histologic, and immunohistochemical appearance of the tumor. A B-scan of the tumor (A) and a whole-mount hematoxylin-eosin–stained section (B) of the left eye show a mushroom-shaped subretinal mass in the posterior pole. C, The tumor was exclusively composed of a nested and trabecular pattern of polygonal epithelioid cells with distinct borders and a granular eosinophilic cytoplasm that sometimes contained brown pigment. The nests and trabeculae were surrounded by a delicate capillary network. Nuclei were enlarged with coarse open chromatin and prominent irregular nucleoli (hematoxylin-eosin, original magnification ×400). D, The cells stained positive for the melanocytic marker HMB-45 (original magnification ×400).

Figure. Ultrasonographic, whole-mount, histologic, and immunohistochemical appearance of the tumor. A B-scan of the tumor (A) and a whole-mount hematoxylin-eosin–stained section (B) of the left eye show a mushroom-shaped subretinal mass in the posterior pole. C, The tumor was exclusively composed of a nested and trabecular pattern of polygonal epithelioid cells with distinct borders and a granular eosinophilic cytoplasm that sometimes contained brown pigment. The nests and trabeculae were surrounded by a delicate capillary network. Nuclei were enlarged with coarse open chromatin and prominent irregular nucleoli (hematoxylin-eosin, original magnification ×400). D, The cells stained positive for the melanocytic marker HMB-45 (original magnification ×400).

1.
Banerjee SS, Harris M. Morphological and immunophenotypic variations in malignant melanoma.  Histopathology. 2000;36(5):387-402PubMedArticle
2.
Jih DM, Morgan MB, Bass J, Tuthill R, Somach S. Oncocytic metaplasia occurring in a spectrum of melanocytic nevi.  Am J Dermatopathol. 2002;24(6):468-472PubMedArticle
3.
Gelman BB, Trier TT, Chaljub G, Borokowski J, Nauta HJ. Oncocytoma in melanocytoma of the spinal cord: case report.  Neurosurgery. 2000;47(3):756-759PubMed
4.
Kacerovska D, Sokol L, Michal M, Kazakov DV. Primary cutaneous signet-ring cell melanoma with pseudoglandular features, spindle cells and oncocytoid changes.  Am J Dermatopathol. 2009;31(1):81-83PubMedArticle
5.
Jih DM, Morgan MB, Bass J, Tuthill R, Somach SC. Oncocytic metaplasia occurring in melanoma.  Semin Cutan Med Surg. 2004;23(1):73-79PubMedArticle
6.
Vancura RW, Thomas JH, Jewell WR, Damjanov I. Bilateral oncocytic malignant melanoma in axillary lymph nodes without evidence of an extranodal primary.  Ultrastruct Pathol. 2005;29(5):399-404PubMedArticle
7.
Schlötzer-Schrehardt U, Jünemann A, Naumann GO. Mitochondria-rich epithelioid leiomyoma of the ciliary body.  Arch Ophthalmol. 2002;120(1):77-82PubMedArticle
8.
Cunha SL, Lobo FG. Granular-cell myoblastoma of the anterior uvea.  Br J Ophthalmol. 1966;50(2):99-101PubMedArticle
9.
Kilic E, van Gils W, Lodder E,  et al.  Clinical and cytogenetic analyses in uveal melanoma.  Invest Ophthalmol Vis Sci. 2006;47(9):3703-3707PubMedArticle
10.
Hamperl H. Benign and malignant oncocytoma.  Cancer. 1962;15:1019-1027PubMedArticle
Research Letters
Nov 2011

Histopathologic, Immunohistochemical, Ultrastructural, and Cytogenetic Analysis of Oncocytic Uveal Melanoma

Author Affiliations

Author Affiliations: Departments of Pathology (Drs Verdijk and Mooy), Ophthalmology (Drs van den Bosch and Naus), and Clinical Genetics (Dr de Klein), Erasmus MC University, and Rotterdam Eye Hospital (Drs van den Bosch and Paridaens), Rotterdam, the Netherlands.

Arch Ophthalmol. 2011;129(11):1501-1502. doi:10.1001/archophthalmol.2011.312

The histological findings of malignant melanoma may be highly variable, and the tumor can mimic many other neoplasms.1 Oncocytic change is defined histologically by abundant, eosinophilic, finely granular cytoplasm due to densely packed mitochondria. Oncocytic change has rarely been described in dermal nevi,2 meningeal melanocytoma,3 cutaneous melanoma,4,5 or metastatic melanoma.6 To our knowledge, we give the first description of exclusively oncocytic uveal melanoma.

Report of a Case

A 73-year-old man visited the outpatient department of ophthalmology with signs of a paracentral scotoma, decreased vision, and metamorphopsia in his left eye for 1 month. Best-corrected visual acuity was 40/40 OD and 20/40 OS. On dilated funduscopic and ultrasonographic examination of the left eye, a mushroom-shaped hypopigmented subretinal mass was seen superior and temporal to the fovea with a thickness of 7.1 mm, a diameter of 11.4 mm, and medium to low internal reflectivity (Figure, A). No atypical cutaneous pigmented lesions were observed. Systemic radiologic evaluation revealed no metastatic lesions. The patient opted for enucleation. After a follow-up of 24 months, there were no signs of metastases.

Sections of the eye confirmed a mushroom-shaped tumor (Figure, B) exclusively composed of a trabecular arrangement of epithelioid cells with abundant, finely granular, eosinophilic cytoplasm (Figure, C). Mitotic figures were present at 2 per 10 high-power fields. Intracytoplasmic brown pigment stained positive with Masson-Fontana stain. The cytoplasm stained positive with periodic acid–Schiff stain with resistance to diastase treatment. Vascular mimicry with a closed loop pattern was present. The tumor did not show extrascleral extension. Tumor cells stained positive for Melan-A, HMB-45 (Figure, D), and tyrosinase, confirming melanocytic lineage. They stained negative for keratin A1/A3, CD56, chromogranin, and synaptophysin, excluding epithelial (neuroendocrine) metastasis.

Ultrastructural studies on formalin-fixed, paraffin-embedded tumor tissue that was deparaffinized, postfixated with osmium tetroxide, and re-embedded in Epon (Hexion Specialty Chemicals, Inc, Danbury, Connecticut) showed cytoplasm densely packed with mitochondria and sparse melanosomes (eFigure). No epithelial features were observed.

Fluorescence in situ hybridization experiments on tumor tissue indicated 2 copies of chromosomes 1, 3, 6, and 8. Multiplex ligation-dependent probe amplification testing with the Salsa P027 uveal melanoma kit (MRC-Holland, Amsterdam, the Netherlands) confirmed this normal disomic state for a total of 31 different regions tested on multiple chromosomes. Single-nucleotide polymorphism array analysis revealed no copy number alterations or regions of heterozygosity on any of the chromosomes. These investigations have been carried out according to the tenets of the Declaration of Helsinki.

Comment

The many histologic faces of melanoma include primary and metastatic carcinoma, neuroendocrine tumors, sarcoma, leukemia, and germ cell tumors.1 Intraocular oncocytoma has been considered in the differential diagnosis of mesectodermal leiomyoma of the ciliary body.7 A granular cell tumor of the iris and ciliary body has been described.8 The diagnosis of choroidal melanoma and exclusion of other cancers was based on the tumor's characteristic mushroom shape, positive immunohistochemical staining for HMB-45, Melan-A, and tyrosinase, and a 2-year follow-up without evidence of another primary cancer.

The prognostic significance of oncocytic change in uveal melanoma is not clear. Our case displayed unfavorable histological prognostic parameters in tumor size, epithelioid cell type, and vascular pattern. This was not corroborated with cytonuclear negative parameters as no cytogenetic aberrations were present. Earlier, it was reported that cytogenetic aberrations were detected in 80% (59 of 74 cases) of a series of uveal melanoma.9 In cutaneous melanoma, no prognostic significance could be determined.5 Oncocytic change is generally proposed to be a reactive degenerative adaptation10; however, the fact that no cytogenetic changes were observed in this tumor poses the possibility of a distinct tumor variant as opposed to a degenerative change.

In conclusion, to our knowledge we give the first description of an oncocytic uveal melanoma that is not to be mistaken histologically for other tumors, including metastatic carcinoma.

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Article Information

Correspondence: Dr Verdijk, Department of Pathology, Erasmus MC University, PO Box 2040, 3000 CA, Rotterdam, the Netherlands (r.verdijk@erasmusmc.nl).

Author Contributions: Drs Verdijk and van den Bosch contributed equally to this article.

Financial Disclosure: None reported.

References
1.
Banerjee SS, Harris M. Morphological and immunophenotypic variations in malignant melanoma.  Histopathology. 2000;36(5):387-402PubMedArticle
2.
Jih DM, Morgan MB, Bass J, Tuthill R, Somach S. Oncocytic metaplasia occurring in a spectrum of melanocytic nevi.  Am J Dermatopathol. 2002;24(6):468-472PubMedArticle
3.
Gelman BB, Trier TT, Chaljub G, Borokowski J, Nauta HJ. Oncocytoma in melanocytoma of the spinal cord: case report.  Neurosurgery. 2000;47(3):756-759PubMed
4.
Kacerovska D, Sokol L, Michal M, Kazakov DV. Primary cutaneous signet-ring cell melanoma with pseudoglandular features, spindle cells and oncocytoid changes.  Am J Dermatopathol. 2009;31(1):81-83PubMedArticle
5.
Jih DM, Morgan MB, Bass J, Tuthill R, Somach SC. Oncocytic metaplasia occurring in melanoma.  Semin Cutan Med Surg. 2004;23(1):73-79PubMedArticle
6.
Vancura RW, Thomas JH, Jewell WR, Damjanov I. Bilateral oncocytic malignant melanoma in axillary lymph nodes without evidence of an extranodal primary.  Ultrastruct Pathol. 2005;29(5):399-404PubMedArticle
7.
Schlötzer-Schrehardt U, Jünemann A, Naumann GO. Mitochondria-rich epithelioid leiomyoma of the ciliary body.  Arch Ophthalmol. 2002;120(1):77-82PubMedArticle
8.
Cunha SL, Lobo FG. Granular-cell myoblastoma of the anterior uvea.  Br J Ophthalmol. 1966;50(2):99-101PubMedArticle
9.
Kilic E, van Gils W, Lodder E,  et al.  Clinical and cytogenetic analyses in uveal melanoma.  Invest Ophthalmol Vis Sci. 2006;47(9):3703-3707PubMedArticle
10.
Hamperl H. Benign and malignant oncocytoma.  Cancer. 1962;15:1019-1027PubMedArticle
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