0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Research Letters |

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

Robert M. Verdijk, MD, PhD; Thomas van den Bosch, MD; Nicole C. Naus, MD, PhD; Dion Paridaens, MD, PhD; Cornelia M. Mooy, MD, PhD; Annelies de Klein, PhD
[+] 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.
Text Size: A A A
Published online

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.

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.

Place holder to copy figure label and caption
Graphic Jump Location

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).

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.

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.

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.

Banerjee SS, Harris M. Morphological and immunophenotypic variations in malignant melanoma.  Histopathology. 2000;36(5):387-402
PubMed   |  Link to Article
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):468-472
PubMed   |  Link to Article
Gelman BB, Trier TT, Chaljub G, Borokowski J, Nauta HJ. Oncocytoma in melanocytoma of the spinal cord: case report.  Neurosurgery. 2000;47(3):756-759
PubMed
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):81-83
PubMed   |  Link to Article
Jih DM, Morgan MB, Bass J, Tuthill R, Somach SC. Oncocytic metaplasia occurring in melanoma.  Semin Cutan Med Surg. 2004;23(1):73-79
PubMed   |  Link to Article
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):399-404
PubMed   |  Link to Article
Schlötzer-Schrehardt U, Jünemann A, Naumann GO. Mitochondria-rich epithelioid leiomyoma of the ciliary body.  Arch Ophthalmol. 2002;120(1):77-82
PubMed   |  Link to Article
Cunha SL, Lobo FG. Granular-cell myoblastoma of the anterior uvea.  Br J Ophthalmol. 1966;50(2):99-101
PubMed   |  Link to Article
Kilic E, van Gils W, Lodder E,  et al.  Clinical and cytogenetic analyses in uveal melanoma.  Invest Ophthalmol Vis Sci. 2006;47(9):3703-3707
PubMed   |  Link to Article
Hamperl H. Benign and malignant oncocytoma.  Cancer. 1962;15:1019-1027
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Graphic Jump Location

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).

Tables

References

Banerjee SS, Harris M. Morphological and immunophenotypic variations in malignant melanoma.  Histopathology. 2000;36(5):387-402
PubMed   |  Link to Article
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):468-472
PubMed   |  Link to Article
Gelman BB, Trier TT, Chaljub G, Borokowski J, Nauta HJ. Oncocytoma in melanocytoma of the spinal cord: case report.  Neurosurgery. 2000;47(3):756-759
PubMed
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):81-83
PubMed   |  Link to Article
Jih DM, Morgan MB, Bass J, Tuthill R, Somach SC. Oncocytic metaplasia occurring in melanoma.  Semin Cutan Med Surg. 2004;23(1):73-79
PubMed   |  Link to Article
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):399-404
PubMed   |  Link to Article
Schlötzer-Schrehardt U, Jünemann A, Naumann GO. Mitochondria-rich epithelioid leiomyoma of the ciliary body.  Arch Ophthalmol. 2002;120(1):77-82
PubMed   |  Link to Article
Cunha SL, Lobo FG. Granular-cell myoblastoma of the anterior uvea.  Br J Ophthalmol. 1966;50(2):99-101
PubMed   |  Link to Article
Kilic E, van Gils W, Lodder E,  et al.  Clinical and cytogenetic analyses in uveal melanoma.  Invest Ophthalmol Vis Sci. 2006;47(9):3703-3707
PubMed   |  Link to Article
Hamperl H. Benign and malignant oncocytoma.  Cancer. 1962;15:1019-1027
PubMed   |  Link to Article

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Data Supplement
Supplemental Content

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 2

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles