Jakobiec FA, Mendoza PR, Colby KA. Clinicopathologic and immunohistochemical studies of conjunctival large cell acanthoma, epidermoid dysplasia, and squamous papilloma. Am J Ophthalmol 2013;156(4):830-46.Abstract
PURPOSE: To evaluate clinicopathologically and immunohistochemically a spectrum of conjunctival squamous proliferations. DESIGN: Retrospective clinicopathologic study. METHODS: One large cell acanthoma, 7 epidermoid dysplasias, and 4 squamous papillomas were evaluated with microscopy and biomarkers Ki-67, p53, epithelial membrane antigen (EMA), Ber-EP4, AE1, AE3, and 8 individual cytokeratins. Normal associated conjunctiva served as a baseline for interpretation. RESULTS: The large cell acanthoma recurred 4 times but retained its benign histopathologic features. The cells were 2-3 times larger than the keratinocytes of the normal conjunctiva and did not display atypia. Immunohistochemistry revealed a low Ki-67 proliferation index (PI) in the large cell acanthoma compared with high indices in dysplasias and papillomas. p53 was negative in the nuclei of normal epithelium while positive in all neoplasms, most intensely in the dysplasias. Immunostaining showed similar staining patterns for cytokeratins in large cell acanthoma and normal conjunctiva, except for full-thickness CK14 positivity and CK7 negativity in the lesion. Dysplasias generally lost normal CK7 expression and frequently abnormally expressed CK17. The papillomas displayed a normal cytokeratin pattern but exhibited a higher than normal PI and weak p53 positivity. CONCLUSIONS: Conjunctival large cell acanthoma is a morphologically distinctive clonal entity with clinical and immunohistochemical phenotypic characteristics denoting a dysplasia of minimal severity. Because of recurrences without invasion, it requires treatment. Dysplasias exhibited more deviant biomarker abnormalities including frequent aberrant full-thickness CK17 positivity and CK7 negativity. The absence of major cytokeratin derangements in the squamous papillomas may be of ancillary diagnostic value for lesions displaying borderline cytologic features.
Jakobiec FA, Gragoudas ES, Colby KA. Biopsy of an anterior episcleral nodule as an aid in managing a ciliary body melanocytic tumor. Cornea 2013;32(8):1174-7.Abstract
PURPOSE: To demonstrate the value of a diagnostic biopsy of a fixed episcleral nodule overlying a uveal mass. METHOD: Clinicopathologic report with immunohistochemical investigations. RESULTS: B-scan ultrasonographic biomicroscopy disclosed in a 67-year-old man an asymptomatic placoid ciliary body tumor measuring 1.28 mm in thickness underlying a poorly pigmented, fixed episcleral nodule 0.56 mm in thickness. Biopsy of the episcleral nodule displayed benign nevus-type spindle cells with small nuclei, punctate nucleoli, no mitoses, and scattered melanophages. Immunohistochemistry demonstrated that the tumor cells were Ki67 negative (proliferation index, 0) and MART-1, HMB-45, and microphthalmia-associated transcription factor positive, all melanocytic markers. The melanophages but not the tumor cells were CD68 positive, a histiocytic marker. CONCLUSIONS: The results from biopsying an episcleral nodule can help to select among therapeutic options in managing an associated ciliary body tumor. A 1-year follow-up study and 3 sequential ultrasonographic studies in the current patient have failed to document the growth of the intraocular tumor, further confirming that it is a nevus. The excised epibulbar tumor has not recurred.
Huynh N, Stemmer-Rachamimov AO, Swearingen B, Cestari DM. Decreased vision and junctional scotoma from pituicytoma. Case Rep Ophthalmol 2012;3(2):190-6.Abstract
Pituicytomas are rare neoplasms of the sellar region. We report a case of vision loss and a junctional scotoma in a 43-year-old woman caused by compression of the optic chiasm by a pituitary tumor. The morphological and immunohistochemical characteristics of the tumor were consistent with the diagnosis of pituicytoma. The tumor was debulked surgically, and the patient's vision improved.
Daniels AB, Lee J-E, MacConaill LE, Palescandolo E, van Hummelen P, Adams SM, Deangelis MM, Hahn WC, Gragoudas ES, Harbour WJ, Garraway LA, Kim IK. High throughput mass spectrometry-based mutation profiling of primary uveal melanoma. Invest Ophthalmol Vis Sci 2012;53(11):6991-6.Abstract
PURPOSE: We assessed for mutations in a large number of oncogenes and tumor suppressor genes in primary uveal melanomas using a high-throughput profiling system. METHODS: DNA was extracted and purified from 134 tissue samples from fresh-frozen tissues (n = 87) or formalin-fixed, paraffin-embedded tissues (n = 47) from 124 large uveal melanomas that underwent primary treatment by enucleation. DNA was subjected to whole genome amplification and MALDI-TOF mass spectrometry-based mutation profiling (>1000 mutations tested across 120 oncogenes and tumor suppressor genes) using the OncoMap3 platform. All candidate mutations, as well as commonly occurring mutations in GNAQ and GNA11, were validated using homogeneous mass extension (hME) technology. RESULTS: Of 123 samples, 97 (79%, representing 89 unique tumors) were amplified successfully, passed all quality control steps, and were assayed with the OncoMap platform. A total of 58 mutation calls was made for 49 different mutations across 26 different genes in 34/98 (35%) samples. Of 91 tumors that underwent hME validation, 83 (91%) harbored mutations in the GNAQ (47%) or GNA11 (44%) genes, while hME validation revealed two tumors with mutations in EGFR. These additional mutations occurred in tumors that also had mutations in GNAQ or GNA11. CONCLUSIONS: The vast majority of primary large uveal melanomas harbor mutually-exclusive mutations in GNAQ or GNA11, but very rarely have the oncogenic mutations that are reported commonly in other cancers. When present, these other mutations were found in conjunction with GNAQ/GNA11 mutations, suggesting that these other mutations likely are not the primary drivers of oncogenesis in uveal melanoma.
Yonekawa Y, Kim IK. Epidemiology and management of uveal melanoma. Hematol Oncol Clin North Am 2012;26(6):1169-84.Abstract
Uveal melanoma is the most common primary intraocular malignancy in adults. The disease overwhelmingly affects white populations. Other risk factors include fair skin, light iris color, ancestry from northern latitudes, and ocular/oculodermal melanocytosis. Historically, enucleation was the definitive treatment of uveal melanoma, but brachytherapy and proton beam irradiation are now the most commonly used treatment methods. However, there are still no effective therapies against metastatic uveal melanoma, which is almost always fatal. Continued advances in understanding of the molecular mechanisms of uveal melanoma will facilitate the identification of prognostic markers and therapeutic targets.
Rankin JK, Jakobiec FA, Zakka FR, Foster SC. An improved approach to diagnosing and treating conjunctival mucoepidermoid carcinoma. Surv Ophthalmol 2012;57(4):337-46.Abstract
The current case of conjunctival mucoepidermoid carcinoma offers features that expand the biologic spectrum afforded by this tumor. More focused strategies should be developed for its earlier histopathologic diagnosis and improved management (historical recurrence rate of 85%). A 63-year-old woman with a history of rheumatoid arthritis and idiopathic sclerosing cholangitis developed scleral thinning, anterior chamber cells and flare, and uveal prolapse. Biopsies of the epibulbar lesion were initially misinterpreted as a squamous cell carcinoma but on review harbored CK7-positive cells and contained rare goblet cells brought out with Alcian blue and mucicarmine staining. Intraocular extension exhibited micro-and macrocysts with minimal goblet cells. Focal CK7 immunopositivity in any epibulbar squamous dysplasia or in invasive carcinoma should lead to suspicion of a mucoepidermoid carcinoma. Behaviorally aggressive or rapidly recurrent epithelial squamous tumors with "inflammatory" features or unusual clinical characteristics should be initially stained at multiple levels for the detection of parsimonious mucus secretion. Surgical options include wide excision and partial sclerectomy with cryotherapy for superficial invasion and/or interferon therapy. Results with radiotherapy and cryotherapy for deep scleral invasion have been unpredictable or unacceptable compared with surgery.