Purchase this article with an account.
Sepideh Siadati, Seyed Muhammed Haeri Hosseini, Jacob Light, Nicholas Mahoney, Esen K Akpek, Zelia Correa, Charles Eberhart; CDK6 amplification in conjunctival adenosquamous carcinoma. Invest. Ophthalmol. Vis. Sci. 2020;61(7):4670.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To describe histopathological and molecular features of in situ and invasive conjunctival adenosquamous carcinoma, as well as recent changes in nomenclature
Retrospective review of microscopic, immunohistochemical and molecular features of two cases of adenosquamous carcinoma diagnosed at our institution. Low and high risk human papilloma virus (HPV) were detected by RNA in situ hybridization. Next generation sequencing analysis interrogated mutations and copy number changes at 450 genetic loci associated with cancer.
Case 1 was a recurrent left eyelid tumor in a 61-year-old man from Kuwait. Resection of the lesion identified squamous differentiation in the superficial tumor, including an in situ component, with increasing degrees of gland formation in deeply invasive components. Alcian blue and mucicarmine stains confirmed the presence of mucin in both glands and cytoplasmic vacuoles. The tumor was immunopositive for CK7 and Ber-EP4, and negative for CK20 and adiopophilin. Low and high risk HPV testing was negative. Sequencing identified amplification of the CDK6 locus on chromosome 7, a mutation in BRCA2 (p.R2488G) reported to be pathogenic in some contexts, and alterations in ARID1B and TGFBR2 of unclear significance.Case 2 was a 79-year-old woman presenting with a conjunctival lesion growing into the cornea. Excisional biopsy revealed adenosquamous carcinoma in situ, with no invasive component. Small intracytoplasmic vacuoles, as well as scattered larger mucin filled spaces, were highlighted by mucicarmine and alcian blue. Tumor cells were diffusely positive for p53 and negative for p16; the Ki67 proliferation index was very high. Low-risk HPV was negative, while high-risk HPV was equivocal. Sequencing revealed amplification of the CDK6 and ERBB2 loci, and a mutation in TP53 (p.M246I).
Adenosquamous carcinoma is a malignant tumor which can arise in a range of organs. In the periocular region, this tumor was previously referred to as mucoepidermoid carcinoma, but its name was changed to conjunctival adenosquamous carcinoma in the 2019 World Health Organization Classification primarily due to a lack of intermediate cells. The genetic basis of adenosquamous carcinoma is unclear, and our findings suggest that amplification of the CDK6 locus may be a common driver. This is clinically significant as pharmacological inhibitors of the CDK6 complex are already in oncology clinical trials.
This is a 2020 ARVO Annual Meeting abstract.
This PDF is available to Subscribers Only