Corneal carcinosarcoma in a patient with Fanconi anaemia

Abstract

A 31-year-old woman of Korean ancestry presented at surgery with a fleshy, pink limbal tumour in her left eye. Her second corneal graft had shortly before perforated despite wide lateral and medial tarsorrhaphies. When the tarsorrhaphies were opened, a corneal tumour became visible (Fig. 1A). The tumour was removed and the eye eviscerated. Histological examination revealed a carcinosarcoma originating at the corneal limbus, invading the eye (Fig. 1A). The tumour had a carcinomatous component (Fig. 1C), a spindle-cell sarcomatous (Fig. 1D) and a round-cell sarcomatous part (Fig 1D). (A) The limbal tumour covering part of the cornea. (B) Micrographic survey of tumour, a: carcinomatous part and b,c: sarcomatous parts. H&E stain, bar = 1 mm. (C) carcinomatous part in high magnification, H&E stain, bar = 100 μm. (D) spindle-cell sarcomatous part, H&E stain, bar = 100 μm. (E) round-cell sarcomatous part, H&E stain, bar = 100 μm, (F) Only the carcinomatous part, a: binds antibodies against the epithelial component cytokeratin, bar = 250 μm. (G) Both sarcomatous parts bind antibodies against the mesenchymal protein vimentin, bar = 250 μm. (H) All tumour parts react with Ki67 that indicates a high proliferation rate, most prominent in the round-cell sarcoma, bar = 250 μm. At the age of nine, the patient was diagnosed with Fanconi anaemia (FA) and with myelodysplastic syndrome at the age of 21. At 23 years, she received a bone marrow transplant from her fully HLA-matched brother. She developed severe graft-versus-host disease (GVH), predominantly in the skin and all mucous membranes, including the eyes. She developed severe dry eye syndrome with repeated corneal ulcers and pannus formations despite massive tear substitution and topical steroids. Also at the age of 23 years, she had bilateral cataract surgery. Postoperatively, she developed corneal melting and received bilateral tarsorrhaphies. At the age of 28, amniotic membranes were sutured to both corneas to prevent imminent perforation. The right cornea was subsequently transplanted twice and the left cornea three times. During the same years, she was surgically treated for carcinomas of the tongue and clitoris. The patient died at the age of 32 from a metastatic carcinoma of the uterus. Carcinosarcoma is a rare tumour that may originate from several tissues, for example the female genital tract, lungs, kidney, bladder, oesophagus, bladder and skin (Prakalapakorn et al. 2008). In the eye region, a carcinosarcoma most often originates in the lacrimal gland (Takahira et al. 2005). The occurrence of a corneo-conjunctival carcinosarcoma in a patient with FA has not been described before. Histologically carcinosarcomas have one component of malignant epithelial cells (carcinoma) and one mesenchymal component (sarcomatous) (Ni et al. 1992). The tumour in our patient appeared to have had its origin in tumour stem cells of the corneal limbus; however, two types, an epithelial and a mesenchymal stem cell cannot be excluded. The history of the patient should be taken into consideration. FA is characterized by a disrupted DNA repair cascade, which facilitates the development of neoplasia (Tischkowitz & Dokal 2004, and Tsilou et al. 2010). In addition, the preparations for the bone marrow transplantation by means of chemotherapy, the following GVH disease and the related dryness of the eyes all might have contributed to the formation of a mutagenic environment and possibly facilitated the development of this rare malignant tumour.