COW-2021-36

Invasive urothelial carcinoma, clear cell (glycogen-rich) type

The tumour exhibited a mostly solid sheet-like and focal nested growth pattern. It was composed of polygonal cells with small to medium sized hyperchromatic nuclei, irregular nuclear borders and inconspicuous nucleoli for the most part. Occasional cells with markedly enlarged hyperchromatic nuclei, prominent nucleoli and irregular borders were present. The most striking feature was the ample clear cytoplasm in more than 95% of the cells. Mitotic figures and apoptotic bodies were easily identified. There was no papillary or tubulocystic architecture and no eosinophilic globules were identified. Focally there was pagetoid proliferation of similar clear cells in the overlying urothelium and tumour invaded into the muscularis propria (not shown). The cells were PAS positive, diastase-sensitive. They were diffusely positive for cytokeratin AE1/AE3, CK7 and GATA-3. CK20 and p63 displayed patchy positivity. PAX-8, mammoglobin and GCDFP-15 were negative. Given the morphological and immunohistochemical features a diagnosis of invasive high grade urothelial carcinoma with clear cell (glycogen-rich) features was rendered. No divergent differentiation and no other subtype/histologic variant histology were present.

Differential diagnoses included primary bladder and metastatic neoplasms. The patient did not have a history of clear cell renal cell carcinoma and the GATA-3+/PAX-8- immunoprofile excluded this possibility. Müllerian type clear cell carcinoma of the urinary bladder (clear cell adenocarcinoma) typically shows morphological pattern similar to those seen in the female genital tract, including tubulocystic, papillary with hyalinised fibrovascular cores and diffuse patterns. There former two patterns were not present. Hobnail cells and eosinophilic globules that can be present in Müllerian type carcinoma were not present. Also they are typically PAX-8+/GATA-3-. The positive cytokeratin excluded other neoplasms with clear cytoplasm, such as PEComa and metastatic melanoma. Lipid-rich urothelial carcinoma is characterised by large lipoblast-like cells with one or more clear cytoplasmic vacuoles that indent the nucleus. Also they contain lipid and not glycogen are therefore PAS negative. The patient did not have a history of other primary carcinomas, such as breast (also GATA-3+/CK7+) and the tumour was negative for mammoglobin and GCDFP-15.

Clear cell (glycogen-rich) urothelial carcinoma is a rare subtype of urothelial carcinoma included in the 2016 World Health Organisation classification of tumours of the urothelial tract. Less than 20 cases originating in the bladder have been reported in the literature. It is significantly more common in male than females (16:1). The mean age is 69 years. The prognostic significance is still unclear due to the subtype’s rarity.

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Laurence Galea
Department of Anatomical Pathology, Melbourne Pathology (Sonic Healthcare), Victoria, Australia

Scott Donellan
Department of Urology, Monash Health, Victoria, Australia

urinary bladder

Urothelial carcinoma, clear cell, glycogen-rich