GATA3 expression in clear cell adenocarcinoma of the lower urinary tract: a potential diagnostic pitfall


Background Clear cell adenocarcinoma of the lower urinary tract (CCACLUT) is a rare primary malignant neoplasm with heterogenous morphology. There is a paucity of data in the literature regarding its immunohistochemical profile.

Methods The immunohistochemical features (extent and intensity) of a multinational cohort of CCACLUT were evaluated with comparison between clear cell adenocarcinoma of the female genital tract (CCACFGT, tissue microarray) and nephrogenic adenoma (NA).

Results 33 CCACLUT (24 female, 9 male; mean age 59 years) were collected. CCACLUT most commonly arose from the urinary bladder (26/33, 78%), particularly from the trigone (10/33, 30.3%) followed by the urethra (8/33, 22%). All 12 NA cases were located at the urinary bladder, whereas the most common CCACFGT location was the ovary (29/56, 52%). None of the CCACLUT patients had, intestinal metaplasia, NA, or urothelial carcinoma. One patient had concurrent endometriosis of the sigmoid colon. Most frequently observed morphology in CCACLUT was papillary/tubulocystic (9/3; 27.3%), followed by papillary/tubular (6/33; 18.2%) and papillary/solid (5/33; 15.2%). GATA3 expression was significantly higher in CCACLUT (18/33, 54.5%) and NA (6/12, 50%), when compared to CCACFGT cases 6/56, 11.7%)(p = 0.001 and p = 0.022, respectively). The extent of GATA3 was significantly higher in CCACLUT group (19.2 ± 16.6%) than the other groups (9.6 ± 22.5% in NA and 2.6 ± 9% in CCACFGT group) (p = 0.001). 4/33 patients (12.1) had weak, 10/33 patients (30.3%) had moderate, and 4/33 patients (12.1%) had strong GATA3 intensity in CCACLUT group. In NA group, one patient (8.3%, 1/12) had weak, one patient (8.3%, 1/12) had moderate and 4 patients (33.3%, 4/12) had strong GATA3 intensity. Most cases (CCACLUT 29/33, 88%; NA 11/12, 92%; CCACFGT 46/56, 82.1%) had positive Napsin A expression, by which CCACLUT had significantly more cases with Napsin A expression (p = 0.034). p63 was consistently negative in all cases (30/33 (91.9%) CCACLUT; 12/12 (100%) NA; 42/56 (75%) CCACFGT. Ki67 (MIB) proliferation index was significantly higher in CCACLUT group (54.6 ± 21%) when compared to NA group (4.5 ± 2.7%) and CCACFGT group (35.5 ± 25.8%) (p = 0.001).

Conclusion CCACLUT has consistent GATA3 expression, which may cause challenge in the diagnosis of urothelial carcinoma but can be used to distinguish CCACLUT from CCACFGT.

Cite As
Akgul, M., Humble, R., Osme, A., Yuce, S., Kocak, E. N., Najafzadeh, P., Sangoi, A., Pattnaik, N., Mishra, S., Sharma, S., Shaker, N., Kaushal, S., Baisakh, M., Lightle, A. R., Balzer, B. L., Xiao, G.-Q., MacLennan, G. T., Osunkoya, A. O., Parwani, A., … Mohanty, S. K. (2022). GATA3 expression in clear cell adenocarcinoma of the lower urinary tract: A potential diagnostic pitfall. Diagnostic Pathology, 17(1), 87.
Diagnostic Pathology
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