Uroplakin II Expression in Breast Carcinomas Showing Apocrine Differentiation: Putting Some Emphasis on Invasive Pleomorphic Lobular Carcinoma as a Potential Mimic of Urothelial Carcinoma at Metastatic Sites

Abstract

Uroplakin II antibody is exclusively specific for urothelial carcinoma. Nonurothelial carcinoma has not been reported to be immunoreactive for uroplakin II. In the present study, we hypothesized that breast carcinoma showing apocrine differentiation, such as invasive pleomorphic lobular carcinoma (IPLC) and apocrine carcinoma (AC), stains positive for uroplakin II. We identified 6 cases of IPLC between 2000 and 2014 by searching a computerized pathological database. We randomly selected 10 cases of each classic invasive lobular carcinoma (cILC) and AC and five cases of apocrine metaplasia (AM) that coexisted in a surgically resected breast carcinoma specimen. Immunohistochemistry was performed for uroplakin II, GATA3, CK7, CK20, and other representative markers positive for urothelial carcinoma. All cases of IPLC, AC, and AM, except those of cILC, showed immunoreactivity for uroplakin II. Poorly differentiated urothelial carcinoma sometimes shows similar morphology to IPLC with the following immunophenotype: CK7+, CK20-, GATA3+, and uroplakin II+. In the present study, this immunophenotype was observed in all the cases of IPLC and AC. Therefore, when studying metastatic, poorly differentiated carcinoma showing the aforementioned immunophenotype, we should consider the possibility of it being IPLC in addition to metastatic urothelial carcinoma.

Figure 1

Histological findings. (a) IPLC case 2: nuclear enlargement and eosinophilic cytoplasm observed in tumor cells (×400). (b) cILC case 2: nuclear enlargement of the tumor cells is modest compared with that of IPLC. Reduced cytoplasm in the tumor cells is observed (×400). (c) AC case 2: cytoplasmic abundance and eosinophilia of the tumor cells are more prominent than those of IPLC (×400). (d) AM case 3: the cytoplasmic abundance and eosinophilia of the constituent cells are conspicuous but the nuclei are less atypical than those of IPLC and AC (×400). IPLC: invasive pleomorphic lobular carcinoma; cILC: classic invasive lobular carcinoma; AC: apocrine carcinoma; AM: apocrine metaplasia.

Figure 2

Immunohistochemical findings. (a) IPLC case 3: immunopositivity for uroplakin II (score 3+) (×400). (b) cILC case 4: immunonegativity for uroplakin II (score 0) (×400). (c) AC case 4: immunopositivity for uroplakin II (score 2+) (×400). (d) AM case 3: immunopositivity for uroplakin II (score 3+). Note immunonegativity for normal breast epithelium (×400). (e) IPLC case 5: immunopositivity for GATA3 (score 3+) (×400). (f) cILC case 3: immunopositivity for GATA3 (score 3+) (×400). (g) AC case 8: immunopositivity for GATA3 (score 1+) (×400). (h) AM case 4: immunonegativity for GATA3 (score 0). Note immunopositivity for normal breast epithelium (×400). (i) IPLC case 3: scattered immunopositive tumor cells for p63 (×400). (j) IPLC case 3: scattered immunopositive tumor cells for p40 (×400). IPLC: invasive pleomorphic lobular carcinoma; cILC: classic invasive lobular carcinoma; AC: apocrine carcinoma; AM: apocrine metaplasia.