Penile extramammary Paget disease associated with urothelial carcinoma in situ: Case report and literature review

Abstract

Background: Extramammary Paget disease (EMPD) is an uncommon disease affecting older men and women. Clinically, it appears as a plaque lesion with an erythematous or leukoplakic background in regions with abundant apocrine glands such as female external genitalia, perineum, scrotum, and penis. Methods:We are presenting an 85-year-old patient with recurrent erythematous plaque lesions involving the penis and known to have urothelial carcinoma (UC) in situ of the bladder. A literature review of EMPD secondary to UC has been conducted through PubMed and Google Scholar search engines. Results:The histopathologic examination revealed a proliferation of Paget cells within the surface squamous epithelium. The lesional cells displayed vesicular nuclei, clear cytoplasm, and a positive staining for CK7, CK20, HER2, GATA3 as well as p40, and negative staining for SOX10, CK5/6, and CDX2. The literature review revealed 18 more cases of EMPD associated with UC, including 4 with non-invasive UC. Most of them were treated surgically, but the disease recurred in nine cases and death of disease was reported in at least four patients, all of them associated with invasive UC. Conclusion:The prognosis of penile EMPD seems to be dictated by the stage of the underlying UC.

Whole genome methylation sequencing reveals epigenetic landscape and abnormal expression of FABP5 in extramammary Paget's disease

“…Since the distal intergenic region does not contain the gene itself, nor the regulatory elements, transcription termination sites (TTS) and TSS of the genes, 23 we chose FABP5, the gene with the largest hypomethylation difference in the promoter region, for subsequent validation. Key pathogenic characteristics of Paget cells include the expression of CK7, CK20 and EMA, and immunohistochemistry and immunofluorescence identification of these proteins is typically regarded as a diagnostic technique for EMPD 8,24 . Using the newly collected three paired patient samples, we found that FABP5 was highly expressed in tumor tissues, and FABP5 was co‐located with CK7, CK20 and EMA that were reported as markers of EMPD 25 .…”

“…Key pathogenic characteristics of Paget cells include the expression of CK7, CK20 and EMA, and immunohistochemistry and immunofluorescence identification of these proteins is typically regarded as a diagnostic technique for EMPD. 8,24 Using the newly collected three paired patient samples, we found that FABP5 was highly expressed in tumor tissues, and FABP5 was co-located with CK7, CK20 and EMA that were reported as markers of EMPD. 25 In contrast, the expression of FABP5 was low in normal tissues of the same patient (Figure 2).…”

International case series of metastasis to penis

“…We did not consider these strictly to be metastases, since these cases are likely due to intraepithelial spread, not hematogenous. Nineteen other similar cases have been reported separately 11 …”