Keynote message

Prostate biopsy via the perineum is a common method to diagnose prostate cancer. A pros- tate biopsy specimen occasionally contains skin tissues. In the current case, EMPD was incidentally found in migrating skin tissues in the prostate biopsy. The present case sug- gests that clinicians should pay attention to migrating skin tissue that can contain important information.

Introduction

Prostate biopsy via the perineum is a standard method to diagnose prostate cancer. Although prostate biopsy specimens occasionally contain skin tissues, only the prostate tissue is consid- ered. In the present case, EMPD was incidentally found in migrating skin tissues in the pros- tate biopsy.

Case report

A 71-year-old male Japanese patient visited our hospital with a chief complaint of high PSA level (8.47 ng/mL). The patient was diagnosed with prostate cancer with a Gleason score of 3 + 3 by transperineal prostate biopsy, and active surveillance was planned. The next year, the patient underwent a 16-core transperineal repeat prostate biopsy according to the active surveillance protocol. Prostatic adenocarcinoma with a Gleason score of 6 was detected. However, one of the 16 cores contained skin tissue, and large, atypical cells with abundant pale mucinous cytoplasm in a single or nested fashion were observed within the epidermis (Fig. 1). These cells had d-PAS-positive intracytoplasmic mucin. Immunohistochemically, the cells were positive for cytokeratin 7 and negative for S-100, human melanin black-45, and PSA. EMPD was suspected, and careful examination of the patient’s skin revealed a faint erythematous lesion in the left perineum. The lesion was 50 9 35 mm, slightly elevated, and it exhibited a whitish color in its periphery with a poorly circumscribed border (Fig. 2). A two-stage surgery was planned. The primary surgery was a mapping biopsy, and the secondary surgery was radical resection. Outside of mac- roscopic boundaries were taken. The incision line was designed by connecting negative biopsy points. The lesion was resected at a depth of adipose tissue. Pathological exam- ination revealed tumor cells with abundant pale cytoplasm and large nucleoli. Dermal and vascular invasion was not observed. Based on these findings, the patient was diagnosed with EMPD and pT1N0M0 stage IA. At the 6-month follow- up, the patient did not have signs of recurrence or metastasis.

Discussion

The diagnostic process for this patient suggests two important clinical issues. First, early-stage EMPD was initially unde- tected by both the patient and urologists. Second, prostate biopsies may contain skin tissue. The clinical course of early- stage EMPD localized within the epidermis is indolent. How- ever, locally invasive EMPD with a tumor thickness ≥3 mm has a 5-year survival rate of 57%.1 Furthermore, distant metastasis is associated with 60% increase in mortality.2 Therefore, early diagnosis of EMPD is important.

In this case, neither the patient nor the urologist noticed EMPD until it was pathologically confirmed. There are sev- eral possible reasons for this finding. First, EMPD is a rare disease. Weng et al. analyzed the SEER database and reported a median age at EMPD diagnosis of 67.7 years.3 The results of a systematic review of transperineal prostate biopsies showed that the median age at biopsy in the group of prostate biopsies with antibiotics was 66 years.4 Although the age at EMPD diagnosis and the age at which prostate biopsy is performed are similar, EMPD is rare, with a reported incidence of 0.11/100 000 person-years in the Neth- erlands population study.5 Therefore, even urologists, who examine male vulvodynia more than other health profes- sionals, rarely encounter EMPD.

Second, the appearance and symptoms of EMPD are not disease-specific. Early-stage EMPD is characterized by multi- focal, well-circumscribed erythematous or leukoplakic pla- ques, or macules with occasional hyperpigmentation or hypopigmentation. While the majority of patients experience pruritus, approximately 10% of patients are asymptomatic.2 Because the clinical findings of EMPD overlap with those of several other diseases, the differential diagnosis for EMPD is very broad, leading to delays in diagnosis. According to Kang et al. and Ito et al., the time from symptom onset to diagnosis is 43.2 and 39.7 months, respectively.1,6 Our patient was asymptomatic, and the urologist did not carefully investigate the skin of the perineum. For these reasons, we could not detect EMPD initially. To date, only two reports of prostate biopsies revealing an unsuspected disease exist. In one report, the unsuspected disease was urothelial carcinoma7; in the other, it was cryptococcal prostatitis.8 There are no reports of EMPD diagnosed by prostate biopsy.

We encountered a rare case of skin cancer incidentally diagnosed by transperineal prostate biopsy. During a prostate biopsy, the focus is usually on suspicious lesions in the pros- tate based on digital rectal examination, echocardiography, and magnetic resonance imaging findings. However, our find- ings suggest that the skin, which is the site of the puncture, should be carefully examined. Further, a dermatologist should be consulted, or a pathological evaluation of a skin biopsy should be performed if an abnormality is detected.

Author contributions

Kengo Fujiwara: Writing – original draft. Takuma Kato: Writing – original draft; writing – review and editing. Emi Ibuki: Resources; writing – review and editing. Nachino Kimura: Resources; writing – review and editing. Yo Kaku: Resources; writing – review and editing. Takayoshi Miura: Resources; writing – review and editing. Hiroyuki Tsune- mori: Resources; writing – review and editing. Reiji Haba: Resources; writing – review and editing. Teruki Dainichi: Resources; writing – review and editing. Mikio Sugimoto: Supervision.

References

1. Ito T, Kaku Y, Nagae K et al. Tumor thickness as a prognostic factor in extra- mammary Paget’s disease. J. Dermatol. 2015; 42: 269–75.

2. St Claire K, Hoover A, Ashack K, Khachemoune A. Extramammary Paget disease. Dermatol. Online J 2019; 25.

3. Weng S, Zhu N, Li D et al. Clinical characteristics, treatment, and prognostic factors of patients with primary extramammary Paget’s disease (EMPD): a ret- rospective analysis of 44 patients from a single center and an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) database. Front. Oncol. 2020; 10: 1114.

4. Basourakos SP, Alshak MN, Lewicki PJ et al. Role of prophylactic antibiotics in transperineal prostate biopsy: a systematic review and meta-analysis. Eur. Urol. Open Sci. 2022; 37: 53–63.

5. Siesling S, Elferink MA, van Dijck JA, Pierie JP, Blokx WA. Epidemiology and treatment of extramammary Paget disease in The Netherlands. Eur. J. Surg. Oncol. 2007; 33: 951–5.

6. Kang Z, Zhang Q, Zhang Q et al. Clinical and pathological characteristics of extramammary Paget’s disease: report of 246 Chinese male patients. Int. J. Clin. Exp. Pathol. 2015; 8: 13233–40.

7. OliaiBR,KahaneH,EpsteinJI.Aclinicopathologicanalysisofurothelialcarcino- mas diagnosed on prostate needle biopsy. Am. J. Surg. Pathol. 2001; 25: 794–801.

8. Shah SI, Bui H, Velasco N, Rungta S. Incidental finding of cryptococcus on prostate biopsy for prostate adenocarcinoma following cardiac transplant: case report and review of the literature. Am. J. Case Rep. 2017; 18: 1171–80.