Uncommon case of metastatic prostate cancer developing cutaneous metastasis

Abstract

We report a case of a man in his early 70s with a known history of prostate adenocarcinoma who presented with an undiagnosed skin lesion on his right lower lateral neck 6 years after his metastatic cancer diagnosis. The painless lesion was pink, lobulated and soft. The differential diagnosis included both primary and metastatic tumours. On resection, the histology and immunohistochemical profile of the lesion were consistent with metastatic prostate cancer. He has been managed with multiple lines of therapy since then due to progressive disease. In the 18 months, since his resection, however, he has had no clinical evidence of recurrent cutaneous metastases.

Background

Prostatic adenocarcinoma is a common malignancy in men, with bone being the most common metastatic site.¹ Cutaneous involvement by prostatic adenocarcinoma is infrequent, accounting for approximately 0.3% of all prostate cancer metastases.² When it occurs, the genitoinguinal or abdominal skin is usually involved; distant cutaneous metastasis is rare.³ Such metastases can be confused with several dermatological conditions owing to a variety of presentations including papules or nodules (sometimes multiple), zosteriform eruptions, polypoid lesions and haemorrhagic vesicles.³

Case presentation

The patient we present was diagnosed with localised prostate cancer 9 years ago after a routine digital rectal exam revealed a suspicious lesion is his left prostate lobe. His PSA was 3.8 μg/L at that time. After an initial prostate biopsy, he went on to have a radical prostatectomy (figure 1A). Pathology showed prostatic adenocarcinoma pT3bN1, Gleason score of 8/10 (4, 4) (figure 1B), 30% involvement of tissue and 1/16 lymph nodes involved. Resection margins were negative but there was seminal vesicle involvement, focal extra prostatic spread, perineural and lymphovascular invasion as shown in figure 1C. He did well postoperatively.

Figure 1.

The prostatectomy resection specimen showing invasive prostatic adenocarcinoma with infiltrative tumour cells growing predominantly in cribriform arrangement, Gleason grade 8 (4,4) (B). Evidence of perineural invasion (green arrow), vascular invasion (blue arrow) and extraprostatic extension (Epe; red arrows) are noted (C).

At his initial presentation, his other medical history included: glaucoma, osteoarthritis and dyslipidaemia with no relevant medications.

Investigations

Over the 2 years proceeding his initial diagnosis, his prostate-specific antigen (PSA) increased gradually from 0.17 μg/L to 0.89 μg/L representing biochemical recurrence. He was started on androgen deprivation therapy (leuprolide) then and his PSA became undetectable from the treatment. However, his PSA started rising again reaching a level of 11.11 μg/L approximately 2 years post-therapy initiation. At that time had evidence of bone metastasis on bone scan. He was started on abiraterone acetate and prednisone with an initial decline in his PSA followed by a slow rise a year later, and thus, prednisone was changed to dexamethasone resulting in a further PSA decline reaching undetectable levels. Despite this response, his PSA started to climb up again reaching 23.57 μg/L the following year. Imaging at that time showed oligoprogression in the left iliac bone and he went on to receive radiotherapy to this site.

Eighteen months ago, his PSA had increased to 35.7 μg/L and bone scan and CT imaging showed progressing bone lesions and new pelvic and retroperitoneal lymphadenopathy. At the same time, he presented to his family doctor with what he described as a ‘skin tag’ on the right lower lateral neck region that had been present for 1 month. On physical examination, the lesion was non-tender, soft, pink, mobile and lobulated. The lesion was resected (gross specimen: 1.5×1.2×0.6 cm). On low power (figure 2A), there was a nodular dermal neoplasm (figure 2B) which on higher power comprised atypical and mitotically active glandular cells with cribriform (figure 2C) and sheeted growth pattern. As shown in figure 2D, there was positive immunohistochemical staining with NKX3.1, a marker highly specific for prostatic adenocarcinoma.⁴ Hence, the overall picture was consistent with prostate cancer metastasised to skin.

Figure 2.

The skin excision specimen at low magnification (A) showing two nodules of a dermal neoplasm. On higher magnification, the tumour shows nodular (B) and cribriform architecture (C). A focus of lymphovascular invasion is noted with the blue arrow (C). (D) highlights positive NKX3.1 immunohistochemical staining.

Differential diagnosis

On histopathological examination, the nodule showed malignant features with marked cellular atypia and a high mitotic count raising suspicion for a malignant neoplasm. Cutaneous adnexal carcinoma was considered as a differential diagnosis based on its dermal location and its histopathological picture alone which showed cribriform architecture of the cells. However, NKX3.1 immunohistochemical staining was performed to reach a definitive diagnosis. The positive NKX3.1 along with the resemblance to the initial prostatic adenocarcinoma and the clinical suspicion rendered the diagnosis of metastatic prostatic adenocarcinoma.

Treatment

Six years after his initial metastatic cancer diagnosis, he was progressing in his bone and lymph nodes and received the diagnosis of a prostate cancer cutaneous metastases. Thus, he was started on chemotherapy initially with docetaxel and subsequently cabazitaxel. A year later, he had subsequent progression, and his therapy was changed to enzalutamide, which he remains on.

Outcome and follow-up

The patient is followed closely by his oncology team. Despite progression in his bones and lymph nodes, he has had no clinical evidence of recurrent cutaneous metastases. He continues to remain independent and able to enjoy regular activities with his family. While the prognosis in cases of cutaneous metastases from prostate cancer is quite poor according to the few published reports (mean survival of 7 months),⁵ this patient has had a better disease course.

Discussion

While very uncommon, prostatic cancer can present with cutaneous metastasis in the advanced stages and given the high prevalence of metastatic prostate cancer, recognising this clinical scenario is of key importance. The presentation can be quite variable and can pose a diagnostic challenge since it can resemble many dermatological conditions. When it occurs, it tends to involve the dermis and pathologically, it recapitulates the appearance of the primary tumour.⁵ Immunohistochemical staining with NKX3.1 plays a major role in the diagnosis of metastatic prostate cancer. While PSA and PSAP stains have been commonly used to identify prostate cancer, they can be variably underexpressed in metastatic settings and poorly differentiated carcinomas.⁴ NKX3.1 expression is retained in metastatic prostatic carcinoma and therefore being more superior to PSA and PSAP.

The mechanism of cutaneous metastasis in prostate cancer is poorly understood. Possible explanations include haematogenous or lymphatic spread as well as direct extension and seeding from the original tumour.⁶ Since it occurs later in the disease course, the prognosis is usually poor. Systemic treatment with chemotherapy can improve outcomes from cutaneous metastasis.⁶

Learning points.

• To recognise that prostate cancer can metastasise to the skin.

• To ensure clinicians have a high index of suspicion in patients with metastatic prostate cancer since cutaneous metastases can mimic many dermatological disorders.

• To highlight the utility of histopathological and immunohistomchemical evaluation of cases with metastatic prostatic adenocarcinoma.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).