Facial cutaneous metastases from prostate adenocarcinoma mimicking benign adnexal tumours

Dear Editor,

Cutaneous metastases from internal malignancies are uncommon (0.7–9%) and usually indicate advanced disease.¹ Breast, lung and colorectal carcinomas are the most frequent primary tumours, whereas cutaneous metastasis from prostate adenocarcinoma is particularly rare with a reported incidence of approximately 0.3–0.36%.^1,2 When present, lesions typically involve regions adjacent to the primary tumour, such as the lower abdomen, groin or genital area, reflecting lymphatic or direct spread.² In contrast, rare craniofacial involvement has been attributed to haematogenous dissemination, including spread via Batson’s vertebral venous plexus.³ Facial involvement is distinctly uncommon and may clinically resemble benign adnexal tumours, posing a diagnostic challenge.³ In a recent systematic review, 9 cases with facial involvement were identified among cutaneous metastases from prostate cancer [Supplementary Table 1].⁴ Since cutaneous metastases are often clinically nonspecific, clinico-pathological correlation with immunohistochemistry is essential.⁵ Herein, we report a case of metastatic prostate adenocarcinoma presenting as multiple benign-appearing papules and plaques on the face, mimicking benign adnexal tumours, and demonstrating a rapid and sustained response to androgen deprivation therapy.

A 53-year-old man presented to the dermatology clinic with a two-month history of multiple, asymptomatic, skin-coloured papules on both cheeks. The lesions had gradually increased in number without associated pain, pruritus, ulceration or bleeding. At presentation, medical history revealed that he had been diagnosed with high-grade prostate adenocarcinoma one month ago after routine health screening detected markedly elevated serum prostate-specific antigen (PSA) level. He sought dermatological evaluation for the facial lesions without a urology referral.

Laboratory evaluation showed a total PSA level exceeding 1,000 ng/mL, consistent with a high tumour burden. Prostate biopsy (performed prior to dermatological consultation) demonstrated high-grade adenocarcinoma with a Gleason score of 9 (5+4), involving 11 of 12 cores. Dermatological examination revealed multiple, firm, skin-coloured papules and plaques measuring 2–10 mm on both cheeks with intact overlying epidermis and no erythema or ulceration [Figures 1a and b]. Based on the clinical appearance, differential diagnoses included benign adnexal tumours (e.g., trichoepithelioma, syringoma), cutaneous lymphoma, basal cell carcinoma and metastatic carcinoma.

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Figure 1: Clinical photographs of facial cutaneous metastases from prostate adenocarcinoma before and after androgen deprivation therapy. (a, b) Before treatment, multiple skin-coloured papules and indurated plaques present on both cheeks. (c, d) Two weeks after initiation of androgen deprivation therapy, the lesions show marked regression with near-complete flattening and minimal residual discolouration.

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A punch biopsy was performed from a representative right cheek lesion. Histopathological examination revealed epidermal sparing with dermal infiltration of atypical epithelial cells forming nodular and plate-like aggregates with adnexal entrapment [Figure 2a]. At higher magnification, poorly differentiated microacinar and cord-like structures with occasional luminal eosinophilic secretions were observed [Figure 2b]. Immunohistochemical staining demonstrated strong cytoplasmic positivity for pan-cytokeratin (AE1/AE3) and α-methylacyl-CoA racemase (AMACR) [Figures 3a and b], while high molecular weight cytokeratin (34E12) and carcinoembryonic antigen (CEA) were negative [Figures 3c and d]. The Ki-67 labelling index was low (<10%) [Figure 3e]. This may reflect sampling at a single time point and intermetastatic heterogeneity; thus, a low Ki-67 index in the biopsied cutaneous lesion does not preclude aggressive systemic disease. These findings supported the diagnosis of metastatic adenocarcinoma of prostatic origin.

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Figure 2a: Histopathological findings of a punch biopsy from the right cheek: Low-power view demonstrates epidermal sparing with dermal-based infiltration by malignant cells forming dense nodular and plate-like aggregates with adnexal entrapment (Haematoxylin and eosin, 40x; scale bar = 200 μm).

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Figure 2b: High-power view shows microacinar and cord-like structures composed of cuboidal to low-columnar tumour cells with prominent nucleoli and occasional luminal eosinophilic secretions (Haematoxylin and eosin, 200x; scale bar = 50 μm).

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Figure 3a: Immunohistochemical image showing membranous staining in tumour cells (Pan-cytokeratin (AE1/AE3), 200x, scale bar = 50 μm).

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Figure 3b: Immunohistochemical image demonstrating strong cytoplasmic positivity for α-methylacyl-CoA racemase (AMACR), 200x, scale bar = 50 μm).

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Figure 3c: Immunohistochemical micrograph shows negative staining for high-molecular-weight cytokeratin (34E12) in tumour cells, 200x (scale bar = 50 μm).

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Figure 3d: Immunohistochemical micrograph shows negative staining for carcinoembryonic antigen (CEA) in tumour cells, 200x (scale bar = 50 μm).

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Figure 3e: Immunohistochemical micrograph shows a low Ki-67 labelling index (<10%) in tumour cells, 200× (scale bar = 50 μm).

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Subsequent systemic staging confirmed advanced metastatic disease. Prostate magnetic resonance imaging (MRI) demonstrated extracapsular extension (cT3a) with enlarged right iliac lymph nodes suspicious for regional metastasis; an abdomino-pelvic computerised tomography (CT) scan revealed right-sided hydronephrosis due to ureteral invasion by a para-aortic metastatic lesion, and bone scintigraphy showed multifocal skeletal metastases.

Systemic androgen deprivation therapy was initiated by the urology team with a gonadotropin-releasing hormone agonist (leuprorelin acetate 22.5 mg, subcutaneous injection every 3 months) plus an androgen receptor antagonist (bicalutamide 50 mg orally once daily). At two weeks follow-up after initiation of therapy, marked regression of the facial lesions was observed with near-complete flattening and minimal residual discoloration, without concomitant skin-directed treatment [Figures 1c and d]. Serial PSA measurements demonstrated a rapid biochemical response, declining from >1,000 ng/mL at diagnosis to 29.17 ng/mL after the first treatment cycle and further to 14.24 ng/mL after the second cycle. At follow-up eight months after initiation of therapy, there was no clinical recurrence or progression of the facial lesions and the abdomino-pelvic CT scan showed improvement of para-aortic and common iliac lesions and hydronephrosis. Further PSA monitoring was planned and additional systemic treatment options (enzalutamide or docetaxel) were to be considered depending on the results. A timeline is provided in Supplementary Figure S1.

Cutaneous metastasis from prostate adenocarcinoma is regarded as a marker of advanced systemic disease and carries a poor prognosis.^1,4 Serum PSA is central to monitoring treatment response in prostate cancer; thus, the marked PSA decline and rapid regression of facial lesions in our patient likely reflect systemic treatment responsiveness, although the independent prognostic significance of cutaneous regression remains uncertain in terms of clinical outcomes.⁶ Facial metastases are particularly rare and may closely mimic benign adnexal tumours, increasing the risk of diagnostic delay.³ Accordingly, thorough history taking, careful clinico-pathological correlation and early multidisciplinary coordination are essential when evaluating atypical facial skin lesions in patients with a known or suspected internal malignancy.