Editor,

A 63-year-old male presented with 6-month history of nocturia, incomplete bladder emptying, and weak urinary stream. Post-void residual was 850 cc. A large hard prostate was palpated on digital rectal examination without any discrete nodule. Serum PSA was 3.85 ng/ml and rest of the labs were unremarkable. Prostate biopsy showed Grade Group 5 prostate cancer. Staging workup showed right pubic bone osseous metastasis.

He was started on clean intermittent catheterization for incomplete bladder emptying. He underwent androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) agonist and enzalutamide. He received 55 Gy in 20 fractions to the prostate and seminal vesicle and 45 Gy in 20 fractions to the pubic bone metastasis. PSA was undetectable at 3 months follow-up visit. Enzalutamide was stopped due to anemia after 6 months of treatment and he was later started on abiraterone acetate.

After 19 months from the initial diagnosis, he developed new mild right sided hydronephrosis. Computerized tomography (CT) urogram was ordered for further evaluation. CT scan showed a new lytic L1 vertebral body lesion with cortical destruction measuring 26 × 14 mm. PSA was undetectable (< 0.10 ng/ml) at this time. Given the finding of a new lytic lesion at L1, prostate-specific membrane antigen (PSMA)-PET scan was ordered for further evaluation. F18-PSMA PET/CT scan showed no discrete radiotracer uptake in the prostate (Fig. 1A) or lytic lesion in L1 vertebral body (Fig. 1B). Patient underwent CT guided biopsy of L1 lytic lesion and it showed metastatic keratinizing squamous cell carcinoma. Workup was started to identify primary site for squamous cell carcinoma.

Fig. 1
figure 1

A F18-PSMA PET/CT scan image of prostate gland with no discrete radiotracer uptake. B F18-PSMA PET/CT scan image through L1 vertebral body with no evidence of radiotracer uptake. C F18-FDG PET/CT scan image of the prostate gland with intense uptake in the majority of the prostate gland. D F18-FDG PET/CT scan image through the L1 vertebral body showing intense radiotracer uptake in the lytic lesion. E Squamous component of adenosquamous carcinoma highlighted by infiltrating cords of malignant squamous cells with eosinophilic cytoplasm and keratin pearls. F Glandular component of adenosquamous carcinoma highlighted by infiltrating complex glandular proliferation with enlarged nuclei and prominent nucleoli

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F18-FDG PET/CT showed intense hypermetabolic prostate mass (Fig. 1C), hypermetabolic lytic lesion in L1 vertebral body (Fig. 1D), hypermetabolic retroperitoneal and right iliac lymphadenopathy. He underwent transperineal prostate biopsy and it revealed poorly differentiated adenosquamous cell carcinoma (Fig. 1E, F). Next generation sequencing of adenosquamous prostate tumor showed microsatellite status stable tumor with TMPRSS2-BRAF fusion, PIK3CA alteration (H1047R), PTEN alteration (D24H), CRKL amplification, MAPK1 amplification, and TP53 alteration (S215N). There was no actionable genetic mutation to drive treatment. There is one reported case in the literature where primary adenosquamous carcinoma of the prostate was PD-L1 positive and patient was treated with immune checkpoint inhibitor (nivolumab) [1]. In our patient, tumor PD-L1 staining (SP263) was negative. He is currently undergoing treatment with carboplatin and paclitaxel chemotherapy.

Adenosquamous carcinoma of prostate is an extremely rare and aggressive prostate cancer variant [2]. Retrospective analysis of prostate adenosquamous carcinoma cases showed a median cancer-specific survival of 16 months [3]. The majority of these patients had prior androgen deprivation therapy and or radiation therapy for prostate adenocarcinoma. Histologically, both malignant glandular and keratinizing squamous carcinoma components are present. Prostatic squamous cell carcinoma is often negative for PSA and PSAP immunohistochemical stains [4, 5].

In our patient, metastatic L1 lytic lesion developed when PSA was undetectable (< 0.10 ng/ml). Lytic bone metastasis is very rare in prostate cancer [6]. Further, the lytic lesion at L1 and prostate had low PSMA expression but intense uptake on F18-FDG PET/CT scan (Fig. 1). In patient with new lytic metastatic lesions and history of prostate cancer, clinicians should suspect metastatic lesions of prostate origin even with undetectable PSA and consider obtaining F18-FDG PET/CT for further evaluation.