PMC8495426_01
Histopathology of liver biopsy. (A) Metastatic prostate adenocarcinoma displaying significant nuclear enlargement and pleomorphism, prominent nucleoli, mitotic figures, and comedo-type central necrosis in this representative field. Note the absence in neuroendocrine features and the surrounding benign hepatocytes [H&E stain, 40x magnification]. (B) Diffuse nuclear positivity with NKX3.1 in tumor cells [NKX3.1 stain, 40x magnification]. (C) Diffuse cytoplasmic positivity with PSA in tumor cells. (D) No cytoplasmic staining with chromogranin in tumor cells [chromogranin, 40x magnification].
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A liver biopsy was obtained given it demonstrated the highest uptake value and showed metastatic carcinoma that was strongly positive for the prostate-specific immunohistochemical (IHC) markers NKX3.1 and PSA and negative for the neuroendocrine markers chromogranin and synaptophysin ( Figure 1 ).
Trends of treatment, prostate serum antigen, and tumor size across patient's treatment course. *Right inferior lobe lesion and  segment 7 lesion.
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PSA trends shown in  Figure 2 . PTEN loss in exon 2c.164, CDKN1B exon 1p.p92fs, tumor mutation burden (5 mutations/Mb), and stable microsatellite instability, and negative for NTRK1/2/3, ATM, BRCA1, BRCA2, FANCA, PALB2, RAD51C, and RAD51D. Second-line therapy with enzalutamide 160 mg was started in July 2020, but in August 2020, he presented to the emergency department with intractable right upper quadrant pain and CT scans showed progression of the hepatic masses with small, new infiltrative lesions ( Figure 3C ). PSA trends are shown in  Figure 2 . His PSA slowly trended down and became stable, as shown in  Figure 2 .
Serial computerized tomography (CT) images of abdomen and pelvis with contrast of the patient's tumor after sequencing treatments. Green oval cycles represent tumors. (A) Prior to docetaxel, March 2020. (B) Six cycles after docetaxel, June 2020. (C) Two months after enzalutamide, August 2020. (D) After three cycles of cabazitaxel, October 2020. (E) After Y-90 embolization to the right lobe of liver concurrent with carboplatin/abiraterone acetate, December 2020. (F) After Y-90 embolization to the left lobe of liver concurrent with carboplatin/abiraterone acetate, January 2021. (G) On carboplatin/abiraterone acetate, May 2021.
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Repeat CT scans after three cycles of docetaxel + ADT showed stable disease; however, the scans repeated after six cycles showed disease progression in the liver ( Figures 3A, B ). PTEN loss in exon 2c.164, CDKN1B exon 1p.p92fs, tumor mutation burden (5 mutations/Mb), and stable microsatellite instability, and negative for NTRK1/2/3, ATM, BRCA1, BRCA2, FANCA, PALB2, RAD51C, and RAD51D. Second-line therapy with enzalutamide 160 mg was started in July 2020, but in August 2020, he presented to the emergency department with intractable right upper quadrant pain and CT scans showed progression of the hepatic masses with small, new infiltrative lesions ( Figure 3C ). PSA trends are shown in  Figure 2 . While on cabazitaxel, his PSA dramatically increased to 188 ng/ml and repeat scans again demonstrated worsening of his extensive hepatic metastases ( Figure 3D ). He also underwent Y-90 embolization of the right lobe of his liver in December 2020 ( Figure 3E ) and a second Y-90 embolization of the left lobe of his liver in January 2021 ( Figure 3F ). He remains on the same chemotherapy/hormonal therapy combination at the time of writing with stable response ( Figure 3G ).
Histopathology of second liver biopsy. (A) Metastatic prostate adenocarcinoma displaying similar features to the previous sample, including significant nuclear enlargement and pleomorphism, prominent nucleoli, mitotic figures, and single-cell necrosis in this representative field. Again, note the absence of neuroendocrine features [H&E stain, 40x magnification]. (B) Diffuse nuclear positivity with NKX3.1 in tumor cells [NKX3.1 stain, 40x magnification]. (C) Diffuse cytoplasmic positivity with PSA in tumor cells. (D) No cytoplasmic staining with chromogranin in tumor cells [chromogranin, 40x magnification].
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A repeat liver biopsy was again consistent with metastatic prostatic adenocarcinoma with similar morphology and IHC profile to the previous biopsy ( Figure 4 ).