PMC9523122_01
Pathological manifestations of initial prostate biopsy. Hematoxylin and eosin staining (magnification, x200): (A) Gleason pattern 4 adenocarcinoma with nuclei unevenly distributed, cribriform, and growing in the form of fused glands is identified. Immunohistochemistry (magnification, x200): (B) chromogranin A, (C) synaptophysin, (D) INSM1, and (E) SSTR2 are negative, and (F) AR, (G) PSA (focal), and (H) PD-L1 (focal) are positive. AR, androgen receptor; INSM1, insulinoma-associated protein 1; PD-L1, programmed death ligand-1; PSA, prostate-specific antigen; SSTR2, somatostatin receptor 2.
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Transrectal prostate needle biopsy was performed in April 2019 resulting in a Gleason score of 4 + 4 adenocarcinoma ( Figure 1 ). The tumor proportion score (TPS) of PD-L1 was approximately 50% using the clone 22C3 pharmDx kit (Agilent Technologies, Inc., Santa Clara, CA, USA) ( Figure 1 ). The patient is still undergoing treatment after more than 14 months of response without any immune-related adverse events.  Supplementary Figure 1  illustrates the transient changes in his PSA, NSE, and proGRP levels and the treatment course received by the patient.
Local prostate lesion and involved lymph nodes on contrast-enhanced computed tomography and somatostatin receptor scintigraphy. Contrast-enhanced computed tomography examination at the first visit to the department: (A) dark staining throughout the prostate and enlarged right obturator lymph node was noted (yellow arrowheads); (B) somatostatin receptor scintigraphy shows mild accumulation in the local prostate lesion (yellow arrowhead).
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Contrast-enhanced computed tomography (CECT) showed an irregular contrast effect over the entire prostate, and somatostatin receptor scintigraphy showed mild accumulation in the prostate ( Figure 2 ).
Pathological manifestations of prostate re-biopsy. Hematoxylin and eosin staining (magnification, x200): (A) the tumor tissue is infiltrated with chromatin-rich, naked nucleated tumor cells with an increased nucleus/cytoplasm ratio of irregular nuclear shape. Immunohistochemistry (magnification, x200): (B) chromogranin A, (C) synaptophysin, (D) CD56, (E) INSM1, (F) SSTR2, and (G) PD-L1 (focal) are positive, and (H) AR and (I) PSA are negative. (J) Ki-67 is also positive with a Ki-67 labeling index over 90%.
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After changing from degarelix to leuprorelin acetate, a prostate re-biopsy was performed in December 2019, and small cell carcinoma was detected ( Figure 3 ).
Local prostate lesion imaging including involved lymph nodes and pancreatic lesion before and after the administration of pembrolizumab. Contrast-enhanced computed tomography examination: (A) before the administration of pembrolizumab and (B) 5 months after the administration of pembrolizumab. There was complete remission of each lesion (yellow arrowheads).
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Following pembrolizumab administration, the local prostate, lymph node, and pancreatic metastases were all reduced, and complete remission was achieved with the resolution of symptoms ( Figure 4 ).