A Case of Prostatic Signet-Ring Cell-like Carcinoma with Pagetoid Spread and Intraductal Carcinoma and Long-Term Survival: PD-L1 and Mismatch Repair System Proteins (MMR) Immunohistochemical Evaluation with Systematic Literature Review

Abstract

Prostatic adenocarcinoma (PA) is the second most common malignancy in men globally. Signet-ring cell-like adenocarcinoma (SRCC) is a very rare PA subtype, with around 200 cases reported in the English literature. Histologically, the tumor cells show a vacuole compressing the nucleus to the periphery. Pagetoid spread in acini and ducts is usually related to metastases from urothelial or colorectal carcinomas, less commonly associated with intraductal carcinoma (IC); histologically, the tumor cells grow between the acinar secretory and basal cell layers. To our knowledge, we report the first prostatic SRCC (Gleason score 10, stage pT3b) associated with IC and pagetoid spread to prostatic acini and seminal vesicles. To our systematic literature review (PRISMA guidelines), it is the first tested case for both PD-L1 (<1% of positive tumor cells, clone 22C3) and mismatch repair system proteins (MMR) (MLH1+/MSH2+/PMS2+/MSH6+). We found no SRCC previously tested for MMR, while only four previous cases showed high expression of another PD-L1 clone (28-8). Finally, we discussed the differential diagnoses of prostatic SRCC.

Prostate Adenocarcinoma with Signet-Ring Cells and Features of Mucin: A Clinical Case and Literature Review

“…Since then, fewer than 100 cases have been published in English literature [ 33 ]. It is a rare, high-grade (Gleason grade 5) acinar adenocarcinoma subtype characterized by its distinctive intracellular substance-containing vacuole, which displaces the nucleus into the periphery of the cell, giving it a crescent shape [ 10 , 34 ]. The content of the vacuole may vary [ 35 ]; however, according to the latest edition of Prostate and Urinary Tract Tumors classification by the World Health Organization, in cases where the vacuole contains mucin, the tumor should be named signet-ring cell-like adenocarcinoma rather than signet-ring cell adenocarcinoma.…”

“…Due to its rare nature, the close epidemiological relation to the gastrointestinal tract, and diffuse, lateral, submucosal growth pattern, a diligent diagnostic workup for differentials must be carried out since the location of the primary tumor may be an independent factor for the cause-related survival and virulence of the disease [ 7 , 13 ]. The investigations should include upper gastric endoscopy, colonoscopy, cystoscopy, and abdominal computed tomography to exclude metastatic involvement of the prostate [ 10 ]. It may not be a routine procedure, yet some patients may benefit from random gastric biopsies [ 14 ].…”

“…SRCC of the prostate is often described as having an aggressive clinical course and unpredictable response to hormonal therapy. Some publications argue that this presumption may have arisen from the fact that most patients were diagnosed at late stages of the disease, before the serum PSA marker era, and if diagnosed early, the variant is of similar prognosis to the usual acinar prostate adenocarcinoma (PA) [ 10 , 20 , 35 ]. Unfortunately, other articles similar to our literature review show that serum PSA values greatly vary and are thus not entirely reliable in the diagnosis of prostate SRCC [ 21 , 41 ].…”

“…Although we lack well-established guidelines, the current treatment of prostatic SRCC is rather similar to that of the traditional adenocarcinomas of the prostate—which includes a variable combination of surgical procedures, hormonal therapy, adjuvant radiotherapy, and/or chemotherapy [ 10 ]. Even though the multimodal aggressive approach is very reasonable, a combination of radiotherapy and hormonal therapy may be an appropriate alternative therapy for prostate SRCC treatment [ 12 ].…”