Difficult-to-manage prostate cancer scenarios illustrating the pathologist’s role: Two case reports

Background:
Prostate cancer remains one of the most common malignancies among men worldwide, and its diagnosis and management rely fundamentally on accurate histopathologic evaluation. Gleason grading, now incorporated into the ISUP Grade Group system, is central to determining tumor aggressiveness, prognosis, and appropriate therapy. Despite its critical role, interobserver variability among pathologists continues to be a major challenge in prostate cancer care. Subtle differences in interpretation—especially in borderline cases such as distinguishing between Gleason pattern 3 and 4, or in the presence of rare histologic variants—can significantly influence clinical decision-making. Misclassification may lead to inappropriate treatment choices, ranging from unnecessary radical interventions to under-treatment of aggressive disease. Therefore, expert pathology review and multidisciplinary discussion remain essential components of optimal patient management.

Case Presentation:
We present two clinically complex cases that illustrate how second-opinion pathology review can directly impact patient care.
In the first case, a 65-year-old male was initially diagnosed with prostate adenocarcinoma, Gleason score 4+4=8, suggesting high-grade disease with a poorer prognosis. Based on this diagnosis, radical prostatectomy followed by adjuvant therapy was initially considered. However, upon expert review at a tertiary referral center, the tumor was reclassified as Gleason score 3+4=7 (Grade Group 2), indicating intermediate risk. This revision significantly altered the treatment approach, shifting from aggressive multimodal therapy toward a more conservative plan involving targeted radiation and active surveillance of biochemical response. The new plan prioritized preservation of sexual and urinary function without compromising oncologic safety.

In the second case, an 80-year-old patient presented with advanced disease and was initially reported to have a mixed adenocarcinoma with small cell carcinoma component—a diagnosis associated with poor prognosis and often requiring systemic chemotherapy. Expert pathology reassessment excluded the small cell morphology and confirmed pure acinar adenocarcinoma. This re-evaluation prevented the initiation of unnecessary cytotoxic chemotherapy, sparing the patient from potential toxicity and allowing for appropriate androgen-deprivation therapy. The outcome underscored how even subtle diagnostic nuances can dramatically shift management strategies.

Conclusion:
These cases emphasize that the pathologist’s role extends far beyond initial diagnosis—accurate histologic interpretation is a cornerstone of precision oncology. Second-opinion pathology review should be considered standard practice in atypical, ambiguous, or high-stakes prostate cancer cases, as it can prevent both overtreatment and undertreatment. Furthermore, the integration of advanced diagnostic modalities—such as multiparametric MRI, MRI-targeted biopsies, digital pathology, and artificial intelligence-assisted grading—holds promise for reducing human variability and improving consistency. Nonetheless, these technologies should complement, not replace, expert clinical and morphologic judgment. Ultimately, multidisciplinary collaboration, continuous education, and expert consultation remain essential to ensure diagnostic accuracy and to deliver personalized, evidence-based prostate

Dr. Drilon Bytyçi is a medical doctor from Kosovo who graduated from the University of Prishtina. He also holds a Bachelor’s degree in Radiologic Technology (2022). His main interests include radiology, otorhinolaryngology, oncology, and medical research. He is skilled in academic writing, medical imaging interpretation, and structured clinical reasoning. Dr. Bytyçi is strongly motivated to engage in new research initiatives, applying evidence-based medicine and integrating current literature into practice to contribute to data analysis and systematic reviews.