Dr. Al-Ahmadie started by highlighting that his talk would comprise a discussion regarding small cell carcinoma of the bladder and prostate. With regard to diagnostic criteria, these two entities are identical to lung small cell carcinoma, and it is important to document any small cell carcinoma component in the report.
Terminology includes:
- Small cell/neuroendocrine carcinoma
- Urothelial carcinoma with (%) neuroendocrine/small cell differentiation
As shown by Teo et al.1 in their assessment of long-term outcomes of local bladder small cell carcinoma, both disease-free and overall survival are improved in patients that receive neoadjuvant or adjuvant chemotherapy versus those that receive radical cystectomy alone.
In another study comparing treatment strategies for bladder small cell carcinoma, Alhalabi et al.2 showed the importance of neoadjuvant chemotherapy versus adjuvant/no chemotherapy on overall and cancer-specific survival:
Dr. Al-Ahmadie notes that these and other studies did not show a correlation between the amount of neuroendocrine component and outcomes.
Previous work from Chang et al.3 determined whether small-cell carcinoma of the bladder arises from a pre-existing urothelial carcinoma or whether it shares a molecular pathogenesis in common with small-cell lung cancer. They found that small cell carcinoma of the bladder had a high somatic mutational burden driven predominantly by an APOBEC-mediated mutational process. TP53, RB1, and TERT promoter mutations were present in nearly all samples. Ultimately, they concluded that small cell cancers of the bladder and lung have a convergent but distinct pathogenesis, with small cell carcinomas of the bladder arising from a cell of origin shared with urothelial bladder cancer:
Recent work from Dr. Al-Ahmadie’s group assessed the differential expression of NEUROD1, ASCL1, and POU2F3 in bladder small cell carcinomas,4 identifying five distinct molecular subtypes in bladder small cell carcinomas based on the expression of ASCL1, NEUROD1, and POU2F3:
• ASCL1+/NEUROD1- (n = 33; 34%)
• ASCL1- /NEUROD1+ (n = 21; 21%)
• ASCL1+/NEUROD1+ (n = 17; 17%)
• POU2F3+ (n = 22, 22%)
• ASCL1- /NEUROD1- /POU2F3- (n = 5, 5%)
They also noted that among patients without metastatic disease who underwent radical cystectomy, PLCG2+ or POU2F3+ tumors had shorter recurrence-free survival and overall survival, but their expression was not associated with metastasis status or response to neoadjuvant/adjuvant chemotherapy:
Dr. Al-Ahmadie then discussed the morphology of neuroendocrine differentiation in prostate carcinoma, of which there are many types:
- Pure high-grade neuroendocrine carcinoma/small cell carcinoma
- Mixed adenocarcinoma and high-grade neuroendocrine carcinoma/small cell carcinoma
- Prostatic adenocarcinoma with diffuse neuroendocrine differentiation
- Prostatic adenocarcinoma with patchy neuroendocrine differentiation
- Prostatic adenocarcinoma with isolated neuroendocrine marker-positive cells
- Prostate adenocarcinoma with Paneth cell-like change
Large cell neuroendocrine carcinoma with no prior treatment has the following immunohistochemistry and molecular profile:
Prostatic adenocarcinoma with diffuse neuroendocrine differentiation post ADT treatment has the following IHC, NKX3.1, PSA, and chromogranin profile:
Dr. Al-Ahmadie concluded his presentation by discussing a study from his group that assessed the Memorial Sloan Kettering Cancer Center’s institutional database of prostate small cell carcinoma with the aim of clinicopathologic characterization of these tumors.5 Among 79 cases (32 primary, 47 metastases), on morphologic assessment, there were (i) 23 pure small-cell/high-grade neuroendocrine carcinoma, (ii) 10 combined high-grade prostate cancer and small-cell/ high-grade neuroendocrine carcinoma, (iii) 15 prostate cancer with diffuse neuroendocrine immunohistochemistry marker positivity/differentiation, (iv) 11 prostate cancer with patchy neuroendocrine differentiation, (v) 9 prostate cancer with focal neuroendocrine marker positive cells, and (vi) 11 prostate cancer with 'Paneth cell-like' change:
Presented by: Hikmat Al-Ahmadie, MD, Pathologist, Memorial Sloan Kettering Cancer Center, New York, NY
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting, Washington, DC, Sun, Sept 29 – Wed, Oct 2, 2024.
References:
- Teo MY, Guercio BJ, Arora A, et al. Long-term outcomes of local and metastatic small cell carcinoma of the urinary bladder and genomic analysis of patients treated with neoadjuvant chemotherapy. Clin Genitourin Cancer. 2022 Oct;20(5):431-441.
- Alhalabi O, Wilson N, Xiao L, et al. Comparative Effectiveness Analysis of Treatment Strategies for Surgically Resectable Neuroendocrine Carcinoma of the Urinary Tract. Eur Urol Oncol. 2023 6;611-620.
- Chang MT, Penson A, Desai NB, et al. Small-cell carcinomas of the bladder and lung are characterized by a convergent but distinct pathogenesis. Clin Cancer Res. 2018 Apr 15;24(8):1965-1973.
- Akbulut D, Whiting K, Teo MY, et al. Differential NEUROD1, ASCL1, and POU2F3 expression defines molecular subsets of bladder small cell/neuroendocrine carcinoma with prognostic implications. Mod Pathol. 2024 Jul 2;37(10):100557.
- Gopalan A, Al-Ahmadie H, Chen YB, et al. Neuroendocrine differentiation in the setting of prostatic carcinoma: Contemporary assessment of a consecutive series. Histopathology. 2022 Aug;81(2):246-254.