Microscopic Description:

Lumen-Spanning Proliferation: Malignant cells span the entire lumen of the affected ducts and acini. These cells expand the normal prostatic ducts, often distorting them.

Basal Cell Layer Preservation: IDC-P retains a basal cell layer, although it may be patchy or partially disrupted in some areas. This feature helps distinguish it from invasive carcinoma, which lacks basal cells.

Histological Patterns:

  • Solid: Proliferation of malignant cells without luminal spaces, often showing central comedonecrosis.
  • Cribriform: Cells form punched-out, round spaces within the luminal structure, occupying more than 50% of the duct space. This pattern may also show comedonecrosis.
  • Micropapillary and Trabecular: These patterns involve smaller cell proliferations without forming solid sheets or large cribriform spaces.

Marked Nuclear Atypia: Nuclei of malignant cells are typically enlarged, pleomorphic, and may be more than six times larger than normal, with prominent nucleoli.

Comedonecrosis: This feature, consisting of necrotic cell debris within the lumen, is frequently observed in IDC-P, especially in the solid and cribriform patterns.

IHC: IDC-P more frequent loss of heterozygosity (LOH) in TP53, RB1, and PTEN compared to invasive prostate carcinoma, with LOH of TP53 found in 60% vs. 40% and LOH of RB1 in 81% vs. 60%; PTEN deletions occur in ~45% of IDC-P cases, while ERG fusions are less common in isolated IDC-P (7%) than when IDC-P is concurrent with invasive carcinoma (55–75%), and BRCA2-mutated familial prostate cancers show a higher incidence of IDC-P.

Discussion:

Intraductal carcinoma of the prostate (IDC-P) is a distinct and aggressive subtype of prostate cancer characterized by the proliferation of malignant epithelial cells within prostatic ducts and acini, with preservation of the basal cell layer.

Pathology: IDC-P is often associated with high-grade invasive prostate cancer and is characterized by architectural patterns such as cribriform, solid, and micropapillary structures. The cells exhibit significant nuclear atypia and mitotic activity.

Clinical Significance: IDC-P is a poor prognostic factor, associated with higher Gleason scores, larger tumor volumes, advanced stages, and worse clinical outcomes, including earlier biochemical recurrence and increased risk of metastasis.5-year survival rates estimated to be 30-50%. Incidence accounts for approximately 5-10% of prostate cancer cases, however, this rising due to increased awareness and diagnostic advancements.

Genomic Features: IDC-P exhibits distinct genomic profiles, including higher rates of gene fusions, loss of tumor suppressor genes (e.g., PTEN), increased genomic instability, and a higher prevalence of germline mutations in homologous recombination repair genes (e.g., BRCA2).

Diagnosis: Diagnosis involves histopathological examination, often supplemented by immunohistochemistry to differentiate IDC-P from mimickers like high-grade prostatic intraepithelial neoplasia and invasive cribriform prostate cancer. Key diagnostic features include the presence of malignant cells within ducts and acini with intact basal cell layers.

Management: The presence of IDC-P is a contraindication for active surveillance. Treatment strategies may include radical prostatectomy, radiation therapy, and consideration of targeted therapies for patients with specific genetic mutations. Emerging evidence suggests that therapies targeting genomic instability, such as PARP inhibitors, may be beneficial.

Future Research Directions: Further research is needed to develop optimal therapeutic strategies based on the distinct genomic features of IDC-P. This includes exploring the efficacy of immune checkpoint inhibitors and PARP inhibitors, as well as utilizing patient-derived xenografts and tumor organoid models for in vitro studies.

References:

Kang M, Lee H, Byeon SJ, Kwon GY, Jeon SS. Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate. Int J Mol Sci. 2021;22(23):13125. doi:10.3390/ijms222313125.

Gandhi JS, Smith SC, Paner GP, et al. Reporting Practices and Resource Utilization in the Era of Intraductal Carcinoma of the Prostate: A Survey of Genitourinary Subspecialists. Am J Surg Pathol. 2020;44(5):673-680. doi:10.1097/PAS.0000000000001417.

Wobker SE, Epstein JI. Differential Diagnosis of Intraductal Lesions of the Prostate. Am J Surg Pathol. 2016;40(6):e67-82. doi:10.1097/PAS.0000000000000609.

Zhao J, Zhu S, Nie L, et al. Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate. Cancer Res. 2023;83(20):e1176. doi:10.1158/0008-5472.CAN-23-1176.

Shi Y, Wang H, Golijanin B, et al. Ductal, Intraductal, and Cribriform Carcinoma of the Prostate: Molecular Characteristics and Clinical Management. Urol Oncol. 2024;42(5):144-154. doi:10.1016/j.urolonc.2024.01.037.

Miura N, Mori K, Mostafaei H, et al. The Prognostic Impact of Intraductal Carcinoma of the Prostate: A Systematic Review and Meta-Analysis. J Urol. 2020;204(5):909-917. doi:10.1097/JU.0000000000001290.

Varma M. Intraductal Carcinoma of the Prostate: A Guide for the Practicing Pathologist. Adv Anat Pathol. 2021;28(4):276-287. doi:10.1097/PAP.0000000000000303.

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