Case 73

A 56-year-old female with a 3.2 cm breast mass.

1.Which chromosomal alteration is commonly observed in this lesion?

A) Gains of 5p, 8q, 17q, and 20q

B) Loss of 16q and gain of 1q

C) Amplifications of 11q13 and 17q12

D) Loss of 8p, 11q, 13q, and 14q

Answer

The correct answer is B. Evidence supports DCIS as a precursor to IBC, with high genomic concordance between synchronous cases. However, DCIS does not follow a linear progression from low to high nuclear grade. Low and high nuclear grade DCIS have distinct molecular and genetic profiles, affecting their progression rates. High-grade DCIS exhibits greater genomic instability, while low-grade DCIS is characterized by 16q loss and 1q gain. In contrast, high-grade DCIS shares chromosomal changes with grade 3 IBC, including gains of 5p, 8q, 17q, and 20q and amplifications of 11q13 and 17q12.

Molecular alterations in DCIS, such as HER2 amplification, negative ER/PR status, and gene methylation, are similar to those seen in IBC. However, no genomic markers have been consistently linked to invasive progression or recurrence risk, limiting their clinical utility. Emerging evidence suggests that DCIS progression to IBC may involve an interaction between tumor copy number changes and the immune microenvironment, particularly tumor-infiltrating lymphocytes.

Reference: https://tumourclassification.iarc.who.int/chaptercontent/32/15

Case credit: UCSD Pathology

Authors: Wangpan Jackson Shi, MD