Assessment of lesions coexisting with various grades of ductal intraepithelial neoplasia of the breast

Ductal intraepithelial neoplasia (DIN) is descriptive of in situ breast lesions from usual ductal hyperplasia (UDH) to advanced ductal carcinoma in situ (DCIS). A total of 2628 cases of DIN diagnosed at the Armed Forces Institute of Pathology were separated based on their grade. These were assessed for the presence of invasive carcinoma (ductal or lobular) and lobular intraepithelial neoplasia (LIN) grades 1-3. The frequency of invasive cancer (ductal and lobular) appearing with DIN increased with increasing DIN grade from 2% in low-risk DIN (UDH) to 37% in DIN 2-3 (DCIS grades 2-3). The frequency of these invasive carcinomas, which were either lobular or displayed lobular features, however, decreased with increasing grade of DIN with a peak of 28% in DIN 1-flat type, (flat epithelial atypia) to a low of 2% in DIN 3. Likewise, the frequency of LIN appearing with DIN decreased as the grade of DIN increased, with a peak of 26% in DIN 1-flat type to a low of 9% in DIN 3. Lower-grade LIN 1 comprised 14% of the LIN in low-risk DIN cases, but only 4% of the LIN seen in DIN 3 cases. Conversely, higher-grade LIN 3 comprised only 6% of the LIN seen in low-risk DIN cases, while accounting for 15% of the LIN in DIN 3 cases. The frequency of invasive carcinoma in DIN 1 ranged from 4% in quantitatively limited DIN 1 less than or equal to 2 mm (atypical ductal hyperplasia) to 27% among the more abundant DIN 1 greater than 2 mm (DCIS grade 1). The frequency of LIN associated with DIN 1 less than or equal to 2 mm was 13.4%, and the frequency of LIN associated with DIN 1 greater than 2 mm was 16.6% when there was no DIN 1-flat type present. However, the frequency of the LIN seen in combination with DIN 1-flat type was reduced by 50% as the quantity of DIN exceeded 2 mm. Based on this retrospective analysis of DIN, we noted that: (1) invasive carcinoma is most frequently associated with the higher grades of DIN; (2) the grade of LIN parallels the grade of coexisting DIN; (3) a relationship exists between DIN 1-flat type and the occurrence of LIN and (4) this relationship in association with DIN less than or equal to 2 mm is not maintained in DIN greater than 2 mm.