Lobular Intraepithelial Neoplasia [Lobular Carcinoma In Situ] With Comedo-type Necrosis

Abstract

The recent finding that lobular, and not ductal intraepithelial neoplasia (DIN) displays loss of E-cadherin expression has greatly facilitated the categorization of a large proportion of morphologically ambiguous intraepithelial neoplasias into ductal or lobular types. One reason for such morphologic ambiguity is the presence of comedo-type necrosis within an intraepithelial lesion that otherwise shows archetypal cytologic and architectural features of lobular intraepithelial neoplasia (LIN). The clinicopathologic features of 18 such cases are described in this report. These 18 cases of classic LIN were accumulated from the recent databases of 6 institutions. All cases, by definition, showed no expression of E-cadherin. The 18 patients, all women, were 41 to 85 years of age (mean 61.3). The lesions were initially identified in an excisional biopsy or mastectomy in 12 cases and in an incisional/core biopsy in the remaining 6 cases. An associated invasive carcinoma was present in 12 (67%) of 18 cases (7 classic lobular, 1 pleomorphic lobular, 1 ductal, 1 mixed lobular and ductal, 1 tubular, and 1 case with ductal and lobular carcinomas as separate foci). The average age of the 6 patients with pure LIN (ie, LIN without an invasive component (62.5 y) was not significantly different from the 12 patients in which there was an invasive component (60.7 y) (P = 0.78). The lesions had associated calcifications, typically within the necrotic foci, in 10 (55%) of 18 cases. Immunoreactivity for estrogen receptor, progesterone receptor (in >10% of lesional cells), and high-molecular weight keratin was present in 17/18 (94%), 15/18 (83%) and 17/18 (94%) of cases, respectively. Overexpression of HER2/neu, as assessed immunohistochemically, was absent in all 15 cases available for such evaluation. Foci of DIN, separate from the lobular lesions, were present in 6 (33%) of 18 cases. LIN with necrosis seems to occur at an older age than classic LIN, is commonly associated with invasive carcinoma and is significantly more frequently associated with lobular than ductal invasive carcinoma. When present without an invasive component, it may be mistaken for DIN 2 (grade 2 ductal carcinoma in situ). Although the necrosis suggests a ductal phenotype for these intraepithelial proliferations, architectural and cytologic features, high-molecular weight keratin[+], estrogen receptor[+], progesterone receptor[+], and human epidermal growth factor receptor 2 /neu[-] immunoprofile, frequent association with invasive lobular carcinoma, and lack of immunoreactivity for E-cadherin, strongly suggests that these lesions are within the morphologic spectrum of lobular neoplasia. Long-term follow-up studies are required to define the true natural history of these lesions. However, because classic LIN with necrosis is apparently rare in its pure form, reexcision is recommended when this lesion is detected in isolation in a core biopsy.