Abstract P5-02-09: The prevalence of invasive lobular carcinomas with unconventional immunohistochemical phenotypes

Background The prognosis of invasive lobular carcinoma (ILC) is controversial. Some studies report equivalent or better outcomes than invasive ductal carcinoma, likely due to ILC’s favorable prognostic phenotype. Classic ILC (CL) is typically of low histologic grade, estrogen receptor (ER) positive and human epidermal growth factor receptor-2 (HER2) negative. However, worse long term outcomes have been observed because ILC tends to be multicentric, bilateral, and to show higher rates of late metastases in uncommon sites. Additionally, subtypes of ILC, including solid (SOL) and pleomorphic (PL), have been reported to display more aggressive behavior. Yet current treatment paradigms are distinguished by hormone receptor profile and stage, not by tumor morphology. This study aimed to evaluate the clinicopathologic and immunohistochemical (IHC) characteristics of ILC, particularly those with unusual patterns. Methods From 2009-2018, consecutive in-house biopsy and resection specimens with the diagnosis of ILC were identified by a retrospective review of our institutional database. Demographic, morphologic, and IHC data were obtained from pathology reports. Cases with equivocal HER2 IHC results are sent for fluorescence in situ hybridization analysis at our Center. CL ILC was defined by small cells with low nuclear grade and discohesive growth arranged in single file or cords. PL ILC is composed of larger, more atypical cells, which still exhibit discohesion typical of lobular phenotype. SOL ILC consists of tumors growing in large sheets with minimal intervening stroma. Results Over the nine year study period, a total of 3,028 ILCs from 2,322 patients were identified. Most (74%, 2229/3028) cases were classified as CL while 22% (665/3028) were PL and 4% (134/3028) SOL (Table 1). The median patient age was 60 years (range 32-95). The median tumor size was larger for PL (2.3 cm) and SOL (2.4 cm) subtypes than CL (1.1 cm). IHC results were available for 896 specimens. The majority of all ILCs showed an expected phenotype: ER positive and HER2 negative (99% CL, 84% PL, 97% SOL). A smaller subset of ER positive ILC were also HER2 positive (1% CL, 8% PL, 3% SOL). No CL or SOL ILC were ER negative; in contrast 8% (21/270) of PL ILC were ER negative. Twelve (5%) PL ER negative cases were also HER2 negative. Overall, 15% of ILC were HER2 positive, with the PL variant showing the highest incidence (11%, 30/270). Lymph node (LN) metastases were seen in 22% (66/291) of CL cases, 55% (53/96) PL and 29% (17/58) SOL. Metastases in 10 or more LN (N3) was seen only in PL and SOL cases (13% and 5%, respectively). Conclusions In this study, up to 8% of ILC cases were found to be ER negative, a finding unique to the PL variant. No CL or SOL ILC was ER negative. HER2 positivity, not typically expected in ILC, was seen in 15% of cases, most commonly in the PL type. ILC that was both negative for ER and HER2 was observed in 5% of cases, and only within the PL subgroup. PL ILC showed higher median tumor size at presentation than CL and nodal metastases were also more common in PL than in CL or SOL ILC (55% vs 22% and 29%, respectively). Our findings are in keeping with prior observations that compared to CL ILC. PL ILC exhibits features associated with unfavorable clinicopathologic features, such as higher tumor and nodal stage at presentation. Additionally, this is the first study to systematically examine the prevalence of unconventional IHC phenotypes of ILC (ER negativity and/or HER2 positivity) in a large series from one institution. Citation Format: Matthew G Hanna, Anne Grabenstetter, Dara S Ross, Lee K Tan. The prevalence of invasive lobular carcinomas with unconventional immunohistochemical phenotypes [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-02-09.