Pleomorphic variant of invasive lobular carcinoma of the breast

doi:10.1016/0046-8177(92)90035-2

Human Pathology

Volume 23, Issue 10, October 1992, Pages 1167-1171

https://doi.org/10.1016/0046-8177(92)90035-2 Get rights and content

Abstract

Infiltrating lobular carcinoma (ILC) of the classic type is well recognized; less well appreciated is a group of variant forms of ILC, which includes solid, alveolar, mixed, apocrine, signet-ring, histiocytoid, and tubulolobular variants. In addition, Page et al (Diagnostic Histopathology of the Breast, Churchill Livingstone, 1987, pp 219–226) recently have emphasized the pleomorphic variant of ILC, which demonstrates the infiltrating pattern of classic ILC; however, the nuclei are more pleomorphic and have features that may overlap with those of infiltrating duct carcinoma. To determine whether pleomorphic ILC shows significant prognostic differences from classic ILC, we reviewed the clinical courses of 25 patients with classic ILC and compared them with 16 patients with pleomorphic ILC. The major determinant in placing ILC into the pleomorphic category was the presence of nuclei of nuclear grade 2 or 3. All classic ILCs had nuclei of grade 1 by the Scarff-Bloom-Richardson criteria. Survival to recurrence was significantly worse (P ≤ .05) for the patients with pleomorphic ILC at lengths of survival greater than 30 months. In addition, node-negative patients with pleomorphic ILC were four times more likely to experience recurrence than node-negative patients with classic ILC; those with positive nodes and pleomorphic histology were 30 times more likely to experience recurrence. Although there appeared to be a trend toward decreased overall length of survival for those patients with pleomorphic ILC when compared with patients with classic ILC, this difference was not statistically significant.

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Cited by (143)

Management of HR+/HER2+ lobular breast cancer and trends do not mirror better outcomes
2022, Breast
Treatment protocols for invasive lobular breast cancer (ILC) have largely followed those for invasive ductal breast cancer. This study compares treatment outcomes of endocrine therapy versus combined chemo-endocrine therapy in hormone-receptor-positive (HR+), HER2-positive (HER2+) ILC tumors in a large national registry.
We sampled the National Cancer Database (2010–2016) for female patients with stages I-III, HR+/HER2+ ILC who underwent surgery. Cochran-Armitage trend test examined trends of treatment regimen administration: Surgery only (S), chemotherapy (C), endocrine therapy (ET), and combined chemo-endocrine therapy (CET), with or without anti-HER2 therapy. Cox proportional hazard model were used to compare overall survival (OS) across ET and CET cohorts, stratifying for anti-HER2 therapy, before and after propensity score match of cohorts (2013–2016). Kaplan-Meier (KM) survival curves were also produced.
N=11,421 were included. 58.7% of patients received Anti-Her2 therapy after 2013. CET conferred better OS over ET in the unmatched (adjusted-5-year-OS: 92.5% vs. 81.1%, p<0.001) and PS-matched (90.4% vs. 84.5%, p=0.001) samples. ET caused lower OS in patients who received Anti-Her2 therapy (HR: 2.56, 95% CI: 1.60–4.12, p<0.001) and patients who did not (HR: 1.84, 95% CI: 1.21–2.78, p=0.004), as compared to CET on multivariable analysis. KM modeling showed highest OS in the CET cohort who received Anti-Her2 (93.0%), followed by the CET cohort who did not receive Anti-Her2 (90.2%) (p=0.06).
Chemotherapy followed by endocrine therapy and Anti-Her2 therapy was shown to be the most effective treatment modality in HR+/HER2+ ILC, contrasting previous data on the inconclusive benefit of chemotherapy in patients with ILC.
Special Histologic Type and Rare Breast Tumors – Diagnostic Review and Clinico-Pathological Implications
2022, Surgical Pathology Clinics
Outcomes of pleomorphic lobular carcinoma versus invasive lobular carcinoma
2019, Breast
Citation Excerpt :
Pleomorphic lobular carcinoma (PLC) is a rare type of invasive lobular carcinoma (ILC) discovered in 1987 by Davies et al. and further described as a unique histologic entity by Eusebi, Weidener, and Semple [1–3].
Pleomorphic lobular carcinoma (PLC) is a rare histologic variant of invasive lobular carcinoma (ILC) that has been associated with worse clinical outcomes than classic ILC. Owing to its rarity, high-volume studies of its clinical characteristics and prognosis are lacking. The purpose of this study was to use a large, contemporary cancer database to investigate the clinical characteristics and survival outcomes for patients with PLC.
The National Cancer Database (NCDB) was queried for women with cT1-4N1-3M0 breast cancer with either ILC or PLC histology having received definitive surgical therapy. Chi-squared analysis was performed to determine differences between the cohorts. Kaplan-Meier analysis evaluated overall survival (OS) between all patients and between patients when stratifying by age and subtype. Cox proportional hazards modeling determined variables associated with OS.
A total of 115,260 patients met the study criteria; of these, 114,859 (99.6%) had ILC, while 401 (0.4%) had PLC. A greater proportion of patients with PLC had T3-4 and node-positive disease, and were more likely to have ER- and HER2+ disease. PLC histology was associated with worse OS on both univariate and multivariate analysis (p < 0.001). PLC was associated with poorer OS in subgroups that were T3-4/N+ (but not T1-2N0) disease and ER+ (but not ER-) cancers, but not by HER2 status.
Patients with PLC, who were more likely to have ER- and HER2+ disease, experienced worse OS than patients with ILC, which may be limited to patients with more advanced clinical stage and ER + disease. Further work is needed to determine the optimal treatment for this more aggressive form of breast cancer.
Invasive Lobular Breast Carcinoma: Pleomorphic Versus Classical Subtype, Associations and Prognosis
2018, Clinical Breast Cancer
Invasive pleomorphic lobular carcinoma (IPLC) has been associated with a worse prognosis compared with classic invasive lobular carcinoma (cILC); however, studies are small and conflicting. We seek to examine the prognosis of women with IPLC compared with cILC.
A retrospective review of women with breast cancer at a single institution from 2003 to 2012 identified 193 women with invasive lobular carcinoma (ILC). IPLC was defined as ILC with a pathological description of primarily pleomorphic features and Nottingham histological grade score of 7, 8, or 9 or overall grade of 3 or mixed classic/pleomorphic features and overall grade of 3. All others were designated cILCs. Clinicopathologic variables, progression-free survival (PFS), per STEEP criteria, and overall survival (OS), using all-cause mortality, were examined in both groups.
Of the 193 women, 46 (24%) had IPLC and 147 (76%) had cILC. The IPLC group had significantly higher stage at diagnosis and more Hispanic women, but there were no differences in other clinicopathologic features or treatment. Median follow-up was 57 months (0.1-155 months). In univariate analysis, IPLC was associated with worse PFS (log-rank P = .09, Wilcoxon P = .01) but no significant differences in OS (log-rank P = .20, Wilcoxon P = .16). In multivariate models adjusting for stage, IPLC was not significantly associated with PFS (hazard ratio [HR] 1.43; 95% confidence interval [CI], 0.73-2.79; P = .30) or OS (HR 1.52; 95% CI, 0.58-4.01; P = .40).
IPLC was initially associated with worse PFS, but this was attenuated after adjustment for cancer stage, and there were no differences in OS.
Lobular Carcinoma In Situ
2018, Surgical Pathology Clinics
Citation Excerpt :
ALH is associated with a fourfold to fivefold increase in the risk of subsequent breast carcinoma. The term “pleomorphic” was first used to qualify a variant of invasive lobular carcinoma (ILC) showing the infiltrative pattern characteristic of classic ILC (single cell files or targetoid arrangement of dyshesive cells), but having marked nuclear pleomorphism.27–30 Compared with classic ILC, pleomorphic ILC (P-ILC) consists of larger cells with round to ovoid shape, abundant cytoplasm, and large hyperchromatic nuclei that tend to be located slightly off-center, and have prominent nucleoli (Fig. 7).
Lobular carcinoma in situ (LCIS) is a risk factor and a nonobligate precursor of breast carcinoma. The relative risk of invasive carcinoma after classic LCIS diagnosis is approximately 9 to 10 times that of the general population. Classic LCIS diagnosed on core biopsy with concordant imaging and pathologic findings does not mandate surgical excision, and margin status is not reported. The identification of variant LCIS in a needle core biopsy specimen mandates surgical excision, regardless of radiologic-pathologic concordance. The presence of variant LCIS close to the surgical margin of a resection specimen is reported, and reexcision should be considered.
Lobular carcinoma in situ of the breast
2018, The Breast: Comprehensive Management of Benign and Malignant Diseases
Lobular carcinoma in situ (LCIS) exists as two main subtypes, classic and pleomorphic. While it may sometimes be an invasive cancer precursor, LCIS can be treated as a risk lesion without complete surgical resection. Bilateral mastectomy has been replaced with programs of surveillance. LCIS is usually discovered incidentally during biopsy for another indication. LCIS incidence appears to be influenced by the use of exogenous hormones. The lifetime risk of invasive cancer is 8 to 10 times that seen among women without LCIS. The risk of invasive cancer development can be decreased by the use of a chemopreventive endocrine agent. When diagnosed on a core needle biopsy, current guidelines recommend consideration of diagnostic surgical excisional sampling for discordant pathology/imaging findings, extensive LCIS, and/or when associated with other atypical findings to eliminate the possibility of a missed malignancy. Observation alone without excision is being offered to increasing numbers of individuals with classic LCIS on core sampling deemed concordant with imaging findings. Aggressive surgical resection of all disease at a surgical margin, even at the time of lumpectomy for a concurrent invasive tumor, is not advocated due to the fact that LCIS is often multicentric, multifocal, and bilateral. Such clinical presentations make bilateral mastectomy the only way to ensure removal of all of the LCIS present, an approach that is drastic for a risk factor lesion unless there are other compelling confounding breast cancer risk factors present. Finally, the biologic behavior of pleomorphic LCIS remains controversial in terms of long-term outcomes and risk of invasive cancer development.

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Original contributionPleomorphic variant of invasive lobular carcinoma of the breast

Abstract

Hum Pathol

Hum Pathol

Hum Pathol

Lobular carcinoma of the breast in situ and infiltrating

Pathol Annu

Invasive lobular carcinoma of the breast: Incidence and variants

Histopathology

Infiltrating lobular carcinoma of the breast

Histopathology

Infiltrating lobular carcinoma of the breast: An evaluation of the incidence and consequences of bilateral disease

Br J Surg

Long-term survivors after breast cancer

Br J Surg

Prognosis in infiltrating lobular carcinoma. An analysis of “classical” and variant tumors

Am J Surg Pathol

Original contribution
Pleomorphic variant of invasive lobular carcinoma of the breast