Diagnostic Challenge of Invasive Lobular Carcinoma of the Breast: What Is the News? Breast Magnetic Resonance Imaging and Emerging Role of Contrast-Enhanced Spectral Mammography

Table of Contents

1. Introduction

Breast cancer (BC) affects millions of women worldwide. Invasive lobular carcinoma (ILC) is the second most common type of invasive breast cancer accounting for 5–15% of cases [1,2,3]. The incidence of ILC is highest in white older women [4] and over the last two decades it has increased, also due to the use of hormone replacement therapies [5,6,7,8,9].

Generally, diagnosis is late at a more advanced tumoral stage than other BC types [10,11,12,13,14]. In fact, ILC tends to be clinically silent and difficult to detect through imaging due to its underhand growth pattern [15].

ILC is well recognized by pathologists and is composed of relatively small, discohesive epithelial cells infiltrating the fibrous stroma in a single-file pattern with minimal stromal reaction. Pathological hallmark features of ILC include lack or loss of cell–cell adhesion molecule E-cadherin (encoded by CDH1 gene) [2,16,17] and positive for both the oestrogen (ER) and progesterone receptors (PgR) and negative for the human epidermal growth factor receptor 2 (HER-2) [2].

Invasive ductal carcinoma (IDC) is generally identified as a mass on clinical and radiological examinations and as it originates from mammary ducts, microcalcifications are also a common sign on mammography [18]. ILC originates in the lobule structures that show individual layers of cells traversing the surrounding tissues similar to the threads of a spider’s web. This infiltrative growth pattern generally does not induce conspicuous desmoplastic reaction and architectural distortion neither forms a mass. The lesion often shows a mammographic density less than or equal to surrounding breast parenchyma, indistinguishable from normal breast tissue [19] and microcalcifications are a rare mammographic finding (variating widely from 0 to 24%) [20].

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These widespread growth patterns make diagnosis particularly challenging.

Digital mammography is the first level imaging examination for breast cancer diagnosis with a sensitivity between 63 and 98% [1]. However, its diagnostic performance in ILC detection is more limited ranging between 57–81% [9], especially in dense breast tissue (in extremely dense breast tissue, ILC detection can be as low as 30%) [17].

Digital breast tomosynthesis (DBT) has the potential to explore breast tissues by producing thin slices of the mammographic view. DBT reduces the tissue-masking effect and improves lesion conspicuity with a better evaluation of parenchymal distortion, asymmetries and ill-defined masses, which are common findings in ILC [21,22]. Despite its advantages, DBT is based on differential tissue X-ray attenuation and can remain suboptimal.

Ultrasound (US) is not used as a screening tool and generally evaluates suspicious findings detected at clinic or at mammographic examinations.

All these imaging diagnostic techniques can help radiologists detect equivocal malignant signs but often a correct diagnosis can be challenging even at later stages when tumors are larger, multifocal, multicentric and metastatic.

Therefore, it is important to improve breast imaging methods to detect and diagnose ILC.

At present, breast magnetic resonance imaging (BMR) is recognized as the most sensitive diagnostic tool to detect and stage ILC. BMR provides information about the morphology of the lesion but also an analysis of tumor neoangiogenesis. BMR is quite useful in patients in whom the diagnosis of ILC is proved and the disease extent is uncertain from physical exam and mammography/ultrasound tests. BMR may detect additional diseases not otherwise appreciated through conventional imaging and may provide more accurate staging information to guide surgical treatment [23,24].

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Recently a new emerging digital mammography technology based on contrast enhancement evaluation, contrast-enhanced spectral mammography (CESM), is improving cancer detection and decreasing misdiagnosis rates [25].

CESM combines conventional mammography with the intravenous administration of an iodinated contrast material offering both morphological and functional information of breast tissue [26,27,28].

Several studies have shown that the diagnostic performance of CESM is similar to that of MRI and that CESM may be useful for indications previously reserved for MRI [25,29].

In our breast diagnostic unit, CESM has been used since May 2019 and our experience is showing the new potential in helping diagnosis in different clinical settings.

In this study, we compare the ability of CESM and BMR in the detection and staging of invasive lobular carcinoma to investigate the potential of CESM in the diagnostic work-up of a patient with ILC.

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About the Author: Tung Chi