Invasive lobular carcinoma: Clinical sciences

Invasive lobular carcinoma is the second most common subtype of invasive breast cancer and occurs when malignant epithelial cells from lobular tissue infiltrate through their basement membrane. It’s more common in older patients and more likely to be at an advanced stage on initial diagnosis. This cancer can be classified as early-stage, locally-advanced, or metastatic disease, and treatment is based on the stage.

As a clinical pearl, shared multi-disciplinary decision making is a central standard to breast cancer care, which is managed by a breast team that consists of a breast surgeon, oncologist, radiation oncologist, pathologist, radiologist, and reconstructive surgeon.

When assessing a patient presenting with a new breast lump or abnormal finding, consider an invasive lobular carcinoma. The first step is to obtain a focused history and physical exam, as well as labs like CBC, CMP, LFTs, and alkaline phosphatase.

Typically, patients present with an abnormal screening mammogram or a new breast finding like a lump or asymmetric area of firmness. The history might also include changes in breast or nipple appearance, nipple discharge, or axillary lymphadenopathy. Make sure to ask your patient about risk factors, such as the personal or family history of breast or ovarian cancer, early menarche, late menopause, nulliparity, or first pregnancy after 30 years of age.

Other important risk factors include age over 40, and alcohol use. Finally, look out for a known history of dense breast tissue, exogenous hormone use, as well as family or personal history of deleterious cancer gene mutations like BRCA.

Physical exam might reveal a palpable breast mass and skin or nipple changes. Now, lobular carcinomas are less likely to form a discrete mass, which makes them more difficult to detect on physical exam. So, pay close attention to any areas that feel asymmetric or firm. Another important finding is lymphadenopathy. When assessing lymph nodes, make sure to examine above and below the clavicle, and in the axilla.

Also pay attention to findings that may indicate metastasis, such as bone pain, neurological changes, or a cough. Finally labs might show elevated LFTs or alkaline phosphatase, potentially indicating metastasis to the liver or bone, respectively.

Once you’re done with history and physical exam, move on to imaging. To start, get a diagnostic mammogram and an ultrasound. If neither of the imaging studies show any suspicious findings or evidence of underlying breast cancer, consider an alternative diagnosis.

Here’s a clinical pearl! Breast findings on imaging can be categorized with a standardized system called BI-RADS, which stands for Breast Imaging-Reporting and Data System. The imaging findings are assigned into categories labeled as 0 to 6. First, 0 means incomplete, which needs additional imaging or comparison with previous images if available. Next, 1 is negative, meaning that mammography is normal, with no findings like masses or calcification; while 2 indicates findings are completely benign, meaning that mammography reveals findings with no probability of malignancy; a category of 0, 1, and 2 can only be used when undergoing routine screening.

On the other hand, 3 is probably benign, meaning that mammography may reveal a finding with minimal malignant potential of less than 2%, so these patients should get follow-up imaging. Next, 4 is suspicious for malignancy, meaning that mammography may reveal a finding with malignant potential between 2 to 94%, where biopsy will likely be indicated. Then, a category of 5 is highly suspicious of malignancy, with malignant potential over 95%. Lastly, 6 is known malignancy that has been proven with biopsy, and requires definitive management with surgery, chemotherapy, or radiation.

Now, let’s talk about imaging findings that are suspicious for invasive lobular carcinoma. Lobular carcinoma can be multifocal and bilateral, so remember to always investigate both breasts. A diagnostic mammogram might show a spiculated or irregular soft tissue opacity or mass. Due to their diffuse growth pattern, well-circumscribed masses are not as common, and it can be difficult to identify the extent of the disease. In addition, imaging might show calcifications. However, in some cases, asymmetry or slight architectural distortion might be the only suspicious findings. On ultrasound, look for a spiculated soft tissue mass of heterogeneous hypoechogenicity that’s taller than it’s wide, with posterior acoustic shadowing. You might even see acoustic shadowing without a mass. In addition, ultrasound can help evaluate for abnormal lymph nodes, which will show an irregular shape, abnormal cortical thickening, or displaced fatty hilum. If you encounter any of these signs, suspect invasive lobular carcinoma.

Okay, after imaging, you need to confirm the diagnosis with a core needle biopsy. If the core needle biopsy doesn’t show any malignant cells, and the biopsy results are consistent with the imaging findings, consider an alternative diagnosis. However, if the core biopsy doesn't show findings that provide a diagnosis consistent with imaging, it could be a false negative, so you should repeat a core biopsy or even get an excisional biopsy!

Okay, histologic findings consistent with lobular carcinoma include small, uniform, malignant epithelial cells of lobular origin. These cells are discohesive and diffusely infiltrate breast stroma in a single-file manner, which indicates loss of cellular E-cadherin. Additionally, they might be encircling ducts. If you see these findings, you can diagnose invasive lobular carcinoma.