Invasive Lobular Carcinoma (ILC) is the second most common form of invasive breast cancer, representing 10 to 15% of all cases. ILC differs significantly from the more prevalent Invasive Ductal Carcinoma (IDC) due to its unique cellular structure. ILC cells lose the ability to adhere to one another, causing them to infiltrate tissue in single-file lines rather than forming a cohesive mass. This diffuse growth allows the cancer to spread in patterns that are often hidden and difficult to detect, traveling to specific locations rarely seen in other breast cancer types.
Standard Sites of Metastasis
Invasive Lobular Carcinoma, like all breast cancers, frequently metastasizes to common distant sites, such as the bones, lungs, and liver. Bone remains the most frequent site for distant spread overall in ILC, often affecting the hips, spine, and ribs. Skeletal involvement frequently leads to bone pain or fractures.
The lungs and liver are also sites where ILC can spread, though typically less frequently than observed in other breast cancer types. Spread to the lung tissue or the pleural lining occurs in fewer ILC patients. ILC also shows a reduced propensity to metastasize to the liver compared to ductal tumors.
Distant lymph nodes outside the immediate axillary region, such as those in the abdomen or chest, are also common targets for ILC spread. The cancer cells can travel through the lymphatic system, establishing new disease sites far from the primary tumor location.
Distinctive Patterns of Spread
The most defining characteristic of ILC metastasis is its propensity to spread to sites rarely affected by other breast cancer subtypes. This atypical pattern often involves the lining of organs and cavities. These unique destinations result directly from the cancer’s non-cohesive cellular behavior.
Gastrointestinal and Peritoneal Spread
One of the most frequently reported atypical sites is the Gastrointestinal (GI) tract, including the stomach, small intestine, and colon. ILC cells infiltrate the wall of the GI tract, causing diffuse thickening rather than forming a distinct mass. This infiltration can lead to vague symptoms like indigestion, abdominal discomfort, or changes in bowel habits. The stomach is the most commonly affected site, often mistaken for a primary GI malignancy.
The peritoneal and serosal surfaces are also highly targeted areas for ILC metastasis, a pattern known as carcinomatosis. Spread to the peritoneum (the membrane lining the abdominal cavity) can lead to the buildup of fluid known as ascites, causing abdominal swelling and pain.
Gynecologic and Other Rare Sites
ILC exhibits a predilection for gynecologic organs, particularly the ovaries and the uterus. Ovarian metastasis from ILC is often mistaken for a primary ovarian tumor, necessitating careful pathology review to determine the true origin. The uterus is also a common recipient of metastatic ILC, sometimes presenting as uterine thickening.
ILC can also spread to the retroperitoneum, the space behind the abdominal lining that houses the kidneys and major blood vessels. Rare patterns include spread to the leptomeninges (the membranes surrounding the brain and spinal cord) and sometimes the orbital structures behind the eye.
The Biological Reason for Unique Metastasis
The unique metastatic pattern of Invasive Lobular Carcinoma stems directly from a fundamental change in the cancer cell’s structure: the near-universal loss of a protein called E-cadherin. E-cadherin is an adhesion molecule that functions like a molecular glue, holding epithelial cells together to form solid, cohesive tissues. The genetic loss of E-cadherin is considered the characteristic feature of ILC.
The absence of E-cadherin allows ILC cells to detach easily from the primary tumor and circulate as individual cells or small, motile chains. This “single-file” growth pattern facilitates a diffuse, infiltrating style of spread, unlike the mass-forming clumps characteristic of IDC. This lack of cellular cohesion permits ILC cells to migrate across surfaces and linings, such as the peritoneum and the walls of the GI tract.
The ability to move as single cells allows for subtle infiltration of tissue layers, explaining why the disease often presents as thickening or induration rather than a measurable nodule. This molecular alteration dictates the cancer’s ability to selectively colonize specific microenvironments.
Screening for Disseminated Disease
The diffuse and non-mass-forming nature of metastatic ILC challenges conventional screening and surveillance imaging. Standard diagnostic tools like computed tomography (CT) or magnetic resonance imaging (MRI) are optimized for detecting solid, defined masses. ILC’s tendency to spread as subtle thickening across surfaces means standard imaging can easily miss the disease, particularly in the abdominal cavity.
Surveillance relies on a combination of imaging modalities and a high degree of clinical suspicion based on new symptoms. Unexplained gastrointestinal symptoms or new-onset ascites may prompt an investigation specifically targeting ILC’s known sites of spread. Diagnosis of these atypical sites frequently requires a biopsy of the suspicious area, with immunohistochemistry confirming the breast origin.
Specialized imaging techniques offer increased sensitivity for detecting ILC metastases. Positron Emission Tomography (PET) scans using FES (Fluoroestradiol) tracers are relevant for ILC because the cancer is almost always estrogen receptor-positive. FES-PET specifically targets estrogen-sensitive cancer cells, which is useful for finding diffuse or occult disease in the peritoneum or gynecologic organs.