What is lobular carcinoma in situ (LCIS)?

Related conditions:
Lobular carcinoma, atypical lobular hyperplasia, ductal carcinoma in situ (DCIS), ductal carcinoma

Definition:



Lobular carcinoma in situ (LCIS) is a type of noninfiltrating breast tumor that originates in the breast lobules. It differs from other breast tumors in its propensity to develop in multiple sites in one or both breasts. Unlike other in situ tumors, LCIS is considered a marker rather than a premalignant lesion for subsequent development of invasive breast cancer. Only 25 to 35 percent of patients with lobular carcinoma in situ develop invasive cancer, compared with patients with other in situ lesions, such as ductal carcinoma in situ (DCIS). Between 25 and 70 percent of those with DCIS will develop invasive breast cancer.

Risk factors: Being a woman is a significant risk factor because men do not possess developed lobular breast tissue. Increasing age (forty and above) also contributes to the risk of LCIS. A family history of breast cancer, especially in first-degree relatives, is another significant risk factor, although not specific to any type of breast cancer. White patients have a twelvefold increased risk of LCIS compared with the general population; however, patients of African American origin have a higher rate of recurrence. Other risk factors include obesity, not giving birth before the age of thirty, and a prior history of breast cancer.

Etiology and the disease process: The etiology of LCIS has been linked in some studies to loss of heterozygosity in chromosome 16q, 17p, and17q (BRCA1 tumor-suppressor gene), which predisposes people to unregulated monoclonal proliferation. An alteration in the E-cadherin adhesion complex has also been noted in LCIS. Lobular carcinoma in situ originates from the terminal duct-lobular apparatus, where it is thought that monoclonal cells from the cellular lining (epithelium) of this apparatus undergo uninhibited proliferation within the lobule. Cells do not possess the atypical findings of other cancer cells, such as increased nucleus-to-cytoplasm ratios, increased cellular division, and loss of cellular cohesion or necrosis. However, the cells are enlarged and possess characteristic mucoid globules that help distinguish LCIS from DCIS. An interesting characteristic of LCIS is that invasion of tissue outside the lobule does not ensue, leaving lobular tissue architecture intact. As a result, LCIS can develop in multiple lobules undetected by clinical breast examinations and mammography. In spite of this, development of invasive cancer from LCIS is slow and may take as long as fifteen to twenty years.

Incidence: The overall incidence of LCIS, as documented by breast biopsies with a suspicious mammogram, is estimated at 2 to 5 percent. LCIS accounts for 9.8 percent of all breast malignancies. The diagnosis of LCIS peaks around the mid-forties. It is also interesting to note that more than 90 percent of women diagnosed with lobular carcinoma in situ are premenopausal, which suggests a plausible role of estrogen in LCIS proliferation.

Symptoms: LCIS is often missed due to the lack of overt signs and symptoms like those associated with other breast lesions, such as incidental discovery of a breast mass on self-examination, changes in the skin or nipples, and the presence of pain or nipple discharge. More often than not, LCIS is an incidental finding in otherwise normal breast biopsies. The presence of “neighborhood calcifications” in normal tissue surrounding the lesion on mammography is unique to LCIS and may aid in diagnosis.

Screening and diagnosis: Screening for all breast cancer follows the American Cancer Society (ACS) recommendations. ACS guidelines recommend that breast examinations be conducted every three years as part of a routine checkup beginning at age twenty (annually beginning at age forty) and that screening mammographies be conducted annually starting at age forty. Diagnosis of LCIS depends on the pathologic findings obtained by needle core biopsy. LCIS may accompany invasive cancer in 5 percent of cases. On microscopic examination, cancer cells may be densely packed and occupy the lobular spaces (acini), terminal ducts, or ductules completely without spread to adjacent structures. The cell nucleus, nucleolus, and cytoplasm are dark-staining and large. Immunohistochemical studies may also reveal E-cadherin-negative cells.

Treatment and therapy: Definitive surgical treatment of LCIS is geared toward removal of the multiple sites presumed to be contained in one breast. This is accomplished by surgical removal of the entire breast (total mastectomy) with optional dissection of axillary lymph nodes. The latter is optional because of the rare (less than 1 percent) occurrence of lymph node spread. Prophylactic removal of the opposite breast in the absence of pathological findings is not recommended in spite of the possibility of development of LCIS. Other treatment options include clinical observation and yearly mammography. Tamoxifen, an estrogen-receptor antagonist may be used in reducing the further development of LCIS in the remaining breast. A bilateral total mastectomy is also an option for patients with a familial inheritance of the BRCA1 gene as demonstrated by genetic studies.

Prognosis, prevention, and outcomes: Prognosis is generally excellent with complete excision. However, progression to multiple or bilateral LCIS is high, approaching 90 percent and 70 percent, respectively. Simultaneous invasive cancer incidence is 5 percent.

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