Lobular Carcinoma In Situ – LCIS
Author Lisa Wiechmann MD
Overview
Lobular carcinoma in situ (LCIS) was first described in 1941 ( Foote and Stewart) and is characterized by three important features: 1) the lesion is a microscopic finding that is not apparent clinically and is usually an incidental finding; 2)the lesion is multicentric in the breast and often bilateral and 3) both infiltrating ductal and lobular carcinomas may develop after LCIS. Lobular carcinoma in situ arises from the terminal lobular duct units.LCIS is a risk factor for bilateral breast cancer (approximately 1% per year) and therefore careful clinical followup is appropriate for most women. Treatment with tamoxifen reduces the risk of breast cancer ( by approximately 55%) and for women who are unwilling to undergo close follow-up, bilateral mastectomy may be indicated.
LCIS is considered a marker of increased risk for invasive breast cancer rather a premalignant lesion .
Statistics
LCIS lacks clinical and mammographic signs and therefore it’s true incidence is not known. Numerous authors have reviewed breast biopsies in an effort to determine the incidence of LCIS and the results varied from 0.5% ( Page et al) to 3.6% ( Haagensen et al) . Incidence is increasing partly because of criteria that contribute to its definition as a pathologic entity and to mammography. LCIS is multicentric in 60-80% of cases and bilateral in at least 26% of cases. LCIS accounts for approximately 10% of all the mammographically detected malignant lesions and is ten times more frequent in white women than in African-American women.screening population.The age at diagnosis is 44-47 years ( vs 52-58 years for DCIS) and 25-35% of women with LCIS develop invasive carcinoma ( 65% of invasive carcinomas that develop are infiltrating ductal, not lobular, carcinomas).
Geogrpahic Distribution
The incidence of breast cancer varies significantly among differennt countries, and is highest in Northern European countries and in the United States, intermediate in Southern America and Southern and Eastern Europe, and lowest in Asia (Japan, Singapore and urban China have seen a rise in rates with the advent of Western-style economy). Breast cancer incidence and mortality vary sigificatly within the United States. The incidence of breast cancer appears to be highest in white women from Hawaii (128:100,000) followed by those from San Fransisco and the Northeast.The lowes incidence is found in Utah(98:100,000) and New Mexico
The variation of incidence for African-American woment is relatively small ( 94-106:100,000).
Socieconomics
Unlike most other illnesses a positive correlation has been noted between the lifetime risk of breast cancer and higher socioeconomic status.
the incidence of LCIS
Genetics
The genetics of LCIS parallel those of invasive breast cancer. Only 5-10% of breast cancers are thought to result from inheritance of a mutated gene. Many Autosomal Dominant conditions have been associated with an increased risk of breast cancer and these include Li-Fraumeni Syndrome, Muir-Torre Syndrome, Cowden disease and Peuts – Jeghers syndreome. Particular attention has been given to BRCA-1 ad BRCA-2 mutations and their association with breast cancer. BRCA-1 is a gene found on the long arm of chromosome 17q wherease BRCA-2 is found on chromosome 13. BRCA- 1 mutations are associated with and increased risk of both breast cancer ( 37-87% by age 70) and ovary (11-42% by age 60) and almost all mutations are found in the germline. BRCA-1 has been associated with orderly and efficient progression of the cell through its life cycle and it appears to play an important role in response to DNA damage. BRCA-2 mutations are associated with a 6% lifetime risk of male breast cancer. The biological function of the BRCA-2 gene is not well understood but it is thought to play a role in DNA damage response. Other types of cancer are associated with mutations in BRCA-2. These include prostate cancer, bladder cancer, pacreatic cancer, Non-Hodgkin’s lymphoma, basal cell carcinoma and fallopian tube tumors.
Sex Distribution
almost exclusively a female disease
Age Distribution
The age at presentation of LCIS is 44-47 years of age.
Associated Diseases
LCIS is associated with a 5% incidence of sychronus invasice cancer. Multicentric LCIS is identified in 60-80% of mastectomy specimens and is found to be bilateral in 26-35% of cases.
Predisposing Factors
Cause of breast cancer and carcinoma in situ is mostly unknown ( 70-80% of cases) but contributing factors include racial origin, parity, menstrual factors, hormonal factors, heredity, and mammary dysplasia. THe predisposing factors for LCIS mirror those of breast cancer but are not as clearly defined.
Pathogenesis
LCIS is characterized by a prolliferation of small cells with uniform nucleithat distend and distort the terminal duct lobular units. Such cancer cells have a normal nucleus-cytoplasm ratio.Two types of cells have been described by Haagensen : Type A , or classical type hav e an eosinophylic cytoplasm that may contain vacuoles; type B cells are larger with large nuclei that diplay pleomorphism. Calcifications may be found in tissues adjacent to LCIS ( neighborhood calcification) and this is a feature of LCIS that contirbutes to its diagnosis.
LCIS cells show a low proliferative rate, are typically estrogen-receptor positive and are characterized by loss of expression of E-cadherin.
Natural History
26-35% with LCIS develop invasive cancer. Most cancers that develop in women with LCIS are infiltrating ductal cancers (65%)
Gross Pathology
LCIS is not detectable on gross examination.
Histopathology
Two types of cells have been described by Haagensen : Type A , or classical type hav e an eosinophylic cytoplasm that may contain vacuoles; type B cells are larger with large nuclei that diplay pleomorphism. Calcifications may be found in tissues adjacent to LCIS ( neighborhood calcification) and this is a feature of LCIS that contirbutes to its diagnosis.
LCIS cells show a low proliferative rate, are typically estrogen-receptor positive and are characterized by loss of expression of E-cadherin.
Clinical Presentation
LCIS lacks clinical and mammographic signs and is often an incidental finding on biopsy. Neighborhood calcifications as described above, are a feature unique to LCIS and contribute to its diagnosis.
Laboratory Tests
no specific laboratory tests are useful in the primary diagnosis
Imaging
Mammography may reveal neighborhood calcifications that may contirbute to diagnosis of LCIS. |
