Lobular carcinoma in situ
Lobular carcinoma in situ | |
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Diagram showing localized and invasive LCIS |
Lobular carcinoma in situ (LCIS) is an incidental microscopic finding with characteristic cellular morphology and multifocal tissue patterns. The condition is a
One subset of LN can be defined as LCIS based on specific cellular traits and tissue changes seen histologically. These lesions are preceded by atypical lobular hyperplasia and may follow a linear progression to invasive lobular carcinoma (ILC), with specific genetic aberrations.[3] This process coincides with the progression of ductal neoplasia to ductal carcinoma in situ and invasive carcinoma. Rarely, terminal ducts may be involved in lobular neoplasia, known as pagetoid spread.
Many do not consider LCIS to be a true case of cancer, but it can indicate an increased risk of future cancer.[4][5][6] In 2018, the eighth edition of the American Joint Committee on Cancer (AJCC) removed LCIS from tumor staging and considers it a benign entity.[7]
Causes
Genetics
Cells of Lobular Neoplasia (LN), including both Atypical Lobular Hyperplasia and LCIS, and ILC share common genetic alterations, perhaps accounting, in part, for the similarities in histologic appearance. Classic LCIS and invasive lobular lesions are low-grade ER and PR-positive cancers, referring to the positive expression of Estrogen and Progesterone receptors on the neoplastic cells (determined via immunohistochemistry).
LCIS often have the same genetic alterations (such as loss of heterozygosity on chromosome 16q, the locus for the e-cadherin gene) as the adjacent area of invasive carcinoma.[9] These observations, along with genomic analysis for clonal relationships between the cells of LCIS and ILC, support LCIS as being a precursor to ILC, and that the lesions encompassed by the broader category of Lobular Neoplasia (LN) fall on a linear spectrum of progression. LCIS is often found concurrently with foci of invasive carcinoma and multiple studies have shown, using genetic sequencing techniques, that synchronous LCIS and ILC share clonal cell populations, or originate from the same line of mutated cells.
Diagnosis
Lobular lesions are incidental findings without reliable clinical correlations. Routine mammograms showing suspicious radiologic findings warrant a core needle biopsy in the abnormal area seen radiologically, and may or may not show lobular neoplasia histologically.
Morphology
Classically, LN, including LCIS, is characterized by enlargement and distension of acini making up the TDLU by proliferation of monomorphic, dyshesive, small, round, or polygonal cells with loss of polarity and inconspicuous cytoplasm. Essentially, groups of round, almost identical looking cells that fill and expand the lobule spaces, occasionally extending into the adjacent terminal ducts – termed Pagetoid extension.
Immunohistochemistry
Lobular Carcinoma In Situ may mimic low grade Ductal Carcinoma In Situ histologically. In these scenarios, pathologists may employ immunohistochemical testing to differentiate between entities.[3] This involves using marked antibodies synthetically developed to bind to target proteins expressed on or inside cells. Specifically, in LCIS, antibodies targeting the e-cadherin protein (or lack thereof) and p120 catenin proteins are used to differentiate LCIS from DCIS. Due to the fact that LCIS shows lack of e-cadherin expression on cell membranes and subsequent p120 catenin buildup in the cytoplasm, lesions that show positive membrane immunoreactivity for e-cadherin are diagnosed as DCIS.[3]
Treatment
Lobular Carcinoma In-situ is both a risk factor and precursor of invasive carcinoma. Furthermore, it is a non-obligate precursor. In other words, LCIS represents a distinct entity in the developmental pathway of cancer that does not guarantee invasive carcinoma. That being said, the historical approach of radical mastectomy (surgical removal of entire breast and axillary lymph nodes) has been substituted by more conservative approaches.
When Lobular Neoplasia, or specifically, LCIS, is found on core needle biopsy during routine workups, the National Comprehensive Cancer Network (NCCN) recommends the surgeon perform an excisional biopsy of the region to allow pathologists to rule out concurrent DCIS or invasive cancer. It has been widely reported in the literature that 10-30% of patients with a diagnosis of LCIS on core needle biopsy will receive an upstaged diagnosis after excisional.[13] If LCIS remains the only diagnosis after the excisional biopsy, NCCN guidelines recommend clinical follow-up every 6–12 months with annual diagnostic mammograms.
Prognosis
Lobular neoplasia is considered pre-cancerous, and LCIS is an indicator (marker) for increased risk of developing invasive breast cancer in women. This risk extends more than 20 years. Most of the risk relates to subsequent
Older studies have shown that the increased risk of developing invasive cancer is equal for both breasts, and more recent studies suggest that while both breasts are at increased risk of developing invasive cancer, the
LCIS (lobular neoplasia is considered pre-cancerous) is an indicator (marker) identifying women with an increased risk of developing invasive breast cancer. This risk extends more than 20 years. Most of the risk relates to subsequent
While older studies have shown that the increased risk is equal for both breasts, a more recent study suggests that the
Epidemiology
LCIS is identified in 0.5-1.5% of benign breast biopsies. These biopsies are often done in response to suspicious mammographic findings, as discussed in the Diagnosis section of this article. LCIS is identified in 1.8-2.5% of all breast biopsies (including those that show histologic evidence of other Lobular or Ductal Neoplasia.[13] The incidence of LCIS in women without prior history of breast neoplasia has increased from 0.90 per 100,000 persons in 1980 to 3.19 per 100,000 persons in 1998 – but this is likely due to the increased frequency of mammography as a screening tool. This is supported by the fact that the magnitude of increase in frequency of LCIS was greatest among women over 50 years of age (the group most likely to participate in routine mammographic screening).
History
In 1941, a seminal publication by Foote and Stewart introduced the term “Lobular Carcinoma In Situ,” using it to categorize a spectrum of cytologic changes that were precursors to invasive cancer. They described these changes as unrecognizable on gross examination, noninfiltrating, and multifocal, with the cells losing their apical-basal distinction (loss of polarity) and varying in shape but not size.[13] They further predicted that though still contained within the basement membrane, LCIS can indicate an increased risk of future cancer. Researchers and physicians currently treat the diagnosis as a precursor lesion and risk factor for subsequent development of breast cancer.[18]
This article has thus far described Classical LCIS, and there are 2 other variants of LCIS: Pleomorphic LCIS (PLCIS) and Apocrine PLCIS, which may be discussed separately in a separate article.[19]
Unlike ductal carcinoma in situ (DCIS), LCIS is not associated with calcification, and is typically an incidental finding in a biopsy performed for another reason. LCIS only accounts for about 15% of the in situ (ductal or lobular) breast cancers.[20]
See also
References
- ^ "Lobular Carcinoma in situ (LCIS)". Breast Cancer. Stanford Cancer Center.
- ^ PMID 29413653.
- ^ PMID 29413656.
- ^ a b "Lobular carcinoma in situ: Marker for breast cancer risk". MayoClinic.com.
- ^ "Breast Cancer Treatment". National Cancer Institute. 27 May 2022.
- S2CID 388045.
- ^ AJCC Cancer Staging Manual, Eighth Edition - Part XI - Breast (PDF). The American College of Surgeons. 2018. p. 590.
- ^ PMID 26041550.
- ^ S2CID 19569431.
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- ^ PMID 25268198.
- ^ ISBN 9780387952703.
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- ISBN 978-0-7216-0187-8.
- ^ a b "Breast Cancer Treatment (PDQ®) - National Cancer Institute - Lobular Carcinoma In Situ". Retrieved 2013-01-12.
- PMID 28646773.
- S2CID 6429291.
- ^ "Lobular carcinoma in situ: Marker for breast cancer risk". MayoClinic.com.
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- S2CID 6429291.