Category Archives: cancer premalignant

Carcinoma In Situ Lobular Carcinoma LCIS

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.

Carcinoma In Situ Ductal DCIS

 

The Common Vein Copyright 2008

Author Lisa Wiechmann MD

Overview

 

The current favored hypothesis on the evolution of breast cancer describes a progression similar to that in colon cancer ( Knudson’s hypothesis) that includes usual ductal hyperplasia, atypical hyperplasia, carcinoma in situ ( ductal carcinoma in situ and lobular carcinoma in situ) and invasive carcinoma. The term of carcinoma in situ of the breast is used to describe cancer cells that don’t invade the basement membrane. Each type of breast carcinoma in situ (DCIS and LCIS) has a distinct clinical and biological behavior. DCIS is defined as the proliferation of epithelial cells confined to the mammary ducts without demonstrable invasion through the basement membrane.

 

 

Ductal carcinoma in situ (DCIS), also known as intraductal carcinoma,  is found in approximately 7%  of all biopsied specimens It is considered a premalignant condition and risk of invasive breast cancer

is increased nearly five times in women with DCIS. Such risk is primarily ipsilateral as a pose to LCIS which is more likely to be multifocal and bilateral. Multicentricity is seen in 60-90

% of patients with LCIS and in 40-80% of patients with DCIS. LCIS occurs bilaterally in 10-20% of of DCIS  cases and in 50-70% of LCIS cases.

 

Before mammography DCIS was primarily diagnosed by physical examination as a palpable lesion. In situ breast cancers constituted approximately 2% of all breast cancers in 1980 and LCIS was more common than DCIS by a ratio of 2:1. Screeing mammography revealed a 14 fold increase in the incidence of in situ cancer (45%) and DCIS was diagnosed more frequently than LCIS.

 

Classification

 

Many different vriants of DCIS have been described. The traditional classification system is based on the architectural pattern of the lesion and identifies five major subtypes: comed , cribriform, micropapillary, papillary and solid. Comedo type DCIS is characterized by the presence of necrosis, cribriform DCID has a fenestrated proliferation fo neoplastic cells, the micropapillary type features groups of cells orieted perpedicular to the basement membrane; the papillary type of DCIS demonstrates intraluminal projections that have central fibrovascular cores( true papillae) and finally the solid type of DCIS the tumor cells fill the involved area without any of the above described architectural patterns.Apocrine DCIS, intraductal signet cell carcinoma , endocrine DCIS and solitary papillary carcinoma are rare variants that are at times identified.

 

More recently Lagios et al proposed a classification based on nuclear grade and necrosis as a pose to architectural characteristics. Three major categories of DCIS are based on a modification of this system : high , intermediate and low grade DCIS. In 1997 a consensus conference was assembled in attempt to identify a classification system that was clinically relevanta and reproducible: although the panel did not endorse a specific system, it was agreed that certain features be routinely documented in pathology reports of DCIS: these included the presence of necrosis ( comedo or punctuate) , nuclear grade (low, intermediate of high) , cell polarization and architectural pattern.

 

 

Statistics

 

DCIS represents approximaately 70% of noninvasive carcinomas and its incidence is now 10-20 per 100,000 woman years. Since the introduction of screening mammography  the reported incidence( or detection rate)  of DCIS has increased significantly and DCIS now accounts for 20-44% of all new screen detected breast neoplasms. Approximately 10-35% of patients with DCIS have a positive family history of breast cancer ( same as for invasive breast cancer). The epidmiology of DCIS reflects that of Invasive breast cancer. SEER ( surveillance, Epidemiology and End Results) data estimated a slightly higher liftime risk of breast cancer for white women ad identified a positive association with higher socioeconomic status.

 

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.

 

Genetics

 

The genetics of DCIS 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

 

DCIS is almost exclusively a female disease

 

Age Distribution

 

The median age of patients with DCIS ranges from 47 to 63 years.

 

Pathogenesis

 

The current favoured hypothesis on the evolution of breast cancer describes a progression similar to that in colon cancer ( Knudson’s hypothesis) that includes usual ductal hyperplasio, atypical hyperplasia, carcinoma in situ ( ductal carcinoma in situ and lobular carcinoma in situ) and invasive carcnioma.Malignant cells proliferate and obstruct the ductal lumen thereby may determine an inflammatory reaction, lymphoid infiltration or stromal response around the duct. Certain factors have been identified as indicative of an aggressive biology and such factors include comedo necrosis and high nuclear grade.

 

Natural History

 

The most important issue in the management of DCIS is the risk of its progression to breast cancer.  Historically DCIS was treated with mastectomy and therefore the question has remained unansweres. Overall the available data quotes a 25-35% risk to develop ivasive breast cancer in the setting of DCIS at 5-10 years.

 

Gross Pathology

 

DCIS can be multifocal  ( two foci separated by 5mm of normal breast tissue  in the same breast quadrant) and multicentric ( a separate focus outside the index quadrant- 30-40%). DCIS of the comedo type is characterized by necrosis which grossly appears as pasty material exuding from the cut surface of the specimen or expressable from the involved ducts by palpation.

 

Histopathology

 

DCIS can by divided into subtypes based on architecture and nuclear grade.

The comedo pattern demonstrates prominent necrosis with cells that are large and show nuclear pleomorphism. The necrotic material becomes calcified and can be detected mammographically as linear calcifications. Mitotic figures are numerous and evident including abnormal ones.

Thw cribriform pattern is characterized microscopically by a fenestrated growth of neoplastic cells and radiologically by fine, scattered calcifications.

The micropapillary pattern is characterized by micropapillae without a fibrovascular core that are perpendicular to the basement membrane and project into the ductal lumen. The nuclei are usually monomorphic.

The papillary pattern is characterized by true papille ( with fibrovascular cores) that project into the lumina.

The solid pattern is charcterized by clumps of cells that lack the above specifics.

Apocrine DCIS, intraductal signet cell carcinoma , endocrine DCIS and solitary papillary carcinoma are rare variants that are at times identified.

 

Cytopathology

 

Neoplastic cells in DCIS are characterized by varying degrees of cellular atypia: nuclear grade appears to be a predictor of local recurrence.

 

Clinical Presentation

 

Before the establishment of screening mammography most patients with DCIS presented with a palpable mass, Paget’s disease of the nipple or nipple discharge. Currently “mammographic” DCIS is more commonly seen.

 

Imaging

 

Mammography is the imaging method of choice. Microcalcifications that are evident on mammograms are more commonly seen in comedo type DCIS and are described as linear branching microcalcifications. Presence of a soft tissue mass is unusual.

 

42739 Case 3 DCIS focal RCCmag Courtesy Priscilla Slanetz MD code breast fx calcifications microcalcifications dx DCIS mammogram mammography

42736 Case 3 IDC with DCIS CC Overlay Courtesy Priscilla Slanetz MD code breast fx mass dx intraductal carcinoma dx DCIS mammogram mammography