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About Breast Cancer > Histologic Types of Breast Carcinoma

Dr. Arthur Lee
Registered Specialist in Pathology
Department of Pathology, St. Paul’s Hospital
MBBS (HK), MD (HKU), Am. Board of Pathology, FHKAM (PATHOLOGY)

Breast cancer is a heterogeneous group of neoplasms, consisting of different histologic subtypes with diverse microscopic appearances. Histologic typing is important as there is a difference in biologic behavior of the various types. The histologic type interacts with other factors to help predict the prognosis and determine the appropriate clinical management.

Breast cancer may be divided into non-invasive and invasive carcinomas.

I. Non-invasive carcinoma (carcinoma in situ)
This makes up about 15-20% of all breast carcinomas. It is carcinoma that is still confined within the anatomical confines of the terminal duct-lobular units and has not invaded beyond the basement membrane boundary into surrounding tissue. Being non-invasive, it is not capable of metastasis (distant spread), and if managed properly has an excellent prognosis. It may however progress to invasive carcinoma.

There are two types of non-invasive carcinoma, with different biologic behavior:

(1.) Ductal carcinoma in situ (DCIS, intraductal carcinoma)
This type represents non-invasive carcinoma involving the ductal system. Mammogram is a sensitive procedure to detect DCIS due to the frequent presence of associated microcalcifications. A substantial proportion of DCIS is not palpable. Again, DCIS is a heterogeneous entity with difference in histologic appearances and risk of subsequent recurrence and development of invasive carcinoma. The subtypes are comedo, cribriform, micropapillary and papillary. They are also stratified into low, intermediate and high histologic grades. There are different schemes of grading in situ ductal carcinomas, but in general they are graded depending on the degree of nuclear atypia and presence or absence of necrosis. In general, comedo DCIS are high grade, with a virtually 100% chance of becoming invasive if left untreated or incompletely excised. Cribriform, micropapillary and papillary subtypes tend to be intermediate to low grade, and have an estimated 30% chance of evolving into invasive carcinoma.

(2.) Lobular carcinoma in situ (LCIS)
LCIS usually does not form a palpable mass and usually cannot be detected by clinical examination or mammographic examination. It is more commonly an incidental finding in breast biopsies performed for other reasons. Also, it is frequently bilateral and multicentric.

If left untreated, about 25-30% of women with LCIS will develop an invasive carcinoma over the next 2 decades after diagnosis. The invasive carcinoma has a roughly equal chance of developing in either breast, and may be invasive ductal or lobular carcinoma.

While DCIS is considered a precursor lesion for developing into invasive ductal carcinoma, the malignant nature of LCIS has been questioned, as progression to invasive cancer may not occur clinically in the lifetime of every patient with LCIS even if left untreated. LCIS is therefore considered as a risk predictor for subsequent development of invasive carcinoma rather than an obligatory precursor of invasive carcinoma, and the term “lobular neoplasia” has been proposed for this lesion.

Unlike DCIS, LCIS is usually not graded unless they are of the high grade pleomorphic type.

II. Invasive Carcinoma
Invasive breast carcinoma has invaded beyond the basement membrane boundary into surrounded tissue. This allows its access to lymphatics and blood vessels, thus the potential for distant metastasis and a fatal outcome. The prognosis depends on several independent parameters, including the axillary lymph node status (if there is spread to the lymph nodes), tumor size, the histologic grade (or the degree of differentiation; please see grading section below), and the histologic type.

There are several histologic types of invasive carcinoma, with different microscopic appearances and clinical behavior. In any given tumor, there may be a mixture of more than one type. Histologic typing correlates with clinical behavior. In general, invasive ductal, lobular and micropapillary carcinomas have the worst prognosis, medullary and mucinous carcinomas are intermediate, and tubular and cribriform carcinomas have the best prognosis.

(1.) Invasive ductal carcinoma, not otherwise specified (NOS)
This is the most common type, accounting for about 80% of invasive breast carcinoma. The infiltrating cancer cells frequently incite a tissue reaction resulting in a hard palpable mass. It ranges from well differentiated carcinomas with abundant gland formation to poorly differentiated neoplasms with solid sheets of malignant cells. The clinical behavior depends on the size and histologic grade.

(2.) Invasive lobular carcinoma
This subtype makes up about 10% of invasive breast carcinoma, has a greater tendency to be bilateral and multicentric and tends to form a subtle, diffuse mass. Most (about 80%) are of the so-called classic type which are mostly histologic grade 2, with a minority being grade 1. About 10% are the so-called variant types, with solid and alveolar patterns, and are also mostly grade 2. The remaining 10% are grade 3 pleomorphic type with a very aggressive behavior.

(3.) Medullary carcinoma
This subtype presents as a circumscribed soft fleshy mass. It is characterized microscopically by a composition of pleomorphic tumor cells with an abundant lymphoid stroma. Traditionally, it is believed to exhibit a relatively less aggressive behavior in spite of its pleomorphic features. Stringent diagnostic criteria must be followed by the pathologist in diagnosing this subtype. The American Joint Committee on Cancer Staging Manual (6th Ed., 2002) recommends that all invasive breast carcinomas be graded except medullary carcinoma.

(4.) Mucinous or colloid carcinoma
This type of carcinoma tends to occur in older women, and appears as a circumscribed soft gelatinous mass. Microscopically it contains sparsely cellular collections of cancer cells suspended in abundant mucus. It is usually well differentiated (grade 1 to 2), and has a favorable prognosis, with a low likelihood of nodal spread and distant metastasis.

(5.) Tubular and cribriform carcinomas
These are low-grade invasive carcinomas, so called because of the histologic appearance of well-formed tubular and cribriform glandular structures. In the pure form, they have a favorable prognosis, with a very low likelihood of metastasis.

(6.) Papillary carcinoma
This histologic type of invasive carcinoma is characterized by a papillary pattern. It is usually well differentiated (grade 1 to 2), with a prognosis that is between ductal carcinomas and tubular carcinomas.

(7.) Micropapillary carcinoma
This histologic type displays a micropapillary pattern. Even when present as a minor component, it is associated with an aggressive behavior, with a predilection for frequent and extensive lymph node metastasis.

(8.) Adenoid cystic carcinoma
This uncommon subtype has microscopic features similar to its counterpart in the salivary gland, but in contrast to the latter location, it has an excellent prognosis and rarely metastasizes.

(9.) Inflammatory carcinoma
This is a combined clinicopathologic diagnosis. Clinically, the breast skin displays edema, inflammation and an orange-peel (peau d’orange) appearance. Microscopically, there is infiltration of skin and its lymphatic channels by cancer cells. This entity is usually secondary to an extensive and advanced underlying carcinoma.

III. Paget’s disease
This is an eczema-like eruption of the nipple skin, due to involvement of major lactiferous ducts of the nipple, with extension to the nipple skin. It may be associated with a subjacent in situ or invasive carcinoma. The prognosis is that of the underlying carcinoma.

Grading of carcinomas
Carcinomas are assigned a histologic grade, according to how well they resemble the normal tissue that they are derived from. Grading of in situ ductal carcinomas has been discussed above. Invasive ductal carcinomas are graded using the Bloom & Richardson/Nottingham scheme. In simple terms, a 3 point system is given to each of 3 histologic parameters, viz., tubular formation, nuclear features and mitotic rate, and the summation score for the 3 parameters determines the grade. Carcinomas are graded as well differentiated (grade 1), moderately differentiated (grade 2) and poorly differentiated (grade 3), and there is progressively increasing aggressiveness from well to poorly differentiated carcinomas.

In summary, the histologic type of breast carcinomas provides valuable prognostic information. It complements other independent parameters including size, grade, nodal status, hormonal receptor status and HER2 oncogene status to help predict the likelihood of recurrence and response to treatment. It is important for the pathologist to provide an accurate, reproducible and skillful characterization of individual carcinomas for optimal management of breast cancer patients.

(July 2009)