Breast Cancer Histology

Updated: Jul 25, 2016
  • Author: Peter Abdelmessieh, DO, MSc; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
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Overview

Overview

Breast cancers usually are epithelial tumors of ductal or lobular origin. Breast cancers are classified as follows:

  • Ductal carcinoma in situ (DCIS)
  • Lobular carcinoma in situ
  • Invasive ductal carcinoma (ductal breast cancer)
  • Invasive lobular carcinoma
  • Medullary carcinoma
  • Mucinous (colloid) carcinoma
  • Tubular carcinoma
  • Papillary carcinoma
  • Metaplastic breast cancer (MBC)
  • Phyllodes tumors
  • Mammary Paget disease (MPD)
  • Inflammatory breast cancer

The following features are all important in deciding on a course of treatment for any breast tumor:

  • Size
  • Status of surgical margin
  • Presence or absence of estrogen receptors and progesterone receptors
  • Nuclear and histologic grade
  • DNA content
  • S-phase fraction
  • Vascular invasion
  • Tumor necrosis
  • Histologic grade
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Ductal Carcinoma In Situ

Ductal carcinoma in situ (DCIS) is noninvasive breast cancer that is limited to the inside of the ducts of the breast. Increased use of screening mammography has resulted in a dramatic increase in the detection of ductal carcinoma in situ (DCIS). Approximately 64,000 cases of DCIS are diagnosed annually in the United States. Ninety percent of DCIS cases are identified on mammography as suspicious calcifications, with a linear, clustered, segmental, focal, or mixed distribution.

The Van Nuys Prognostic Index{ref 1} is used to assess grade in DCIS. See Table 1, below.

Table 1 The Van Nuys Prognostic Index (VNPI) Scoring System (Open Table in a new window)

Score* 1 2 3
Size <15 mm 16-40 mm > 41 mm
Margins >10 mm 1-9 mm < 1 mm
Pathologic



Classification



Non–high grade without necrosis (nuclear grade 1 and 2) Non–high grade with necrosis (nuclear grade 1 and 2) High grade with or without necrosis (nuclear grade 3)

The grading of invasive carcinoma is also important as a prognostic indicator, with higher grades indicating a worse prognosis. Grade I tumors are associated with a 10-year survival rate of 85%, but the survival rate falls to 45% for grade III tumors. See the descriptions of invasive carcinoma, below.

DCIS is divided into comedo (ie, cribriform, micropapillary, solid) and noncomedo subtypes, which provides additional prognostic information on the likelihood of progression or local recurrence (see the images below). Less common subtypes of DCIS are as follows:

  • “Clining” carcinoma
  • Indraductal signet ring carcinoma
  • Cystic hyerpsecretory duct carcinoma

 

Breast cancer. Intraductal carcinoma, comedo type. Breast cancer. Intraductal carcinoma, comedo type. Distended duct with intact basement membrane and central tumor necrosis.
Breast cancer. Intraductal carcinoma, noncomedo ty Breast cancer. Intraductal carcinoma, noncomedo type. Distended duct with intact basement membrane, micropapillary, and early cribriform growth pattern
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Lobular Carcinoma In Situ

Lobular carcinoma in situ (LCIS) arises from the lobule at the terminal end of the duct and shows a rather diffuse distribution throughout the breast, which explains its presentation as a nonpalpable mass in most cases (see the images below). Over the past 25 years, LCIS incidence has doubled and is currently 2.8 per 100,000 women. The peak incidence is in women aged 40-50 years.

Breast cancer. Lobular carcinoma in situ. Enlargem Breast cancer. Lobular carcinoma in situ. Enlargement and expansion of lobule with monotonous population of neoplastic cells.
Breast cancer. Lobular carcinoma in situ. Enlargem Breast cancer. Lobular carcinoma in situ. Enlargement and expansion of lobule with monotonous population of neoplastic cells

A study by Tran-Thanh et al found that the prolactin receptor gene is a potentially important target in the pathogenesis and progression of lobular neoplasia. Because this gene was found to be potentially less important in ductal carcinomas, the conclusion is that lobular and ductal carcinomas may evolve along separate pathways [2]

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Invasive Carcinoma

Invasive ductal carcinoma

Invasive ductal carcinoma is the most commonly diagnosed breast cancer and has a tendency to metastasize via lymphatics. This lesion, which accounts for 75% of breast cancers, has no specific histologic characteristics other than invasion through the basement membrane of a breast duct, as seen in the image below. DCIS is a frequently associated finding on pathologic examination.

Breast cancer. Infiltrating ductal carcinoma. Low- Breast cancer. Infiltrating ductal carcinoma. Low-grade carcinoma with well-developed glands invading the fibrous stroma.

The National Comprehensive Cancer Network [3] recommends using the Nottingham Criteria [4] in grading invasive carcinoma of the breast. [4] Separate scores are given for gland (acinus) formation, nuclear atypica/pleomorphism, and mitosis counts.

Gland (acinus) formation is scored as follows:

  • Score 1: >75% of the whole carcinoma forms acini
  • Score 2: 10-75% of the whole carcinoma forms acini
  • Score 3: <10% of the whole carcinoma forms acini

Nuclear atypia/pleomorphism is scored as follows:

  • Score 1: Nuclei only slightly larger than benign breast epithelium (<1.5 × normal area); minor variation in size, shape, and chromatin pattern
  • Score 2: Nuclei distinctly enlarged (1.5–2 × normal area), often vesicular, nucleoli visible; may be distinctly variable in size and shape but not always
  • Score 3: Markedly enlarged vesicular nuclei (>2 × normal area), nucleoli often prominent; generally marked variation in size and shape but atypia not necessarily extreme

Mitosis counts, which involve a pathologist counting cells with definite mitosis in 10 consecutive fields, result in a score of 1-3.

Final grading results from the addition of all the above, with a total score between the range of 3-9. Scores and grades are as follows:

  • Total score 3-5 = grade 1
  • Total score 6 or 7 = grade 2
  • Total score 8 or 9 = grade 3

Invasive lobular carcinoma

Invasive lobular carcinoma has a much lower incidence than infiltrating ductal carcinoma, constituting less than 15% of cases of invasive breast cancer. It is characterized histologically by the “Indian file” arrangement of small tumor cells.

Staining for E-cadherin can add in distinguishing lobular carcinoma from invasive ductal carcinoma. Studies have illustrated a link between cadherin (CDH1) gene and invasive lobular breast cancers, with approximately 50 % of this subtype of breast cancer containing E-cadherin mutations. However, like ductal carcinoma, infiltrating lobular carcinoma typically metastasizes to axillary lymph nodes first. However, it also has a tendency to be more multifocal. Despite that, the prognosis is comparable to that of ductal carcinoma. [1]

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Medullary Carcinoma

Medullary carcinomas appear commonly in a younger patient population, and are more frequent in women who have BRCA1 gene mutations. These tumors have a more favorable prognosis that infiltrating ductal carcinoma. Most patients present with a bulky palpable mass with axillary lymphadenopathy. Diagnosis of this type of breast cancer depends on the following histologic triad:

  • Sheets of anaplastic tumor cells with scant stroma
  • Moderate or marked stromal lymphoid infiltrate
  • Histologic circumscription or a pushing border

 

 

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Mucinous Carcinoma

Mucinous (colloid) carcinoma is another rare histologic type, seen in fewer than 5% of invasive breast cancer cases. It usually presents during the seventh decade of life as a palpable mass or appears mammographically as a poorly defined tumor with rare calcifications, and tends to be well circumscribed

Mucin production is the histologic hallmark. Two main forms occur, type A and B, with AB lesions possessing features of both. Type A mucinous carcinoma represents the classic variety with larger quantities of extracellular mucin (see the image below), whereas type B is a distinct variant with endocrine differentiation, with histology showing more granular cytoplasm then type A carcinomas.{ref 5}

Breast cancer. Colloid (mucinous) carcinoma. Nests Breast cancer. Colloid (mucinous) carcinoma. Nests of tumor cells in pool of extracellular mucin
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Tubular Carcinoma

Tubular carcinoma of the breast is an uncommon histologic type constituting 1-2% of all breast cancers. Characteristic features of this type include a single layer of epithelial cells with low-grade nuclei and apical cytoplasmic snoutings arranged in well-formed tubules and glands.

Tubular components constitute more than 90% of pure tubular carcinomas and at least 75% of mixed tubular carcinomas. This type of breast cancer has a low incidence of lymph node involvement and a very high overall survival rate. Because of its favorable prognosis, patients are often treated with only breast-conserving surgery and local radiation therapy.

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Papillary Carcinoma

Papillary carcinoma of the breast encompasses a spectrum of histologic subtypes. There are two common types: cystic (noninvasive form) and micropapillary ductal carcinoma (invasive form). Papillary breast cancer is usually seen in women older than 60 years and accounts for approximately 1-2% of all breast cancers. Papillary carcinomas are centrally located in the breast and can present as bloody nipple discharge. They are strongly estrogen receptor (ER) positive and progesterone receptor (PR) positive.

Cystic papillary carcinoma has a low mitotic activity, which results in a more indolent course and a good prognosis. However, invasive micropapillary ductal carcinoma has a more aggressive phenotype, even though approximately 70% of cases are ER positive. A retrospective review of 1,400 cases of invasive carcinoma identified 83 cases (6%) with at least one component of invasive micropapillary ductal carcinoma.

Additionally, lymph node metastasis is seen frequently in this subtype (70-90% incidence), and the number of lymph nodes involved appears to correlate with survival.

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Metaplastic Breast Cancer

Metaplastic breast cancer (MBC) accounts for less than 1% of breast cancer cases, tends to occur in older women (average age of onset in the sixth decade), and has a higher incidence in blacks. It is characterized by a combination of adenocarcinoma plus mesenchymal and epithelial components.

MBC encompasses a wide variety of histologic patterns, including the following:

  • Spindle-cell carcinoma
  • Carcinosarcoma
  • Squamous cell carcinoma of ductal origin
  • Adenosquamous carcinoma
  • Carcinoma with pseudosarcomatous metaplasia
  • Matrix-producing carcinoma

This diverse group of malignancies is identified as a single entity based on a similarity in clinical behavior. Compared with infiltrating ductal carcinoma, MBC tumors have the following characteristics:

  • Larger size
  • More rapid growth
  • Commonly node-negative
  • Typically ER negative, PR negative, and HER2 negative
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Phyllodes Tumor

Phyllodes tumors rare tumors of the breast, accounting for less than 1% of breast tumors. The name "phyllodes," which is taken from the Greek language and means "leaflike," refers to that fact that the tumor cells grow in a leaflike pattern. These tumors may be considered benign, borderline, or malignant depending on the following histologic features:

  • Stromal cellularity
  • Infiltration at the tumor's edge
  • Mitotic activity

Malignant phyllodes tumours behave like sarcomas and are known to develop hematogenous metastases. Occurrence is most common in premenopausal women age 40 and 50. The hematogenous spread of this subtype of breast cancer makes wide local excisional biopsy paramount, as chemotherapy or radiation are not effective in recurrent or metastatic disease. 

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Mammary Paget Disease

Mammary Paget disease (MPD) is relatively rare, constituting 1-4% of all breast cancers. Peak incidence is seen in the sixth decade of life (mean age, 57 years).

This adenocarcinoma is localized within the epidermis of the nipple-areola complex and is composed of the histologic hallmark Paget cells within the basement membrane. Paget cells are large, pale epithelial cells with hyperchromatic, atypical nuclei, dispersed between the keratinocytes singly or as a cluster of cells.

Lesions are predominantly unilateral, developing insidiously as a scaly, fissured, oozing, or erythematous nipple-areola complex. Retraction or ulceration of the nipple is often noted, along with symptoms of itching, tingling, burning, or pain.

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Inflammatory Breast Cancer

Inflammatory breast cancer (IBC) is a highly aggressive locally advanced breast cancer. It is rare, comprising only 1 to 5% of invasive breast cancers. Due to its aggressive nature, patients often have lymph node involvement at the time of presentation. IBC is characterized by diffuse erythema and edema (peau d'orange) involving a third or more of the skin of the breast (see the image below).

Inflammatory breast cancer illustrating the classi Inflammatory breast cancer illustrating the classical peau d’orange of involved skin. Courtesy of Dr Giorgio M Baratelli, Radiopaedia.org, rID 43353.

The classic histologic finding in inflammatory breast cancer on biopsy of affected skin is dermal lymphatic invasion by tumor cells. These malignant cells form tumor emboli (see the image below), which are responsible for both the local signs and symptoms and for the development of metastatic disease.

Histologic section of an inflammatory breast cance Histologic section of an inflammatory breast cancer specimen. Courtesy of Sofia D Merajver, MD, PhD.

 

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