a) Ductal Carcinoma In Situ (DCIS)

Ductal carcinoma in situ or DCIS is a common diagnosis in the screened population. It is thought to be a precursor lesion to invasive breast carcinomas (with the exception of lobular carcinoma of the breast).

Epidemiology

Prior to the introduction of mammographic screening for breast cancer, isolated DCIS was an uncommon finding, with most cases being clinically undetectable. DCIS was frequently seen in combination with invasive carcinoma during this era.
DCIS, if present, is usually visible on mammogram and the establishment of widespread screening programs in the latter half of the 20th century increased the incidence of the disease 5- or 6-fold. It now makes up about 20-30% of breast carcinomas, and about half of patients who have a mammographic abnormality will be diagnosed with DCIS.

Risk Factors

The factors that increase the risk of DCIS are thought to be similar to invasive disease:

  • Gender - DCIS is far more common in women than men
  • Age - DCIS is very uncommon in young women
  • Menstruation - Early age (< 11y) of menarche and late menopause are both risk factors
  • Pregnancy - Pregnancy before the age of 20 is protective, with women in this group having half the risk of women > 35 years at first pregnancy. Nulliparous women have the highest risk.
  • Ethnicity - Breast cancer is more common in white women, but tends to present earlier and be more aggressive in African-American and Hispanic women.

Other risk factors are also important, including previous radiotherapy, oestrogen replacement, previous breast or endometrial cancers, lack of breastfeeding, diet, obesity and fitness. Smoking has not been strongly associated with breast cancer risks.

Aetiology

DCIS is thought to arise from similar processes to ductal carcinomas of the breast, and many invasive carcinomas are thought to arise from DCIS, suggesting it is one step in the path of carcinogenesis. The cell of origin is thought to lie in the terminal ductal-lobular unit (TDLU).

Natural History

Without mammographic screening, most cases of DCIS are not detected clinically. DCIS is often found in association with an invasive tumour when screening is not performed.
In the era of mammography screening, DCIS is usually picked up before an invasive component is detected.

Clinical Presentation

Over 90% of DCIS (without invasion) is detected on screening mammography. Most cases are not palpable. Rarely, patients present with nipple discharge and very rarely a mass.
On imaging, most cases of DCIS are visible as microcalcifications, which may be branching (high grade) or granular (low grade). Other imaging findings include an asymmetrical mass.
On autopsy specimens, about 6-8% of breasts will have DCIS. About 33% of cases will progress to invasive disease after 10 years, although this data is based on limited observations.

Tumour/Normal Tissue Features

Macroscopic

DCIS may be invisible macroscopically, particularly if it is only low grade disease. High grade lesions distant and distort the ducts; necrosis may be visible macroscopically as comedo-like (acne).

Microscopic

There are five common architectural subtypes of DCIS:

  • Comedo: High grade disease, demonstrating ducts filled with malignant appearing cells and central necrosis
  • Solid: Medium-high grade, with ducts full of solid tumour
  • Cribriform: Medium grade, with a cribriform pattern of tumour growth and microlumens
  • Papillary: Projections of cytologically abnormal cells into the lumen of the duct, with fibrovascular cores
  • Micropapillary: As for papillary but without fibrovascular cores

Despite the association of these patterns with particular grades of disease, the grade of DCIS is also based on nuclear features and the presence of necrosis. High grade features include pleomorphic cytology, high NC ratio, coarse chromatin, and presence of multiple nucleoli. Low grade DCIS nuclei are typically smaller and more uniform, have a single nucleolus and smooth chromatin. Intermediate grade nuclei are pleomorphic, but not to the same extent as high grade. They often are of similar size to each other (rather than the large differences in size seen in high grade DCIS). Other features, such as chromatin consistency, may vary considerably.

Immunohistochemistry

Low grade lesions are usually positive for hormonal receptors and negative for ERBB2 and TP53. Higher grade lesions are usually opposite to this; intermediate grade lesions have less reliable findings.

Genetics

Genetic abnormalities are still being investigated in DCIS. Chromosomal abnormalities are more common in high grade DCIS; the types of chromosomal abnormalities also vary between the different grades.

Summary

Most tumours are not visible or palpable macroscopically; the exception is high grade comedo-DCIS which may be visible as an area with dilated ducts with central comedo-like (acne) necrosis.
There are a variety of histological appearances. Comedonecrosis is always high grade; the other types vary depending on cytological and nuclear features

Staging / Classification

All DCIS tumours are stage Tis. Grade is based on cytological features and the presence of necrosis.

Risk Factors for Recurrence

When reading the pathology report, the following needs to be taken into account:

  • Margin status (< 2 mm associated with significantly higher risk of recurrence than > 2 mm)
  • Grade (high grade more likely to recur)

The patient's age is also an important factors, as many recurrences do not occur for 10 years or more.


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