DCIS

The purpose of this case is to illustrate some fundamental concepts of ductal carcinoma in situ. The mammographic and sonographic features will be discussed.

The term DCIS (ductal carcinoma in situ) should not be confused with LCIS (lobular carcinoma in situ). As their names suggest, they are respectfully separated by their cytological resemblance to normal ductal or lobular epithelium. While they may co-exist or they may histologically overlap, it is usually possible to distinguish between the two entities. They have separate histological and prognostic features. This case and discussion focuses only on DCIS.

Ductal carcinoma in situ (DCIS), also commonly called intraductal carcinoma refers to the intra-epithelial carcinoma of mammary ducts. By definition, it is separated by an intact basement membrane complex from the lymphatic and vascular circulations. The World Health Organization International Histological Classification of Breast Tumors therefore refers to the entity as “non-invasive” cancer. 

Some authors refer to ductal carcinoma in-situ as pre-invasive. This term better reflects the dynamic nature of the condition. There is a non-obligatory potential of DCIS to evolve into an invasive malignancy. It is now apparent that this progression does not occur within the lifetime of all patients.

Various pathological classification schemes have been used to describe DCIS. It is not uncommon for reports to employ a combination of these schemes. This creates inconsistency and confusion in the literature.

Traditionally, DCIS was first described by architecture. The most common types were designated by 5 categories:

(1) Comedo – characterized by prominent necrosis. Named because of pasty material exuding from cut surface of specimen. Necrotic debris often becomes calcified.

(2) Cribriform – fenestrated, sieve-like growth pattern.

(3) Micropapillary – small tufts of cells perpendicularly oriented to the basement membrane and projecting into the lumina.
 
(4) Papillary – intraluminal projections of tumor cells. Distinguished from micropapillary by fibrovascular cores.

(5) Solid – tumor cells fill and distend ducts, without significant necrosis, fenestrations or papillations.

Some authors then simplified this scheme by subdividing the DCIS into 2 groups – the comedo and non-comedo. This has some clinical relevance because of the comedo variant appearing more malignant cytologically, having a higher predilection for microinvasion, and more often exhibiting biologic markers.

Some DCIS lesions do not fit in either the architectural classification or the dichotomous comedo/non-comedo classification schemes. Alternative classification schemes have therefore been proposed including that by Lagios in the U.S.A., investigators in Nottingham, England, and the European Organization for Research and Treatment for Cancer. Although the individual terminology differs amongst the three groups, all three schemes recognize three grades of DCIS – high, intermediate and low – and they are transposable between the three classifications.

High grade DCIS predominantly refers to the presence of comedo-type DCIS with necrosis of the central intraductal contents. Calcifications seen mammographically in high grade DCIS are from calcification of the necrotic intraductal debris. The calcifications therefore typically are ductally oriented, irregular, pleomorphic (i.e. of variable shape), and segmentally distributed. 

In low grade DCIS, the calcifications are found to be related to calcifications of secretions in the milk ducts and lobules. The calcifications mammographically tend to be more punctate in nature, but again ductally oriented.

High-resolution sonography of breast calcifications is being studied. Sonographically, breast calcifications appear as non-shadowing hyperechoic foci. Calcifications can be distinguished by real-time scanning from breast parenchymal lines and artifactual speckle by their reproducibility in multiple planes and transducer positions. Variable sonographic characteristics of DCIS have been described in the literature, including focally enlarged ducts, diffuse reduction in echogenicity of the parenchyma surrounding the calcifications, and intracystic mass. As this case illustrates, breast ultrasound sometimes may guide percutaneous breast biopsy of breast calcifications.

The incidence of occult invasion of DCIS into the breast ranges at least from 0-26% in the literature. The likelihood of microinvasion increases with increase in size of the lesion. The rate of microinvasion also increases with a higher grade of the DCIS. Incidences of microinvasion is higher in DCIS presenting clinically (e.g. mass, discharge, Paget's disease) than in incidental mammographically-detected DCIS.

Mastectomy is virtually curative in 98% of patients with DCIS of the breast. Removal of the breast effectively eradicates the disease at this stage because the worrisome sequelae of invasion and metastases have not commenced. Another potential advantage of mastectomy is the opportunity to detect clinically and mammographically occult foci of invasive carcinoma within the surgically removed breast. 

Controversy exists over such a drastic treatment for all patients because progression to invasion does not occur in all patients with DCIS. It is theoretically conceivable that some DCIS may regress over time. However, there are no known current methods to assess the likelihood of progression to invasion in any given patient, thus the dilemma in management.

Breast conservation approaches have therefore been tried, including surgical excision alone and excision with radiation therapy. The incidence of recurrence in patients treated with wide excision alone ranges from 8-43% in the literature. The recurrences occur most frequently at or adjacent to the primary tumor site. Approximately one-half are DCIS and one-half are invasive malignancy. Some authors are still currently advocating wide surgical excision for treatment of small, 1 cm low grade DCIS. 

Although there is dramatic variability in the literature, the local recurrence rate with excision and radiation therapy is about 50% less than excision alone. Studies of breast conservation with radiation therapy for breast malignancy demonstrate a 10-15% recurrence rate within the first 10 years. Again, the majority of these recurrences occur in the same quadrant as the primary malignancy. Approximately half of these recurrences are invasive carcinoma (5-7%) and half are DCIS. The risk of death from invasive carcinoma of the breast is about one-third of rate of development, so about 2-3% will die from recurrence within the first 10 years. The comparable 10-year death rate of patients treated for DCIS with mastectomy is 1-2%. Whether or not all patients treated with breast conservation require radiation therapy remains controversial.

For patients who elect breast conservation, pre-operative needle localization should guide surgical excision of mammographically detected clinically occult DCIS. Bracketing with two or more wires is helpful in widespread DCIS. Intra-operative specimen mammography is absolutely critical in the management of these patients. If margins are involved in the specimen, the interpreting radiologist must immediately alert the surgeon and additional tissue must be excised if anatomically possible. In cases where the calcifications are diffuse or approach the edge of the specimen, postexcision mammograms are helpful to confirm complete surgical removal of calcifications. If residual calcifications are present in the postoperative region, re-excision is often warranted.

For both mastectomy and lumpectomy specimens, detailed pathological handling and evaluation are essential. The specimen should be oriented and inked prior to sectioning. The report should document the grade of DCIS, presence or absence of necrosis, correlation of calcifications with DCIS, extent of margin involvement or proximity to the margin. 

There is about a 1% incidence of axillary lymph node metastases in patients with DCIS with no evidence of microinvasion by light microscopy. In these cases, invasion is presumably present but either not detected by the pathologist or not detectable because of sampling error. Axillary dissection is therefore not routinely indicated in women with DCIS, because of the low incidence of axillary metastases. In the patient undergoing mastectomy, some surgeons with informed consent from the patient are performing sentinel node excision to potentially avoid reoperation in the event of occult microinvasion at the site of DCIS or remote occult invasive carcinoma. 

In summary, a woman with DCIS should be presented with the options for management for DCIS. The risks and benefits of each option should be reviewed and discussed at length with the patient. This enables an informed treatment choice for this biologically heterogeneous entity. Irrespective of whether or not a woman elects a breast conservation approach or mastectomy, lifetime mammographic and clinical surveillance of the contralateral breast is mandatory.

A 38-year-old Caucasian pre-menopausal female presented with self-detected thickening in the upper portion of her right breast of one-month duration.

The patient had no personal history of breast cancer, no history of prior breast surgery or biopsy, and no significant family history of breast, ovarian or uterine cancer. Menstrual history of menarche age 13, three live childbirths, last menstrual cycle 1 week prior to presentation. Past medical history of asthma, rheumatoid arthritis and osteoporosis. Current medications included prednisone 10 mg/day, Prilosec, calcium, and Didronel. She had taken oral contraceptives for 1 year approximately 18 years prior to presentation. She was not taking hormonal therapy at time of presentation.