Type and grading of Ductal Carcinoma in Situ, or ‘DCIS’
Grading of ductal carcinoma in situ (DCIS) determined by size and shape of nuclei and patterning.
All DCIS is considered “stage 0 breast cancer” – or the earliest stage possible. Once DCIS as an early stage cancer is confirmed, it may be given a specific DCIS ‘grade‘ based upon the particular kinds of cells which are growing, the characteristics of their nuclei and their growth patterns. The lower the grade, the more slowly the cancer cells grow and the more closely they resemble normal breast cells. Based on this information, the pathologist will describe the DCIS as either grade one (low), grade two (medium) or grade three (high).
Ductal Carcinoma in Situ: proliferating cancer cells still contained within the breast duct
DCIS differs from Atypical Ductal Hyperplasia in that the atypical cell growth is now disturbing the stroma or supporting-framework cells of the duct, but has not yet penetrated the duct wall. Another way to look at it is that the new cell growth is occurring in a completely unpredictable way. This would suggest the presence of tumor cells to be the cause.
DCIS Grading based on characteristics of nuclei
Low and Intermediate Grade DCIS
Low and medium grade DCIS implies that the cancer cells are growing at a relatively slow rate. People with low-grade DCIS face an increased risk of invasive breast cancer compared to people without DCIS, but it is unlikely to appear until after five years. However, women with low-grade DCIS are less likely to have a recurrence of the breast carcinoma or to develop new cancers. Grade I or low-grade DCIS cells appear very much like normal breast cells or atypical ductal hyperplasia cells. Grade II or moderate-grade DCIS cells look less like unaffected cells and grow faster than normal.
In the image below, malignant cells have completely filled the lumen (empty space) of the duct, but have regular-looking nuclei. This is considered low-grade DCIS. Note that the presence of microcalcifications is not necessarily a malignant indictor for the pathologist.
The image below also shows DCIS, in which malignant cancer cells have partially filled the duct. However there is noticeable variation in the size and shape of the cancer cell’s nuclei, with a probable intermediate-grade diagnosis. Also present in the duct are ‘crushed-stone‘ microcalcifications and various bi-products, which would not necessarily increase malignant criteria for the pathologist.
In the high-grade pattern, DCIS cells tend to grow more quickly and the cells look much different from healthy breast cells. High-grade DCIS is indicative of cancer cells which are growing rapidly and has the highest risk of progressing to invasive cancer within the first five years following DCIS diagnosis. High-grade DCIS also poses a significantly increased risk for the cancer to return which is likely within the first five years.
In the image below the malignant cells have once again completely filled the duct, but they also show a significant variation in the size and shape of their nuclei. This tends to suggest a more malignant carcinoma, likely diagnosed as grade III or ‘high‘. Also present in the duct are evidence of dead cancer cells (necrosis), and ‘casting‘ microcalcifications. However the casting-like microcalcifications are not necessarily a malignant indicator.
DCIS grading based on breast cancer cell growth patterns: Cribriform, Solid, Papillary.
Cribiform Growth pattern
A “cribriform” pattern has gaps between the cancer cells within the duct, with an appearance similar to the ‘holes in swiss cheese‘ or perhaps ‘ripples‘. A cribriform pattern is consistent with a low or medium grade DCIS.
Solid and ‘Comedo’ DCIS
A “Solid” cell pattern is one in which the cancer cells have completely filled the duct. Sometimes this is called “Comedo” DCIS , which literally means ‘plug‘. The breast duct is completely plugged by cancer cells. Solid or comedo growth patterns are high grade ductal carcinoma in situ, if there is a corresponding variation in nuclei or evidence of necrosis.
‘Necrosis‘ refers to the remnants and debris from cells that have died. The cancer cells are growing so quickly that some of them don’t get enough nourishment and die.
“Comedonecrosis” describes a situation where the entire breast duct is plugged and there are dead cancer cells scattered amongst the live ones. It is categorized as High grade DCIS with a high risk of escalation.
In the image below the necrosis is seen as the dark regions surrounded by white at the tips of the arrows. The entire upper-right quadrant is “comedo” or plugged.
A ‘papillary‘ DCIS pattern is one arranged in a ‘fern-like‘ pattern within the duct. Unlike the cribriform pattern, the papillary has no isolated ‘holes‘ of cancer cells, but they are all connected in a kind of asymmetrical or undulating pattern throughout the duct. If the cancer cells comprising this pattern are very small by comparison, it is often termed “micropapillary“. Necrosis and mitiotic figures may be seen in paplillomas for women over the age of 40.
Papillary DCIS may actually present as one of four pattern types. These are:
- Cribriform- with a high resemblence to cribiform DCIS but of a larger size
- Tall-hyperchromatic or stratified spindle cell, according to the ‘tall‘ or ‘spindle‘ cell shapes. Stalks are thin, delicate fibrovascular, typically with no myoepithelial cells present. Cells may also have a clear nucleus.
- Compact Columnar, in which the cancer cells are in uniform columns of cells
- Transitional cell, which resembles a kind of cancer that can occur in the bladder, but this is rare.
Papillary DCIS comes in many forms and subtle variations, and tends to fall from the intermediate to high-risk grades. Micro-papillary DCIS is now thought to be a highly malignant, dangerous presentation of DCIS, and is of the highest risk. With micropapillary DCIS the ducts are dilated and lined by a stratified population of monotonous cells. The pattern may show small finger-like protuberances with bulbous ends, which may form arches. Micropapillary DCIS is often multifocal and multicentric. When the presentation is pure, it is often considered grounds for mastectomy in hopes of avoiding invasive micropapillary carcinoma.
Papillary DCIS likely to be removed surgically
Complete removal of benign papillomas has shown to dramatically reduce the appearance of subsequent breast cancer. For malignant papillomas or where there is intracystic carcinoma, there is a high rate or recurrence and associated DCIS. A wide surgical removal is usually recommended. Among women, papillary carcinomas account for 1-2% of all breast cancers. Most commonly occurring with women in the 62-67 age range.
Now for some Q&A’s
I have just had a biopsy for DCIS what will the report say? The report back on the breast tissue taken at biopsy will include DCIS histological grade and type. That is how abnormal the cells actually appear when compared to normal cells of the breast duct and how rapidly they are growing. The report may well indicate whether the cells are positive to estrogen receptor (know as er-positive breast cancer) or progesterone receptors. If the cells are hormone positive they may be growing faster in response to these hormones.
What is the difference between DCIS and invasive breast cancer? In DCIS the abnormal cells are contained within the breast ducts. If the cancer cells break through the walls of the breast ducts and into the breast tissue this is then known as ‘invasive breast cancer’. The can also spread to the lymph nodes, the nearest nodes are the axillary lymph nodes (underarm glands) these may well be tested for cancer cells if you have an invasive cancer diagnosis. It is a good idea to check your underarm lymph node for swelling or tenderness and always have anything unusual checked out (swollen lymp nodes can also be a symptom of non-hodgkin lymphoma).
What is the treatment for DCIS? The main treatment for DCIS is surgical removal of all affected cells with a portion of healthy tissue too (known as a margin). Depending on the grade of DCIS this could be a lumpectomy to remove the affected area or a total mastectomy. Radiation therapy is often given afterwards to try and prevent recurrence and spread. Regular screening mammography is essential after any breast cancer diagnosis and treatment.
What are the risk factors for DCIS? Clinical studies have indicated that a diagnosis of DCIS in itself does not affect survival rates but identifies a group of women (around 60,000 a year in the US) who are at increased risk for developing invasive cancer and need to be screened more closely for breast tumors or abnormalities. Strangely there is evidence to suggest that African-American women diagnosed with invasive cancer have an increased mortality rate and tend to develop a more aggressive form of the disease. Apart from attending regular screening programs and breast self-exams for abnormalities you need to keep healthy – cut down on the alcohol, give up cigarettes, eat a healthy diet, exercise regularly and sleep well. Avoid hormone replacement therapy after the menopause as evidence links HRT with the development of some breast cancers.
What is the difference between Ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS)? We have a new post on early-stage breast cancers including ductal carcinoma in situ and lobular carcinoma in-situ visit here for everything you need to know.
- Tavassoli F.A, Pathology of the Breast, 1999.
- www.bcbreastcancer.ba.ca. "Grading system for invasive carcinoma of the breast".
- Tot, Tibor., and, Tabár, László., Papillary Lesions of the Breast: histologic examination of contiguous tissue can predict the need for surgical excision. The 12 th Annual Multidisciplinary Symposium on Breast Disease,February 15-18, 2007
- Tavassoli,. F.A. Papillary Lesions of the Breast. Yale University School of Medicine, New Haven, CT.
- Kim MJ, Gong G, Joo HJ, Ahn SH, Ro JY. Immunohistochemical and clinicopathologic characteristics of invasive ductal carcinoma of breast with micropapillary carcinoma component. Arch Pathol Lab Med. 2005 Oct;129(10):1277-82.
- Tang P, Wang X, Schiffhauer L, Wang J, Bourne P, Yang Q, Quinn A, Hajdu SI. Relationship between nuclear grade of ductal carcinoma in situ and cell origin markers. Ann Clin Lab Sci.(Winter 2006)36(1):16-22.
- Lagios, MD., Heterogeneity of duct carcinoma in situ (DCIS): Relationship of grade and subtype analysis to local recurrence and risk of invasive transformation. Cancer Letters ,Breast Cancer Research. (1995)Volume 90, Issue 1, 23 . Pages 97-102
- Hannemann J, Velds A, Halfwerk JB, Kreike B, Peterse JL, van de Vijver MJ. Classification of ductal carcinoma in situ by gene expression profiling. Breast Cancer Res ( 2006)8(5):R61.
- Evans, AJ., Pinder, SE., Ellis, IO., Wilson, ARM., Screen detected ductal carcinoma in situ (DCIS): overdiagnosis or an obligate precursor of invasive disease? J Med Screen 2001;8:149–151
- Silverstein, MJ., Ductal Carcinoma In Situ of the Breast: Controversial Issues. The Oncologist, (1998)Vol. 3, No. 2, 94-103
- Douglas-Jones AG, Gupta SK, Attanoos RL et al. A critical appraisal of six modern classifications of ductal carcinoma in situ of the breast (DCIS): correlation with grade of associated invasive disease. Histopathology 1996;29:397-409
- Silverstein MJ, Lagios MD, Lewinsky BS et al. Breast irradiation is unnecessary for widely excised ductal carcinoma in situ (DCIS) of the breast. Breast Cancer Res Treat 1997;46:23.
- Fadare O, Clement NF, Ghofrani M.High and intermediate grade ductal carcinoma in-situ of the breast: a comparison of pathologic features in core biopsies and excisions and an evaluation of core biopsy features that may predict a close or positive margin in the excision. Diagn Pathol.(Aug 2009) ;4:26.