Invasive ductal cancer with Central Necrosis
“Necrosis” refers to the debris left behind when cells die. In the context of a suspected breast cancer tumor doctors usually consider necrosis as an indicator of a more aggressive breast carcinoma.
It is quite common to see cell necrosis in mature invasive breast cancers. However, in the case of central necrosis, when the necrosis collects in a ‘central‘ location ( i.e. in the middle of the tumor) doctors commonly associate this with ‘comedo DCIS‘ or comedo carcinoma and not infiltrative breast cancer.
Central Necrosis on Breast Cancer Screening
When a suspicious lesion appears on breast cancer screening then a biopsy may well follow. At this point, the pathologist may well encounter a characteristic ‘central necrosis’ pattern in the lesion.
The danger however, is that doctors and specialists may underestimate the suspicious lesion and diagnose Ductal Carcinoma In-Situ (DCIS). However, the lesion may in fact be evidence of a larger, invasive ductal carcinoma with central necrosis.
Infiltrating ductal carcinoma with central necrosis is an uncommon but readily identifiable sub type of breast carcinoma. Furthermore, Invasive Ductal Cancer with Central Necrosis is a highly aggressive breast cancer. Sadly it often has early systemic metastasis and an accelerated clinical course.
Immunohistochemistry determines between Invasive and In-Situ Breast Cancer
Though somewhat rare, physicians who specialize in breast cancer diagnosis will tell you that it is quite possible for a breast carcinoma to present with both ‘in situ’ and ‘infiltrative’ characteristics. A mix.
An infiltrative ductal carcinoma with a central necrosis will so closely mimic a ‘DCIS with central comedo necrosis‘ that the initial morphological evaluation might well mislabel the lesion as high grade comedo DCIS.
In order to determine the true extent and potential threat of the breast carcinoma, one has to perform additional biopsies and imaging studies from various locations. Also, doctors must pay very close attention to the immunohistochemical analysis of the biopsy specimen.
There are certain proteins present in an infiltrating ductal carcinoma that are distinct from comedo breast carcinoma in situ. The key feature is an assessment of the myoepithelial lining of the duct. So, myoepithelial cell involvement tends to be indicative of an infiltrative or pre-invasive status for breast cancer.
Immunohistochemical evidence for either a deficient or absent basement membrane and myoepithelial cell layer will generally confirm a diagnosis of infiltrative breast carcinoma with central necrosis, rather than a comedo type DCIS.
but before that I tend to stick to four letter words!
Some breast cancer tumors can be ‘in situ’-like, but still Invasive
The physical appearance of the breast cancer cells is usually informative, but can also be misleading.
The ‘central necrosis’ feature of infiltrative ductal carcinoma with central necrosis is so much like comedo breast carcinoma in situ, that it can lead to a mistaken diagnosis.
The pathologist must realize that there are some breast cancer tumors in which some or all of the tumor can be DCIS-like, but it is still an infiltrative or invasive breast tumor. Sometimes an ‘irregular circumference’ of invasive foci carcinoma is evident when compared to true DCIS comedo circumference, (which is more regular).
Additional immunohistochemical markers for infiltrative ductal carcinoma with central necrosis
Most invasive breast cancers will lack both a basement membrane and myoepithelial cells.
However, in actuality, there are many breast cancers that produce basement membrane components.
In addition, there are several invasive cancer that have myoepithelial cell elements. So, when trying to determine if a suspicious breast cancer lesion featuring central necrosis is comedo DCIS or an infiltrative breast carcinoma with central necrosis, there are a number of myoepithelial markers that may help.
Common myoepithelial cell markers include:-
- S-100, smooth muscle actine
- SMM-HC, Calponin: Is probably the most specific myoepithelial cell marker
- HMW-CK. SMM-HC .
- CD10, p63
- P63: Is quite a useful marker in breast cancer differentiation because it stains the myoepithelial nuclei only, and also has high sensitivity and specificity.
There is no ‘accepted’ correlation between type and grade of DCIS and probability of future invasive breast cancer status
In the ongoing attempt to discover and treat breast cancer at the earliest possible stage, there have been a number of studies that speculate on the features of DCIS that are most likely to evolve into an invasive breast cancer.
The two factors specialists most commonly discuss in this regard are the nuclear grade of malignant cells and the presence of necrosis. Which of these two factors is of greater importance is still a subject of debate and interpretation.
Models of DCIS Progression to Breast Cancer
The conventional ‘model’ of DCIS progression to breast cancer goes something like this:-
- Atypical ductal hyperplasia
- Low grade DCIS
- Intermediate grade DCIS
- High grade DCIS
- Invasive ductal carcinoma.
But there are alternative models emerging now, suggesting that DCIS does not necessarily have to be of a high grade before transforming into an invasive breast cancer.
Some breast cancer researches propose that if certain features are present in an intermediate grade DCIS, such as a certain nuclear feature or the presence and degree of necrosis, then the carcinoma might proceed directly to invasive breast cancer status.
This has not been definitively proven, but there is a general consensus that the presence of necrosis in any early stage breast carcinoma is usually considered as an indicator of a potentially more aggressive breast cancer.
By and large, however, it would appear that analysis of the nuclear grade and not the presence, degree, and pattern of necrosis, is the more consistent indicator of malignancy in breast carcinoma. Moreover, some researchers believe that high grade DCIS is itself a unique genetic pattern, that may not develop from low and intermediate grade DCIS.
More about Invasive Breast Cancer with Central Necrosis
Sometimes medics refer to an infiltrative breast carcinoma with central necrosis as a ‘centrally necrotizing breast carcinoma’, (CNC). Historically, centrally necrotizing breast carcinomas have an aggressive course.
Histologically, the composition of infiltrating ductal carcinoma with central necrosis is a well-circumscribed nodule with an extensive region of central necrosis. This area of necrosis is usually surrounded by a narrow ‘rim’ of high-grade tumor cells. But these tumor cells usually show only minimal if any ductal differentiation, ie. they tend not to form into ‘tubules’.
The average age of development of an infiltrative ductal carcinoma with central necrosis is hard to estimate, but generally occurs in the mid 50’s. Most infiltrative breast carcinomas with central necrosis are estrogen and progesterone receptor negative, making them more resistant to treatment.
Treatment of Breast Cancers with Central Necrosis
Treatment of these type of tumors is usually surgical, with lumpectomy or mastectomy. In addition, doctors may prescribe adjuvant radiation therapy. Nonetheless, about 60% of infiltrative centrally necrotizing ductal carcinomas do either recur locally or metastasize to a distant site.
Prognosis of Breast Cancers with Central Necrosis
When compared to infiltrating ductal carcinomas without central necrosis, there is unfortunately a significantly worse prognosis for breast cancers featuring a central necrosis pattern.
What happens in these breast cancers is that the cells are dividing fast enough to grow outward faster than blood vessels can develop, which is why the necrosis pattern develops.
The average duration between treatment and recurrence of disease tend to be around 16 to 17 months, and up to 70% of patients with a centrally necrotizing breast carcinoma succumb to the disease within two years.
However, if a proper diagnosis is made in the early stages, the outlook is certainly more positive.
- Maiorano E, Regan M, Viale G, Mastropasqua MG, Colleoni M, Castiglione-Gertsh M. (et al). Prognostic and predictive impact of central necrosis and fibrosis in early breast cancer: Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy . Breast Cancer Research and Treatment Volume 121, Number 1, 211-218 https://www.ncbi.nlm.nih.gov/pubmed/19280340
- Yu L, Yang WT, Cai X, Lu HF, Fan YZ, Shi DR. (2009) Clinicopathologic study of centrally necrotizing carcinoma of breast. Zhonghua Bing Li Xue Za Zhi. 2009 Oct;38(10):657-62. https://www.ncbi.nlm.nih.gov/pubmed/20078968
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