Invasive Lobular Carcinoma and Lobular Carcinoma in situ.
Breast Cancer Lesions may originate anywhere in the breast, but are most often found either in the ducts, or the lobules.
Once again, the lobules are really the milk producing glands, which present milk to the ducts, which in turn carry it to the nipple. LCIS ,and of course lobular carcinoma, are considered more serious diagnosis than Lobular Neoplasia, and indicates that breast cancer is present and must be dealt with. Invasive Lobular Carcinoma typically only accounts for 10% of all breast cancers. Ductal carcinoma is much more common. (90%)
This page is getting kind of old, but still has great information! However, I have created a newer version of this page with more up-to-date material on Lobular Carcinoma.
Lobular carcinoma is more difficult to visualize on mammo and ultrasound
Lobular breast carcinoma is frequently discovered ‘by accident‘ when looking for something else, and it can be difficult for physicians to visually determine the full extent of lobular carcinoma from mammography an ultrasound. So one of the issues surrounding lobular carcinoma and LCIS is the ability for doctors to remove all of the cancer cells in treatment. When lobular carcinoma becomes a serious illness, it was usually because the full extent of the malignancy could not be determined and fully removed. Unlike ductal carcinoma, lobular carcinoma does not usually form into a hard mass, but rather a rather a vague thickening of the breast tissue.
LCIS or ‘in situ‘, means that the cancer is still contained in the lobular lining and has not yet infiltrated into the lobule itself. Lobular carcinoma in situ is not a precursor of breast cancer, but rather a sure indication of the presence of breast cancer. Approximately 20-30% of LCIS will develop into infiltrating carcinoma, with about a 50/50 split between ductal and lobular presentations. The risk of contralateral breast cancer development is about 15% The risk of infiltrating carcinoma developing is still low, at about 1% per year and increasing at that rate. A little clarification of language and terminology is warranted here; LCIS is a precursor lesion in the sense that it is the clear presence of breast cancer and not something that might later evolve into breast cancer. However, it is not as clear as to whether or not this breast cancer sitting ‘in situ‘ in the breast nodules, will spread (develop into ‘invasive‘ breast cancer’). Ductal carcinoma (DCIS) will definitely become invasive if not treated, but the behavior of lobular carcinoma in situ is far more difficult to predict.
Calcifications are not necessarily relevant indicators with LCIS
Lobular breast lesions are associated with calcifications around 30% of the time. An excisional biopsy is recommended for lobular carcinoma in situ, atypical lobular neoplasia and lobular neoplasia when there is an associated synchronous breast mass lesion. Whether or not lobular neoplasia is associated with calcifications has little bearing on the decision to take a small, core biopsy sample, or a larger excisional biopsy sample. What is more important is the perceived aggressive nuclear features in the biopsy specimen, and this can usually be accurately determined with a core biopsy only.
If histological features of LCIS are ‘grade 2’, an excisional biopsy is warranted
Grading of lobular carcinoma in situ is often based on several pathologic features, including nuclear grade, necrosis, and pleomorphism. The informal ‘three-tier‘ grading system used for LCIS, described below, is not uniformly among all laboratories and hospitals. One of the ways in which these different LCIS grades have been established has been the percentage of time that LCIS subsequently needs to be ‘upstaged‘, following the initial diagnosis. When LCIS is given a grade of 2 or higher, a follow up excisional biopsy is frequently recommended. Invasive ductal carcinoma can occur in up to 18% or more or grade 1 and 2 LCIS, when analyzed from only core needle biopsy specimens. So, a follow up excisional biopsy, which is unfortunately more inconvenient and is a surgical procedure with some cosmetic effects to the breast, is something that has to be seriously considered when the informal LCIS is about ‘grade 2‘.
Florid LCIS may be more aggressive than ‘classic’ LCIS
Florid Lobular Carcinoma in situ can be described as an ‘architectural subtype‘ of LCIS, which often features luminal necrosis and distended ductules. Florid LCIS, which tends to present in a more ‘solid‘ pattern, can give a similar histological appearance to DCIS, but while DCIS is considered a ‘precursor‘ breast lesion, florid LCIS is not necessarily a precursor for invasive carcinoma. Studies on the behavior of florid LCIS are somewhat inconsistent. The presence of either LCIS or florid LCIS does not appear to have a consistent relationship with either the size or, hormone receptor status of subsequent or concurrent invasive lobular carcinomas. Findings are inconsistent, but florid LCIS does appear to have a higher incidence rate of lymph node metastasis; certainly higher than one might expect proportional to lesion size. But florid LCIS accompanies grades 1, 2, and 3 invasive lobular carcinoma all at about the same rate. (around 30%), while classical LCIS is far more likely (about 60% of the time) to be associated with grade 1 invasive lobular carcinomas only. This would tend to suggest that florid LCIS is more aggressive than classical LCIS. Florid LCIS, which has been described only since about 2000, tends to feature marked ductal expansion, comedonecrosis, and calcifications.
Risk of invasive breast cancer following LCIS diagnosis remains very low over 15 years
The risk of developing invasive breast cancer, when compared with the general population, is about 17% after 15 years for women diagnosed with LCIS. This corresponds to a RR or ‘relative risk‘ of breast cancer of about 8 in the first 15 years of follow-up. (A women with LCIS is about 8x more likely to develop breast cancer than a women without LCIS, but that risk is still quite low). But the bottom line appears to be that the risk of invasive breast cancer for LCIS is simply not as predictable. Women who have developed histologically ‘flagrant‘ examples of lobular neoplasia (like LCIS) are about 9 times more likely than the average women to develop breast cancer, while women with the more subtle histological lobular subtypes (atypical lobular neoplasia) are perhaps 4 times more likely than the average women in terms of risk of developing breast cancer. But when we are talking about statistics over a 15 to 25 year period, with so many other factors and changes which might be contributing factors over that time span, it is really hard to make definitive conclusions.
Infiltrating lobular carcinoma indicators
By mammography, infiltrating lobular carcinoma is identified by when a lesion demonstrates asymmetric density, an architectural distortion without a central nidus, and is seen in only one projection. Cytologically, one often finds lobular carcinoma forming into characteristic strands of ‘single file‘ of malignant cells.
The image below show infiltrating lobular carcinoma identifiable by the apparent isolation of malignant cells, and also the single file or ‘strands‘ of malignant cells.
In terms of the pathological evaluation as infiltrating lobular carcinoma, one looks for neoplastic cells in single files (strands), signet ring cells, and histiocytoid cells. Tubulo-lobular and pleomorphic cells are also strong indicators. One also looks for any deviation from the ‘classical pattern‘ of lobular neoplasia. The ‘classical‘ pattern of lobular neoplasia is basically a largely uniform, ‘bunched-up‘ collection of malignant cells. When they begin to ‘break apart‘ into strands and isolated cells, this signals an evolution to infiltrating lobular carcinoma.
Infiltrating lobular carcinoma. (single file ‘strands’)
Specific criteria for Lobular Carcinoma Grading
Infiltrating lobular carcinoma grade and/or prognosis rating is based on specific criteria and the perceived ‘aggressiveness‘ of the situation. The ‘grading‘ of the nuclei is especially important, and is generally a factor of the measured variability in size and shape (pleomorphism) of the nuclei.
Grade 1, which is considered a “Good Prognosis“, is sometimes called “Tubulolobular carcinoma“. It features tubular structures that are lined by uniform small cells. Identical cells in single file are also present.
Grade 1, can also be considered as having a “fairly good prognosis” when it is characterized by small uniform cells, with grade 1 nuclei, single-file rows of cells in a fibrous stroma, and “targetoid” (concentric or ‘bulls-eye‘) pattern of cells around ducts.
Grade 2 lobular carcinoma, which is considered to have an “intermediate prognosis” is characterized by a classical cell pattern with grade 2 nuclei. There may be an ‘alveolar variant‘ of cells characterized by round and oval ‘nests‘ of uniform small cells. There may also be unusually ‘large‘ cells. (called the ‘large cell variant‘), and mixed patterns of lobular carcinoma.
Grade 3 or “poor prognosis” lobular carcinoma usually shows a ‘solid variant‘, with large sheets of uniform small cells with round nuclei. There may be a ‘pleomorphic pattern‘, which resembles the classical pattern but has larger grade 2-3 nuclei. In addition, the mitoses are easily identified, apocrine change is common, the ER is often negative. Signet-ring cell may also be prevalent. If there are more than 20% of cells of this shape, this also suggests a more serious prognosis and grade 3.
Note: “ER negative” refers to a situation when the tumor cells do not have estrogen receptors on their surfaces. This implies that the cancer cells may not be effectively treated by estrogen inhibiting drugs, which tend to slow down new cell growth.
‘Signet ring’ strands of infiltrating lobular carcinoma
Disease free survival is about the same for ductal and lobular carcinoma, but overall survival is higher for lobular
The overall survival rates for invasive lobular carcinoma have in some studies been shown to be about 25% higher than for invasive ductal carcinoma. The reasons for this may have to do with subtle differences in histological subtypes between lobular and ductal breast cancer. Invasive lobular carcinoma tends to present, initially in a more diffuse pattern than invasive ductal carcinoma. As a result, it is not as easy to confidently remove all of the malignant cells. As a consequence, there are higher rates of ‘positive margins‘ indicative of local recurrence with invasive lobular carcinoma after breast conservation surgery. This would seem to be a bad thing, but in fact, with invasive breast cancer local recurrence is a secondary concern; the main worry is metastasis to the lymph nodes and beyond. One would assume that the higher rates of local recurrence in invasive lobular carcinoma would also reflect higher rates of lymph node and regional metastasis, but this is not the case. Disease free survival is about the same for both ductal and lobular breast carcinoma, but overall survival is lower for ductal carcinoma.
Below are a few Q&A…
- What is the meaning of lobular carcinoma in situ? LCIS is an uncommon condition in which abnormal cells form in the lobules or milk glands in the breast. LCIS is not cancer, but being diagnosed with LCIS indicates that you have an increased risk of developing breast cancer.
- What are the symptoms associated with lobular carcinoma in situ? LCIS doesn’t cause any signs nor symptoms. Rather, your doctor might discover incidentally that you have LCIS. For example, after a biopsy to asses a breast lump or an abnormal area, such as microcalcifications, found on a mammogram.
- When should I see a doctor? Make an appointment with your doctor if you notice a change in your breast, such as a lump, an area of puckered or otherwise unusual skin, a thickened region underneath the skin, or nipple discharge. Ask your doctor when you should consider breast cancer screening as well as how often should it be repeated. Most groups recommend routine screening beginning in your 40’s. Talk with your doctor about what’s right for you.
- What causes lobular carcinoma in situ? It’s not clear what causes LCIS.
- How does lobular carcinoma in situ start? LCIS begins when cells in a milk-producing gland, known as a lobule, of a breast develop genetic mutations that cause the cells to appear abnormal. The abnormal cells remain in the lobule and don’t extend into, or invade, nearby breast tissue.
- What is the percentage of risk for developing lobular carcinoma in situ? The risk of breast cancer in women diagnosed with LCIS is thought to be approximately 20%. Your individual risk of breast cancer is based on many factors. Talk to your doctor to better understand your personal risk of breast cancer.
- What are the risk factors? You have a family history of breast cancer, you’ve taken hormone replacement therapy for menopause, and if your a women in your early 40’s.
- What can you do to prepare for your appointment? A few simple things you can do to be prepared for your doctor’s appointment would be to write down any symptoms you may be experiencing, write down your medical history, note any family history of breast cancer or any other type of cancer as well, and make a list of your medications.
- What are the tests and diagnoses of lobular carcinoma in situ? LCIS may be present in one or both breasts, but it usually isn’t visible on a mammogram. The condition is most often diagnosed as an incidental finding when you have a biopsy done to evaluate some other area of concern in your breast. Types of breast biopsy that may be used include fine-needle aspiration, core needle, or surgical.
- How is lobular carcinoma in situ treated? There are three main approaches to treatment, these include careful observation, taking a medication to reduce cancer risk (chemoprevention), and/or surgery. If you’ve been diagnosed with LCIS, your doctor may recommend more frequent exams to closely monitor your breasts or signs of cancer, these may include frequent self-exams, clinical breast exams, screening mammograms, or other imaging techniques such as MRI. Two selective estrogen receptor modulator (SERM) drugs are approved to reduce the risk of invasive breast cancer, these medications may be tamoxifen or raloxifene. You could also consider participating in a clinical trial as well, to explore an emerging therapy for preventing breast cancer.
- What are a few lifestyle and home remedies? If your worried about your risk of breast cancer, steps to reduce your risk may be drinking alcohol in moderation (if at all), exercise most days of the week, and maintain a healthy weight. Healthy eating plans such as the Mediterranean and Dash Diets are a good place to start and keeping your weight within a healthy range is a good idea too. Losing your abdominal fat may reduce your risk for some hormone-receptor negative cancers.
For some more questions and answers on invasive lobular carcinoma, you may want to visit this page.
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