Lobular Carcinoma In-Situ and Invasive Lobular Carcinoma

Breast cancer lesions may originate anywhere in the breast, but they most often occur either in the breast 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 a more serious diagnosis than Lobular Neoplasia. 

Lobular Carcinoma and LCIS indicate that breast cancer is present and treatment will be necessary.

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 However, I have a newer version of this page with more up-to-date material on Lobular Carcinoma.

Lobular carcinoma is more difficult to see on Mammogram and Ultrasound

Specialists often discover lobular carcinoma of the breast by accident when looking for something else, and it can be difficult for physicians to visually determine the full extent of lobular carcinoma from mammogram and 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 is usually because doctors can not determine or remove the full extent of the malignancy.

Unlike ductal carcinoma, lobular carcinoma does not usually form into a hard mass, but rather a vague thickening of the breast tissue.

Lobular Carcinoma In-Situ (LCIS)

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% to 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 necessary 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 without treatment, 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 usually necessary 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 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 necessary

Doctors grade lobular carcinoma in situ on several pathologic features, including nuclear grade, necrosis, and pleomorphism.

The informal three-tier grading system in use for LCIS, described below, is not uniform among all laboratories and hospitals.

One of the ways in which specialists establish these different LCIS grades is the percentage of time that LCIS subsequently needs to be upstaged following the initial diagnosis.

When specialists grade LCIS at a grade of 2 or higher, a follow up excisional biopsy is frequently necessary. 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 to seriously consider when the informal LCIS is about grade 2.

Florid LCIS may be more aggressive than ‘classic’ LCIS

Florid Lobular Carcinoma in situ is an architectural subtype of LCIS, which often features luminal necrosis and distended ductules. 

This type of LCIS, which tends to present in a more solid pattern, can give a similar histological appearance to DCIS.    However, whilst medics consider DCIS  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%).

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 medics have only described since about 2000, tends to feature:-

• marked ductal expansion
• comedo necrosis 
• calcifications

Risk of invasive breast cancer following LCIS diagnosis remains very low over 15 years

The risk of developing invasive breast cancer, in comparison with the general population, is about 17% after 15 years for women with LCIS. 

This corresponds to a RR or relative risk of breast cancer of about 8 in the first 15 years of follow-up. (So, a woman with LCIS is about 8 times more likely to develop breast cancer than 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.

However, 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 when a lesion demonstrates asymmetric density. 

This is an architectural distortion without a central nidus and is only present in one projection. Cytologically, one often finds lobular carcinoma forming into characteristic strands of single file malignant cells.

The image below shows 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 of infiltrating lobular carcinoma, one looks for:-

• neoplastic cells in single files (strands)
• signet ring cells
• 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 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:  Medics consider Grade 1 to be a good prognosis and sometimes call it Tubulolobular carcinoma. It features tubular structures that uniform, small cells line. Identical cells in a single file are also present.

Grade 1, can also have a fairly good prognosis when there are 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, has an intermediate prognosis 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 to 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.

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Below are a few Q&A’s …

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 having a diagnosis of LCIS indicates that you have an increase in the risk of developing breast cancer.

What are the symptoms of lobular carcinoma in situ?

LCIS doesn’t cause any signs or 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 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 puckering or otherwise unusual skin
• a thickening under the skin
• nipple discharge

Ask your doctor when you should consider breast cancer screening as well as how often. Most groups recommend routine screening beginning in your 40’s. Talk to your doctor about what is right for you.

What causes lobular carcinoma in situ?

It is 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 do not extend into, or invade nearby breast tissue.

What is the percentage of risk for developing lobular carcinoma in situ?

The risk of invasive breast cancer in women with LCIS is approximately 20%. Your individual risk of breast cancer is dependant upon many factors. Talk to your doctor to better understand your personal risk of breast cancer.

What are the main risk factors?

• a family history of breast cancer
• hormone replacement therapy for menopause
• Age: if you are a woman in your early 40’s.

What can you do to prepare for your appointment?

There are a few simple things you can do to prepare for your doctor’s appointment:-

• write down any symptoms you may be experiencing
• make a note of your medical history
• note any family history of breast cancer or any other type of cancer as well
• list your medications

What are the tests for lobular carcinoma in situ?

LCIS may be present in one or both breasts, but it usually is not visible on a mammogram. The condition is most often diagnosed as an incidental finding when you have a biopsy to evaluate some other area of concern in your breast. Types of breast biopsy include

• fine-needle aspiration
• core needle
• surgical

What is the treatment of lobular carcinoma in situ?

There are three main approaches to treatment, these include:-

1. Careful observation
2. Medication to reduce cancer risk (chemoprevention)
3. and/or surgery

If you have a diagnosis of LCIS, your doctor may recommend more frequent exams to closely monitor your breasts for signs of cancer.  These may include:-

• Frequent self-exams
• clinical breast exams
• screening mammograms
• other imaging techniques such as MRI
• The FDA approves two selective estrogen receptor modulator (SERM) drugs 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?

To reduce your risk of breast cancer there are a few steps that you can take.  These include:-

• drink alcohol in moderation (if at all)
• exercise most days of the week
• maintain a healthy weight – Healthy eating plans such as the Mediterranean and the Dash diet are a good place to start.   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.

• Types of Invasive Lobular Carcinoma
• Lobular Carcinoma In-Situ and Invasive Lobular Carcinoma
• Ductal Carcinoma In-Situ and Lobular Carcinoma In-Situ
• Lobular Carcinoma In-Situ (LCIS)
• Index of ALL our Articles on Types of Breast Cancer
• Index of ALL our Articles on Breast Cancer Incidence and Survival Rates
• Articles about Breast Cancer Treatment

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References

• Dunne. B, and Going. J.J., “Scoring nuclear pleomorphism in breast cancer” Histopathology, Volume 39, Number 3, September 2001 , pp. 259-265(7)
• Middleton, LP., Grant, S., Stephens, T., Belling, CB., Sneige, N., Sahin, AA. Lobular Carcinoma In Situ Diagnosed By Core Needle Biopsy: When Should It Be Excised? Mod Pathol 2003;16(2):120–129.
• Bagaria, SP., Shamonki, J., Ray, PS., Giuliano, A. Prognostic significance of florid lobular carcinoma in situ when it accompanies patients with invasive lobular carcinoma of the breast: Preliminary report. 2009 breast cancer symposium. American Society of Clinical Oncology.
• Gao F, Carter G, Tseng G, Chivukula M. Clinical importance of histologic grading of lobular carcinoma in situ in breast core needle biopsy specimens: current issues and controversies. Am J Clin Pathol. 2010 May;133(5):767-71.
• Chivukula, M., Haynik, DM., Brufsky, A., Carter, G., Dabbs, DJ., Pleomorphic Lobular Carcinoma In Situ (PLCIS) on Breast Core Needle Biopsies: Clinical Significance and Immunoprofile. American Journal of Surgical Pathology: November 2008 – Volume 32 – Issue 11 – pp 1721-1726
• Bagaria, SP., Shamonki, J., Ray, P., Guilano, A., Florid lobular carcinoma in situ–Precursor lesion for invasive lobular carcinoma? American society of clinical oncology. 2009 breast cancer symposium.
• Ciocca RM, Li T, Freedman GM, Morrow M. Presence of lobular carcinoma in situ does not increase local recurrence in patients treated with breast-conserving therapy. Ann Surg Oncol. 2008 Aug;15(8):2263-71.

 

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• Chen, UU., Rabban, J., Patterns of Lobular Carcinoma In Situ and Their Diagnostic Mimics in Core Needle Biopsies.Pathology Case Reviews: (July/August 2009) – Volume 14 – Issue 4 – pp 141-146
• Brogi, E., Murray, MP., Corben, AD., Lobular Carcinoma, Not Only a Classic. The Breast Journal. (sept./Oct. 2010) Volume 16, Issue Supplement s1, pages S10–S14
• Sapino, A. , A. Frigerio , and J. L. Peterse . et al. Mammographically detected in situ lobular carcinomas of the breast. Virchows Arch( 2000). 436:421–430.

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