Pleomorphic LCIS

Yeah! Life is good!

Hey Kelly -

Hang in there.  The waiting is always the hardest part, isn't it?  Waiting to get a test done, waiting for results, waiting, waiting!!  It sounds as if you have come to a decision about the PBM (same decision I made).  PLCIS is definitely more complicated than "plain" LCIS - there is much that is unknown about it, and doctors disagree on the best course of action to take.  Unfortunately, that means that each one of us has to come through decisions based on little science and lots of gut feelings.  There is no "right" decision on this one - the right decision is whichever one you feel most comfortable with.   I had my surgery in Feb 2010.  It was absolutely, without a doubt, the right decision for me.  There are other women who are perfectly comfortable with increased screening. However, it does not sound like you fall into that category.  So I am not surprised that you have decided on a PBM. 

Please let us know how the MRI goes, and feel free to send me a private message if you want to talk more.

I was curious how you interpreted this section of an abstract in a Sept 2010 entry, especially the highlighted sentence.

Does this mean that PLCIS is much more commonly ER negative than classic LCIS, and that possibly classic LCIS turns into PLCIS which is more commonly ER negative?

Ten cases of core biopsy-diagnosed, screen-detected PLCIS were identified. Core biopsy findings were compared with pathological findings at subsequent surgery. Two cases were associated with possible microinvasion on the core. Two of 10 had invasive lobular carcinoma and one had microinvasive lobular carcinoma on subsequent surgical excision (positive predictive value for malignancy = 30%). There was associated conventional LCIS on either core or excision biopsy in all cases except one. All three cases of oestrogen receptor (ER)-negative PLCIS arose in the context of ER+ conventional LCIS. http://www.ncbi.nlm.nih.gov/pubmed/20727019

Well, in this 2008 paper, it sounds like they are implying (in speculation) that PLCIS may take longer to develop than LCIS.  I guess this would include the *possibility* that PLCIS could develop from LCIS.  (Emphasis is mine.) Here's some snippets from a 2009 article.   I included more text so you have more context.

PLCIS was originally described and is commonly seen in association with invasive pleomorphic lobular carcinoma (7, 17).However, it may also present as an isolated lesion without concurrent invasive disease (i.e. pure PLCIS) (4, 24). Prior to its recognition, this lesion was probably most often classified as high grade DCIS due to the presence of nuclear pleomorphism and the frequent presence of comedo-type necrosis. With the availability of E-cadherin immunohistochemistry, carcinomas in situ showing features of both classic LCIS (loss of cell cohesion and loss of E-cadherin expression) and DCIS (high nuclear grade and/or the presence of necrosis and microcalcifications) have been diagnosed more frequently.
PLCIS lesions demonstrated overlapping histologic features between CLCIS and DCIS (Figure 1). All 31 cases shared some features of CLCIS such as a solid proliferation of dyshesive cells that filled and distended TDLUs. Pagetoid involvement of ducts was noted in the majority of the cases. In addition, in 27 cases (87%) there were synchronous foci of CLCIS. The CLCIS cells were usually a mixture of type A and type B cytology and they were found both in close proximity to the PLCIS (sometimes in the same TDLU) and/or breast tissue away from the PLCIS. However, PLCIS lesions also demonstrated some features considered to be more typical of DCIS including considerable nuclear enlargement (≥ 4x of lymphocyte) and moderate to marked nuclear pleomorphism (>2–3x variation in nuclear size). Further, necrosis was identified in 22 lesions (71%) (comedo-type in 18 and punctate in 4), and in 29 cases (94%) calcifications were present in association with the lesion...
Of note, these PLCIS cases did not represent a homogeneous group, displaying some variation in cytologic features. In particular, 13 cases stood out as a distinct subtype characterized by large cells with abundant eosinophilic cytoplasm imparting an apocrine appearance (a variant we termed apocrine PLCIS). These lesions typically exhibited foci of comedo necrosis. The combination of large cells with abundant cytoplasm, nuclear pleomorphism, and comedo necrosis produced a histologic appearance that could readily be mistaken for DCIS (Figure 1B). However, the cells in these cases were dyshesive and had frequent intracytoplasmic vacuoles that in some instances were large enough to produce signet ring cell forms...

One of the most striking differences between PLCIS and CLCIS was the clinical presentation. Patients with PLCIS were significantly older than those with CLCIS. If PLCIS and CLCIS were indeed clonally related, it might be speculated that PLCIS requires a longer time for development. Unlike CLCIS which is usually an incidental microscopic finding without a detectable mammographic lesion, PLCIS typically presented as mammographic abnormalities including microcalcifications, architectural distortion and/or density. The clinical presentation and mammographic findings of PLCIS are similar to DCIS and different from CLCIS, as has been described previously (4, 8, 24).
.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2783988/?tool=pubmed

Then, I guess if you're anything like the women in this study, you're a youngster. :-).  I was 51 at my diagnosis of classic LCIS.

All of the PLCIS patients in this study were female with a mean age 55 years (range 40–86 years). Compared to CLCIS (mean age of 50), patients with PLCIS were significantly older (p= 0.03) and this difference was mostly attributed to the apocrine PLCIS. Apocrine PLCIS were seen primarily in postmenopausal women with a mean age of 60 years, whereas the mean age for non-apocrine PLCIS was 51 (p= 0.008).

I think they are hypothesizing that apocrine may be associated with more aggressive disease, though they don't have any clinical evidence for this. (I think that AR stands for androgen receptor, though I may be wrong about this.)

PLCIS lesions were further categorized as either apocrine or non-apocrine types, the former characterized by cells with abundant eosinophilic cytoplasm....

All of the PLCIS patients in this study were female with a mean age 55 years (range 40–86 years). Compared to CLCIS (mean age of 50), patients with PLCIS were significantly older (p= 0.03) and this difference was mostly attributed to the apocrine PLCIS. Apocrine PLCIS were seen primarily in postmenopausal women with a mean age of 60 years, whereas the mean age for non-apocrine PLCIS was 51 (p= 0.008)...

Of note, these PLCIS cases did not represent a homogeneous group, displaying some variation in cytologic features. In particular, 13 cases stood out as a distinct subtype characterized by large cells with abundant eosinophilic cytoplasm imparting an apocrine appearance (a variant we termed apocrine PLCIS). These lesions typically exhibited foci of comedo necrosis. The combination of large cells with abundant cytoplasm, nuclear pleomorphism, and comedo necrosis produced a histologic appearance that could readily be mistaken for DCIS (Figure 1B). However, the cells in these cases were dyshesive and had frequent intracytoplasmic vacuoles that in some instances were large enough to produce signet ring cell forms.

All PLCIS and CLCIS cases were E-cadherin negative. Overall 74% of PLCIS were GCDFP-15 positive. GCDFP-15 expression was significantly more frequent in apocrine than non-apocrine types (100% vs 50%, p<0.05). While ER and PR expression was noted in all CLCIS and virtually all non-apocrine PLCIS, only a small fraction of the apocrine PLCIS (~20%) showed ER and PR expression. When compared to CLCIS, PLCIS showed significantly lower levels of ER and PR expression. Even among the non-apocrine PLCIS, the ER and PR expression level as measured by H-score was significantly lower than that in CLCIS. Although AR expression was identified in all LCIS lesions, non-apocrine PLCIS had significantly lower AR levels than both CLCIS and apocrine PLCIS. The average Ki-67 proliferation index was significantly higher in PLCIS than in CLCIS (11.5% vs 4.2%, p<0.05). Furthermore, apocrine PLCIS showed a higher proliferation index than the non apocrine type, but this difference did not reach statistical significance (p=0.06)...

Overexpression of HER2 was identified in 13% of PLCIS and was not observed in any of the CLCIS cases. Of note, HER2 overexpression was restricted to the apocrine subtype of PLCIS in this cohort. When compared to CLCIS and non- apocrine PLCIS, the differences in the frequency of HER2 overexpression in apocrine PLCIS were statistically significant. There was no difference in the frequency of expression of basal cytokeratin CK5/6 among LCIS subtypes...

Of note, amplification of 17q and gain of 16p were only noted in the apocrine but not in the non-apocrine subtype of PLCIS. In addition to 1q gain and 16q loss, recurrent copy number changes for apocrine PLCIS included gains of 16p (36%) and 6p (15%), losses of 3q (22%), 11q (32%), 13q (25%) and 17p (45%), and amplification of cyclin D1 gene (3/8, 38%) and HER2 gene (2/8, 25%); for non apocrine PLCIS, no additional recurrent change was observed....

Likewise, the overall extent of genomic alterations was similar between CLCIS and non-apocrine PLCIS. However, more genomic changes were observed in the apocrine PLCIS. Specifically, apocrine PLCIS had significantly higher FGL (p=0.04), more whole chromosomes changes (p=0.04), more amplifications (p=0.02) and more chromosomes with amplifications (p=0.02) than CLCIS. A trend of increased FGA (p=0.06), increased number of break points (p=0.05), and increased chromosomes with break points (p=0.06) was also noted when apocrine PLCIS was compared to CLCIS. Within PLCIS, apocrine PLCIS also demonstrated more genome alterations than non apocrine type. Apocrine PCLIS had significantly more chromosomal breakpoints (p=0.02), more chromosomes with break points (p=0.03), more whole chromosomes changes (p=0.02), higher FGG (p=0.02), higher FGL (p=0.02) and higher FGA (p=0.01). Of note, amplifications of 17q and 11q and gain of 16p were only noted in the apocrine subtype of PLCIS...

The distinct apocrine morphologic subtype of PLCIS had especially aggressive phenotypic features...

With regard to immunophenotype, we found both similarities and differences between PLCIS and CLCIS. All PLCIS were negative for E-cadherin expression, as is characteristic of CLCIS. However, unlike CLCIS lesions which are consistently positive for ER and PR, negative for HER2, and have low mitotic activity, PLCIS often showed low to negative ER and PR expression, a higher proliferation rate, and an increased incidence of HER2 overexpression. These findings are similar to those reported previously in PLCIS (1, 4, 17, 24). This “unfavorable” biomarker profile suggests that PLCIS represents a biologically more advanced lesion than CLCIS. All PLCIS, especially those of apocrine morphology, were strongly positive for AR. Activation of the AR pathway may be important in the progression of these lesions, and drugs targeting this pathway may constitute a novel therapeutic option for management of PLCIS. 

There is a proposed pathway (figure 6) which I don't know how to reproduce here.  Some of the pathways mentioned below are characterized by specific genome changes, such as decreased ER,PR; 16p+, 11q-,17p-.

It essentially says that normal TDLUs can become ALH, nonapocrine PLCIS, or apocrine PLCIS.  ALH can become classic LCIS, which can cause classic ILC.

It is hypothesized that ALH can also cause nonapocrine PLCIS or apocrine PLCIS.  Classic LCIS can also become nonapocrine PLCIS or apocrine PLCIS.  

Nonapocrine PLCIS can become nonapocrine pleomorphic ILC, and apocrine PLCIS can become apocrine pleomorphic ILC.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2783988/?tool=pubmed

Of course you're welcome, KellyMaryland.  It helps me to understand my own situation too.

However, I also learned that while education and knowledge are a good thing, you have to be very careful when reading the literature.  I'm sure leaf will back me up on this - there are lots of reports that provide the researchers conclusions from existing data, and it may or may not be of use to someone with the condition being researched.

I sure do agree, cornellalum!  This is only ONE study, and ONE hypothesis.  There is so little information about PLCIS that I was grabbing at straws for ANY ideas researchers may be tossing around.

I would have a slightly different analysis than cornellallum about PBMs vs tamoxifen, though.  I'm sure it is biased because so far I have chosen tamoxifen.  But do research all of your risks and benefits thoroughly, and the estimated risks you take with each option:

The worst thing that can happen if I get the PBM is that I over-reacted, and I no longer have breasts.  The worst thing that can happen if I do the tamox and monitoring is that my PLCIS morphs into invasive breast cancer, and I could die from it, knowing that I could have prevented it.  Which situation is worse?

I think you have to look at ALL of the risks and benefits of each option.

  I don't think the worst case scenario for PBMs is that you lose your breasts.  With PBMs there is the possibility of lifetime lymphedema, or post-mastectomy pain syndrome.  Some of the potential risks of tamoxifen with monitoring are the anxiety of monitoring, potential quality of life issues with tamoxifen (though it hasn't been at all uncomfortable for me), possibility of uterine cancer or stroke.

  On the plus sides, PBMs greatly reduces the bc risk, more so than with tamoxifen and monitoring. However, since you are more closely monitored, they often get it in earlier stages, so it is less likely you would die.   In the Port study, they didn't have any LCIS patients diagnosed with anything worse than stage II. http://www.ncbi.nlm.nih.gov/pubmed/17206485  (This of course is a very small sample, and probably are mostly/all classic LCIS.)

On the tamoxifen side, you get to keep your breasts. 

You can probably think of more risks and benefits for each option. Some of these risks and benefits can be quantified, but of course it is an extremely personal decision.

I think the most helpful thing a surgeon can do is to give you a choice.  My bs essentially didn't (with my classic LCIS.)  'If you want PBMs, I will fall over in a chair.'  and 'I don't want to do any further surgery on you.' I don't think that stance helped me psychologically, even if I would have made the same choice.  But then again, I can't stand this bs, for this and other reasons.

Sheepishly dipping my toe in here. I'm still gathering info and trying to accept everything that has gone on in the past 2 months.

You guys unforunately know the story. Routine mammogram over 2 months ago picked up changes to calcifications and a small new cluster. U/S, 2 stereo needle biopsies, MRI and excisional biopsy later, I just received dx of PLCIS. Needle biopsy yielded result of LCIS and ALH. I'm assuming now I have all 3. Will confirm today at post surgical follow up.

 This is my second dr, since I really didn't like the first one. Although I realize PLCIS is very rare, this dr seems to know what she's doing in that she sent the samples back for futher testing. I know I'm suppose to feel good about the "no invasive cancer" finding, but that lasted all of one afternoon. It's 2 days since that call, and I'm still reeling from the upgrade of PLCIS from LCIS. She briefly told me she would be discussing my 3 options which we all know about. She said the drug option probably wasn't good for PLCIS (which I assume has something to do with the ER component). We will talk about that further today.

 So I reluctantly join this club that none of us want to be in. I am scared. I am sad. And no one else truly understands that unless they've understand that which many drs don't understand. I wish I never had to look for this board, and I wish none of you had to be here. But I'm relieved it's here.

 In the midst of all of this, I turned 48. It certainly wasn't the best birthday I've had, but I'm trying hard to remind myself that even though I hate this situation, it probably has given me a chance to have many more birthdays. But it all still sucks. =(

Thank you Kelly. I can't tell you how much your quick response means to me. I'm not sure I'll be able to relay what the dr says about the tamox since much of this stuff is way over my head. I listen and watch for words I recognize all the while trying to control my shaking that always rears its head at these appts. It would be so nice to be able to talk with a dr without all the emotional stuff that invades the conversation. I'm also still trying to get over the whole squeamish thing, too. lol I'll do my best though.

It's such an odd place to be. I only chose to tell a handful of people I was going through this, and when I called them all a few days ago to tell them I do not have cancer, they were all grateful for me that "it's over." It's not though. It's really only just begun. That has been a difficult thing to accept. It takes time and lots of pacing.

 Wishing you the best as well.

Thank you nanannlan. I'm sorry you're in this club, too.  It sounds like you're handling this very well which really is no easy task.

 Kelly, my ER thingie was +, so my dr said Tamox would work. Maybe it's not good with -? Not sure. However, I probably can't take it anyway because of family hx of stroke. She's referring me to an oncologist to discuss.

Though the P in LCIS does denote a more aggressive nature, she said it's not like things are going to go full blown in between screenings. Though she thinks of PCLIS of more if a precancer than a marker. *scared*

I'm sorry, I don't know the right appreviations yet (is there a list?). I asked about skin and nipple sparing mastectomy, and she thinks I'm a good candidate. I'll look more into that, but right now I'm still very nervous about reading things that scare me. Baby steps. My calcifications are closer to the center of the breast, and I think that's a good thing (if there's any good in this junk).  She'll set up a consult with a plastic surgeon. He will determine whether or not I can hold implants. I lost 50 pounds last year, so the girls are rather floppy right now anyway. I think that could be an asset for this type of surgery.

I told them not to be in a rush to make those appts for me. Although I am very eager to get on with this, I feel I need to slow down a little and make an informed decision. My dr did say I have time.

I've noticed that many women who post on these boards have opted for mastectomy. Though at the moment I am leaning that way, I'd love to hear from others like Kelly and Nanannlan who are taking the the careful screening approach.

Thank you all and I wish you all many, many blessings on this difficult journey.

Crescent,

I know how overwhelming this all is.  All the acronyms, the statistics, a whole new language. There are many people on this board, like Anne, who do the high risk surveillance and feel good with that.  There are many people who decide on prophylactic bilateral mastectomies (PBM).  There are others still who are high risk but can't bring themselves to or just don't want to do anything about it, just taking their chances. You have to pick one of those paths, whichever is right for you and only you.   I think it's really very important to take your time (you do have time) and research and ask alot of questions, making sure that you're making an informed decision.   At the same time I do believe in gut reactions.  One of my breast surgeons told me that people generally fall into two categories: "take them off please" or "do anything you can not to take them please".

I am doing the high risk screening right now.  Though now I'm being asked to do imaging every three months...which is a drag logistically, emotionally, and definitely physically when they want to biopsy some other weired spot.  For me this is too much.  (I've been monitored for the PLCIS only 7 months now but have been monitored for the past 2 1/2 years for other breast funkiness.)  I'm very slowly making my way to PBM. 

I will tell you that personally, I tend to be a people pleaser and can be intimidated by what people say or think about my decisions.  So it's been a struggle for me to stand up for myself and make my own choices about my own body.  But I keep coming back to the same realization that my body has known all along what it wanted to do- it just took some time for my brain to catch up. 

For me, getting a number- what % chance of getting invasive BC I have- was helpful in making a decision.  As was my age (42)- that's alot of monitoring over the course of my life.  Also my family situation- I have 4 young kids (all under 7) and logistically all of these appointments caused great stress for me trying to get childcare, etc. and the kids feel this stress very accutely.

Anyway, these are some of my rambling thoughts.  I'll be here for you while you research and will support you in whatever path you choose.

Kelly

Thank you for responding Anne & Cathy. I'm sorry you're in the club, too. I got a chuckle out of "climbing the lobular ladder." I have a feeling I'll be using that one sometime if you don't mind.

Kelly, I hear you on the people pleaser thing. 2 things popped into my head. 1) if one of your kids were struggling with that, what would you say to them? 2) while at my BS's office yesterday, as we were getting info from the nurse, I heard the dr on the phone saying she was leaving work in 15 minutes. I adore and trust her, but it really & truly occured to me: This is her job. This is my life. I'm going to be the one driving this bus, and if no one likes or respects my decisions, that's not my problem.

When I was dx'd with classic LCIS, there were many people who didn't get what all the angst was about. "So, you just have a little more increased risk." Many couldn't comprehend why I even opted for the excisional biopsy after that finding. When I made my phone calls the other day to let friends and family know I did not have invasive, I started opting out of adding the PLCIS finding. There was really no sense arguing that point with the ones who didn't get it. I'm driving this bus.

 If there comes a time when I go for PBM, I'm not interested in anyone saying to me "but you don't have cancer." Yeah, I kinda do. Sure it's benign, and maybe some experts don't even consider it cancer, but it's certainly not "all clear, sorry for the inconvenience."

Anyway, I hope it's OK for me to babble here. There's so much to think about. After 2 months of testing, the uncertainty, the fear and all that comes along with it, it's near impossible to just step back into my life as it was before that problematic mammogram. I want to do something today to fix this. I don't want to get complacent. But I know that I'm not necessarily thinking too clearly right now as much as I think I am. So it's good to take your time to make decisions. And it's good to change your mind if something you tried isn't working. But I guess right now the most important thing is for us to talk about it. Unfortunately, someone else is going to come along soon with this diagnosis. Perhaps these threads will help her.

That is absultely fabulous news, Kelly! I recently had to remind myself that there is a lot of good news mixed into this mixed bag dx. I'm glad you got your good news yesterday.

Crescent5 you are absolutely right about driving your own bus!  I hope if nothing else, the women on this discussion board get that point.  I work in a hospital and you are right on that it is the doctor's job, but it is your life.  Well said.  There are a handful of docs who are exceptional and truly put themselves in your shoes, however, I have seen these things become routine in their minds and complacency kills.  We have 3 radiologists at our hospital, and luck of the draw, I got the one who wasn't satisfied with just watching the minute changes that had occurred in my mammo from my previous one.  He felt bad about putting me through the biopsy anxiety, waiting, etc. but thank God he did.  Everytime I look at him I think to myself... "that man saved my life".  I'm in a small town and my case was unusual for the local docs and it took them forevever to determine the pathology.  They kept going back and forth between lcis and dcis.  Turns out it was plcis (which is often mistaken for dcis).  Thanks to the radiologist who cared, it was all removed via double mastectomy prior to it becoming invasive.  Also did not have to have chemo or radiation.  Not even tamoxofin.  Hard to reconcile that I don't need further treatment even though the pathology was so "ugly".  I asked my pathologist (lucky me, I work at a hospital so I can talk to the "guy behind the curtain")  why pleomorphic is so bad and he explained that it changes your dna the most.   I just wish there was more known about this kind of cancer.  I worry about a recurrence, although I have been told by several physicians that the chance is remote.  KellyMaryland, I am 43 and have 3 young children, so I can really relate to you.  My advice is this is not the time to be a people pleaser.  You need to please those 4 beautiful children who, no doubt, want their mom around for a very long time.  I got a 2nd and 3rd opinion when I was marinating in my  decision and not 1 doctor, from the radiologists to the surgeons and pathologists thought I should watch and wait (there were 9 docs total and a tumor board), mostly because of the reasons you stated... you're young and have young children.  I'm 2.5 months post-op and feel great.  I'm done with my "fill ups" and my new breasts look great.  I go in for the transfer (saline to silicone) in January.  Hope my input has been helpful in some way.  All the best to you and I hope you have a great Holiday Season with your family.