Confused about the term carcinoma in situ

[CuriousGeorge2]

So, I don't quite understand what the term carcinoma in situ means - I took a look in Robbins and the text says that it refers to a situation when there are dysplastic changes that involve the full thickness of an epithelium, but are not invasive. Doesn't the term carcinoma imply malignancy, which itself implies invasion/ spread? So, since carcinoma in situ is not invasive, does this mean it is a technically a benign neoplasm (despite the carcinoma name)? Also, based on the definition in Robbins, it seems that this term is only used to distinguish between high and low grade dysplasia for a straitified squamous epithelium - b/c for any other epithelium type (ex. simple columnar), full thickness dysplasia would be the same thing as plain old dysplasia since there would only be one cell layer...

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[CuriousGeorge2]

Maybe carcinoma in situ is not even a neoplasm at all (not benign or malignant) - Robbins says that dysplasia refers to disorderly, but non-neoplastic proliferation. If cacrcinoma in situ is just high grade dysplasia, then it wouldn't even be a neoplasm based on this definition...

 

[TexasMDtobe]

Carcinoma in situ refers to a severe dysplasia with a very high likelihood of progression to invasive carcinoma - but the basement membrane is still intact for the moment.

 

[OveractiveBrain]

So, I don't quite understand what the term carcinoma in situ means - I took a look in Robbins and the text says that it refers to a situation when there are dysplastic changes that involve the full thickness of an epithelium, but are not invasive. Doesn't the term carcinoma imply malignancy, which itself implies invasion/ spread? So, since carcinoma in situ is not invasive, does this mean it is a technically a benign neoplasm (despite the carcinoma name)? Also, based on the definition in Robbins, it seems that this term is only used to distinguish between high and low grade dysplasia for a straitified squamous epithelium - b/c for any other epithelium type (ex. simple columnar), full thickness dysplasia would be the same thing as plain old dysplasia since there would only be one cell layer...

X = Cancer cells
O = Happy Cells
_ = Basement membrane

OOOOOOO
OOOOOOO Normal Epithelium "yay!"
OOOOOOO
------------------

XXXXXXX
XXXXXXX Carcinoma in Situ "uh oh"
XXXXXXX
------------------

XXXXXXX
XXXXXXX Invasive Carcinoma "cancer'd!"
XXXXXXX
-----X------------
XXXXXX
XXX..XX..XX
XX...XX.X.X..X..X..X..XX.X

now here's a real kicker... There are different degrees of dysplasia. Lets look at the nomenclature for squamous cell carcinoma

XXXXXOO
OOOOOO CIN I, "meh, mild dysplasia"
OOOOOO
OOOOOO
---------

XXXXXOO
XXXXXOO CIN II "meh, moderate dysplasia"
OOOOOO
---------

XXXXXXX
XXXXXXX Carcinoma in Situ, CIN III "ooh, severe dysplasia"
XXXXXXX
-----------------

So carcinoma in situ is NOT "benign" because if you don't do anythign about it, it will eventually progress.
CIN 1 --> CIN 2 --> Carcinoma in Situ = CIN 3 --> Invasive carcinoma.

If you've followed this so far, lets keep going. Once its invasive, it depends on spread. If its all over the body (mets) then its stage 4. If its just a little invaded (and this differs from cancer to cancer on "how much invasion does it take to upstage"), its stage 2 or 3. Carcinoma in situ by defintion is Stage 1, that is, limited to the tissue without invasion through the basement membrane.

How does it get into the rest of the body? Either by local invasion (the picture i showed) or by lymph or blood spread. What is right on the other side of that basement membrane? Yep. Blood vessels and lymph. Also neural tissue, which is why reports will usually see no vascular or perineural involvement.

Think of the basement membrane as the flood gate. You've got the mighty mississippi on one side (the cancer), and the entirety of southwest louisiana on the other (the body). If you don't get this reference, you should pay more attention to CNN. As long as the flood gates are closed (basement membrane intact) the river stays in the river. But once you open that gate up (invasion), the mississippi is going to flood everywhere. Neurons, Lymph, Blood, and then its up to you to stage, that is, find how far the cancer has gotten to determine treatment.

To get back to benign vs not, there are tumors that will grow. And they grow alot. But a benign tumor just never invades. That's what makes it benign. Benign = will not invade. It can get huge, steal all the person's blood, destroy organs, literally eat the person from the inside out, but its still "benign" because it wont invade.

Malignant tumors invade. Malignant tumors are those that will invade. A carcinoma in situ squamous cell carcinoma of the cervix, for example, is malignant. I suppose, much like a polyp in the colon, it could be considered "pre-malignant" because it "hasn't invaded yet." But "premalignant" and "benign" are not the same thing. Using colon cancer as an example, a tubular pedunculated polyp is benign, as in, not precancer, so you only have to increase the screening a little. A Sessile, villous tumor with active dysplasia is premalignant, and screening is stepped up alot.

So in summary:
Benign = tumor will not invade
Malignant = tumor will invade
Premalignant = tumor hasn't invaded yet but it will
Carcinoma in Situ = tumor that hasn't invaded the basement membrane
Carcinoma in Situ = Stage 1 = curable with local resection only
Stage 2 = a little out of the basement membrane (variable per cancer)
Stage 3 = a little more out from the basement membrane (variable per cancer)
Stage 4 = Metastasis.

 

[werd]

carcinoma in-situ is malignant, but has not yet "invaded." By invaded, folks usually mean spread below the basement membrane. the term carcinoma does not imply invasion, it implies a biologic behavior that includes the potential to invade. for instance, many cutaneous squamous cell carcinomas in-situ spread laterally, ablating surrounding epidermal structures and bleeding and ulcerating spontaneously. some eventually become invasive, but they behave in a malignant fashion before growing vertically.

 

[Substance]

Carcinoma means epithelial malignancy. Epithelium is cells resting on a basement membrane.

Dysplasia is in theory a reversible lesion. The cells might revert back to normal.

Carcinoma is an irreversible lesion. These cells are never going back to normal.

Carcinoma in-situ has not invaded the basement membrane.

Invasive carcinoma has invaded the basement membrane.

 

[osumc2014]

X = Cancer cells
O = Happy Cells
_ = Basement membrane

OOOOOOO
OOOOOOO Normal Epithelium "yay!"
OOOOOOO
------------------

XXXXXXX
XXXXXXX Carcinoma in Situ "uh oh"
XXXXXXX
------------------

XXXXXXX
XXXXXXX Invasive Carcinoma "cancer'd!"
XXXXXXX
-----X------------
XXXXXX
XXX..XX..XX
XX...XX.X.X..X..X..X..XX.X

now here's a real kicker... There are different degrees of dysplasia. Lets look at the nomenclature for squamous cell carcinoma

XXXXXOO
OOOOOO CIN I, "meh, mild dysplasia"
OOOOOO
OOOOOO
---------

XXXXXOO
XXXXXOO CIN II "meh, moderate dysplasia"
OOOOOO
---------

XXXXXXX
XXXXXXX Carcinoma in Situ, CIN III "ooh, severe dysplasia"
XXXXXXX
-----------------

.

Best ASCII art explanation ever

 

[rentedmule]

I have some studying to do...

 

[Dral]

Malignancy = invasion and spread is where you are getting tripped up. Malignancy does not necessarily mean invasion has occurred.

Melanoma is a good example. Malignant Melanoma in situ means the tumor is confined to the epidermis and that several factors exist in the tumor, such as pagetoid spread UP through the epidermis, atypical cells, presence of mitoses, etc. (these characters and others mean it has malignant character).

It is invasive (no longer in situ) melanoma when the tumor breaks the epidermal/dermal junction. It is not classified as metastatic until tumor or tumor cells are located elsewhere in a node or other organ.

 

[Alvarez13]

X = Cancer cells
O = Happy Cells
_ = Basement membrane

OOOOOOO
OOOOOOO Normal Epithelium "yay!"
OOOOOOO
------------------

XXXXXXX
XXXXXXX Carcinoma in Situ "uh oh"
XXXXXXX
------------------

XXXXXXX
XXXXXXX Invasive Carcinoma "cancer'd!"
XXXXXXX
-----X------------
XXXXXX
XXX..XX..XX
XX...XX.X.X..X..X..X..XX.X

now here's a real kicker... There are different degrees of dysplasia. Lets look at the nomenclature for squamous cell carcinoma

XXXXXOO
OOOOOO CIN I, "meh, mild dysplasia"
OOOOOO
OOOOOO
---------

XXXXXOO
XXXXXOO CIN II "meh, moderate dysplasia"
OOOOOO
---------

XXXXXXX
XXXXXXX Carcinoma in Situ, CIN III "ooh, severe dysplasia"
XXXXXXX
-----------------

So carcinoma in situ is NOT "benign" because if you don't do anythign about it, it will eventually progress.
CIN 1 --> CIN 2 --> Carcinoma in Situ = CIN 3 --> Invasive carcinoma.

If you've followed this so far, lets keep going. Once its invasive, it depends on spread. If its all over the body (mets) then its stage 4. If its just a little invaded (and this differs from cancer to cancer on "how much invasion does it take to upstage"), its stage 2 or 3. Carcinoma in situ by defintion is Stage 1, that is, limited to the tissue without invasion through the basement membrane.

How does it get into the rest of the body? Either by local invasion (the picture i showed) or by lymph or blood spread. What is right on the other side of that basement membrane? Yep. Blood vessels and lymph. Also neural tissue, which is why reports will usually see no vascular or perineural involvement.

Think of the basement membrane as the flood gate. You've got the mighty mississippi on one side (the cancer), and the entirety of southwest louisiana on the other (the body). If you don't get this reference, you should pay more attention to CNN. As long as the flood gates are closed (basement membrane intact) the river stays in the river. But once you open that gate up (invasion), the mississippi is going to flood everywhere. Neurons, Lymph, Blood, and then its up to you to stage, that is, find how far the cancer has gotten to determine treatment.

To get back to benign vs not, there are tumors that will grow. And they grow alot. But a benign tumor just never invades. That's what makes it benign. Benign = will not invade. It can get huge, steal all the person's blood, destroy organs, literally eat the person from the inside out, but its still "benign" because it wont invade.

Malignant tumors invade. Malignant tumors are those that will invade. A carcinoma in situ squamous cell carcinoma of the cervix, for example, is malignant. I suppose, much like a polyp in the colon, it could be considered "pre-malignant" because it "hasn't invaded yet." But "premalignant" and "benign" are not the same thing. Using colon cancer as an example, a tubular pedunculated polyp is benign, as in, not precancer, so you only have to increase the screening a little. A Sessile, villous tumor with active dysplasia is premalignant, and screening is stepped up alot.

So in summary:
Benign = tumor will not invade
Malignant = tumor will invade
Premalignant = tumor hasn't invaded yet but it will
Carcinoma in Situ = tumor that hasn't invaded the basement membrane
Carcinoma in Situ = Stage 1 = curable with local resection only
Stage 2 = a little out of the basement membrane (variable per cancer)
Stage 3 = a little more out from the basement membrane (variable per cancer)
Stage 4 = Metastasis.

Can you come teach at my school? Our PHDs go out of their way to make this stuff impossible to understand.

 

[Substance]

So in summary:
Benign = tumor will not invade
Malignant = tumor will invade
Premalignant = tumor hasn't invaded yet but it will
Carcinoma in Situ = tumor that hasn't invaded the basement membrane
Carcinoma in Situ = Stage 1 = curable with local resection only
Stage 2 = a little out of the basement membrane (variable per cancer)
Stage 3 = a little more out from the basement membrane (variable per cancer)
Stage 4 = Metastasis.

I love the art. But I just want to make clear that stage is different depending on the type of cancer. Also, in the TNM staging, metastases are the M part, not stage 4. But otherwise your post was damn good!

 

[CBG23]

Carcinoma means epithelial malignancy. Epithelium is cells resting on a basement membrane.

Dysplasia is in theory a reversible lesion. The cells might revert back to normal.

Carcinoma is an irreversible lesion. These cells are never going back to normal.

Carcinoma in-situ has not invaded the basement membrane.

Invasive carcinoma has invaded the basement membrane.

I have heard different things about CIS being reversible. My lectures notes from 2nd year say that it is not reversible, but straight from Robbins:

"CIN III: Severe dysplasia and carcinoma in situ

...With CIN III (CIS), the likelihood of regression is only 33%...it should be noted that in many cases even the higher grade lesions do NOT progress to cancer."

This implies that it can be reversible, but is not very likely (unless CIN III is different from CIS - the text implies that they are one and the same). It also implies that the CIS is not malignant. I'm more inclined to believe some of the residents' posts on here and probably chalk up the text to being poorly written/ not completely precise...

 

[adaptation1]

Malignancy is defined by Metastatic POTENTIAL. If CIS has the potential to metastasize, then it is considered malignant -- even if eventually doesn't, or eventually regresses. Period. If CIS were benign, it doesn't have the potential, unless it develops into a malignant cancer, at which point it does.

I have heard different things about CIS being reversible. My lectures notes from 2nd year say that it is not reversible, but straight from Robbins:

"CIN III: Severe dysplasia and carcinoma in situ

...With CIN III (CIS), the likelihood of regression is only 33%...it should be noted that in many cases even the higher grade lesions do NOT progress to cancer."

This implies that it can be reversible, but is not very likely (unless CIN III is different from CIS - the text implies that they are one and the same). It also implies that the CIS is not malignant. I'm more inclined to believe some of the residents' posts on here and probably chalk up the text to being poorly written/ not completely precise...

 

[45408]

I love the art. But I just want to make clear that stage is different depending on the type of cancer. Also, in the TNM staging, metastases are the M part, not stage 4. But otherwise your post was damn good!

But as soon as you have distant metastases, most cancers jump up to a stage IV.

 

[hot sauce]

If you've followed this so far, lets keep going. Once its invasive, it depends on spread. If its all over the body (mets) then its stage 4. If its just a little invaded (and this differs from cancer to cancer on "how much invasion does it take to upstage"), its stage 2 or 3. Carcinoma in situ by defintion is Stage 1, that is, limited to the tissue without invasion through the basement membrane.

So in summary:
Benign = tumor will not invade
Malignant = tumor will invade
Premalignant = tumor hasn't invaded yet but it will
Carcinoma in Situ = tumor that hasn't invaded the basement membrane
Carcinoma in Situ = Stage 1 = curable with local resection only
Stage 2 = a little out of the basement membrane (variable per cancer)
Stage 3 = a little more out from the basement membrane (variable per cancer)
Stage 4 = Metastasis.

A lot of good explanation but carcinoma in situ is not stage 1. Tis N0 M0 = Stage 0. Stage I means the patient has invasive Ca. Treatment is generally needed for stage 0 but it is not invasive cancer.

The further staging you listed are bit too simplistic for a medical student. You probably know that stage isn't simply decided by the size of the tumor but also lymph node involvement which isn't really a little out of the basement membrane and really at that point we aren't thinking about how far it is from the basement membrane.

I also would not say stage 1 = curable with local resection only. There are many stage I cancers that require chemo or radiation to increase the chance of a cure.

It is not simply that the cells haven't grown enough to get through the basement membrane but the dysplastic cells generally need a further mutation to be able to become invasive. Carcinoma in situ has a high risk of progressing to invasive carcinoma but it is not a given for all CIS.

Sorry to be critical as I love your pictures just a couple points to clarify.

 

[OveractiveBrain]

A lot of good explanation but carcinoma in situ is not stage 1. Tis N0 M0 = Stage 0. Stage I means the patient has invasive Ca. Treatment is generally needed for stage 0 but it is not invasive cancer.

The further staging you listed are bit too simplistic for a medical student. You probably know that stage isn't simply decided by the size of the tumor but also lymph node involvement which isn't really a little out of the basement membrane and really at that point we aren't thinking about how far it is from the basement membrane.

I also would not say stage 1 = curable with local resection only. There are many stage I cancers that require chemo or radiation to increase the chance of a cure.

It is not simply that the cells haven't grown enough to get through the basement membrane but the dysplastic cells generally need a further mutation to be able to become invasive. Carcinoma in situ has a high risk of progressing to invasive carcinoma but it is not a given for all CIS.

Sorry to be critical as I love your pictures just a couple points to clarify.

I was going for understanding, not truth.

You are right though, and appreciate the details. If anyone reading understood my explanation enough to read further, they would be even further knowledged. The problem is that "cancer" isn't a disease, so speaking generally is almost impossible. Getting too specific too soon kills the student's drive to learn, leaving them thinking "holy **** thats a lot to learn. maybe ill do it later."

Thanks to everyone for clarifying some of the details revolving around a simplified explanation.