Download General Patholog: Neoplasia I pg. 1 Clay McEntire It`ll probably help

General Pathology
9/18/2008
Neoplasia I
Transcriber: Clay McEntire
55:19
It’ll probably help to download the PP file, so you can see the pictures. Some are still missing
though. I did my best to describe them.
1. Dr. Bell is a pathologist and it’s his job when a lesion is biopsied to look at it grossly and
microscopically and to decide whether it’s reactive or neoplastic. If it is neoplastic, they’ll
determine whether it’s benign or malignant. If it is malignant, they then need to determine if it’s
metastized (spread). They then decide what treatment is appropriate.
2.
Terms. Neoplasia = “New growth” and the loss of responsiveness to normal growth controls.
Tumor means swelling, and is used interchangeably with the word “neoplasm.” Oncology is the
study of tumors. It’s important to determine whether the tumor is benign or malignant, and the
term “cancer” is applied to a malignant neoplasm.
3. Tumors are composed of: parenchyma- the neoplastic cells that determine the biologic behavior
of the tumor. There are also stromal cells- the supporting tissues (non-neoplastic), that provide
connective tissue and vascular support. The tumors’ names are derived from the parenchymal
component, meaning we look at the cell type and use this to name it.
4. How do we name tumors? This terminology is going to be important in future classes too.
Benign neoplasms end in the suffix “-oma.” If it is benign tissue that arises from fibrous tissue,
fibroblasts, then it’s referred to as a fibroma. If it arises from cartilaginous tissue, then it’s a
chondroma. Fibromas and chondromas are considered “mesenchymal” by origin. For epithelial
tumors, we keep the “-oma” suffix, but we name them based on the cell type and sometimes
the architecture. If it’s glandular tissue, it’s an adenoma. If it has a papillary growth pattern
(meaning that it has fingerlike projections), then it’s a papilloma. If we have a cystic growth
pattern, the tumor is considered a cystadenoma.
He showed a slide that isn’t shown in the PP file that we have access to via Blackboard. This slide
showed an oral lesion. He described it as a well circumscribed small lesion in the buccal mucosa.
If we were to look at this histologically, we’d see that it’s made of fibrous tissue, and it’s benign.
Therefore we’d call it a fibroma.
He showed another slide that had a radiograph of a finger. You can see a radiolucent area on the
radiograph representing a tumor. If we look at the tumor histologically, we see that it’s made of
hyaline cartilage next to the bone; therefore, it’s a chondroma. It’s an intraosseous lesion that is
well circumscribed (I think maybe this word refers to the capsule that is traditionally seen with
benign tumors). This particular chondroma is an “enchondroma,” but we’ll talk more about that
in systemic path.
5. How would you describe this? What’s the architectural pattern? We have little finger-like
projections… It’s an intra-ductal papilloma of the breast. This is a breast duct that’s dilated.
General Patholog: Neoplasia I
Clay McEntire
pg. 2
6. This is an ovarian mass in a 60 year old woman. We inked this so that we could see the margins,
and then we opened it up. So what do we see architecturally? It’s papillary—you can see raised
papillary projections. What about this big space? It’s cystic…, so we have a cystic papillary tumor
here. We’d call this a papillary cyst, and it’s either an adenoma or an adenocarcinoma because it
arrises from glandular epithelium, depending on whether it’s malignant or not. It is malignant,
so it’s a papillary cystadenocarcinoma. Furthermore, we see that these are mucinous cells, so
it’s a mucinous papillary cystadenocarcinoma.
7. If we have a malignant tumor, it’s called a sarcoma. A malignant tumor of fibrous origin is a
fibrosarcoma. A malignant tumor of cartilaginous origin is a chondrosarcoma. Epithelial cancers
are called carcinomas. They’re named based on their cell of origin. If we have a malignant tumor
of squamous epithelium, it’s called a squamous cell carcinoma. Squamous epithelium is
normally located at the skin, esophagus, cervix, recto-anal junction. An adenocarcinoma is a
malignant tumor arising from a gland/ glandular structure. Examples of these would be thyroid
cancers, or breast cancers, or prostate cancers. There is also glandular tissue in the GI tract
below the stomach that can also have cancer. Another example is a basal cell carcinoma that
arrised in the skin. It has the appearance of a basal cell—a small uniform cell.
8. General concepts of neoplasias. Neoplasms are monoclonal, arising from a single cell which has
undergone neoplastic transformation. But the stem cells can undergo divergent differentiation
leading to mixed tumors (ie they’re made up of different cell types). Classically, there are
pleomorphic adenomas that the dental students will see in practice. This is a salivary gland
tumor that is usually seen in the parotid, but it can also be seen in minor salivary glands too. It
has divergent differentiation, so there are multiple cell types (epithelial and mesenchymal
components) within the tumor. A teratoma is another example of a mixed tumor. A
fibroadenoma is mixed by appearance only because now we know that the epithelial
component of the tumor is a bystander—it’s not neoplastic like the mesenchymal component is.
9. This is a pleomorphic carcinoma—a benign mixed tumor of a salivary gland. You can see that it’s
encapsulated and we have small glands and we have what looks like cartilage too. So we have
epithelial and mesenchymal cells in the tumor. It’s still all from a single neoplastic cell, but that
cell diverged as it differentiated, leading to multiple cell types. This is a table taken from our
book.
10. These are other magnifications of slide 9. Here you can see the cartilage component.
11. Here you can see the glandular component more prominently.
12. This is an ovarian mass from a woman in her thirties. It’s a cystic lesion that’s been opened up.
You can see a tooth-like structure. There’s also a tuft of hair. This is a terratoma. It’s a mature
cystic terratoma, and here you see mature differentiation from any number of tissue lines. You
can see any kinds of tissue in these. He’s seen brain cells lined up or even a jaw bone with teeth
lined up. The point is that this is a mixed tumor that arose from one cell that underwent
divergent differentiation to lead to the formation of other cell types.
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pg. 3
13. This is a table taken from our book that just talks about nomenclature. It lists the tissues of
origin and the names of the neoplasms that can be formed.
14. There are a few tumor types that don’t follow the normal rules that we’ve established. You
would think a lymphoma would be a benign tumor of lymphocytes, but it’s actually malignant. A
mesothelioma is a malignant tumor arising from the mesothelial lining cells that line the pleural
space and the abdominal cavity. It’s more commonly noted around the lungs and is seen with
asbestos exposure. A melanoma is a malignant tumor of melanocytes. It’s fairly aggressive. A
seminoma is a malignant germ cell tumor seen in the male testes. A hepatoma is a malignant
tumor and it’s an old term used for a hepato cellular carcinoma, but this name is still used
sometimes. A choristoma is not a neoplasm at all. It’s actually a rest of normal tissue left behind
by embryogenesis. It presents as a neoplasm, but it’s benign normal tissue.
Another slide added that we don’t have… This is an organ—a lung (probably from an autopsy).
The lung tissue is very deteriorated at the center of the picture and there is a good bit of white
tissue around the lung. This thick white proliferation is a mesothelioma—a malignant tumor of
the lining of the lung.
This lesion is a pigmented lesion. It’s a malignant melanoma. It has irregular borders. In a normal
specimen you can see at the dermoepidermal junction that there are small nests of
melanocytes. But with the malignant melanoma, these are all melanocytes. They’re going up
into the epidermis, and are also going down into the dermis. (The slide showed a ton of
melanocytes, almost covering the picture). These cells tend to have irregular edges—called
“shouldering.”
15. Determining malignant vs. benign is very important. This may need to be done quickly while the
patient is in the operating room because the surgeon needs to know whether marginal tissue
should be removed with the tumor (to reduce reoccurrence of a metastasizing tumor). There
may also need to be an evaluation of regional lymph nodes to look for evidence of spreading.
And it must also be determined if there’s a need for radiation.
16. So what do we look at? The first thing we look is the degree of differentiation. Do the
parenchymal cells look like the normal cells of the tissue present? Benign neoplasms are usually
well differentiated. If there’s a lack of differentiation, you see “anaplasia.” This shows bizarre
nuclei, atypical division, and a loss of cell polarity. The degree of differentiation correlates to
what we’d call the grade of the tumor. This is determined by microscopic examination.
17. This is thyroid tissue. Here we have thyroid follicles with the eosinophilic colloid within the
follicles. This looks like normal thyroid. But this is actually taken from the center of a mass. It’s a
well differentiated neoplasm, so we’d say that this is a benign tumor.
There was a slide that showed the mass grossly. The mass was encapsulated completely, and it
stood out from the surrounding tissue. What would we call this? It’s a follicular thyroid
adenoma—derived from the follicular cells, and it’s benign glandular tissue.
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Clay McEntire
pg. 4
18. This is an oral cavity lesion. The cell type is squamous epithelium. You can see some keratin that
was produced. It’s malignant, sotThis is a squamous cell carcinoma.
19. This is an example of an anaplastic tumor. It’s of skeletal muscle origin, and it’s called a sarcoma
(actually a rhabdomyo sarcoma because it’s skeletal muscle). If it was smooth muscle, it’d be a
lyomyo sarcoma. This is a good example of anaplasia with the bizarre nuclei and multinucleate
cells. “Rhabdo” means “rod-like.”
20. Dysplasia is a pre-neoplastic change that occurs with epithelia. This is common in the cervix or
the oral mucosa, but any squamous epithelium can undergo neoplastic change. Not all dysplasia
digress to cancer!
21. Don’t worry about this in any detail. We grade dysplasias. Mild dysplasias are confined to the
base of the epithelia. And as they progress up toward the surface, you have an increase in risk
developing cancer. This is important for dental students; you’ll be looking for these types of
lesions. It’s important to catch these quick because they can be treated before progression to
squamous cell carcinoma. This is also the reason for screening by pap smears.
22. Back to differentiation. In general function correlates with differentiation. With poorly
differentiated tumors, unanticipated functions can emerge. The tumor can begin to make
hormones that are not usually by that cell type, and also fetal proteins may be produced.
23. The next thing that we’ll look at is the tumor’s rate of growth. Most benign tumors grow slowly
and malignant tumors grow fast. Rapid growth may lead to necrosis. The rate of growth is
related indirectly to the degree of differentiation (ie a poorly differentiated tumor tends to grow
rapidly). Benign tumors usually take years to become noticeable. With rapid growth (malignant)
tumors, you may see necrosis. They grow so rapidly that they outgrow their blood supply-- you’ll
see necrosis because the tumor can’t acquire the nutrients it needs.
24. This is probably a cervical biopsy showing a proliferation marker. You can see squamous
epithelium, where normally you’ll see proliferation in the basal layer, but here you see that the
marked proliferating cells are extending all the way up to the surface. So this is a severe
dyspasia or a carcinoma in situ.
25. Another feature of malignant tumors is the ability to invade. Benign tumors don’t invade. They’ll
develop a defined fibrous capsule (as was saw with the gross picture of the thyroid).
26. This is a breast lesion is a 22 year old woman. There’s a glandular component and fibrous tissue
too. There’s a sharply circumscribed capsule, so it’s benign. We’d call this a fibro adenoma of
the breast.
27. In contrast this is a breast excision from a malignant tumor from a woman in her fifties. These
are epithelial cells. There is glandular tissue too. There is no sharp order between the gland and
the tissue, so it’s malignant. We’d call this an adeno carcinoma. Then, we’d look at the cell
type—these are ductile cells, so it’s a ductile adeno carcinoma. Repeated features of malignancy
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Clay McEntire
pg. 5
seen here: There’s invasion into the surrounding tissue, and we’re seeing a lack of
differentiation. We’d probably call this a moderately differentiated tumor.
28. The presence or absence of metastasis are another way to determine malignant vs. benign.
Metastases are secondary, remote implants of tumor. These are almost always a sign of a
malignant tumor (the most important hallmark of malignancy). Basal cell carcinoma of the skin
(very common around the eye) is an exception though—these rarely metastasize. Squamous cell
carcinomas of the oral cavity/ larynx tend to spread to the cervical lymph nodes. Breast cancer
will spread to the axillary lymph nodes.
Methods of metastasis varies. There can be spread by direct seeding, which could be seen in
the abdominal cavity if you have a tumor on the ovary. The tumor could spread from the surface
of the ovary to somewhere else in the abdominal cavity. Some tumors undergo lymphatic
spread—breast cancers, lymphatic cancers, papillary cancers of the thyroid are some that we’ve
mentioned that do this. Other tumors tend to spread through the blood vessels (hematogenous
spread), and can then spread to the bone or other organs. Follicular carcinoma of the thyroid is
an example, and it tends to go to the bone. Prostate cancer metastasizes to bone. Colon cancer
goes both ways—regional lymph nodes and bone, liver, and lung.
29. This is a liver. You can see multiple nodules. This is a metastatic colon cancer. When there is
hematogenous spread of a tumor, you tend to see multiple nodules in the organs. So if you see
multiple lesions in the liver, you’d think metastasis. If you see 1 lesion, you’d think it’s a primary
tumor if there’s no other history.
30. This is a spinal column. This patient had prostate cancer, and you can see multiple nodules that
spread from the prostate.
31. This is a summary of features of malignancy vs. benign. Benign on the left: small, well
circumscribed lesion in the smooth muscle arising from the myometrium. This would be slow
growing, doesn’t invade the surrounding tissue, hasn’t metastasized. If we look at it
histologically, we’d see that there is a high degree of differentiation of smooth muscle cells, so
we’d call this a lyomyoma—a benign tumor in smooth muscle. Malignant on the right: large,
bulky tumor that infiltrates surrounding tissue, fast growing with necrosis. If you look at it
histologically, you see poor differentiation. The cells are starting to become more compact with
irregular nuclei. If we were to get something like this, where cells are VERY poorly differentiated
(and you can’t tell the cell type), we’ll use antibodies to determine the cell type (ie an antibody
specific to actin molecules could tell you if there is smooth muscle differentiation).
32. Epidemiology gives us information about relationships of factors that help us determine the
frequency and distribution of diseases in the human community. This contributes to our
understanding of risk factors (ie who’s going to get what type of tumor and why?) For example
smokers are more prone to squamous cell carcinoma of the lung, and people with fatty diets are
more prone to colon cancer. There are some types of lung cancer that isn’t more particular to
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smokers: lympho epithelioma type of carcinoma, which is common in China and is associated
with the Epstein Bar virus.
33. This is looking at the cancer incedence. In men you can see that the most common cancer is
prostate cancer, followed by the lung and colo-rectal cancers. In women, breast cancer is most
common, followed by the lung and colo-rectal also.
34. This shows death by site. It’s a little different. Even though prostate is most common in men, it’s
not the leading cause of death. Lung cancer is. This is similar with women—even though breast
cancer is most common, lung contributes to the most deaths. A lot of this is related to our ability
to catch and treat these various types.
35. This shows the changing cancer rates over time with women. You can see that there are some
dramatic changes related to gastric cancer, probably related to changing diet (maybe changes in
food preservation). You can see a drop in uterine cancer, which can be explained by the advent
of the pap smear and screening for cervical carcinomas. There is a rise in lung cancer probably
attributable to increased smoking.
36. In men we see the same drop in gastric cancer that we saw in women. We see a rise and then
drop in lung cancer due to changes in smoking rates.
37. Geographic and environmental factors influence risk of development of specific cancer types
too. Breast cancer has a 4-5X higher rate in the US and Europe than in Japan. Stomach cancer
has a 7X higher rate in Japan than in the US. Hepatocellular carcinoma is rarely seen in the US,
but it’s one of the most common types of cancer seen in some African populations. These
geographic patterns don’t appear to be genetic, but instead seem to be exposure related (diet
and environment).
38. You can see that by looking at immigrant populations. Japanese people have a high incidence of
stomach cancer, but when they move to the US, the rate drops. It drops anymore for their kids.
39. Age. The frequency of cancer increases with age with a peak between 55 and 75. This is due to
an increased accumulation of somatic mutations. About 5-10 % of cancers are linked to
hereditary factors. There are some hereditary syndromes associated with these (ie there’s LiFraumeni syndrome associated with an abnormal p53 inheritance). There are brachomutations
(sp?) that can occur—increasing the risk of ovarian cancer. Most cancers don’t have this
hereditary connection though. Acquired preneoplastic disorders (ie dysplasias) increase the risk
of developing cancer. We talked about how cervical dysplasias are associated with an HPD
infection. Adenomas of the colon are also examples of preneoplastic lesions.
40. Clinical features of malignancy. A prominent feature is cachexia: decreased body fat, weakness,
anorexia, and anemia. Cachectic patients will have more infections. The reason for cachexia is
the increased metabolic rate due to the metabolic demands of the tumor. Some abnormalities
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of taste may also occur, decreasing the patient’s desire to eat as much. This correlates with the
size of the tumor.
41. Patients can develop paraneoplastic syndromes. These are syndromes that can’t be explained by
the spread of the tumor or by indigenous hormones. There can be endocrinopathies within the
tumor (ectopic hormone production). There could be syndrome inappropriate ADH secretion
(SIADH) or hypercalcemia because of a tumor producing hormones that wouldn’t normally be
present. You can also have neuropathies associated with a tumor (nerve and muscle disorders).
You can have vascular and hematologic changes so that you develop coaggulopathies with an
increased risk of thrombosis.
42. Cancer diagnosis. There are a number of ways that we make these diagnoses. The most
common way is biopsy: a clinician removes a piece of a mass lesion and sends it to a lab. It’s
then determined whether it’s a neoplasm or not. Malignant or benign? Can then classify it and
tell them how aggressive it looks. Appropriate therapy can then be determined. This is a tissue
diagnosis.
There are some less invasive techniques too: fine-needle aspiration (FNA) where a needle can be
put into a tumor and some of the tumor’s fluid can be removed and cells can be observed via
microscope. All you can look at with this is degree of differentiation. Are these normal cells or
not? Can’t get any architectural details—can’t determine if there’s invasion going on.
There are some biochemical markers that can be observed to check for tumor presence.
Prostate specific antigen can be used as a screening tool to check for prostate cancer. This is a
serum test—blood is drawn, and if there’s an elevated PSA, the patient may have prostate
cancer. Then you’d confirm with a biopsy. This technique can also be used to follow treatment
to see if a tumor comes back after removal.
43. This is an example of how the criteria are applied. This is a normal pap smear. You can see
squamous epithelial cells, abundant cytoplasm, small uniform nuclei, some endocervical
glandular cells, and a few scattered inflammatory cells.
44. This is a pap smear from a patient with cancer. You can see large irregular nuclei, irregular
cytoplasm, and spindle-shaped cells. This is abnormal and we’d call this either high-grade
dysplasia or “carcinoma outright.” This would prompt a biopsy and possibly further therapy.
45. There are two more concepts that we need to be aware of. Grade is a microscopic term of
differentiation. It’ll either be well differentiated, moderately differentiated, or poorly
differentiated. More importantly is the stage: the pathologic and clinical findings describing the
extent of the disease. This is determined by tables—you look at tumor size and the extent of
tumor involvement. For instance, for colon cancer we’d look at the depth of invasion (ie is it
confined to the muscularis mucosa or has it progressed further? The depth of invasion gives you
the T-stage value. We’d also look at N- the presence or absence of nodal metastases, and M- the
presence or absence of distant metastases. Stage is a stronger predictor that grade!
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pg. 8
46. We’re going to try to name somethings. What do you see here? It’s an encapsulated lesion. This
is a benign fatty tumor—it’s a lypoma. The capsule is a fibrous capsule.
47. Where do you think you are here? There’s ulceration of the intestine. The tumor invades into
the fat tissue (so it’s invasive- think malignant). You have a glandular epithelium that lines the
colon. The tumor is malignant and it’s glandular epithelial tissue, so it’s an adenocarcinoma.
Histo slide of same specimen:
48. Here’s the invasion histologically. This is the glandular epithelial tissue.
49. Here we see a lesion on the lip. It’s squamous epithelium. It’s invasive (you can see this in the
top slide). In the bottom slide you can see the keratin produced by the squamous cells. This is
squamous cell carcinoma.
50. Here we have a bone tumor in a 14 year old male. You can see expansion of the bone and
invasion out into the soft tissue (malignant!). The cells are producing bone matrix. It’s called
osteo sarcoma.
51. This one is on the skin. You can see other lesions forming, so it’s spreading (metastasizing). It has
irregular edges. So this is a melanoma, arising from the melanocytes. Something interesting
about these is that the lesion itself isn’t very pigmented, but when the macrophages around the
lesion take up the melanin, they show pigmentation.
52. This shows 2 organs. Bottom left is lung. Liver is top left. You can see multiple nodules. If you
look at the histological slide, you can see glandular tissue. This is metastatic adenocarcinoma
because it’s glandular epithelial tissue that’s metastasizing. This was actually coming from the
colon (hematogenous metastasis).
53. This is just a beautiful picture. The pigmented lesion is a primary ocular melanoma.
54. THE END
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