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looking for volunteers to describe the three specimens in lab today....
if not, he's going to pick three blindly from the page...here we go:

heather chalfont.

is today anyone's birthday?

no. ok. Sarah greenberg

and...Sean Sawyer. Dr Weber will autograph sean's notes in return.

Note to those who already saw specimens: BACK THE F*CK OFF AND LET OTHERS 
TAKE A LOOK AT THEM TODAY!

we should be able to start going over them by 3:30

schedule says friday lec 11-12. we will have that. but also it says 1-3 
path lab review. that will be 4 people in lab - drs goldschmidt, van 
winkle, chacko, and weber, total of 12 specimens. there will be questions 
and answers prepared. can ask any additional questions. use the time as 
you see fit. people usually find this presents a good summary of the 
course, and a useful review. but you do not have to attend. we are a 
unique group. maybe we won't like it.

EXAM: according to our schedule, the exam is monday, may 19th, 10-1 or 
so.
he suggests we all show up on time, because the exam will be set up in 
MDL 12, which will be off limits. assemble in MDL 11 and look at wall 
posters. then, go into other room. half the class will start with 
practical, half won't. you have ten minutes to look at the specimen. you 
make notes on it in rough form, then go back to desk and write it up 
(legibly). he's gonna flip a coin: heads, first half, tails, second half 
of alphabet (does practical first). tails. so tail end of alphabet starts 
with practical. oops, that's TOTALLY wrong. starting with z, you go look 
at specimens, and we'll work back toward the beginning of alphabet.

READ HISTORY that goes with the specimen. do not IGNORE it. pay attention 
b/c it will have CLUES. it is not there to mislead you. there will also 
be one or two projectors set up with related slides. so you should be 
able to tell chronic infl from tumor, etc.

practical is worth 10 points on final exam. can't get less than zero. 
just try your best. you can't get less than zero!

there will be a gross specimen and some correlating slides.

a few things about effects of tumors on the host:

realize that location of tumor is often CRITICAL. even some benign tumors 
can have devastating effects in some locations. a 1/2 cm adenoma in 
pituitary can cause pressure atrophy of pituitary: bad. a 0.5 cm diameter 
leiomyoma of renal artery could cut off blood flow to whole kidney. a 1 
cm or 2 cm benign brain tumor can seriously affect various functions and 
be very difficult to treat - we do not do brain surgery on pets, 
generally speaking.

tumors of endocrine organs have very profound effects on metabolism. a 
1/2 cm diameter benign tumor of islet cells can cause sudden death from 
hyperinsulinemia and hypoglycemic shock. benign tumors as well as 
malignant ones can be functional and in fact are more likely to be 
functional, since benign tumors tend to be more differentiated. 
malignancies tend to be more anaplastic and less functional. in adrenal 
gland, can have functional cortical tumor causing cushings dz. in thyroid 
gland an adenoma can cause hyperthyroidism and greatly accelerated 
metabolism. you usually don't know from looking at a specimen whether or 
not the tumor is functional. could be hyper or hypofunctional. you need 
clinical history and chemistry to say for sure. some very tiny tumors are 
only detected from these chem screens showing some abnormality. a patient 
may present with metabolic aberration that turns out to be a tumor like 
this.

other times, many tumors can ulcerate and obviously any skin surface 
tumor or third eyelid or whatever can be licked, rubbed, traumatized and 
ulcerate from that, but malignancies also tend to spontaneously ulcerate 
due to tissue destruction, and to bleed more. eg, a gastric carcinoma 
will invade, destroy blood vessels - cause death. a hemangiosarcoma in 
spleen can rupture, and if it had cavernous blood vascular spaces, animal 
can bleed out internally and die.

necrosis of tumors: we frequently discuss central portions of many tumors 
that become necrotic, esp w/malignancy. tumor outgrows its blood supply, 
basically. not enough angiogenesis occurs so tumor becomes ischemic and 
necrotic. but also, a factor made in animals that have neoplasms (and in 
chronic infl response) exists which is called TNF tumor necrosis factor. 
this factor comes from plasma and is liberated there but the product is 
produced either by mphage or TH cells (t cells). you get two different 
kinds of TNF that we lump together. a pleotropic molecule that has 
varying effects. the TNF was isolated and injected into tumor bearing 
animals...caused hemorrhagic necrosis of some but not all tumors. so for 
many tumors with necrotic centers, this factor may be playing a role in 
causing that- TNF may induce tumor necrosis (SURPRISE!). TNF can in fact 
kill tumor cells, but doesn't kill normal cells. now the number of 
receptors on tumor cell doesn't seem to correlate with whether cell is 
killed by TNF. but, nonetheless, TNF seems to play a role in causing 
tumor necrosis in some but not all tumors.

TNF is necessary for angiogenesis, you may recall dr webber saying that 
during the regeneration/healing lectures. remember, it has many 
functions, is pleotropic, it also stimulates fibroblasts and causes 
collagen production. but we're not discussing that right now, thanks for 
playing. we're talking about its effects on tumors.

CACHEXIA: cachexia is really a term for gradual wasting of animal that 
carries a tumor burden. that means they lose body fat, body weight, are 
often anorexic, don't eat well. that alone though, the lack of food 
intake, doesn't explain the wasting away we see. apparently, in tumor 
bearing animals, in contrast to low-caloric intake individual, metabolic 
rate does not drop in compensation. in cachectic animals, metabolism 
stays HIGH. may also have FEVER perhaps from secondary infection of some 
kind, because tumors are immunosuppressive probably from TGFB being 
produced by many tumors, which suppresses lymphoid system. so you have 
depressed immunity, increased metabolic rate, anorexia, and gradual 
wasting away. TNF may also cause accelerated metabolism of fat and 
protein, contributing to this problem. 

PARANEOPLASTIC SYNDROMES:
these occur in about 5-10% of tumor bearing animals. actual textbook 
definition of paraneoplastic syndrome is incomprehensible. but it means 
that it is some aberrant metabolic activity which usually can be traced 
back to the tumor, but it's totally unexpected that this tumor would 
produce any functional protein molecules to cause this aberration. eg, 
may have a fibrosarcoma, and then see the patient has hyperinsulinism. 
hmm. pancreas must be involved. but pancreas is totally normal. in fact, 
the fibroblastic transformation is producing insulin. totally unexpected! 
why? well, probably due to expression of genes due to "unrepression" of 
genes. these neoplastic cells are more undifferentiated, and may express 
genes that more diff cells wouldn't. eg, in some lung CA - squamous cell 
bronchogenic CA, or in some leukemias, you may see tremendous 
hypercalcemia causing probs w/heartbeat, mineralization, etc. why would 
this occur? parathyroid is being stimulated. how? why? well the tumor 
involved can suddenly start making a PTH-like protein, which acts on the 
totally normal parathyroid gland, making it act, leading to 
hypercalcemia. this is a frequent paraneoplastic syndrome in our 
patients. you should consider it on your ddx list for hypercalcemia! 
(with malignancies, btw. you don't see this with benign tumors). so 
paraneoplastic syndrome is this aberrant metabolic expression, induced by 
tumors in totally unexpected way.

in tumors of kidney, you may get increased erythropoiten production (in 
primary renal CA). this will increase HCT, can be a problem, b/c you can 
also get problems with clotting/thrombosis as a paraneoplastic syndrome. 
you can see venous thrombosis of unexplained origin. you can see 
noninfectious thrombotic endocarditis - thrombus formation on valves of 
heart unrelated to infxn -in these situations, the tumor cells may be 
making procoagulant substances, predisposing animal to DIC or other 
problems.

can you kill a tumor by cutting off its blood supply? theoretically. but 
you really wouldn't be able to find all the vessels to ligate. right now, 
people are looking at ways to interfere with angiogenesis by tumors - to 
prevent growing neoplasm from getting enough ingrowth of new vessels so 
that it can't grow. want to produce thrombosis of those vessels and 
ischemic necrosis of those tumors. far from clinical application. and 
some tumors aren't well vascularized.

you can use TNF in tissue culture and it may not kill any tumor cells. 
but it CAN kill some types of tumor cells in vivo, although activity 
doesn't really relate to the number of TNF receptors there are on the 
surface of the tumor cell which troubles people.

do tumors get innervated? like, with nerves, asks dr weber? ha. most 
tumors don't have nerves in them, except for say ganglioneuromas, or 
maybe teratomas that have nerve in them. but, while you are talking about 
nerves...most tumors are painless in and of themselves. if you are 
palpating a peripheral LN and animal responds, probably inflammation at 
work. but w/lymphosarcoma, usually no pain response to palpation of LNs. 
but, what about lymphatics? do tumors have lymphatic vessels? can you 
inject chemo into lymphatics and have it reach a neoplasm? there seem to 
be some lymphatics coming OUT of the tumor, but none going in. the 
lymphatics form as blood supply is forming, but they only drain out of 
tumor, not into tumor, so cannulating lymphatic doesn't really help to 
reach the tumor. only way to get into the tumor w/chemo is through 
blood...so whenever you get to a mass over 2 cm in diameter, it's very 
hard to get stuff in high enough concentration to kill 100% of tumor 
cells w/o adversely affecting rest of animal!!

[slides]

very large kidneys on this animal. lymphoid tumor - renal lymphosarcoma. 
this is the "abdominal form" of lympho seen in cats (opposed to thymic 
form seen in younger animals). this form is seen in older animals and 
secondary to FeLV. usually thymus not involved. you ahve massive 
involvement of kidneys, which are diffusely infiltrated by this 
grey-white tissue. you could have a cat come in w/renal problems and 
those problems could be due to advanced renal lympho which has totally 
obliterated normal renal parenchyma, and all through kidney is immense, 
diffuse proliferation of tumor cells which here presents as grey bulging 
tissue w/a few areas of hemorrhage.

remember normal cat kidney cortex usually has a lot of fat and is light 
and yellow with pronounced vasculature on the surface.

another abnormal cat kidney: can tell from cat due to yellow color and 
vascularity on subcapsular surface, and size. these kidneys are from two 
cats and are different processes: one has pale pink coalescing raised 
areas on one pole of the kidney. these lesions do not invade beneath the 
cortex (except for a few small foci) and on cut surface are pinpoint 
discrete nodules within the cortex...they are granular and gritty - this 
is a granulomatous response to a virus.
the other has coalescing multinodular grey tissue taking over whole 
capsule, with areas of hemorrhage - here we see major growth of bulging 
grey white tissue into cortex and poking into medulla...this is 
lymphosarcoma.
note that they look extremely similar. nodularity does NOT always imply 
neoplasm. it COULD BE GRANULOMA! granulomas will probably tend to be 
gritty inside. need to do histo to be sure.

how to take biopsy properly - will go over that soon.

one of most common lesions we'll see in spleen of old dogs is a so called 
splenic nodular hyperplasia. NOT precursor to neoplasm. poorly explained. 
just a nodular proliferation of mostly lymphoid tissue w/some 
vascularity. if you see this in atrophic spleen with wrinkled grey 
surface, from older dog, consider splenic nodular hyperplasia. could also 
be hemangioma, need to consider that. sometimes the proliferation of 
lymphoid tissue shows up as white tissue in clumps on the surface of the 
nodule. it's not a benign tumor, it's just a hyperplastic situation.

if you have a benign tumor in the brain, it can cause pressure on the 
brain, eg in this old cat with meningioma, a benign slow growing tumor. 
it can cause atrophy and necrosis of adjacent brain tissue. this is very 
bad, just as bad as malignancy!

two examples of trying to decide if you have primary or metastatic 
neoplasia in an organ:

lung - one lobe is a very large, grey, almost well defined tissue mass, 
very vascular, grey yellow tissue extending somewhat into adjacent lobe. 
when you have one major tumor focus like this, you should always consider 
it being a primary tumor rather than metastatic - USUALLY,mets are 
diffuse multiple lesions (nodules). rarely does a neoplasm metastasize to 
a remote site and form one discrete mass there. it is POSSIBLE, but 
unlikely, does't really fit profile of hematogenous spread.

neoplasia in kidney: no other tumor in animal. 3/4 of kidney totally 
obliterated by tumor mass. complete replacement of normal tissue by this 
grey/pink mass w/necrosis in it. what could this be? probably tubular 
epithelial carcinoma, aka renal carcinoma, or renal adenocarcinoma if 
looks glandular on histo. but it's a primary tumor - no other tumor in 
animal.

lastly, how do you tell in a glandular structure if something is 
hyperplastic or neoplastic? eg, adenoma vs hyperplastic nodule. 

adrenal glands: bulging cortex, enlarged, in some areas projecting into 
medulla.
other adrenal glands: discrete nodule situated in the medulla.
the first would be called cortical nodular hyperplasia, the second would 
be called an adrenal cortical adenoma. both could be functional. you 
would have to figure it out, if its a functional tumor or hyperplasia. 
this can be hard. pathologists will argue about it all day. sometimes 
nobody knows. these decisions can be quite arbitrary and often totally 
wrong. pathologists are not perfect.

ok, how to take a biopsy: assume you have a neoplasm growing in the skin. 
you have a defined, palpable mass, and you wanna send in a biopsy. what 
do you do? say it's 4 cm diameter, growing deep into the skin. first 
thing to do is to take the mass out of the skin. remove the sucker 
surgically. no reason to leave it in there! then, some people send the 
whole mass in, stuffing the whole thing into a tiny jar of formalin. but, 
that makes the tissue very hard, and hard to get out of the jar and 
stuff. so it's better if you take a section of the border between normal 
and tumor - make sure to include both kinds of tissue together in one 
section. don't take a section from the center of the tumor - it's 
probably necrotic anyway and no one can tell what it is. usually take a 
few sections from around the edges, and a piece from the surface. thin 
enough - like 1/2 cm wide - then in a jar with about 10x amount of 
formalin, and send it in.


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