Sets of genes.

Neoplasia

Post 27: (Dated: Feb 13 - 2009)

Main difference between benign and malignant: Benign does't metastasize but Malignant do.

Invasive Mole: Benign tumor which metastasize to lungs.

Basal cell carcinoma: most common skin cancer which can invade but does't metastisize.

Qs: Most common benign tumor in a women which most commonly located in which of the following organs - Ans, uterus and the most common benign tumor is leimyoma (smooth muscle tumor).

Term fibroid - "Oid" means looks like fibrous tissue, but its a smooth muscle. It becomes so hard they look like scar tissues; No transformation to leimyosarcoma.

The most common benign tumor in a man, "Yellow", around elbow , Lipoma; Most common in womens, Leimyoma of uterus.

Benign tumors of glands = Adenomas

Adenomas of adrenal: Thinness of adrenal cortex, which must be functioning, making cortisol (cushings)---> ACTH suppressed ---> Fasciculata and Reticularis undergoes atrophy;

If the tumor is producing mineralocorticoid = Conn syndrome (atrophy of zona glomerulosa).

GFR = Glomerulosa (salt), Fasciculata (glucocorticoids), Reticularis (sex hormones)

Tubular adenoma: MC Precursor lession for Colon cancer looks like a strawberry on a stick.

Carcinoma is the malignancy of epithelial tissues (sq, glandular, transitional).

In Sq.Carcinoma: Little spirals of increase redness called as Sq.Pearls

Glandular carcinoma: Glands, looks like round and have something in the middle ---> Adenocarcinoma (things inside the glands)

Transitional cell Ca: Comes from genitourinary tract (bladder, ureter, or renal pelvis)

Malignant Melanoma: Rx Excission; malignancy of malenocytes; Benign form is Nevus. Most Rapidly increasing cancer in USA. S100-Antigen positive, APUD tumors (Amine Precursor Uptake and Decarboxylation = apud cells uptake precursors of amines n the decarboxylates them to make amine!!) which have neurosecretory or neurocrest origin. On EM, they have neurosecretory granules. S100 Antigen which is used for staining things with APUD origin or Neurocrest origin, most of them do not take stain.

Melanoma is an APUD tumor; S.C.C of lung also APUD tumor, its less malignant counterpart called bronchial carcinoid; The carcinoid tumor at the tip of appendix is APUD tumor; Neuroblastoma in renal medulla in a child is APUD neurosecretory tumor.

Qs: 2 year old that has nodules all over the skin. The biopsy showed small hyperchromatic cells which are s100 antigen postive, where is the tumor coming from? Ans - Renal medulla,neuroblastoma - metastatic to skin.

Sarcoma is the malignancy of Mesenchymal tissues, Not epithelial tissues.

Osteosarcoma THE MC PRIMARY MALIGNANT TUMOR OF BONE ----> Metaphysis of distal femur, proximal tibia & humerus ---> malignant cells produce bone matrix--> X-ray shows Codman's triangle (as new bone lifts up the periostium n we can see it growing out!!). This particular tumor makes bones and on xray shows sunburst appearance ---> diagnosis, Osteogenic sarcoma (Osteogenic means bone making sarcoma) --à asso. With RB gene mutation!!

Slide: Biopsy of a little girl, that had a necrotic mass coming out of vagina. Biopsy showed, vimentin negative, keratin negative, desmin positive ---> Embryonal rhabdomyosarcoma; striations in muscles can be seen. Most common sarcoma in childrens, comes out of vagina of little girls and penis of little boys.

Sarcoma of smooth muscle: Leimyosarcoma

Sarcoma of striated muscle: Rhabdomyosarcoma

Sarcoma of Fat: Liposarcoma

All of these are malignancies of mesenchymal tissues.

Carcinomas are of epithelial tissues.

Qs: Movable at the angle of Jaw: Mixed tumor. The organ affected is Parotid which is the most common overall salivary gland tumor usually benign occasionally malignant.

10. Mixed tumor of the parotid These tumors are considered the MOST COMMON type of salivary gland tumor. They arise from the same germ cell layer but there are two distinct types of histologic patterns within the tumor. These tumors usually have a glandular type of tissue plus a myxoid stroma. (Neo012)

Term Mix means: Two histologic different types of tissues like they derive in the same germcells layers, which is not in teratoma.

Teratoma: Tooth, hair etc. Teratoma derived from all three cell layers; ectoderm, endoderm and mesoderm.

Cystic teratoma of the ovaries Qs: 16 year old girl with onset of right lower quadrant pain (always make right lower quadrant pain making confusion with appendicitis, crohn disease, ectopic pregnancy or follicular cysts). Xrays showed some calcification in the pelvic area ---> cystic teratoma; calcifications could be bones or teeth.

Neoplasia

Post 28: (Dated: Feb 14 - 2009)

Germ cell tumors: They have tendency of staying in the mid line. Ovaries are reasonably in midline. Ant.Mediastinum is right in the midline. So teratoma is commonly developed there in the Pineal gland, which is in midline. Therefore these are midline tumors the teratomas which are Germ cell tumors.

Leukemia and Lymphomas:
Auer rod in a myeloblast ---> Leukemia
Hypersegmented neutrophils ---> B12, folate deficiency

Leukemia: Malignancy of stem cells in bone marrow. Like all cancers they can metastasize out of it and always do. They have gen.lymphadenopathy, and hepatosplenomegaly.

Malignant Lymphomas arise from lymph nodes. Because they are all malignant, can metastasize where ever they want including bone marrow.

The most common site of body where lymphoma are not developing in the lymph nodes is stomach. Most of them are extranodal (outside lymph nodes), primary lymphomas occurs in stomach; H.Pylori can produce Prim.lymphomas. The second most common location is in payers patches of terminal ileum.

Mix tumors Vs Teratoma
Leukemia Vs Lymphomas

Follicular B-Cell Lymphoma (MC Lymphoma), knocks off apoptosis gene. It is a translocation (14;18) of a heavy chain, B-Cells makes Bcl2 protein which inactivates the apoptosis gene in the B-Cell. The cells become immortal. Therefore it is the inactivation of apoptosis gene, common of all the lymphomas. Two cell types: centrocytes smaller n centroblasts larger!! Incurable, approach should be to palliate patients with low dose chemo n radio when they become symptomatic. 50% transforms to diffuse large b cell lymphoma!!

Trophoblastic tumors: We see in pregnancy. Males can get as well which are non-gestational.

Hydatidiform Mole(not a neoplasia but can transform into choriocarcinoma)(cystic swelling of chorionic villi with trophoblastic hyperplasia):

Looks like bunch of Grapes. Which presents in 1st trimester with signs of Pre-Eclampsia. So any patient that has HTN, proteinuria and edema in 1st trimester, U/S shows uterus too large for gestational age and "Snow Storm", which is the classic mole (complete mole). Complete mole has the highest tendency of going into choriocarcinoma.

Complete mole: Partial mole:

1. almost all villi are oedematous 1. Some villi are edematous

2. Diffuse trophoblast hyperplasia 2. Focal trophoblast hyperplasia

3. Androgenesis meaning the cells are diploid(46XX or 46XY) 3. Triploid (69XXY) due to fertilization of an egg with

but all of them are derived from the father due to fertilization chromosomes by one diploid or two haploid

of an egg that has lost its chromosomes by two haploid sperms sperms.

or one diploid sperm.

4. No embryogenesis so no fetal parts can be seen. 4. Embryo is viable for weeks so fetal parts are seen.

A mole is the benign tumor of the chorionic villus. Chorionic villi are lined by trophoblastic cells; including syncitiotrophoblast on the outside which is in contact with blood and O2 is extracted; Under the syncitiotrophoblast is the cytotrophoblast; then you have Wharton's jelly in chorionic villus; then there is a little vessel in the middle of the chorionic villus which eventually becomes umbillical vein which has the most O2 then fetus's.

Choriocarcinoma: which is not the malignancy of the chorionic villus but malignancy of the linning of villus (ie syncytotrophoblast and cytotrophoblast).

Syncytiotrophoblast makes B-HCG and Human placental lactogen (GH of pregnancy which gives AA, glucose from mommy to baby).

These are highly malignant but, they are gestationally derived; Metastatic to lungs; they respond incredibly to chemotherapy like Methotrexate, etoposide, actinomycin D, chlorambucil and they go away.

All thats ends in "OMA" not necessarily benign. Like:
Melanoma - Malignant tumor of melanocytes
Lymphoma - Malignant tumor of lymph nodes.

Hamartoma is a overgrowth of tissue that is normally present in that area; Like bronchial hamartoma - a benign cartilage which presents as the solitary coin lesion also “POP CORN APPEARANCE” (rounded focus of radioopacity on x ray) in the lung which makes you wonder about it is either granuloma or something of that nature but it is hamartoma, so they are not neoplasm. Lung hamartoma = peripheral solitary well circumscribed lesions made of nodules of connective tissue(cartilage is mc) intersected by epithelial(ciliated or non ciliated columnar epi.) clefts!

Polyp of Peutz Jagers syndrome is a hamartoma, its not even a neoplasm. There is no increase risk of colon cancer because the polyps are not neoplasms.

The Hyperplastic polyps which is the most common polyp of GIT is Hamartoma.

		18. Peutz-Jeghers This is a AD genetic syndrome associated with mucocutaneous pigmentation and hamartomatous polyps of the GI tract.high risk of intususception and developing carcinomas of breast, pancreas, lung, ovary n uterus.(Neo021)
		19. Hyperplastic polyps These are hamartomatous polyps of the GI tract which are the MOST COMMON type of non-neoplastic polyp. Microscopically, they show increased numbers of goblet cells.(Neo022)

Section of Stomach: In the muscle wall of the stomach presence of benign pancreatic tissue.

When you have benign tissue in a place where it should't be called Choristoma or Heterotopic rest. Meckel's Diverticulum lying on the antimesenteric side of bowel within 2 feet of ileocaecal valve, is the classic example as 50 % of them contains heterotopic rests of gastric mucosa or pancreatic tissue. Its true diverticulum meaning that it contains all three layers: mucosa, submucosa n muscularis propria. The MC complication of M.Diverticulum is bleeding from either ulcerated gastric mucosa and sometimes pancreatic tissue causing the ulceration.

Meckel’s Diverticulum: Classic example of CHORISTOMA

20. Choristoma (heterotropic pancreas) This is a section of duodenum showing an aggregate of pancreatic tissue in the wall. The pancreatic tissue is normal in appearance but in an abnormal location. This is a non-neoplastic process. (Neo023) Othe ex. Some adrenal cells found in ovary!!

Misconception is that increase mitotic rate means cancer - No. The thing which really make mitosis malignant is, 4N cell, more chromosomes in it then normal. We have atypical mitotic spindles which is related to the fact that they are aneuploid and have more than normal 46 chromosome like 63, thats malignant.

Neoplasia

Post 29: (Dated: Feb 15 - 2009)

Malignant cells have longer cell cycle than the cells they have derived from.

Qs: How many doubling time as it takes to get a tumor clinically detected? - Ans. 30 doubling times means 30 times going through the cell cycle and you get a tumor 1 sonometer (10)-9 in size.

Malignant cells are immortal and can live forever.

Burkits lymphoma cells are used in test for immune complexes. We can grow Burkits lymphoma cells in culture.

Malignant cells: They dont like each other so dont stick to each other, but like adhesion so they can infiltrate the tissues. They have very simple biochemical system usually anaerobic metabolism. They have lots of enzymes. They have proteases to break through the tissues, and Collagenase to break through the basement membranes.

Metastasis: Three modes of metastasis. Lymphatic, hemotogenous and seeding.

We have carcinomas and sarcomas.

Carcinomas: usually, initially metastasize by means of draining into regional lymph nodes. For breast cancer thats the axillary nodes, they can also go to internal mammary nodes. Colon cancer, they have nodes right around them. For esophageal cancers the node is right around it, so they go to the local lymph node.

What part of the lymph node? Ans. Subcapsular sinus.

Slide: This is showing cancer cells in lymphatic here, and showing a lymph node that has been partially replaced by malignant tumor.

So the rule is, cancer first goes to the lymph nodes ---> then goes to efferent lymphatics ---> thoracic duct ---> subclavian ---> Hematogenous.

Dont think that carcinoma are not hematogenously spread. When hematogenous it means they have gone through the lymph nodes. So they can go to bones, liver, and other places.

This thing is good. We can pick that node in clinical exam. We can pick cancer in early stage.

Unlike sarcomas which donot like go into the lymph nodes. They just like, going through the blood vessels, and usually chracterstically metastasize directly hematogenously. Thats why lungs and bones are such common sites for sarcomas.

If you have angiosarcoma of the breast would you do a radical dissection of axilla? - Ans. No, because the angiosarcoma does't go to the lymph nodes, you will do the simple mastectomy. But in case of carcinoma, you will take out the breast or lumpectomy ---> you sample a couple of lymph nodes or do a complete dissection, that would be part of it as carcinoma go there.

Slide: This is lymphatic spread. You can see lymph nodes here. This is tumor in a vessel.

Slide: As sarcoma likes to go into the blood vessels. Here is the tumor in the blood vessel.

Actually it is the follicular carcinoma of the thyroid. There are some carcinomas that dont always like to go to lymph nodes but wanna go hematogenously. So follicular carcinoma of the thyroid does't like to goto lymph node (transvestite).

Renal adenocarcinoma: Likes to invade the renal vein. Determines the prognosis. Goes through the renal veins upto IVC.

Hepatocellular carcinoma always invades the vessels. So there is always exception in every rule.

In general cacinoma first like to go to lymph nodes, then they have potential to become hematogenous.

Sarcomas dont like lymph nodes and go directly hematogenous, which makes them dangerous.

Seeding: Is the concept of seeding.... So we have cancers in cavities. Classic example of ovarian cancers, that have tendency of seeding little malignant implants. Most ovarian cancers are surface derived cancers, so it means they derive from the linning around the ovaries. Its easy for them to seed, through out malignant implants of small little pieces of cancers, and over the omentum and into the pouch of douglas (posterior to the uterus and anterior to rectum and can be felt by rectal exam).

Pouch of douglas is to women, as prostate gland to a man. When you rectal on a man you press forward thats the prostate, but in women you feel pouch of douglas (most important area as it is the most dependant part of the womens pelvis ---> things like to go there like clotted blood in ruptured ectopic, endometrial implants go in endometriosis, and seeding of ovarian cancers)

Ovarian carcinoma, which is seeded to the omentum, it actually can invade. It can actually seed into pleural cavity, eg peripherally located
lung cancer ---> they can get to pleura and seed to the pleural cavity.

Glioblastoma Multiforme: Most common primary malignancy of the brain in adults. It can seed into the spinal fluid and implant the entire spinalcord, so do the medulloblastoma in a little child.

Qs: If they ask you about most common cancers stuff. Is metastasis more common than the primary cancer? Ans - In most cases, metastasis is the most common cancer in an organ, not a primary cancer. Exception in Renal adenocarcinoma that is the most common one, not metastasis to it.

When we talk about lungs, most common is metastasis ---> from breast cancer; so womens are more likely to get the metastasis to lungs.

Bones, most common cancer is not MM or Osteogenic carcinoma; but its metastasis. Most common metastasis is from breast because of the Batasom system (its a venous complex that goes through the base of the skull down to the sacrum, it has no valves in it and little tributaries communicates with the V.Cava and also to the verterbral bodies and then they collect all together around the spinal cord area and goes back up).

Neoplasia

Post 30: (Dated: Feb 16 - 2009)

A women with breast cancer: May be she got a little plug of tumor in her intercoastal vein. She goes and pick something of the ground ---> dislodges the little piece of cancer from vein ---> vena cava ---> Batasom plexus ---> vertebral bodies ---> 3 month latter she complains of back pain. All of a sudden she is staged for cancer, just by bending over due to batasom system. The most common bone getting breast metastasis is vertebral colum. 2nd most common is the head of femur.

The Batson venous plexus, or Batson veins, is a network of valveless veins in the human body that connect the deep pelvic veins and thoracic veins( draining the inferior end of the urinary bladder, breast and prostate ) to the internal vertebral venous plexuses. ^[1] Because of their location and lack of valves, they are believed to provide a route for the spread of cancermetastases.^[2][3][4] These metastases commonly arise from cancer of the pelvic organs such as the rectum^[5] and prostate^[6] and may spread to the vertebral column or brain.^[7][8] There is less evidence of spread of cancers from extra-pelvic origins, such as lung cancer.^[9] The plexus is named after anatomist Oscar Vivian Batson, who first described it in 1940.^[2]

Batson's venous plexus may also allow the spread of infection in a similar manner. Urinary tract infections like pyelonephritis have been shown to spread to cause osteomyelitis of the vertebrae via this route. The osteomyelitis in such a case will resolve concurrently with the same antibiotic that treats the urinary tract infection because both infections are from the same organism.

Old person with removal of femoral head, always take sections through it because its metastasize to it ---> Women with breast cancer, realated to degenerative arthritis.

Most common organ of metastasis ---> lymph nodes. Since carcinomas are more common then sarcomas. Carcinomas like to go to lymph nodes, that would be the most common metastasis too.

Whats the most common cancer of liver? Ans- Mestastasis; The most common primary metastasis? Ans- (1)Lung beats (2)colon

Where would a testicular cancer metastasize first? Ans- Paraortic lymph nodes.
Why not the inguinal lymph nodes? Ans- Testis derive from the abdomen and then descend there.

So testicular cancers like a seminomas are malignant, first place not the inguinal nodes but it would be paraortic nodes.

Left supraclavicular nodes (virchow nodes ): MC Primaryà stomach cancer Metastasis Scenario - There is a mass in the left supraclavicular node.

Some one with weight loss and epigastric distress ---> stomach cancer ---> metastasis

Radionucleotide scan: Best test for bone metastasis. Everywhere you see black except the lucency(metastasis)??? down over there ---> its metastasis and the women is with breast cancer.

Most common bone metastasis is to is vertebral colum, higher vertebral colum (acromioclavicular area).

We have metastasis that are lytic and blastic

Lytic: They break bone down. Multiple myeloma ---> punched out lessions ---> all malignant Plasma cells have IL1 (osteoclast activating factor) in them ---> pathologic fractures + Metabolic abnormality (hypercalcemia).

Some cancers go into bones and induce osteoblastic response. Bone becomes dense ---> alkaline phos. elevated ---> Males with prostate cancer which is almost always osteoblastic (which is making bone and releasing Alk.Phos); Most common location for prostate metastasis is lumbar vertebrae.

Qs: 80 year old man with lower lumbar pain with point tenderness. First step in management?
a- Bone scan
b- PSA
c- Transrectal U/S
Ans: Digital Rectal exam. Its stage 4 disease which means that prostate definitely will be palpable. Then any other test.

Xrays:
Lytic metastasis ---> vertebrae colapse ---> lucencies (absence of bone)
Blastic ---> Densities???

image of patient with breast cancer metastasized to bones( osteoclastic ).(increased isotope accumulation in affected area)

Image of prostate cancer(osteoblastic) metastasized to chest wall seen as dark shadows.

CT scan of liver: If you see a gross specimen an xray, CT, MRI etc ---> Multiple lessions in it ---> Ans- metastasis (dont pick abcess or whatever). Dont pick prim.cancer which is usually in one area or the other but not all over the place. Just find out where that choice deals with metastasis, never pick benign ever.

Brain: Most common cancer ---> metastasis from lung.

Most common killer in man and women ---> Lung cancer; therefore the most primary site for cancer in brain ---> lung cancer.

Lung: most common cancer of the lung ---> metastasis from breast; most common primary ---> breast.

Adrenals: the most common tumor : metastasis from Lungs; thats why they always do the CT of Hillar lymph nodes and the adrenal glands in the staging of all lung cancers as they go so commonly to adrenal glands.

Bone: Lytic or Blastic? ---> Blastic ---> most likely cause? Ans- Prostate cancer.

Stains:
Desmin: wonderful stain for muscles; thats why used in muscle tumor like embryonal rhabdomyosarcoma.
We have stains for Keratin. Most carcinomas have a keratin in them.

EM:
APUD tumor ---> we see neurosecretory granules
Histiocytic tumor like histiocytosis X ---> Birbek granules; cluster designation ---> CD1
Muscle ----> Actin and myosin filaments.
Vascular malignancy ---> weibel palade bodies (str. that have Vw.factors in them ); we canactually see these things so we know that they have endothelial origin.

Oncogenesis:
First step in malignancy is initiation that means mutations.
2nd step - Promotion: you make multiple copies of that mutation; G1 to S phase, you got a mutation there and cell enter cell cycle ---> bad news ---> cell making multiple copies --->promotion.

Neoplasia

Post 31: (Dated: Feb 18 - 2009)

3. Progression: Incharge of whole thing ---> progressed ---> 3rd step ---> different kinds of cancer cells have different functions (community of malignant cells that has one purpose --->kill you).

Culturing cancer cells to check sensitivity to diff, chemo agents: Like Melanomas ---> tumors placed in the culture medium and disk with different chemotherapy agents ---> you can see who kills them ---> they can give you exact chemotherapy agent that can kill them; Cannot do this for every cancer.

Stage1: Initiation ---> mutation
Stage2: Promotion ---> Dividing (multiple copies)
Stage3: Progression ---> sub specialization

sets of genes.

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