Metastasis, Common Cancer

Question 1

Know ;the ;definition ;of ;metastasis.

Answer 1

Metastasis - the transfer of malignant cells from the primary site to a non-connected (secondary) site.

Question 2

Discuss ;the ;mechanisms ;of ;metastasis: ; ;lymphatogenous, ;hematogenous, ;cavitary

Answer 2

Cavitary: direct seeding of body cavities or surfaces (ovarian cancer)Can travel through blood or lymph to reach new destinations.

Question 3

What are some ;theories ;regarding ;why ;and ;how ;metastasis ;occurs? ;What ;“motivates” ;cancer ; cells ;in ;a ;primary ;tumor ;to ;metastasize?

Answer 3

There exists a strong positive relationship between primary tumor size and risk of developing metastasisThus - In the primary tumor it becomes advantageous to move beyond basement membrane when conditions get crowded & harsh (hypoxia caused by limited blood supply and lack of nutrients). Thus, there is selective pressure to gain the ability to move out” or metastasize.Carcinoma cells must:breech the underlying basement membranetraverse the interstitial connective tissue,gain access to the circulation by penetrating the vascular basement membrane, a process called (intravasation). ;

Question 4

Discuss ;4 ;major ;theories ;to ;explain ;the ;bias ;of ;metastasis ;of ;certain ;types ;of ;cancer ;towards ; certain ;organs.

Answer 4

Some tissues are inhospitable to metastases (skeletal muscle).Some tissues have cytokines that attract metastases.Some metastases spread to the tissue at the end of the first capillary bed available to them. ;Only certain clonal populations can express the appropriate genes that lead to a successful metastasis phenotype

Question 5

Know ;the ;steps ;in ;the ;metastatic ;cascade (4).

Answer 5

;Invasion, ;intravasation ;, ;extravasation, ;colonization.

Question 6

Discuss ;the ;role ;of ;metastasis ;in ;death ;by ;cancer: ; ; ;What ;are ;the ;ultimate ;effects ;of ;metastasis?What ;are ;some ;of ;the ;ultimate ;causes ;of ;mortality ;due ;to ;cancer?

Answer 6

Direct: Invasive ;masses ;which ;interfere ;with ;normal ;functionIndirect: “Paraneoplastic ;Syndrome” ;(paracrine/endocrine ;effects): ; ;occur ;in ;7% ;to ;15% ;of ; patients ;with ;cancer.Bad effects: infection, organ failure, hemorrhage, thromboembolism, emaciation. ;Also can get ulcers, pain, seizures, cerebral dysfunction, obstructions, perforations, bone destruction, inflammation, localized loss of sensory and motor function, and edema. ;Yowch.

Question 7

Discuss ;paraneoplastic ;syndrome ;and ;the ;signs/symptoms/changes ;that ;occur ;in ;this ;syndrome.

Answer 7

A paraneoplastic syndrome is a disease or symptom that is the consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells. These phenomena are mediated by humoral factors (by hormones or cytokines) excreted by tumor cells or by an immune response against the tumor.Effects can include: Ectopic ;Hormone ;Production, ; ; Cutaneous ;Lesions, ;Arthropathies, ; ; ; ; Myopathies , ; ; ;Neuropathies, ; ; Multiple ;Thromboses, ; ; Nephrosis, ; ; ; ; Cachexia, ; ; ; ; D.I.C

Question 8

Tell me about the four steps of invasion.

Answer 8

Invasion of the ECM is an active process that can be resolved into several steps1. Changes “loosening up” of tumor cell-cell interactions: loss of E-cadherin, for example2. Degradation of ECM3. Attachment to ECM components4. Migration of tumor cells

Question 9

Tell me about intravasation.

Answer 9

The tumor cells enter the vasculature. ;Once ;in ;the ;circulation, ;tumor ;cells ;are ;vulnerable ;to ;destruction ;by: ;mechanical ;shear ;stress, ; apoptosis ;stimulated ;by ;loss ;of ;adhesion ;(anoikis) ;innate ;and ;adaptive ;immune ;defenses. ; ;• Within ;the ;circulation, ;tumor ;cells ;tend ;to ;aggregate ;in ;clumps. ;Adhesions ;among ;tumor ;cells ;as ; well ;as ;heterotypic ;adhesion ;between ;tumor ;cells ;and ;blood ;cells, ;particularly ;platelets, ;which ; may ;enhance ;tumor ;cell ;survival ;and ;implantability. ;Tumor ;cells ;may ;also ;bind ;and ;activate ; coagulation ;factors, ;resulting ;in ;the ;formation ;of ;emboli.

Question 10

Tell me about extravasation.

Answer 10

Extravasation: Where do the tumor cells get out of blood or lymph vessels and why do you get organ trophism? ;Arrest ;and ;extravasation ;of ;tumor ;emboli ;at ;distant ;sites ;involves ;adhesion ;to ;the ;endothelium, ; followed ;by ;egress ;through ;the ;basement ;membrane ;(involving ;adhesion ;molecules ;(integrins, ; laminin ;receptors) ;& ;proteolytic ;enzymes). ;Of ;particular ;interest ;is ;the ;CD44 ;adhesion ;molecule, ; expressed ;on ;normal ;T ;lymphocytes ;and ;used ;by ;cancer ;cells ;to ;migrate ;to ;selective ;sites ;in ;the ; lymphoid ;tissue ;and ;overexpression ;of ;CD44 ;may ;favor ;metastatic ;spread. ;• Site ;at ;which ;circulating ;tumor ;cells ;leave ;the ;capillaries ;is ;sometimes ;due ;to ;the ;anatomic ; location ;of ;the ;primary ;tumor ;(many ;metastases ;occur ;in ;the ;1st ;capillary ;bed ;available ;to ;the ; tumor).

Question 11

Tell me about colonization.

Answer 11

Seed and soil theory. ;Molecular ;mechanisms ;of ;colonization ;are ;just ;beginning ;to ;be ;unraveled ;in ;mouse ;models, ;a ; pattern ;seems ;to ;be ;that ;tumor ;cells ;secrete ;cytokines, ;growth ;factors, ;and ;ECM ;molecules ;that ; act ;on ;stromal ;cells, ;which ;in ;turn ;make ;the ;metastatic ;site ;habitable ;for ;the ;cancer ;cell.

Question 12

Understand the pathologic features that distinguish a benign and malignant tumor.

Answer 12

The term cancer refers to a malignant neoplasm which possesses the ability to “invade” adjacent tissues and tissue structures, and “metastasize”, spread to distant sites, colonize, and grow into tumor masses.Benign tumors never invade or metastasize.

Question 13

Understand what histological feature defines “invasion”.

Answer 13

;Invasion means that somewhere along the edge of the growth of the carcinoma within the epithelium, small groups of tumor cells have broken through the basement membrane that separates the epithelium from the underlying sub mucosal, connective tissue stroma, and thereby “invades” or enters the connective tissue stroma. In general, invasion precedes metastasis, because metastasis requires access of the emigrating tumor cells to lymphatic and venous tributaries that course through the sub mucosa but are absent from the epithelium.

Question 14

Understand the distinction between stage and grade, and the principles of the TNM grading system.

Answer 14

Stage refers to the extent of tumor spread at the time of diagnosis. This is the strongest predictor of prognosis for nearly all types of carcinoma.T = size of tumor, N = lymph node involvement, M = presence of metastasisGrade refers to the state of differentiation of the tumor cells seen in histological sections. Low grade, means that the cells are well differentiated and exhibit features of normal cells.

Question 15

Know the risk factors for major types of lung cancer.

Answer 15

SmokingAge, starting at 40, peaking at 70Occupational historyExposure to air pollutantsFamily history

Question 16

Know the pathologic features of the four major types of lung carcinoma.

Answer 16

Squamous cell carcinoma (25-40% of cases): The cancers arise in areas of squamous metaplasia and dysplasia, in major branches of the bronchial tree, “centrally”. With chronic smoking, the epithelium can be replaced by squamous epithelium.Adenocarcinoma (25-40% of cases). Most common type in women and non- smokers, although many patients are smokers. the cancer cells grow out along the alveolar septae, and along airspace structures. There is very little stroma.The cancer cells attempt to form primitive gland-like structures, and stain positive for mucin.Large cell carcinoma (10-15% of cases). An undifferentiated, high grade lung cancer in which the anaplastic appearing cancer cells may not produce either keratin or mucin.Small cell (formerly called oat cell) carcinoma, 20-25% of cases. No glandular or squamous differentiation; a high grade cancer. Cells are small and dark staining, and form clusters, stain + for neuroendocrine markers. These are aggressive cancers that metastasize widely, especially to the brain. Terrible prognosis.

Question 17

Know the pathologic features of pancreatic carcinoma, risk factors, prognosis, and treatment options.

Answer 17

Pathologic features: ;starting in focal areas of non-invasive foci of epithelial cell proliferations within pancreatic ducts and ductules. The cancer cells attempt to form primitive gland-like structures, and produce mucin. Most pancreatic adenocarcinomas elicit synthesis of a very prominent connective tissue stroma, a phenomenon called “desmoplasia”, as the cancer grows.Clinical: back pain, unexplained, painless jaundice, migratory thrombophlebitis, cachexiaRisk factors: age, smoking, chronic pancreatitis from alcoholism, diabetes mellitus, family history.Prognosis: ;Pancreatic cancer has a terrible prognosis, even worse than lung cancer (less than 5% of patients alive in 5 years), because the cancer grows silently without causing any symptoms or signs.Sugery, Treatment modalities of non-resectable tumors include radiation alone, or radiation in combination with chemotherapy.

Question 18

Know the pathologic and clinical features of colorectal carcinoma, and the germline mutations and other disease states that increase the risk for colorectal carcinoma.

Answer 18

Starts in polyps, invades submucosa and muscularis propria, then spreads by blood and lymph. ;L colon: constipation, change in stool caliber, colon obstructionR side: abdominal pain, blood or mucous in stool, anemiaRare familial adenomatous polyposis (APC), HNPCC (error in DNA mismatch repair), inflammatory bowel disease

Question 19

Know the principles of Gleason grading of prostate cancer, clinical presentation, and the screening methods to detect prostate cancer.

Answer 19

Asymptomatic until late stage, then: urinary outflow obsturction, increase in urinary frequincy, nocturia, bone pain. ;Rarely, reduced ejectile volume, hematospermia, impotence, deep vein thrombosis.Grade 1 is very well differentiated (lowest grade), and the neoplastic glands appear uniform. Grade 5 indicates no gland formation (highest grade), and the tumor cells infiltrate as sheets and cords. In Gleason grading, the Gleason grade of the predominant pattern and the Gleason grade of the subordinate pattern are added together. Values of 8 to 10 indicate aggressive behavior.PSA screening, digital rectal exam, ultrasound, biopsies

Question 20

What structures do adenocarcinomas try to form?

Answer 20

Glands

Question 21

What is cancer of the epithelia called? Is it common?

Answer 21

CarcinomaYes

Question 22

What is an adenocarcinoma?

Answer 22

Cancer of epithelia originating in glands