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Is a neoplasm always cancer?
No, it could be a benign tumor
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What are the classifications of tumors?
- According to cell type and function
- Epithelial vs mesenchymal
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What is the difference in distinguishing benign and malignant growth according to the name? What are exceptions to these rules?
- Benign: tissue + -oma
- Malignant: Carcinoma (epithelial), sarcoma (mesenchymal)
- Exceptions: melanoma, lymphoma, leukemia
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Definition: normal benign tissue in abnormal location.
Hamartoma
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Definition: composed of several different BENIGN tissues (teeth, hair, bone, other).
Teratoma
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Definition: composed of several different tissues but NOT benign.
Teratosarcoma
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What are the CAUTION signs of cancer?
- Change in bowel/bladder habits
- A sore that doesn't heal
- Unusual bleeding or discharge
- Thickening or lump in breast/elsewhere
- Indigestion/difficulty swallowing
- Obvious change in wart or mole
- Nagging cough or hoarseness
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What are the epidemiology factors associated with cancer?
- Most cancer mortality: 55-75 yo
- Environmental causes: about 65%
- Inheritable factors: about 26-42% of cancer risks (heredity)
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What are the possible causes for cancer?
- Most cases: unknown
- Carcinogenic agents: chemicals, microbial, viral, radiation, genetic
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What are some chemical carcinogens of particular concern?
- Asbestos: mesothelioma (tumor of pleura, other lung cancers)
- Nitrosamines: colon cancer
- Naphthylamine in dyes: bladder
- Arsenic: skin
- Aflatoxin (Aspergillus fungus): liver
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What are some examples of microbial carcinogens?
- Helicobacter pylori: causes peptic ulcers (adenocarcinomas, B cell lymphomas)
- Various parasites: schistosoma haematobium (bladder cancer)
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What are examples of some viral carcinogens?
- RNA oncogenic: Human T cell leukemia Virus type 1
- DNA oncogenic: HPV (cervix, penis, anus carcinoma), EBV (Burkitt's lymphoma), hepatitis B (hepato-cellular carcinoma)
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How does radiation exposure cause cancer?
- It causes DNA damage which can lead to mutations.
- UV light (light skin more susceptible to develop squamous cell carcinoma, basal cell carcinoma, melanoma)
- Ionizing radiation (alpha, beta, gamma)
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How does ionizing radiation damage cells?
Electromagnetic energy knocks electrons out of molecules causing release of free radicals that interact with other molecules and damage DNA.
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What are the average radiation doses?
- 300 mrem/yr from natural sources
- 60 mrem/yr from man-made sources (mostly medical)
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What are the effects of ionization on different tissues? What are examples of tissues from most to least sensitive of radiation?
- Same tissues that are easily damaged by radiation are also more readily treated by radiation therapy.
- Most sensitive tissues: hematopoietic (blood forming) organs
- Medium sensitive tissues: reproductive organs, skin, bones/teeth, muscle
- Least sensitive tissues: nervous system
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What are some autosomal dominant inherited syndromes for developing masses?
- Retinoblastoma (eye)
- Neurofibromatosis (neurofibromas, cafe au lait spots, meningioma, pheochromocytoma)
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What are some autosomal recessive inherited syndromes for developing masses?
- Xeroderma pigmentosum
- Hereditary polyposis coli (multiple adenomatous colon polyps, can cause cancer at young age)
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What is a hereditary cancer that occurs in children?
Wilm's tumor (nephroblastoma)
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What do proto-oncogenes do? What is an oncogene? What protects against these?
- Proto-oncogenes: encode proteins for basic cell function
- Oncogene: mutated proto-oncogene
- Tumor suppressor genes protect against activated/newly acquired oncogenes.
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What protective genes are of particular importance in which testing for absence or mutation indicates possible development of cancer?
- BRCA 1 and 2 mutation: breast and ovarian cancer
- APC (adenomatous polyposis coli) mutation: hereditary colon cancer
- p53 loss or mutation: many different cancers
- **mutated genes are often inheritied**
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Definition: process by which normal cells are transformed into cancer cells.
Carcinogenesis
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What is the process of carcinogenesis/the hallmarks of cancer?
- Self sufficient growth signals
- Insensitivity to growth inhibiting signals (tumor suppressor genes)
- Evasion of apoptosis
- Limitless replication
- Development of sustained angiogenesis (forms blood vessels)
- Ability to invade and metastasize
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Where are tumor markers found?
- Blood
- Urine
- Stool
- Other body fluids/tissues
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Is testing for tumor markers recommended for routine screening?
NO
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What are some helpful uses for testing tumor markers?
- Helps predict a patient's response to certain cancer therapies.
- Checks a patient's response to treatment
- Determine whether cancer has returned
- May be used in high risk patients to help with diagnosis
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What are some of the tumor markers currently in use?
- Alpha-fetoprotein (AFP): liver and germ cell
- CA125: ovarian
- Carcinoembryonic antigen (CEA): colorectal/breast, others
- Prostate-specific antigen (PSA): prostate
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What are the tumor markers in serum and how are they used/tested for?
- Prostate specific antigen (PSA): screening tool for prostate cancer (needs informed consent); levels can also be elevated in prostatitis
- Carcinoembryonic antigen (CEA) surface marker: used to assess recurrence NOT for screening (colon, pancreatic, some breast, other cancers); anti-CEA Ab can be used for treatment
- CA125: ovarian cancer, NOT for screeing
- Alpha Fetoprotein (AFP): lever, testes
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How is cancer diagnosed?
With examination of a biopsy (cells/tissue obtained from polyp/mass/tumor).
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What are the different biopsy techniques used depending on tissue?
- Cytology: cells scraped from surface (Pap smear), cells from centrifuged fluid examed (sputum)
- Endoscopic (biopsy forceps through 'scope): bronchoscopy (lesions in trachea, bronchi/nearby), colonoscopy and esphago-gastro-duodenoscopy (EGD) to evaluate polyps and other masses
- Palpable masses and those seen on imaging procedures: fine needle aspiration (FNA) or core biopsy, incisional biopsy (removes piece not all of mass), excisional biopsy (remove all of mass)
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Definition: disorderly arrangement and layering of cells with nuclear atypia (pre-cancerous, might become cancer).
Dysplasia
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What must be done to a tissue specimen retrieved by open biopsy of a palpable mass before being sent to the pathologist? Why?
- Specimen is "oriented" by surgeon who indicates superior/inferior margins with sutures, etc.
- This is so the pathologist knows which way is superior, inferior, right, left.
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With an elliptical excision, why would a specimen be inked and studied microscopically?
To see if the lesion is close to the lateral and deep margins.
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What tissue removal technique is described as the tissue being removed in horizontal layers and mapped? How is the specimen examined for cancer? When does the procedure end?
- Moh's technique
- Layer by layer
- When no more cancer is seen in a layer
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How do pathologists look for cancer metastasis?
By examining the first (sentinel) one or two nodes in a lymphatic chain.
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If the first (sentinel) one or two lymph nodes are positive for Ca what should be done?
- Remove the rest of the nodes in the chain.
- **if negative for Ca no further lymph node removal is necessary**
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What is the object of sentinel lymph node biopsy? How is this achieved?
- Locate the first node and remove it for study.
- Tc-sulfur colloid is injected around the tumor and patient has a gamma scan pre-operatively to see general location of sentinel lymph node; then just prior to surgery blue dye is injected around the tumor site which travels to the sentinel node (like radioactive tracer). Gamma-probe is used to find radioactive sentinel node and incision is made.
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What are important aspects to the labeling of a specimen to be sent to pathology?
- Date/time
- Doctor's name
- What the tissue is/from what part of body
- Specimen is labeled and identical label is put in clinic or specimen log which are both taken to pathology. Lab personnel sign clinic log to acknowledge receipt of specimens.
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When are specimens sent for "intra-operative evaluation"?
- Only if the result will change the current operation being done.
- **sent as "fresh specimen"- tissue not initially put in formalin**
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How is an "intra-operative evaluation" conducted on a specimen using touch imprint cytology?
- Tissue is touched to slide and stained.
- Pathologist interprets it (what tissue? cancer or not?).
- Calls OR to tell surgeon.
- Rest of specimen is processed for "permanent section".
- **not suitable for all tissue**
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How is an "intra-operative evaluation" conducted on a specimen submitted to pathology as a frozen section?
- Tissue is frozen at about -20 degrees C.
- Some sections are cut and stained (about 30 mins).
- Pathologist interprets frozen section and calls surgeon in OR.
- Rest of specimen is processed for "permanent section".
- **not suitable for all tissue**
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How else besides the pathologist calling can a surgeon find out a result for an "intra-operative evaluation" of a specimen?
- Pathologist can give result over intercom.
- Might be frozen section room in OR suite.
- Pathologist can come to the OR door to talk to surgeon.
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What are examples of tissue not suitable for frozen section evaluation?
Bone and fat.
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How is a biopsy permanent section handled?
- Specimen sent to lab in formalin.
- Pathologist "grosses in" specimen (describes and records label and gross appearance, dissects out needed tissue).
- Outside surface "inked" to see how close to the edges the specimen (margins) the tumor is.
- Specimen is imbedded in paraffin, thinly sliced, mounted on slides and stained.
- Some tissue is tested for tumor markers.
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What are most specimens taken from surgery for? What is the typical stain once the specimen has been preserved (fixed in formalin), embedded in formalin and mounted to slides?
- Most specimens are for permanent section.
- Hematoxylin and eosin (H&E).
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How long does evaluation of a permanent section by a pathologist typically take?
Takes within days to get results.
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Why is it important to put the surgeon's name (not student's) on the specimen label for tissue taken during surgery?
If result is "bad" surgeon will be contacted directly by pathologist so they can follow up with the patient.
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Definition: width of apparently normal tissue around lesion.
Margin
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What would the margin of an excised lesion be if it is suspected to be benign? If suspected to be cancer?
- Few mm of margin is taken.
- Larger margin is taken (depending on type of cancer).
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If a lesion was thought to be benign and was excised with a narrow margin but turns out to be cancer what should be done?
Re-excise the incision with a wider margin (often no cancer is found when re-excised).
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What is the sequence of events for processing a specimen after biopsy?
- Put specimen in labeled container with formalin.
- Record label in surgery specimen log.
- Fill out Tissue Exam form (electronic now).
- Send specimen and Tissue Exam form to pathology.
- Lab personnel sign surgery log after receiving specimen.
- Pathologist "grosses in" the specimen (description, enters info on Tissue Exam form).
- Tissue is "fixed" in formalin, sliced, mounted on slides, stained.
- Pathologist "reads" slides, dictates results on Tissue Exam form.
- Patient returns for follow up.
- Surgeon retrieves Tissue Exam and explains findings to patient.
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How are benign and malignant growths differentiated?
- Benign: rate of growth slower, expansive (pushes), localized in a fibrous capsule
- Malignant: rapid growth, invasive into other organs, progressive infiltration, invasive and destructive, penetration (infiltrates surrounding tissue)
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What are the cellular features that differentiate benign from malignant while examining a slide?
- Cell: mature
- Differentiation: well differentiated, normal cell
- Size/Shape: similar
- Nuclei: normal
- Nuclear to cytoplasmic ratio: 1:4 to 1:6
- Nucleoli: not prominent
- Mitoses: scant "few mitotic figures"
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What are the cellular features that differentiate malignant from benign while examining a slide?
- Cell: variable maturity
- Differentiation: variable (undiff to well diff)
- Size/Shape: Pleomorphism (variable size/shape)
- Nuclei: hyperchromic
- Nuclear to cytoplasmic ratio: 1:1
- Nucleoli: prominent
- Mitoses: numerous "many mitotic figures"
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Is hyperplasia in a breast duct considered a cancer precursor?
- No
- Dysplasia (hyperplasia with atypia) IS a cancer precursor.
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Which type of breast cancer is confined to inside a duct (metastasis unexpected)?
Ductal Carcinoma in Situ
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How does breast cancer become invasive?
Cancer escapes out of the duct and can metastasize (Infiltrating Ductal Carcinoma).
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What are metastases features of benign and malignant tumors?
- Benign: no metastases
- Malignant: metastasis to various degrees and sites depending on cancer...if present this clearly identifies lesion as malignant
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What is defined as a carcinoma that has NOT penetrated the basement membrane, allowing more successful removal with a local excision, and is not expected to metastasize or invade local tissues?
Carcinoma-in-situ (CIS)- NOT metastasized
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Why is it important to do screening colonoscopies?
Finding and removing adenomatous polyps at an early stage before it has dysplasia prevent it from becoming colon cancer.
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How are cancers graded and classified?
- Grade is based on histologic exam of the tumor (possibly other factors too).
- Classified as I, II, III, IV
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What do the classifications of cancers reflect?
- Degree of differentiation and mitosis (more differentiation=less aggressive tumor; more mitoses=more aggressive tumor).
- I, II, III, IV goes in order of increasing anaplasia (abnormal growth).
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How does TNM staging work? What is the value of staging a carcinoma as compared to grading?
- T: size of primary TUMOR & local invasion (T1, T2, T3, T4)
- N: number and distribution of lymph NODES containing cancer cells (N0, N1-does not necessarily mean 1 node, etc)
- M: presence & extent of distant METASTASIS (plural metastases) (M0-none, M1-metastasis)
- **staging has more prognostic value than grading does**
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Definition: metastasis discovered at the same time as primary cancer (or within a few months).
Synchronous
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Definition: discovered at a later time as primary cancer.
Metachronous
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What must malignant cells due in order to survive at a new site?
- Must elicit angiogenesis (blood vessel formation).
- Avoid body's immune cells (NK, T cells, macrophages).
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What are the ways in which cancer cells can metastasize?
- 1: seeding of cancers (ie., intra-abd cancers produce peritoneal implants)
- 2: lymphatic spread (more typical of carcinomas-epithelial cells)
- 3: Hematogenous spread (typical of sarcomas-mesenchymal cells; typically spread to liver, lungs, bone, brain)
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What are some signs/symptoms of cancer that has metastasized to the adrenal glands? What causes this?
- Fatigue, salt-craving (low serum Na), weight loss, high K, etc.
- Adrenal glands are destroyed by tumor and can't produce normal amounts of hormones (adrenal insufficiency).
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What are examples of paraneoplastic syndromes caused by cancer?
- Non-small cell lung cancer (NSCLC): hypercalcemia (high calcium) caused by tumor producing parathyroid hormone (PTH)-like substance or bone metastases that cause hypercalcemia.
- Small cell lung cancer: tumor produces ADH-like substance causing syndrome of inappropriate anti-diuretic hormone (SIADH) which leads to low serum Na/ ectopic production of ACTH which stimulates the adrenal cortex causing high serum cortisol leading to Cushing's syndrome and glucose intolerance.
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