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
How is cancer diagnosed?
With examination of a biopsy (cells/tissue obtained from polyp/mass/tumor).
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)
Definition: disorderly arrangement and layering of cells with nuclear atypia (pre-cancerous, might become cancer).
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.
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.
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?
Layer by layer
When no more cancer is seen in a layer
How do pathologists look for cancer metastasis?
By examining the first (sentinel) one or two nodes in a lymphatic chain.
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**
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.
What are important aspects to the labeling of a specimen to be sent to pathology?
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.
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**
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**
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**
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.
What are examples of tissue not suitable for frozen section evaluation?
Bone and fat.
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.
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).
How long does evaluation of a permanent section by a pathologist typically take?
Takes within days to get results.
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.
Definition: width of apparently normal tissue around lesion.
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).
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).
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.
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)
What are the cellular features that differentiate benign from malignant while examining a slide?
Differentiation: well differentiated, normal cell
Nuclear to cytoplasmic ratio: 1:4 to 1:6
Nucleoli: not prominent
Mitoses: scant "few mitotic figures"
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)
Nuclear to cytoplasmic ratio: 1:1
Mitoses: numerous "many mitotic figures"
Is hyperplasia in a breast duct considered a cancer precursor?
Dysplasia (hyperplasia with atypia) IS a cancer precursor.
Which type of breast cancer is confined to inside a duct (metastasis unexpected)?
Ductal Carcinoma in Situ
How does breast cancer become invasive?
Cancer escapes out of the duct and can metastasize (Infiltrating Ductal Carcinoma).
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
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
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.
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
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).
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)
**staging has more prognostic value than grading does**
Definition: metastasis discovered at the same time as primary cancer (or within a few months).
Definition: discovered at a later time as primary cancer.
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).
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)
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).
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.