week 10- pathology Flashcards
• What are 2 types of pathology, and examples?
o Anatomical: Cyto-, Surgical
o Clinical: Hematology, Coagulation, Flow cytometry, Microbiology, Virology, HLA (tissue typing)
What is surgical pathology? Methods?
o Gross and micro exam of surgical specimens, bx, resections; helps w/ dx
o Bx: used to dx CA (benign vs malignant), inflammation, infx
o Core: large-bore needles
o Incisional: removal of part of the lesion
o Excisional: removal of the entire lesion
• What is cytopathology? Advantages and dis compared to bx?
o Dx by look at single cells; important in CA dx
o Ad: easier to get, less discomfort, less serious complications, costs less
o Dis: bx can be more accurate (although cytology fluid may be just as)
• What are 2 types of cytology:
o Body fluids: urine, sputum, CSF, pleural, pericardial, ascetic (peritoneal)
o Scrape or brush: from the organ or tissue; ex: Pap smear; others: esophagus, stomach, bronchi, mouth
• What are 2 ways cytology tests can be used?
o Diagnostic: for ppl who have ssx, or suspect a certain dz (like CA); finds if dz is present, and precisely and accurately classifies
o Screening: to find ppl with dz before they show ssx; should find everyone with dz, but doesn’t prove its there; if (+) -> use a dx test
• How was clinical cytology begun?
o 1928, Pananicolaou, vaginal smears of guinea pigs
o Noticed CA cells coming from the cervix
o 1939, began Pap smear screening
• What is the impact of the pap smear?
o Decreased incidence of cervical CA and death by 80%
o Cervical CA is still 3rd most common gynecological malignancy, most common death worldwide (gyn malig)
• What is the pap smear/thin prep?
o Collect cervical and endometrial cells shed in cervical mucus
o Optimal time: week after menses stops (proliferative phase=day 14)
o Look for abnormal cell changes, at risk for cervical cancer
o Stain: hematoxylin (nucleus) and OG/EA (orange G and Eosin and Fast green stain cyto)
o Moderately sensitive, but highly specific=low false positives
• How was pap smear done in 1943?
o Scraper, broom and glass slide
o Dependent on dr skill
o Some of collected cells remain on scraper
o Cells mb thick and clumped on slide, examined by computer and cytologist
o Blood and mucus interfere
o Maximum chance to see pathogens
• How was pap smear done in 2005?
o Liquid based collection= thin prep=diluted, easier to see single cells
o Sampling device placed directly in liquid preservative
o All cells get to lab, on slide
o Computer looks for abnormal cells, cytologist examines those
o Blood and mucus are removed
o Reduction of preserved pathogens
• What is the transformation zone?
o Most common place for abnormal cells
o Pre-puberty: all columnar
o Post-puberty: some gets turned outward, becomes squamous
• What is HPV?
o Small dsDNA virus infects endocervical glandular or stratified squamous epithelium
o Attacks and stimulates proliferation: vagina, cervix, anal-rectal, pharynx
o Most are asx
o Abs in 12-15 months after infx
o >100 types
o Low risk: 6, 11, 42, 43, 44
o 6 , 11: benign lesions, condylomata acuminatum, mild dysplasia
o 16, 18: CIN and CIS (high risk)
o 16= causes 50% of cervical CA
• What is CIN, CIS?
o Cervical intraepithelial neoplasia
o Carcinoma in situ
• What is the Bethesda system for pap results? Specimen adequacy?
o Standardized; descriptive dx and evaluation of specimen adequacy
o Sa: quality insurance, min req for satisfactory (5000 cells from thin-prep); >10 columnar endocervical cells
• What is Bethesda classification, based on tx?
o WNL
o benign cellular changes: included Candida and herpes, for dx; also reactive/reparative changes: radiation, IUD, inflammation
o epithelial cell abnormality
• what are the Bethesda epithelial cell abnormalities?
o ASC-US: Atypical squamous cells of undetermined significance; abn, but not lesions
o ASC-H: Atypical Squamous cells, cannot exclude HSIL; bx may have CIS/CIN 2 & CIN 3, so refer directly to colposcopy with bx
o LSIL: Low Grade Squamous Intraepithelial Lesion; transiently infected with HPV; Must do colposcopy and bx; 42% assoc. with CIN 1,15-30% with CIN 2/3.
o HSIL: High Grade Squamous Intraepithelial Lesions; persistent HPV infection and risk for cervical CA. Refer directly to colposcopy with biopsy; 31% assoc. with CIN 2/3, 1-2% with CA
• What is Bethesda classification of glandular cells?
o Includes benign endometrial cells, atypical glandular cells of undetermined significance (AGUS) either endocervical or endometrial, and adenocarcinoma
o AGC: endocervical, endometrial, or glandular. HSIL in 10-39%
o AGC, favor neoplastic: more likely HSIL, but not AIS; refer colposcopy; 27-96% CIN 2/3
o AIS: adenocarcinoma in situ; mx may show invasive carcinoma
o Other non-neoplastic findings:
o Reactive cellular changes associated with inflammation
o Atrophy -> from maturation index
o Glandular cell status post hysterectomy
• What are the WHO terms for pap results?
o Mild Dysplasia/CIN I: in lowest 1/3 of the cervical epithelium.
o Mod Dys/CIN 2: lower 2/3
o Severe Dys/CIN 3: extends into the upper 1/3 of the epithelium, but not involving the full thickness. Both HSIL and CIS (carcinoma in situ).
o CIS/CIN 3: squamous intraepithelial lesion, involve epithelial full thickness.
o AIS: Early glandular CA of cervix
o CIN 3 and AIS are defined as Stage 0 cancer according to FIGO Federation International of Gynecology and Obstetrics classification.
• Compare the WHO and Bethesda pap results:
o CIN1/mild dys= LSIL (lower 1/3)
o CIN2/mod dys= HSIL (middle 1/3)
o CIN3/sev dys= HSIL (>2/3 epithelium)
o CIN3/CIS = HSIL (full thickness)
• What are the pap screening guidelines as of 2012?
o Start at 21, not dependent on sexual activity
o 21-29: pap every 3 yrs; no HPV screening
o 30-65: papa dn HPV every 5 years
o 65+: none, unless hx of abn paps
o Hysterectomy (including cervix): none, unless tx for CA
o High risk: HIV, DES -> screened annually
• What is the disclaimer about pap specificity?
o Not reliable for detection of endometrial lesions
o Alone, have 15-25% false neg rate
• What are peak ages for cervical carcinogenesis?
o HPV infx: 21
o HSIL: 31
o CA: steady after 35
• What are risk factors for cervical CA?
o #1: HPV o Early onset sex activity o Low socioeconomic (dec screenings) o >3 children o Smoking: 2x risk o Long term BCP (5-9 yr) = 3x risk, reduced to normal 10 yrs after stop o HIV+ o If mom took DES during pregnancy (clear cell adenocarcinoma)
• What is HPV DNA testing?
o Approved by the FDA in 2009
o Indicates presence of high risk type of HPV, but doesn’t specify.
o If Pap is normal but HPV positive, retest in 1 year. If Pap is abnormal but HPV is negative, retest in 3 years.
o Test on sample of cervical or vaginal cells, same as Pap
o 2 FDA approved high risk HPV type tests: hybrid capture 2, invader third wave HPV test
o For 16/18: Cervista
o Most HPV infx detected when clinical appearance (warts, pre/cancers)
• What is interpretation and follow-up for pap results, based on 3 Bethesda tx category?
o WNL: no intraepithelial lesion or malignancy; no sign of infx, irritation, inflammation, cell repair, atypical cells, pre-CA changes, CA; no tx req’d; repeat pap in one year o Benign cell changes: tx infx or inflammation if sx (actinomyces, vaginitis, candida, gardnerella, herpes, Trichomonas); no extra pap; pap can’t detect gonorrhea or syphilis o ASCUS (atypical squamous cells of undetermined significance):not diagnostic, mb HPV, dysplasia, or inflammation; repeat pap, colposcopy, or bx; HPV DNA probe
• What are other interpretation and follow-up of Bethesda classification?
o LSIL w/ HPV: repeat pap, colp, or bx; HPV differential test for hi or lo risk virus
o HSIL (mod dys): colp and bx
o HSIL (sev dys): colp and bx
o Invasive carcinoma: refer to specialist
o Inadequate/unsatisfactory: repeat pap
• What are indications for a cervical bx?
o Abn Pap -> colposcopy, identify lesions with vinegar (3%) or iodine Lugol’s solution -> see abn vascularization
o Hx of HPV
o Unexplained post-coital bleeding
• When should you refer for cervical conization or LEEP (loop electroexcision procedure)
o CIN on bx with 3-4 quadrants affected
o No improvement with initial treatment
o Non-compliant pt, or poor follow-up tendencies
o Unable to visualize the entire SCJ for lesions present
• What are 2 types of cervical bxs?
o Punch bx-with forceps
o Cone bx- with scalpel
• What are risks of LEEP?
o More likely to have preterm birth, LBW<, PPROM (preterm premature rupture of membranes)
o Perinatal death, incompetent cervix
o Risks inc with depth and # LEEPs
o Similar risks with conization or laser tx
o Absolute risk inc is small
• What are additional uses of the pap smear?
o the “Maturation” Index. Request MI evaluation.
o evaluate hormones; E and P balance
o Sample lateral vaginal wall
o Hormonal imbalance: pituitary & ovarian dysfunction, menopause, feminizing or virilizing tumors
o Menopausal women w/ mostly basal cells = “atrophic vaginitis”
• What are interfering factors with pap tests?
o Intercourse or douching 24-48 hrs before
o lube on glove or speculum prior to collection
o Delay in applying fixative to slide
o Menstruation
o Infections
o Failure to sample transition zone
o Drugs
• What are indications for endometrial bx (EMB)?
o Dysfunctional Uterine Bleeding (DUB)
o Dx of EM CA
o E and P imbalance
o Ovarian dysfunction: perimenopause, amenorrhea, infertility
• What is the EMB procedure?
o Pelvic exam determines uterine position and locates cervix
o Insert speculum, then pipelle, tube, to aspirate cells
o sent to lab in formalin
• what are normal findings of an EMB?
o No atypical cells
o “Proliferative” tissue before ovulation & “secretory” tissue before menses is normal
• What are complications and contraindications of EMB?
o Comp: Perforation of uterus; Excessive uterine bleeding; Interference with pregnancy; Infection
o Cont: Vaginal or cervix infection; Pregnancy; Inability to visualize cervix
• What is the Gardasil FDA approved HPV vaccine?
o Target 16/18 and 6/11: 70% cerv CA, 90% gen warts
o Study: prevented 100% HSIL assoc with 16/18
o Dose: 3 inj over 6 mos
o Cervarix: now FDA approved; 16/18 only
• What are the recommendations for Gardasil?
o Given to all 11-12 yo girls; recommended 11-12 yp boys
o mb girls 12-26 w/o prev vaccine
o not for women >30
o Not for pregnant women.
o Not cost effective for boys in developing countries
o Still need to do paps
o As of August 2014, each dose of Gardasil is $141
o The Vaccines for Children (VFC) program offers low to no cost options for those who qualify
• Are Gardasil and Cervarix safe? What is VAERS?
o Safe by FDA and CDC
o 3/10000 adverse events
o VAERS=vaccine adverse event reporting systems: by CDC and FDA, reports from public
• How long do Gardasil and Cervarix last?
o At least 5 yrs
o G: 8.5 yrs for 16
o C: hi abs for 7.3 yrs
• What is sputum cytology?
o Indicated when CA is suspected, not a screening tool
o Sens 36%, spec 99.6%
o Only 1/4 lung CAs are detected by cytology alone
• What is sputum cytology procedure? Who needs it?
o Ideally 3 (one a day) First morning sample is best.
o Refrigerated – NO Preservative
o Most useful for abn CXR, productive cough, negative bronchoscopy
o Bronchoscopy & lung bx used more often now.
• What is clinical significance of sputum cytology?
o Trachea, bronchus and lung malignancies
o Benign cellular changes dt infx, toxin exposure, viral pneumonitis.
o Asthmatic often show eosinophils
• What are interfering factors with sputum cytology?
o Failure to adequately rinse mouth prior to collection
o Insufficient sample *QNS
o Saliva instead of sputum
• What are indications for urine cytology?
o Unexplained hematuria
o Irritation voiding symptoms
o Suspected CA or pts monitored for recurrent bladder CA
o Viral diseases: CMV
• How is specimen collected for urine cytology?
o by cytoscopy
o Can use voided CCMS (clean-catch mid stream) or random urine
o Sample refrigerated: NO Preservative
• What is random voided urine useful for? Other options? Benign conds?
o Most useful to detect neoplastic cells; at least 3 spec collected over 2 wks (50% sens for bladder CA)
o Other: washings (lavage with 50 mL saline); brushings
o Benign: infx (bacteria UTI, candida, CMV, herpes, HPV); granulomatous inflammation (TB); parasitic infx (schistosome eggs)
• What are the bladder CA statistics in US?
o The 5th most common cancer in men
o over 50,000 people per yr, avg age 68
o M:F = 3:1
o 10,000 deaths a yr
o 5 yr survival rates: 98% stage 0, 15% stage IV
o >90% are transitional cell carcinomas, 6- 8% SCC, 2% adeno
o ~75% are superficial
• What is normal nipple discharge?
o Only during lactation
o Some during pregnancy, perimenopause, BCP
• What are indications for nipple d/c cytology?
o Occurs at other than normal times, especially unilateral
o BR CA often starts in the cells lining the milk ducts
o Assoc w/ 3% BR CA and 10% benign breast lesions
o Generally limited to pts w/o palpable breast masses or other evidence of possible BR CA
o Most often performed by a surgeon as part of a ductoscopy
• What is the nipple d/c procedure? Interfering factors?
o Identify side, nipple washed and pat dry
o Obtain discharge with stripping motion and spread onto glass slide
o Fixative applied to slide
o Interfere: drugs that alter hormone balance
• What is clinical sig of nipple d/c cytology?
o identify benign conditions: mastitis (subareolar abcess) or intraductal papilloma
o identify malignant conditions: intraductal CA or intracystic infiltrating CA
• what are indications for a skin bx?
o Any growth that cannot be identified as benign on gross examination
o Moles w/ ABCD: Asymmetry, Irregular Borders, Irregular Color, Large Diameter > 6mm
o Any mole that changes, bleeds or itches
• What is skin bx procedure?
o Include margin and adjacent healthy tissue
o Punch bx or ellipse incision, or aspiration?
o in formalin and identify site of excision.
• What are contraindications for a skin bx?
o NOT if you even suspect MALIGNANCY
o Best to refer because precise assessment and excision of depth of possible invasion is critical for cancer staging.
o Unless you are a skilled minor surgeon, best to refer if a wide excisional biopsy is dictated by the size of the lesion you want evaluated.
• What is fine needle aspiration?
o A bx
o from a cyst or solid mass
o in office if nodule is palpable.
o for detection or r/o thyroid and breast CA
o Usu 25 ga needle; vacuum (usu multiple)
o In formalin, to pathologist for interpretation
o Rate of accuracy depends on skill of physician obtaining sample
• What are solitary thyroid nodules?
o Fluid-filled cysts, adenomas, or malignancies
o Some do radioactive iodine uptake test to see if nodule is hot or cold
o 10% cold nodules are malignant, doesn’t take up radioactive iodine
o Hot nodules never CA, overactive, take up more I than normal tissue
• What is occurrence of renal stones?
o Urinary caliculi can be found anywhere in the urinary tract
o Common cause of pain and bleeding, obstruction and secondary infection
o Occurrence is about 1 in 20 people
o About 1:1000 adults are hospitalized due to urinary stones
• What symptoms are suspicious of renal stones?
o Sudden onset, intractible/intermittent “colicky” pain in abdomen, back, groin, side
o Gross hematuria
o Fever and chills
o Vomiting
o Dysuria
o Possible foul smelling urine – associated with struvite “infection stones”
• How are kidney stones formed?
o Dec urine vol or inc excretion of stone forming components: calcium, oxalate, urate, cysteine, xanthine, and phosphate.
o form in renal pelvis and cause back pain which can migrate as they pass down the ureter.
• What are predisposing factors for kidney stones? Lab identification?
o Reduced fluid intake, dehydration, hx of gout, diuretic medications that cause hyperuricemia.
o Lab: Macroscopic, acid/alkaline solubility, infra-red spectrophotometry, crystallography.
• What are % of kidney stone types?
o Calcium: 80
o Struvite: 12
o Uric acid: 7
o Cysteine: 1
• What are gall stones?
o Clinical d/os of the extrahepatic biliary tract are related to gallstones
o Higher frequency in women: “Female, Fair, Fat, Forty, Fertile”
o 20% individuals > 65 have them, may be asx
o Obesity and SAD American diet contribute
• How are gallstones diagnosed?
o Real-time U/S (ultrasound) is most accurate
o Static U/S, oral cholecystography, ERCP
• What is composition of gall stones?
o Cholesterol is major component of most stones
o Bile that is supersaturated is predisposed to form stones
o Cholesterol monohydrate crystal formation is the major instigator of formation
