week 10- pathology

Question 1

• What are 2 types of pathology, and examples?

Answer 1

o Anatomical: Cyto-, Surgical

o Clinical: Hematology, Coagulation, Flow cytometry, Microbiology, Virology, HLA (tissue typing)

Question 2

What is surgical pathology? Methods?

Answer 2

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

Question 3

• What is cytopathology? Advantages and dis compared to bx?

Answer 3

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)

Question 4

• What are 2 types of cytology:

Answer 4

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

Question 5

• What are 2 ways cytology tests can be used?

Answer 5

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

Question 6

• How was clinical cytology begun?

Answer 6

o 1928, Pananicolaou, vaginal smears of guinea pigs
o Noticed CA cells coming from the cervix
o 1939, began Pap smear screening

Question 7

• What is the impact of the pap smear?

Answer 7

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)

Question 8

• What is the pap smear/thin prep?

Answer 8

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

Question 9

• How was pap smear done in 1943?

Answer 9

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

Question 10

• How was pap smear done in 2005?

Answer 10

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

Question 11

• What is the transformation zone?

Answer 11

o Most common place for abnormal cells
o Pre-puberty: all columnar
o Post-puberty: some gets turned outward, becomes squamous

Question 12

• What is HPV?

Answer 12

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

Question 13

• What is CIN, CIS?

Answer 13

o Cervical intraepithelial neoplasia

o Carcinoma in situ

Question 14

• What is the Bethesda system for pap results? Specimen adequacy?

Answer 14

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

Question 15

• What is Bethesda classification, based on tx?

Answer 15

o WNL
o benign cellular changes: included Candida and herpes, for dx; also reactive/reparative changes: radiation, IUD, inflammation
o epithelial cell abnormality

Question 16

• what are the Bethesda epithelial cell abnormalities?

Answer 16

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

Question 17

• What is Bethesda classification of glandular cells?

Answer 17

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

Question 18

• What are the WHO terms for pap results?

Answer 18

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.

Question 19

• Compare the WHO and Bethesda pap results:

Answer 19

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)

Question 20

• What are the pap screening guidelines as of 2012?

Answer 20

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

Question 21

• What is the disclaimer about pap specificity?

Answer 21

o Not reliable for detection of endometrial lesions

o Alone, have 15-25% false neg rate

Question 22

• What are peak ages for cervical carcinogenesis?

Answer 22

o HPV infx: 21
o HSIL: 31
o CA: steady after 35

Question 23

• What are risk factors for cervical CA?

Answer 23

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)

Question 24

• What is HPV DNA testing?

Answer 24

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)

Question 25

• What is interpretation and follow-up for pap results, based on 3 Bethesda tx category?

Answer 25

``` 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 ```

Question 26

• What are other interpretation and follow-up of Bethesda classification?

Answer 26

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

Question 27

• What are indications for a cervical bx?

Answer 27

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

Question 28

• When should you refer for cervical conization or LEEP (loop electroexcision procedure)

Answer 28

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

Question 29

• What are 2 types of cervical bxs?

Answer 29

o Punch bx-with forceps | o Cone bx- with scalpel

Question 30

• What are risks of LEEP?

Answer 30

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

Question 31

• What are additional uses of the pap smear?

Answer 31

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”

Question 32

• What are interfering factors with pap tests?

Answer 32

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

Question 33

• What are indications for endometrial bx (EMB)?

Answer 33

o Dysfunctional Uterine Bleeding (DUB) o Dx of EM CA o E and P imbalance o Ovarian dysfunction: perimenopause, amenorrhea, infertility

Question 34

• What is the EMB procedure?

Answer 34

o Pelvic exam determines uterine position and locates cervix o Insert speculum, then pipelle, tube, to aspirate cells o sent to lab in formalin

Question 35

• what are normal findings of an EMB?

Answer 35

o No atypical cells | o “Proliferative” tissue before ovulation & “secretory” tissue before menses is normal

Question 36

• What are complications and contraindications of EMB?

Answer 36

o Comp: Perforation of uterus; Excessive uterine bleeding; Interference with pregnancy; Infection o Cont: Vaginal or cervix infection; Pregnancy; Inability to visualize cervix

Question 37

• What is the Gardasil FDA approved HPV vaccine?

Answer 37

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

Question 38

• What are the recommendations for Gardasil?

Answer 38

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

Question 39

• Are Gardasil and Cervarix safe? What is VAERS?

Answer 39

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

Question 40

• How long do Gardasil and Cervarix last?

Answer 40

o At least 5 yrs o G: 8.5 yrs for 16 o C: hi abs for 7.3 yrs

Question 41

• What is sputum cytology?

Answer 41

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

Question 42

• What is sputum cytology procedure? Who needs it?

Answer 42

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.

Question 43

• What is clinical significance of sputum cytology?

Answer 43

o Trachea, bronchus and lung malignancies o Benign cellular changes dt infx, toxin exposure, viral pneumonitis. o Asthmatic often show eosinophils

Question 44

• What are interfering factors with sputum cytology?

Answer 44

o Failure to adequately rinse mouth prior to collection o Insufficient sample *QNS o Saliva instead of sputum

Question 45

• What are indications for urine cytology?

Answer 45

o Unexplained hematuria o Irritation voiding symptoms o Suspected CA or pts monitored for recurrent bladder CA o Viral diseases: CMV

Question 46

• How is specimen collected for urine cytology?

Answer 46

o by cytoscopy o Can use voided CCMS (clean-catch mid stream) or random urine o Sample refrigerated: NO Preservative

Question 47

• What is random voided urine useful for? Other options? Benign conds?

Answer 47

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)

Question 48

• What are the bladder CA statistics in US?

Answer 48

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

Question 49

• What is normal nipple discharge?

Answer 49

o Only during lactation | o Some during pregnancy, perimenopause, BCP

Question 50

• What are indications for nipple d/c cytology?

Answer 50

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

Question 51

• What is the nipple d/c procedure? Interfering factors?

Answer 51

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

Question 52

• What is clinical sig of nipple d/c cytology?

Answer 52

o identify benign conditions: mastitis (subareolar abcess) or intraductal papilloma o identify malignant conditions: intraductal CA or intracystic infiltrating CA

Question 53

• what are indications for a skin bx?

Answer 53

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

Question 54

• What is skin bx procedure?

Answer 54

o Include margin and adjacent healthy tissue o Punch bx or ellipse incision, or aspiration? o in formalin and identify site of excision.

Question 55

• What are contraindications for a skin bx?

Answer 55

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.

Question 56

• What is fine needle aspiration?

Answer 56

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

Question 57

• What are solitary thyroid nodules?

Answer 57

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

Question 58

• What is occurrence of renal stones?

Answer 58

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

Question 59

• What symptoms are suspicious of renal stones?

Answer 59

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”

Question 60

• How are kidney stones formed?

Answer 60

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.

Question 61

• What are predisposing factors for kidney stones? Lab identification?

Answer 61

o Reduced fluid intake, dehydration, hx of gout, diuretic medications that cause hyperuricemia. o Lab: Macroscopic, acid/alkaline solubility, infra-red spectrophotometry, crystallography.

Question 62

• What are % of kidney stone types?

Answer 62

o Calcium: 80 o Struvite: 12 o Uric acid: 7 o Cysteine: 1

Question 63

• What are gall stones?

Answer 63

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

Question 64

• How are gallstones diagnosed?

Answer 64

o Real-time U/S (ultrasound) is most accurate | o Static U/S, oral cholecystography, ERCP

Question 65

• What is composition of gall stones?

Answer 65

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