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