Reproductive Pathology Flashcards

1
Q

ddx for testicular lesions

A

*tender: torsion, orchitis, epididymitis
*non-tender:
1. hydrocele (transillumination +)
2. varicocele (“bag of worms”)
3. malignancy (testicular cancer, lymphoma)

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2
Q

testicular neoplasms - epidemiology

A

*Caucasian males between 15-45 years
*risk factors:
-associated with cryptorchidism
-intersex syndromes (androgen insensitivity syndrome; gonadal dysgenesis)
-family history (fathers & sons; 8-10x increased risk)
-increased risk in contralateral testis

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3
Q

testicular neoplasms - pathogenesis

A

*poorly understood
*precursor lesion = germ cell neoplasia in situ

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4
Q

testicular neoplasms - clinical examples

A

*painless, solid testicular masses

  1. seminomas:
    -may reach considerable size before diagnosis
    -metastases occur first in abdominal lymph nodes
    -hematogenous metastases occur late
  2. non-seminomatous tumors (NSGCT):
    -may have widespread metastases (liver/lungs)
    -absent palpable testicular mass
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5
Q

testicular neoplasms - serum markers

A

*useful in diagnosis and following therapeutic response
1. alpha fetoprotein (AFP)
2. hCG

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6
Q

testicular neoplasms - treatment

A

*radical orchiectomy (diagnosis & treatment - presumption of malignancy)

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7
Q

seminoma - overview

A

*most common germ cell tumor in males
*present with bulky mass:
-soft, well-demarcated, gray-white tumor
-confined to tunica albuginea

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8
Q

seminoma - pathology

A

*large, uniform cells with distinct borders, abundant clear cytoplasm (fried egg appearance)
*lymphocytic infiltrate present
*few syncytiotrophoblasts release hCG (minimally elevated serum levels)

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9
Q

embryonal carcinoma (testicular neoplasm)

A

*type of non-seminomatous germ cell tumors
*peak incidence 3rd decade of life
*classic presentation: PAINFUl mass, elevated hCG
*more aggressive than seminoma: vascular-lymphatic invasion is common
*ill-defined, invasive mass; extends through albuginea, epididymis, spermatic cord
*undifferentiated cells forming sheets; frequent component of mixed tumors

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10
Q

yolk sac tumor (testicular neoplasm)

A

*type of non-seminomatous germ cell tumors
*prepubertal, usually < 3 years of age
*histology:
1. Schiller-Duval bodies = perivascular growth (resemble glomeruli)
2. hyaline globules with elevated alpha-fetoprotein (AFP)

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11
Q

choriocarcinoma (testicular neoplasm)

A

*type of non-seminomatous germ cell tumors
*highly malignant; widespread metastases (liver, lungs); often associated with hemorrhage
*hCG MARKEDLY ELEVATED
*differentiate into placental trophoblasts:

-cytotrophoblasts = small cuboidal cells
-syncytiotrophoblasts = multinucleated cells

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12
Q

teratoma (testicular neoplasm)

A

*type of non-seminomatous germ cell tumors
*present any time from infancy to adulthood
*germ cells differentiate along MULTIPLE cell lineages:
-heterogenous collection of differentiated organoid structures
-neural brain tissue, cartilage, skin, thyroid, bronchi, intestine

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13
Q

where is BPH most commonly found in the prostate gland?

A

central zone (PZ) of prostate

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14
Q

benign prostatic hyperplasia (BPH) - overview

A

*common cause of prostatic enlargement
*increased frequency progressively with age, reaching 90% by 8th decade of life

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15
Q

benign prostatic hyperplasia (BPH) - pathogenesis

A

*excessive androgen-dependent growth of stromal and glandular elements:
-dihydrotestosterone (DHT) synthesized by 5-alpha reductase mediates prostatic growth

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16
Q

benign prostatic hyperplasia (BPH) - clinical presentation

A

*lower urinary tract obstruction sx:
-difficulty in starting urine stream, intermittent interruption of stream while voiding
-urgency, frequency, nocturia
*increased risk of UTI due to incomplete voiding
*may completely obstruct urinary tract

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17
Q

benign prostatic hyperplasia (BPH) - pathology

A

*well-circumscribed nodules:
-inner periurethral/transition zone
-urethra compressed to slit
-bulge from cut surface

*variable proportion of glands and fibromuscular stroma:
-small to large to cystic glands
-infolding glands produce a papillary architecture

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18
Q

benign prostatic hyperplasia (BPH) - treatment

A
  1. 5-alpha reductase inhibitors (finasteride, dutasteride - inhibit DHT formation)
  2. alpha-1 adrenergic receptor antagonists (tamsulosin, terzosin - relax prostatic smooth muscle)
  3. surgical techniques for unresponsive cases
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19
Q

prostatic adenocarcinoma - overview

A

*most common cancer in men
*20% of all male cancers (2nd cause of cancer-related death in men)
*disease of aging; increased incidence after 50 years

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20
Q

prostatic adenocarcinoma - pathogenesis

A

*androgens: induce expression of pro-growth and pro-survival genes
*inherited genetic factors: increased risk if first-degree relative with prostate cancer
*acquired genetic aberrations

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21
Q

prostatic adenocarcinoma - clinical findings

A

*most are asymptomatic lesions
*subset detected on digital rectal exam or needle biopsy to investigate increased PSA

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22
Q

prostatic serum antigen (PSA)

A

*product of normal and neoplastic prostatic epithelium
*increases with age
*serum assay widely used in diagnosis/management of prostate cancer
*limitations: NOT cancer-specific

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23
Q

prostatic adenocarcinoma - treatment

A

*localized: radical prostatectomy and radiotherapy
*“watchful waiting” approach for older men
*metastatic carcinoma: treated by androgen deprivation

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24
Q

prostatic adenocarcinoma - pathology

A

*usually located in peripheral zone; does not produce urinary symptoms
*malignant glands may be admixed with benign:
-nucleoli
-perineural invasion
-absent basal cells
-racemase positive

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25
Q

prostatic adenocarcinoma - grading (Gleason Score)

A

*architecture of glands from multiple (at least 2) zones
*smaller glands = higher score from 1-5
*higher score = worse prognosis

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26
Q

how does HPV transform cells?

A

*high-risk HPV types express oncoproteins which immortalize epithelial cells:
1. E6: prevents apoptosis (degrades p53); activates telomerase
2. E7: allows progression in cell cycle; binds RB and displaces E2F; blocks p21 and p27
*co-transfection with a mutated RAS gene results in full malignant transformation

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27
Q

HPV oncogenesis

A

*implicated in the genesis of several cancers:
-benign squamous papillomas (warts)
-squamous cell carcinomas (cervical, anogenitial, oropharynx)

*low risk types = 6 and 11
*high risk types = 16, 18, 31, 33, 35

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28
Q

cervical dysplasia - pathogenesis

A

*HPV; tropic for immature squamous cells in transformation zone
*squamous intraepithelial lesions (SIL):
-precancerous epithelial changes
-PAP smear = screening (cells scraped from transformation zone)
-determines low-grade vs. high-grade SIL

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29
Q

cervical carcinoma - overview

A

*arises from cervical epithelium
*usually from ectocervical squamous epithelium = squamous cell carcinoma (SCC)
*some arise from endocervical glands = adenocarcinoma
*4th most common cancer in women
*9valent vaccine very effective in preventing HPV infection

30
Q

cervical carcinoma - clinical presentation

A

*most commonly middle-aged women (40-50 years)
1. vaginal bleeding, esp post-coital
2. cervical discharge
*risk factors:
-high risk HPV (16, 18)
-smoking
-immunodeficiency

31
Q

cervical carcinoma - pathology

A

*fungating (exophytic) or infiltrative masses
1. squamous cell carcinoma:
-nests/tongues of malignant squamous epithelium, either keratinizing or nonkeratinizing, invading cervical stroma
2. adenocarcinoma:
-proliferation of malignant endocervical glands

32
Q

endometriosis - overview

A

*benign endometrial glands and stroma outside the uterus
*occurs in up to 10% of women in reproductive years and nearly half of women with infertility

33
Q

endometriosis - pathology

A

*functional endometrial stroma and glands
*undergo cyclic bleeding and appear as red-brown nodules or implants
*may form large, blood filled chocolate cysts

34
Q

endometriosis - clinical findings

A

*frequently multifocal
*pelvic structures, eg. ovaries, uterine ligaments
*dysmenorrhea and pelvic pain
*scarring of fallopian tubes/ovaries → sterility

35
Q

uterine glandular proliferations: hyperplasia - overview

A

*benign hyperplasia of endometrial epithelial glands
*prolonged/marked excess estrogen relative to progestin
*clinically: post-menopausal bleeding

36
Q

uterine glandular proliferations: hyperplasia - etiology

A

*estrogen excess, due to:
1. obesity: adipose tissue converts steroids into estrogens
2. failure of ovulation (perimenopause)
3. estrogen therapy
4. estrogen-producing ovarian lesions

37
Q

uterine glandular proliferations: hyperplasia - pathology

A

*crowded glands with increased gland:stroma ratio:
1. simple hyperplasia:
-without cellular atypia
-rarely progress
2. complex hyperplasia with atypia:
-“back-to-back” glands; little to no stroma
-progresses to carcinoma in 20-50% of cases

38
Q

uterine glandular proliferations: CARCINOMA

A

*malignant neoplasm of endometrial epithelial glands
*most frequent cancer occurring in the female genital tract
*manifests between the ages of 55 and 65 years
*classically presents with post-menopausal bleeding

39
Q

endometrioid endometrial adenocarcinoma

A

*mutations in PTEN tumor suppressor gene
*background of endometrial hyperplasia

40
Q

serous endometrial adenocarcinoma

A

*mutations in TP53 tumor suppressor gene
*background of endometrial atrophy in older women (>70)

41
Q

leiomyoma - overview

A

*benign tumor of myometrial smooth muscle cells (“fibroid”)
*affect up to 50% of women of reproductive age
*estrogens stimulate growth; tumors shrink post-menopause

42
Q

leiomyoma - morphology

A

*sharply circumscribed, firm gray-white masses
*whorled cut surface
*often multiple
*bundles of smooth muscle cells mimic normal myometrium

43
Q

leiomyoma - clinical features

A

*often asymptomatic and discovered incidentally
*present with menorrhagia +/- metrorrhagia

44
Q

leiomyosarcoma - overview

A

*malignant tumor of myometrial smooth muscle cells
*arise de novo, NOT from leiomyoma (fibroids do not cause this)
*complex, highly variable karyotypes, frequent chromosomal deletions

45
Q

leiomyosarcoma - morphology

A

*usually solitary hemorrhagic masses
*marked necrosis
*cytologic atypia
*increased mitotic activity

46
Q

leiomyosarcoma - clinical features

A

*most often occur in post-menopausal women
*recurrence after surgical resection is common
*many tumors metastasize to lung, bone, brain
*prognosis: overall 5-year survival rate ~40%

47
Q

ovarian surface epithelial neoplasms - overview

A

*benign or malignant neoplasms derived from ovarian surface epithelium
*most common type of ovarian neoplasm
*TP53 mutations > 95% of cases
*familial germline mutations in BRCA1 or BRCA2

48
Q

ovarian surface epithelial neoplasms - classification based on epithelium

A
  1. serous = cuboidal epithelium with thin, watery fluid
  2. mucinous = columnar epithelium with mucus
  3. endometrioid = endometrial epithelium
49
Q

ovarian surface epithelial neoplasms - pathology

A

*cystic, large to huge
1. benign tumors:
-serous cystadenoma; mucinous cystadenoma
-smooth cysts lined by simple epithelium layer
2. borderline tumors:
-majority behave in a benign manner
-can recur; some progress to carcinoma
3. malignant tumors:
-serous cystadenocarcinoma; mucinous cystadenocarcinoma
-markedly atypical stratified epithelium layer
-exuberant papillary projections
-epithelial invasion
-spread by peritoneal implants and through lymphatics to regional lymph nodes

50
Q

ovarian germ cell neoplasm: teratoma - overview

A

*usually present in first 2 decades of life
*more than 90% are benign (typically malignant in very young pts)

51
Q

ovarian germ cell neoplasm: MATURE teratoma

A

*aka dermoid cyst
*benign
*ovarian mass or incidental imaging studies; infertility or ovarian torsion may be presenting sign
*mature tissues derived from ALL THREE germ layers:
-ectoderm, endoderm, and mesoderm
-cysts lined by epidermis with skin adnexa
-produce hair, teeth, bone, cartilage, and other tissues

52
Q

ovarian germ cell neoplasm: IMMATURE teratoma

A

*malignant
*arise early in life (<18 years)
*typically are bulky & solid, with areas of necrosis
*immature elements or minimally differentiated tissues

53
Q

risk factors for the development of breast carcinoma

A

*first-degree relatives with breast carcinoma
*early menarche
*late menopause
*nulliparity
*obesity
*proliferative fibrocystic disease
*inheritance of mutant copy tumor suppressor genes (TP53, BRCA1, BRCA2); individuals who inherit a mutation develop carcinomas at a younger age

54
Q

significance of estrogen receptor expression in the pathogenesis of breast cancer

A

*estrogen may bind to the receptors on the tumor cells and promote their growth
-estrogen is not mutagenic, so it is a tumor promoter, not a tumor initiator
*therapeutic strategies for estrogen receptor + breast cancer:
1. tamoxifen
2. aromatase inhibitors
3. oophorectomy

55
Q

significance of HER2 expression in the pathogenesis of breast cancer

A

*HER2 is a growth factor receptor:
-gene amplification → increased overexpression of HER2 receptor and constitutive tyrosine kinase activity → promotion of growth and survival of tumor cells
*respond to treatment with drugs that block HER2 activity

56
Q

benign breast epithelial lesions - overview

A

*derived from proliferation of epithelial cells
*majority incidental findings detected by mammography
*major clinical significance is subsequent risk of malignant transformation

57
Q

benign breast epithelial lesion: papilloma

A
  1. large duct papillomas:
    -lactiferous sinuses of the nipple
    -usually solitary
    -more than 80% with nipple discharge (may be bloody)
  2. small duct papillomas:
    -multiple and located deeper in ductal system
    -clinically small palpable masses, or densities on imaging
  3. multiple branching fibrovascular cores:
    -epithelial hyperplasia and apocrine metaplasia are frequently present
58
Q

benign breast epithelial lesion: fibrocystic changes

A

*most common change in pre-menopausal breast
*vague, irregular breast tissue; “lumpy breast”
*spectrum of morphology:
1. cysts: flattened atrophic epithelium or by metaplastic apocrine cells
2. fibrosis: cyst rupture → fibrosis; may calcify, leading to image detection
3. adenosis: increase in the number of acini per lobule

59
Q

benign breast epithelial lesion: usual duct hyperplasia (UDH)

A

*proliferative disease
*1.5-2x increased risk of malignancy
*usually incidental finding
*increased NORMAL epithelial and myoepithelial cells:
-fill and distend ducts and lobules
-cells maintain normal appearance
-irregular peripheral lumers

60
Q

benign breast epithelial lesion: atypical ductal hyperplasia (ADH)

A

*proliferative disease
*4-5x increased risk of malignancy
*both breasts are at increased risk
*increased ATYPICAL epithelial and myoepithelial cells:
-epithelial cell proliferation expands ductal/lobular spaces
-resembles in situ carcinoma

61
Q

breast carcinoma: in situ - overview

A

*malignant neoplastic breast epithelial proliferation limited by basement membrane
*may not produce palpable mass
*detected as calcifications on mammography

62
Q

breast carcinoma: ductal carcinoma in situ (DCIS)

A

*distorts lobules and ducts
*necrotic debris or secretory material produces Ca2+ (comedo necrosis)

63
Q

breast carcinoma: lobular carcinoma in situ

A

*expands involved lobules
*may be MULTIFOCAL
*rarely produces Ca2+; usually incidental

64
Q

breast carcinoma: invasive - overview

A

*malignant neoplastic breast epithelial proliferation that penetrates basement membrane

65
Q

breast carcinoma: invasive ductal carcinoma

A

*haphazard infiltrating tubules:
-no organized growth
-lack myoepithelial cell layer

*induces a desmoplastic response:
-results in a mammographic density
-eventually produces hard, palpable, irregular mass

66
Q

breast carcinoma: invasive lobular carcinoma

A

*makes up 10-15% of invasive carcinomas
*typically infiltrate as discohesive SINGLE CELLS (single file), NOT tubules/ducts; E-cadherin negative
*may FAIL to produce a desmoplastic response; difficult to detect by palpation and imaging

67
Q

breast carcinoma: invasive medullary carcinoma

A

*subtype of triple-negative cancer
*well-circumscribed mass
*pushing borders of large anaplastic cells
*lymphocytic T-cell infiltrates

68
Q

breast carcinoma: invasive inflammatory carcinoma

A

*“inflamed” reddening, thickening, and fine pitting edema of the skin (peau d’orange)
*lymphatic carcinomatosis

69
Q

breast stromal proliferations - overview

A

*neoplasms derived from proliferation of intralobular fibroblasts with entrapped non-neoplastic epithelial cells

70
Q

breast stromal proliferation: fibroadenoma

A

*most common benign tumor in breast
*typically presents in women < 30yrs
*frequently multiple and bilateral
*HORMONALLY RESPONSIVE (grow with menses and pregnancy)
*well-circumscribed, mobile, rubbery
*fibroblasts distort/elongated slit-like ducts

71
Q

breast stromal proliferation: Phyllodes tumor

A

*typically post-menopausal
*vary in size from small to huge
*fibroadenoma-like but more stromal overgrowth:
-characteristic “phyllodes” (leaflike) growth pattern