Pathology Study Guide

Pathology Study Guide:

Intraepithelial Neoplasm Staging:
I: Limited to upper epithelium
Limited to upper 2/3 of epithelium
Involving full thickness of the epithelium

Uterine Pathology:

Dysfunctional Uterine Bleeding: Abnormal bleeding (Amenorrhea, dysmenorrhea, menorrhagia, metrorrhagia, oligomenorrhea) due to functional causes.
PCOS
Hypothalamic/Pituitary/Gonadal Disorders
Ovarian Lesions
Hypothyroidism
Abnormal Uterine Bleeding: Abnormal bleeding due to organic causes

Disease / Clinical Presentation / Gross Pathology / Microscopic Path / Etiology / Other Info
Benign Neoplasms/Non-Neoplastic Entities
Leiomyoma- MOST COMMON TUMOR IN WOMEN / Abnormal bleeding, mass, asymptomatic, dystocia / Well circumscribed gray whorled nodule(s) / Mature smooth muscle with rare mitoses. Well circumscribed / Heightened sensitivity to estrogen / Not a pre-malignant lesion
Endometrial hyperplasia / Abnormal uterine bleeding / 4 types:
Simple wo/atypia
Simple w/atypia
Complex wo/atypia
Complex w/atypia
(Complex=gland packing with abnormal shape) / Prolonged estrogen exposure / Often found in conjunction with ovarian tumors, PCOS, HRT, etc. Lesions with atypiahave a 2-30% chance of becoming carcinoma.
Endometriosis / Cyclic dysmenorrhea, menorrhagia, infertility, dyspareunia / Chocolate cysts on the surface of ovaries, uterine tubes, peritoneal structures, / Presence of normal endometrial tissue outside of the uterus / Unknown: Some combination of genetic, hormonal, and immune factors. / Theories: Regurgitation, metaplasia, lymp/vascular spread, mechanical implantation.
Adenomyosis / Colicky dysmenorrhea, menorrhagia, dyspareunia, pelvic pain / Chocolate cysts embedded in the uterine myometrium / Presence of irregular nests of endometrial stroma (with or without glands) in the myometrium / Unknown
Ectopic Pregnancy / Acute abdomen, pelvic pain, shock-like state, missed periodhCG / Placental tissue, amniotic sac, and fetal tissue outside the uterus / Placental tissue, amniotic sac, and fetal tissue outside the uterus / Extrauterine implantation / Predisposing Factors: PID, chronic salpingitis, adhesions
Molar Pregnancy
Complete Mole / Uterine size larger than expected, vaginal bleeding, passage of “grape like” structures, hCG / Mass of thin-walled friable semi-translucent cystic “grape-like” structures involving entire chorion / Hydropic villous swelling with diffuse trophoblastic proliferation / Fertilization of an empty ovum by two sperm or a single sperm whose genetic material replicates (karyotype 46XX or 46XY fully paternal) / 10% become invasive, 2% become choriocarcinoma, Tx, curettage or hysterectomy
Partial Mole / Uterine size larger than expected, vaginal bleeding, passage of “grape like” structures, hCG / Mass of thin-walled friable semi-translucent cystic “grape-like” structures not involving entire chorion / Partial villous hydropic swelling with focal syncytiotrophoblastic proliferation, amniotic and fetal parts may be present / Fertilization of an ovum by a diploid sperm, or two sperm (Karyotype 69XXX, or 69 XXY) / Rarely become aggressive or recurrentTx, curettage or hysterectomy
Invasive Mole / Recurrent vaginal bleeding, irregular uterine enlargement, hCG / Hemorrhagic mass adherent to the uterine wall or invading the uterine wall. / Persistence of molar pregnancy after evacuation, benign in nature, locally invasive, Tx chemotherapy
Malignant Neoplasms
Choriocarcinoma / hCG, late postpartum bleeding, bloody and sometimes smelly vaginal discharge, moderate uterine enlargement / VERY hemorrhagic mass invading the uterine wall / Proliferation of cytotrophoblasts and syncytiotrophoblasts with absence of villous formation, marked cytologic atypia / Malignant transformation of chorionic structure / Exquisitely sensitive to chemotherapy, risk factors: >35 yo, increasing parity, OCP, very aggressive and widely metastasizing
Placental site trophoblastic tumor / Postpartum or post-abortion abnormality, hPL / Discrete mass within the myometrium / Proliferation of intermediate trophoblast at implantation site (polygonal cells) / 10% disseminate and result in death
Carcinoma (type I) 85% of endometrial carcinomas / Abnormal bleeding with or without enlarged uterus / Diffuse or polypoid masses within the uterine wall / Endometrioid patterns of cells invading the myometrium / Prolonged estrogen exposure, obesity, EIN, P10 mutations. / Stage I & II surgery w/radiation gives 95% 5 year survival. Drops to 50% for stage III & IV. Often found concurrently with ovarian neoplasms.
Carcinoma (type II) / Abnormal bleeding with or without enlarged uterus / Masses within the uterine wall / Clear cell, serous, and carcinosarcoma (both squamous and adenoid hyperplasia) / P53 mutations / Worse prognosis than type I
Leiomyosarcoma / Abnormal bleeding or uterine mass / Bulky mass with hemorrhage / Tumor of abnormal smooth muscle cells that show nuclear pleomorphism / Unknown

Grading of Uterine Cancers:

<5% solid area
5-50% solid area
>50% solid area

Staging of Uterine Cancers:

Remains in body of uterus
Invades cervix
Invades adjacent structures
Invades extrapelvic structures

Fallopian Tube Pathology:

Suppurative salpingitis: 60% Caused by N. gonorrhea. Causes PID. Outcome: Tubal ovarian abscess.
Tuberculous salpingitis: Caused by M. tuberculosis. Classic micro. path.: caseating granuloma.
Paratubal Cyst: Benign lesion, translucent cyst filled with clear fluid.
Adenocarcinoma: Hard to distinguish primary tubal tumors from secondary ovarian lesions. Presents as watery or bloody discharge. Has to satisfy certain criteria:
Dominant tubal mass
Involvement of the tubal lumen
Arising from tubal mucosa
Excluding ovarian or peritoneal cancers

Breast Pathology:

Non-proliferative Proliferative without atypia proliferative with atypia Carcinoma in-situ Carcinoma

Disease / Clinical Presentation / Gross Pathology / Microscopic Path / Etiology / Other Info
Fibroadenoma (benign) / Well circumscribed mass that is freely movable, rubbery, and hormonally responsive / Freely movable, grayish white, rubbery nodule / Well circumscribed fibrous myxoid stroma and fibrous dilation of ducts with bi-layered epithelium (different from FCC) / No increased risk for malignancy
Phyllodes Tumor (benign) / Small to large multilocular mass that is “leaf-like” / Bulbous protrusions with slit-like spaces / Stromal overgrowth, infiltrating margins, and great cellularity / Can be high grade and aggressive
Fibrocystic change (nonproliferative change) / Lumpy bumpy tenderness that increases with the luteal phase of menses and abates with menstruation / Cyst formation with fibrosis and adenosis (and often apocrine metaplasia with single layered glands) / Hormonal imbalance and end-organ insensitivity / No increased risk for malignancy
Proliferative change without atypia / Incidental finding on biopsy or mammographic abnormality / Epithelial hyperplasia, sclerosing adenosis, complex sclerosing lesions, papillomas, fibroadenoma / 1.5-2X increased risk for malignancy
Atypical ductal hyperplasia (proliferative change with atypia) / Small unilateral mass or mammographic abnormality / Resembles DCIS (no invasion through basement membrane) but not qualitatively or quantitatively / 8-10X increased risk for DCIS
Atypical lobular hyperplasia (proliferative change with atypia) / Usually an incidental finding / Resembles LCIS (no invasion through basement membrane) but not qualitatively or quantitatively / 4-5X increased risk for LCIS
Ductal carcinoma in-situ / Small unilateral mass or mammographic abnormality / Ductal hyperplasia that does not extend beyond the basement membrane / Increased estrogen exposure, family history / 80% of CIS in the breast. 30% increased risk for invasive carcinoma
Lobular carcinoma in situ / Incidental finding, can be bilateral. / Acini filled with non-cohesive small cells / Increased estrogen exposure, family history / 30% increased risk for invasive carcinoma
Paget’s disease / Hyperemia, edema, oozing and ulceration from the skin of the nipple / DCIS extending from the ductal cells into the nipple and areola. “Paget cells” can be seen that DO NOT invade the basement membrane / Hormonal, environmental, and genetic factors / 50-60% chance of finding ipsilateral, contralateral, or bilateral carcinoma
Ductal carcinoma (NST) / Pain, breast mass, nipple discharge, mammographic abnormality / Firm non-mobile gritty mass that is infiltrating and retracted / Tubules, nests, cords, and sheets of pleomorphic cells / Hormonal, environmental, and genetic factors / 79% of invasive breast cancer, metslymph nodes, lung, pleura, and bone, inflammation worsens prognosis
Lobular carcinoma / Mass/density in a small %, mostly vague thickening or mammographic abnormality, can be bilateral / Hard with irregular margins / Single-file “marching” poorly cohesive tumor cells frequently infiltrating around ductal structures / Hormonal, environmental, and genetic factors / Metslymph nodes, peritoneum, retroperitoneum, meninges, GI, ovaries, and uterus, inflammation worsens prognosis
Medullary carcinoma (2%) / Fleshy and well circumscribed / Solid syncytium-like sheets of pleomorphic cells with lymphocytic infiltrate / Better prognosis than NST
Mucinous carcinoma (2%) / Circumscribed, slowly growing, gelatinous mass / Clusters and islands of cells floating in lakes of mucin pushing into stroma / Better prognosis than NST
Tubular carcinoma (10%) / Usually detected as mammographic densities (VERY SMALL TUMORS) / Well formed tubules without myoepithelial layer / Excellent prognosis
Papillary carcinoma (1%) / Can be bilateral / Firm non-mobile gritty mass that is infiltrating / Papillary arrangement of ductal carcinoma / Better prognosis than NST

Major Prognostic Factors:

In-situ VS Infiltrating
Local aggressiveness
Lymphatic spread
Distant metastasis
Size of tumor
Inflammatory?

Minor Prognostic Factors:

Histologic subtype
Nuclear grade
Estrogen and progesterone receptors
Her2/neu expression
Lymphovascular invasion
Proliferative rate
DNA content

Staging:

DCIS/LCIS
<2cm –nodes
<5cm +nodes OR >5cm
>5cm +nodes
Distant mets

Prostate Pathology

Disease / Clinical Presentation / Gross Pathology / Microscopic Path / Etiology / Other Info
Prostatitis / Dysuria, retention, dribbling, purulent discharge, abscesses / Edema, redness, ulcerations, abscesses, purulence. / PMN or lymphocytic infiltrate, purulent exudate, or granuloma formation / Acute: E. coli, klebsiella, enterobacter, serratia.
Chronic: any acute cause or abacterial
Granulomatous: TB, cocci, BCG, crypto, blasto, non-specific (keratin).
Benign prostatic hypertrophy (90% of men >70) / Associated with compression of the urethra: retention, dysuria, dribbling, hesitance, nocturia.PSA / Nodularity of the transitional zone not often felt on digital rectal exam / Nodularity, stromal hyperplasia, and glandular hyperplasia with maintenance of basal and luminal cells (High MW cytokeratin stain to determine) / Androgen (DHT)
Tx: alpha blockers, 5-alpha reductase blockers, TURP / Consequences: bladder hypertrophy, cystitis, hydronephrosis, pyelonephritis, urethritis. Not associated with increased risk of malignancy
Prostatic intraepithelial neoplasm (PIN) / Usually asymptomatic / None / Hyperplasia of luminal cells without disruption of glandular structure (doesn’t invade basement membrane) / Unknown / Precursor lesion to carcinoma
Prostatic carcinoma (70% of men >70) / Associated with compression of the urethra: retention, dysuria, dribbling, hesitance, nocturia, PSA / Yellow-white, gritty, and firm mass, often not distinguishable from normal prostate / Proliferation of small glands that is of luminal origin ONLY with cytologic atypia possible / Unknown / Note staging and grading scale below. Tx. T I & II-Radical prostatectomy, TIII+ requires radiation and hormone therapy (LH agonist), metastasisobturator nodes, BONE (osteoblastic lesions)

Gleason grading scale:
Grade lesions within prostate on a scale of 1-5
Add two most common grades (IE 3+4)
>7=Bad prognosis
Staging prostate cancer:
T:Tumor
1: incidental finding
2: confined to prostate(a. unilateral small, b. unilateral large, c. bilateral)
3: Invades capsule (a. unilateral, b. bilateral, c. invades seminal vesicle)
4: Invades contiguous organs
M: Mets
0: No mets
1: Mets
N: Nodes
0: no nodal involvement
1: nodal involvement

Urethra/Penis/Scrotal Pathology:

Congenital/acquired urethral defects:
Priapism: Pathologic engorgement of corpus cavernosa with blood
Peyronie’s DZ: Banana penis disease (fibrosis of tunica vaginalis)
Phimosis/Paraphimosis: Constriction of foreskin behind/in front of glans penis
Hypo/Epispadias: Congenital development of the urethra with the opening on bottom/top of penis (rather than in glans)

Disease / Clinical Presentation / Gross Pathology / Microscopic Path / Etiology / Other Info
Urethritis / Purulent discharge, dysuria / PMN infiltrate with/without presence of organisms demonstrated / N. gonorrhea MOST COMMON, chlamydia, trichomonas, E. coli / Can lead to Reiter’s syndrome: “Can’t see (conjunctivitis), can’t pee (urethritis), can’t climb a tree (arthritis). Autoimmune origin (HLA-B27).
Balanoposthitis / Nonspecific infection of the glans penis with pain, erythema, and possible ulceration / Non-specific: Staph/strep, tinea, candida,
Specific: HSVII, HPV 6, 11.
CondylomaAcuminatum (benign) / Painless raised verrucous areas on the glans/penis / Raised red scaly excrescences / Branching papillary architecture with koilocytosis in surface layers indicative of viral infection / HPV 6 and 11 / No increased risk of malignancy
Bowen’s Disease, Erythroplasia of Queyrat (precancer) / White scaly/red shiny patches on the penis with or without ulceration / White scaly/red shiny patches on the penis with or without ulceration / Malignant epithelial cells within the epithelium that do not invade the basement membrane / HPV 16 and 18 / These lesions ARE PRECANCEROUS
Penile squamous cell carcinoma / Painless, slow growing warty mass with or without ulceration / Nests, cords, or sheets of abnormal appearing epithelial cells that invade beyond the basement membrane / Significant association with lack of circumcision, smoking, and high-risk sexual behaviors. Metastasisinguinal iliac lymph nodes

Testicle and epididymis pathology

Causes of testicular atrophy: (will see Leydig hyperplasia)

Estrogen exposure
Exogenous testosterone
Malnutrition
Medications
Cryptorchidism
Atherosclerosis
Hypopituitarism
Klinefelter’s

Disease / Clinical Presentation / Gross Pathology / Microscopic Path / Etiology / Other Info
Cryptorchidism / Failure of testicles to descend from abomen / Poorly understood / Outcomes: Infertility, 5-10X increase in germ-cell cancers, atrophy. Tx: Orchiopexy.
Torsion (MEIDCAL EMERGENCY) / Rapid onset of intense testicular pain / Blue/black hemorrhagic testicle / Hemorrhagic infarct with fibrosis, extravasation of RBC’s, venous infarction. / Infants: Unknown
Adolescents: Bell-clapper abnormality
Orchitis / Painful inflammation of the testicle(s) / Often subsequent to infection of another proximal structure. Non-specific: Staph/strep
Specific: N. gonorrhea, syphilis
Granulomatous: Non-infectious or M. TB
Germ Cell Tumors/Seminomatous
Seminoma (female counterpart: dysgerminoma) / Testicular mass, hyperechoic on ultrasonography. Stains PLAP (Placental Alkaline Phosphate) + / Grey, cream, or pale homogenous lobulated mass with well-defined border / Uniform population of seminoma cells arranged in sheets or clusters with lymphocytic infiltrate / Isochromosome of the short arm of chromosome 12 / Exquisitely radiosensitive. Metastasispara-aortic lymph nodes.
Spermatocytic seminoma / Testicular mass / Soft well-circumscribed mass with bulging cut surface / Non-cohesive tumor cells similar in morphology to seminoma, but without lymphocytic infiltrate / Isochromosome of the short arm of chromosome 12 / Exquisitely radiosensitive. Metastasispara-aortic lymph nodes
Non-Seminomatous Germ Cell Tumor (NSGCT)
Yolk sac tumor (NSGCT) / Testicular mass. Stains FP + / Non encapsulated pale gray gelatinous tumor with or without necrosis / Lace-like arrangement of cells, with Schiller-Duval bodies. / Isochromosome of the short arm of chromosome 12 / Good prognosis. Metastasispara-aortic lymph nodes
Embryonal carcinoma (NSGCT) / Testicular mass. Stains CD30 + / Soft, gray, granular mass with or without necrosis and is not well demarcated / Primitive gland formation with large irregular cells / Isochromosome of the short arm of chromosome 12 / Grows relatively fast so may be painful. Metastasispara-aortic lymph nodes
Choriocarcinoma (NSGCT) / Testicular mass. Stains hCG+ / Hemorrhagic nodule with rim of fibrous tissue / Malignant syncytiotrophoblast and cytotrophoblast cells without villous formation / Isochromosome of the short arm of chromosome 12 / Metastasispara-aortic lymph nodes. Very aggressive tumor that is widely metastasizing
Teratoma (NSGCT) / Testicular mass / Presence of cartilage, hair, bone, fat, CT, etc can be seen. Well circumscribed tumor / One cell type from every embryonal lineage found. Can be mature (cartilage, fat, bone, etc), or immature. / Isochromosome of the short arm of chromosome 12 / Metastasispara-aortic lymph nodes. Prognosis is good when found in pre-pubertal boys. Post-puberty, all teratomas have malignant potential.
Stromal Tumors
Leydig cell tumor (functional stromal tumor) / Testicular mass, gynecomastia, and precocious puberty may be seen. Androgen and estrogen concentrations in serum. / Well circumscribed, often encapsulated, small masses / Hyperplasia of normal Leydig cells with some cytologic atypia. / Isochromosome of the short arm of chromosome 12 / Metastasispara-aortic lymph nodes. 10% are malignant
Sertoli cell tumor (stromal tumor) / Testicular mass / Lobulated, well circumscribed mass with focal hemorrhage / Hyperplasia of normal Sertoli cells often forming tubules with a basement membrane / Isochromosome of the short arm of chromosome 12 / Metastasispara-aortic lymph nodes. 10% are malignant
Gonadoblastoma (stromal tumor) / Testicular mass / Mixture of stromal and germ-cell components / 46X/46XY mosaicism / Metastasispara-aortic lymph nodes. Germ cell components can become malignant and become seminomas
Lymphoma (stromal tumor) MOST COMMON TESTICULAR TUMOR >60 Y/O / Testicular massStains CD45, CD19 and CD20+ / Poor distinction from surrounding testicular tissue / Diffuse large B-cell lymphoma / Isochromosome of the short arm of chromosome 12 / Metastasispara-aortic lymph nodes. Bad prognosis

Seminomatous tumors:

3rd-4th decade
Metastasize late
Exquisitely radiosensitive
Lymphatic spread

Non-seminomatous germ-cell tumors (NSGCT):

2nd-3rddecate
Metastasize early
Radioresistant
Hematogenous + lymphatic spread

Ovarian Pathology

Distinctions:
Cystadenoma: Benign with single layer glandular proliferation
LMP: Low malignant potential tumor with stratification of glandular structures
Cystadenocarcinoma: Malignant tumor with areas of glandular and solid architecture with cytologic atypia

Disease / Clinical Presentation / Gross Pathology / Microscopic Path / Etiology / Other Info
Epithelial Tumors (65-75% of ovarian cancers. Seen in older women)
Serous (cystadenoma, LMP cystadenoma, and cystadenocarcinoma) / Adnexal mass with or without tenderness, bloating, ascites, abdominal pain. Stains CA125+. / Serious filled cystic dilation of the ovary with areas of solid tumor proliferation / Serious filled cystic spaces lined by tall columnar ciliated epithelium of various stratifications + psammoma bodies. / Risk Factors: #1-Family history, long reproductive span, nulliparity, increased estrogen exposure. DECREASED RISK WITH OCP USE.
Mucinous (cystadenoma, LMP, cystadenocarcinoma) / Same-these tumors can be VERY large and bilateral. Stains CA125+. / Larger cystic masses than seen in serous, filled with mucin / Mucin filled cystic spaces lined by tall columnar epithelium of various stratification + psammoma bodies. Can be intestinal or endocervical type. / Same
Endometrioid adenocarcinoma / Same. Can be bilateral. / Solid or cystic / Tubular glands resembling endometrial primary tissue present in the ovary / Same / Associated with uterine endometrioid neoplasm, endometriosis, and clear cell carcinoma of the ovary
Clear cell / Same / Vacuolated cells forming glands, papillae, or sheets. “Clear cells”. / Same / Aggressive tumor with 50% 5 year survival wo/mets, and 0% 5 year w/mets.
Brenner tumor / Same / Fibrous stroma with nests of transitional epithelium / Same
Germ Cell Tumors (15-20% of ovarian cancers. Seen in younger women)
Choriocarcinoma / Same. Stains + for hCG. / Hemorrhagic tumor / Syncytio/ Cytotrophoblast hyperplasia without villous formation / Same / Very aggressive tumor usually of placental origin that often has metastasized when identified
Teratoma / Same. Can be bilateral. / Can be cystic (dermoid) or solid containing multiple tissue types / Mature or immature combinations of tissue types from each of the three embryonal cell layers / Parthenogenetic event
Dysgerminoma (sister to seminoma) / Same / Solid, nodular, and rubbery / Primitive cells with nests and sheets of homogenous cells with lymphocytic infiltrate / Same / Aggressive but responsive to chemotherapy
Endodermal Sinus Tumor (AKA Yolk Sac Tumor) / Same. Stains + for FP. / Loose gelatinous stroma / Schiller-Duval bodies / Same
Stromal Tumors (Wide age range)
Granulosa/Theca cell tumor / Same. Causes precocious puberty in young women and endometrial hyperplasia with possible carcinoma in older women / Yellowish hormone-producing tumors / Call-Exner bodies (coffee bean nuclei) / Same / Often seen in conjunction with endometrial hyperplasia/ carcinoma
Leydig/Sertoli cell tumor / Same. Causes masculinization due to hyperandrogenism: hirsutism, acne, etc. / Yellowish hormone-producing tumors / Resemble granulosa/theca tumor / Same
Krukenburg Tumor / Bilateral tumor, usually with colicky pain / Signet ring cell gastrointestinal carcinoma within both ovaries
Benign Lesions
Follicular cyst / Larger cysts can cause pelvic pain, adnexal mass and tenderness / Cystic dilation of follicle that is smooth and glistening with clear serous fluid content / Attenuated inner granulosa, luteinized theca. / Unrupturedgraafian follicle, ruptured follicle that sealed immediately
Luteal Cyst / Larger cysts can cause pelvic pain and adnexal masses with tenderness / Cystic dilation of CL that has a yellow surface and bloody fluid content / Luteinized theca and granulosa cells
Polycystic Ovaries / Elevated LH, androgens, and estrogen, IDDM, hirsutism, / Ovarian enlargement, thickening of the cortex, cortical cysts / Multiple follicular cysts with inner granulosa and outer theca layers / Unknown / Increases risk of endometrial cancer

PseudomyxomaPeritonei: Extension of ovarian mucinous tumor into peritoneum (implants), location of choice-appendix.

Vagina/Vulva/Cervical Pathology