Gynecology

Gynecologic Pathology

VAGINA

STAGING

• § T0: no evidence of primary tumor
• § Tis: carcinoma in situ (preinvasive carcinoma)
• § T1a:  confined to vagina
• § T2:  invades paravagina but not pelvic wall
• § T3:  tumor extends to pelvic wall
• § T4:: bladder or rectum or beyond the true pelvis

 

SYNOPTIC REPORT

• § PS, HHoTTeLL  MaNiC
  • Ø +
• § Pagetoid spread
• § Presence of VAIN, condyloma accuminatum

 

 

VULVA

PRENEOPLASTIC LESIONS

1. LICHEN SCLEROSIS (ET ATROPHICUS)

• § Clin: post-menopausal, ↑risk of ca with HP
• § Gross: white patch
• § Micro: +/-hyperkeratosis
• § -hypergranulosis
• § -hypcellular edematous layer + PVLI

 

2. CONDYLOMA ACCUMINATUM

• § Gross: polypoid with cauliflower appearance
• § Micro: hyperkeratosis, papillomatosis, acanthosis, koilocytosis in middle and upper epithelium
• § -includes warty, basaloid VIN, Bowen disease, Bowenoid papulosis
• § Clin: HPV-related, young
• § Basaloid:flat, small uniform cells, ↑mitoses

3. VULVA INTRAEPITHELIAL NEOPLASIA (VIN)

3a. CLASSIC

-koilocytes rare, poorly defined membranes

Warty: warty, spiky, acanthotic,

-koilocytes, well defined membranes

• § IHC: p16
• § Clin: not HPV-related, post-menopausal
• § -assoc/ lichen sclerosis
• § -type most likely to progress to ca.(older or immunosupressed)
• § Micro: parabasal atypia, keratinization, hyperplasia
• § IHC: p53 staining full thickness
• § Entities:
• § dermatoses→lichen simplex chronicus, psoriasis

3b. WELL-DIFFERENTIATED/SIMPLEX

4. VULVAR DYSTROPHIES

2.  VIN

3.  chronic vulvar dystrophies →

a. lichen sclerosis

b. keratosis

EPITHELIAL TUMORS

1a. SQUAMOUS CELL CARCINOMA

Clinical

• § post-menopausal women, most non-HPV-related

Risk factors:

• § -HPV, smoking (younger population)
• § -immunosupp., lichen sclerosis (older pop’n)
• § Microinvasive:
• § <1mm
• § Tx:
• § radical vulvectomy with 1cm margin + bilateral radical inguinal lymph node dissection

Variants:

• § Verrucous:
• § large size and pushing club-shaped fingers. Very well differentiated. DD condyloma
• § Warty:
• § marked atypia associated with koilocytosis and HPV DNA

 

1b. BASAL CELL CARCINOMA

 

1c. VIN

 

1d. BENIGN CONDITIONS

• § Condyloma acuminatum
• § Vestibular papilloma
• § Fibroepithelial polyp
• § Seborrheic and inverted follicular keratosis
• § Keratoacanthoma
• § Clin:
• § primary (vulva only) or secondary (from adenoca. anorectum, urothelium, prostate)
• § -crusting, weeping, oozing lesion; may be erythematous
• § Micro:
• § nests of cells within epidermis, not touching the bm.
• § -abundant cytoplasm, lg nuclei
• § -intracytoplasmic melanin,
• § -unlike in breast, not necessarily assoc/
• § invasive tumour

2a. PAGET DISEASE

IHC:

• § Primary: GCDFP15+, CK7+/CK20-
• § Secondary: GCDFP15-, CK7-/CK20+ (anorectal)

 

2b. BARTHOLIN GLAND TUMORS

• § Adenocarcinoma
• § SCC
• § AdCC
• § Adenosquamosu
• § TCC
• § Small cell
• § Adenoma
• § Adenomyoma

 

2c. PAPILLARY HIDRADENOMA

• § Micro:
• looks like intraductal papilloma of breast
• § -complex papillary pattern with 2 layers of cells:1.lining cells, 2.myoepithelial cells

 

2e. ADENOCARCINOMA OF SKENE GLAND

 

2h. MIXED TUMOR OF VULVA

 

3. TUMORS OF SKIN APPENDAGES

 

MESENCHYMAL TUMORS

1. RMS

2. LMS

3. EPITHELIOID SARCOMA

4. ASPS

5. LPS

6. DFSP

 

7. AGGRESSIVE ANGIOMYXOMA

Clinical

• § Large slow growing mass, locally infiltrative

Micro

• § Hypocellular and mxyoid with lg-sized vessels

IHC

• § Actin and desmin

DD

• § FEP: bizarre stromal cells, bigger and deeper

 

8. SUPERFICIAL ANGIOMYXOMA

 

9. ANGIOMYOFIBROBLASTOMA

 

10. CELLULAR ANGIOFIBROMA

 

11. LM

 

12. GRANULAR CELL TUMOR

 

STAGING

• § T0: no evidence of primary tumor
• § Tis: carcinoma in situ (preinvasive carcinoma)

 

• § T1a:  <2cm (vulva/perineum) + stromal inv <1mm
• § T1b:  <2cm (vulva/perineum)+ stromal inv <1mm T2:  >2cm  (vulva/perineum)
• § T3:  any size + with adjacent spread to urethra, vagina or anus
• § T4:: upper urethral, bladder, rectal mucosa, or pubic bone

 

DECISION POINTS

• § <1mm → wide local excision

>1mm → mod. radical vulvectomy with nodes (unilateral if off to one side OR bilateral if midline)

 

STAGING

• § T1  <2cm
  • Ø T1a  <1mm stromal
  • Ø T1b  >1mm stromal
• § T2  >2cm
• § T3  vagina, anus, lower urethra
• § T4  bladder/rectum/upper urethra

 

N0

• § N1   unilateral regional nodes
• § N2   bilateral regional nodes

 

M0

• § M1  distant mets

 

SYNOPTIC REPORT

• § PS, HHoTTeLL  MaNiC

+

• § Tumour extent:
• § -anus/bladder/rectum/perineum/upper OR lower urethra
• § -depth of invasion

 

Margins:

• § Deep→soft tissue
• § Peripheral and skin
• § Central→vaginal/urethra

CERVIX

Name 5 types of cervical metaplasia.

• § Squamous metaplasia (TZ)
• § Transitional metaplasia (exo)
• § Tubal metaplasia (endo)
  • Ø All 3 cells present (ciliated, peg, secretory)
• § Tuboendometrial metaplasia (endo)
• § Intestinal metaplasia (endo)
  • Ø Mucin in stroma
• § Atypical oxyphilic metaplasia

 

 

Mesonephric lesions

• § -Wolfian duct remnant
• § -remnants (rests) or HP

 

Types of cervicitis

• § Follicular cervicitis→ often assoc/ Chlamydia

Papillary cervicitis → 2^o to chronic cervicitis

HSV/CMV cervicitis

Eosinophilic cervicitis

Xanthogranulomatous cervicitis

Actinomyces, Shisto, Malakoplakia

 

Microglandular HP

• § -cribriforming, polypoid, bland cytology, no mitoses, basal vacuolization

 

HPV

Lesions assoc/ HPV infection

• § -condyloma accuminatum
• § -SIL
• § -AIS (adenoca in situ)
• § -invasive SCC, adenoca, (adenoid cystic and basal ca)

Function of HPV in the cell

• § HPV intergrates into host genome
• § overexpresssion of E6 and E7 proteins
• § HPV E6 protein interacts with p53; HPV E7 protein interacts with Rb (retinoblastoma) protein
• § induce genetic instability, cell cycle progression which promotes selection of a malignant phenotype

Low and High Risk HPV

• § Low: 6, 11
• § High: 16, 18

Methods of detection

• § IHC: p16 (for HSIL)
• § Molecular: Southern blot or in-situ hybridation

 

CONDYLOMA ACCUMINATUM

• § Gross:
• § polypoid with cauliflower appearance
• § Micro:
• § hyperkeratosis, papillomatosis, acanthosis, koilocytosis in middle and upper epithelium
• § -if ↑ atypia then grade as LSIL or HSIL

 

SQUAMOUS PAPILLOMA

• § Gross: polypoid
• § Micro: papillomatosis, NO koilocytosis

 

HSIL VS. ATROPHY

kI-67:

HSIL → full thickness

p16:

HSIL → upper 2/3

(CDKI assoc/ incorporation into host genome)

Both are negative with atrophy

 

EPITHELIAL TUMORS

1a. SCC

• § Risk factors:
• § Sex (early age, mult. partners, male partner with mult. partners), HSIL, smoking
• § Prognosis:
• § TNM stage, (size, depth of invasion, parametrial involvement, nodes)
• § IHC:
• § CK, CEA, p63

 

-Keratinizing

-Non-keratinizing

-Basaloid

-Verrucous

-Warty

-Papillary

-Lymphoepithelioma-like

-Squamotransitional

1b. MICROINVASIVE SCC

 

1c. SIL

-LSIL

• § Koilocytosis:
• § nuclear pleomorphism, wrinkled hyperchromatic nucleus, binucleated, perinuclear halo with peripheral condensation
• § Gross:
• § Slightly raised (condylomas) or flat;
• § Micro:
• thickened (acanthotic) epithelium with koilocytotic atypia in middle or upper epithelium
• § ▪lower third dysplastic

 

-HSIL

• § Micro:
• § -at least 1/3 to total replacement of epithelium by atypical cells in at least part of the lesion with loss of maturation; koilocytes

Ddx of SIL:

• § -atrophy
• § -pseudokoilocytosis in post-menopausal
• § -invasive SCC
  -TCC metaplasia
• § -reactive changes

Microinvasion

• § -maximal depth of 3mm (T1a <3mm, T1b <5mm)
• § -maximal horizontal spread of 7mm
• § -no angiolymphatic invasion
• § -low recurrence risk and nodal involvement
• § Tx:
• § conservative therapy w/ loop if fertility req.

1d. BENIGN

-Condyloma

-Squamous papilloma

-FEP

 

2a. ADENOCARCINOMA

DD

• § Adenoca. from the endometrium, microglandular HP, papillary cervicitis

Cervical adeno	Endometrial adeno
<40yo	>40yo
AIS
CEA+
ER- or weak
VIM-
HPV+ by FISH
P16+
HPV by ISH

Variants: “M^cEVANS”

• § Mucinous
• § Clear cell (Ddx Arias Stella reaction)
• § Endometroid
• § Villoglandular
• § Adenoma malignum
• § ‘Nephric carcinoma
• § Serous papillary adenoca
• § Endocervical
• § Intestinal
• § Signet-ring cell
• § Minimal deviation
• § Villoglandular

-Mucinous

-Endometrioid

 

-Clear cell

-Serous

-Mesonephric

 

2b. MICROINVASIVE ADENOCARCINOMA

 

2c. ADENOCARCINOMA IN SITU

• § Clin:
• § 30-40
• § Assoc/
• HPV
• § Micro:
• AIS has sharp demarkation from normal epithelium
• § Microinvasive
• <3mm, age 40-45 {invasive, age 45-55}

 

2d. GLANDULAR DYSPLASIA

 

2e. BENIGN

-Mullerian papilloma

-Endocervical polyp

 

OTHER EPITHELIAL TUMOURS

• § Adenosquamous carcinoma
  • Ø Glassy cell
• § AdCC
• § Adenoid basal carcinoma
• § NE (usual 4 types)
• § Undifferentiated

 

MESENCHYMAL

• § LMS
• § ESS
• § Undifferentiated stromal sarcoma
• § RMS
• § Alveolar soft part sarcoma
• § Postoperative spindle cell nodule
• § Genital rhabdomyoma

 

BOTRYOIDES RHABDOMYOSARCOMA

Clinical

• § Young children

Gross

• § Polypoid growth into a cavity (uterus, cervix, conjunctiva)

Micro

• § Cambium layer beneath cervical, loose myxoid stroma, cartilage in older women; occ mitoses

IHC

• § Desmin, MSA, SMA, myoD1

 

MIXED EPITHELIAL AND MESENCHYMAL

• § Adenosarcoma
• § Carcinosarcoma
• § Wilms tumour

 

• § Melanoma
• § Lymphoma, Myeloid sarcoma
• § Germ cell tumor (YST, teratoma)

 

STAGING

• § Tx-cannot be assessed
• § T0-no evid of primary tumour
• § T1a-microscopically invasive
  • Ø T1a1-<3mm deep, 7mm wide
  • Ø T1a2-<5mm deep, 7mm wide
• § T1b-visible invasion
  • Ø T1b1-<4cm
  • Ø T1b24cm
• § T2-beyond uterus
• § T3-pelvic wall OR lower 1/3 vagina
• § T4-bladder/rectum
• § Measuring depth of invasion

 

DECISION POINTS

• § ▪ 3mm deep and <7mm wide (T1a1) with no LVI→LOOP excision

▪ otherwise → TAH +/- staging

 

• § GROSSING-KEY POINTS

CONE BIOPSY

• § open at 12 o’clock (open like this:“O”→”U”)
• § 2. pin on corkboard with mucosa up and fix
• § 3. ink margins
• § 4. cut parallel sections and submit from 12-3, 3-6,6-9 and 9-12 o’clock & mark on drawing
• § 5. submit in toto

 

SYNOPTIC REPORT

CONE BIOPSY

• § Macroscopic tumor site (quadrant: either 12-3, 3-6, 6-9 or 9-12 o’clock)
• § Tumor size
• § Histologic tumor type (WHO)
• § Tumor grade
• § Depth of invasion (mm)
• § Width (horizontal extent) of tumor (mm)
• § Margins (endocervical, exocervical, deep) margin – involved by intraepithelial/invasive carcinoma (focal or diffuse) or __ mm from closest invasive carcinoma

 

• § HYSTERECTOMY
• § Specimen type
• § Other organs present
• § Macroscopic tumor site (quadrant: either 12-3, 3-6, 6-9 or 9-12 o’clock)
• § Tumor size
• § Histologic tumor type (WHO)
• § Tumor grade
• § Depth of invasion (mm)
• § pTNM / FIGO staging
• § Margins
• § Distal margin – involved or not involved by carcinoma in situ

 

 

UTERUS

CONGENITAL ANOMALIES

Types (hint: BAD US)

• § Bicornuate: shorter incomplete septum vs didelphys
• § Arcuate: even shorter septum than bicornuate
• § http://babyjava.net/main/index.php?blog=3&title=uterine_abnormalities&more=1&c=1&tb=1&pb=1
• § Didelphys[1]: 2 UTERUS!!!
• § Unicornuate
• § Septate

ATROPHY

Dx (DECREASED GS ratio, SIMPLE cuboidal eptihelium, NOT dark nuclei, no mitoses, cystic if previous HP)

• § Demo: prepubertal, postmenopausal

Micro

• § Simple cuboidal (no stratification), no mitosis, collagenized stroma, DECREASED GS ratio, cystic, THIN endometrium, sometimes TUBAL METAPLASIA (Steinberg). Inactive (no mitoses), cystic changes, flat surface epithelium, fibrotic stroma

DD

• § Lower uterine segment: fibrous spindle stroma, hybrid endometrial-endocervical glands
• § Polyp
• § Progestin
• § Simple hyperplasia: also have cystic dilation but proliferative epithelium

Variants

• § Cystic
  • Ø Etio (previous HP from estrogen hyperstimulation).
  • Ø Thin endometrial layer with scattered glands, some of which are cystic but no budding and no proliferation (mitoses) (Steinberg, Robbins)
  • Ø Caveat: cystic dilation due to previous hyperplasia, which will remains once estrogen stimulation is ceased and to cause cystic atrophy (Robbins)

 

ENDOMETRIUM

procedures

• § D&C-endometrial
• § Fractional curretage-sampling from EC and EM cavities→done for ?extension

Endometrial biopsy: done for ?endometrial HP,ca

Asherman’s syndrome: interuterine adehesions from previous D&Cs

 

What are the effects of estrogen?

• § -stimulus for endometrium
• § -↑risk of endometrial HP and ca

-tamoxifen has estrogenic effect on endometrium

Discuss the histologic features seen in normal cycling endometrium

Menstrual[2]

• § Stromal hemorrhage
• § Detached glandular frags + stromal “blue” balls
• § Vascular fibrin thrombi
• § Regenerating cells

Proliferative

• § Early: glds: staight and narrow, pseudostratified, mitoses; spiral arterioles: straight
• § Mid: glds: coiled, pseudostratified, mitoses;
• § ↑stromal edema
• § Late: glds: very coiled, pseudostratified, mitoses; ↓stromal edema

Secretory

• § Early:
  • Ø POD2: >50% subnuclear vacuoles
  • Ø POD4: all supranuclear vacuoles
• § Mid:
  • Ø glds: coiled with secretions, no vacuoles; stroma:edema
• § Late:
  • Ø glds: tightly coiled “serrated” , no vacuoles; stroma: predecidualized patchy (around spiral arterioles), granulocytes

 

DISORDERED PROLIFERATIVE ENDOMETRIUM

Cause

• § unopposed estrogen stimulation

Micro

• § Glands: proliferative glands, cystically dilated, various sizes (no uniform development), stroma: proliferative w/ mitoses
• § + may have stromal breakdown
• § Regular at lower power: quite uniform with cysts (Mutter)
• § Irregular at high power: some crowding, tubal metaplasia, thrombi (Mutter)

MENTRUAL DATING

Hallmarks of NORMAL endometrium (UNIFORM development, NO complexity such as branching/budding, GS ratio can vary). Conditions for dating on biopsy (SURFACE epithelium present, not from LUS, based on more advanced area, no exogenous hormone).

• § Caveat: compactum only occurs in secretory phase and is immediately underneath surface epithelum; it shows straight TUBULAR glands and they are NORMAL (Mazur). Compactum does not react well to hormonal change (Mazur)
• § Caveat: dating based on most advanced area. Difficult if IUD or not uniform
• § Caveat: ideal sample for dating should have surface epithelium (for specimen orientation) (Mazur). Careful with your interpretation when you can’t find any surface epithelium because sampling may be from basalis (Mazur).
• § Caveat: menstrual endometrium, lower uterine segment, compactum and basalis NOT suitable for dating (Mazur, SenGupta). Same for chronic endometritis and polyps (Mazur)
• § Lab: other means of evaluating ovulation include rise of basal body temperature, serum LH surge, transvaginal US for follicular or corpus luteum, serum progesterone level (Mazur)
• § Most useful features in (Mazur). 7 useful morphologic features are gland mitoses, tortuosity of glands, basal vacuolation, secretion, stromal edema, predecidual reaction and leukocytic infiltration (Robbins)
  • Ø Glands: nuclear orientation (pseudostratified vs single layered), subnuclear vacuoles, secretory exhaustion
  • Ø Stroma: edema, predecidual change, grnaular lymphocytes
• § Caveat: hallmark of normal endometrium is UNIFORMITY of development (Steinberg).

Micro

• § Based on GLANDS, STROMA and BV; mitose and luminal secretions not reliable (Mazur). Normal endometrial glands NEVER have branching or budding (these fined GLANDULAR COMPLEXITY and are features of HP and cancer) (Steinberg)

Mechanism (Mazur)

• § Proliferative: granulosa cells estradiol growth of glands, stroma and BV
• § Secretory: luteinized granulosa and theca cells of CORPUS LUTEUMà progesterone and estradiol

Define

• § Decidualization
  • Ø Etio: pregnancy or progesterone
  • Ø Plump stromal cells (definition of decidualization, Robbins), nuclear pleormophism, hyperchromasia, marked vacuolization, maybe necrotic. Large epithelioid cells with round-oval vesicular nuclei and abundant pink to clear cytoplasm and distinct borders (Robbins). Remember plump epithelioid and even spindly cells (vs round in normal stroma, me)
  • Ø Caveat: may mimic sarcoma or adenocarcinoma
• § Predecidualization
  • Ø Milder deciduation

What diagnostic criteria?

• § 2 consecutive cycles, secretory histologic dating at least 2 days earlier than expected

 

PROLIFERATIVE

Dx proliferative (straight glands becoming more and more coiled, pseudostratified columnar, dark elongated nuclei, increased NC, NEVER branching/budding, mitoses, no secretion, edema at mid-stage). Breakdown with proliferative=anovulation.

Micro

• § STRAIGHT TUBULAR (the thicker endometrium, the more tortuous) glands lined by regular TALL PSEUDOSTRATIFIED COLUMNAR cells, numerous mitoses (best indicator but also during menses because repair and breakdown simultaneously), NO mucus secretion, NO VACUOLATION (Robbins, Osler). Stroma composed of compact spindle cells with scant cytoplasm but abundant mitoses (Robbins)
• § Caveat: focal hemorrhage beneath surface epithelium due to biopsy (do not overinterpret as menstrual or breakdown) (Mazur)
• § Caveat: REGULARLY spaced glands with UNIFORM shape (gland irregularity or dilation should raise disordered proliferative or simple hyperplasia) (breakdown should raise anovulation, disordered proliferative or hyperplasia) (Mazur, Childs)
• § Caveat: trust only endometrium lined by surface epithelium (Mazur, Robbins).
• § Caveat: vascular proliferation with small THIN-walled BV in stroma (Mazur)
• § Caveat: very early proliferative endometrium may have residual stromal breakdown (especially at late menstrual and  early proliferative transitional phase); misdiagnosed as anovulation (Crum)
• § Spectrum: weakly proliferative-> proliferative-> anovulation (no gland irregularity and dilation)-> disordered proliferative (focal gland irregularity and dilation)-> simple hyperplasia (diffuse gland irregularity and dilation)-> complex hyperplasia (marked increased ratio) (me, Childs)

Variants by phase: no need to know

• § Early (4-7 days): cuboidal cells, short straight glands, thin endometrium, mitoses, compact stroma, large nuclei with scant cytoplasm. Residual stromal breakdown leftover from prior menstrual cycle (Crum)
• § Mid (8-10 days): COLUMNAR SURFACE epithelium, LONGER CURVING glands, VARIABLE STROMA EDEMA
• § Late (11-14 days): pseudostratified epithelium, long curved glands, undulent surface epithelium, moderately DENSE stroma

Variants

• § Disordered proliferative
• § Weakly proliferative

 

DISORDERED PROLIFERATIVE

• § Between anovulation and simple HP*. Etio (CHRONIC and REPEATED ANOVULATIONS). Outcome (NO* increased malignant risk). Dx* (PROLIFERATIVE glands with FOCAL CYSTIC DILATION because NON-uniform development, mitoses, NORMAL GS ratio, often TUBAL METAPLASIA, +/- stromal breakdown). Ddx simple HP* (DIFFUSE cystic dilation, GS ratio increased).
• § Demo: perimenarchal or perimenopausal (Steinberg)
• § Diagnosis: reserved for curretage/hysterectomy (not for biopsy) (Steinberg)
• § Etio: anovulation
• § Mechanism: occurs when chronic anovulatory cycles results in abundant proliferative tissue with mild degree of disorganization characterized by focal glandular dilation (Mazur).
• § Nature: disordered proliferative (proliferative with FOCAL gland irregularity and dilation suggestive of simple hyperplasia, +/- breakdown) is between anovulation (UNIFORM proliferative with breakdown WITHOUT glandular dilation or irregularity) and simple hyperplasia (UNIFORM proliferative WITH diffuse glandular dilation and irregularity +/- breakdown) (Childs)
• § Nature: regarded as variant of proliferative endometrium (Mazur).
• § Outcome: no risk for cancer (Steinberg)

Micro

• § Normal GS ratio, DYSYNCHRONIZED development (areas of cystic irregular glands with areas of regular tubular glands; hallmark), proliferative stroma and glands, TUBAL METAPLASIA common, +/-breakdown (Steinberg, Mutter). Key word is irregularly regular pattern (quite unform with focal cystically dilated glands at low power but irregular with glandular crowding at high power) (Mutter).
• § Caveat: fibrin thrombi never occur in normal menses (Mutter)
• § Caveat: diagnosis reserved to intact well-oriented endometrium (Mazur)
• § Caveat: basically is simple hyperplasia (cystic dilation) intermixed with normal proliferative glands (Mazur).

DD

• § Normal proliferative: uniform (Steinberg)
• § Simple hyperplasia: increased ratio (Steinberg)

 

WEAKLY PROLIFERATIVE

Dx (PSEUDOSTRATIFIED but no mitoses).

• § Nature: less active than normal proliferative
• § Demo: normal in prepubertal girls (Steinberg)
• § Pseudostratified, no mitoses (Steinberg). Budding/branching (Steinberg).

DD

• § Atrophy (Steinberg): no pseudostratification, no budding/branching
• § Normal proliferative (Steinberg): mitoses present

 

INTERVAL (14-15)

No change!!!

• § Aka 16-day endometrium (Crum)-> better say that it’s 15-16 (me)

Micro

• § NO datable changes during day 14-15 (Mazur). Subnuclear vacuolation begins on POD2 (Mazur, Robbins).
• § Caveat: first 2 days after ovulation is called interval endometrium, characterized by proliferative glands and only scattered subnuclear vacuoles (Mazur).

 

SECRETOY

Dx (ROUNDER and larger nuclei, visible nucleoli, INCREASED GS ratio). Early secretory (same nuclei as late PROLIFERATIVE, >50% subnuclear at POD2, all supranuclear at POD4). Mid-secretory (round vesicular, simple cuboidal, small but visible nucleoli, eosinophilic cytoplasm, INCREASED GS ratio, thick walled spiral arteries, coiled glands, SECRETIONS, no vacuoles, stromal edema). Later-secretory (SERRATED glands, no vacuoles, predecidualized stroma, granulocytes). Define decidualization (stromal cells with round vesicular nuclei and abundant eosinophilic cytoplasm with WELL-defined borders).

• § Caveat: day-1 defined as first day of clinical menses (Crum)

Micro

• § INCREASED GS ratio (similar to HP and carcinoma) (Steinberg). Nuclei rounder, larger and with nucleoli in glands (Mutter)
• § Decidualization: normal stromal cells have spindled or oval nuclei with scanty cytoplasm with ILL-defined cell borders (Steinberg). They have larger, round vesicular nuclei with abundant eosinophilic to clear cytoplasm with WELL-defined borders when decidualized (Steinberg). It’s called pre-decidualization when these features are not as prominent (Steinberg).

Variants

• § Early
• § Mid
• § Late

 

 

DUB

Goal (clinician wants to know whether DUB of patient is ovulatory or anovulatory; if ovulatory, try to date secretory phase for any lag). How (biopsy taken DURING bleeding event, don’t give progesterone before biopsy). Requisition (age, date and characteristic of mens, chief complaint, meds including OCP and progestin). Dx (1:1 GS ratio, STROMAL BREAKDOWN, karyorrhexis, fibrin thrombi but NO cystic glands (vs yes in anovulation), NO proliferative glands). Etio (FUNCTIONAL disturbances of mens or systemic dz. ANOVULATION no1 cause but others possible such as LUTEAL PHASE DEFECTS but NO organic cause). Exogenous hormones can mimic any changes of DUB. Mechanism (too much or too little estrogen or progesterone-related). Ddx mens (secretory background, predecidual stroma, DIFFUSE and uniform, NO chronic changes), complex HP (not fragmented, increased GS ratio), cancer (not fragmented, increased GS ratio), organic causes (clinical correlation needed). Variants divided by ovulation or not (anovulatory, luteal phase-related).

• § Def: stromal breakdown and gland karyorrhexis in ABSENCE of cystic glandular dilation (Crum). Benign endometrium with stromal breakdown; ddx includes hormone therapy or alterred cycle (Crum)
• § Def: unscheduled bleeding due to HORMONAL/FUNCTIONAL (usually ANOVULATORY but NOT always) but NO ORGANIC cause (Crum, Robbins). By definition, excludes postmenopausal bleeding and organic causes (polyp, inflammation, polyps, HYPERPLASIA, cancer, exogenous HORMONES, pregnancy) (Mazur).
• § Demo: mainly perimenarcheal and perimenopausal, a bit less in reproductive (Mazur)
• § Etio(Mazur, Crum)
  • Ø ANOVULATION: no1 by far
  • Ø LUTEAL PHASE abnormalities: luteal phase defects LPD, abnormal persistence of corpus luteum
• § Mechanism (Mazur)
  • Ø Estrogen-related: too much or too little (atrophy). Anovulation (proliferative with glandular and stromal breakdown), atrophy (severe estrogen-deprivation)
  • Ø Progesterone-related: less common
• § Nature: implies ovulatory dysfunction (Mazur).

Micro

• § INTACT functionalis, tubular glands (WITHOUT cystic dilation), DIFFUSE stromal breakdown (fairly NORMAL endometrium with breakdown) (in other words, breakdown without glandular dilation) (Crum). Glandular and stromal breakdown (Mazure). Stromal collapse (blue balls due to stromal condensation, mixed with nuclear debris), stromal cell clusters separated by lakes of blood, FIBRIN THROMBI in small BV (can extend into stroma), nuclear debris in basal cytoplasm of glandular cells (sign of early breakdown) (Mazur).
• § Caveat: exogenous hormone can mimic any DUB patterns (Mazur)
• § Caveat: fibrin thrombi cause microinfarcts with stromal breakdown and secondary adjacent epithelial collpase mimicking hyperplasia (Crum)
• § Caveat: glandular and stromal breakdown non-specific (Mazur).
• § Caveat: in absence of tissue ovulation, anovulation vs DUB can not be excluded nor confirmed (Crum). I don’t understand this sentence.
• § Caveat: remember exogenous hormones can mimic any morphology caused by endogenous hormones (Mazur, SenGupta)
• § CHRONIC CHANGES (absent in menstrual endometrium): eosinophilic syncytial change of surface epithelium (aka SYNCYTIAL PAPILLARY METAPLASIA, virtually always associated with active bleeding), hemosiderin, foam cells, stromal fibrosis and hyalinization (Mazur)
• § Patterns: regularly irregular (Crum)

DD

• § Complex hyperplasia/cancer (due to cell crowding in DUB): NO fragmented glands vs yes in DUB (Mazur, Crum)
• § Menstrual endometrial: LATE SECRETORY background with predecidual stroma (vs no in DUB), DIFFUSE and uniform breakdown THROUGHOUT uterine cavity (vs focal in DUB with fragments of intact endometrium admixed with broken tissue), NO chronic changes such as hemosiderin, eosinophilic syncytial change or foam cells because mens occurs acutely (Mazur).
• § Organic causes: hyperplasia, inflammation, polyps and cancer can mimic DUB histologically (Mazur)

Variants

• § Anovulation
• § Luteal phase defect

 

ANOVULTION

<2% cancer risk. PROLIFERATIVE glands, cystic glandular dilation REQUIRED, tubal metaplasia, pink cytoplasm, fibrin thrombi, blue stromal balls, karyorrhexis. Due to dysfunctional axis which causes estrogenic hyperstimulation and persistent proliferative development. Etio (axis problem, any hyperestrogenic condition such as obesity, menarche, perimenopause, PCOD, chronic dz). Rule out atypia.

• § Aka disordered proliferative endometrium (Mazur does not equate them) (Crum)
• § Complications: endometrial cancer in <2% (Crum)
• § Def: persistent follicles with no ovulation (Mazur, Crum)
• § Demo: mostly before 20 and after 40 (Crum). Good hint is perimenopausal age (Childs)
• § Etio (Mazur)
  • Ø Hypothamalic dysfunction (hyperPRL), obesity, increased androgen production by adrenals and ovaries (Mazur)
  • Ø Menarche, perimenopause, PCOD, obese, any chronic disease state, pituitary problems (Robbins)
• § Incidence: no1 cause of DUB (Robbins).
• § Mechanism: failure of ovulation PERSISTENT ESTROGENIC stimulation persistent proliferative phase (PERSISTENT CYSTIC GLANDULAR DILATION with regularly irregular gland distribution aka disordered proliferative endometrium) stromal breakthrough when too thick endometrium can not be supported by structures (Mazur, Robbins, Crum).
  • Ø Caveat: FOCAL fibrin thrombi PATCHY stromal breakdown (Crum)

Micro

• § Proliferative glands, CYSTIC GLANDULAR DILATION required (suggestive of simple hyperplasia), PATCHY breakdown with FIBRIN THROMBI (reason why regularly irregular distribution), blue stromal balls, karyorrhexis, TUBAL METAPLASIA, pink cytoplasm (Mutter, Crum, Childs). Must check carefully for atypia. Brief, breakdown with proliferative glands with dilation (Crum).
• § Caveat: any acute inflammation??? Seems not… must check
• § Caveat: focal subnuclear vacuolation permitted because still caused by estrogen (not indicate secretory change) (Mazur)
• § Caveat: cystic dilation of glands not present if no persistent estrogenic stimulation (Crum)
• § Ovary: follicles without corpus luteum in ovary.

Variants by onset (Mazur)

• § Chronic anovulation: causing breakthrough bleed because endometrium outgrows supporting structures you will see thicker and more proliferative endometrium with venules, thrombosis and METAPLASIA (due to chronicity)
• § Sporadic anovulation: due to sudden estrogen withdrawal therefore, you will only see weakly proliferative endometrium with breakdown (can mimic menstrual endometrium)

 

LUTEAL PHASE DEFECT

• § How (must do biopsy during luteal phase). Etio (LOW PROGESTERONE due to inadequate corpus luteum). Complications (INFERTILITY with EITHER INCREASED BLEEDING OR AMENORRHEA). Dx (secretory changes but LAG behind expected date by 3 days).
• § Def: occurrence of inadequate corpus luteum function and low progesterone output, with irregular ovulatory cycle, often clinically manifested as INFERTILITY with either increased bleeding or amenorrhea (Robbins).
• § Mazur has good talk p26
• § Biopsy shows secretory endometrium but LAGS behind expected date by 3 days (Steinberg, Outlines, Robbins)

 

ARIAS-STELLA REACTION

• § Cause:
• § pregnancy-related change
• § Micro:
• § glands enlarged, abundant clear or eosinophilic cytoplasm, marked nuclear changes, rare mitoses; decidualized stroma
• § DD
• § clear cell carcinoma (post-menopausal,$ mitoses, no decidual reaction)

ENDOMETRITIS

Causes

• § TB, Sarcoid, Coccidimyocosis, actinomyces, herpes, CMV, Shisto, fungus, foreign body, xanthogranulomatous
• § Cause:
• § retained POC, instrumentation, abortion
• § organisms: gonorrhea, chlamydia, actinomyces
• § Micro:
• § must microabcess formation (nφ in glds and stroma)
• § Micro:
• § plasma cells (often seen w/ spindled stroma) + lφ follicles (can be seen in normal)
• § Cause:
• § secondary to pyometra or hematometra
• § Micro:
• § foamy mφ or hemosiderin-laden mφ
• § Path:
• § tubo-ovarian abcess, chronic endometritis, Actinomyces often present
• § Cause:
• § Fungi, pinworm, Shisto, foreign bodies, sarcoid, TB
• § Clear cell metaplasia: tall cells, apical nuclei, clear cytoplasm; no atypia

ACUTE ENDOMETRITIS

CHRONIC ENDOMETRITIS

XANTHOGRANULOMATOUS ENDOMETRITIS:

IUD:

GRANULOMATOUS ENDOMETRITIS:

ENDOMETRIAL METAPLASIA

DD

• Ø Clear cell adenocarcinoma, Arias-Stella chg.)
• § Tubal (ciliated cell) metaplasia
  • Ø Ciliated cells, seen with ↑ estrogen
• § Eosinophilic metaplasia:  like tubal but no cilia
• § Mucinous metaplasia: :endocervical mucosa or intestinal with goblet cells)
  • Ø DD
    • § mucinous adenoca
• § Papillary synctial metaplasia: papillary projections of benign epithelial cells, may be degenerative change; no fv cores[3]
• § Squamous metaplasia
  • Ø Etiology:
    • § exogenous hormones, PCOD, foreign-body, chemical irritants, endometritis
    • Ø DD
      • § well differentiated endometrial adenocarcinoma with squamous metaplasia
• § STROMAL METAPLASIA
  • Ø Formation of smooth muscle, cartilage, bone
  • Ø DD
    • § retained fetal parts

 

ADENOMYOSIS

Dx (STROMA +/-glands at >1LPF). PAIN and increased bleeding. NOT hormone-responsive (vs functional in endometriosis). In REPRODUCTIVE except under TAMOXIFEN. Ddx invasive adenocarcinoma (no stroma), ESS (no glands).

• § Caveat: not hormone-responsive because made of basal layer of endometrium (vs functional for endometriosis) (Rosai)
• § Complications: uterine rupture!!!
• § Def: downgrowth of endometrial glands and stroma in myometrium (Robbins).
• § Demo: reproductive, rare in postmenopausal except under tamoxifen (Rosai)
• § RF?
• § Incidence: 1/5 of uteri (Robbins).
• § Ssx: menorrhagia, dysmenorrhea, dyspareunia, pelvic pain especially during premenstrual period (Robbins)

Gross

• § Globular, symmetrical and spongy (cysts) (Robbins).

Micro

• § Endometrial STROMA +/- glands at >1 LPF (5mm for 4x) or >2-3mm deep from endomyometrial junction (Childs, Rosai, Robbins). Usually proliferative epithelium (Rosai). SM hypertrophy around glands

DD

• § Endometriosis (Rosai)
• § ESS (Rosai): larger foci with no glands
• § ESN?: how to ddx???
• § Invasive adenocarcinoma (Rosai): no stroma

EPITHELIAL TUMORS[4]

Variants (WHO)

• § Endometrioid
  • Ø With squamous differentiation
  • Ø Villoglandular
  • Ø Secretory
  • Ø Ciliated cell
• § Mucinous
• § Serous
• § Clear cell
• § Mixed
• § SCC
• § TCC
• § Small cell
• § Undifferentiated
• § Endometrial HP
  • Ø Simple
  • Ø Complex
  • Ø Simple with atypia
  • Ø Complex with atypia
• § Endometrial polyp
• § Tamoxifen-related lesions

 

ENDOMETRIAL CARCINOMA

***Risk factors for endometrial ca?

• § -↑estrogen use, tamoxifen

-obese, DM, HTN, PCOD,

-functioning granulosa cell and thecoma tumours

-gonadal dysgenesis (Turner syndrome)

 

Genetics:

• § Endometrioid: mutations and MSI in PTEN, k-ras and b-catenin
• § Non-endometrioid: mutations in p53
• § Invasion:
• § Muscular invasion (deep or assoc/ granulation tissue) vs. 1) Expansion of endometrial-myometrial junction 2) Adenomyosis

Treatment

• § Endometrioid:TAH-BSO
• § {+/- surgical staging (pelvic and para-aortic nodes & peritoneal cytology)}
• § Serous: TAH-BSO+ surgical staging + adjuvant therapy

 

1. ENDOMETRIOID CARCINOMA

Variants

• § Villoglandular
• § Adenoma malignum
• § Secretory (subnuclear vacuolization, resembles POD2)
• § Ciliated (cilia, ddx is cilia cell metaplasia)

Micro

• § Thin, long, delicate fronds with pseudostratified endometrium (villoglandular)
• § Low grade nuclei

DD

• § Serous papillary endometrial adenoca (p53- in villoglandular endometrial adenoca)
• § Endometrial vs. cervical endometrioid adenoca:
• § Use the IHC panel (vim +, CEA -, ER +, HPV -, p16 -)

 

-With squamous differentiation

-Villoglandular

-Secretory

-Ciliated cell

 

2 . MUCINOUS CARCINOMA

Micro

• § Endocervical-type lining of glands w/ pseudostratification
• § Need >50% differentiation

IHC

• § Mucicarmine, Alcian blue

Grading

• § Same as endometrial

 

3. SEROUS CARCINOMA

Micro

• § Short papillae with FV cores, slit like glands
• § HG nuclei, mitoses, nucleoli?
• § Cuboidal lining[5]
• § Psammoma bodies

Spread

• § Peritoneum[6]

IHC

• § P53+ in >70% of nuclei (DD of endometrial)

 

4. CLEAR CELL CARCINOMA

• § Micro: “STP” pattern
• § -high grade nuclei
• § -hobnail cells
• § SS:-PAS+ glycogen in cytoplasm

5. MIXED

6. SCC

7. TCC

8. SMALL CELL

9. UNDIFFERENTIATED

10. ENDOMETRIAL HYPERPLASIA

Different types, micro, risk of progression to ca:

• § Simple HP: ↑gl: stroma, glds random orientation, usu round to cystically dilated with sl. irreg contours, -lined by prol. endometrium (1%)
• § Complex HP: markedly crowded glds, irreg and serrated outlines w/ outpouching, thin rim or endometrial stroma surrounds glds (3%)
• § Simple HP w/ atypia (8%)
• § Complex HP w/ atypia (29%)
• § Features of endometrial ca:
• § Glands back to back
• § Desmoplastic rxn
• § endometrial stromal foam cells (seen in HP too)

Micro

• § Atypia (2 irregular, 3 increases)[7]

Genetics (PTEN loss marks transition from HP to ATYPIA/cancer; PTEN normally blocks Akt/PI3K anti-apoptotic pathway). Etio (anything related to estrogen hyperstimulation). RF (menopause, PCOD, granulosa cell tumor, stromal hyperplasia, prolonged HRT). RR (0-1 in simple, 3 in complex, 9 in simple atypia, 27 in complex atypia) (x3 each time). Dx (increased GS ratio in ANY type of HP, irregular and dilated glands, mitoses NOT required, amount of stroma determines simple vs complex). Define gland complexity (BRANCHING, BUDDING, CRIBRIFORMING). Ddx anovulation (no increased GS ratio)

• § Caveat: progestin treatment can minimize mitoses and induce secretory change and lead to UNDERDIAGNOSISdiagnosis of carcinoma (Childs).
• § Def: noninvasive proliferation of endometrium resulting in glands with irregular shapes and variable size from sustained unopposed estrogen stimulation (Mazur)
• § Demo: perimenopausal (Mazur)
• § Genetics: loss/inactivation of PTEN (key step) makes endometrial cells more sensitive to estrogen (Robbins). PTEN loss in 60% of ATYPICAL hyperplasia and 50-80% of endometrial carcinomas (Robbins). PTEN marks transition from non-atypical to ATYPICAL hyperlasia (Robbins)
  • Ø PTEN mainly blocks Akt/PI3K pathway (important pathway in anti-apoptosis); unopposed estrogen normally increase native endometrial gland PTEN expression, which is constantly present in proliferative phase but absent in secretory phase (Robbins)
• § Etio: menopause, estrogen-producing tumors, HRT, PCOS, nulliparity, DM, HTN (related to obesity), obesity, ovarian stromal hyperplasia, granulosa cell tumors, ANOVULATION (Robbins, Osler, Mazur)
• § Ssx: meno-metrorrhagia (Robbins)

Gross

• § PAPILLARY fronds (Robbins)

Micro

• § All HP has INCREASED G/S, irregularity in gland shapes and size (Mazur). Same cytology as proliferative epithelium but mitoses NOT required for diagnosis (Mazur).
• § Caveat: remember BRANCHING and BUDDING are features of HP or cancer because normal endometrial glands are UNBRANCHED (Steinberg)
• § Caveat: needs GS ratio >2:1 (normal being 1:1) to call hyperplasia instead of disordered proliferative endometrium) (Steinberg, Osler)
• § Caveat: villoglandular resembling colonic adenoma permitted especially when exophytic (Steinberg)
• § Architecture: CYSTIC DILATION (simple hyperplasia) vs BUDDING/BRANCHING (complex hyperplasia) (Steinberg). Amount of stroma separating glands determines simple vs complex hyperplasia (Mazur)
• § Caveat: various types of metaplasia including SQUAMOUS, tubal, mucinous (Robbins)
• § Caveat: careful with diagnosis of various hyperplasias because huge difference in treatments (progestin to hysterectomy!!!) (Robbins)

Variants

• § Variants (WHO): atypia more important than gland complexity (Mazur, WHO, ASCP)

DD

• § Mimickers: exogenous hormones, biopsy artifacts, menstruation, late secretory phase can create false glandular crowding with increased G/S ratio (Childs).

 

-SIMPLE HYPERPLASIA

Dx (increased GS ratio, cystically dilation with mildly irregular glands, lined by proliferative epithelium).

• § Aka cystic or mild hyperplasia (Robbins)
• § Defined as architectural glandular changes with cystic glandular dilatation (Robbins). Synomymous with anovulation (Robbins)
• § Evolution: often regress and become CYSTIC atrophy (Robbins)
• § Prognosis: 5% risk if no atypical; 7.5% if atypical.

Micro

• § GS ratio >2:1 (definition of hyperplasia), +/-cystic dilation (irregularity in shapes and size) (Mazur, Steinberg, SenGupta). Proliferative epithelium (at least pseudostratified, CIGAR to OVAL nuclei, smooth nuclei, uniform chromatin, no nucleoli, +/- mitoses in glands and stroma) (Steinberg, Mazur). Diffuse, small spiral arteriole-like BV (Steinberg). Squamous and tubal metaplasias common (Robbins, Mazur). Not as many mitoses as in proliferative endometrium (Robbins). Often DIFFUSE (vs focal for complex hyperplasia).
• § Caveat: too much estrogen will cause cystic dilation of endometrial glands (Mutter)
• § Patterns: haphazard gland distribution (Mazur).

DD

• § Polyp: thick-walled BV, dense stroma, covered on 3 surfaces by epithelium, polypoid configuration
• § Cystic atrophy: simple cuboidal, dense fibrotic stroma
• § Disordered proliferative endometrium:
• § Compression artifacts:
• § Chronic endometritis:

 

-COMPLEX HYPERPLASIA

Dx (gland complexity such as BUDDING/BRANCHING, HIGHER GS up to nearly back-to-back glands but NO 3 C’s or myoinvasion, FOCAL)

• § Aka adenomatous hyperplasia (Robbins)
• § Prognosis: 15% risk if no atypical, 50% if atypical

Micro

• § Same (including cytology) as simple hyperplasia except HIGHER GS ratio and more glandular complexity (branching and budding) (Mazur, Osler). No desmoplasia or back-to-back (Steinberg, Robbins, Crum). Usually FOCAL (Osler).
• § Patterns (hints): nearly back-to-back with some branching/budding and intervening stroma (Fletcher, Mazur).
• § Invasion: SOLID or CRIBRIFORMING or VILLOGLANDULAR or MYOINVASION (Fletcher, Mazur)

 

-ATYPICAL HYPERPLASIA

Same as EIN but NOT same as EIC (precursor for serous carcinoma). IDEALLY treated with hysterectomy because high recurrence but progresterone acceptable for young. PTEN loss. 25% progress. Atypia (LARGE ROUNDED vesicular IRREGULAR coarse nuclei with NUCLEOLI, EOSINOPHILIC cytoplasm, TRUE stratification, 2 cell populations). Invasion (3 C’s=confluent, continuous, cribriform, myoinvasion) and must >2.5mm. Ddx APA (SM, premenopausal, LUS), carcinoma (3 C’s).

• § Aka EIN (NOT same as EIC, which is precursor to serous carcinoma), adenomatous HP with atypia (WHO, Mazur, Robbins).
• § Genetics: PTEN loss (Robbins)
  • Ø Premalignant neoplasms are already malignant (cancer) because monoclonal (Mutter)
• § Nature: PRECURSOR to adenocarcinoma vs nonatypical hyperplasia that is largely self-limited (Mazur)
• § Treatment: hysterectomy IDEALLY (because of high recurrence and persistence) but progestin for young patients wanting to keep fertility with close follow-up (Robbins, Crum)

Complications

• § Complications: 30% of EIN progress to carcinoma (Mazur).
• § Even with progesterone treatment, 25% progress to carcinoma, 50% PERSIST and 25% recur (Robbins).

Micro

• § Atypia: ROUNDED (due to loss of polarity or perpendicularity), vesicular (due to chromatin clumping along nuclear membrane), TRUE STRATIFICATION (vs pseudostratification in normal proliferative endometrium), EOSINOPHILIC abundant cytoplasm (not always), PROMINENT NUCLEOLI, SECOND population (Mazur, Rosai, Childs, ASCP, Steinberg).
• § +/-squamous metaplasia (Mazur).
• § Caveat: cut-off between atypical hyperplasia and WDCA ill-defined (Steinberg)
• § Caveat: important to ddx complex hyperplasia with atypia (or EIN) from carcinoma because former not requires surgical staging (Mutter)
• § Caveat: sometimes LG architecture+HG nuclei (nuclear pleomorphism noticeable at low power)=cancer (Steinberg). IG nuclei+HG architecture=cancer (Steinberg). IG nuclei+IG architecture=borderline (Steinberg).
• § Low-grade architecture: large back-to-back glands (aka macroglands, Steinbrg). Intermediate-grade: back-to-back with budding (aka labyrinth-like, Steinberg). High-grade: exophytic villoglandular or extensive stratification or crifibriforming or solid (Steinberg)
• § Invasion: 3 C’s (confluent/solid, continuous, cribriform), mazelike, villoglandular, mosaic (threadlike dividing stroma between back-to-back glands), myoinvasion (Crum, Childs, Farmer, Mutter, Fletcher, Mazur). Childs wants to have >2.5mm before calling carcinoma (Childs).

IHC

• § P53-: helpful to ddx from serous carcinoma (Crum)

DD

• § APA: premenopausal, in LUS or endocervix, SM in stroma. Morules present in both
• § Carcinoma: 3 C’s, myoinvasion, >2.5mm
• § Tubal and eosinophilic metaplasia: confounding at lower power due to eosinophilia but no atypia

 

-EIN (Mutter’s talk)

Treatment (EIN in polyp treated same way as EIN elsewhere). Dx (atypia NOT required but always 2 populations, clear cut transition, G>S, >1mm, exclude mimicker, exclude cancer, CAN be diffuse)

• § Caveat: use LOW power to spot EIN; do not use high power because EIN sometimes do not show any ATYPIA (you must use two cell population rule) (Mutter). Remember EIN is a LOW power diagnosis (Mutter)
• § Complications: RR=45x for carcinoma (Mutter)
• § http://www.endometrium.org
• § Outcome: about 1/3 of EIN will develop concurrent carcinoma within 1 year (Mutter)
• § Treatment: EIN in polyp is treated same way as EIN elsewhere in endometrium because impossible to know stalk on biopsy (Mutter). Choice between hysterectomy vs progestin is made by clinicians (Mutter)
• § Cystic changes following too much estrogen
• § Carcinoma needs staging but EIN not (Mutter)
• § Premalignant already (because clonal) (Mutter)
• § EIN must meet all 5/5 criteria (Mutter)
• § Use low power to spot EIN
• § PTEN+ in EIN not used clinically
• § EIN is a low power diagnosis

Gross

• § NOT visible grossly (Mutter)

Micro

• § Glands vs stromal area very clear cut and objective (branching and budding used to call complex hyperplasia often subjective and different from one Pathologist to another) (Mutter). When calculating gland areas, must avoid large benign cysts (Mutter). Usually at low power, can see a very neat lesion interface (Mutter).
• § Caveat: can have squamous metaplasia (NOT hormonally responsive; therefore does not respond to progestin and may persist and bounce around in endmetrium with menses) (Mutter). Important lesson is that presence of morules is a FLAG to look carefully for EIN or carcinoma because they indicate prior EIN (Mutter)
• § Caveat: EIN are clusters of INDIVIDUAL glands; once became connected, should think of carcinoma (Mutter)
• § Caveat: diagnosis of EIN must meet all 5 criteria (Mutter)
• § Caveat: EIN in polyps must compare with endometrial glands in polyp and not in functionalis (Mutter)
• § Caveat: EIN must be >=1mm to be clinically significant; measurement good on pipelle or curettage specimens but NOT on hysterectomies (Mutter).
• § Caveat: EIN usually focal but 1/5 cases diffuse; even for diffuse cases, can still see entrapped normal glands for comparison (Mutter).
• § Caveat: not all EIN’s have cytological atypia but all EIN’s are different from background endometrium (Mutter).
• § Caveat: progestin makes normal endometrium more ugly (secretory change=larger, rounder nuclei with nucleoli) but makes EIN more benign appearing (Mutter). Reason why not to rely on cytological atypia for diagnosis of EIN but better rely on concept of two distinct cell populations (Mutter)
• § Caveat: remember EIN’s not always endometrioid (can be mucinous, squamous,… except serous or clear cells) (Mutter)
• § Caveat: remember to exclude mimickers (Mutter)
• § Criteria: gland large than stroma area, 2 cell population, diameter >1mm, exclude mimickers, exclude cancer (Crum, Mutter)
• § Invasion: exclude carcinomas (different because forms a spectrum) (Mutter). Any of the following (cribriforming, papillary, folded sheets of epithelium or so-called maze) on biopsy or myoinvasion on resection specimens make it carcinoma (Mutter)

11. ENDOMETRIAL POLYPS

Typical:

• § Micro: endometrial glds +fibrotic stroma, glds out of sync with endo, lg blood vessels, often prol, can get HP, ca

Adenomyomatous

• § Micro: abundant sm. muscle in typ. endo polyp

Atypical adenomyomatous polyp

• § Micro: arch + cytologic atypia (mitoses, nuclei)
• § -squamous morules, -swirling sm. muscle
• § DD muscle invasive adenoca, adenomyosis(has endometrial stroma though)

 

12. TAMOXIFEN-RELATED LESIONS

MESENCHYMAL TUMOURS

Variants (WHO)

• § ESS
• § ESN
• § Undifferentiated endometrial sarcoma
• § LMS
  • Ø Epithelioid
  • Ø Myxoid
• § STUMP
• § LM[8][9]
  • Ø Cellular
  • Ø Atypical
  • Ø Lipoleiomyoma
  • Ø Mitotically active
  • Ø Hemorrhagic
  • Ø Epithelioid
  • Ø Myxoid
• § Adenomatoid tumor
• § PEComas

 

1. ESN

• § Gross: yellow, well circ.
• § Micro:  bland stromal cells, concentrically arranged around bv
• § -no veins, lymphatics invasion
• § Gross: yellow, well circ.
• § Micro:  low power: sharply defined tumour islands with pointy edges
• § -occasional mitoses
• § -vascular invasion
• § -arborizing vasc, hyalinized stroma
• § IHC: CD10,
• § DDx: epithelioid LM (this is CD10 – and h-cald, desmin +)

2. ESS

 

3. UNDIFF UTERINE SARCOMA

• § -no features of differentiation
• § -high grade, numerous mitoses

4. LEIOMYOMA

• § Clin: common, esp blacks
• § Gross: subserosal, intramural, submucosal
• § Micro:-NOS, cellular, epithelioid, atypical,, myxoid, lipoLM, granular cell change, hydropic degeneraton, mitotically active
• § Mitotically active: 5-10mit/10HPF no coag necrosis or cytologic atypia

Leiomyomatosis (infilatrating leiomyoma)

 

-Cellular

-Atypical

-Lipoleiomyoma

-Mitotically active

-Hemorrhagic

-Epithelioid

-Myxoid

 

5. STUMP

• § >10mit/10HPF, ? coag necrosis, some cytologic atypia
• § Older women

6. LEIOMYOSARCOMA
Clinical

Gross

• § Fleshy w/ necrotic or hemorrhagic areas

Micro: 2 of 3: “MAN”

-mitoses

-atypia

• § -coagulative necrosis -hyaline vs. tumour type necrosis (no hyaline in b/w tumour and necrosis)
• § IHC: h-CD, desmin, calponin, SMA

Prognostic factors:

• § -grade
• § -stage (depth of invasion into myometrium, cervical extension)
• § -histologic type (serous and clear cell higher grade)
• § -lymphatic and vascular invasion
• § -estrogen dependent tumours have better px

7. ADENOMATOID TUMOR

8. PECOMAS

MIXED

Variants (WHO)

• § Carcinosarcoma
• § Adenosarcoma
• § Carcinofibroma
• § Adenofibroma
• § Adenomyoma
  • Ø Atypical polypoid adenomyoma

 

1. CARCINOSARCOMA (MALIGNANT MIXED MULLERIAN TUMOURS)

Clinical

• § Post-menopausal women
• § Gross:  lg, soft polypoid
• § Micro: carcinoma + sarcoma elements
• § -sharp demarcation
• § -homologous or heterologous sarcomatous elements (sk. muscle, bone, fat, cartilage)
• § -look for x-striations
• § -thought of as “carcinomas” b/c epithelial component more invasive and metastatic
• § -lymphatic and vascular invasion
• § IHC: keratin + in epithelial and in sarcomatous component in 50% of cases
• § Prog: very aggressive

 

2. ADENOSARCOMA

• § Gross:  firm, knobby polyp
• § Micro: broad club shaped papillae lined by endometrium + stromal coree
• § 0-1 mitoses/10hpf
• § Elderly women

Clinical

Gross

• § Bulky polyp filling endometrial cavity

Micro

• § Analagous to phyllodes tumour of breast
• § Epithelial (benign) and stromal (hypercellular)
• § Glands large with periglandular stromal cuffing
• § Leaf-like projections into glandular lumina;
• § 2+ mitotic figures/10 high power fields

3. CARCINOFIBROMA

 

4. ADENOFIBROMA
Clinical

• § Older women, benign counterpart of

 

5. ADENOMYOMA

• § Gross:  polyp
• § Micro: endometrial glands in benign smooth muscle

 

5a. ATYPICAL POLYPOID ADENOMYOMA
Gross:  polyp (hard and gray)

Micro

• § Endometrial glandsà architectural atypia +/- cytological atypia
• § Benign swirling smooth muscle
• § Squamous morules

DD

• § Invasive adenoca.

Prognosis

• § Usually benign. Rare cases of recur, ca

 
 

STAGING

• § Tx-cannot be assessed
• § T0-no evid of primary tumour
• § T1a-confined to the endometrium
• § 1b-confined to inner half
• § 1c-confined to outer half
• § T2a-endocervical glands
• § T2b-endocervical stroma
• § T3-serosa, adnexa or washings
• § T4-bladder/rectum

 

DECISION POINTS

• § ▪Atypical HP or ca. →TAH (unless preg. or morbid reasons)

▪>50% myometrial inv.→ ext beam boost

▪Poorly diff ca. → ext. beam boost

▪Cervical involvement → vaginal vault boost

 

GRADING

Endometrioid and mucinous:

• § -measure % of solid growth
• § Grade 1:<5%
• § Grade 2:5-50%
• § Grade 3:>50%
• § *if nuclear grade is predominantly high grade then upgrade by 1
• § **do not include squamous metaplasia

Serous and clear cell:

• § -considered high grade

 

• § GROSSING-KEY POINTS

HYSTERECTOMY

• § open along lateral sides
• § open tumour if large to allow fixation
• § make parallel sections 1cm apart from EC canal to superior aspect
• § if cervical tumour suspected, ampuate cervix and process as a cone biopsy
• § ink margins of resection including vaginal margin
• § examine: shape, serosa, myometrium, endometrium, cerivx, myomas
• § Sections:
• § ▪non-tumour: anterior and posterior: endometrium, myometrium (full thickness), LUS, cervix;
• § ▪myomas: at least 1 section, submit more if fleshy; polyps submit in toto;
• § ▪tumour (1section/cm/minimum 3 sections);
• § different appearing regions? deepest invasion
• § ▪each ovary (cortex, hilar region)
• § ▪each fallopian tube
• § ▪lymph nodes

 

SYNOPTIC REPORT

• § Tumor size and location
• § Histologic type
• § Histologic grade
• § Depth of invasion (uterine wall thickness, maximum depth of myoinvasion, measured from endomyometrial junction)
• § Angiolymphatic invasion
• § Preserve of cervical involvement
• § Features of uninvolved uterus (hyperplasia, metaplasia)
• § Margins
• § Nodal involvement (# positive nodes, # total lymph nodes)

FALLOPIAN TUBE

histology

• § Cells: secretory, peg cells, ciliated
• § -Nφ present at menstruation
• § -muscle layers: ICOL

SALPINGITIS

Causes

• § Gonorrhea, chlamydia, TB, coliform organisms, Actinomyces (assoc/ IUD),

Types of inflammation

• § Acute inflammation with
  • Ø Pyosalpinx
  • Ø Hematosalpinx
  • Ø Tuboovarian abcessà if infx abscess spread to ovary
  • Ø Granulomatous inflammationà Actinomyces, TB, Schistosomia, pinworm
• § Xanthogranulomatous inflm

Micro

• § Gland like spaces, reactive HP, heavy inflm infiltrateà may simulate carcinoma
• § Often get cystic change
• § Surface epithelial tumours
• § Adenomatoid tumour
• § Cysts from mesonephric and Mullerian derivatives

TUMORS SEEN IN FT

 

GROSSING-KEY POINTS

• § If BRCA1/2 risk or if done for prophylaxis → submit in toto and submit fibriae on edge

OVARY

histology

• § -simple pseudostratified layer
• § -epthelial inclusion glands→cysts if >1cm

-may be ciliated, may have psammoma bodies

-called endosalpingiosis elsewhere (omentum, peritoneum

-can be lined by other Mullerian cell types (endometrioid, mucinous)

-can have urothelial differentiation (Walthard rest (of transitional epithelium)

 

THE DEVELOPING FOLLICLE

Primordial follicle:

• § oocyte + granulosa cell (1 layer)

Primitive follicle

• § oocyte + granulosa cell (1 layer)

→enlarged oocyte and polygonal gr. cells

Secondary/preantral follicle

• § oocyte + granulosa cell (stratified layers) + theca interna/externa

Antral follicle

• § oocyte + granulosa cell (stratified layers) + theca interna/externa → with fluid filled antrum

 

INFLAMMATORY

TUBO-OVARIAN ABSCESS

• § Etilology: Gonorrhea, Chlamydia, Mycoplasma, Aerobes
• § If unilateral r/o appedicitis, perf diverticulum, IBD, ca with fistula, IUD with Actinomyces

 

GRANULMATOUS INFLM

• § TB, fungal, pinworm (Enterobius vermicularis), shisto,actinomyces w/ IUD, Crohn’s disease (extension from bowel), foreign materials (talc, keratin from ruptured teratoma), post-surgical, xanthogranulomatous

 

ENDOMETRIOSIS

• § Gross: blueberry spots → chocolate cyst
• § Micro: endometrial glds, stroma, blood (hemosiderin, fresh)

 

CYSTS

Benign cysts

Surface inclusion cysts

• § -epithelial or mesothelial (invagination from serosa)
• § -flattened columnar epithelium

Follicular cysts

• § -lined by granulosa layer and thecal cells (often luteinized)

Luteinized follicular cysts

• § -multiple, assoc with hydatitiform moles

Polycystic ovaries

• § -follicular cysts lined by prominent luteinized theca layer and dense fibrous capsule

Endometriotic cyst

Corpus luteum cysts

• § -occur at end of menstrual cycle or during pregnancy (usu. bigger)
• § 3cm, cyst composed of luteinized granulosa and theca cell layers
• § -fluid content bloody

Developmental cysts

-from Wolfian and Mullerian remnants

Epidermoid cysts

Epithelial tumours

• § -bordeline epithelial tumors, cystadenocarcinomas

 

SURFACE EPITHELIAL TUMORS

Variants (WHO)

• § Serous
  • Ø Malignant
    • § Adenocarcinoma
    • § Surface papillary adenocarcinoma
    • § Adenocarcinofibroma
    • Ø Borderline
      • § Papillary cystic tumor
      • § Surface papillary tumor
      • § Adenofibroma, cystadenofibroma
      • Ø Benign
        • § Cystadenoma
        • § Papillary cystadenoma
        • § Surface papilloma
        • § Adenofibroma, cystadenofibroma
• § Mucinous
  • Ø Malignant
  • Ø Borderline
    • § Intestinal
    • § Endocervical
    • Ø Benign
    • Ø With mural nodules
    • Ø With pseudomyxoma peritonei
• § Endometrioid
  • Ø Malignant
    • § MMMT
    • § Adenosarcoma
    • § ESS
    • § Undifferentiated ovarian sarcoma
    • Ø Borderline
    • Ø Benign
• § Clear cell
  • Ø Malignatn
  • Ø Borderline
  • Ø Benign
• § Transitional
  • Ø Malignant
    • § TCC
    • § Malignant Brenner
    • Ø Borderline
    • Ø Benign
• § Squamous
  • Ø SCC
  • Ø Epidermoid cyst
• § Miexed
• § Undifferentiated
• § Micro: ciliated/non-ciliated columnar cells
• § -single layer (no mucin)
• § -note: serous adenofibroma has broad shaped papillae
• § Micro: ↑ stratification, ↑ atypia, free floating buds

1. SEROUS TUMORS

BENIGN (CYSTADENOMA)

BORDERLINE

-no stromal invasion

-can have overlying mesothelial HP

-microvasion- clusters of tumour cells in stroma < 10mm²

Implants:

Non-invasive:

1. epithelial: non-invasive papillary epithelial cells, stroma normal, “stuck on” or “b/w lobules of fat”

2. desmoplastic: tumor nodules have more abundant cytoplasm, inflm! and granulation tissue

Invasive

-infiltrative pattern of growth into fat (some desmoplasia), irreg margins

-have retraction artifact

DD endosalpingeosis→difficult to sort out.

MALIGNANT (CYSTADENOCARCINOMA)

• § Micro: high grade, obvious stromal invasion
• § -branching papillae with no stromal support
• § -slit like spaces
• § -psammoma bodies often seen
• § IHC: WT-1,
• § Ddx from mucinous CEA- and CK7+/CK20-
• § Micropapillary serous ca: filigree pattern of branching, no stromal invasion

 

2. MUCINOUS TUMORS

BENIGN (CYSTADENOMA)

• § Micro:endocervical-type lining, minimal stratificaton and minimal atypia
• § -can arise in a dermoid cyst
• § -90% of mucinous borderline tumours
• § Micro: complex papillae, mild atypia, nuclear stratification, no stromal invasion

BORDERLINE

ENDOCERVICAL-TYPE

i.with microinvasion or with microinvasive ca.

• § -single cells, glds, clusters, cribriform nests <10mm²

ii. with pelvic or abdo implants

INTESTINAL-TYPE

• § -10%
• § Micro: intestinal type epithelium w/ goblet cells and Paneth cells
• § -stratification, mild to mod atypia, no stromal inv.

i. with IEC (intraepthelial carcinoma)

• § -grade 3 nuclei

ii.with microinvasion or with microinvasive ca.

• § -single cells, glds, clusters, cribriform nests <10mm²

MALIGNANT (CYSTADENOCACINOMA)

Micro: ↑atypia, ↑stratification

i. Expansile type→ no destructive stromal invasion but back –back complex malignant glands &  > 10mm²

ii. Infilatrative type→ obvious stromal invasion

• § IHC: CEA+ and CK7+/CK20+(50%)
• § Other variants:
  Mucinous cystic tumour w/ mural nodules
• § Mucinous cystic tumour w/ pseudomyxoma peritonei

 

3. ENDOMETRIOID TUMORS

• § Gross: solid/cystic with hemorrhagic contents
• § Micro:-like endometrial cyst but no endometrial stroma or hemorrhage.
• § -cytologically malignant endometrioid cells without obvious invasion
• § Microinvasion: nests <10mm²
• § Assoc/: 50% squamous diff., 20% endometriosis, 20% assoc/ concurrent uterine endometrial ca.

BENIGN

BORDERLINE

MALIGNANT

How do determine the primary with 2 endometrial tumours in ovary and uterus?

• § Pre-existing lesion: endometrial HP?
• § Size
• § Angiolymphatic invasion
• § Grade
• § Surface involvement of ovary
• § Bilateral favors endometrium primary

Other tumours:

• § -adenoca, carcinosa, adenosa, ESS, undiff. ovarian sa

 

4. CLEAR CELL TUMOURS

• § Micro: STP pattern, eosinophilic hyaline globules (PAS+), hobnail pattern, dense hyalinized cores in papillae

Ddx of micro:

• § -dysgerminoma
• § -met. RCC
• § -YST tumour
• § -Krukenberg (signet ring)
• § -steroid cell tumour
• § -Arias stella change

 

5. TRANSITIONAL CELL TUMOURS

BENIGN: BRENNER TUMOUR

• § Gross: solid white whorled tumor mass <2cm
• § Micro: sharply demarcated nests of round/polygonal cells with oval-shaped nuclei with grooves, hyalinization in nests, dystrophic calc.
• § -endocervical-lined microcysts +/- papillary TCC
• § TCC only
• § Brenner (benign/bordeline) tumour + TCC

BORDERLINE BRENNER TUMOUR

MALIGNANT TCC

MALIGNANT BRENNER TUMOUR

 

6. SQUAMOUS CELL TUMOURS

• § -epidermoid cyst
• § -SCC

7. MIXED EPITHELIAL TUMOURS

8. UNDIFFERENTIATED CARCINOMA

 

SEX CORD-STROMAL TUMOURS

Variants (WHO)

• § Granulosa cell tumors
  • Ø Adult
  • Ø Juvenile
• § Thecoma-fibroma
  • Ø Thecoma
  • Ø Fibroma
  • Ø Cellular fibroma
  • Ø Fibrosarcoma
  • Ø Sclerosing stromal tumor
  • Ø Signet-ring stromal tumor
  • Ø Fibrothecoma
• § Sertoli cell tumors
  • Ø SLCT (androblastoma)
  • Ø Sertoli cell
• § Mixed
  • Ø Sex cord tumor with annular tubules
  • Ø Gynandroblastoma
• § Steroid cell tumors
  • Ø Stormal luteoma
  • Ø Leydig cell tumor group
    • § Hilus cell tumor
    • § Leydig cell tumors: non-hilar or not
• § Malignant
• § Clin: hyperestrogenic state (precocious puberty or meterrohagia)
• § Micro: macrofollicular type pattern with marked atypia and mitoses, cells have abundant cytoplasm (no grooves)
• § Clin: child bearing age, hyperestrogenic state (meterrohagia)
• § Gross: solid/cystic yellow/white, can have hemorrhage
• § Micro: patterns: microfollicular, Call-Exner bodies, macrofollicualr, diffuse, Moire silk, insular
• § cells: angled nuclei with grooves and nucleoli, scant cytoplasm
• § + thecomatous or fibromatous component
• § IHC: inhibin, calretinin, vim, melanA,

1. GRANULOSA CELL TUMOURS:

JUVENILE

ADULT

 

2. FIBROMA-THECOMAS

• § Clin: post-menopausal women
• § Meigs’ syndrome: right pleural effusion, ascites, ovarian fibroma
• § Gross: solid yellow/white
• § Micro: oval-spindle cells w/ lipid-rich cytoplasm, bands of dense collagen
• § SS: oil red O, reticulin around individual cells
• § Micro: eosinophilic, abundant cytoplasm, central nucleus with nucleoli
• § Micro: bland spindle cells, no atypia, no mitoses, storiform
• § Micro: cellular, no sign. atypia, <3mit/10HPF
• § Micro: >4mi/10HPF, atypia and cellular
• § *Can have sex-cord elements

2a. THECOMA:

LUTENIZED THECOMA:

2b. FIBROMA:

2c. CELLULAR FIBROMA:

2d. FIBROSARCOMA:

2f. SCLEROSING STROMAL TUMOUR

2h. FIBROMA-THECOMA

 

3. SERTOLI-LEYDIG CELL TUMOURS:

• § Clin: more common in young women

3a. SERTOLI-LEYDIG CELL TUMOUR

SERTOLI CELL TUMOUR (SMALL HOLLOW TUBULES OR CORDS→TRY TO RECAPITUATE SEMINIFEROUS TUBULES_

LEYDIG CELL TUMOUR (EOSINOPHILIC CYTOPLASM W. CRYSTALS OF RENKE)

HILUS CELL TUMOUR (EOSINOPHILIC CYTOPLASM)

STEROID CELL TUMOUR (LIPID LADEN CELLS)

GYNANDROBLASTOMA (GRANULOSA+ SERTOLI CELLS)

 

GERM CELL TUMORS[10]

Variants (WHO)

• § Dysgerminoma
• § YST
• § EC
  • Ø Polyembryoma
• § Teratoma
  • Ø Biphasic or triphasic
    • § Immature
    • § Mature
      • Solid
      • Cystic (dermoid cyst)
      • Fetiform
      • Ø Monodermal
        • § Struma ovarii
        • § Carcinoid[11]
          • Insular
          • Trabecular
          • Mucinous (goblet)
          • Strumal carcinoid
          • Mixed
          • § Neuroectodermal
            • Ependymoma
            • PNET
            • Medulloepithelioma
            • GBM
            • § SCC
            • § Adenocarcinoma
            • § Melanoma
            • § Sarcoma
            • § Sebaceous carcinoma

 

BIPHASIC OR TRIPHASIC TERATOMA

MATURE TERATOMA

• § Gross: solid, cystic, Rokitansky’s protruberance
• § Micro: 3 germ cell layers
• § -immature germ cells (neural, chondroid)
• § -grade <1LPF/slide 1-3LPF/slide >3LPF/slide
• § Clin: carcinoid syndrome
• § Gross: solid, tan
• § Types: trabecular, insular, mucinous (similar to appx goblet cell carcinoid), struma carcinoid (thyroid + carcinoid)
• § -usu unilateral, if bilateral think mets

IMMATURE TERATOMA

MONODERMAL TERATOMAS:

STRUMA OVARII: >90% THYROID, MICRO/MACROFOLLICULAR PATTERN, TTF-1 +→MALIGNANT CHANGE TO PTC (RARE)

CARCINOIDS

NEUROECTODERMAL TUMOURS

Types:

• § well differentiated→ ependymoma

2. poorly diff→ PNET

3. anaplastic→GBM

MALIGNANT TRANSFORMATION: SCC, ADENOCA MOST COMMON

DYSGERMINOMA

• § -female counterpart of seminoma
• § Clin: 40 years, mass, pain, ↑serum b-hCG,
• § Gross:solid gray (rare hemorrhage and necrosis)
• § Micro:-fibrous bands with lymphocytes (also mingle with seminoma cells)
• § -sheets of polygonal cells with clear→eos. cyto

-central nuclei with 1-2 nucleoli

-granulomatous reaction

IHC/SS

-PAS (glycogen)

-c-kit

-PLAP

-synctiotroblast-like cells→bhCG +

Prog: excellent treat with oophorectomy

Variants:

-germinoma with trophoblast giant cells

-germinoma with yolk sac elements

-germinoma with early carcinomatous differentiation (>30mitoses/10HPF)

EMBRYONAL CA

Clin: 30yrs,

Gross: large, friable, foci hemorrhagic and necrotic, firm and gray

Micro:

-usu mixed

-STP pattern

-ill-defined cell borders

-atypical cells, large nuclei, lg. nucleoli

-nuclear overlapping

-coagulative necrosis

-mitoses

++vascular invasion

IHC: CD30, CK

POLYEMBRYOMA (EMBYRONAL CARCINOMA WITH EMBRYOID BODIES)

 

YOLK SAC TUMOUR

• § Clin:  ↑serum AFP most
• § Gross:  large, cystic/solid  +/- hemorrhage, necrosis

Micro:

Name 5 variants of yolk sac tumours

-endodermal sinus pattern (Schiller-Duval bodies), -microcystic (reticular)

• § -others: hepatoid, polyvesicular vitelline, solid, glandular
• § -hyaline globules (DPAS, AFP, AAT+) (outside cells)

IHC/SS

-AFP diffuse!, CK

 

CHORIOCARCINOMA

• § -can develop in 3 ways:
• § metastatic to ovary
• § from an ovarian pregnancy (gestational type)
• § from germ cell neoplasm (non-gestational type)
• § Gross: hemorrhagic and necrotic
• § Micro: mononuclear and multinuclear synctial cells with hemorrhage and necrosis
• § IHC: hCG

 

GONADOBLASTOMA

• § -dysgerminoma (germ cell) + Sertoli/granulosa cells(sex-cord)

TUMORS OF RETE OVARII

Variants (WHO)

• § Adenoma
• § Adenocarcinoma
• § Cystadeoma
• § Cystadenofibroma

 

TUMOUR LIKE CONDITIONS

• § Luteoma of pregnancy
• § Stroma hyperthecosis (bilateral, estrogenic)
• § Stromal HP
• § Fibromatosis
• § Massive ovarian edema (stromal edema +dilated follicles, secondary to hCG)

 

LYMPHOMA/LEUKEMIA/PLASMACYTOMA

 

GRADING

• § For all tumours, except endometrioid and mucinous (see Uterus section)
• § Pattern
• § glandular
• § papillary
• § solid
• § Nuclear
• § variation in size <2:1
• § variation in size 2-4
• § variation in size >4:1
• § Mitoses
• § <10 mitoses
• § 10-24 mitoses
• § >25 mitoses

 

• § Grade 1= 3,4,5 (well-differentiated)
• § Grade 2 = 6,7 (moderately-differentiated)
• § Grade 3 = 8,9 (poorly-differentiated)

 
STAGING

	a	b	c
T1	§ Single ovary § Both ovaries § ruptured capsule, surface, + cells in wash/ascites
T2	Ovary(ies) + Pelvic extension
	§ uterus or tube § other pelvic tissues § pelvic extn + cells in wash/ascites
T3	§ microscopic peritoneal mets § macroscopic peritoneal mets <2cm § macroscopic peritoneal mets <2cm OR reg. nodes

 

GROSSING-KEY POINTS

• § Ink outer surface over irregular areas
• § Open all cysts
• § If suspicion of malignancy submit 1section.1cm of cyst
• § Describe cyst and contents

 

DECISION POINTS

• § Benign tumourà unilateral BSO
• § Borderline tumourà BSO only if young, otherwise TAH
• § Carcinomaà TAH/BSO + omentectomy + pelvic lymphadenopathy + washings/ascites collection + peritoneal biopsies
• § Fetal RBC from 6wks to 12wks
• § Umbilical BV
  • Ø Artery: no internal elastic lamina, 2 muscular layers
  • Ø Vein: only internal elastic lamina?, 1 muscular layer
• § Villi=outer ST[12], inner CT[13], Hofbauer cells
• § -HTN, edema, proteinuria, coagulation abN, DIC
• § -Eclampsia if convulsion and hyperreflexia
• § -HELLP

PLACENTA

NORMAL

TOXEMIA OF PREGNANCY (PREECLAMPSIA AND ECLAMPSIA)

Pathology:

Placenta

• § -infarct
• § -retroplacental hematoma
• § -villous ischemia (synctial knots, thick trophoblast bm

Uterus

• § “atherosis”:
• § -fibrinoid necrosis in uterine vessels
• § -foamy macrophages in media

Fetus

• § -weight <10^th percentile for GA

Liver

• § -mildly abnormal liver enzymes but severe coagulopathy
• § -fibrin thrombi in sinusoidsà hemorrhage into Disse spaceà periportal coagulative necrosisà hematoma

Kidney

• § -subendothelial fibrin deposition
• § -endothelial cell swelling
• § -mesangial hyperplasia

Brain

• § -microscopic hemorrhages and small vessel thromboses

 

 

AMNION NODOSUM

• § -secondary to oligohydramnios
• § -small nodules proteinaceous material with entrapped squames

 

CHORANGIOMA

• § -placental hemangioma

 

TYPES OF ABNORMAL PLACENTATION

• § Placenta accreta (villi adhere to myometrium-no intervening layer of decidua)
• § Placenta increta (villi in between myometrium)
• § Placenta percreta (villi through the entire thickness of the myometrium)

 

TYPES OF CORD INSERTION

• § Central
• § Eccentric
• § Velamentous
• § -membrane insertion
• § Circummarginate
• § -insertion at edge
• § Circumvallate
• § insertion at edge with membranes folding back on themselves
• § -assoc/clinical complications (eg.IUGR)

 

SPONTANEOUS ABORTION

• § Causes: Defective implantion,inflammatory, trauma, infectious (Toxo, Myco, Listeria, Viral)

 

ECTOPIC PREGNANCY

• § Causes: PID, peritubal adhesions from appendicitis, endometriosis
• § Path: -implantation in tube
• § -hemorrhage in fallopian tube
• § Sequelae:-can cause hemorrhage w/ rupture, may have resorption, tubal abortion thru fimbriae

 

INFECTIONS

• § Organisms: TORCHS
• § -can be acute or chronic
• § nφ → Listeria

ACUTE FUNISITIS:

-NΦ IN UMB. BV

VILLITIS

pφ → Chlamydia

nuclear/cytoplasmic inclusions → HSV (nuc only), CMV

granulomatous → TB, fungi,

lφ, mφ → VUE (villitis of unknown etiology)

 

CHORIOAMNIONITIS

• § -usu secondary to bacteria (GBS, E.coli, Staph)
• § uses: PID, peritubal adhesions from appendicitis

 

PLACENTAL INFARCTION	PERIVILLOUS FIBRIN DEPOSITION
§ Gross: red and firm § Gross: red and firm § No § Trophoblast proliferation in intervillous space § Villous crowding § Spacing of villi maintained § Intravillous hemorrhage § No § Neutrophils at edge § No § Karyorrhectic debris § No § Atherosis (fibrinoid necrosis and foamy mφ) § No § Location: Basal and marginal aspect § Thoughout placenta

 

GESTATIONAL TROPHOBLASTIC LESIONS

Variants (WHO)

• § Choriocarcinoma
• § Plascental site trophoblastic tumor
• § Epithelioid trophoblastic tumor
• § Molar pregnancies
• § Placental site nodule and plaque
• § Exaggerated placental site

 

 

 

 

 

 

 

HYDATIDIFORM MOLES

	COMPLETE MOLE	PARTIAL MOLE	HYDROPIC ABORTUS
Fertilization	2 sperms (or 1 sperm which divides) + empty egg=46XX or XY	2 sperms + normal egg = 69XXY,XXX, XYY	none
Origin of chrom.	Paternal (Daddy’s girl)	Paternal and maternal	N/A
Embyro/fetus	Absent	Present	may be present
Villous outline	Smooth	Scalloped with inclusions	no scalloping or inclusions
Villous size	Large with central cisterns	Variable, cisterns less prominent	Lg swollen villi, Uniform population
Villous fibrosis	None	Present
Troph. prolif	Circumferential with atypia	Focal with minimal atypia	Attenuated, no atypia
Stroma	Karryohexis	No karryohexis	No karryohexis
IHC	p57– (paternal imprinting, so gene shut off) ++++hCG,  +PLAP	p57+[14] +hCG, ++++PLAP Ki67+	p57 + Ki67-
*p57 is normally positive in intervillous trophoblasts

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