ASCP GYN

What is the pictured entity on the vulva? and describe histologic characteristics

[image]

ANSWER: Lichen sclerosus (et atrophicus)

-hyperkeratosis, effaced rete ridges, band of subepithelial hyalinization; with underlying band of chronic inflammatory cells

ASCP GYN

What is the entity in the picture?  clinical significance

[image]

ASNWER: Squamous hyperplasia

no clinical significance, except may be confused with condyloma or HPV changes

ASCP GYN

What is the entity?  What is it associated with (specific types)?  Is it dyplastic?

[image]

[image]

ANSWER: Condyloma accuminatum

-very common

-80% associated with LR HPV types 6 and 11

-contain mild dysplasia

ASCP GYN

VIN: risk factors; percentage recurring after local treatment, percentage progress to invasion

-IHC

Vulvar intraepithelial neoplasia (VIN)

-classic form: risk factors

-HPV- mainly 16, 18, 31, 33

-smoking

-immunosuppression

-Age: mean 40 yrs

- 50-80% are multifocal

-50-60% have synchronous lesions in cervix, vagina, urethra or anus

-** 30-50% recur after local treatment

-some may regress (usually younger)

-** 4-7% progress to invasion after treatment

-IHC: + for p16 and Ki-67 high

3 basic subtypes:

-basaloid 

[image] 

-warty type

[image]

-Simplex (differentiated) type= not classic, not a/w HPV, found in elderly

Comparing classic VIN and differentiated characteristics and percentages that cancer develop from each:

[image]

ASCP GYN

Grade the VIN:

[image]

ASCP GYN

What is the entity in the pictures?

- typical patient characteristics

-histologic features

-prognosis/associated disease

[image]

[image]

ANSWER: VIN Simplex (Differentiated)

-found in elderly pts, **NOT HPV-related**

-most invasive squamous cell carcinomas of the vulva originate from this lesion

-a/w well-differentiated inv SCC

Histology: prominent parakeratosis, thickened epidermis, elongated and branched rete ridges; abnormal keratinocytes with large vesicular nuclei; focal macronucleoli; abundant eosinophilic cytoplasm; prominent intercellular bridges; mitoses common in basal layer; basal layer cells have smaller hyperchromatic nuclei with irregular contours (folded)

-cut off for depth of invasion (measured from tip of most superficial papillae):

- <1mm= microinvasion

[image]

->1mm= invasive SCC

**IHC: basal cells/several layers are +p53

[image]

ASCP GYN

what is the entity

main ddx/diagnostic problems

IHC

[image]

ANSWER: Paget's disease (extramammary paget's)

histologic appearance is same as in breast tissue

diagnostic problems:

-may be a/w squamous lesions- acanthosis, fibroepithelioma-like hyperplasia or papillomatous hyperplasia

-**DDx:  #1= MELANOMA

far less common #2- pagetoid VIN (p63 +)

-there is a high frequency of incomplete excision

-20-30% recur

-IHC:  *mucicarmine- shows good intracellular mucin

[image]

-primary vulva pagets: + for CAM 5.2, CEA, EMA, CK7, G6PD and *HER2neu

[differentiate from melanoma- pagets is negative for all typical melanoma markers- Melan A/MART 1; HMB-45, S-100, etc]

-secondary vulvar involvement from anorectal primary- CK7 (-), CK20+

-secondary involvement from urothelial primary- CK7 and CK20 +; uroplakin +

ASCP GYN

describe measurement for tumor thickness and depth of invasion in vulvar SCC and risk of LN mets

-Tumor thickness: measurement from granular layer (or surface if nonkeratinized) to deepest point of invasion

-Depth of invasion: measurement from epithelial-stromal junction of adjacent most superficial dermal papillae to deapest point of invasion

A. DOI and tumor thickness may be the same or nearly the same if the overlying epidermis is markedly thin

[image]

B. DOI may be less than tumor thickness if epithelium is markedly thickened

[image]

C. DOI may be more than tumor thickness if tumor is ulcerated

[image]

risk of LN mets is essentially 0 if DOI is less than 1mm, anything over 1mm gets a LN dissection

[image]

Less than 1mm = micro/early invasion

[image]

ASCP GYN

What is the vulvar lesion in the pictures?

-clinical/gross findings

-prognosis

-histologic features/IHC

[image]

[image]

ANSWER: Aggressive angiomyxoma

clinically- an ill-defined- vulvar, perineal, vaginal and/or inguinal mass; mimcs a Bartholin cyst clinically

-gross- bulky, soft, rubbery/gelatinous

-prog: indolent, but tendency to recur locally and be aggressive

DDx:

-angiomyofibroblastoma (well-circumscribed, cellular, no vessels, different IHC)

-neurofibroma

-myxoma (bulging tumor, but also ill-defined)

Histology: thickened hyalinized vessels, myxoid background, small mesenchymal cells which are actin and SMA +

[image]

ASCP GYN

Miscellaneous soft tissue lesions, vulva

A. [image]

B. [image]

A. Angiomyofibroblastoma-

    --well-circumscribed, generally more cellular than aggressive angiomyxoma

[image]

    --IHC: desmin+, esp around vessels, and stroma cells ER+

[image]

B.  Cellular angiofibroma:

    --like an angiofibroma with more cells, lots of vessels, lacks hyalnized, thick vessels and myxoid stroma of agg angiomyxoma

[image]

-CD34 highlights the increased small vessels

[image]

ASCP GYN

Risk factors for CIN

• HPV- 16, 18, 31, 33, 35, 45 (HR)
• HPV- 6, 11, 40, 54 (LR)- not a/w inv SCC
• sexual activity at young age
• multiple sex partners
• parity (>7)
• chlamydial infection
• smoking
• high viral load
• persistent SIL/HPV

Colposcopy images

[image][image]

ASCP GYN

grade the CIN if present

A. [image]

B.[image]

C. [image]

D. [image]

E. [image]

F. [image]

G. [image]

ANSWERS

A.  Normal cervix, maturation, distinct basal layer

[image]

B. CIN I- with koilocytic atypia/HPV effect at surface, mild atypia and basal cell hyperplasia

[image]

C. CIN I- atypical mitosis above basal layer, but not reaching 1/3, mold cytologic atypia.  Appears more atypical than B, but is still CIN I

[image]

D.  Reactive squamous mucosa- no dysplasia, matures as expected with reactive changes.

[image]

E.  CIN III- high-grade dysplasia, lack of maturation, involves full-thickness

[image]

F.  Immature squamous metaplasia- no dysplsia

[image]

G.  CIN III involving endocervical glands- lack of maturation, partially involves glands

[image]

p16 can be used to differentiate pre-malignant from benign mimickers

[image]

[image]

ASCP GYN

Describe the difference between measuring depth of invasion in SCC of the vulva vs cervix

Vulva:  DOI measured from uppermost dermal papillae, not BM; critical level= 1mm

Cervix: DOI measured from BM of adjacent surface epithelium or endocervical gland

[image]

A= if invades from CIN

B= if invades from CIN involving endocervical gland

C= if invasive foci, but no tumor above it, measure from basal lamina of overlying surface

early invasion [image]

stromal reaction indicates invasion[image]

Criteria for staging of early invasive SCC of cervix:

-FIGO:  depth <5mm

           width < 7mm

     --stage Ia:

         ---stage Ia1= stromal inv <3mm in depth; <7mm in width

         ---stage Ia2= stromal inv >3 mm in depth; >7 mm in width

      --stage Ib: any clinically apparent tumor but early invasion

-LVI does not alter stage but should be included

The society of gynecologic oncologists (SGO): stromal invasion 3mm or less; NO LVI

stage Ia SCC found in 5% of serially sectioned cone biopsies for HSIL; margins in CONE very important

ASCP GYN

what is the lesion, is it malignant IHC and characteristics

[image]

[image]

ANSWER: Endocervical adenocarcinoma in situ (AIS)

Age- mean in 4th decade

20% have hx of CIN

asymptomatic

-visible lesion is absent/rare

-multifocality in 15%

**Associated lesion of CIN in 50-70%

a/w HPV 16, 18

Histology: must see mitoses and apoptosis

+/- stratification and hyperchromasia

[image]

IHC: are p16+, high Ki-67

[image][image]

ASCP GYN

Endocervix- identify the pseudoneoplastic mimicker

A. [image]

B. [image]

C. [image]

D. [image]

E. [image]

F. [image]

G. [image]

Endocervical pseudoneoplastic changes/mimickers

A.  Tubal metaplasia- can resemble AIS, but has peg/clear cells and CILIA!  TM is vimentin + and AIS is p16+

[image] [image]

B. Mesonephric remnants- found at lateral sides, particularly in cone specimens

[image]

C.  Tunnel cluster- lobules

[image]

D.  Microglandular hyperplasia- a/w hormonal tx or pregnancy

[image]

E. Reactive endocervical glands- smudgy, irregular nuclei, ugly cells, but a/w inflammation/neutrophils; no mitoses!; may show pseudostratification

[image] [image]

F. Arias-stella reaction- a/w, during or after pregnancy

[image]

G. Radiation changes/atypia- retains low N:C ratio

[image]

ASCP GYN

What is the endocervical lesion?

[image]

ANSWER: Villoglandular carcinoma

-a very well-differentiated variant of endocervical adenocarcinoma

-rare entity

-can be deceiving; in otherwise classic adenocarcinoma with villoglandular growth- can call it: with villoglandular features

ASCP GYN

What is the diagnosis?

[image][image]

ANSWER:  Adenoma malignum, aka minimal deviation adenocarcinoma

-very rare, very aggressive

-a/w peutz-jehgers and sex cord tumor with annular tubules

-neg for HPV and p16!

-histology- very well-differentiated glands, with rare nucleoli, but multiple foci of loose desmoplastic stromal reaction in multiple fields

[image]

ASCP GYN

types of endometrial metaplasia

-characteristics of pts with endometrial metaplasia

12-20% of non-ovulatory endometrium shows metaplasia

-perimenopausal and post-menopausal more often

-in young women- usually a/w S-L syndrome

-estrogenic stimulation (increased obesity-> a/w increased incidence of metaplasia and adenocarcinoma

-co-exists with hyperplasia and carcinoma

-long-term effect unknown

types:

A. Papillary (syncytial) metaplasia- clean background, lots of pink cytoplasm; a/w neutrophils and shedding

[image][image][image]

B. Eosinophilic metaplasia- overlaps with papillary (syncytial) metaplasia (A)

[image]

C. Tubal metaplasia- cilia, clear cells/peg cells; stratification

[image]

D.  Clear cell metaplasia/changes- remniscent of squamous metaplasia; p53 is not as helpful here as will others (ie hobnail), b/e p53 is only + in ~80% of clear cell ca.

[image]

E. Hobnail metaplasia- often seen together with clear cell and eosinophilic metaplasia; differentiate from serous carcinoma with p53

[image][image][image]= for comparison, serous carcinoma with higher N:C ratio; p53+

F. Squamous metaplasia- don't overcall as SCCa or hyperplasia

[image]

G. Mucinous metaplasia- no pic, but would look like endocervical/intestinal mucosa

ASCP GYN

What drug is commonly associated with the lesion in the picture?

describe specific characteristics of these lesions caused by the drug

[image]

ANSWER: endometrial polyp

Answer: Tamoxifen polyp

-Chx- tamoxifen polyps are large in size, typically multiple; with small, cystic glands, metaplasia, hyperplasia and myxoid changes

Tamoxifen and cancer:

= RR: 4-7x vs placebo

- higher risk after 5 years; or over 50 yrs old

-mostly a/w endometrioid type, low- grade/stage

-occassional MMMT, stromal sacroma

ASCP GYN

The W.H.O. recognizes 4 types of endometrial hyperplasia- what are the names?; description of each/diagnostic criteria; relative proportion of each type

1.  Simple Hyperplasia without atypia

2.  Complex hyperplasia without atypica

3. simple atypical hyperplasia

4. Complex atypical hyperplasia

Simple hyperplasia- cystic, dilated glands, with more than avg # of glands (increased gland:stroma ratio)

[image][image]

Complex hyperplasia without atypia- nearly back-to-back glands, with little stroma between; lack cytologic atypia; less common

[image]

Can have both simple and complex together in same specimen

[image]

Simple atypical hyperplasia- far less common; but appears like simple hyperplasia with some cytologic atypia

[image]

Complex atypical hyperplasia- more common; can still see some stroma between glands

** Criteria for calling atypia: 

     --nuclear enlargement (2-3x RBC)

     --Pleomorphism

     --Vesicular change

     --Chromatin irregularity

     --Loss of polarity

     --Prominent nucleoli

     --Cellular stratification

[image][image]

[image]- atypia adjacent to proliferative endometrium

ASCP GYN

Describe the use of PTEN staining in endometrium

used to differentiate EIN from atypical complex hyperplasia

EIN (endometrial intraepithelial neoplasia)- if >1mm area of atypia and increased gland:stroma

Loss of PTEN= neoplastic

retaining PTEN staining= complex atypical hyperplasia

[image]

ASCP GYN

This entity was present in the EMB of an elderly pt, what is it?

[image]

ANSWER: Cystic atrophy

-very thin atrophic lining, cystic dilation and atrophic stroma

ASCP GYN

What is Kurman and Norris' criteria for distinction between atypical hyperplasia and cancer

-what will be the difference in treatment

Kurman and Norris:

1. Desmoplastic stromal response (=ca, but rare to find it)

2. Cribriform pattern- fused glands= CA[image]

3. Replacement of stroma by squamous epithelium

4. Extenisive papillary pattern

*** the last 3 (#2,3,4)- to qualify for invasive ca- must be at > 2mm (1/2 of one LP field)

If the patterns are <2mm--> ACH

Tx is essentially the same:

if older pt (done with fertility)- TAH-BSO

if younger pt, wants to keep fertility--> progestational agents until done with fertility --> then TAH-BSO

ASCP GYN

List variants of endometrioid carcinoma

Describe grading of endometrioid

VARIANTS:

-Villoglandular[image]

- with squamous differentiation [image]

-Secretory[image]

-Ciliated [image]

-Oxyphilic[image]

-Sertoliform [image]

-With trophoblastic differentiation

-with giant cell component

- with argyrophil cells (old entity- not diagnosed anymore)

Grading of Endometrioid adenocarcinoma:

Grade I: 5% or less of a non-squamous non-morular solid growth pattern

Grade II: 6-50% solid pattern

Grade III: >50% solid pattern

-marked nuclear atypia raises the grade of an architectural grade I to a grade II

* only the glandular component is graded.

ASCP GYN

Describe the difference between type 1 and type 2 endometrial carcinoma

Type 1

- Endometrioid adenocarcinoma = 80-90%

   --estrogen dependent

   --a/w obesity, anovulatroy bleeding, late menopause

   --good prognosis

   --a/w endometrial hyperplasia

   --Surgical stage III and IV in <20% at dx

   --IHC:  loss of PTEN; +mut Kras and Microsatellite instability (MSI)

Type 2

-Serous carcinoma (<10%)

   --non-estrogen-dependent

   --poor prognosis

   --usually a/w atrophy (older pts)

   --surgical stage III and IV in75% at dx

   --IHC: retains PTEN; p53+

Other less common types of endometrial ca- Clear cell adenocarcinoma; mucinous adenocarinoma (endocervical or intestinal type); squamous cell carcinoma; transitional cell carcinoma

extremely rare variants: Hepatoid carcinoma; lymphoepithelial-like carcinoma; indifferentiated carcinoma (large cell or small cell); mixed carcinoma

ASCP GYN

what is the entity in the picture?

- clinical features

[image]

ANSWER: Low-grade endometrial stromal sarcoma

-uniform cells, resembles proliferative stroma

**must see mitoses

[image]

-frequently have extenisive lymphovascular invasion

[image]

Main DDx: cellular leiomyoma

clinical fx: it represents 10-15% of uterine sarcomas

-75% are younger than 30 yrs old

-a/w vaginal bleeding and pain

- extrauterine extension at dx in 1/3 of cases

- rare cases: d/t prolonged estrogen stimulation; tamoxifen or radiation

IHC: + for CD10, Vimentin, MSA, SMMT; rarely + for desmin

- ER/PR receptors, inhibin, CD99

leiomyoma- + for CD99 and SMA

Behaviour- indolent, clinically low-grade; a/w late recurrence in 1/3-1/2 of pts

stage I- recurrence 36%; survival 92%

ASCP GYN

List the classifications of smooth muscle tumors of the uterus

-diagnostic approach and 3 features necessary to indicate malignancy

Classification of SMTU:

-Leiomyoma

-Mitotically active leiomyoma (>10 mit/10hpf)

-Atypical (symplastic) leiomyoma

-Leiomyosarcoma

-Smooth muscle tumor of uncertain malignant potential (STUMP)

3 features to evaluate for malignancy:

1. Nuclear aytpia (needs to be significant)

[image]

2. Mitotic index

3. Necrosis (coagulative tumor necrosis)

Use the following algorithms

[image]

[image]

[image]

Tumor necrosis should be coagulative, not typical of ischemic type necrosis, with tumor cells immediately adjacent to necrosis

[image]

ASCP GYN

Identify this smooth muscle tumor of the uterus.

-no tumor necrosis was identified and MI was <10/10hpf

However, the cells shown were present diffusely throughout the tumor

[image]

ASCP GYN

describe the main prognostic factors of the pictured tumor from the ovary

[image] 

ANSWER: Serous borderline tumor

-mild-mod atypia, no invasion

[image]

Prognostic factors:

-5yr survival for stg I, II and III= 90-95%

-* Recurrence for stg II or > = 10-15%

     --** most important prognostic factor is if residual dz remains after removal of tumor

-*invasive implants- poor prognostic factor

-Microinvasion-- <5mm linear extent or 10 mm²-- a/w late recurrence

[image]

-Lymph node mets- still up in the air, currently considered NOT a met, but just an implant and not tx'd as a met.

ASCP GYN

Ovarian serous borderline tumor- assessment of peritoneal implants

Catergories:

1. Invasive

2. Non-invasive

   a. epithelial

   b. desmoplastic

   -these distinctions no longer used in clinical practive, but may be tested on boards

Invasive: irregular infiltration; fibrotic, edematous or myxoid stroma; solid or cribriform nests; substantial atypia

[image][image]

Non-invasive: sharp demarcation from normal tissue; fibrotic or inflammatory response; glands, papillary clusters or single cells; moderate atypia

[image][image]

Desmoplastic- can be confusing b/c of fibrotic/irregular tissue reaction

[image]

Don't confuse endometriosis OR endosalpingosis as tumor implant

[image]

ASCP GYN

features of this ovarian tumor and IHC, clinical chemistries

[image]

ANSWER: Invasive serous carcinoma

-slit-like spaces, hobnailing, papillary growth and significant atypia; many mitoses

-serous is most common histologic subtype of ovarian carcinoma;

-frequently bilateral (60%)

- 80% present in advanced stage

grading based on MD Anderson- low-grade and high-grade

-Elevated CA125 in serum

-IHC: CK7 and WT-1 + (to determine if primary or secondary- ie from endometrium)

-p53 + (high-grade have p53 mutations)

GYN LEFKOWITCH

What is associated with this entity?

[image]

What is Meig's syndrome?

Answer (lesion)= fibrothecoma

they have endocrine function- commonly estrogen--> unopposed estrogen stimulation of the endometrium--> hyperplasia or carcinoma

Meig's syndrome- a/w fibroma + ascites, right hydrothorax (rare)

-benign entities; usually unilateral

[image]

GYN LEFKOWITCH

Vulvar melanoma:

-depth of invasion is measured from?

-surface of the epithelium to deepest portion of tumor

* different from squamous cell ca- which is measured from the adjacent dermal papillae to the deepest portion of tumor.

GYN LEFKOWITCH

What is the ovarian lesion?  what is it associated with?  what is a potential future lesion?

[image]

Answer: Gonadoblastoma

most often a/w mixed gonadal dysgenesis, with some Y chromosome material present

-composed of nests of germ cells and sex cord cells

[image]

-a benign entity- but MAY undergo malignant transformation--> malignant germ cell tumor

-most commonly- will become dysgerminoma

GYN LEFKOWITCH

What is the ovarian tumor, what are the distinctive structures called?

-what do these tumors produce?

[image]

ANSWER: Granulosa cell tumor

-have Call-Exner bodies = spaces contain cellular debris and the nuclei around them are not making gland structures; they are found in the most common growth pattern- microfollicular; 

-but GCT can have many growth patterns- solid, trabecular, etc.

-Adult type- has nuclear grooves (coffee-bean nuclei)

-the juvenile form does not have grooves

grossly- are cystic and solid, with areas of hemorrhage and necrosis;  and may frequently rupture intraoperatively

-** They produce estrogen- causing stimulation of endometrium with hyperplasia or carcinoma possible.

Indolent behavior, low-grade malignancy, but tendency to recur late.