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AP RCPA VIVA > The Holy Organs > Flashcards

The Holy Organs Flashcards

1
Q

Tumours Associated With Endometriosis

A

Polypoid endometriosis
Endometrioma

Seromucinous borderline tumour
Endometrioid carcinoma of ovary
Clear cell carcinoma

Rarely: mesonephric-like carcinoma, adenosarcoma, ESS, somatically derived YST.

NB:
Once seromucinous borderline tumour invades it is classed as an endometrioid carcinoma.

Need to do MMR on all endometrioid carcinomas, both ovary and endometrial.

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2
Q

Classification of Ovarian Tumours

A

Surface Epithelial:
Brenner, seromucinous borderline tumour / endometrioid, clear cell, SBT / LGSC, HGSC

Germ Cell:

Teratoma, yolk sac tumour, dysgerminoma, choriocaricinoma, embryonal carcinoma

Sex-Cord Stromal:

Fibroma, fibrothecoma, AGCT, JGCT, SCTAT, sclerosing stromal tumour, microcystic stromal tumour, signet ring stroma ltumour, Sertoli-Leydig cell tumours, steroid cell tumour

Metastases

Misc: Small cell carcinoma of hypercalcaemic type, FATWO, gonadoblastoma

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3
Q

Gynae Biomarkers

A

ER, PR, HER2

p53, p16

MMR proteins

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4
Q

Tumour Syndromes Associated with Gynae Neoplasms

A

Hereditary breast and ovarian cancer (BRCA1/BRCA2)

Lynch syndrome (endometrial & ovary)

PJS (SCTAT, HPV independent cervical adeno)

DICER1 (SCCOHT)

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5
Q

FIGO Staging Tube / Ovary / Peritoneum

A

Features to Include from Macro:

Intact / Ruptured (and timing of rupture)

Omental biopsy

Perintoneal washings

FIGO STAGING

I - Limited to one or both ovaries / fallopian tubes

  • substaged based on surgical spill and positive washings

II - Extension / implants on uterus / pelvic tissues below brim

III - LN involvement / peritoneal disease outside pelvis

IV - Distant metastases incl: positive pleural cytology, extension to liver / spleen / intestine, extraabdominal organs

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6
Q

Molecular Classification of Endometrial Cancer

A

Based on TCGA data the PROMISE risk classifier divided endometrial carcinom into four molecular groups:

1. POLE mutated (ultramutated ) (PCR / NGS)

2. MMR deficient (hypermutated) (IPX)

3. p53 mutant (CN high / “serous like” (IPX)

4. p53 WT / CN low / NSMP

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7
Q

FIGO Staging Endometrial Carcinoma

A

I : Confined to uterine corpus

IA < 50% myometrial invasion

IB > 50% myometrial invasion

II : Invasion of cervical stroma

III: Local / Regional spread

IIIA uterine serosa and / or adnexal structures

IIIB: vaginal and / or parametrial involvement

IIIC: Pelvic and / or paraaortic nodes

IV: Invasion of bladder / bowel / distant metastases

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8
Q

FIGO Grading Endometrial Carcinoma

A

High grade by definition:

Serous

Clear cell

Carcinosarcoma

Dedifferentiated and undifferentiated carcinoma

Endometrioid carcinomas

Grade 1

< 5% solid, non glandular, non squamous growth

Grade 2

5 - 50% solid, non glandular, non squamous growth

Grade 3

> 50% solid, non glandular, non squamous growth

NB:

Can increase grade by one if there is significant cytologic atypia. Also, some authorities suggest using a binary grading system (low - grade 1 / 2 and high = grade 3).

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9
Q

Sentinel Lymph Nodes in Endometrial Carcinoma

A

(sn) prefix if sentinel node
(it) suffix if ITC’s only
(mi) suffix if micrometastasis

Size criteria same as breast i.e.

ITC’s = < 0.2mm or < 200 cells

Micrometastasis = 0.2 - 2mm

Macrometastasis = > 2mm

Nodal Staging: pTNM / AJCC

N1 = regional nodal micrometastasis

N2 = regional LN macrometastasis or paraaortic nodes

pM = metastases to inguinal lymph nodes

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10
Q

Syntopic Reporting Elements in Endometrial Cancer

A

Specimen type

Site and size of tumour

Histologic subtype

FIGO grade

FIGO staging - depth of myometrial invasion, involvement of cervical stroma, involvement of uterine serosa, adnexal structures, parametria and vagina

MELF pattern of invasion

LVI

Peritoneal washings

Omental biopsy

Immunomolecular classification and biomarkers:

MMR (+/- methylation profile) and p53

ER / PR

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11
Q

FIGO Staging Cervix

A

I - Strictly confined to cervix (extension to corpus allowed)

IA substage based on depth of stromal invasion (3, 5 mm)

IB substage based on greatest tumour size (2, 4 cm)

II: Into upper vagina or parametria

III: Into lower vagina, pelvic side wall, hydronephrosis, pelvic and paraaortic lymph nodes

IV: Beyond true pelvis, bladder or bowel mucosa, distant organs

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12
Q

Discordance Cervical Histology and Cytology?

A

Do levels and review cytology

Discuss at MDM

Consider lesion elsewhere in lower anogenital tract and need for re-examination or re-biopsy

All else fails need to consider and exclude a specimen mix up

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13
Q

Benign Mimics of HSIL on Cytology

A

Atrophy (basal / parabasal cells only)

High sampling (LUS post LLETZ)

Squamous metaplasia

Reactive atypia

Radiation atypia

Endometrial cells

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14
Q

Mimics of LSIL on Cytology

A

Reactive atypia (associated with infections e.g. Candida, BV, trichomonas)

HSV viral cytopathic effect

IUD cells - degenerative vacuolar changes

Tubal and tuboendometrioid metaplasia

Endometrial cells

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15
Q

Why is P16 positive in HSIL

A

HR HPV (subtypes 16 / 18) integrate into host genome

Production of viral oncoprotein E7 which binds to RB causing it to degrade

Without RB acting as a brake on the cell cycle, the CDKN2A gene can continue to produce p16 protein

When overexpressed p16 causes downstream effects on cellular proliferation and increased cell survival

NB: E6 viral oncoprotien binds to p53 with similar downstream effects

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16
Q

How does p57 help in the diagnosis of molar pregnancy?

A

Poor interobserver variability between CHM, PHM and hydropic abortus on histology alone. Can use p57 IPX and FISH to distinguish these.

Partial mole:
p57 positive (nuclear expression in at least 10% of villous stromal cells and cytotrophoblasts)
NB: p57 also positive in normal fetus / hydropic abortus
FISH shows triploidy in partial mole

Complete mole:
p57 negative
FISH shows diploidy (diandric)

P57 negative in CHM because p57 is a paternally imprinted, maternally expressed gene and complete moles are diandric (dispermy, empty ova)

17
Q

What are the TORCH infections?

A

The acronym ‘TORCH’ has been used as a reminder of infections that cause congenital defects.

Toxoplasmosis

Others (syphilis, listeria, parvovirus B19, VZV, HIV)

Rubella

Cytomegalovirus (CMV)

Herpes (simplex) virus (HSV).

18
Q

Features and Significance of CMV in Placenta

A

DNA virus that causes 10% of chronic villitis cases

Often no clinical symptoms.

Hearing and visual loss, neurologic deficit, IUGR

Macro:

Placenta may be large and edematous or small and fibrotic

Micro:

Lymphocytic or plasmacytic villitis with hyalinized villi

Hofbauer cell (fetal macrophage) hyperplasia

Rare intranuclear and cytoplasmic inclusions

19
Q

Features and Significance of Listeria in Placenta

A

Gram positive bacteria strongly associated with stillbirth, premature delivery and sepsis

Macro: Small white nodules (microabcesses) scattered throughout parenchyma

Micro: Acute intervillositis with intervillous microabcesses; organisms identified with gram stain

20
Q

Features and Significance of Syphilis in Placenta

A

Often associated with stillbirth or early neonatal death

Macro: Umbilical cord often normal but 36% have necrotizing funisitis; large oedematous disc

Micro: Immature, edematous villi with increased fetal erythroblasts, endarteritis and perivasculitis of stem vessels and lymphoplasmacytic villitis

Necrotizing funisitis or acute villitis have also been reported

Ancillary: Most cases with positive PCR have negative histology so do PCR of placental tissue if suspect syphilis

Positive stains: visualize spirochetes in cord using silver (Warthin-Starry) stain and / or Spirochete IPX

21
Q

Synoptic Report for Vulval Cancer

A

Location & Laterality of Tumour

Uni / Multifocal

Macroscopic Size

Histologic Subtype of tumour: SCC-HPV associated, SCC HPV-independent, adenocarcinoma, carcinosarcoma, NEC, MINEN.

LVI / PNI

Neoadjuvant therapy

Additional findings: condyloma, VIN, dVIN, LSC

P16 immunohistochemistry

pTNM Staging (AJCC 8th):

pT1 Size of tumour (< / > 2cm) and depth of stromal invasion

pT2 Invasion into lower uretha / periurethal structures

pT3 Upper urethra / vagina / bladder / rectum

NB: no pT4

22
Q

Sentinel Lymph Nodes in Breast

A

sn (ITC) = < 0.2mm or < 200 cells

sn (mi) > 0.2mm and < 2mm

macrometastasis >2mm

macro: size of largest deposit and ENE

23
Q

Microinvasive Breast Carcinoma

A

Invasive carcinoma <1mm in size outside interlobar stroma

Usually arises in a field of DCIS

Can be single or multiple

Staged as pT1mi

24
Q

Grading of Breast Cancer

A

Histologic grading is based on the Nottingham Score / Modified Bloom & Richardson Score

Tubule formation (1 - 3 points):

> 75% (1 point)

10 - 75% (2 points)

< 10% (3 points)

Nuclear pleomorphism (1 - 3 points):

Small, regular, uniform, similar to normal ductal epithelial cells, 2 - 3x RBC (1 point)

Moderate increase in size / variability (2 points)

Large nuclei, marked variation, often vesicular chromatin with prominent nucleoli (3 points)

Mitotic count (1 - 3 points)

Per 10 HPF, score dependent on microscopic field area

Total score

3 - 5 points: grade 1

6 - 7 points: grade 2

8 - 9 points: grade 3

25
Q

Reporting Features for DCIS

A

Size of DCIS / In situ component

Nuclear grade

Architecture

Presence of necrosis (and calcifications)

Margins

26
Q

Interpretation of HER2 IPX in Breast

A

+ Complete, strong membranous staining in >10%

Assessing invasive carcinoma cells

Number of cells staining, intensity of staining and whether or not it is complete membranous

Usually assessed on core biopsies (better fixation) but repeat if negative on resection specimen as can be heterogenous

0 = No staining or weak membranous staining in <10%

1+ = Faint / barely perceptible membranous staining in >10%

2+ = Weak to moderate complete membranous staining in >10%

27
Q

Interpretation of HER2 ISH

A

Complicated - ideally use CISH or FISH dual fusion probe to compare ratio of number of HER2 gene loci to number of CEP17

(CEP17 = centromere chromosome 17, needed to quantify # of chromosomes present in each cell given aneuploidy is common)

Positive:

Single probe average HER2 copy number ≥ 6.0 signals/cell

Dual probe HER2/CEP17 ratio ≥ 2.0 with any average HER2 copy number or HER2/CEP17 < 2.0 with an average HER2 copy number ≥ 6.0 signals / cell

28
Q

Reporting Elements in Invasive Breast Cancer

A

TUMOUR (pT)

Specimen type and laterality

Tumour focality

Tumour size (invasive and in situ)

(Size cutoffs 5, 10, 20 and 50mm)

Histologic Type

Histologic Grade (Nottingham score)

Involvement of skin (epidermis, dermis, dermal lymphovascular spaces)

Involvement of skeletal muscle

DCIS (size, grade, architecture, necrosis)

LVI and PNI

Post neoadjuvant treatment effect (tumour and lymph nodes)

Margins: invasive and in situ

Biomarkers: ER / PR / HER2

NODES (pN)

Sentinel versus non-sentinel

Sentinel nodes: Number involved, ITC, micro or macrometastases

Non sentinel: Number involved, size of largest deposit and ENE

METASTASES (pM)

Non regional lymph nodes, lung, liver, bone, brain

29
Q

Treatment Response in Post NAT Breast

A

Loss of tumour may occur due to concentric shrinking of the tumour or as scattered loss / drop out of tumour cells

Tumour is replaced by loose fibrous tissue containing a variable infiltration of histiocytes, lymphocytes, giant cells, hemosiderin and vascular proliferation

Similar changes are seen in lymph nodes

Changes in normal breast tissue may include lobular atrophy, lobular cellular atypia and fibrous stromal involution

Classification Systems

Residual Cancer Burden (RCB 0 - IV)

  • calculator on MD Anderson site
  • submit entire maximum cross sectional area of tumour bed, and calculate % of tumour bed that contains residual cancer and % that is residual in situ.
  • includes number of positive LN’s, size of largest deposit

Miller & Payne (1 - 5)

30
Q

Myoepithelial Markers in Breast

A

p63 / p40

SMMHC

calponin / SMA

31
Q

Tumour Syndromes Associated With Breast Cancer

A

BRCA1 / BRCA2

Cowden / PTEN Hamartoma Syndrome

Li-Fraumeni Syndrome

Peutz-Jegher Syndrome

Ataxia-Telangiectasia Syndrome

Hereditary diffuse gastric cancer syndrome (lobular)

32
Q

Grading of Phyllodes Tumours

A

Criteria:

Stromal cellularity

Stromal overgrowth (> 4x field)

Stromal pleomorphism

Infiltrative border

Mitoses / 10 HPF

Presence of heterologous elements = malignant (except ALT)

33
Q

Explain How You Would Cut Up this Specimen

A
  1. PPE, 3 points of ID, check MDM (imaging / biopsy results)
  2. Orient specimen, weigh and measure in 3D
  3. Ink ant / sup blue, ant / inf green and deep black
  4. Section from medial to lateral (removing HW in process), lay out slices, label and photograph
  5. Describe tumour, including size, circumscription, appearance of cut surface and measure to all margins.
  6. Block tumour: if DCIS (and small ish) all through otherwise Xray and block widely around biopsy clip / calcs. If invasive tumour usually 2 full faces of specimen and any other close margins (aiming 2 blocks / cm incl margins).
34
Q

DDX Low Grade Spindle Cell Lesions in the Breast

A

Metaplastic Carcinoma: HMWCK / P63 / P40 positive

Stromal component of Phyllodes: CD34 +, usually ER positive

Fibromatosis: SMA positive, Nuclear beta catenin

Nodular Fasciitis: SMA positive, USP6 rearranged

Myofibroblastoma: SMA, Desmin, ER and CD34 positive

35
Q

Type of VIN

A

HPV-Associated:

Younger women / immunocompromised, p16 block positive

Slower progression to SCC

Usually basaloid with peripheral palisading

HPV-Independent:

Older women, associated with LSC, p16 negative

Rapid progression to SCC

“dVIN” acanthosis, hyperparakeratosis, basal atypia with glassy pink cytoplasm. p53 parabasal, null, or cytoplasmic

When invasive -> Well differentiated, keratinising SCC

36
Q

NAT Treatment Response in Ovarian Epithelial Tumours

A

CRS - chemotherapy response score

Assessed in omentum (and other sites) post NAT for HGSC

Score 1: No or minimal tumor response (mainly viable tumor with no or minimal regression-associated fibro-inflammatory changes, limited to a few foci);

Score 2: Partial tumor response (multifocal or diffuse regression associated fibro-inflammatory changes, with viable tumor ranging from diffuse sheets, streaks or nodules, to extensive regression with multifocal but easily identifiable residual tumor;

Score 3: Complete or near-complete response (mainly regression, with few irregularly scattered individual tumor cells or cell groups, all measuring <2 mm, or no residual tumor identified).

AP RCPA VIVA (14 decks)

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