PathCrap Flashcards

Question

For bladder SCC: Epidem RFs Macro Histo IHC

Answer 1

Epidem: Rare - <5% of primary bladder cancers. RFs: Chronic irritation/inflammation (e.g. long term IDC, chronic UTIs, caculi, neurogenic bladder), smoking, schistosomias infection (in endemic areas), previous bladder SCC, radiation. Macro (not asked): Appear white due to keratin, bulky, polypoid, necrotic. Histo: Must not show component of conventional urothelial carcinoma (if present, tumour should be classified as urothelial carcinoma with squamous differentiation)!!! Keratin and intracellular bridging. IHC: CK 5/6, p53, GATA and HMWCK -ve

Answer 2

3% of prostate cancer Periuthral disease may cause haematuria. More likely to have distant disease at Dx Mets including to unusual sites (e.g. the dick). Similar mortality rate to Gleason score 8 - 10 PSA can be highly variable, but on average lower than acinar. More likely to have a PSA < 4.0 ng/mL; Histo: Frequently mixed with acinar adenocarcinoma Tall columnar cells with pseudostratified nuclei. Patterns include cribriform, papillary, solid and prostatic intraepithelial neoplasia-like pattern

Answer 3

Grade I to III. Is based on the presence or extent of Mitosis, Atypia, Invasion and Necrosis. Grd I: (80% of mengiomas): NO Mitosis, no necrosis, No brain invasions. These are hypocellular. 13 Subtypes: Fibroblastic most common. Grd II: (10%): Brain invasion OR frequent mitoses (>4/10xHPF) OR 3 or more atypical cellular features: Hyper-cellularity, high N:C ration, prominent nucleoli, pattern-less growth of focal necrosis. There are 3 subtypes (ACC): Atypical (most common), Clear Cell, Chordoid Grd III (<=5%): Very frequent mitosis (>20),OR melanoma, carcinoma, sarcoma features. Also 3 sub-types (RAP): Rhabdoid Anaplastic Papillary. Molecular classification: TERT promotor mutation or CDKN2A/B may be grade III.

Answer 4

Well circumscribed, attached to dura, can be lobulated, separates easily from brain (separated by arachnoid plane) Micro: * Syncytial cells with indistinct cell membrane * lobulated architecture (meningothelial whorls) * may contain psammoma bodies * May have morphology features of mitoses, atypia, brain invasion, necrosis (‘MAIN’) IHC * Vimentin + (strong) (expressed in mesencymal cells) * EMA+ (may be weak/ focal, 70%) * S100+ * PR+ (70% of cases) – however, hormonally manipulation not proven to be effective) SWOG S9005 (Ji 2015 JCO) – mifepristone (n=80) vs. placebo (n=84) in unresectable meningioma; no difference in PFS and OS between arm

Answer 5

* 30% of primary intracranial neoplasm * Most common benign intracranial tumour in adult * F: M 2:1 for all meningioma; 1:1 for anaplastic meningioma

Answer 6

Grade 3: - Small glands, discrete/ separate (i.e. not fused), no cribriform glands, no comedonecrosis IHC benign v.s Malig: 1) Malignant loose basal cells and become HMWCK -ve 2)p63 Expressed in basal cell nuclei - malignant = loss of basal cell → p63 IHC negative 3) AMACR - +ve in prostate cancer. Expressed on Apical portion

Answer 7

For both Bx and RRP specimens a primary (most prevalent) and secondary score (most aggressive or 2nd most common - see below) are reported. For RRP specimens a tertiary score is also reported - namely the 3rd most prevelent score. constituting <5% (if present). Grading is based on the extent and quality of glandular fromation and the presence of necrosis as follows: Gleason 1-2 - Non maligant glandular tissue Gleason 3: Small glands, with no comedo necrosis or solid component. 4: Slit like glandular lumens, fused glands, cribiform architecture 5: Solid architecture, comedo necrosis

Answer 8

- ISUP GG1 = Gleason 3+3 - ISUP GG2 = Gleason 3+4 - ISUP GG3 = Gleason 4+3 - ISUP GG4 = Gleason 8 (4+4, 3+5, 5+3) - anything that adds to 8 - ISUP GG5 = Gleason 9 (4+5/ 5+4/5+5) - anything>=9

Answer 9

Actinic keratosis (solar keratosis) o pre-malignant dysplastic lesion, a/w build-up of excess keratin o 1% progress to SCC, but 80% of SCC arise from them o Macro: brown rough sand-paper from excess keratin, ‘cutaneous horn’ o Micro: cytologic atypia of basal cells with hyperplasia, intracellular bridges, thickened stratum corneum, due to excess keratin production Bowen’s disease (SCC in situ) o 3% progress to SCC o Macro: sharply defined red macule/ papule/ plaque o Micro: atypical cells in all layers of epidermis but does not invade basement membrane (cf: actinic keratosis where dysplasia limited to basal layer of epidermis) SCC o Macro: nodular, ulcerative, varying amount of hyperkeratosis o Micro: atypical cells (variable cellular differentiation, descriptors of anaplasia), intracellular bridges, infiltrates dermis (WD – keratin pearls; PD – focal necrosis, no keratin) IHC: CK5/6+ve, AE1/3+ve, p63+ve, !!EMA +ve (cf: EMA -ve in BCC) DDx Keratokanthoma.

Answer 10

Micro: Monotonous basoloid cells (large nuclei, scant cytoplasm), no intercellular bridge Architecture = Palisading peripheral cells, peripheral clefting, fibroblastic stroma IHC: BCL2+ve, p63+ve, EMA-ve (cf EMA+ve in SCC), CK20-ve

Answer 11

Solid, grey white tumour, firm, invasive with ill-defined margins (<10% surrounded by complete capsule). Dx based heavily on distinct nuclear features: ▪ **Changes in nuclear size and shape**: large ovoid nuclei, nuclear elongation ▪ ***Irregularities of nuclear membranes***: abundant nuclear grooves (from infolding of nuclear membrane), highly irregular nuclear contour ▪ ***Chromatin pattern**: empty appearance of nucleoplasm, ground-glass nuclei (Orphan-Annie nuclei. i.e. empty looking) o Papillary Architecture o Presence of psammoma bodies (rounded, concentrically laminated calcification, from necrosis) in 50% of cases

Answer 12

(15%) (arise from follicular cells) Epi: 75% women, older age than PTC (peak 40-60y/o), rare in children Clinical: o Associated with iodine deficiency (response to RAI, except Hurtle cell variants) o Usually solitary ‘cold’ nodule on radionuclide scan

Answer 13

Dx is a bit of a contasting with PTC findings: o Trabecular or solid pattern of follicles (small, normal, or large size) o No nuclear features of PTC o Capsular invasion: capsule is typically thickened and irregular, needs penetration through the capsule (full thickness), may have reactive pseudo-capsule around invasion edge o Vascular invasion: vessel within or beyond capsule, tumour covered with endothelium, attached to wall/ with thrombus o May have nuclear atypia, focal spindled area, low mitotic figures (<1 per 10HPF) o No necrosis, usually no squamous metaplasia, no psammoma bodies, no/ rare lymphatic invasion

Answer 14

Uncommon (1-4% of Breast cancers) clinical presentation of breast cancer Most often presents as an eczematous / erythematous change of the nipple areolar skin Cutaneous manifestation is due to tumor cells involving the epidermis and disrupting intercellular junctions Underlying high grade ductal carcinoma in situ (DCIS) or invasive carcinoma is present in > 95% of patients Majority of Paget cells and associated underlying carcinoma are HER2+

Answer 15

OncotypeDx - Developed in the NSABP-B18 and B20 cohort - Based on 21-gene DNA micro-array - Used in women with ER+, N0 who have endocrine therapy - Predict risk of distant metastases and benefits from adjuvant chemotherapy - Stratified into 3 groups based on risk score – low (<18), intermediate (18-30), high (>30) Mamma Print (Amsterdam-70) - RCT prognostic validation - despite clinical high risk, low genomic risk pts have 95% distant met free survival without chemo

Answer 16

When a RANZCR path question says "describe" they want epi, macro, micro, bio beh. Epi - 15-20% of breast cancer - Young patients, - a/w BRCA1 mutation Micro: High proliferation rate Usually grade 3, high mitotic indices, with necrosis, pushing borders, conspicuous LVI Molecular/IHN Tripple negative p53 often mutated HMWCK + Biological behaviour: More aggressive local growth and spread. Higher benefit to anthracycline CTx.

Answer 17

- Younger patients - p53 mutation - BRCA mutation carriers - Gynae: early menarche, e arly age at first pregnancy - More commonly a/w pregnancy-related breast cancer, inflammatory breast cancer

Answer 18

Fi-Frau -90% by age 60 Lynch - 5%, unless PMS2 - then 25% Fi-frau (SBLA syndrome): - Sarcoma (soft tissue and bone) - Brain cancer - Leukaemia - Adrenal cancer Lynch (ECOG): - Colorectal cancer - Endometrial cancer - Ovarian cancer - Gastric cancer

Answer 19

10 to 15% of cases overall, more common in women 45-55, estrogen exposure appears a greater risk factor (e.g. HRT), CDH1 mutation increase risk of lobular but not ductal cas, BRAC2 increases risk of both : rubbery texture, poorly visible on mammogram (better w/ MRI). “Indian filing” histology, Often bilateral/multicentric, >80% ER+, spreads to unusual locations such as meninges, serosal surfaces, BM, ovary, and RP - ?WHY????

Answer 20

80% cases. Often well seen on mammogram. Macro: Firm mass (cartilagenous feeling) irregular mass with desmoplastic reaction, advanced can show teathering to sking (dimpling of the skin surface). Micro: Invasive malignant epithelial cells with degree of tubule formation suggestive of grade (more = lower) along with nuclear pleomorphism and mitotic rate. Surrounded by desmoplastic stroma. Lack characteristic feature suggestive of special type. IHC: Ck7, E-cadherin +, 60% ER+, 60%PR+, 25%HER2

Answer 21

EGFR Exon 19, and 21 33% (Osimertinib, older getfitinib) KRAS - 25% (not yet targeted) Alk - 5% - Mutually exculsive w/EGFR (alectinib) ROS-1 - 1% crixotinib BRAF V600E 1%

Answer 22

OsimERtnInb - has better CNS penetrance than older (Erlotinib, Getfitinib, possibly slower resistance). 15% (white ppl) to 50% (yellow ppl) of lung adeno Have EGFR mut. Must commonly Exon 19 or 21associated (40% each). T790M (Exon 20) increase treatment with EGFR TKI -> 50% cases of erlotinib/ gefitinib resistance. BUT T790M mutation are less aggressive than tumour with EGFR TKI resistance due to other mechanisms Osi side effects: Acne/rash, dry skin, diarrohoea (fuck with EGFR get gastro - like cetux), the need to eat bats.

Answer 23

EGFR - dont bother with IHC, go straight to Next Gen Sequencing. ALK - IHC for increased protein expression. If present do FISH.

Answer 24

While not yet a therapeutic target: Predictive: poor response to EGFR TKI Prognostic: More aggressive spread/poorer prognosis

Answer 25

RT induced sarcoma: osteosarcoma (21%), Undifferentiated pleomorphic sarcoma, (17%), angiosarcoma (15%) GRADING (FNCLCC) – based on: Differentiation + mitotic count + necrosis

Answer 26

Children and adolescents rhabdomyosarcoma and synovial sarcoma; Adults: 1) Undifferentiated pleomorphic sarcoma, 25% 2) liposarcoma, 15% 3) leiomyosarcoma, ~5% myxofibrosarcoma and synovial sarcoma

Answer 27

Lipo - MDM2 overexpressed especially in de-differentiated lipo do (12q13) FISH test Leio - Most common Li-Fraumini = TP53 Synovial t(X:18)(p11:q11) involving genes SS18, and either SSX1, SSX2: o SS18-SSX1 inhibit Snail gene, o SS18-SSX2 inhibit Slug gene (X,18) Rhabdo: FOXO1 translocation for alveolar rhabdomyosarcoma Fibrosarcoma = anueploidy.

Answer 28

Location of tumour – retroperitoneal (compared to extremities) = poorer (often may not be completely resected) - Grade (take into account differentiation, mitotic count, and tumour necrosis) – higher grade = worse - Differentiation – differentiated (compared to well-differentiated) = more likely to have distant mets - Myogenic differentiation = increased risk of distant mets - Histological subtype – e.g. leiomyosarcoma = higher propensity for distant mets -Cyto gentics: e.g SS18-SSX1/2

Answer 29

Fibrosarcoma: Highly cellular fibroblast proliferation in herringbone pattern, cyto = anueploidy WD Lipo: Mature adipocytes with variable size - Bizarre and hyperchromatic stromal cells within fibrous stroma Cyto= MDM2 amplification Synovial: 2 subtypes: spindle cell only (monophasic) or biphasic, spindle-epithelial. Chromosomal translocation t(X:18)(p11:q11), involving SS18, and SSX1/ SSX2 Leimyosarcoma: intersecting fascicles of spindle cells - Elongated ‘cigar-shaped nuclei - Necrosis common in large tumour - Mitotically active No key cytogentics, but most common Li-Fraumini (p53) associated.

Answer 30

Type 1: Estrogen exposure: early menache, late menopause, null parity. Obsesity/low exercise, tamoxifen (2-3x risk). Poly cystic ovarian syndrome, estrogen producing tumours (e.g Ovarian granulosa) Genetic: Lynch Syndrome (mutations in MMR genes: MSH1, MLH2, MLH6, PMS2, or EPCAM gene silencing), Cowdens syndrome (PTEN). Protective: OCP (>6months associated w/decreased risk), child birth, Smoking Biobeh: Slower growing than type 2, 2/3 present early due to bleeding. Endometrial spread including to ovaries and cervix/vagina and myometrial invasion. Risk of nodal spread increases with degree of invasion (including LVI), early haematogenous spread rare. Distant met sites: Lung (most common), bone, liver, brain.

Answer 31

Type 2: No clear risk factors. Age>70 most commonly occur in atrophy uterus. Less clear risk factors, modern research suggest estrogen exposure is also a risk. BioBeh: Aggressive local growth (compared to Type 1), Early spread to nodes and peritoneum (requires Bx at surgery) and higher rate of systemic spread. Distant met sites: Lung, bone, liver, brain.

Answer 32

1) Receptor/target mutations decreasing or preventing monoantibody binding 2) Bypassing mutations - e.g. signal transduction pathway amplifications, receptor independent signalling.

Answer 33

Colorectal 50% Endometrial 33% 10%Ovarian 5% Gastric. 5% Pancreas Turcotts - CRC + GBM

Answer 34

Clinical; Mediastinal BNHL: Often presents late/bulky with symptoms of mass effect (e.g. cough, dyspnoea, SVC obstruction), can present B symptoms (fever, night sweats, wt loss). Tends to occur in adults mean age 35, F>M. Extra-mediastinal involvement uncommon at time of Dx. Classic HL: Tends to occur in younger patients mean age 25. M=F. Mediastinum involvement common. As above may present with Sx of bulky disease/mass effect, B Sx - Also Pel-Ebstein fevers (alternating weeks of high-fever, and no fever). Histological: M.NHL: Intermediate size malignant B-cells, densely packed (more so than HL) and or clustered. Clear cell change (abundant cytoplasm), prominent scelerosis (may mimic HL). Classic HL: Nodules within broad bands of sclerosing collagen along with eosinophils, plasma cells, atypical mononuclear cells and Reed-Sternberg cells. IHC: M.NHL: CD19, CD 20, PAX 8, BCL2, and BCL 6 may be present C.HL: CD15, Cd30

Answer 35

Upfront glioma IHC: IDH R132H, ATRXloss, p53 Astro: ATRXloss p53 Oligo: ATRX retained 1p19q codeleted Astro grd III -> IV is CDK2NA/B, necrosis, or microvascular proliferation

Answer 36

IDH + at least 1 of: Endothelial proliferation Necrosis Microvascular profliferation TERT mut EGFR mut MGMT - rescues cells from alkylating agent induced damaged (e.g. tamzolomide). IDH: 2 roles - glucose metabolism, oxidative damage control.

Answer 37

IDH - obvious. ATRX mut/retained - Differentiate astro from oligo. Not prognostic. MGMT - predeictive and independently prognostic (unmethylated is poor) H3K27M - associated with midline glioma and por prognosis (often unmethylated) 1p19q - oligodenroglioma if 1p19q + IDHmut. Codel is a good prognostic and predictive feature. BRAF V600E - BRAF + histo consistent = pilocytic astro, Good prognostic and predictive (response to verafinib)

Answer 38

Both are diffusely infiltrating. Both OS>10years. Astro: Hypercellular, infiltrative, monotonus cells, fibrillary background, NO mitosis or Necrosis. ATRX loss, no codeletion, TP53 mutation. IDH mut. Oligo: Diffusely infiltrating, 'fried-egg' apperance (due to perinuclear halo), chicken wire fine capillary network. ATRX retained + IDHmut (definitive), also 1p19q

Answer 39

Prognostic factors = Factors in COGS staging (‘SAND-S’) - Stage: higher stage = worse - Age (>18mo = worse) - N-MYC protein amplified = worse - DNA ploidy (diploid = worse; hypo/ hyperploid = better) - Shimada classification (SAD-MiNd). SHIMADA (SAD-MiNd): o Stroma pattern (rich = better; poor = worse) o Age o Differentiation of neuroblast (differentiated = better; undifferentiated = worse) o Mitotic=karyorrhexis index (low = better; high = worse) o Nodularity (diffuse = better; nodular = worse) - Cytogenetic abnormalities o Favourable – hyperploidy DNA, TrK-A amplification o Unfavourable – N-Myc protein amplification, diploid DNA, deletion of 1p chromosome, del 11q, TERT rearrangement, ALK amplification

Answer 40

SHIMADA (SAD-MiNd): o Stroma pattern (rich = better; poor = worse) o Age o Differentiation of neuroblast (differentiated = better; undifferentiated = worse) o Mitotic=karyorrhexis index (low = better; high = worse) o Nodularity (diffuse = better; nodular = worse) - Cytogenetic abnormalities o Favourable – hyperploidy DNA, TrK-A amplification o Unfavourable – N-Myc protein amplification, diploid DNA, deletion of 1p chromosome, del 11q, TERT rearrangement, ALK amplification

Answer 41

Benign - Polycystic kidney - Haematoma - Renal abscess - Granuloma - Sarcoid deposit. Malignant - Too old for wilms - Neuroblastoma - Rhabdoid tumour of kidney (RTK) - Clear cell sarcoma of kidney (CCSK) - Renal cell carcinoma (RCC) - Rhabdomyosarcoma (RMS) - Adrenal carcinoma - Lymphoma - Haemangiocytoma

Answer 42

Presence of classic triphasic histology - Blastemal – presence of small round blue cells - Epithelial – variable epithelial differentiation in the form of tubule/ glomeruli - Stroma – manifest as immature spindle cells Unfavourable histology - Presence of extreme anaplasia (nuclei enlargement, nuclear hyperchromasia, abnormal mitotic figures) Presence of anaplastic histology – most powerful adverse prognostic features for Wilms

Answer 43

90% sporadic 9% genetic syndrome - WAGR syndrome – mutation in WT1 gene - BWS syndrome – mutation in WT2 gene 1% familial/ hereditary

Answer 44

Neuo Classic egg shell calcification on XR - in 85% Wilm’s tumour No tumour calcification (may have calcification if haemorrhage)

Answer 45

* Maternal use of alcohol, diuretics, opioid/ codeine, * Paternal exposure to hydrocarbon, wood dust, solders * No clear correlation with maternal age, smoking, infection, X-ray exposure, recreational drug, maternal hypertension/ diabetes * Majority sporadic, only 1-2% hereditary * Genetic syndromes: Hirschsprung disease, NF-1, foetal hydantoin syndrome

Answer 46

HIV increases x 8 risk of HL (x10-20 NHL) via: Chronic antigenic stimulation, inflammation, and cytokine dysregulation. Furthermore, patients with HIV/AIDS have a higher risk of contracting oncogenic viruses (e.g. EBV). Thus, the pathogenesis of HIV/AIDS-associated lymphoma is a combination of factors, including an impaired immune system, genetic alterations, viral infection, and chronic B cell activation.

Answer 47

BCC 3-4mm SCC and at least 4 mm for a low-risk SCC. There are no published guidelines for a high-risk SCC. 6-10mm is accepted range.

Answer 48

a. the macroscopic features, Solid white/grey tumour, not encapsulated, poorly defined, invasive. 20% multifocal. b. the microscopic features Malignant glandular cells, with higher grade consisting of more solid component, surround desmoplastic stroma. PNI and LVSI common. IHC: Mapsin, CK7, pS100. c. the biological behaviour of the tumour. Aggressive local growth with invasion into adjacent structures, majority are unresectable at diagnosis, early nodal spread and metastatic spread to lung, liver and bone. 5year OS unresctable 5% (or less)

Answer 49

Gross: Distance from resection margin – proximal, distant, circumferential Micro: "Tumour Response Grade" CDX2 + (points to upper or lower GI), CK 20, MUC2+, CK7 negative (upper GI CK7 positive) Molecular: dMMR (often serrated, more proximal, resistant to 5-FU, more response to immunotherapy, MSI mor favourable prog), KRAS (mut is resistant to Cetuxumab)

Answer 50

1) Cellular response – amount of residual viable tumour in relation to stromal fibrosis (TRG) 3)Fibro-inflammatory response – more extensive inflammatory response = lower recurrence rate 2) Acellular mucin – mucin pools (not regarded as residual tumour and not counted towards ypTstage)

Answer 51

Familial adenomatous polyposis (FAP) - Typically >100 adenomations polys. Other cancers - Papillary thyroid, pancreas, gastric. Benign Stuff: Desmoid tumours, fibromas, sebaceous cysts. Lynch: 50%CRC, 30%endo, 20% ovarian. Peutz-Jaeger (STK11) - Pancreas, gastric, breast. Skin Melanocytic macules present in 90% MUTYH- associated polyposis Peutz-Jeghers syndrome Serrated polyposis Juvenile polyposis serrated polyposis

Answer 52

Autosomal dominant, complete penetrance. avg age of Dx 15 Typically found to have >100 adenomatous polys

Answer 53

A Mormon Missionary...... Adenocarcinoma (55%_ Mucinous (15%) Micropapillary (10%) Serrated (10%) Medullary (5%) KRAS will not respond to Cetux.

Answer 54

RCC 85-90% - Clear cell (80%): abundant clear cytoplasm, vary degrees of atypia leading to heterogenous population. - Papillary (15%): Finger-like papillary projections - Chromophobe (5%): Large, prominent cell borders. Sarcomatous (5%): Sarcom like features - more aggressive often Dx at advanced stage. Not from the kidney: Urothelial carcinoma.

Answer 55

* Biphasic tumour with ductal and myoepithelial component * 3 different architectural pattern: tubular (most favourable), cribriform, solid (most aggressive) * Grading based on solid component (G1= no, G2<30%, G3 >30%)

Answer 56

SCC: HPV16 (60%) HPV18 (10%) Adenosquarmous: HPV16 (35%) - HPV18 (35%) HPV 18 more virulent - helps explain why

Answer 57

HPV infection esp. HPV18 Cervical screening less sensitive for detection of adenocarcinoma precursor (false negative 30-50%) Increasing in cervix adenocarcinoma risk factors e.g. increasing use of OCP/ HRT Better diagnosis/ tumour classification – in the past classified as SCC

Answer 58

1) Grade: based on mitosis, differentiation, necrosis 2) Differentiation 3) Myogenic differention = bad 4) Aggressive sub type (i.e. Leimyosarcoma) 5) Location - e.g. retroperitoneal worse. 6) Cytogenetics ect: E.g. FOX01 (causes alveloar rhabdo, way worse than embryonal)

Answer 59

Whatever the approach (surg or RT): VCD-IE 6 cycles upfront. Mnemonic= MASSSive LDH Response: Male, Age (>17), Site (pelvic/ truncal), Size (>8cm), Stage (Mets), high LDH, Response to chemo (especially necrosis, < or >90%)

Answer 60

Of prognostic value, only Oncotype Dx has validation for prediction and can be potentially beneficial in identifying low-risk patients not requiring CTX. Oncotype Dx - 21 gene array (16 cancer genes and 5 controls). The current on Mamma Print (Amsterdam-70) - RCT prognostic validation - despite clinical high risk, low genomic risk pts have 95% distant met free survival without chemo

Answer 61

100% life-time risk of breeast cancer. SBLA syndrome!!! Sarcoma (e.g. leimyosarcoma) Brain Leukaemia Adrenal Adenocarcinoma

Answer 62

High grade anaplastic cells in complex papillary, glandular, solid growth pattern, with features of necrosis, psammoma bodies, myometrium invasion and vascular invasion

Answer 63

>50% non-squamous solid growth pattern (i.e. more sold, less glandular)

Answer 64

ER/PR = 70% (Cohort data - PR expression was correlated with worse clinicopathologic characteristics, and associated with increased risk of recurrence, distant metastasis, and death compared with strong PR expression group) Her2 = 25% -3= 15%

Answer 65

>90% predominant pattern - Tubular - small well-differentiated - Medullary - Agressive, BRAC1 associated, younger patients. Lobular nodular, necrosis. - Papillary - Older patients, often multifocal, early spread. - Mucinous - Older patients, favourable. Phyllodes is a separate cancer.

Answer 66

Adriamycin.

Answer 67

Node + (most important predictor of distant and LR) Histo subtype and special subtype (e.g Medullary and papillary high risk spread) Grd (Mitosis/10HPF, nuclear pleo, tubule formation) Size and T-Stage LVSI Margins Receptor status Multifocality Surrounding DCIS Ki-67 DNA micro array classification

Answer 68

1) A rapid onset of erythema (redness), edema (swelling), and peau d'orange appearance (ridged or pitted skin) and/or abnormal breast warmth, with or without a lump that can be felt. 2) Sx present for < than 6 months. 3) Erythema covers at least 1/3 of boob. 4) Initial Bxs show invasive carcinoma. 75% are IDC. Neoadj AC+T + 12months Herceptin if HER2+

Answer 69

Soft tissue sarcoma in any part of GIT- arising from interstitial cell of Cajal (regulate contraction of GIT smooth muscle). Syndromes: Carney's Triad (C-kit), NF1, Familial GIST Epi: Rare, M=F, 50-70; almost never occur before 40 Prog: T stage/size and mitotic rate (grd = High/low based on rate) are most important. Absent c-kit (90%C-kit +ve target w/Imitanib), R1/or rupture, site (stomach best location). Beh: Stomach (60%), small bowel (35%), other (rectum, oesophagus, omentum, mesentery) (<5%). IHC: ANO1, DOG1, C-kit (CD99 - targetable with TKI), SDH loss targetable with TKI = sunitinib

Answer 70

Micro: Same as mesothelioma: its a "MES" (same as synovial sarcoma) - Spindle - Endothelial - Mixed Also nuclear pallisading. Surgery where possible, -nibs as below, RT in palliative setting. IHC: - DOG1+ (98%) - CD117/ c-KIT + (95%) - target w/ initinib - SDH deficient - Succinate dehydrogenase (SDH) deficient GIST - Target w/sunitinib. STS any part of GIT- arising from interstitial cell of Cajal Epi: Rare, M=F, 50-70; almost never occur before 40 Prog: T stage/size and mitotic rate are most important. Absent c-kit (90%C-kit +ve target w/Imitanib), R1/or rupture, site (stomach best location). Beh: Stomach (60%), small bowel (35%), other (rectum, oesophagus, omentum, mesentery) (<5%).

Answer 71

(tend to be short, scoliosis, pigmented skin lesions). Heam = AML Solid = Head and neck cancer and anogenital cancers are the most diagnosed solid tumors.

Answer 72

SIADH and LE are most common 1) SIADH: Short-term - fluid restriction, review medications (some anti deps, cisplatin), endocrine review if severe/intractable, consider 3%saline. Main intervention is to treat underlying cause (i.e. tumour debulk). 2) Cushings: adrenal enzyme inhibitors and glucocorticoid antagonists. Debulk underlying cause. 3) Lambert-Eaton (anti v-g Ca2+2 channel antibodies). Initial Mx is prednisone. 4) Paraneoplastic cerebellar degeneration syndrome. 5) Opsiclonus-Myoclonus

Answer 73

* Small round blue cells (SRBC) * Neuroendocrine type architecture – nests, trabecula, ribbons, rosette * High N/C ratio, enlarged ovoid nuclei, granular nuclear chromatin, inconspicuous nucleoli, nuclear moulding, scanty cytoplasm * Salt and pepper chromatin * High mitotic count, along with apoptotic bodies, and areas of necrosis

Answer 74

Neuroendocrine type architecture = nests, trabecula, ribbons, rosette

Answer 75

Synaptophysin+, Chromogranin A+, TTF-1+ Neg: Ck7, p63, CK20 (merkel cell are the only NE cancer that is CK20 +)

Answer 76

Patient: Sex (Female = better; male =worse) ECOG> 0-1 Weight lose = worse Tumour: ES-SCLC Para-neoplastic syndrome (=worse) LDH – increase LDH = worse; increase disease burden, raise concern re: bone marrow involvement Sodium – <135 Albumin low

Answer 77

Go from head to pelvis: - Menigioma - Prolactinoma - Papillary thyroid cancer - Mesothelioma - Papillary serrous endometrial cancer - Ovarian cystadenoma

Answer 78

1) Ovarian cancer 2) Endometrial adenocarcinoma 3) Cervix adenocarcinoma 4) Also, fallopian, breast pancreas and PCOS.

Answer 79

1) 80-90% of pancreatic Ca 2) Hepatobilliary cancers (705) To a lesser degree in CRC, and stomach cancer

Answer 80

1) CEA: Colorectal Ca, colangiocarcinoma, medullary thyroid 2) CA15.3: Breast 3) CA 125: Ovarian 4) CA19.9: Pancreatic Ca 5) AFP: NSGCTs = yolk sac and embryonal, Liver HCC 6)Beta or just hCG: choriocarcinoma, some mixed NSGCTs, and approx 10%seminomas that express it. 7) LDH: Melanoma, Myeloma, Folicular lymphoma, DLBCL 8) Calcitonin: Medullary thyroid ca 9) NSE: can be a marker of SCLC 10) S100: melanoma - not routine at Dx/or ever

Answer 81

Are key proteins involved in homologous recombination repair of DNA double strand breaks. BRCA1 and BRCA2 Pts should have transvaginal USS 1-2/year. Screening with CA-125 is also recommended. Prophylactic salpingo-oophorectomy is recommended at age 35-40 for BRCA1, and 40-45 for BRCA2. An increasing number women who test positive for faulty BRCA1 or BRCA2 genes choose to have risk-reducing surgery.

Answer 82

6 items scored 1 to 3. Score 7-12=potentially unstable, >=12 unstable. Score of 7 or more warrants surgical consultto assess for instability prior to any RT. SINS>12 is a contraindication to SABR. 1) Pain 2) Alignment: 3) Location: rigid=0, semi rigid, mobile, junctional 4) Vert body collapse 5) Posterior elements involved 6) Blastic, mixed, lytic

Answer 83

M>F Bi modal peak: 4 and 16 40% occur in H&N, 30% Genitourinary. Good - Embryonal (66%) - 3 subtypes - classic botryoid (10%), spinde (5%). Botryoid and spindle have best prognosis. Worst - Alveolar (30%) - more common in adolescents. More associated with FOXO1 Rare - Undifferentiated = very bad.

Answer 84

Histological negative margin = no ink on tumour (for invasive) and >2mm (for DCIS) (as per ASCO/ NCCN guidelines)

Answer 85

Slit-like vascular spaces formed by spindled endothelial cells with minimal-moderate atypia Mitosis common, pleomorphism minimal Haemorrhage (extravasated erythrocytes) + hemosiderin + plasma cells are key histological clues HHV8 (also referred to as LANA1) + vascular markers (CD34/ CD31)+ Neg: SMA, desmin, cytokeratin, S100, MelanA

Answer 86

Patch -> Plaque -> Nodule/Tumour. Can say the same for Mycosis fungoides.

Answer 87

Multifocal Superficial BCC (30%) (nodular are 60%) Macro: Typically occur on trunk, scaly papule, no hyperkeratosis. Micro: Tumour nests growing multifocally from dermis, radial growth with MINIMAL dermal component. Bio Beh: Suitable for topical Mx, but high LRR.

Answer 88

MF and Sezary syndrome are the most common cutaneous T-Cell lymphomas. MF is rare 6/million/yr - 5% of NHL. M>F (x2) Localised or widespread patches->plaques->tumour, can be generalised erythroderma and puritic. Can spread to nodes and organs Stg IV. Histo: small/medium mononuclear cells in upper dermis, especially at dermal-epiderm junction. IHC: CD3 (if T-cell tumour always say this), also CD2 and CD5 Genetics: no syndromes but TCR and JAK-Stat mutations are common.

Answer 89

A met e.g from lung, adrenal carcinoma, RCC, (is child neuroblastoma), Wilms, benign cyst, abscess

Answer 90

(adrenocortical (opp for RCC): +ve melanA, inhibin, synaptophysin, vimentin; -ve for PAX2 and 8, CD10, EMA, Cam 5.2)

Answer 91

(Li Fraumeni syndrome and Beckwith-Weidemann syndrome) - Remember the A in SBLA syndrome

Answer 92

Full history and thorough physical examination; bloods incl TSH/T3/T4 +/-calcitonin/CEA if medullary ca; FNA thyroid; USS thyroid or thyroid scan Nb. MRI, CT, and PET not done routinely prior to thyroidectomy)

Answer 93

RT esp during childhood incl TBI, H&N, and accidental exposure; iodine insufficiency; Genetic: medullary – familial MTC, MEN 2a, MEN2b; Follicular – Cowden’s; Papillary – Gardner’s, Turcot’s, FAP, familial papillary carcinoma)

Answer 94

The conditions associated with MEN syndrome? MEN I – pituitary, parathyroid, pancreatic; MEN IIa – phaechromocytoma, parathyroid, medullary thyroid ca; MEN IIb – phaechromocytoma, medullary thyroid ca, mucosal neuroma/marfanoid habitus What is the recommendation regarding thyroidectomy for MEN2 families? Prohylactic thyroidectomy based on specific DNA mutation on RET proto-oncogene)

Answer 95

SCC, verrocous SCC, ACC, small cell, lymphoma, sarcoma, leukoplakia, erythroplakia, mucocitis/infection. Glottic – tend to present with hoarseness/odynophagia and otalgia, unusual to have neck mass as virtually no LN drainage. Supraglottic – tend to present with hoarseness/odynophagia/dysphagia/neck mass/otalgia/airway obstruction due to rich lymphatics and absence of barriers which promotes early bilateral LN spread to nodal spread levels II-IV.

Answer 96

90% harbour a somatic reciprocal translocation, t(11;22) causing EWSR1-FLI1 fusion.

Answer 97

1) Classic - 3 types: - Osteoblastic: 50% cases; abundant production of osteoid - Chrondroblastic: 25%; differentiation towards cartilage - Fibroblastic: spindle cell stroma with “herring bone” pattern similar to fibrosarcoma 2) Telangetasic 3) Small cell

Answer 98

PAX 8, PAX2, EMA. CK7 negative

Answer 99

Compact or nested growth. Cells have clear or granular abundant cytoplasm. Fine but prominant capillary network. IHC PAX 2 and PAX8 Sarcomatid RCC (sRCC) 5% of RCCs. Worst prognosis (followed by clear cell)

Answer 100

Itself a "subtype" of Low grade NHL: 1. Nodal marginal zone lymphoma 2. Splenic marginal zone lymphoma – no need for immediate therapy; consider splenectomy 3. Extra-nodal marginal zone lymphoma of mucosa-associated lymphoid tissues (MALT)

Answer 101

Heterogenous small B cells including marginal zone (centrocyte-like) cells, mono-cytoid-like cells, small lymphocytes and scattered immune-blasts - Plasma cell differentiation often present B cell+ CD79 andCD 20. Germinal marker negative (eg CD10) - since matured to the margins. T-cell marker -ve (CD3-, CD5-)

Answer 102

Neuroblastoma Rhabdo RCC Clear cell

Answer 103

Anaplasia refers to the loss of differentiation of cells) (~5%) 3 cytological abnormalities: 1) Mitotic figures 2) Nuclear enlargement (3x or more than normal) 3) Hyperchromatic and pleomorphic nuclei * Anaplasia may be diffuse or focal (even in one or two foci indicate poor prognosis) * Related to high rates of relapse and death

Answer 104

1) Injection of blue dye/radioactive substance around tumour; 2) Injected material is located visually and/or with device that detects radioactivity from radionuclide (Geiger counter; sentinel node appears in 5-60mins; node is then removed and checked for tumour cells). Adv – presence of occult or micromets may alter treatment approach, reduces unnecessary LN dissection thereby eliminating increased risk of lymphoedema, infection and wound breakdown, used to prognosticate; Disadv – false negative rate 5%. Breast and melanoma; also vulva, merkel, penile, endometrial Ca (investigational)

Answer 105

N3c SEER database known to have a very poor prognosis (still stage 3), potentially curable. >60Gy is asosciated with better outcomes. I would give 40Gy/15# (or 50/25) then boost to 60Gy in 2Gy/#. Brachial plexus OAR 66Gy).

Answer 106

"PB KTL" = Lead (Pb Kettle) Prostate, Breast, Kidney (RCC), Thyroid, Lung Solid/scerotic = Prostate Mixed = Breast. Lytic = KTL Also lytic = Melanoma and myeloma.

Answer 107

- Rare <10% of CNS tumours - Bimodal age: <5 and 30-40 - 90% CNS, 10% spinal (especially Myxopapillary in adults) RFs: NF2, no other clear RFs Histo: Monomorphic round to oval cells with speckled chromatin. Perivascular pseudorosettes and, less frequently, true ependymal rosettes. IHC: GFAP, EMA, S100 Grd 1 = sub ependymoma and myxopapillary Grd 2 = "Classic" Grd 3 = Anaplastic Grd 4 = ependymablastoma - basically a medullo. Grade, location (spine, cranium),extent of resection, mets, determine RT dose/technique (i.e. mets get 36/20 CSI). Molecular subtype (there are 9) is more prognostic. 1q gain is bad (opposite of neuroblastoma)

Answer 108

There. are nine (including divisions between kid = A and adult =B) WOrst post-fossa Group A Best Myxopapillary

Answer 109

t(11,18) - predicts resistance to Abx.

Answer 110

Sx: Increased ICP – (headaches, vomiting, altered mentation), visual changes eg. bitemporal hemianopia, Endocrine e.g. diabetes insipidus, panhypopituiarism. Types: Adamantinomatous mostly seen in paeds Papillary - mostly adults Path Features: Adamantinomatous – poorly circumscribed NESTS of EPITHELIUM; peripheral cells show nuclear palisading; contents resembles crank case oil; stellate reticulum, wet keratin, calcification and xanthogranulomatous inflammation. Papillary – well-circumscribed CORES of STROMAL CELLS; no wet keratin, no calcification, and fluid does not resemble crank case oil; IHC – CK 20 and CK8 –ve

Answer 111

Size>1cm, sessile serrated, High grade dysplasia. Hyperplastic Polyp Hamartoma (also a good differential in: lungs, skin, heart, breast, liver). Divertucular Polyp Inflammatory Polyp.

Answer 112

Malignant: AdenoCa Carcinoid GIST Sarcoma - leimyosarcoma, angisarcoma Met Benign: Hyperplastic poly Unfammatory polyp Hamatoma Diverticular polyp

Answer 113

Only one of the following: T2b (more than 1/2 of one lobe) –T2c (both), or GS 3 + 4 = 7/grade group 2, or PSA 10–20 ng/mL, and Percent of positive biopsy cores <50%

Answer 114

Automatic Unfav if - Gleason 4+3 (ISUP 3) - &/Or, >50%cores. 2 or 3 intermediate risk factors: GS 3 + 4 PSA 10–20 ng/mL T2b–T2c

Answer 115

T3a OR Gleason 8 or higher (if 5+any then very high risk) OR PSA>20

Answer 116

Very high risk: T3b–4 (tumour in SV or organ invasion) or Primary GS 5 or >4 cores with GS 8–1

Answer 117

Spindle and pyramidal cells invading basement membrane. HMWCK GATA3 CL7, p63. Negative for PSA and AMACR PAX8. Grading based on atypia and mitotic figures.

Answer 118

Disease localised to the cervix AND less than 2cm (Stage IA and IB1) OR IIA (upper 2/3rds of vag) NB: 1B2 (limited to the cervix but big = 2 to 4cm) = Chemo RT Peters (for post op chemo) = 3Ps = Parametrial Invasion, Pos Margin, Pos Node Sedlis (for adj RT) = SDLvi = based on size>4cm, deep or middle stromal invasion, LVI

Answer 119

SCC, cervical adenocarcinoma, Adenosquarmous carcinoma, clear cell carcinoma, Endometrial endometriod carcinoma Endometrial papillary serrous adenocarcinoma Small cell carcinoma Undifferentiated Sarcoma Lymphoma Metastais Melanoma Benign: Cervical ectropian

Answer 120

NF 2 MEN sounds like a 90s boy band Meningioma - 25% lifetime risk Ependymoma (especially spibal) Neruomas: accousric/Schwannoma

Answer 121

MASSive LDH response Male, Age >17years, size>8cm, Site (Pelvis/Trunk is bad). Elevated LDH, poor response to chemo. Cytogenetics - 90% T(11,22), 10% t(21,22) = bad.

Answer 122

Both: CD 99, S100, vimentin Ewings: Fli1, SAPB2 Osteosarcoma:

Answer 123

Osteosarc - metaphysis Giant cell - epiphysis Ewings - diaphysis.

Answer 124

LG and High grade gliomas Osteosarcoma Other sarcomas Leukaemia Papillary thyroid Prostate and breast

Answer 125

Lung adeno Kidney (PAX 8) Colorectal (upper GI are CK7 -, but CDX2 +) Liver Adrenal adenocarcinoma Cholangiocarcinoma

Answer 126

Colon cancer (90%), Merkel cell tumor (86%), Urothelial carcinoma (68%), gastric adeno (56%), and pancreatic carcinoma (56%)

Answer 127

III, IV, V(1 and 2), IV Oculomotor: upper eyelid, down and out Trochlea - upward gaze Abducens = lateral rectus palsy. Diplopia V1: supra orbital fissure ->supraorbital notch V2: Rotundum V3: Ovalis

Answer 128

HCC: Hep Par1 AFP Glycogen3. CK7 neg Cholangio: Ck7 CEA

Answer 129

HCC: Trabecular (most common) with 4+ atypical hepatocytes surrounded by flattened endothelial cells - Sinusoidal vessels surrounding tumour cells Cholangio: - Sclerosing with malignant gland - Desmoplastic stroma - Resemble duct rather than hepatocytes

Answer 130

Patients with EPN-PFA, EPN-ZFTA, and EPN-MYCN tumors showed the worst outcome with 10-year overall survival rates of 56%, 62%, and 32%. EPM-MYC Also bad is 1q Gain Overall - The five-year survival rate for ependymomas is nearly 85%.

Answer 131

Papillary cystic architecture with: Dense lymphoid stroma and a double layer of oncocytic epithelium.

Answer 132

Chordoma is a slow growing cancer of tissue found inside the spine (thought to arise from notocord remnant). Chordoma can happen anywhere along the spine. It is most often found near the sacrum (33-50%) or Clivis (33%) Smaller treat 25/5 Otherwise >60Gy needed if primary Tx. R1 resection 54/30.

Answer 133

Infection: 50%clear 8 months, 90%2yrs, 10% persistent, 10% precursor, 10% malig Persistence: Failure to clear (e.g. due to immune sup), viral host genome integration Precursor Lesion: Development of high grade squamous intra-epithelial lesion (HSIL) - Increased risk with multi-parity, long-term OCP use, and smoking Malignant invasion: Transformation into cancer

Answer 134

1. VHL 2. Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) 3. Birt-Hogg-Dubé Syndrome 4. Hereditary papillary RCC

Answer 135

Hx exam for clinical/symptomatic anaemia, bladder mass, DRE (after PSA), bowel/bladder changes Urine: cyctology, MSU Bloods: Hb, renal function, PSA. CT KUB Consider Cytoscopy Bx. Digrected imaging such as staging CT/PET and MRI based on above.

Answer 136

A plasma/BC-cell neoplasm that secretes monoclonal gamma immunoglobulins (M-Proteins). 80%IgG, followed by IgA. Does not occur in kids Very rare before age 35 Mean age 70 Age, toxic exposures, family Hx, immunesupression

Answer 137

MGUS - very common in ppl age >70 (~5%) 1%/year risk transformation. No CRAB - SPEP <3ng/L, BMAT<10% clonal plasma cells. Smouldering: NO CRAB But SPEP >3, and monoclonal cells>10% on BMAT.

Answer 138

Lung Adeno is separated into 5 main histological patterns (LAMPS): o Low grade: lepidic o Intermediate grade: Acinar, Papillary o High grade: Micropapillary, Solid

Answer 139

Tumour confined to one hemithorax (including ipsi and contralateral mediastinum) and ipsilateral SCF nodes

Answer 140

Patient: Sex (Female = better; male =worse) ECOG 0-1 Weight lose = worse Tumour: Stage Para-neoplastic syndrome (=worse) LDH – increase LDH = worse; Sodium – Na< 135, MS 9 months vs. Na>135 MS 13 months (P<0.001) Albumin Treatment: Can have durvulmab Can have Etoposide + Platinum

Answer 141

Patient: Male Age ECOG Fitness for interventions such as extra-pleural pneumonectomy Tumour: * Histology most important: Epitheloid (best) biphasic (mixed) Sarcomatid (by far the worst - Sarcomatid dont get surgery!) * Stage/nodal involement/distant mets. * Elevated LDH * Hematologic abnormalities (thrombocytosis, leucocytosis, anaemia) Treatment: Chemo and surgery most impactful

Answer 142

Mycosis fungoides and Sézary syndrome are types of cutaneous T-cell lymphoma. A sign of mycosis fungoides is a red rash on the skin. In Sézary syndrome, cancerous T-cells are found in the blood

Answer 143

Histo: inside out growth pattern. Typically Er+ 4-5% of invasive breast. Typically early post-meno Relative to IDC NST: faster local growth, earlier nodal spread, more frequently multifocal. I would boost these patients.

Answer 144

DCIS implies that the basement membrane is preserved despite carcinoma in situ cells arising from the ductal epithelium. Typically grows toward nipple. Nuclear pleomorphism, mitotic rate and cell morphology determine grade: I,II or III Encompasses a heterogeneous groupin terms of histomorphology, underlying geneticss, biomarkers and potential for progression. Five histologic subtypes (mnemonic: C2PMS): cribriform, comedo (worst prognosis), papillary, micropapillary, solid (second worst prog). prognosis).

Answer 145

(1) presence of tumor in a previously irradiated region, (2) sufficient latency time between the original and new tumors, generally measured in years, (3) histology of the new tumor must be distinct from the original, (4) no Hx of disease predisposing to tumor development (e.g. Li Fraumeni) Other features: Often sarcomas occurring 5-10years post - e.g angiosarcoma for breast, or characteristic tumours at a given site - e.g. mucoepidermal carcinoma of parotid after oral scc RT. Or leukaemia after pelvic RT.

Answer 146

The fundamental insult is DNA damage (single &/or double strand breaks, &/or base changes) via direct ionizing radiation or indirect ionised mediators (i.e ROS). This damage is not or is improperly repaired, and the cell escapes immune surveillance carrying either mutations, or changes to gene expression. Another mechanism is ocogenic viral activation. Radiation oncogenesis has been compared to chemical carcinogenesis: with 3 steps - Initiation, Promotion, progression.

Answer 147

3 steps = Initiation, promotion, progression: Initiation: Irreversible genetic alteration via direct injury from carcinogen or metabolically activate carcinogen (procarcinogen) to DNA such as adducts that are not repaired (or inappropriately repaired). Promotion: Initiated cell evades immune surveillance/apoptosis, and these premaligant cells undergo enhanced proliferation. Progression: Genome/karyotype instability and maligant transformation with invasive growth.

Answer 148

Occupational exposures across a wide range of industries (e.g. plastics/metal fabrication/hairdressing) have been linked to bladder cancer. In particular: Aromatic hydrocarbons, disel exhaust, hair and textile dyes. Drugs that increase risk: Cyclophosphamide Pioglitazone Some old analgesia discontiinued in the early 1980s

Answer 149

Risk factors: - Smoking - Schistosomiasis infection - Chronic irritation e.g. from recurrent UTI, bladder calculi, indwelling catheter ii. PATHOGEN: Chronic irritation and injury to the urothelial lining → squamous metaplasia → dysplasia → carcinoma in situ → squamous cell lining of the bladder with keratinisation and intercellular bridging → squamous cell carcinoma

Answer 150

E6 protein binds and facilitates degradation of p53 tumour suppressor protein * Normal p53: DNA damage -> p53 up-regulated CDK1-p21 -> inactive cyclin-CDK complex -> cell cycle halted at the G1/S check point * Degraded/ absent p53: G1/S check point disrupted -> progression through G1/S check with damaged DNA. E7 protein binds to and phosphorylate Rb protein (tumour suppressor) * Normal: Rb binds to and inhibit E2F transcription factor (in G1 checkpoint of all cell cycle) * E7 binds to and phosphorylate Rb -> release of E2F transcription factor -> transition of cell from G1 to S phase of cell cycle with damaged DNA

Answer 151

I: No capsular invasion II: A= microsopic invasion. B=macroscopic III: Invasion into adjacent structures IVa: Mets to pleura and pericardium Ivb: distant mets. RT from IIA to IVA "curative intent"

Answer 152

WHO A->AB->B->BC-C A- Medullary Spindle cells NO lymphocytes (AB has some). B = Lymphocyte Rich. B2 Thymus begins to look abnormal, OS drops to 60%@5yrs B3= Well differentiated thymic carcinoma with few lymphocytes. = Thymic carcinoma5-yr OS 35%

Answer 153

* FBE/ UEC/ CMP. Consider lymphoma/LDH * beta-HCG and AFP (?germ cell tumour) * Thyroid function test (?thyroid primary) * Serum anti-ACh antibodies to assess for myasthenia gravis (before surgery) * CT chest with contrast * FDG PET * Lung function test * If thymoma suspected and considered resectable, Bx may be omitted and resection performed * If unresectable/inoperable, do core bx to confirm Dx (Bx should not violate pleural space!)

Answer 154

Patient: Ecog, age, fit for surgery, ongoing risk factors Tumour: TYpe: ductal adeno w/squarmous compnent is worse. Acinar very slightly better than ductal (5yr OS 10 vs 5%) Grade and Kloppel grade Invasion (i.e resectability) Location: Head of panc better (earlier presentation, more resectable). TNM. Treatment: Rescetable = 25% 5yr OS. +margin shit OS.

Answer 155

May help suggest a diagnosis or direct further investiation (e.g. colonoscopy for CEA++). The adenocarcinoma markers: CEA: CRC, cholangio, gastric CA125: Ovarian CA15.3: Boob CA 19.9: Pancreas PSA LDH is elevation is a poor prognostic sign.

Answer 156

Initial cytokeratins: CK7, CK20 upper GI primary CK7+, CK20- lower Ck7- CK20+ Target cytokeratins: GATA3 - Breast CDX2 - colorectal (especially if CK20+) TTF-1 - Lung PAX8 - Ovarian/endometrial (RCC is PAX 8 and PAX2) Non-cytoketatins: ER and PR.

Answer 157

- NB CUP (e.g. SCC) has better prog than ACUP. - Single metastatic site - Aim surgical excision or ablative. - Tumour can put in a clincicopathological subgroup (about 40%): E.g. Female with axillary lymph mets, female with carcinomatis peritonii - where tumour directed treatment offers better OS. - Comprehensive Molecular Profile or Tumour Molecular Burden suggest targetable mutation or response to immunotherapy. - Good response to initial therapy

Answer 158

If markers/IHC and Ix fail to identify: 1) Molecular cancer CLASSIFIER assay - can "predict" to some degree in in about 60% of cases. 2) Establish actionable mutations (Comprehesive Molecular Profile) and predictors of of response to immunotherapy - Tumour Mutational Burden (Mutations create neoantigens that the immune system may attack - e.g. T-cell directed Ipilumimab). Tx: If solitary met (much better prognosis) aim resection or ablative. If belongs to a clinicopathological subgroup (30-40%) e.g. Female with axillary mets (better prog), Female with peritoneal carcinomatosis, dude with bone mets and elevated PSA - then directed therapy has much better PFS. If target mut, or high TMB score, then directed therapy. If and only if none of the above "Empiric Chemo" doublet w/platinum: Classic combos Carbo Pac, Cis Gem.