Oncology Flashcards

Question

WHO 2021 The critical importance of identifying mutations other than the canonical IDH1 R132H mutation in diffuse gliomas, especially in patients younger than 55 years of age, is emphasized

Answer 1

1p/19q codeletion on fluorescence in situ hybridization (FISH) isocitrate dehydrogenase (IDH) mutant or IDH-wildtype on immunohistochemistry loss of ATRX expression TERT promoter mutations TP53 histone H3 mutations EGFR amplification CDKN2A/B alterations- BAD (grade 4 astrocytoma)

Answer 2

Four general groups of diffuse gliomas are recognized in the 2021 WHO classification: 1) adult-type diffuse gliomas, 2) pediatric-type diffuse low-grade gliomas, 3) pediatric-type diffuse high-grade gliomas 4) circumscribed astrocytic gliomas.

Answer 3

Adult-type diffuse gliomas are astrocytoma IDH-mutant; oligodendroglioma IDH-mutant and 1p/19q-codeleted glioblastoma, IDH-wildtype. IDH-mutant diffuse astrocytomas the terms IDH-mutant “anaplastic astrocytoma” and “glioblastoma” have been dropped. In addition, if an IDH-mutant diffuse astrocytoma exhibits CDKN2A/B homozygous deletion, it is designated as a CNS WHO grade 4 neoplasm, even if histologic features of malignancy such as necrosis and microvascular proliferation are absent.

Answer 4

p53 (NF1, Li-Fraumeni Turcot Ollier Maffucci Radiation M>F White>black>asian Peak age 65-75, usually after 40s

Answer 5

TP53 gene, located on chromosome 17, is a tumor suppressor gene, responsible for the production of the p53 protein, a transcription regulatory protein which works in concert with a number of other proteins, together forming the p53 pathway Inherited mutations in this gene result in the rare hereditary cancer condition known as Li-Fraumeni syndrome, which predisposes to a wide variety of malignancies 1

Answer 6

Isocitrate dehydrogenases are enzymes that catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate (α-ketoglutarate). This reaction also produces NADPH (IDH1 and IDH2) or NADH (IDH3) 4,5. Isocitrate dehydrogenase acts at the rate-limiting step of the tricarboxylic acid cycle (also known as Krebs cycle). IDH1 - located on the long arm of chromosome 2 (2q32) - encodes for cytosolic isocitrate dehydrogenase mutations affect a single amino acid residue 132, in -- most instances (>85%) resulting in arginine being replaced with histidine and thus denoted R132H 8 IDH2 - located on the long arm of chromosome 15 (15q21) -encodes for mitochondrial isocitrate dehydrogenase - mutations affect a single amino acid residue 172, analogous to the R132 residue in IDH1 MUTANT ARE BETTER TTHAN WILD mutant prognosis than gliomas without the mutation (WILDTYPE) 3. In other words: IDH-wildtype = IDH negative = no mutation = poor prognosis ((ALL GBM ARE WILD) IDH-mutant = IDH positive = mutation present = better prognosis (LOW GRADE ARE MUTANT)

Answer 7

Somatic mutations of IDH result in enchondromatosis syndromes: Ollier disease and Maffucci syndrome

Answer 8

POOR PROGNOSIS (All GBMs are IDH WILD)

Answer 9

The majority (90%) of IDH mutations in gliomas affect IDH1 with a single amino acid missense mutation at arginine(R)132 replaced by histidine (H); thus denoted as IDH1 R132H. This is the mutation generally tested by immunohistochemistry

Answer 10

... the chances of an IDH mutation being detected by next-generation sequencing is low and not considered mandatory

Answer 11

IDH1 R132H negative tumor actually harbors a less common mutation. Generally IDH mutated (IDH1 and IDH2) tumors are more likely to also have MGMT methylation (80% for IDH-mutant compared to 60% of IDH-wildtype tumors)

Answer 12

bad prognosis High activity of MGMT (i.e. unmethylated) results in reduced efficacy of alkylating agents, and thus is a poor prognostic factor It is also predictive of pseudoprogression following Stupp protocol

Answer 13

Ch5 GBM! can be seen in oligodendroglioma, follicular thyroid, melanoma, TCC, HCC

Answer 14

They are characterized by IDH mutation and 1p19q codeletion and can be WHO CNS grade 2 or 3. third most common glioma Middle age men 40s 50s, older > higher grade Male 1.3:1 Rare in children well-circumscribed, gelatinous, grey mass often calcified (70-90% of histological oligodendrogliomas: one of the most frequently calcifying tumors)

Answer 15

Grade 3 oligodendrogliomas (formerly known as anaplastic oligodendrogliomas) demonstrate increased cellular density, increased mitotic activity, microvascular proliferation and necrosis. Nuclear anaplasia is also common.

Answer 16

Importantly, and unlike astrocytomas, oligodendrogliomas with necrosis and microvascular proliferation are considered only WHO grade 3 and NOT grade 4 tumors

Answer 17

TERT promoter mutation CIC mutation FUBP1 mutation NOTCH1 mutations

Answer 18

Astrocytic tumors are primary central nervous system tumors that either arises from astrocytes or appear similar to astrocytes on histology having arisen from precursor cells. They are the most common tumors arising from glial cells and can be broadly divided into three groups: - diffuse, adult-type Astrocytoma IDHm WHO2-4 GBM IDH wild, WHO 4 - diffuse, pediatric type low vs high grade LOW GRADE: angiocentric; diffuse astrocytoma MYB1/MYBL1; MAPK altered HIGH GRADE 4: H3 K27, G34, IDHw, - circumscribed grade 1 - 3 PXA WHO1 pleomorphic xanthoastrocytoma , chordoid glioma, astroblastoma

Answer 19

Temporal lobe epilepsy young adults seziure 75% presentations WHO 2-3 difficult to distingish between it and epitheloid glioblastomas can have spindles, MNC, polygons GFAP and S100 _ve, and synaptophysin, MAP2 NF1

Answer 20

WHO 1 Cortical or deep grey matter Temporal>frontal>caudate>cerebellum and pons Asso. cortical dysplasia 80% , noonan Temporal lobe epilepsy Children specific glioneuronal element (SGNE)"+

Answer 21

Importantly, DNETs are negative for IDH mutations, TP53 mutations, and do not demonstrate 1p19q co-deletion 8. These features are helpful in distinguishing DNETs from low-grade astrocytomas (usually IDH mutated) and oligodendrogliomas (IDH mutated and 1p19q co-deleted). DNETs usually harbor fibroblast growth factor receptor tyrosine kinase domain duplication (FGFR1-TKDD),

Answer 22

ganglion cells (large mature neuronal elements): ganglio- neoplastic glial element: -glioma primarily astrocytic, although oligodendroglial or pilocytic astrocytoma components are also encountered 9

Answer 23

synaptophysin: positive neurofilament protein: positive MAP2: positive chromogranin-A: positive (usually negative in normal neurons) 9 CD34: positive in 70-80% The glial component may also show cytoplasmic positivity for GFAP. Genetics BRAF V600E mutations are encountered in 20-60% of cases 9 IDH: negative (if positive then the tumor is most likely a diffuse glioma)

Answer 24

tumor suppressor gene (cyclin-dependent kinase inhibitor 2A) that encodes for the p16 protein, involved in the CDK4/6–RB1 cell-cycle pathway - p16 +ve in HNSCC indicates a better prognosis - upregulated by HPV - p16 +ve cervical scc associated with high grade SIL (HSIL) - CDNK2A gene inactivation (p16-ve) by somatic mutation/deletion is seen in GBM is BAD

Answer 25

M > F peak 50-70s, second peak in young adults HPV/p16+ve oropharynx most common, decreasing oropharyngeal increasing

Answer 26

plummer vinson syndrome classic triad of dysphagia, iron-deficiency anemia and upper esophageal webs. ?iron deficiency anaemia

Answer 27

In the parotid gland, they are the most common malignant primary neoplasm. A slight female predilection most common in middle age (35-65 years of age) However, it is the most common malignant salivary gland tumor of childhood

Answer 28

The tumors are composed of a mixture of: mucus-secreting cells (muco-) squamous cells (-epidermoid) lymphoid infiltrate often also present 3 - low/intermediate or high grade - clear mucin-containing cells, which stain reddish pink with the mucicarmine stain 80% MAML2: alteration that appears to be specific for mucoepidermoid carcinoma

Answer 29

Multiple myeloma is a common malignancy in patients above 40 - 70% of cases are diagnosed between ages 50 and 70 with a median age of diagnosis being 70 years - male predilection (M: F 2:1) - Black populations are affected at nearly twice the rate as White populations 14.

Answer 30

Fracture Amyloidosis recurrent infection sec. to leukopenia plasmacytoma (solitary lesion in bone OR extramedullary) typically progress to MM

Answer 31

Monoclonal proliferation of MALIGNANT PLASMA cells Produce immunoglobulin (commonly IgG) Infiltrate haemopoietic locations (red marrow) - renal failure common - obstructive casts form in tubules (BJP, Ig,albumin, tamm-horsfall proteins) direct nephrotoxicity to renal tubules BJP high calc, dehydration, hyperuricemia and urate nephropathy amyloidosis AL type

Answer 32

Integrated diagnosis (combined tissue-based histological and molecular diagnosis) Histological diagnosis CNS WHO grade Molecular information (listed) e.g. Diffuse low-grade glioma, MAPK pathway-altered Subtype: Diffuse low-grade glioma, FGFR1 TKD-duplicated Histopathological classification: Oligodendroglioma CNS WHO grade: Not assigned Molecular information Duplication of the FGFR1 tyrosine kinase domain (next-generation sequencing)

Answer 33

Newly Recognized Tumor Types Diffuse astrocytoma, MYB- or MYBL1-altered Polymorphous low-grade neuroepithelial tumor of the young Diffuse low-grade glioma, MAPK pathway-altered Diffuse hemispheric glioma, H3 G34-mutant Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype Infant-type hemispheric glioma High-grade astrocytoma with piloid features Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (provisional type) Myxoid glioneuronal tumor Multinodular and vacuolating neuronal tumor Supratentorial ependymoma, YAP1 fusion-positive Posterior fossa ependymoma, group PFA Posterior fossa ependymoma, group PFB Spinal ependymoma, MYCN-amplified Cribriform neuroepithelial tumor (provisional type) CNS neuroblastoma, FOXR2-activated CNS tumor with BCOR internal tandem duplication Desmoplastic myxoid tumor of the pineal region, SMARCB1-mutant Intracranial mesenchymal tumor, FET-CREB fusion positive (provisional type) CIC-rearranged sarcoma Primary intracranial sarcoma, DICER1-mutant Pituitary blastoma

Answer 34

emphasized that the criteria defining atypical or anaplastic (ie, grade 2 and 3) meningioma should be applied regardless of the underlying subtype.

Answer 35

chordoid and clear cell meningioma are noted to have a higher likelihood of recurrence than the average CNS WHO grade 1 meningioma and have hence been assigned to CNS WHO grade 2

Answer 36

chordoid and clear cell meningioma are noted to have a higher likelihood of recurrence than the average CNS WHO grade 1 meningioma and have hence been assigned to CNS WHO grade 2

Answer 37

historically, rhabdoid and papillary morphology qualified for CNS WHO grade 3 irrespective of any other indications for malignancy.

Answer 38

SMARCE1 (clear cell subtype), BAP1 (rhabdoid and papillary subtypes), and KLF4/TRAF7 (secretory subtype) mutations, TERT promoter mutation and/or homozygous deletion of CDKN2A/B (CNS WHO grade 3), H3K27me3 loss of nuclear expression (potentially worse prognosis), and methylome profiling64 (prognostic subtyping).

Answer 39

4 principal molecular groups: WNT-activated, sonic hedgehog (SHH)-activated (SSH1 or SSH 2 poor prognosis) TP53 status Wild or mutant 4 subgroups of SHH and 8 subgroups of medulloblastoma, WNT-activated medulloblastoma, SHH-activated and TP53-wildtype medulloblastoma, SHH-activated and TP53-mutant medulloblastoma, non-WNT/non-SHH

Answer 40

Histopathological Molecular Anatomical site posterior fossa (60%) supratentorial (30%) (children) spinal cord (10%) - supertentorial - ZFTA (BAD), YAP1 (GOOD); GFAP almost always +ve; EMA , S100 and vermentin +ve, OLIG2 negative - posterior fossa - Group A (good) /B (bad) - spinal NOS or MYCN amplification (aggressive), (most common spinal tumour in adults, asso NF2) Myxopapillary -myxopapillary ependymoma is now considered CNS WHO grade 2, high recurrence

Answer 41

epithelial pleomorphic adenoma: this is the most common (≈50%) tumor of the parotid Warthin tumor: essentially only found in the parotid, in older, usually male patients; it is bilateral in 10-15% intraductal papilloma of salivary glands oncocytoma of salivary glands myoepithelioma: until recently considered a subtype of pleomorphic adenoma; they can also originate in breast and bronchus non-epithelial hemangioma lymphangioma lipoma

Answer 42

Malignant *****mucoepidermoid carcinoma: most of the malignant lesions****** adenoid cystic carcinoma myoepithelioma adenocarcinoma (not otherwise specified) acinic cell carcinoma of salivary glands squamous cell carcinoma of salivary glands lymphoepithelial carcinoma malignant mixed tumors of the salivary glands carcinoma ex pleomorphic adenoma carcinosarcoma (true mixed tumor of the salivary glands) metastasizing pleomorphic adenoma salivary duct carcinoma metastases (mostly to intraparotid lymph nodes) cutaneous squamous cell carcinoma malignant melanoma testicular seminoma (rare) lymphoma (rare) primary: arising from the parotid gland as a MALToma 6 secondary: involving the intraparotid lymph nodes

Answer 43

Malignant mucoepidermoid carcinoma: most of the malignant lesions adenoid cystic carcinoma myoepithelioma adenocarcinoma (not otherwise specified) acinic cell carcinoma of salivary glands squamous cell carcinoma of salivary glands lymphoepithelial carcinoma malignant mixed tumors of the salivary glands carcinoma ex pleomorphic adenoma carcinosarcoma (true mixed tumor of the salivary glands) metastasizing pleomorphic adenoma salivary duct carcinoma 7 metastases (mostly to intraparotid lymph nodes) cutaneous squamous cell carcinoma malignant melanoma testicular seminoma (rare) lymphoma (rare) primary: arising from the parotid gland as a MALToma secondary: involving the intraparotid lymph nodes

Answer 44

Warthin tumors are the 2nd most common benign parotid tumor (after pleomorphic adenoma) Lymphomatous papillary cystadenomas benign lymphoid origin most commonly arise from the parotid tail. bilateral or multifocal in up to 20% of cases most common neoplastic cause of multiple solid parotid masses. typically 6th decade, Men 2.2 vs 1 Associated with smoking and radiation 1% transformation

Answer 45

rare histological subtype of adenocarcinoma. NOTABLE TENDENCY FOR PERINEURAL SPREAD generally low grade

Answer 46

Perineural tumor spread is more frequently associated with 1,2,5: mucosal/cutaneous squamous cell carcinoma oral cavity/laryngeal (2-30%) > cutaneous (3-8%) most common overall 5 salivary gland carcinoma adenoid cystic carcinoma (highest incidence per individual tumor 5) mucoepidermoid carcinoma mucosal/cutaneous basal cell carcinoma (2-5% demonstrate perineural tumor spread) 4 melanoma 0.8 - 2.6% demonstrate perineural spread8 65% are desmoplastic subtype lymphoma sarcoma meningioma (rare) 6

Answer 47

70-80% of benign salivary gland tumors females than males (2:1) ill defined margins, can locally recur large size risk for maligancy

Answer 48

Glioblastomas have been defined as diffuse astrocytic tumors in adults that MUST** be IDH-wildtype Now an entirely separate diagnosis from astrocytoma, IDH-mutant grade 2, 3 or 4 Primary GBM are largely wild type Secondary GBM now equates to astrocytoma IDH MUTANT Histology variants giant cell glioblastoma gliosarcoma epithelioid glioblastoma

Answer 49

GFAP: positive but of variable intensity S100: positive nestin: positive p53 protein: positive if TP53 mutated EGFR: positive in 40-98% of cases 16 IDH-1 R132H: negative (by definition, otherwise not an IDH-wildtype glioblastoma, but rather an astrocytoma, IDH-mutant WHO CNS grade 4) 16 H3 K27M mutation: negative (if positive then diffuse midline glioma H3 K27-altered)

Answer 50

EGFR gene amplification TERT promoter mutations combined gain of whole chromosome 7, loss of chromosome 10 [+7/-10] alterations of the CDK4/6–RB1 cell-cycle pathway: 80% due to deletions of CDKN2A

Answer 51

Despite all of this, even in the best-case scenario, glioblastoma carries a poor prognosis with a median survival of <2 years 15. Negative prognostic factors include: increased necrosis greater enhancement deep location (e.g. thalamus) MGMT not-methylated increased age lower pre-diagnosis functional status (e.g. ECOG performance status)

Answer 52

Arabic numbers Grading emphasize molecular markers in grading Essential and desirable diagnostic criteria NOS NEC not elsewhere classified -fully characterised but not fitting in established classification system Dropping variant and anaplastic

Answer 53

Pediatric-type diffuse low-grade gliomas - diffuse astrocytoma, MYB- or MYBL1-altered - angiocentric glioma - polymorphous low-grade neuroepithelial tumor of the young - diffuse low-grade glioma, MAPK pathway-altered Pediatric-type diffuse high-grade gliomas - diffuse midline glioma, H3 K27-altered - diffuse hemispheric glioma, H3 G34-mutant - diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype - infant-type hemispheric glioma

Answer 54

Adult-type diffuse gliomas - astrocytoma, IDH-mutant - oligodendroglioma, IDH-mutant, and 1p/19q-codeleted - glioblastoma, IDH-wildtype IDH positive + 1p19q codeletion = oligodendroglioma = BETTER prognosis IDH positive + no 1p19q codeletion = astrocytoma When diffuse adult gliomas have non-mutated IDH (i.e. "wild-type"), the status of 1p19q is of uncertain clinical significance and the tumor is considered to be not elsewhere classified (NEC) 6,7. Similarly, if deletion is partial (e.g. 1p loss with 19q retention), then tumors should also be considered NEC IDH-wildtype = IDH negative = no mutation = poor prognosis IDH-mutant = IDH positive = mutation present = better prognosis

Answer 55

In most instances, IDH status is obtained by performing immunohistochemistry on surgical biopsy specimens. The majority (90%) of IDH mutations in gliomas affect IDH1 with a single amino acid missense mutation at arginine(R)132 replaced by histidine (H); thus denoted as IDH1 R132H. This is the mutation generally tested by immunohistochemistry IDH-wildtype (negative) As of the 5th edition (2021) of the WHO classification, all glioblastomas are now, by definition, IDH-wildtype

Answer 56

enchondromatosis syndromes: Ollier disease and Maffucci syndrome

Answer 57

WHO grade 1 75% in first 2 decades, M=F Most common primary brain tumor of childhood Strong association with NF1 (optic pathway glimas) 60 % PF ; 30% Optic pathway >brainstem and spine supratentorial in adults,

Answer 58

GFAP: positive S100: positive OLIG2: positive IDH R132H mutation: negative p53 protein: negative or weak Pilocytic astrocytoma, as well as pleomorphic xanthoastrocytomas, frequently have BRAF alterations (present in ~70% of cases). Importantly they, along with other pediatric low-grade gliomas, lack IDH mutations and TP53 mutations

Answer 59

10 yr survival >95%

Answer 60

- middle age and elderly - NF1 association - **Defined by characteristic DNA methylation profile - Prognosis similar to GBM Other molecular characteristics, common alteration NF1 BRAF FGFR1 CDKN2A/B deletion ATRX (mutations or loss)a MGMT promoter methylation

Answer 61

IDH status - IDH stands for “Isocitrate Dehydrogenase.” This is an enzyme involved in the production of energy by brain tumour cells, and in GBM it may have a mutation which confers a better prognosis. Research has indicated that different forms of GBMs have differences between these enzymes, though their role in tumour initiation (how a tumour first begins) and tumour growth is still being explored. As part of this research, a number of drugs that can potentially influence IDH enzymes are being investigated. IDH 'wild' type status - This occurs in about 90% of GBM brain tumours and usually indicates that the tumour formed as glioblastoma since the very beginning (primary GBM) and carries a worse prognosis than those classified as being IDH mutant. IDH mutant - This represents approximately 10% of GBMs, and indicates a secondary glioblastoma tumour, meaning that it was previously a lower grade glioma and carries a better prognosis than a 'wild' type status. IDH NOS - This stands for “Not Otherwise Specified”, meaning that in rare cases, it cannot be determined whether a GBM is 'wild' type or mutant for IDH. MGMT methylation - This is short for O6-methylguanine-DNA methyltransferase and whether it is 'methylated' or 'unmethylated' indicates how effectively the tumour cells can repair the damage inflicted on them by certain chemotherapy drugs, such as Temozolomide. Patients with higher levels of MGMT methylation respond better to Temozolomide treatment. Methylation means the transfer of a methyl group (CH3) from one molecule to another, which affects the way the tumour behaves. 1p/19q deletion - The word “deletion” refers to the fact that when you look at one of the chromosomes, the genes at positions 1p and 19q are missing. Tumours with a 1p/19q deletion may respond better to certain chemotherapy drugs such as Temozolomide or Carmustine, than other tumours without the deletion.

Answer 62

IDH 'wild' type status - This occurs in about 90% of GBM brain tumours and usually indicates that the tumour formed as glioblastoma since the very beginning (primary GBM) and carries a worse prognosis than those classified as being IDH mutant. IDH mutant - This represents approximately 10% of GBMs, and indicates a secondary glioblastoma tumour, meaning that it was previously a lower grade glioma and carries a better prognosis than a 'wild' type status. NOS- cant be determined

Answer 63

MGMT methylation - This is short for O6-methylguanine-DNA methyltransferase and whether it is 'methylated' or 'unmethylated' indicates how effectively the tumour cells can repair the damage inflicted on them by certain chemotherapy drugs, such as Temozolomide. Patients with higher levels of MGMT methylation respond better to Temozolomide treatment. Methylation means the transfer of a methyl group (CH3) from one molecule to another, which affects the way the tumour behaves. 1p/19q deletion - The word “deletion” refers to the fact that when you look at one of the chromosomes, the genes at positions 1p and 19q are missing. Tumours with a 1p/19q deletion may respond better to certain chemotherapy drugs such as Temozolomide or Carmustine, than other tumours without the deletion.

Answer 64

1p/19q deletion - The word “deletion” refers to the fact that when you look at one of the chromosomes, the genes at positions 1p and 19q are missing. Tumours with a 1p/19q deletion may respond better to certain chemotherapy drugs such as Temozolomide or Carmustine, than other tumours without the deletion.

Answer 65

Usually WHO grade 1/2. 955 Anaplastic grade 3 BRAF V600E mutation 10-60% (not specific) p53 mutation (not specific) RFx NF1 TUBEROUS SCLEROSIS

Answer 66

A number of tumours share similar histology, composed of relatively uniform primitive small round blue cells. They also share many demographic, radiographic and clinical similarities. They include: Ewing sarcoma peripheral primitive neuroectodermal tumour (pPNET) Askin tumour neuroblastoma Wilms tumour hepatoblastoma embryonal rhabdomyosarcoma medulloblastoma pineoblastoma retinoblastoma embryonal tumour with multilayered rosettes, which was formerly known as CNS primitive neuroectodermal tumour (CNS-PNET) neuroepithelioma desmoplastic small round cell tumour small cell mesothelioma acute leukaemia

Answer 67

Urothelial carcinoma 90%

Answer 68

Schistosomiasis endemic regions

Answer 69

Cigarette smoking, occupational carcinogens schistosomiasis 9p9q deletion and TP53 mutations

Answer 70

Entirely benign

Answer 71

Papilloma Papilloma urothelial neoplasm of low grade potential Low grade papillary urothelial High grade papillary urothelial carcinoma carcinoma

Answer 72

Positive staining for PAS periodic acid Schiff in Paget.

Answer 73

Young Middle age HPV 16 18 Smoker Often from precancerous VIN, leukoplakia HPV forms multifocal and warty Old people HPV neg (well differentiated keritanising SCC, uniformed From Lichen sclerosis or inflammatory disease

Answer 74

Diethylstilbestrol during pregnancy Vaginal adenosis a precursor to clear cell adenocarcinoma

Answer 75

LKBI gene First identitfied in peutz jegher Cervizlx everts at adolescents Columnar cells exposed in transitional zone. Undergo squamous metaplasia CIN 1 low grade LSIL 2&3 high grade HSIL

Answer 76

HPV (16/18/31/33) Vaccine protection 16/18 Early age at first sexual intercourse multiple Partners with multiple partners Smoking Immunodeficiency HPV express E6 and E7 proteins inactivating TP53 and Rb tumour suppressor gene Loss of LKB1 gene 20% Mets risk 1% under 3mm vs 10+% greater than 3mm

Answer 77

Differential Diagnosis ❚ Metastatic adenocarcinoma ● Presentation with multiple lung masses favors metastasis ● Metastatic colonic adenocarcinoma is typically CK7 negative and CK20 positive ● CDX2 is positive in mucinous BAC and gastrointestinal lesions ● Estrogen and progesterone receptors and gross cystic disease fluid protein-15 are often positive in breast carcinomas ● Prostate-specific antigen, prostatic acid phosphatase are positive in metastatic prostate carcinoma ● TTF-1 is positive in primary lung and metastatic thyroid carcinoma; thyroglobulin is positive in the latter, and mucin staining is positive in the former

Answer 78

Micropapillary pattern is associated with poorer prognosis

Answer 79

acinar pattern papillary pattern bronchioalveolar pattern solid pattern well differentiated fetal adenocarcinoma WDFA mucinous adenocarcinoma mucinous cystoadenocarcinoma signet ring adenocarcinoma clear cell adenocarcinoma lung adeno CK7 +ve!! CK20 -ve, TTF1+ve bronchiolalveolar carcinoma (BAC) is CK7 +ve!! CK20 -ve, TTF1-ve

Answer 80

●Deletion of chromosome 3p is a consistent finding in SCLC, and this region may include the fragile histidine triad gene (FHIT) located at 3p14.2 ● About 20% of SCLCs show mutations in the Rb gene ● About 70% to 95% of SCLCs show Bcl-2 expression ● SCLC shows the highest rate of p53 mutation of all lung carcinomas, and consequently a strong nuclear p53 staining pattern in greater than 10% to 20% percent of cells is strongly suggestive of a p53 mutation

Answer 81

Three histologic categories: epithelioid70% , sarcomatoid, and biphasic ● Rare tumor showing a male predominance and an association with asbestos exposure ● Most patients are between 50 and 70 years old ● Associated with a poor prognosis, with average survival of less than 1 year Positive for keratin AE1/AE3, CAM5.2, and CK7; specific markers include calretinin, CK5/6, WT-1, D2-40 Other Techniques for Diagnosis ● Inactivation of the CDKN2A/ARF locus at 9p21, which codes for the tumor suppressor genes p16INK4a and p14ARF, is a common finding Calretinin stains both nucleus and cytoplasm with stronger nuclear staining, which is a helpful feature of mesothelial cells ● Invasion is the best indication of malignant mesothelioma ● Patients with purely epithelioid mesothelioma show the longest survival, whereas the shortest survival occurs with sarcomatoid histology—yet the difference between the two survival rates is only a matter of months

Answer 82

Lymphoma ● Positive for leukocyte common antigen (LCA) and other lymphoid markers (e.g., CD3 (T-CELLSs), CD20 (B-cells), CD30) and negative for cytokeratin

Answer 83

Woman 20s-30s anterior mediastinal mass most common nodular sclerosing variant most common type- best determined by nodal analysis (some Dx features may not be present on extranodal sites) Classic Reed-Sternberg cells in a background consistent with Hodgkin lymphoma are needed to establish a new diagnosis of Hodgkin lymphoma in an extranodal site can be cystic (degeneration) MOST COMMON type of lymphoid malignancy. 2nd on e is DLBCL

Answer 84

F>M peak 20-40s typically anterior mediastinum , usually invovles thymus complication SVC obstruction CD19, CD20, CD22, and CD45 positive ● CD10, CD5, CD43, CD21, and immunoglobulin negative (resembling the phenotype of normal thymic B cells) ● Negative for CD15 ● Significant percentage of these cases can be CD30 positive ● Sclerosis and necrosis are common findings ● Good response to multiagent chemotherapy with consolidation radiation therapy ● Almost always B-cell lineage Positive for CD20; negative for TdT, CD99, CD1a

Answer 85

M=F, wide age range 3 types - hayline vascular (80), plasma cells, mixed hepatosplenomegaly, pancytooenia 1/3 have other malignancies more frequent in HIV ASSOCIATED WITH HHV8!!!

Answer 86

lymphoma, cd45 is a leukocyte common antigen

Answer 87

Gastric cardia adenocarcinoma ● May be identical to Barrett esophagus–associated adenocarcinoma ● Staining for CK7 and CK20 can help distinguish Barrett esophagus–related adenocarcinoma (CK7 positive; CK20 negative) from gastric adenocarcinoma

Answer 88

● Overall prognosis is dismal for invasive adenocarcinoma (75% 5-year survival); prognosis is better for small, well-differentiated adenocarcinoma with fewer than four positive nodes

Answer 89

Most asymptomatic, some have peptic ulcer sx. diffuse antral gastritis commonly in whites multifocal atrophic gastritis - more in blacks, Asians, Hispanic and Scandinavians strongly associated with duodenal and gastric ulcers > MALT or gastric adenocarcinoma Gram neg spiral rods

Answer 90

Single best predictor of survival is depth of invasion; survival is 95% for tumors confined to the submucosa but drops to 50% with involvement through the muscularis propria to the subserosa (T3); T2 lesions have intermediate survival

Answer 91

DLBCL many gastric lymphomas derived from MALT 50s-60s Hpylori involved in 92+% treatment of H pylori - regression of 77% early lesion

Answer 92

excellent if confined to stomach

Answer 93

distribution - Most gastrointestinal carcinoid tumors occur in the vermiform appendix, followed by the small intestine (typically ileum), rectum, stomach, and colon 1% duodenal, 7% jejunal, 80% ileal, and 10% rectal ● Most patients are 50 to 70 years old types - hormone antibodies — Serotonin — Somatostatin — Gastrin — VIP — ACTH — Insulin — chromogranin, synaptophysin +ve Cytokeratin positive in 65% to 70% of cases metastatic risk ● All carcinoids are potentially malignant ● Risk for metastasis increases with tumor size — Less than 1 cm: 2% — One to 2 cm: 50% (ileal)

Answer 94

— Carcinoid syndrome ◆ Occurs in 10% of patients; more common in patients with an ileal carcinoid tumor ◆ Usually indicates hepatic metastasis (precluding hepatic degradation of vasoactive amines) ◆ Symptoms include flushing, sweating, cardiac symptoms, and diarrhea ◆ About 50% of patients have endocardial right heart lesion ◆ Symptoms arise because of increased levels of 5-HT and 5-HIAA

Answer 95

— May also be associated with MEN-I syndrome and hypoglycemia — Usually benign behavior

Answer 96

Gastrinoma — Often multiple, but typically small — Associated with Zollinger-Ellison syndrome and MEN-I syndrome — Usually malignant behavior

Answer 97

Clinically the important distinctions are size, villous component, and presence of high-grade dysplasia or carcinoma - colonic adenoma - villous architecture - presence of high grade dysplasia Other subtypes Hyperplastic polyp, most common, asymptomatic, M>F inflammatory -IBD, trauma etc adenoma - tubular most common, 70%, pedunculated -tubulovillous -larger than tubular - villous - sessile, flat, broad, small pedicle <1cm 1% cancer >2cm, 45% harbor cancer Carcinoma cells that infiltrate into the muscularis mucosae or lamina propria alone (intramucosal adenocarcinoma) have virtually no risk for metastasis; many advocate classifying these lesions as high-grade dysplasia Only when the carcinoma cells infiltrate through the muscularis mucosae into the submucosa or beyond are they considered invasive (and clinically significant) Pathology report should include — Highest degree of dysplasia present in the biopsy specimen and presence of villous component — Degree of differentiation and distance from the margin, if invasive carcinoma is present, as well as the presence or absence of vascular and lymphatic invasion

Answer 98

adenocarcinoma, Squamous cc, adenocarcinoma with lepidic patten NSCC - favoured adeno/squamous/spindle and/or giant cells Small cells NSCC with neuroendocrine morphology, positive neuroendocrine marker, possible large cell nuroendocrine ca

Answer 99

bronchial adenoma/ciliated micronodular papillary tumor benign, peripheral GGO, some with cavitation middle age to elderly, median 72yrs, M=F TTF1 stain and P40

Answer 100

thoracic SMARCA4 deficient undifferentiated tumor median age 39-59 MF 9:1 rapid progressive tumors mediastinum>pul hilum, pleura with/out chest wall often multiple sites and metastatic 77-83% tumor diameter - large 3-21cm TP53 mutation 60%

Answer 101

divide cores - 2 tissue block IHC based on morphology dual stain (TTF-1/p40) p40 (nuclear)/Napsin (cytoplasmic) CK5/TTF-1 neuroendocrine markers only if morphology indicates if ordering stains - get unstained - beware of short shelf life of unstained slides

Answer 102

tumour cells within airspaces beyond the (MAIN) edge of the main tumor present in 15-56% NSCLC patterns: micropapillary structures, solid tumor cell nests, discohesive single tumor cells should NOT be included in tumor size. e.g. speculations occurs in adeno, SQCC, neuroendocrine (all subtype), pleomorphic increase risk of recurrence or OS sublobar resection > may indicate further resection/lobectomy

Answer 103

OSTEOSARCOMA (NOS) majority - small - telangiectatic - conventional COS SECONDARY osteosarcomas subtypes In the latest classification, secondary osteosarcoma is divided into six subtypes: [4] a) Osteosarcoma in Paget’s disease of bone, (poorer prognosis) b) Radiation-induced osteosarcoma (poorer prognosis) c) Infarct related osteosarcoma d) Chronic osteomyelitis related e) Implant-related osteosarcoma f) Osteosarcoma secondary to fibrous dysplasia. ------------------------------------------------ The prognosis of secondary osteosarcoma occurring as a result of Paget’s disease of bone and radiation treatment is poorer than COS. The previous classification included secondary osteosarcoma in the conventional osteosarcoma (COS) subtype, but now, the recent classification has described it in a separate category. Now osteosarcoma not otherwise specified (NOS) includes only three subtypes: COS, telangiectatic osteosarcoma, and small cell osteosarcoma. COS accounts for the majority of osteosarcoma [Figure 5]. Osteosarcoma NOS can also be subdivided into different types based on the dominant matrix: Osteoblastic, chondroblastic, and fibroblastic; However, this subdivision has no role in predicting prognosis. COS and telangiectatic osteosarcoma are more commonly encountered in the metaphyseal region of long bones whereas small cell osteosarcoma is predominantly seen in the diaphysis. Recent classification has also removed Clear cell and chondroblastoma-like osteosarcoma subtypes from the osteogenic tumors.[4]

Answer 104

Breslow thickness to the nearest 0.1mm T1 0.8 vs 0.8-1.0 mm T2 1-2 T3 2-4mm T4 >4 mm Presence of Ulceration Mitotic index 1mitosis/mm2 vs >1mit/mm2 LDH elevation/no elevation Node Clinical vs path (pN0 is better than cN0) Regional lymph nodes represent the most common first site of metastasis in patients with primary melanoma. Metastasis status M1a distal node M1b lung M1c viscera M1d CNS

Oncology Flashcards

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