Ch 1 - SCC through Teratocarcinosarcoma

Question 1

Age and gender for KSCC and NKSCC of the sinonasal tract?

Answer 1

KSCC:6-7th decades, men 2x women

NKSCC: 6-7 decades, men more frequent than women

Question 2

What % of sinonasal papillomas undergo malignant transformation and which type do they transform into?

Answer 2

2-10% into keratinizing SCC most often

Question 3

What is the most frequent site for sinonasal KSCC?

Answer 3

Maxillary sinus

Question 4

Which has a better prognosis: KSCC in the nasal cavity or KSCC in the paranasal sinuses?

Answer 4

Nasal cavity (maybe easier to access?)

Question 5

What is the distinct histo characteristic of sinonasal NON-keratinizing SCC?

Answer 5

“Ribbon-like” growth pattern (and absent to limited maturation)

Question 6

What % of sinonasal NKSCC harbour transcriptionally active high-risk HPV?

Answer 6

30-50%

Question 7

Most common locations (2) for sinonasal NKSCC?

Answer 7

Maxillary sinus or nasal cavity

Question 8

How are NKSCCs graded?

Answer 8

Trick question -theyre not

Question 9

What is a common feature of the basal/superficial cells of a NKSCC tumor nest/ribbon?

Answer 9

Peripheral palisading

Question 10

DDx for NKSCC (5)

Answer 10

SNUC, NE Ca, AdCyCa (Solid Variant), SMARCB-1 deficient carcinomas, NUT carcinoma (if abrupt keratinization)

Question 11

What should be considered if abrupt keratinization is seen in a NKSCC?

Answer 11

NUT carcinoma

Question 12

NKSCC positive stains (5ish)

Answer 12

CKs (including high-molecular weight CK5/6), p63, p40, p16 (diffuse), HPV ISH or PCR

Question 13

NKSCC pert neg stains (4ish)

Answer 13

Nuclear retention of SMARCB-1 (INI1), NE markers, S100, NUT1

Question 14

How does prognosis of NKSCC compare to KSCC in the sinonasal tract?

Answer 14

NKSCC possibly improved prognosis, but not as clear as Oropharynx

Question 15

What are 2 factors that can improve prognosis in sinonasal NKSCC?

Answer 15

high-risk HPV or EGFR over-expression (probably cause their susceptible to EGFR inhibitors (TKIs and monoclonals)

Question 16

What is the gender ratio for the newly discovered NKSCC with AdCyCa-like features? What is the suspected etiology?

Answer 16

Female to male 7:2…high-risk HPV

Question 17

What tumor can be mimicked when an NKSCC with AdCyCa-like features has true ductal cells surrounded by basaloid to clear myoepithelal cells?

Answer 17

epithelial-myoepithelial carcinoma

Question 18

Positive stains for NKSCC with AdCyCa-like features (8)…Pertainant negatives (1)

Answer 18

Myoepi: S100, calponin, p63, actin Ductal: KIT, CKs. BOTh cell types: p16 and High-risk HPV ISH

NO MYB translocations (as seen in 50% of true AdCyCa)

Question 19

Age and gender for sinonasal spindle cell (sarcomatoid) SCC…what are the 2 primary risk factors?

Answer 19

elderly men…smoking and radiation exposure…HPV negative in the few cases tested

Question 20

Sinonasal lymphoepithelial carcinoma most closely resembles the histo of which other carcinoma?

Answer 20

Non-keratinizing nasopharyngeal carcinoma, undifferentiated subtype

Question 21

What are the demographics for most cases of sinonasal LEC?

Answer 21

Men in 5-7th decades from Asia, where EBV is endemic

Question 22

What is the etiology of sinonasal LEC?

Answer 22

> 90% of cases harbor EBV

Question 23

What is the most common location for sinonasal LEC? What must be ruled out to determine that the LEC is truly sinonasal primary?

Answer 23

Nasal cavity… invasion of a nasopharyngeal carcinoma from a nearby structure must be excluded (clinically, radiographically, pathologically)

Question 24

Positive stains for sinonasal LEC (5)…Pertinent negatives (2 general categories)

Answer 24

Positive: PanCK, CK5/6 (vs SNUC which is CK5/6neg), p63, p40, EBER

Neg: lymphoid and melanocytic markers

Question 25

Differential for sinonasal LEC (3)

Answer 25

lymphoma, melanoma, SNUC

Question 26

Differentiate sinonasal LEC from SNUC (4 features)

Answer 26

SNUC lacks the syncytial growth pattern (lack of cytopasmic borders, etc) of LEC, is consistently EBER negative, and lacks CK5/6 with limited to absent p63

Question 27

LETS GET IT: DDx for SNUC (10)

Answer 27

1. Lymphoma 2. NKSCC 3. Basaloid SCC 4. NE Carcinoma 5. Olfactory Neuroblastoma 6. NUT carcinoma 7. Alveolar Rhabdomyosarcoma 8. Ewing Sarcoma 9. Adenoid Cystic Carcinoma, solid type 10. Melanoma

Question 28

What's the small round blue cell ddx again? (7)

Answer 28

``` Melanoma Rhabdomyosarcoma SNUC Lymphoma Esthesioneuroblastoma (Olfactory Neuroblastoma) Ewing sarcoma Pitutiary adenoma ```

Question 29

What are the age and ethnicity demographics for SNUC?

Answer 29

teenagers to elderly, avg pt age: 50-60...60-70% caucasian males

Question 30

SNUC should be negative for which two viruses?

Answer 30

EBV and HPV

Question 31

2 most common sites for SNUC

Answer 31

nasal cavity and ethmoid sinuses

Question 32

Name that sinonasal carcioma based on the histo: 1. Small nests of neoplastic cells with numerous squamous pearls in a desmoplastic stroma 2. Interconnecting squamous RIBBONS invading the stroma with a broad pushing border, peripheral palisading of tumor nuclei 3. Solid and cribriform nodules of basaloid tumor cells, inconspicuous eosinophilic ducts 4. loosely arranged, moderately pleomorphic spindle cells with brisk mitotic activity 5. Sheets of malignant cells, vesicular chromatin, prom nucleoli, indistinct cytoplasmic borders imparting a SYNCYTIAL quality. Every cell EBER positive 6. Lobules and ribbons of malignant epithelial cells, one may say undifferentiated with tumor necrosis, vesicular chromatin, and prominent nucleoli 7. Epithelioid nests of large, undifferentiated cells with abundant eccentrically located eosinophilic cytoplasm imparting rhabdoid appearance

Answer 32

1. KSCC 2. NKSCC 3. HPV-related carcinoma with AdCyCa-like features 4. spindle cell SCC 5. LEC 6. SNUC 7. SMARCB1-deficient sinonasal carcinoma

Question 33

What is unique about the spread of SNUC?

Answer 33

60% spread to adjacent structures, but only 10-15% met to LNs

Question 34

SNUC IHC: pos (6ish), neg (6)

Answer 34

Pos: PanCK (AE1/AE3), "simple CKs" (CK7,CK8,CK18), Neuron-specific enolase (NSE), +/- p63, focal/patchy Synapto/Chromo, p16 (regardless of HPV status) Neg: CK5/6, p40 (which is more SQUAMOUS specific), carcinoembryonic antigen (?), S100, CD45, calretinin

Question 35

Differentiate SNUC from KSCC

Answer 35

KSCC histo squamous diff CK5/6 pos, p63 pos, p40 pos

Question 36

Differentiate SNUC from NE carcinoma

Answer 36

NE has speckled chromatin, rosette formation, palisading and positive for NE markers

Question 37

Differentiate SNUC from NUT carcinoma

Answer 37

NUT has squamous diff (focal), pos for p63, p40, NUT protein positive on IHC

Question 38

While NO specific genetic alteratons have been ID'd in SNUC, which gene is amplified in 1/3 of tumors? Which protein is frequently strongly expressed?

Answer 38

SOX2....KIT (CD117)

Question 39

What is the gene that is rearranged in NUT carcnioma?

Answer 39

NUTM1

Question 40

Median age and gender of NUT carcinoma?

Answer 40

21 years, slight female

Question 41

65 % of NUT carcinoma present in which 2 areas?

Answer 41

nasal cavity and paranasal sinuses (generally midline, hence the alternate name of NUT midline carcinoma)

Question 42

Name that tumor: poorly diff epitheliod cells with pale to clear glycogenated cytoplasm with abrupt keratinization possible

Answer 42

NUT carcinoma (dx is made on FISH of NUT rearrangement, not histology though)

Question 43

What is the NUT monoclonal antibody?

Answer 43

C52

Question 44

Stains for NUT carcinoma: 9 positive

Answer 44

Pos: NUT monoclonal C52, P63, p40, CK, CD34, Syn, Chromo, p16, TTF1

Question 45

Whats a good ddx for NUT carcinoma? (6)

Answer 45

SCC (poorly diff), Ewing, SNUC, Leukemia, Germ Cell Tumor, Olfactory Neuroblastoma

Question 46

How do you differentiate between NUT carcinoma and SMARCB1-deficient sinonasal carinoma?

Answer 46

NUT = focal keratinization SMARCB1-def = basaloid cells with rhabdoid or plasmacytoid features AND loss of SMARCB1 (INI1) on IHC

Question 47

What is the fusion 70% of the time for NUT carcinoma?

Answer 47

NUTM1-BRD4 t(15;19)

Question 48

Which has a better prognosis: NUT-BRD4 or NUT-variant?

Answer 48

NUT-variant may have a longer survival than NUT-BRD

Question 49

Age and gender for sinonasal NE carcinomas?

Answer 49

middle aged to older men

Question 50

Most common location for sinonasal NE ca?

Answer 50

ETHMOID sinus

Question 51

Stains for sinonasal NE carcinoma: 9 positive (which one is unique for small cell NE ca?)

Answer 51

Positive: CKs (CAM5.2, AE1/AE3), EMA (perinuclear dot formation), NE markers: synaptophysin (most sensitive and specific),, chromogranin, NSE (neuron-specific enolase - less common in large cell NEca), CD56...S100 is diffusely positive in small cell NEca), p16

Question 52

What is a key stain to differentiate sinonasal NEca from SNUC? What separates these two if both stain positive for neuroendocrine markers?

Answer 52

p16 is positive in LCNEC and SmCC and negative in SNUC...if both positive for NE markers, morphology will separate them

Question 53

Negative stains for sinonasal NEca (3)

Answer 53

CK5/6, EBER, CK20

Question 54

Which gene expression is higher in sinonasal NE ca compared to Olfactory neuroblastoma and rhabdomyosarcoma?

Answer 54

ASCL1 (hASH1)

Question 55

DDx for sinonasal Neuroendocrine Carcinoma (3)

Answer 55

Olfactory neuroblastoma, SNUC, and NUT carcinoma

Question 56

Which has a better prognosis: LCNECs or SmCCs?

Answer 56

LCNECs

Question 57

Name that tumor: Small cells with nuclear molding, even chromatin distribution

Answer 57

Small cell NEca

Question 58

Name that tumor: large cells with high N:C ratio, small nucleoli, and salt-and-pepper chromatin distribution

Answer 58

large cell NEca

Question 59

Which stain shows a cytoplasmic dot-like (perinuclear) pattern in small cell neuroendocrine carcinoma?

Answer 59

pancytokeratin

Question 60

What are the demographics for intestional type sinonasal adenocarcinoma?

Answer 60

WOOD or LEATHER-WORKERS...MALES 3-4x more likely, 6th-7th decades

Question 61

Besides leather or wood-workers, what are two other occupational exposures that can increase the risk for ITAC?

Answer 61

Formaldehyde or dust

Question 62

Most common site for ITAC?

Answer 62

LATERAL nasal wall, middle turbinate

Question 63

Name that sinonasal tumor: papillary growth with numberous goblet and Paneth cells, possible cribriform pattern, possible signet ring cells

Answer 63

Sinonasal Intestinal Type Adenocarcinoma

Question 64

Stains for ITAC: positive: the nasty 9

Answer 64

Positive: Mucicarmine, PAS/distase resistant, PanCK, CK7+/-, Carcninoembryonic antigen +/-, CK20+, CDX2, MUC2, villin, +/- NE markers

Question 65

What is the majority of genetic mutations found in ITAC? Are they MSI?

Answer 65

KRAS...they are microsatellite-stable and do not lose expression of mismatch repair proteins

Question 66

What do you call a sinonasal adenocarcinoma that does NOT have salivary gland features or intestinal features?

Answer 66

Sinonasal non-intestinal-type adenocarcinoma (non-ITAC) lol

Question 67

Which one favors men? Low Grade non-ITACs or High Grade non-ITACs?

Answer 67

High grade non-ITAC favors men

Question 68

Where do most low grade non-ITACs show up? What about high grade?

Answer 68

LG: nasal cavity (middle turbinate)...HG: both sinuses and nasal cavity

Question 69

Name that tumor: tubules that grow back to back as they invade the stroma or papillae lined by a single layer of columar epithelium. Calcispherules are rarely seen

Answer 69

sinonasal low grade non-intestinal type adenocarcinoma

Question 70

Name that tumor: predominantly solid growth pattern with occasional glandular structures and/or individual mucocytes

Answer 70

sinonasal high grade non-intestinal type adenocarcinoma

Question 71

What substance causes the clear cells in sinonasal renal-cell like carcinoma?

Answer 71

glycogen

Question 72

Name that tumor: monomorphous cuboidal to columnar glycogen-rich clear cells in nests with possible microcysts that lack mucin production, overall impression is low-grade neoplasm

Answer 72

sinonasal renal-cell like carcinoma

Question 73

LG and HG non-ITAC stains: positive (5), (1 special set of positive markers for HG), negative (4)

Answer 73

Positive: PAS/Distase resistant, CK7, DOG1, SOX10,S100...HG non-ITAC + NE markers Negative: CK20, p63, CDX2, MUC2

Question 74

Renal cell-like carcinoma stains: 2 positive, 2 negative

Answer 74

positive: CAIX, CD10 Negative: PAX8, RCC marker

Question 75

Age and gender for teratocarcinosarcoma...wait. location too

Answer 75

60 years STRONG male predilection..nasal cavity

Question 76

Name that tumor: admixture of epithelial, mesenchymal, and neuroepithelial components, nests of immature epithelium with clear so-called FETAL-appearing cells, , spindle cells (fibroblasts/myofibroblasts/etc), and round to oval cells in nests or neurofibrillary background +/- rosette formation

Answer 76

Teratocarcinosarcoma

Question 77

Teratocarcinosarcoma: Positive (3 groups of stains, give one example of each), Negative (4)

Answer 77

Positive: epithelial (CK), mesenchymal (vimentin), neuroepithelial (synapto/chromo, S100) Negative: PLAP, alpha-fetoprotein, hCG, CD30