Ch 1 - Sinonasal Papilloas through Sarcomas

Question 1

Which sinonasal papilloma type is the most common?

Answer 1

Inverted

Question 2

What are two featured cells in inverted sinonasal papillomas?

Answer 2

mucocytes and transmigrating neutrophils

Question 3

If you get an inverted sinonasal papilloma on boards, look for malignancy…up to what % transform? Also what are the gender demographics?

Answer 3

up to 27% and 2.5-3x more in males

Question 4

What percent of inverted sinonasal papillomas are HPV positive, which strains?

Answer 4

38.5% HPV positive, low risk 2.8x more freq than high

Question 5

INTERESTING! p16 is accepted as a serrogate marker for HPV, but which sinonasal papilloma has NO correllation?

Answer 5

inverted

Question 6

2 most common locations for inverted sinonasal papillomas

Answer 6

nasal cavity and MEDIAL WALL of the maxillary sinus

Question 7

What is the MRI description of an inverted sinonasal papilloma?

Answer 7

septate striated appearance

Question 8

What is the gross description buzzword for an inverted sinonasal papilloma?

Answer 8

gray, undulating surface resembling a MULBERRY

Question 9

Which CKs are positive for the squamous/columnar cells in an inverted sinonasal papilloma? (3)

Answer 9

CK10, CK10/13, CK1/2/10/11

Question 10

Which gene has been linked to activating mutations in inverted sinonasal papillomas and concurrent SCCs arising from ISNPs?

Answer 10

EGFR

Question 11

What tumor am I? A papilloma composed of both exophytic fronds and endophytic invaginations lined by multiple layers of columnar cells with oncocytic features, intraepithelial microcysts containing mucin and neutrophils

Answer 11

Oncocytic sinonasal papilloma

Question 12

Gender, age, location for oncocytic sinonasal papilloma

Answer 12

Even male to female, >50 years, LATERAL nasal wall

Question 13

Give the HPV association with each of the three sinonasal papillomas

Answer 13

Inverted: 38.5%, most 6/11, some 16/18

Oncocytic: no association

Exophytic: 63.5% HPV, mostly 6/11HIGHEST association

Question 14

Which sinonasal papilloma displays both exophytic and endophytic growth?

Answer 14

Oncocytic

Question 15

What ultrastructural component of the cell causes the oncocytic appearance in an oncocytic sinonasal papillomas?

Answer 15

high cytochrome c oxidase content and numerous mitochondria

Question 16

What histo feature helps distinguish an oncocytic sinonasal papilloma from rhinosporidosis?

Answer 16

Oncocytic papilloma: small cysts filled with mucin or neutrophils in the EPITHELIUM

Rhino: microcysts, but in the STROMA

Question 17

What can oncocytic sinonasal papillomas be confused with histologically? What features help distinguish them?

Answer 17

low-grade papillary adenocarcinoma (wtf is this?)…intact basement membranes and absence of infiltrative growth pattern = benign

Question 18

Up to what % of oncocytic SN papillomas can harbor a carcinoma (SCC, MEC, NE, SNUC have all been seen with these)

Answer 18

up to 17 %

Question 19

Age and gender for EXOPHYTIC SN papillomas?

Answer 19

males (up to 10x) and 20-50 yrs

Question 20

About 64% of Exophytic SN papillomas have been shown to harbor HPV…are they high risk or low risk?

Answer 20

low. 6 & 11…malignant transformation is rare for these

Question 21

Most common location for exophytic SN papillomas

Answer 21

lower anterior nasal septum

Question 22

What does REAH stand for? What other entity is it on a spectrum with?

Answer 22

Respiratory Epithelial Adenomatoid Hamartoma….SH (Seromucinous Hamartoma)

Question 23

Age and gender for REAH and SH

Answer 23

Male 6th decade (56 years)

Question 24

Location for REAH and SH

Answer 24

Posterior nasal septum

Question 25

How do you rule out a met when evaluating REAH?

Answer 25

REAH = CK20 & CDX2 negative

Question 26

What components DEFINE a pleomorphic adenoma?

Answer 26

1. Epithelial 2. Myoepithelial/Mesenchymal are essential for the diagnosis of a PA

Question 27

gender and location of a sinonasal PA?

Answer 27

female (slight), nasal septal mucosa

Question 28

what is unique about the histology of a sinonasal PA when compared to a PA elsewhere?

Answer 28

sinonasal PAs have a more EPITHELIAL predominant population compared to myoepithelial/stromal

Question 29

Which has a higher recurrence: sinonasal PA or parotid PA?

Answer 29

parotid PA higher recurrence

Question 30

WHat % of sinonasal PAs have malignant transformation? How does this compare to a parotid PA?

Answer 30

Sinonasal: up to 2.4-10% vs Parotid: 6.2%..so pretty similar

Question 31

What are the two most common sinonasal sarcomas?

Answer 31

1. Rhabdomyosarcoma | 2. Fibrosarcoma

Question 32

What is the most common location for a sinonasal fibrosarcoma?

Answer 32

maxillary sinus

Question 33

Name that sarcoma: herringbone or chevron pattern lacking profound pleomorphism

Answer 33

fibrosarcoma

Question 34

What is a good histo differentiator between fibrosarcoma and undifferentiated pleomorphic sarcoma?

Answer 34

Undif pleo sarc = significant pleomorphism and storiform areas

Question 35

Sweet. Since Fibrosarcoma is a diagnosis of exclusion....what 10 entities should you exclude before giving up? Also, what is a good stain, molecular, or histo feature to differentiate them?

Answer 35

1. Sarcomatoid carcinoma (CK positive) 2. Synovial sarcoma SSX-SS18 / t(x;18) 3. leiomyosarcoma (SMA, MSA, h-caldesmon pos) 4. spindle cell rhabdomyosarcoma (myogenin, myod1 pos) 5. spindle cell melanoma (s100, HMB45, sox10 pos) 6. MPNST (s100 pos) 7. Biphenotypic sinonasal sarcoma (s100,SMA, t(2;4) PAX3-MAML3 fusion) 8. glomangiopericytoma (D240 pos) 9. Desmoid fibromatosis (B-catenin, CyclinD1, Calret pos) 10. fibroblastic osteosarcoma (bone formation, CDK2, MDM2 over exp)

Question 36

What two stains are fibrosarcomas usually positive for? (still not very helpful)

Answer 36

vimentin and actins

Question 37

Name that sarcoma: pleomorphism, numerous mitoses, areas of tumor necrosis, histiocyte-like cells, foamy cells, giant tumor cells with large poly-lobulated nuclei

Answer 37

undifferentiated pleomorphic sarcoma

Question 38

While many stains are negative, what can be focally positive in UPS?

Answer 38

SMA...histiocytic antigens are usually negative (eventhough the alternate name is malignant fibrous histicytoma lol)

Question 39

UPS is a dx of exclusion, what are the 8 entities you should exlude?

Answer 39

1. Carcinomas 2. Melanoma 3. lymphoma 4. rhabdomyosarc 5. leiomyosarcoma 6. MPSNT 7. Dediff/Pleomorph liposarcoma 8. High grade myxofibroma

Question 40

Name that sarcoma: spindle cells in interlacing fascicles, nuclei are oval or elongate and frequently blunt-ended. Variable atypia. Eosinophilic cytoplasm perinuclear vacuoles. Epitheliod cells rare. Giant cells possible. Psammomatous calcification

Answer 40

Leiomyosarcoma

Question 41

What are 4 positive stains for leiomyosarc? How many should be positive for the diagnosis?

Answer 41

1. Desmin 2. h-caldesmin 3. SMA 4. MSA 2 of them should be positive

Question 42

What are the 4 categories of rhabdomyosarcoma?

Answer 42

1. Embryonal 2. Alveolar 3. Pleomorphic 4. Spindle-cell

Question 43

Age and gender of sinonasal rhabdomyosarcoma? What is the most common variant among the most common age?

Answer 43

0-10 years old, no sex predilection Embryonal variant most common in young patients

Question 44

What is the most common location for a rhabdomyosarcoma?

Answer 44

paranasal sinuses

Question 45

Which type of rhabdomyosarc is more common in children? Which one for adults?

Answer 45

Children: embryonal Adults: Alveolar

Question 46

Stains for rhabdomyosarcoma (6)

Answer 46

MOST USEFUL: 1. Desmin 2. Myogenin Also: Alveolar: myogenin 100% Embryonal: myogenin +/- Less specific: 3. MyoD1 4. fast myosin 5. myoglobin 6. MSA

Question 47

What unique, non-muscle stains might an alveolar rhabdomyosarc also express (7)?

Answer 47

1. CKs 2. EMA 3. CD56 4. Chromo 5. Synapto 6. CD20 7. CD99

Question 48

Which rhabdomyosarcs harbor the gene fusion? What is the fusion?

Answer 48

Alveolar: PAX3-FOX01 (less commonly PAX7-FOX01)

Question 49

Genetic profile of embryonal rhabdomyosarc?

Answer 49

allelic losses in various chromosome 11 loci

Question 50

Rearrangement for pediatric spindle cell rhabdomyosarc?

Answer 50

NCOA2

Question 51

Name # syndromes that are associated with rhabdomyosarcoma?

Answer 51

1. Li-Fraumeni 2. Costello 3. NF1 4. Beckwith-Wiedemann

Question 52

Which has a poorer prognosis: alveolar or embryonal rhabdomyosarc?

Answer 52

Alveolar (later age, usually present with regional and met spread)

Question 53

Compare the mean patient age and gender for a sinonasal angiosarcoma compared to a skin/soft tissue angiosarcoma

Answer 53

Sinonasal: 47 years, male Skin: Older, male

Question 54

Exposure to radiation, vinyl chloride, coal dust are risk factors for which sinonasal sarcoma?

Answer 54

angiosarcoma (used for PVC)

Question 55

Two most common sites for sinonasal angiosarc?

Answer 55

nasal cavity and maxillary sinus

Question 56

What is a histo buzz term for what the freely anastomosing vascular channels create in an angiosarc? WHAT IS THE PATHOGNOMONIC HISTOLOGY SIGN FOR ANGIOSARC?

Answer 56

"cleft-like" spaces PATHOGNOMONIC: Intracytoplasmic lumina (often containing erythrocytes)

Question 57

9 stains for angiosarc

Answer 57

1. Vimentin (lol) 2. CD34 3. CD31 4. Claundin 5 5. ERG 6. FLI1 7. D2-40 8. factor VIII 9. focal keratin (epithelioid variant)

Question 58

MPNST: what % are associated with NF1? How does NF1 affect the mean age of a patient presenting with an MPNST? How does NF1 status affect prognosis?

Answer 58

25-30% of MPNST are with NF1 (not as many as i expected) NF1 pts with MPNST present in their 20-30's compared to non-NF1 in their 40's NF1 = WORSE prognosis

Question 59

What are the two most common nerves involved by a MPNST?

Answer 59

vestibular (VIII) and vagus (X)

Question 60

MPNSTs usually arise in either a pre-existing NF or schwannoma...which one is more common?

Answer 60

NF

Question 61

Name that sarcoma: marbled effect with alternating cellular and myxiod areas, perivascular cuffs, poorly defined nuclear palisading

Answer 61

MPNST

Question 62

Remind me of the components of a Malignant Triton Tumor

Answer 62

MPNST + Rhabdomyosarcoma

Question 63

Immunoprofile: MPNST (3), Epithelioid MPNST (2)

Answer 63

MPNST: S100 (nuc and cyto), SOX10 (nuc), Nestin Epithelioid MPNST: strong S100, loss of SMARCB1 (INI1)

Question 64

Remind me: chromosome for NF1 gene

Answer 64

17q11

Question 65

Gene fusion and translocation for biphenotypic sinonasal sarcoma....oh what are the biphenotypes again?

Answer 65

Gene fusion: PAX3-MAML3 t(2;4) Biphenotypes: sarcoma (spindle cell proliferation) + epithelial proliferation (entrapped glands and surface)

Question 66

Age and gender for biphenotypic sinonasal sarcoma

Answer 66

FEMALE 2:1 mean 52 years

Question 67

2 most common sites for BSNS

Answer 67

(Biphenotypic sinonasal sarcoma) SUPERIOR nasal cavity and ethmoid sinus

Question 68

Part of the histomorphology of a BSNS has a herringbone pattern spindle-cell population resembling which other sarcoma?

Answer 68

synovial sarcoma

Question 69

Since the histology of a BSNS is spindle and epithelial, which other neoplasm can the epithelial component resemble?

Answer 69

a sinonasal papilloma

Question 70

What are the 3 primary stains that are at least focally positive for BSNS?

Answer 70

1. S100 2. SMA 3. MSA

Question 71

While PAX3-MAML3 is the most common gene fusion in BSNS, what is the other possibility? What other entity is it shared with?

Answer 71

PAX3-FOX01 = alveolar rhabdomyosarcoma

Question 72

Name that sarcoma: variable degree of epithelial differentiation including gland formation

Answer 72

synovial sarcoma

Question 73

Most common age range for synovial sarcoma and most common risk factor?

Answer 73

patients in their 20s-30s...prior radiation therapy

Question 74

What are 3 common histo subtypes for monophasic synovial sarcoma? What are the two most common histology features of a biphasic synovial sarcoma?

Answer 74

mono: spindle cell, calcifying/ossifying, myxoid) Bi: spindle cells with: glandular or solid epithelial cells

Question 75

Stains for synovial sarcoma (6)

Answer 75

1. TLE1 positive in 95% 2. CD99 3. BCL2 4. CD56 5. CK7 6. EMA

Question 76

How might you differentiate from a BSNS and a Biphasic Synovial Sarcoma?

Answer 76

TLE1 posittive in biphasic synovial sarcoma