Ch10 Epithelial Flashcards
What type of virus is HPV? (RNA? DNA? DS? SS?) oral HPV infection is present in approximately __ to __% of normal, healthy individuals.
Double stranded DNA virus….5-12%
Oral HPV infection is prevelent in children under what age?
1 year
What is the bimodal age range for oral HPV infection?
30-34 yrs and 60-64 years
What is the range of incubation for benign HPV disease?
3 weeks to 2 years
When HPV stays in a basal cell of the epithelium, what is the name of its circular form?
episomal
What are the 4 high risk HPV strands?
16,18,31,33
What are the 2 low risk HPV strands?
6,11
What HPV strands are vaccinated against in the bivalent (Carvarix) vaccine?
16,18
What HPV strands are vaccinated against in the quadravalent (Guardasil)?
6,11,16,18
What are the two HPV strands most associated with oral squamous papillomas?
6,11
What are the two HPV strands most associated with recurrent respiratory papillomatosis?
6,11
What are the two HPV strands most associated with Focal Epithelial Hyperplasia
13,32
What HPV strand is most associated with oropharyngeal SCC?
16
What HPV strand is most associated with verruca vulgaris? What are two main histological features that help distinguish a VV from a squamous papilloma?
HPV strand 2
VV = “cupping” (converging) effect” of the rete ridges
VV= prominent granular cell layer
What HPV strands are most associated with condyloma acuminatum (genital warts)?
6,11
What 6 HPV strands are most associated with intraepithelial neoplasia?
6,11,16,18,31,33
What at HPV strands are most associated with cervical SCC?
16,18
What is the MOST COMMON soft tissue mass arising from the soft palate?
Papilloma
What 5 syndromes have multiple papillomas (papillomatosis) associated with them?
- nevus unius lateris, 2. acanthosis nigricans, 3. focal dermal hypoplasia (Goltz-Gorlin) syndrome, 4. Down syndrome 5. Recurrent Respiratory Papillomatosis
What is the recurrence for papillomas?
“unlikely”
Which HPV strain is known for exceptionally aggressive behavior in benign papillomas?
11
What % of verrucae resolve on their own within 2 years?
2/3
What % of condyloma acuminatum are caused by HPV 6,11? Can they be co-infected?
90%..yes, 6 and 11 can be coinfected with 16/18 etc
What is the incubation period for condyloma acuminatum?
1-3 months
What distinguishes an oral condyloma acuminatum from a squamous papilloma?
1 clinical feature
2 histological features
Clinical: CA tend to be double the size of a SP
Histo: CA papillary projections are MORE BLUNTED and BROADER than SP or VV
CA tend to have less koilocytosis than SP or VV
Anogenital condylomata infected with _______ are associated with an increased risk for malignant transformation to squamous cell carcinoma, but such transformation has not been demonstrated in oral lesions
HPV 16 or 18
Fungiform sinonasal papilloma usually arises where? Gender predilection? Recurrence?
nasal septum…2:1 male to female…20-30% (pretty high!)
sinonasal papillomas location?
majority on lateral wall of nasal cavity…however - fungiform are mostly found on the nasal septum
basophilic viral inclusions in molluscum contagiosum
Henderson-Paterson bodies
What are the 2 variants of Heck Dz? Which one is more common?
What is the characteristic histo feature in multifocal epithelial hyperplasia (Heck Dz)?
- Papulonodular (more common - buccal/labial mucosa)
- Papillomatous (less common - gingiva/tongue)
Mitosoid cell
form of SebK in blacks
Dermatosis papulosa nigra
sudden appearance of many SebKs with pruritus= a sign of internal malignancy
Leser-Trelat sign
irritated SebK is AKA
Inverted follicular keratosis of Helwig
description of sebaceous hyperplasia in the oral cavity
“Cauliflower appearance”
freckle (no increase in # of melanocytes) is AKA
Ephelis
Nevus cells are derived from _______ origin
neural crest
superficial nevus cells in small round aggregates
Theques
solitary or coalescent eosinophilic globules within the epidermis or at the epidermal dermal junction in spitz nevus
Kamino bodies
creates the blue color of a blue nevus- interaction of light with particles in colloidal suspension
Tyndall effect
Epithelial dysplasia is found in up to ____% of oral leukoplakias
25%
Malignant transformation rate for mild dysplasia?
<5%
Malignant transformation rate for moderate dysplasia?
up to 11%
Malignant transformation rate for severe dysplasia?
up to 46%
tobacco pouch keratosis - 3 histologic features
- Intracellular vacuolization 2.parakeratin chevrons 3. amorphous eosinophilic material in subjacent CT
generalized oral burning is aka and is seen in WHAT condition?
Stomatopyrosis…oral submucous fibrosis
Bowenoid actinic keratosis is histologically equivalent to:
full thickness dysplasia
Characteristic acute angle formed between the normal adjacent epithelium and a KA on histology
“Buttress”
4x increased risk of DORSAL tongue carcinoma in ________ patients
tertiary syphilis
Tongue carcinomas account for __% of intraoral cancers
50%
Old name for PVL
oral florid papillomatosis
Parakeratin on the surface of verrucous carcinoma
“Parakeratin clefts”
Spindle cell carcinoma presents as a ________ polypoid mass
pedunculated
Adenosquamous carcinoma may just be high grade _________
mucoepidermoid carcinoma
Which sinus is the most common site for carcinoma of the paranasal sinuses?
Maxillary
“SNUC” = _______….. The cell of origin may be the ________ membrane or olfactory epithelium
sinonasal undifferentiated carcinoma….schneiderian
Nasopharyngeal carcinoma is most common in what geographic region and gender? What virus is a risk factor? Where is the PRIMARY lesion usually located?
southern Chinese men…EBV…lateral nasopharyngeal wall
Old name for nasopharyngeal carcinoma =
lymphoepithelioma
3 histologic types of nasopharyngeal carcinoma
- Keratinizing SCC 2. Differentiated nonkeratinizing carcinoma (EBV associated) 3. Undifferentiated non keratinizing carcinoma (EBV associated)
Most common of all cancers =
BCC
Intraoral BCC may look like _________…… The _______ surface protein expressed in cutaneous BCC helps differentiate
peripheral ameloblastoma…. Ber-EP4
Cell of origin for merkel cell carcinoma = Pluripotent ______ or ______ stem cells
epidermal or dermal
AEIOU of Merkel cell carcinoma
Asymptomatic, rapidly Enlarging, Immunosuppression, Old age, UV exposure
HPV type: recurrent respiratory papillomatosis
6/11
HPV type: verruca vulgaris
2
HPV type: condyloma accumenatum
6/11 (also sometimes high risk 16/18)
HPV type: multifocal epithelial hyperplasia
13/32
HPV type: Fungiform type of sinonasal papillomas
6/11
HPV type: some inverted sinonasal papillomas
6/11, 16/18
What are the 5 conditions with multifocal squamous papillomas (papillomatosis)
- Nevus unius lateris 2. Acanthosis nigricans 3. Focal dermal hypoplasia (Goltz-Gorlin) syndrome 4. Down syndrome 5. Recurrent respiratory papillomatosis (HPV 6/11)
Patients with Darier disease and atopic dermatitis are at risk for a severe or prolonged form of which infection?
molluscum contageosum
What are the 3 components of Muir-Torre syndrome?
- Visceral malignancies 2. Sebaceous adenomas / carcinomas 3. Keratoacanthomas
Lentigo simplex is found in what 3 conditions?
- lentiginosis profusa 2. Peutz-Jeghers syndrome 3. LEOPARD
What is the rare, potentially fatal congenital syndrome with multiple congenital nevi, melanotic neoplasms of the CNS, leptomenengial melanosis and melanomas?
Neurocutaneous melanosis
What 3 conditions are more susceptible to actinic cheilosis?
- xeroderma pigmentosum 2. Albinism 3. Porphyria cutanea tarda
What 2 conditions show EARLY ONSET of KAs?
Ferguson-Smith syndrome, Witten-Zak Syndrome
What condition is associated with late onset of KAs?
Grzybowski syndrome (hundreds to thousands of KAs on skin and aerodigestive tract
What 2 iron def syndromes increase susceptability to SCC?
Plummer-Vinson Syndrome, Paterson-Kelly Syndrome
What are the 7 conditions associated with BCCs?
- NBCCS 2.Xeroderma pigmentosum 3.Albinism 4. Rasmussen syndrome 5.Rombo Syndrome 6.Bazex-Christol-Durpe Syndrome 7.Dowling-Meara subtype of Epidermolysis Bullosa Simplex
Familial Hecks Disease is related to which allele?
HLA-DR4 allele
Which variant of Heck’s is more common?
Papulonodular (pink, smooth surface)…the less common = papillomatous (white, pebbly)
What is the histo buzzword for the rete ridges in Heck’s disease?
“club shaped”
Inverted papilloma: proteins increased?
p63, p21
Inverted papilloma: decreased ____ (cell adhesion)
CD44
Inverted papilloma: Presence of HPV ___ and ___
16 and 18
Inverted papilloma: what % have malignant trans
up to 24%
What is the clinical feature of a CYLINDRICAL cell papilloma?
BEEFY-RED or brown mass
What causes Molluscum?
DNA poxvirus called MCV (molluscum contagiosum virus)
VX: gene mutation (somatic)
3BHSD
What stain is positive in VX?
PAS-D
What are the two somatic mutations in SebK?
FGFR3 and PIK3CA
What inheritance for dermatosis papulosa nigra (periorbital / zygomatic papules)…up to 77% blacks affected
AD
What is the gene variation of an ephelis?
MC1R
Genetic alterations for actinic lentigo?
PIK3CA and FGFR3
How is lentigo simplex differentiated from a melanocytic nevus?
Nevus = BRAF mutation
What does LEOPARD stand for?
Lentigines, ECG abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnromalities of genitalia, Retarded growth, Deafness
Melasma is AKA:
mask of pregnancy
Gender predilection for melanoacanthoma?
female
80% of aquired melanocytic nevi have what genetic mutation?
BRAF
BRAF is a proto oncogene that encodes serine/threonine kinase involved in the ______ pathway
MAPK
Aquired nevus = maturation pattern…superficial cells arranged in ______ (nested), further down they resemble _______, and deepest more ______ shaped
theques….lymphocytes…elongated/spindle
Aquired nevi start ______ and then move to ______
the epithelium (junctional)….then move to the mucosa/dermis (compound –> intradermal/intramucosal)
Congenital nevi harbor _____ mutations
NRAS
What is the malignant transformation rate of a congenital nevus?
2-3%
What are the two other names for a Halo nevus?
Sutton nevus, leukoderma acquisitum centrifugum (fucking evil name)
Genetic mutation in Spitz nevus?
HRAS
Other names for Spitz nevus?
benign juvenile melanoma (wtf?!), spindle and epitheloid cell nevus
What age do Spitz nevi show up in?
children
Genetic mutation in a blue nevus?
GNAQ
Two alternate names for Blue nevus?
dermal melanocytoma, Jadassohn-Tieche nevus
What is the most common intraoral melanocytic? 2nd?
- ? maybe intramucosal nevus? 2.Blue nevus
The __________ is probably the most common of all human “tumors,” with an average of 10 to 40 cutaneous nevi per white adult.
acquired melanocytic nevus
Which KA syndrome occurs in patients of Scottish decent?
Ferguson-Smith
Where does the SCC go? Lower lip and floor of mouth?
submental nodes
Where does the SCC go? Posterior mouth
superior juggular and digastric
Where does the SCC go? oropharynx
jugulodigastric or retropharngeal
In adenosquamous carcinoma what do both components stain positive for?
HMCK
SNUC is positive for which 2 stains?
CK and EMA
What gene is associated with NBCCS? (you better get this)
PTCH
What is the virus found in 80% of merkel cell carcinomas?
MCPYV (merkel cell PolYoma virus)
What is the most common melanoma genetic abnormality? What about MUCOSAL melanomas?
BRAF (50%)….mucosal = KIT
What is the most common histo form of melanoma?
superficial spreading (70%)
What are two alternate terms for a lentigo maligna?
Hutchinson freckel or melanoma in situ
What is the most common oral form of melanoma?
acral lentigenous melanoma
What % of oral melanomas are Amelanotic?
10%
What is the alternate name for a pilomatrixoma?
Calcifyed Epithelioma of Malherbe
What are the three types of sinonasal papillomas?
- Fungiform (almost always on nasal septum, 65% HPV related, minimal malignant potential)
- Inverted (most common, greatest potential for malignant transformation (3-24% SCC), 38% HPV related, lateral nasal wall)
- Cylindrical cell (least common, lateral nasal wall, 23% HPV related)
Inverted sinonasal papilloma: gender?
3:1 to 5:1 MALE
What are 3 proto-oncogenes associated with Oral SCC?
What are 3 tumor suppressor genes associated with oral SCC?
Oncogenes:
- Ras
- Myc
- EGFR
Tumor suppressors:
- p53
- pRB
- p16
- E-cadherin
Head and neck squamous cell carcinomas associated with tobacco and alcohol use often exhibit ______TP53, pRb _______, and ________ p16 expression
mutated TP53, pRb overexpression, and decreased p16 expression
HPV-associated HNSCC cases typically express _______ TP53, _________ of pRb, and _________ levels of p16.
HPV-associated HNSCC cases typically express wild-type TP53, low levels of pRb, and increased levels of p16.
What is the gold standard for determining active HPV causing oropharyngeal carcinoma?
high-risk HPV E6 and E7 oncogene expression analysis by qRT-PCR (needs fresh frozen tissue)
p16 IHC is more widely available and is a highly sensative (not specific) surrogate for transcriptionally active, high-risk HPV infection in oropharyngeal SCCs
What is the molecular basis for using p16 as a surrogate marker in HPV+ SCC?
overexpression of p16 results from inactivation of pRB which is a result of the HPV E7 oncogene
E7 –> blocks pRB —> overexpresses p16
How does HPV 16 ISH compare to using p16 IHC for detection of HPV+ SCC?
ISH exhibits strong agreement with p16 immunohistochemistry, although it may fail to detect
the minority of oropharyngeal tumors caused by other HPV types
What is the best prognostic indicator for lip and oral SCC?
What are the 3 best prognostic indicators for oralpharyngeal SCC?
lip/oral: tumor stage
oropharyngeal: HPV status, then tobacco, then stage
conventional squamous cell carcinoma develops concurrently within up to ____% of verrucous carcinomas.
20%
Approximately ___% of verrucous carcinoma patients are disease free 5 years after surgery
90%