Chapter 10: Epithelial Pathology PART 3 Flashcards
___ is a chronic, progressive, scarring, high-risk precancerous condition of the oral mucosa
oral submucous fibrosis
oral submucous fibrosis is linked to chronic placement of ___ or ___
betel quid or paan
- quid - areca nut from a palm tree
- slaked lime
- betel leaf
- +/- tobacco
- +/- sweeteners
betel quid is seen primarily in the ___ subcontinent, but ___ million people worldwide use it regularly
- india
- 600
___ releases alkaloids from the areca nut, which results in ___
- slaked lime
- euphoria
how often do betel quid users typically use it?
16-24 hours/day
betel quid ingredients can be purchased in the US. they have a higher concentration of ___ and cause ___
- areca nut
- lesions more rapidly than conventional
oral submucous fibrosis is characterized by ___
mucosal rigidity
T or F:
a few patients developed oral submucous fibrosis after only a few contacts with areca nut
true
what is the first chief complaint of patients with oral submucous fibrosis?
trismus and mucosal pain from eating spicy foods
what sites are most commonly affected by oral submucous fibrosis?
buccal mucosa, retromolar areas, soft palate
the surface of oral submucous fibrosis lesions is typically what color?
white
___% of oral submucous fibrosis lesions show frank malignancy
5%
do oral submucous fibrosis lesions regress with habit cessation?
no
___ is mandatory in the management of oral submucous fibrosis lesions
frequent follow-up
___% of oral submucous fibrosis lesions undergo malignant transformation
10%

oral submucous fibrosis
nicotine stomatitis produces a ___ change on the palate
white keratotic
(can be diffusely gray or white)
nicotine stomatitis is due to ___
heat (long-term hot beverage use can cause the same clinical changes)
is nicotine stomatitis premalignant?
no
what is reverse smoking?
the lit end is held in the mouth
describe nicotine stomatitis that results from reverse smoking
significant potential for malignant transformation, requires a biopsy
nicotine stomatitis is most commonly found in males or females? of what age?
white males older than age 45
how does nicotine stomatitis present clinically?
- numerous, slightly elevated papules
- typically have punctuate red centers
- may appear like dried mud
the punctuate red centers in nicotine stomatitis lesions represent what?
inflamed minor salivary glands and their ductal orifices
is nicotine stomatitis reversible?
yes - palate returns to normal within 2 weeks of habit cessation

nicotine stomatitis

nicotine stomatitis
actinic keratosis is a common ___ lesion
cutaneous premalignant
what is actinic keratosis caused by?
cumulative UV radiation
actinic keratosis develops in over half of white adults with significant lifetime ___ exposure, and is seldom found in patients younger than age ___
- sun
- 40
actinic keratosis lesions are ___, ___ plaques that vary in color from ___ to ___ to ___
- scaly, irregular
- white, gray, brown
actinic keratosis lesions have a ___ texture
sandpaper
what happens if keratotic scales from actinic keratosis are peeled off?
the lesion will recur
is dysplasia present on biopsy of actinic keratosis?
yes, by definition
actinic keratosis should be destroyed or excised due to ___
its precancerous nature
approximately ___% of actinic keratosis will progress to squamous cell carcinoma in ___ years
- 10%
- 2 years

actinic keratosis
___ is a common premalignant alteration of the lower lip vermillion that results from long-term exposure to ___
- actinic cheilosis
- UV light
___ is associated with actinic cheilosis
outdoor occupation
- farmer’s lip
- sailor’s lip
actinic cheilosis is similar to actinic keratosis in ___ and ___
pathophysiologic and biologic behavior
actinic cheilosis is rare in persons under what age?
45
what is the male:female prevalence of actinic cheilosis?
M:F is 10:1
actinic cheilosis is slowly developing, and the patient is usually not aware of the lesion. what are the earliest clinical changes in actinic cheilosis?
- atrophy of the lower lip vermillion border, characterized by a smooth surface and blotchy pale areas
- blurring of the margin between the vermillion zone and cutaneous portion of the lip
after the earliest clinical changes seen in actinic cheilosis, as the lesion progresses, scaly areas develop on the ___. further progression leads to ___, which suggests ___
- drier portions of the vermillion
- ulceration
- transformation into squamous cell carcinoma
are changes seen in actinic cheilosis reversible? what should patients be instructed to do to prevent further damage?
- no
- patients should use lip balms
actinic cheilosis lesions that exhibit which characteristics should be submitted for biopsy? ___% of patients with these characteristics will develop squamous cell carcinoma
- induration (firm to touch), thickening (leukoplakia), and/or ulceration
- 10%

actinic cheilosis

actinic cheilosis
keratoacanthoma is also known as ___
squamous cell carcinoma, keratoacanthoma type
keratoacanthoma is a ___, ___ proliferation
self-limiting, epithelial
keratoacanthoma has a strong clinical and histopathological similarity to well-differentiated ___
SCCA
patients with ___ have a hereditary predisposition for multiple keratoacanthoma lesions
muir-torre syndrome
keratoacanthoma has a predilection for males or females? over what age?
males over the age of 45
10% of keratoacanthoma cases occur where?
on the outer edge of the vermillion border of the lips
how does keratoacanthoma present clinically?
a firm, well-demarcated, painless, sessile, dome-shaped nodule with a central plug of keratin
what are the 3 phases of keratoacanthoma?
- growth - rapidly grows up to 2cm in 6weeks; distinguishes from SCCA
- stationary
- involution - within 1 year of onset
surgical excision of ___ lesions is recommended, despite the propensity to involute
keratoacanthoma

keratoacanthoma

keratoacanthoma

keratoacanthoma

keratoacanthoma
1 in ___ americans develop a malignancy. of those, how many survive?
- 3
- 2/3
cancer accounts for ___% of all deaths in the US; oral cancer accounts for ___%; ___% of these are SCCA
- 20%
- 3%
- 95%
the cause of SCCA is ___
multifactoral
there are many contributing factors
what are the possible contributors to the development of SCCA?
- tobacco
- betel quid
- alcohol
- phenolic agents
- radiation
- iron deficiency
- vitamin-A deficiency
- syphilis
- oncogenic viruses
- immunosuppression
- oncogenes
- tumor suppressor genes
___% of US adults smoke, and ___% of patients with oral SCCA have a history of smoking
- 20%
- 80%
___ and ___ smoking carries a greater oral cancer risk than ___ smoking
- pipe and cigar
- cigarette
the smoker’s risk for oral SCCA compared with that of a nonsmoker is dependent on what?
- dose
- 2 ppd = 5x increase risk
- 4 ppd = 17x increase risk
- risk increases the longer the person smokes
___ results in the greatest risk of SCCA development from tobacco
reverse smoking
can alcohol alone initiate carcinogenesis?
it is uncertain, but in combination with tobacco, it is a significant risk factor for SCCA
what is the indirect evidence provided that suggests alcohol in combination with tobacco is a significant risk factor for SCCA?
1/3 of men with oral SCCA are heavy drinkers compared to 10% of the general population (nutritional deficiencies may contribute)
which population is at increased risk for SCCA caused by phenolic agents?
workers in the wood industry who are chronically exposed to phenoxyacetic acids
describe SCCA development risks relative to radiation
- effects of UV radiation are well known
- x-irradiation (for cancer treatment) also increases the risk
___ is required for normal function of the epithelial cells in the upper digestive tract, and can produce esophageal webs, resulting in an increased risk for SCCA development
iron
patients with severe, chronic forms of what syndrome, characterized by difficulty swallowing and iron deficiency, are at increased risk for SCCA?
plummer vinson syndrome
patients that are iron deficient tend to have impaired ___
cell-mediated immunity
describe the relationship between vitamin A deficiency and SCCA
- deficiency produces excessive keratinization
- researchers believe normal levels are protective
which stage of syphilis can cause SCCA, and on what location in the mouth? what is it possibly due to?
- tertiary stage
- dorsal tongue SCCA
- may be due to old treatment with aresenical agents and heavy metals
which oncogenic viruses can cause SCCA?
HPV 16, 18, 31, 33
describe the relationship between immunosuppression and the development of SCCA
- immune reaction to malignant cells is diminished
- patients at risk include AIDS patients and patients undergoing immunosuppressive therapy for other malignancy or organ transplantation
___ are chromosomal components capable of being acted on by a variety of causative agents
oncogenes
normal genes are proto-oncogenes
proto-oncogenes can be transformed into activated oncogenes via what 3 things?
viruses, irradiation, or chemical carcinogens
once oncogenes are activated, they may stimulate the production of an excessive amount of ___
new genetic material
___ allow tumor production when they become inactivated or mutated
tumor suppressor genes
SCCA may have what 5 possible characteristics?
- exophytic (mass forming, fungating)
- endophytic (invasive, burrowing, ulcerated)
- leukoplakic
- erythroplakic
- erythroleukoplakic
what is the most common site of intraoral SCCA? what is the second most common site? third? fourth?
- most common site is the posterior lateral or ventral tongue
- second most common site is the floor of the mouth
- third most common site is the soft palate
- fourth most common site is the gingiva
the majority of lingual SCCAs are ___, ___ masses or ulcers on the ___ border of the tongue
- painless, indurated
- posterior lateral
floor of mouth SCCA lesions are most likely to be associated with prior ___ or ___
leukoplakia or erythroplakia
floor of mouth SCCA lesions are typically located where?
midline, near the frenum
___ and ___ intraoral SCCAs are usually painless
gingival and alveolar
gingival and alveolar SCCAs have a propensity to mimic ___ or ___
benign lesions or periodontal disease
of all intraoral SCCA lesions, gingival and alveolar carcinomas are least associated with ___ use and is more common in males or females?
- tobacco
- females
oropharyngeal SCCAs develop where?
on the soft palate or tonsillar area
oropharyngeal SCCAs have the same appearance as SCCAs located more anteriorly, except ___. therefore when it is doscovered, ___ is more likely
- the patient is usually unaware of its presence
- metastasis
80% of oropharyngeal wall SCCA lesions have ___ or ___ at the time of diagnosis
metastasized or extensively involved surrounding structures
metastatic spread of SCCA is largely via ___, and tends to spread to ___
- lymphatics
- ipsilateral lymph nodes
in cases of SCCA metastasis, how will cervical lymph nodes present?
- firm to stony hard
- painless
- enlarged
- fixed - if the cells have perforated the capsule of the node and invaded into surrounding tissues
distant metastasis of SCCA is below the ___, and most commonly found where?
- below the clavicles
- most commonly found in the lungs, liver, and bones
what is the best indicator of patient prognosis in cases of SCCA?
stages
SCCA staging is determined by ___ and ___
tumor size and extent of metastatic spread (TNM system)
what is the TNM system for staging?
- T = size of primary local tumor in sontimeters
- N = involvement of local lymph nodes
- M = distant metastasis
what does it mean if any TNM is followed by an X? what about if it is followed by a 0?
- X = no available information
- ex. Nx = nodes could not be or were not assessed
- 0 = no evidence of primary tumor
- ex. M0 = no evidence of distant metastasis
in the TNM system, T indicates ___. what do the following indicate?
Tis
T1
T2
3
T4a
T4b
primary tumor size
- Tis = carcinoma in situ
- T1 = tumor is 2cm or less
- T2 = tumor is 2-4cm
- T3 = tumor is more than 4cm
- T4a = tumor is resectable and doesn’t involve major anatomy
- T4b = unresectable tumor; involves major anatomy
in the TNM system, N indicates ___. what do the following indicate?
N1, N2, N3
regional node involvement
- N1 = single ipsilateral node, 3cm or less
- N2 = ipsilateral or contralateral node or nodes; 6cm or less
- N3 = any metastasis in a node more than 6cm
in the TNM system, M indicates ___. what do the following indicate?
M0, M1
involvement by distant metastases
- M0 = not present
- M1 = present
what are the TNM classifications that accompany stage I?
T1, N0, M0
what are the TNM classifications that accompany stage II?
T2, N0, M0
what are the TNM classifications that accompany stage III?
T3, N0, M0 or any T, N1, M0
what are the TNM classifications that accompany stage IV?
any M, any T4, any N3
what allows for tumor grading?
histologic features
tumors that most closely resemble their parent tissue seem to grow at a lower rate. which grade does this describe?
- grade I
- low-grade
- well-differentiated
tumors that less resemble their parent tissue are which grade?
- grade II
- intermediate-grade
- moderately-differentiated
tumors that show little resemblance to their parent tissue tend to enlarge rapidly and metastasize early. which grade is this?
- grade III (or IV, depending on scale)
- high-grade
- poorly-defferentiated
___ staging is a better prognostic indicator than histologic grading
clinical
lip carcinoma is typicaly treated with ___ with excellent results. what percent recurs? what is the 5-year survival?
- wedge resection
- 10%
- reaches 100% on the lower lip
___ guides treatment for intraoral carcinoma
clinical stage
what is the treatment for SCCAs?
- wide surgical excision and/or radiation therapy
- chemotherapy is sometimes administered
- does not improve survival time
patients with intraoral tumors larger than 3mm depth of invasion receive ___
radical neck dissection
patients with one carcinoma of the mouth or throat are at an increased risk for ___
additional SCC
- concurrently (synchronous)
- different time (metachronous)
___ is the tendency toward development of multiple mucosal cancers
field cancerization
verrucous carcinoma is also called ___
snuff dipper’s cancer
___ is a low-grade variant of oral SCC that can be caused by smokeless tobacco
verruccous carcinoma
verruccous carcinoma is found predominantly in men or women? over what age?
men older than 55
what are the most common sites of involvement of verruccous carcinoma?
mandibular vestibule and gingiva
verruccous carcinoma is typically ___ by the time of diagnosis and is present for ___ years before diagnosis
- extensive
- 2
verruccous carcinoma appears as ___
a diffuse, well-demarcated, painless, thick plaque with papillary or verruciform surface projections
verruccous carcinoma has a ___ microscopic appearance
deceptively benign
why is adequate sampling of a verrucous carcinoma biopsy is important?
because up to 20% have a SCCA developing within the verrucous carcinoma
what is the treatment of verrucous carcinoma? what percent of patients survive disease-free?
- surgical excision without neck dissection
- 90%
what is the malignant transformation potential, from most to least, of the following pathologies?
oral submucous fibrosis, erythroleukoplakia, proliferative verrucous leukoplakia, erythroplakia, actinic cheilosis, granular leukoplakia, nicotine stomatitis in reverse smokers
- proliferative verrucous leukoplakia
- nicotine stomatitis in reverse smokers
- erythroplakia
- oral submucous fibrosis
- erythroleukoplakia
- granular leukoplakia
- actinic cheilosis

nicotine stomatitis in reverse smokers

verrucous carcinoma

verrucous carcinoma

actinic keratosis

actinic keratosis
___ refers to a group of malignancies that arise from the lining epithelium of the nasopharynx
nasopharyngeal carcinoma
nasopharyngeal carcinoma is most prevalent in what population?
chinese men
what are the possible contributory factors of nasopharyngeal carcinoma?
- EBV infection (strongly associated)
- vitamin C deficiency
- consumption of salt fish with N-nitrosamines
- +/- tobacco
what age patient does nasopharyngeal carcinoma occur most commonly in?
all ages, but most commonly age 50
what is the M:F prevalence of nasopharyngeal carcinoma?
3:1 M:F
the primary lesion of nasopharyngeal carcinoma is usually found where?
on the lateral nasopharyngeal wall
what is the first sign of disease in nasopharyngeal carcinoma cases?
in half of patients, it is cervical lymph node metastasis
what is the treatment for nasopharyngeal carcinoma?
- radiotherapy
- +/- chemotherapy
what is the prognosis of nasopharyngeal carcinoma?
- ranges from good to poor depending on the stage of disease
- stage I = 100% 5-yr
- stage IV = 35% 5-yr
- patients with 2+ clinical symptoms have a worse prognosis
nasopharyngeal carcinoma
what is the most common of all cancers?
basal cell carcinoma
___ is a locally invasive and slowly spreading epithelial malignancy
basal cell carcinoma
80% of basal cell carcinomas are found where?
in the head and neck regions
basal cell carcinoma results from what?
UV radiation
- frequent sunburns and freckling in childhood increase risk
- occupational sun exposure and sunburns as an adult are not significant risk factors
what is the most common form of basal cell carcinoma?
nodular (noduloulcerative)
nodular (noduloulcerative) basal cell carcinoma begins as a ___, and slowly enlarges, gradually developing into a ___. one or more ___ are typically seen, and ___ borders are usually present
- firm, painless papule
- central depression and unbilicated appearance
- telangiectatic blood vessels
- rolled
is metastasis common in basal cell carcinoma?
no, it is extremely rare
what are the 4 other clinicopathologic varieties of basal cell carcinoma?
- pigmented - same as nodular, but clinically brown or black
- sclerosing (morpheaform) - mimics scar tissue; deeply invasive before discovery
- superficial - skin of trunk; appear as multiple scaly red patches that somewhat resemble psoriasis
- those associated with nevoid basal cell carcinoma
treatment of basal cell carcinoma depends on what? what is the treatment?
- depends on size and location of the lesion
- Mohs micrographic surgery - essentially uses frozen-sections to evaluate margins during surgery
treatment of basal cell carcinoma have a ___% cure rate
98%
is recurrence of basal cell carcinoma common after treatment? is metastasis common?
- recurrence is uncommon with properly treated disease
- metastasis is exceptionally rare
describe death associated with basal cell carcinoma
death is usually the result of local invasion into vital structures, though it is unusual to have such uncontrollable disease

nodular basal cell carcinoma
notice the telangiectatic blood vessels and the central depression

nodular basal cell carcinoma
notice the telangiectasia and central depression

basal cell carcinoma
___ is a malignant neoplasm of melanocytic origin
melanoma
melanoma arises from a ___ or ___
- benign melanocytic lesion
- de novo from melanocytes within otherwise normal skin or mucosa
most melanoma lesions develop where?
on the skin, but can develop anywhere melanocytes are present
what is a major causative factor of melanoma?
- damage from UV radiation
- chronic sun exposure is not a significant factor; acute sun exposure is
the risk of melanoma increases 2-8x with what?
a family history of disease
other than family history and acute UV radiation, what are additional risk factors of melanoma?
- fair complexion
- light hair
- tendency to sunburn easily
- history of painful/blistering sunburns in childhood
- personal history of melanoma
- personal history of dysplastic or congenital nevus
melanoma is the ___ most common skin cancer, but accounts for the most ___
- 3rd (1/60 will be diagnosed)
- deaths
___% of melanomas arise on the skin, ___% of which are in the head and neck region
- 90%
- 25%
50% of ___ melanomas occur in the head and neck region
mucosal
- oral cavity
- sinuses
1/3 people with oral melanoma have a history of ___
a pigmented macule in the region
mucosal melanoma presents at a ___ state and is more ___
- advanced
- aggressive
this is why oral melanoma is really bad
melanoma exhibits two directional patterns of growth. describe them
- radical - malignant melanocytes spread horizontally through the basal layer (flat lesion)
- vertical - malignant cells invade underlying connective tissue (tumor)
___ is melanoma’s benign counterpart
melanocytic nevus
what is the ABCDE system used to distinguish between melanoma and melanocytic nevus that has been developed to describe the clinical features of melanoma?
- Asymmetry
- Border irregularity
- Color variation
- Diameter greater than 6mm
- Evolving lesions
what is the treatment of choice for melanoma?
- surgical excision with a 3-5cm margin
- 1cm margins are now being used for cutaneous tumors less than 2mm in thickness
melanomas are traditionally considered ___
radioresistant
___ has promise in the treatment of melanoma
newer chemo therapy
what are the locations of melanoma associated with a worse prognosis?
BANS
- intrascapular area of the Back
- posterior upper Arm
- posterior and lateral Neck
- Scalp
what is the prognosis for oral melanoma?
extremely poor
- 5-year survival is 15-20% due to inability for wide resection and a tendency for early hematogenous metastasis

nasopharyngeal carcinoma
which patients have a better survival from melanoma?
younger patients
patients with ___ melanoma have a very poor prognosis
amelanotic
patients with melanoma usually die from ___ rather than lack of local control
distant metastasis

melanoma

oral melanoma

oral melanoma

oral melanoma
___ correlates with prognosis of melanoma
depth of invasian - clark’s classification
___ is an adverse prognostic indicator for cutaneous melanomas
ulceration
ulceration has not been proven to be a prognostic indicator in ___ melanomas
mucosal
any invasion more than ___mm in oral mucosal melanoma has a poor prognosis
0.5mm