Pathology of the GI Tract- Oral cavity and salivary glands (part 3 of 4) Flashcards
what is the odontogenic tumor we discussed?
keratocystic odontogenic tumor
the keratocystic odontogenic tumors are most commonly seen in what age group?
most often diagnosed in patients between 10 and 40
95% of head and neck cancers are what type?
squamous cell carcinomas (SCCs)
what is the etiology of SCC in the head/neck?
it is multifactorial–> 1) HPV 2) tobacco and alcohol 3) Betel quid and Paan (india/asia) 4) actinic radiation and pipe smoking
what is now the leading cause of SCC in the head/neck?
HPV
what variants of HPV are associated with OPSCC?
HPV 16 and 18
what is at the most risk for HPV related cancers of the head and neck?
white, non-smoking males age 35-55
in the head and neck, HPV demonstrates tropism for what?
lymphoid-associated structure of the oropharynx, including the palatine and lingual tonsils
what does infection of the tonsillar epithelium with HPV result in?
aberrant basal cell differentiation, dysplasia, carcinoma in situ, and finally invasive carcinoma
the oncogenic potential of HPV can largely be explained by the activity of what?
two viral genes encoding E6 and E7
what does HPV E7 inhibit/block?
p21 and RB pathways
what does HPV E6 inactivate/inhibit?
p53
what happens to the HPV genome and what does this suggest?
the HPV genome is integrated into the host genome, suggesting that integration of viral DNA is important for malignant transformation
how do patients with HPV-positive SCC compare to patients with HPV-negative tumors?
patients with HPV-positive SCC have greater long-term survival than those with HPV negative tumors
what are the clinical presentations associated with OPSCC?
non specific symptoms such as sore throat, ear ache, pain on swallowing, and weight loss; can present as a metastatic tumor in the lymph node
how can you identify if the OPSCC is caused by HPV?
if there is overexpression of p16 (a cell cycle inhibitor); or if the brown staining is positive
what is the second most common cause of classic oral SCC?
smoking/ tobacco
the development of classic oral SCC is driven by what?
the accumulation of mutations and epigenetic changes that alter the expression and function of oncogenes and tumor suppressor genes
several genes have been proposed as playing critical roles in SCC- what are they?
TP53, CDKN2A, and PIK3CA
a number of novel and potentially targetable genetic alterations have been identified in cases of SCC, what are they?
NOTCH1 and FAT1
what is the most frequently mutated gene in cases of SCC?
TP53
where are the common locations for oral SCC to present?
ventral tongue, floor of mouth, lower lip, soft palate, gingiva (look under dentures)
what are the classic SCCs typically preceded by?
the presence of premalignant lesions
what are two examples of premalignant lesions associated with classic oral SCC?
erythroplakia and leukoplakia
how is leukoplakia defined?
a white patch or plaque that cannot be scraped off and cannot be characterized clinically or pathologically as any other disease
what % of leukoplakias end up to be precancerous?
25%
how is erythroplakia defined?
a red, velvety, possibly eroded area within the oral cavity that usually remains level with or may be slightly depressed in relation to the surrounding mucosa
which is worse, leukoplakia or erythroplakia?
erythroplakia- this premalignant lesions is almost always associated with severe dysplasia/ carcinoma in situ
what are the characteristics of dysplasia?
pleomorphism, increased mitotic figures, loss of architectural orientation, and loss in cell uniformity
what two histologic terms should point you directly towards SCC?
keratin pearls and intercellular bridges
what is a marker for SCC?
p63 and cyclin D1
what is the theory of field cancerization?
multiple independent primary tumors develop as the result of years of chronic exposure of the mucosa to carcinogens
how do first primary tumors compare to second primary tumors?
first primary tumors have a much higher survival rate, whereas second primary tumors are the most common cause of death
