Oral cavity
Premalignant / in situ conditions
Dysplasia

Author: Hedieh Honarpisheh, M.D. (see Authors page)
Editor: Christel Haberland, DDS, MS

Revised: 24 April 2018, last major update November 2013

Copyright: (c) 2004-2018, PathologyOutlines.com, Inc.

PubMed Search: Dysplasia[TI] oral cavity[TIAB]

Cite this page: Honarpisheh, H. Dysplasia. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/oralcavitydysplasia.html. Accessed July 19th, 2018.
Definition / general
  • Dysplasia, a premalignant condition, refers to abnormal epithelial growth characterized by a spectrum of cytologic, maturational and architectural changes
  • Carcinoma in situ means abnormal changes are seen in the entire thickness of epithelium, extending from basal cell layer to surface
  • Vulva and cervix: moderate and severe degrees of dysplasia carry increasing risk of subsequent progression to invasive squamous cell carcinoma
  • Oral cavity: relationship of dysplasia with invasive carcinoma is less well defined; for moderate dysplasia, the malignant transformation potential is 4 - 11%; for severe dysplasia it is 20 - 35%
Terminology
  • Terms mild, moderate and severe dysplasia are applied if architectural and cytologic atypia (see micro description) affect < 1/3, 1/3 to 2/3 and > 2/3 of epithelium respectively
  • Carcinoma in situ (CIS): full thickness cytological or architectural atypia, without invasion of the neoplastic keratinocytes through the basement membrane into the supporting connective tissue
Epidemiology
  • Oral cavity CIS has same age and sex distribution as invasive oral squamous cell carcinoma (SCC) - males in fifth to eighth decade of life who are smokers and drinkers
  • Risk of oral SCC increases with age
  • Male gender predilection (3:1) historically related to greater use / abuse of tobacco and alcohol by men
  • Human papillomavirus (HPV) has been implicated in etiology of oral and base of tongue / pharyngeal SCC but has not been consistently seen in dysplasia / CIS
Sites
  • Most common sites of occurrence in the oral cavity, in descending order of frequency, are tongue (posterior - lateral and ventral) > floor of mouth > soft palate > gingiva > buccal mucosa > labial mucosa > hard palate
Pathophysiology
  • Moderate and severe dysplasia progress to invasive squamous cell carcinoma through accumulation of histological and molecular defects
  • HPV carcinogenesis affects cell control of transcription and cell cycle via the E6 and E7 viral oncoproteins that bind to and inactivate the tumor suppressor proteins p53 and pRb (retinoblastoma gene product) and activate telomerase
Etiology
  • Similar ethologic factors as SCC
  • Lifestyle habits of smoking and drinking are most important risk factor
  • High risk HPV types 16 and 18 and far less commonly, low risk HPV types 6 and 11 have been found in oral carcinomas (Mod Pathol 2006;19:1310)
    • HPV16+ oral cavity and oropharyngeal tumors appear to represent a distinct disease process with a more favorable survival
  • History of head and neck SCC in a first degree relative is a risk factor
  • Other risk factors include:
    • Nutritional factors include such as Plummer-Vinson syndrome (chronic iron deficiency) and vitamin A deficiency
    • Areca nut habit (betel nut)
    • Smokeless tobacco use: usually occurs at site where tobacco is placed
    • Immunocompromised states: immunosuppressive therapy for malignancy or organ transplant
    • AIDS
    • Environmental factors include exposure to phenolic agents (wood workers)
    • Syphilis: tertiary syphilis has increased risk for dorsal tongue SCC
    • Long term pegylated liposomal doxorubicin for ovarian cancer (Oncologist 2012;17:1541)
Clinical features
  • Small lesions may be asymptomatic or present with minimal findings and vague symptoms
  • Larger lesions, depending on size and location, may present with ulceration, pain (local and referred), bleeding; also difficulty swallowing, speaking, chewing, opening the mouth
  • Oral squamous mucosa responds to chronic injury or carcinogenic stimuli by either hyperplasia or atrophy, presenting as leukoplakia or erythroplakia respectively:
    • Leukoplakia or "white patch": represents benign hyperkeratosis in 80% of cases, dysplasias in 12%, carcinoma in situ (CIS) in 3%, and invasive carcinomas in 5% of cases
    • Erythroplakia or "red patch": is a particularly ominous oral mucosal lesion, representing carcinoma in 51% of cases, severe dysplasia or CIS in 40% of cases, and mild to moderate dysplasia in 9% of cases
    • Erythroleukoplakia or speckeled leukoplakia: combination of leukoplakia and erythroplakia, also has higher frequency of advanced dyplasia present on biopsy
    • These lesions may be exophytic (papillary, fungating mass) or endophytic (ulcerated surface with induration of soft tissue, usually rolled borders) (Int J Clin Oncol 2011;16:5)
Diagnosis
  • Any persistent nonhealing lesion of the oral cavity or pharynx should be biopsied within one month of initial appearance
Prognostic factors
  • Extension and spread of dysplastic cells from the surface epithelium down excretory salivary ducts without evidence of stromal invasion is accompanied by the same recurrence rate as for invasive squamous cell carcinoma; this may, in part, explain recurrences in the floor of mouth after superficial excision or laser ablation
Case reports
Treatment
  • Elimination of risk factors such as drinking and smoking
  • Removal of oral epithelial dysplasia by conventional surgical excision, laser and cryosurgery
  • Recurrence is not uncommon, and may warrant surgical intervention
Clinical images

Images hosted on other servers:

Leukoplakia of buccal mucosa

Microscopic (histologic) description
  • Architectural features of dysplasia include:
    • Irregular epithelial stratification, loss of normal stratification and polarity, drop shaped rete ridges
    • Mitoses in the mid and upper epithelium, premature keratinization in single cells (dyskeratosis), basal cell hyperplasia and anaplasia, keratin pearls within rete pegs
  • Cytological features are similar to those used for other epithelia: nuclear enlargement and pleomorphism, increased nuclear to cytoplasmic ratio, prominent nucleoli, hyperchromasia
Positive stains
Molecular / cytogenetics description
  • Squamous intraepithelial neoplasia share similar molecular and genetic changes with squamous cell carcinoma
  • Loss of heterozygosity in 3p, 9p and 17p are associated with dysplasia
  • Increased expression of p53 in moderate and severe dysplasia and carcinoma in situ
  • "Gold standard" to evaluate dysplasia is still routine histology
Differential diagnosis
  • Chronic traumatic ulcer: must identify a focal source of trauma (broken down tooth, sharp edge on a dental prosthesis)
  • Frictional keratosis related to chronic mechanical trauma to oral mucosa
  • Lichen planus
    • Chronic mucocutaneous disorder with an immune mediated etiology, typically women (2/3) between ages 30 and 60 years
    • Clinically, lesions are bilateral and symmetric and not isolated
    • Have band-like lymphocytic infiltrate immediately underneath the epithelium exhibiting partial dissolution of the basement membrane and focal migration of lymphocytes into the epithelium; no epithelial dysplasia is seen
  • Oral candidiasis: hyperplastic candidiasis
  • Pyogenic granuloma
    • Reactive mass of proliferating granulation tissue presenting as a red, ulcerated, rapidly growing round mass typically on gingiva, tongue or buccal mucosa
    • Seen in second to fifth decades, with a predilection for females more frequently in pregnancy and likely caused by endocrine imbalance
  • Snuff dippers / tobacco pouch keratosis:
    • White keratotic plaque associated with smokeless tobacco products
    • Typically located only in areas of direct contact with snuff or chewing tobacco (buccal mucosa, floor of mouth)
    • Almost always completely reversible when the affected patient stops using tobacco