38 ODA JOURNAL October 2011

CLINICAL
DAVID M. LEWIS, DDS MS
OUCOD DEPARTMENT OF ORAL AND MAxILLOFACIAL PATHOLOGY
Clinical Case:
This is a 25 year-old male with an asymptomatc white lesion of the lateral
border of the tongue. He is in apparent good health, does not smoke,
but does have an occasional alcoholic drink. On clinical exam he has
several palpable lymph nodes of the anterior and posterior cervical chain
varying in size from 0.5 cm to 2 cm. The lesions have been present for
approximately 3 months. Fig. 1 - Right
The diferental Diagnosis should include:
a. Leukoplakia
b. Frictonal keratosis
c. Candidiasis
d. Oral hairy leukoplakia
e. All of the above
The correct answer is e. All of the above: all of the above may present as white lesions. Leukoplakia by defniton is any white lesion that
cannot be characterized clinically or pathologically as any other disease. Frictonal keratosis is a separate entty from leukoplakia but can be
clinically similar. It is secondary to mechanical trauma and is readily reversible afer removal of the source of trauma. They are hyperplastc
lesions (similar to a callus on the skin) and should never show dysplastc changes. Candida is usually thought of as a wipeable white lesion with
a red base, however the hypertrophic variant will appear as a non-wipeable plaque most commonly on the lateral border of the tongue or
anterior buccal mucosa. It is the least common of the variants of candidiasis and may simply represent superimposed candidiasis on a pre-
existng leukoplakia. Ofen such lesions will show an increased frequency of epithelial dysplasia. Oral hairy leukoplakia is a white lesion that is
associated with HIV-infected patents and characteristcally presents as vertcal streaks of keratn on the lateral border of the tongue.
The appropriate plan for the work up of this lesion would include:
a. Follow the patent for change in the lesion
b. Cytology
c. Biopsy
d. Refer to the primary care physician for clinical evaluaton of the persistent lymphadenopathy
e. Order an HIV test
The correct answer would be d. The patent is showing signs of a systemic disease process with persistent generalized lymphadenopathy
and clinical lesions that are a classic presentaton of oral hairy leukoplakia. This patent needs to be evaluated for his chronic persistent
lymphadenopathy and an immunodefciency disorder. Biopsy could also be considered; however, if the patent is HIV positve, the diagnosis
of oral hairy leukoplakia is usually a clinical diagnosis and does not require biopsy. The histopathologic fndings, while distnctve, are not
diagnostc. Following the patent for changes in the lesion, cytology, or ordering an HIV test are incorrect answers.
Discussion:
Human immunodefciency virus and acquired immunodefciency syndrome have now been with us for 30 years, having been frst reported
in the Morbidity and Mortality Weekly Report on June 5, 1981. Initally the disease was thought to be nearly 100% fatal. Since that tme,
through treatment advances and awareness of the disease, the annual incidence of AIDS and related death have been dramatcally altered
in the United States. Cases of AIDS in the United States expanded rapidly during the 1980s,peaked in 1992 at an estmated 78,000, and
decreased each year untl 1998 when the annual incidence stabilized at about 40,000 cases per year. The advent of highly actve ant-retroviral
therapy (HAART) has changed dramatcally the prognosis of the disease. Extended survival has increased the number of people living with
the virus. The percentage of individuals surviving two years has increased from 44% in 1981 to 1992, to 64% in 1993 to 1995, to 85% in 1996
to 2000. Subsequent to HAART the prevalence of oral manifestaton has also decreased, including signifcant reductons in the frequency of
oral candidiasis, oral hairy leukoplakia, HIV-associated periodontal disease, and Kaposis sarcoma. The frequency of all HIV-related lymphomas
has not demonstrated signifcant change and in contrast many researchers have reported an increase in the prevalence of benign human
papillomavirus (HPV)-induced pathoses.
2
Oral hairy leukoplakia is clinically a white mucosal plaque that does not rub of and is characterized histopathologically by a distnctve (but not
diagnostc) patern of hyperkeratosis and epithelial hyperplasia. Greenspan frst described it in 1984.
1
OHL is an Epstein Barr virus (EBV) lesion
associated with HIV-infected patents. The prevalence has been reported to be 20% in asymptomatc HIV infecton in the United States to 36%
in Tanzania with full-blown Acquired Immunodefciency Syndrome (AIDS).
4
The lesions usually occur on the lateral border of the tongue and
appear as faint white vertcal streaks to thickened and furrowed areas of leukoplakia, exhibitng a shaggy keratotc surface (Fig. 1). The lesions
Oral Hairy Leukoplakia
October 2011 okda.org 39
infrequently become extensive and cover the entre dorsal and lateral surfaces of the tongue. Rarely, they may involve the buccal
mucosa (Fig. 2), sof palate (Fig. 3), pharynx, or esophagus.

Below: Fig. 2. Buccal mucosa lesions of oral hairy leukoplakia.
Histologically, OHL exhibits thickened parakeratn that
demonstrates surface corrugatons or thin projectons. The
epithelium is acanthotc and exhibits a band-like zone of lightly
stained cells with abundant cytoplasm (balloon cells) in the
upper spinous layer (Fig. 4). Within the superfcial epithelium
scatered cells with nuclear clearing and a characteristc patern
of peripheral marginaton of chromatn termed nuclear beading
is caused by replicaton of the EBV that displaces the chromatn
to the nuclear margin (Fig. 5). Dysplasia is not noted.
5
The clinical fndings are usually sufcient for presumptve
diagnosis in HIV-positve patents. When defnitve diagnosis
is necessary, demonstraton of EBV within the lesion is
required and can be achieved by in situ hybridizaton, PCR,
immunohistochemistry, Southern blotng, or electron
microscopy.
2
Treatment of OHL is usually not needed. Systemic antherpesviral
drugs produce rapid resoluton, but recurrence is expected when
therapy is discontnued. Topical retnoids or pedophyllum resin
has resulted in temporary remissions. Patents on HAART with
reduced viral load and increased CD4 counts show a signifcant
reducton in prevalence of OHL.
2
Right: Fig. 3. Palatal lesions of oral hairy leukoplakia.

Rare instances of OHL have been reported in immynocompetent
individuals, however most cases arise in immunocompromised
persons.
6
OHL has also been reported in heart, kidney, liver,
and bone marrow transplant recipients. The presence of OHL in
the absence of a known cause of immunosuppression strongly
suggests an HIV infecton. The fnding of OHL in a normal
patent requires a thorough physical evaluaton to rule out
immunocompromised status. The presence of OHL in HIV-
infected patents is a signal of
severe suppression and more
advanced disease.
2
References:
1. Centers for Disease Control and
Preventon: Twenty-fve years of
HIV/AIDS in the United States, 1981-
2006. MMWR Morb Mortal Wkly
Rep 55:585-589, 2006.
2. Neville BM. Damn DD, Allen CM,
Bouquot JE.: Oral and Maxillofacial
Pathology. 3rd ed. Philadelphia:
Saunders. 2009.
3. Greenspan D, Greenspan
J,Conant M, Peterson V, Silverman
S, DeSouza Y: Oral hairy
leukoplakia in male homosexuals:
Evidence of associaton with both
papillomavirus and a Herpes-group
virus. Lancet 1984:2;831-4.
4. Greenspan D, Greenspan
J.: Signifcance of oral hairy
leukoplakia. Oral Surg Oral Med Oral path, 1992; 73:151-4.
5. Triamtos D, Porter S, Scully C, Teo CG.: Oral Hairy Leukoplakia: Clinicopathologic Features, Pathogenesis, Diagnosis and Clinical Signifcance. Clinical
Infectous Disease, 1997; 25:1392-6.
6. Eisenburg et al: Incidental oral hairy leukoplakia in immunocompetent persons: a report of two cases. Oral Surg Oral Med Oral Path, 1992; 74: 332-3.
CLINICAL
Right: Fig. 4. Balloon cells in the upper spinous layer.
Below: Fig. 5. Peripheral marginaton of
chromatn (nuclear beading).