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Focal epithelial hyperplasia (Heck's disease): a case report and review.

Focal epithelial hyperplasia (FEH), or Heck's disease, is a virus-induced, local proliferation of oral squamous epithelium. (1) It is a rare contagious disease caused by the human papillomavirus (HPV), a nonenveloped DNA virus. (2) It was first described in Navajo, Chavante Indian, and Alaskan Eskimo children in 1965 by Archard et al. (3) Since 1965, the majority of published cases report FEH in Eskimos and North, South, and Central American Indians. (4) In more rare instances, FEH has been reported in western European, African, Caucasian, and Asian populations. (5) The frequency of this disease is variable with a wide range from 0.002% to 35%, depending on the population studied and the geographical region. (6) Worldwide, FEH is predominantly seen in children with no gender predilection. However, cases are reported in young, middle-aged, and older adults, with an almost 5:1 female to male ratio in some populations. (4,7,8) Intraoral lesions associated with FEH have been seen to spontaneously regress, however, lesions can persist the lifetime of the affected individual. Many studies link FEH to malnutrition, poor oral hygiene, low socioeconomic status, and communal lifestyles. (7) Interestingly, recent reports have indicated the presence of FEH in HIV patients, indicating that immunosuppression leaves patients vulnerable to opportunistic infections, including HPV. (4) The etiology of FEH may have a genetic component, as it is found in the presence of HLA-DRB1*0404. (8) This HLA-DR allele is commonly present in some indigenous Americans, such as the Mazatecans, Nahuas, and Mexican mestizo populations. (8) Remarkably, since 1965, FEH has been detected in animals, including chimpanzees (Pan troglodytes), pygmy chimpanzees (Pan paniscus), howler monkeys (Alouatta fusca), and Asian lions (Panthera leo persica) (9)

As established by Pfister et al (10) and Ozden et al, (4) HPV subtypes 13 and 32 have been identified as the cause for FEH lesions through polymerase chain reaction (PCR) analysis and Southern blot hybridization, respectively. Other studies show that HPV DNA has been detected in 80.3% of FEH lesions. (8) A site-specific attraction for keratinized and nonkeratinized epithelial surfaces of the oral cavity has been observed in HPV subtypes 13 and 32, respectively. (4) The lesions associated with FEH are usually multiple, generally involving the labial and lingual mucosa. (1,4,11) Other sites include the lower lip, tongue, and less often on the upper lip, gingiva, palate, and tonsils. (1,4,11) The lesions are 3 mm to 10 mm papules or nodules, varying in color from pink to white. (8,12) Lesions are well demarcated, but they can often cluster closely together to form a cobblestone or fissured appearance. (1) Focal epithelial hyperplasia has 2 clinical forms: papulonodular and papillomatous. (8) The papulonodular variant is more common. This clinical variant usually occurs on the buccal and labial mucosa, as well as on the commisures of the mouth. (8) The papillomatous variant is less common and is usually located on the masticatory mucosa such as the tongue and attached gingiva. (8) Although the diagnosis of FEH can sometimes be made by clinical examinations, biopsy is the gold standard for accurate diagnosis. (8)

Histologically, the trademark of FEH is dramatic acanthosis of the oral epithelium. The thickened oral mucosa extends upward, away from the underlying connective tissue with the lesional rete ridges at the same level as adjacent normal rete ridges. The lesional rete ridges are widened, elongated, thickened and fused. (8) Epithelial surface cells show vacuolated cytoplasm around irregular, pyknotic nuclei. (12) Superficial keratinocytes can show viral koilocytic changes seen in other HPV infections. Viral particles and viral antigens have been identified in lesional keratinocytes with electron microscopy and immunohistochemistry, respectively. (6,13) Oral epithelial cells can exhibit an altered nucleus resembling a mitotic figure (mitosoid cell) with rare inflammatory changes. (1,14) Although FEH is associated with HPV, there seems to be no risk for dysplasia or malignant transformation. (1) Individual lesions generally show no ulceration or erosion. (8) In this article, we report a histopathologically diagnosed case of FEH in a young adult male of Eskimo (Inuit) descent.


A 32-year-old male active duty Soldier of Eskimo descent reported to the Oral and Maxillofacial Surgery clinic at Womack Army Medical Center, Fort Bragg, NC. This patient had a chief complaint of long-standing mucosal colored lesions on the right and left lateral borders of his tongue, creating a cosmetic concern. His medical history was unremarkable. He took no medications and had no history of serious illness or operations. His risk factors were minimal, being a non-smoker with only occasional social alcohol intake.



Upon clinical examination, 5 pink mucosal colored sessile papules were identified on the patient's lateral tongue borders. On the right lateral border, there were 3 distinct 3 mm lesions. On the left lateral border, there were single 8 mm and 2 mm lesions observed anteriorly and posteriorly, respectively (Figures 1 and 2). As reported in past studies, removal of FEH lesions may not be necessary except in cases of chronic trauma and aesthetic concerns. (4) Possible treatment modalities have been reported, including surgical excision, laser ablation, cryotherapy, electrocauterization, interferon, and retinoic acid. Low recurrence is seen with all treatment methods. In our case, the patient had cosmetic concerns.



We decided to perform an excisional biopsy of all tongue lesions to address his chief complaint and evaluate for more significant pathology.

Excisional biopsies of all lesions were performed and sent to our facility's Oral and Maxillofacial pathologist for histopathological examination (Figure 3). Setting the diagnosis of FEH is important to ensure differential diagnosis from other more serious conditions including inflammatory fibrous hyperplasia, inflammatory papillary hyperplasia, verruciform xanthoma, verrucous carcinoma, condyloma acuminatum, Cowden's Syndrome, Crohn's disease, and Amyloidosis. (4,8) In our case, FEH was diagnosed based on the presentation of considerable acanthosis (Figures 4 and 5) of the oral epithelium and mitosoid cells present in superficial keratinocytes (Figures 6 and 7). Our patient progressed postoperatively without incident. The biopsy sites healed optimally without recurrence after a 12-month follow-up period.


Focal epithelial hyperplasia, or Heck's disease, is a rare, viral-induced proliferation of oral squamous epithelium. As described in the literature, FEH is a benign condition that can regress spontaneously without surgical intervention. It has been linked to HPV subtypes 13 and 32 using PCR analysis and Southern blot hybridization. Focal epithelial hyperplasia is benign with no risk of malignant transformation, however, evaluating lesions is prudent to rule out more serious conditions. Detection of oral disease can, in many cases, result in early diagnosis of HIV and other states of immune system compromise.





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(2.) de Villers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H. Classification of papillomaviruses. Virology. 2004;324(1):17-27.

(3.) Archard HO, Heck JW, Stanley HR. Focal epithelial hyperplasia: an unusual oral mucosal lesion found in Indian children. Oral Surg Oral Med Oral Pathol. 1965;20: 201-212. Cited by: Ozden B, Gunduz K, Gunhan O, Ozden FO. A case report of focal epithelial hyperplasia (Heck's disease) with PCR detection of human papillomavirus. J Maxillofac Oral Surg. 2011;10(4):357-360.

(4.) Ozden B, Gunduz K, Gunhan O, Ozden FO. A case report of focal epithelial hyperplasia (Heck's disease) with PCR detection of human papillomavirus. J Maxillofac Oral Surg. 2011;10(4):357-360.

(5.) Liu N, Li Y, Zhou X, Zeng X. Focal epithelial hyperplasia (Heck's disease) in two Chinese females. Int J Oral Maxillofac Surg. 2012;41(8):1001-1004.

(6.) Hashemipour MA, Shoryabi A, Adhami S, Mehrabizadeh Honarmand H. Extensive focal epithelial hyperplasia. Arch Iran Med. 2010;13(1):48-52.

(7.) Harris AM, Van Wyk CW. Heck's disease (focal epithelial hyperplasia): a longitudinal study. Community Dent Oral Epidemiol. 1993;21(2);82-58.

(8.) Said AK, Leao JC, Fedele S, Porter SR. Focal epithelial hyperplasia-an update. J Oral Pathol Med. 2013;42(6):435-442.

(9.) Sa LR, DiLoreto C, Leite MC, Wakamatsu A, Santos RT, Catao-Dias JL. Oral focal epithelial hyperplasia in a howler monkey (Alouatta fusca). Vet Pathol. 2000;37(5):492-496.

(10.) Pfister H, Hettich I, Runne U, Gissmann L, Chilf GN. Characterization of human papillomavirus type 13 from focal epithelial hyperplasia Heck lesions. J Virol. 1983;47(2):363-366.

(11.) Sapp JP, Eversole LR, Wysocki GR. Contemporary Oral and Maxillofacial Pathology. St. Louis, MO: Mosby, Inc; 1997:214.

(12.) James WD, Berger TG, Elston DM. Andrews' Diseases of the Skin: Clinical Dermatology. 10th ed. Philadelphia, PA: Saunders Elsevier; 2006: chap 21, chap 29.

(13.) Stiefer RE, Solomon MP, Shalita AR. Heck's disease (focal epithelial hyperplasia). J Am Acad Dermatol. 1979;1(6):499-502.

(14.) Tan KN, Medak H, Cohen L, Burlakow P. Focal epithelial hyperplasia in a Mexican Indian. Arch Dermatol. 1969;100(4):474-477.

MAJ Zachary H. Highberger, DC, USA

MAJ Joseph W. Ivory, DC, USA

CPT Andre C. Ledoux, DC, USA

COL Jeffrey Almony, DC, USA

MAJ Highberger is Chief Resident, Oral/Maxillofacial Surgery, Womack Army Medical Center, Fort Bragg, North Carolina.

MAJ Ivory is a Staff Surgeon, Oral/Maxillofacial Surgery, Womack Army Medical Center, Fort Bragg, North Carolina.

CPT Ledoux is a Surgery Resident, Oral/Maxillofacial Surgery, Womack Army Medical Center, Fort Bragg, North Carolina.

COL Almony is Department Chief, Oral/Maxillofacial Surgery, Womack Army Medical Center, Fort Bragg, North Carolina.
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Author:Highberger, Zachary H.; Ivory, Joseph W.; Ledoux, Andre C.; Almony, Jeffrey
Publication:U.S. Army Medical Department Journal
Article Type:Clinical report
Date:Apr 1, 2014
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