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Medicina Oral, Patología Oral y Cirugía Bucal (Ed. impresa)

versão impressa ISSN 1698-4447

Med. oral patol. oral cir. bucal (Ed.impr.) vol.10 no.5  Nov./Dez. 2005


Multifocal epithelial hyperplasia. Report of nine cases
Hiperplasia multifocal del epitelio. Reporte de nueve casos


Constantino Ledesma-Montes (1), Elisa Vega-Memije (2), Maricela Garcés-Ortíz (1)
Maritza Cardiel-Nieves (1), Claudia Juárez-Luna (1)

(1) Facultad de Odontología, Universidad Nacional Autónoma de México
(2) Departamento de Dermatología. Hospital Manuel Gea González. México, D.F. MÉXICO

Dr. Constantino Ledesma Montes.
Apartado Postal #86-194.
Agencia de Correos #86.
Col. Villa Coapa.
México, D.F. 14391.
Tel-Fax: +52+5+671-1389.

Received: 9-05-2004  Accepted: 25-12-2004

Ledesma-Montes C, Vega-Memije E, Garcés-Ortíz M, Cardiel-Nieves M, Juárez-Luna C. Multifocal epithelial hyperplasia. Report of nine cases. Med Oral Patol Oral Cir Bucal 2005;10:394-401.
© Medicina Oral S. L. C.I.F. B 96689336 - ISSN 1698-4447


Multifocal epithelial hyperplasia (MEH) is also known as focal epithelial hyperplasia, Heck’s disease or multifocal papillomavirus-induced epithelial hyperplasia. It is characterised by the presence of multiple lesions in the oral mucosa of children and it has been associated with the presence of the human papillomavirus. The aim of this study was to determine the clinico-pathological features of the cases diagnosed as MEH in the Service of Dermatology of the Hospital Manuel Gea González (SDHMGG). The files of the SDHMGG were reviewed and all cases diagnosed as MEH were retrieved. Nine MEH cases were found. Most of the patients were 20 year-old or younger (67%) and females were more commonly affected (78%). All patients presented multiple lesions and always, close relatives with similar lesions were found. Lesions were located most commonly in the buccal mucosa, lower lip and comissures. MEH is a soft tissue intraoral condition that needs treatment solely of the traumatised lesions or those with cosmetic problems. Remaining lesions will disappear with the age of the patients. It is suggested that this entity should be named multifocal epithelial hyperplasia since this name describes better the clinico-pathological and microscopic features of the disease.

Key words: Multifocal epithelial hyperplasia, human papillomavirus, Heck’s disease.


La hiperplasia multifocal del epitelio (HME) conocida también como hiperplasia epitelial focal, enfermedad de Heck ó hiperplasia multifocal del epitelio por papiloma virus, se caracteriza por la aparición de lesiones múltiples en la mucosa de la cavidad bucal en población pediátrica y se asocia a la presencia del virus papiloma humano. El objetivo de este estudio fue conocer las características clínico-patológicas de los casos diagnosticados de esta enfermedad en el Servicio de Dermatología del Hospital Manuel Gea González. Se revisaron los archivos de esta institución y se seleccionaron los casos diagnosticados como HME. Se encontraron 9 casos. La mayoría de los pacientes fueron menores de 20 años (67%) y del sexo femenino (78%), todos los casos presentaron lesiones múltiples y siempre hubo parientes directos con lesiones similares. Los lugares que se afectaron con mayor frecuencia fueron: mucosa bucal, labio inferior, paladar y comisuras. La HME es una condición de la mucosa de la cavidad bucal que solamente necesita tratamiento de aquellas lesiones que representan un problema cosmético ó aquellas que se traumatizan secundariamente. Las demás remitirán conforme avanza la edad del paciente. Se sugiere usar el nombre de hiperplasia multifocal del epitelio pues describe mejor las características clínico-patológicas y microscópicas de la enfermedad.

Palabras clave: Hiperplasia multifocal del epitelio, papilomavirus humano, enfermedad de Heck.



In 1956, Estrada reported on the presence of multiple intraoral soft tissue lesions discovered in Colombian Caramanta Indians (1). Later, he reported on the same lesions in Katio Indians of El Chocó (2). Reyes communicated that this disease was present in Guatemalan population; he diagnosed these lesions as verrucae of the oral cavity (3). Several years later, Soneira and Fonseca (4) reviewed 160 Venezuelan Indians, of them, 54 patients presented papulo-nodular lesions in their oral mucosa. They must be credited with the first complete description of this entity, since they described in full the clinical and microscopic features, gave details on the exfoliative cytology findings and their article is profusely illustrated with numerous clinical pictures and photomicrographs. They suggested this disease was of viral origin. In the European dermatological literature there is the Stern’s report (5) he presented several cases with similar lesions in the intraoral soft tissues (verrucae). In his article, Praetorius-Clausen (6) mentioned that in 1894, Helms described lesions resembling this disease in Greenlandic Eskimos.

Afterwards, unaware of the previously published Latin American and European reports on this disease, Archard et al and Witkop and Niswander (7,8) published 19 cases in the English language literature. Their cases were found in different Indian tribes and they named this disease as focal epithelial hyperplasia (FEH). In the last years, different reports of lesions found in American Indians (9-11), European (12-14), Asiatic (15,16) and African patients (17-19) had been published. Lesions clinically and microscopically similar to this disease were found in two chimpanzees and one rabbit (20,21). The most recent study was made by Carlos and Sedano (22), they analysed 110 Guatemalan cases and proposed the name multifocal papilloma virus epithelial hyperplasia. To date, this disease is known in Latin America as multifocal epithelial hyperplasia (MEH).

MEH has preference for appearing in children. Clinically MEH is characterized by the presence of multiple lesions, but rarely isolated lesions can be found (11,13,19,22). MEH lesions are papulo-nodular, elevated, asymptomatic and smooth surfaced swellings, when they are of verrucous or papillomatoid surface they can be confused with papillomas. Usually, they are round or oval, well defined nodules which present no changes with the surrounding mucosa, most of them are 0.1 to 0.5 cm in diameter, but lesions measuring several centimetres are not rare, they are formed by coalescence of several minor nodules. They are slow growing lesions and malignant transformation has not been observed (11,22). It is characteristic that nodules disappear when they are stretched and when tension is liberated, they come into view (11). Previous reports communicated that MEH is more common in females, the more frequently affected locations are labial, lingual and buccal mucosa. Some authors reported it is more regularly found in children (11,22) but there are some communications in adults (15,23).

It is widely known that MEH lesions are frequently associated to human papillomavirus (HPV) types 13 and 32 (24-28). Immunocytochemical and in situ hybridization estudies demonstrated the presence of VPH-16, VPH-11 (29) and an 11-related HPV (27), VPH-1 (30) and VPH-6 (31). Other reported associated factors are: a recessive gene, galvanic electricity from dental amalgams, tobacco chewing and lack of vitamin K (4,7,12,15,32,33).

Most of the patients had at least one affected relative, this lend to think some authors this disease was hereditary (7,10,18,34). Recently, it has been proposed that familial transmission of this disease is through devices for common use as spoons, forks or knives (11). Frequency in the studied populations varied widely among 0.06% (10) to 33.75% (4).

The aim of this work is to report the clinico-pathological findings and treatment carried out in MEH patients reviewed and attended in the Department of Dermatology, Hospital “Manuel Gea González” (DDHMGG) in Mexico City.


The files of the DDHMGG (1983 to 1991) were reviewed and those cases with a diagnosis of MEH were separated. One lesion each patient was biopsied, the tissue was immersed in aqueous neutral formalin solution for fixation during 24 hours and routinely processed to obtain 5µ thick, paraffin embedded, H and E stained slides. Analysed data were: gender, age, mean size, location and number of the lesions, clinical features, evolution and affected relatives. The corresponding slides were reviewed in order to confirm the MEH diagnoses. Furthermore, we visited the patients’ home, a clinical review with artificial light was done to each patient and socio-economical status was determined by: monthly income, kind of home, the presence of: potable water, electric energy and the number of persons living in each room for determination of their socio-economical status. Also, we asked if some relatives had similar lesions to those found in our patients. Data was registered and tabulated. All patients were treated with liquid nitrogen local applications.


Of the 1000 reviewed files, nine corresponded to MEH cases (0.009%). Their main clinical findings are summarized in table 1.

We found that lesions were more frequently found in females (seven cases, 78%) than in males (two cases, 22%). Age of the reviewed patients was from six to 36 years with a mean age of 13.3 years. 67% of the patients were in the 1st and 2nd decades of the life. All adult patients referred that lesions appeared in childhood and with the age they disappeared.

Clinical findings. MEH lesions presented several characteristics. They were multiple, round to oval, papulo-nodular, soft and asymptomatic swellings. Their colour was red, pink, white or they were similar in colour to the surrounding mucosa (Fig. 1). Clinically, all the lesions were well-defined, some times irregularly shaped, smooth surfaced swellings (Fig. 2). Duration of the lesions was from “several weeks” to 30 years. The most frequently affected intraoral location was buccal mucosa, followed by lower lip, palate and comissures. 

Fig.1. Patient with elevated, well-defined lesions in comissure and lower lip.

Fig.2. Patient with multiple lesions in buccal mucosa.


The clinical files showed that that four patients showed palatal lesions (patients 2,3 and 7) and other lesion in the junction of the soft and hard palate (patient 4). In table 2, location of the lesions in each patient is specified. Size of the lesions varied from 0.1 cm to 2.3 cm with a mean size of 0.9 cm. Larger lesions were formed by confluence of several smaller nodules.

Microscopic findings. All of them showed identical microscopic features. We observed the presence of parakeratinized squamous stratified epithelium, marked acanthosis and long, wide, blunted rete ridges, some of them were confluent to each other or to the center of the lesion (Fig. 3). Commonly it was observed that rete ridges joined at different levels, leaving connective tissue areas apparently to be inside the epithelium. Lesional epithelium had cells with clear cytoplasm showing picnotic or absent nucleus (koilocytes). These cells were mainly located in the upper strata of the epithelium but excepting basal layer, they were found at any level in lesser quantities (Fig. 4). It was very notorious the presence of cells containing a nucleus similar to that found in the mitotic process (mitosis-like or mitosoid cells). They were found in all the epithelial layers (Fig. 5).

Fig. 3. Koilocytes are cells with clear cytoplasm in the lesion. H and E. 100X.

Fig. 4. High power view of the mitosoid cells. H and E. 400x.


Associated lesions. Of the affected patients, only one of them showed a lesion associated to MEH, it was median rhomboidal glositis.

Affected relatives. All the patients referred at least one known close relative with similar lesions. They included fathers, mothers, sons, daughters, brothers, sisters, aunts, uncles and cousins.

Socio-economical status. All the patients informed that monthly family income was less than 200 American dollars and were classified in the low socio-economical level (poverty).

Treatment. All patients were treated with liquid nitrogen applications to the lesions.

During our visit to the patients’ home, we were aware that no clinical signs of the disease were evident.


In the past, MEH was known as focal epithelial hyperplasia. This disease is well-known by medical practitioners and despite studies in the Mexican population are few (10,11,24,32,35), its frequency is not high.

As the name MEH indicates, the most prevalent clinical finding is the presence of multiple nodular lesions in the oral mucosa. It affects lips, buccal mucosa, tongue and comissures mainly (11,22). It is more common in children. There is not a precise explanation for this last feature but it is possible that the less developed immunologic system in children can be related with the beginning of the disease and later, developing of immunity is responsible for vanishing of the lesions. This can account for the feature that in adults, normally no lesions are found. This change can be related with maturation of the immune system and development of its capacity to recognize and attack the viral particles. Another factor associated to this disease is poverty (11,22), it is supported by our findings since all the patients included in this study were classified in the low socio-economical level. It is important to note that the aetiology of the disease has been received several points of view. Even no conclusive studies exist, since the first reports, several authors consider it had a familiar aetiology suggesting a possible relationship with an autosomic dominant gene (23). To date, according to the first report published by Estrada (1) who suggested that MEH was of viral origin, actual data support that the presence of the human papillomavirus types 13 and 32 identified within the lesional epithelium (24,25,30,31), families with several affected relatives and its preference by economically poor population with deficient medical care and limited access to the health system, support the theory that a viral infection is the aetiological agent of MEH.

It is important to diagnose this disease, since it is frequently confused with the “florid oral papillomatosis”, vulgar verrucae, papilloma, condiloma acuminatum or lesions related to child abuse.

Treatment for MEH is commonly the surgical excision, but application of liquid nitrogen was also used (35). Archard et al suggested administration of sulfamides and vitamin A (7). General agreement exists that MEH lesions should not be excised, since it is a self-limiting disease and because lesions will disappear with the age of the patient. Only should be excised those lesions found in traumatic areas. Surgical excision of the lesions and as it was in this study, the use of local cryotherapy by means of liquid nitrogen applications gave very good results.

It is expected some resistance of the Oral Pathologists to change the name focal epithelial hyperplasia to multifocal epithelial hyperplasia, this can be related to the fact that not all the patients had multiple lesions at the time of their first oral examination. In our experience, all the patients, including those children with one lesion at first examination, more lesions will appear in the oral soft tissues in the following weeks or months and if they are adults, clinical interrogation will demonstrate that at the beginning of the disease the patient presented multiple lesions. It is important to note that during the interrogatory, all adult patients recognized that they presented several lesions during childhood.

We consider that the name FEH should be discarded and the name used in this article, multifocal epithelial hyperplasia should be adopted, since for the experience all the patients have two or more lesions during the course of the disease. The use of this name has the advantage to describe both the main clinical feature of the disease (the presence of multiple lesions) and the main microscopic finding (epithelial hyperplasia). We agree with the proposal to abandon the eponym Heck’s disease since the first well documented cases were published by Estrada (1,2) and Soneira and Fonseca (4) should be credited as the first authors to describe MEH in full.

In view of the above mentioned reasons, we propose that the names of focal epithelial hyperplasia and Heck’s disease should be discarded and replaced by the name of multifocal epithelial hyperplasia, since this name is widely used in Latin America and it is the most appropriated to describe clinically and microscopically this entity.


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