Multifocal epithelial hyperplasia.

Dear Editor,

In 1956, Estrada reported on the presence of multiple intraoral soft tissue lesions discovered in Colombian Caramanta Indians.[1] Later, Soneira and Fonseca reviewing Venezuelan Indians, found 54 patients with oral papulo-nodular lesions. They must be credited with the first complete description of this entity and suggested this disease was of viral origin.[2] Afterwards, this disease was found in several ethnic groups.[3]

Multifocal epithelial hyperplasia (MEH) appears more commonly in children, but there are some communications in adults. It is characterized by the presence of multiple slow growing, papulo-nodular, elevated, and smooth surfaced asymptomatic lesions. Usually, they are sessile, round, or oval, well defined nodules with color similar to the normal mucosa, measuring from 0.1 to 0.5 cm in diameter. Coalescence of several small swellings gives rise to multinodular lesions of several centimeters. It is characteristic that isolated nodules disappear when they are stretched.[3-6] MEH is more common in females and the more frequently affected locations are labial, lingual, and buccal mucosas.[46] It is well known that MEH lesions are regularly associated with human papillomavirus types 13 and 32.[7]

Microscopically, MEH is composed by a parakeratinized, acantotic, stratified squamous epithelium with numerous koilocytes, and mitosis-like cells.

We reviewed three healthy, Mexican Mestizo children living in Mexico City urban area. One was a 14-years-old boy. His oral mucosa displayed several slow growing, asymptomatic, slightly elevated, sessile, soft, smooth surfaced lesions with the same color of the surrounding mucosa, present during 4 years. Lesions were located in tongue, lower and upper lips mucosa, and buccal mucosa [Figure 1a]. One cousin presented similar lesions. Other was a 12-years-old girl. She exhibited several smooth surfaced, elevated, sessile, asymptomatic, slow growing lesions, seen during 6 months in her buccal mucosa and lower lip [Figure 1b]. Two cousins showed similar lesions and, a 10-years-old boy complaining on the presence of numerous slightly elevated, soft, sessile, asymptomatic, pale pink in color, and well defined lesions in his buccal and lower lip mucosas of 5 months duration was reviewed. He informed that new lesions appeared during the last 15 days [Figure 1c]. Three brothers and two cousins presented identical lesions; no permission for biopsies in the relatives was obtained.

Figure 1

(a) Case 1. Numerous lesions in tongue and lips mucosa are observed (b) Case 2. Elevated, sessile lesions in lower lip mucosa are seen (c) Case 3. Pale pink lesions in buccal mucosa are observed

Characteristically, when we stretched the isolated lesions, they disappeared. After 3 years follow-up, no changes in the number and size of the lesions were seen.

One lesion each patient was biopsied by local anesthesia, immersed in aqueous neutral formalin solution, and routinely processed to obtain H and E stained slides. Microscopic examination showed the presence of parakeratinized squamous stratified epithelium with marked acantosis. Also, thick epithelial rete ridges and numerous koilocytes were observed [Figure 2a]. Mitosis-like cells were identified accompanied with epithelial cells showing two nucleoli [Figures 2b and c]. Final diagnosis in all three cases was MEH.

Figure 2

(a) Photomicrograph showing a hyperplastic, acantotic, stratified squamous cell epithelium with numerous koilocytes. H and E. 100× (b) High power photomicrograph of a rete peg showing a mitosis-like cell. H and E. 200× (c) Photomicrograph showing a mitosis-like cell and some big koilocytes. Note some bi-nucleolated epithelial cells. H and E. 400×

As the name MEH indicates, the most prevalent clinical finding is the presence of multiple nodular lesions in the oral mucosa. This disease affects lips, buccal mucosa, tongue and commissures, and is more common in children.[4-6] Actual data support that the HPV types 13 and 32 are the causative agents.[7] Families with several affected relatives are almost always found. MEH shows preference by economically poor population with deficient medical care and limited access to the health system,[346] These findings support the theory that a viral infection is the etiological agent. In our experience, if the relatives are reviewed, always some of them present, or presented MEH lesions.[3-5] It has been reported that only HPV-13 was present in Mexican population.[8]

The usual treatment for MEH has been the surgical excision but actually there is a general agreement that MEH lesions should not be excised, because it is a self-limiting disease and since lesions will disappear with the age of the patient, we consider that only lesions in traumatized areas should be prophylactically excised.

We believe that the name MEH proposed by our study group[3-5] should be adopted since it describes both, its main clinical feature (the presence of multiple lesions) and its main microscopic finding (epithelial hyperplasia).

Several years ago, our study group suggested that the presence of familial MEH lesions could be related to the common use of knives, forks, and spoons and that transmission could be associated with the use of these contaminated objects.[25] This point of view is supported by reports in the presence of HPV-13 in saliva of affected patients.[8]

It is important to diagnose adequately this disease, since it is frequently confused with the so-called “florid oral papillomatosis”, vulgar verrucae, papilloma, condiloma acuminatum, or lesions related to child abuse.[9] In our experience, any of the children with MEH had lesions similar to the above mentioned entities and we consider that this disease should not be related with children sex abuse.