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Focal epithelial hyperplasia in Israeli families of Libyan origin
Focal epithelial hyperplasia in Israeli families of Libyan origin Amos Buchner, D.M.D., Tel Aviv, Israel SACKLER TEL
AVIV
SCHOOL
M.S.D.,”
OF MEDICINE
AND
SCHOOL
OF DENTAL
MEDICINE,
UNIVERISTY
The occurrence of focal epithelial hyperplasia (Heck’s disease) in seven Israeli families is reported. All the casesinvolved children and young adults whose parents had immigrated to Israel from Libya. The familial occurrence and possible etiologic factors of the condition are discussed. A genetic predisposition for the disease is suggested.
Fhyperplastic ocal epithelial hyperplasia, also known as Heck’s disease, is an unusual benign, lesion of the oral mucosa. The condition is characterized by discrete multiple papules and nodules at various sites in the oral cavity. The lesions are usually flat, vary in size (pinpoint- to pea-sized) and shape (round to ovoid), and generally do not cause discomfort. They are usually pink in color, very much like the adjacent normal mucosa. The papules and nodules are soft and tend to disappear when the mucosa is stretched. The disease was first discovered by Heck in 1961 and named focal epithelial hyperplasia in 1965 by Archard, Heck, and Stanley.’ It is relatively common among Indians of the American continents’, 2 and in the Eskimo populations of eastern Canada and western Greenland3, 4 and rare in other populations,’ A familial history is mentioned in the literature, and there are several case reports describing involvement of several members of the same family. l* 2* 6-10 The present report describes focal epithelial hyperplasia in several Israeli families, all of whom were found to be of Libyan origin. CASE
REPORTS
In a routine dental examination of schoolchildren in 1970 in the Tel Aviv area, focal epithelial hypetplasia was discovered in two siblings. Examination of the whole family revealed that four of *Associate Professor, Department of Pathology, Sackler School of Medicine, and Head of Department of Oral Pathology and Oral Medicine, School of Dental Medicine, Tel Aviv University. 64
CO30-4220/78/0146-0064$00.64VO
0
1978 The C. V. Mosby
Co.
Volume 46 Number1
Fig. 1. Lesions on vermilion border
Fig. 2. Lesions on
lower
lip.
the eleven children were affected-two boys and two girls. No other children in the same class or school were affected by the condition. This family was followed for 2 years and has been described in detail previously.” At the time no particular attention was paid to the fact that the parents of these Israeli-born children had immigrated from Libya, from the town of Tripoli. After we discussed the cases at various national dental scientific meetings, other similar cases were referred to us from different areas of the country. While the referral patients were usually severely affected by the condition, other family members were also found to be afflicted but to a lesser degree. Some were not even aware of the presence of the lesions in their mouths. The cases, which were dispersed throughout Israel, and most of which were born in Israel, all shared one thing in common-all the parents had immigrated to Israel from Libya, most from Tripoli or its surroundings. Seven families have been seen in our deuartment at Tel Aviv Universitv to date. Most of the
66
Oral Surg.
Buchner
July, 1978
Fig. 3. Lesions on tongue.
Fig. 4. Histologic section exhibiting epithelial hyperplasia.
Volume 46 Number I
Focal epithelial hyperplasia 67
Fig. 5. Histologic section exhibiting nuclear aberrations in epithelium. patients were children and young adults. In one family, four of eleven children were involved,” in another, three of eight,” and in another, three of seven. In the remaining four families, all members were not available for examination, but at least two from each were afflicted. In addition to these familial cases of focal epithelial hyperplasia, since 1969, we have observed six single cases in young adults serving in the Israeli army. Two of these cases were of Libyan origin; information on the birthplace of the parents of the other four was unavailable. The mucosa of the lower lip was involved in all cases, the buccal mucosa and the mucosa of the upper lip less frequently, and the tongue least frequently (Figs. 1 to 3). The gingiva, palate, anterior faucial pillars, and the floor of the mouth were never involved. The histologic picture was similar in all cases, with only slight variations. The lesion was composed of stratified squamous epithelium that exhibited acanthosis and elongation and anastomosis of the rete ridges (Fig. 4). The surface was nonkeratinized, except for some areas which showed slight parakeratosis. The underlying lamina propria was normal and exhibited slight chronic inflammation. In some patients the epithelium also exhibited varying amounts of cells with a clear cytoplasm in the basal and spinous layers. In others, the epithelium contained single large epithelial cells in the spinous layer with mitosis-like nuclear degeneration or other forms of nuclear aberrations (Fig. 5). Ultrastructural observations of several lesions from different patients did not reveal viruslike particles in the epithelial cells, as has been reported. ‘a
68
Oral Surg.
Buchner
July,
1978
DISCUSSION
Several hundreds of casesof focal epithelial hyperplasia have been reported in the literature since 1965. Most of them have been Indians of the American continents’* 2 and Eskimosin southwestGreenland and the easternCanadianArctic,3, 4 although it has also been reported in other races and continents. The condition is rare in Caucasians,and only single caseshave been described in America and Europe. Van Wykr4 recently reported seventy-six casesof focal epithelial hyperplasiaencounteredin an epidemiologic survey in Western Cape Province of South Africa. The condition affected only Negroes and was confined to pupils of reform schoolsand residentsof an isolated community. Focal epithelial hyperplasia is confined only to the oral mucosa and does not affect other mucousmembranesor the skin. The predominant location of the lesionsin most of the reported casesin the literature, except in Eskimos, has been, in order of frequency: mucosaof the lower lip, buccal mucosaand labial mucosaof the upper lip, the tongue, gingiva, and palate. In Eskimos, more than 50 percent of the lesionswere on the tongue.3 The age distribution of the condition varies in the different populations. Among American Indians, mainly children were affected,‘* 2 while most affected Eskimos were over 30 years old.3, 4 In our study, most were children and young adults. There is a strong familial occurrence, but no hereditary caseshave been reported. The condition was found in two siblings by three different authors’, g, lo; in two first cousins2; in three pairs of siblings out of sevencasesstudied’$in seven children in one family’; and in four membersof one family.” The cause of focal epithelial hyperplasia is still unknown. Several authors have suggestedthe possibility of a communicable agent (especially viral) and hereditary factors. Some ultrastructural studiespoint to a possibleviral etiology,r4* ‘j* l6 while others have failed to reveal any viral particles.s*“3 I3 Some authors claim that the occurrence of the condition in one single family in a milieu in which no others are affected is suggestiveof an hereditary background.‘3s Our finding of isolated affected families scattered throughout the country, all of Libyan origin, is compatible with a genetic background for the disease.It is possiblethat both genetic and viral factors play a role, whereby a genetic disturbance may predispose certain families of Libyan origin to infection with a specific viral agent. REFERENCES
I. Archard, H. O., Heck, J. W., and Stanley, H. R.: Focal Epithelial Hyperplasia: An Unusual Oral Mucosal Lesion Found in Indian Children, ORAL SURG. 20: 201-212, 1965. 2. Witkop, C. .I., and Niswander, J. D.: Focal Epithelial Hyperplasia in Central and South American Indians and Ladinos, ORAL SWRG. 20: 213-217, 1965. 3. Clausen, F. P., Mogeltoft, M., Roed-Petersen, B., and Pindborg, J. J.: Focal Epithelial Hyperplasia of the Oral Mucosa in a South-West Greenlandic Population, Stand. J. Dent. Res. 78: 287-294, 1970. 4. Jarvis, A., and Gorlin, R. J.: Focal Epithelial Hyperplasia in an Eskimo Population, ORAL SURG. 33: 227-228, 1972. 5. Buchner, A., and Ramon, Y.: Focal Epithehal Hyperplasia: Report of Two New Cases from Israel and Review of Literature, Arch. Dermatol. 1W: 97-98, 1973. 6. Perriman, A., and Uthamn, A.: Focal Epithelial Hyperplasia; Report of Seven Cases from Iraq, ORAL SURG.
31:
221-225,
1971.
7. Gomez, A., CaIle, C., Arcila, G., and Pindborg, J. J.: Focal Epithelial Hyperplasia in a Half-Breed Family of Colombians, J. Am. Dent. Assoc. 79: 663-667, 1969. 8. Schock, R. K.,: Familial Focal Epithehal Hyperplasia: Report of a Case, ORAL SURG. 28: 598-602, 1969. 9. Orfanos, C. E., Strunk, V., and Gartmann, H.: Fokale Epitheliale Hyperplasie der Mundschleimhaut: Hecksche Krankheit, Dermatologica 149: 163- 175, 1974.
Volume 46 Number I IO,Starink, T,M,,and Woerdeman, M,J,:Focal Epithelial Hyperplasia oftheOral Mucosa, Br,JoDumatol,
96:375.380, 1977, I I. Buchner, A., and Mass, E.: Focal Epithelial Hyperplasia in an Israeli Family, ORAL SURG. 36: 507-51 I, 1973. 12. Buchner, A., and Ramon, A.: Focal Epithelial Hyperplasia of the Oral Mucosa, Harefuah 90: 221-223, 1976.
13. Buchner, A., Bubis, J. J., and Ramon, Y.: Ultrastructural Study of Focal Epithelial Hyperplasia, SURG.
39: 622-629,
ORAL
1975.
14. Van Wyk, C. W.: Focal Epithelial Hyperplasia of the Mouth: Recently Discovered in South Africa, Br. J. Dermatol. 96: 381-388, 1977. 15. Clausen, F. P., and Willis, M. M. : Papova Virus-Like Particles in Focal Epithelial Hyperplasia, Stand. J. Dent. Res. 79: 362-365, 197 I. 16. Hanks, C. T., Fischman, S. L., and Guzman, M. N.: Focal Epithelial Hyperplasia: A Light and Electron Microscopic Study of One Case, ORAL SURG. 33: 934-943, 1972. Reprint
requests
to:
Prof. Amos Buchner School of Dental Medicine Tel Aviv University Ramat Aviv, Israel
AVIV
SCHOOL
M.S.D.,”
OF MEDICINE
AND
SCHOOL
OF DENTAL
MEDICINE,
UNIVERISTY
The occurrence of focal epithelial hyperplasia (Heck’s disease) in seven Israeli families is reported. All the casesinvolved children and young adults whose parents had immigrated to Israel from Libya. The familial occurrence and possible etiologic factors of the condition are discussed. A genetic predisposition for the disease is suggested.
Fhyperplastic ocal epithelial hyperplasia, also known as Heck’s disease, is an unusual benign, lesion of the oral mucosa. The condition is characterized by discrete multiple papules and nodules at various sites in the oral cavity. The lesions are usually flat, vary in size (pinpoint- to pea-sized) and shape (round to ovoid), and generally do not cause discomfort. They are usually pink in color, very much like the adjacent normal mucosa. The papules and nodules are soft and tend to disappear when the mucosa is stretched. The disease was first discovered by Heck in 1961 and named focal epithelial hyperplasia in 1965 by Archard, Heck, and Stanley.’ It is relatively common among Indians of the American continents’, 2 and in the Eskimo populations of eastern Canada and western Greenland3, 4 and rare in other populations,’ A familial history is mentioned in the literature, and there are several case reports describing involvement of several members of the same family. l* 2* 6-10 The present report describes focal epithelial hyperplasia in several Israeli families, all of whom were found to be of Libyan origin. CASE
REPORTS
In a routine dental examination of schoolchildren in 1970 in the Tel Aviv area, focal epithelial hypetplasia was discovered in two siblings. Examination of the whole family revealed that four of *Associate Professor, Department of Pathology, Sackler School of Medicine, and Head of Department of Oral Pathology and Oral Medicine, School of Dental Medicine, Tel Aviv University. 64
CO30-4220/78/0146-0064$00.64VO
0
1978 The C. V. Mosby
Co.
Volume 46 Number1
Fig. 1. Lesions on vermilion border
Fig. 2. Lesions on
lower
lip.
the eleven children were affected-two boys and two girls. No other children in the same class or school were affected by the condition. This family was followed for 2 years and has been described in detail previously.” At the time no particular attention was paid to the fact that the parents of these Israeli-born children had immigrated from Libya, from the town of Tripoli. After we discussed the cases at various national dental scientific meetings, other similar cases were referred to us from different areas of the country. While the referral patients were usually severely affected by the condition, other family members were also found to be afflicted but to a lesser degree. Some were not even aware of the presence of the lesions in their mouths. The cases, which were dispersed throughout Israel, and most of which were born in Israel, all shared one thing in common-all the parents had immigrated to Israel from Libya, most from Tripoli or its surroundings. Seven families have been seen in our deuartment at Tel Aviv Universitv to date. Most of the
66
Oral Surg.
Buchner
July, 1978
Fig. 3. Lesions on tongue.
Fig. 4. Histologic section exhibiting epithelial hyperplasia.
Volume 46 Number I
Focal epithelial hyperplasia 67
Fig. 5. Histologic section exhibiting nuclear aberrations in epithelium. patients were children and young adults. In one family, four of eleven children were involved,” in another, three of eight,” and in another, three of seven. In the remaining four families, all members were not available for examination, but at least two from each were afflicted. In addition to these familial cases of focal epithelial hyperplasia, since 1969, we have observed six single cases in young adults serving in the Israeli army. Two of these cases were of Libyan origin; information on the birthplace of the parents of the other four was unavailable. The mucosa of the lower lip was involved in all cases, the buccal mucosa and the mucosa of the upper lip less frequently, and the tongue least frequently (Figs. 1 to 3). The gingiva, palate, anterior faucial pillars, and the floor of the mouth were never involved. The histologic picture was similar in all cases, with only slight variations. The lesion was composed of stratified squamous epithelium that exhibited acanthosis and elongation and anastomosis of the rete ridges (Fig. 4). The surface was nonkeratinized, except for some areas which showed slight parakeratosis. The underlying lamina propria was normal and exhibited slight chronic inflammation. In some patients the epithelium also exhibited varying amounts of cells with a clear cytoplasm in the basal and spinous layers. In others, the epithelium contained single large epithelial cells in the spinous layer with mitosis-like nuclear degeneration or other forms of nuclear aberrations (Fig. 5). Ultrastructural observations of several lesions from different patients did not reveal viruslike particles in the epithelial cells, as has been reported. ‘a
68
Oral Surg.
Buchner
July,
1978
DISCUSSION
Several hundreds of casesof focal epithelial hyperplasia have been reported in the literature since 1965. Most of them have been Indians of the American continents’* 2 and Eskimosin southwestGreenland and the easternCanadianArctic,3, 4 although it has also been reported in other races and continents. The condition is rare in Caucasians,and only single caseshave been described in America and Europe. Van Wykr4 recently reported seventy-six casesof focal epithelial hyperplasiaencounteredin an epidemiologic survey in Western Cape Province of South Africa. The condition affected only Negroes and was confined to pupils of reform schoolsand residentsof an isolated community. Focal epithelial hyperplasia is confined only to the oral mucosa and does not affect other mucousmembranesor the skin. The predominant location of the lesionsin most of the reported casesin the literature, except in Eskimos, has been, in order of frequency: mucosaof the lower lip, buccal mucosaand labial mucosaof the upper lip, the tongue, gingiva, and palate. In Eskimos, more than 50 percent of the lesionswere on the tongue.3 The age distribution of the condition varies in the different populations. Among American Indians, mainly children were affected,‘* 2 while most affected Eskimos were over 30 years old.3, 4 In our study, most were children and young adults. There is a strong familial occurrence, but no hereditary caseshave been reported. The condition was found in two siblings by three different authors’, g, lo; in two first cousins2; in three pairs of siblings out of sevencasesstudied’$in seven children in one family’; and in four membersof one family.” The cause of focal epithelial hyperplasia is still unknown. Several authors have suggestedthe possibility of a communicable agent (especially viral) and hereditary factors. Some ultrastructural studiespoint to a possibleviral etiology,r4* ‘j* l6 while others have failed to reveal any viral particles.s*“3 I3 Some authors claim that the occurrence of the condition in one single family in a milieu in which no others are affected is suggestiveof an hereditary background.‘3s Our finding of isolated affected families scattered throughout the country, all of Libyan origin, is compatible with a genetic background for the disease.It is possiblethat both genetic and viral factors play a role, whereby a genetic disturbance may predispose certain families of Libyan origin to infection with a specific viral agent. REFERENCES
I. Archard, H. O., Heck, J. W., and Stanley, H. R.: Focal Epithelial Hyperplasia: An Unusual Oral Mucosal Lesion Found in Indian Children, ORAL SURG. 20: 201-212, 1965. 2. Witkop, C. .I., and Niswander, J. D.: Focal Epithelial Hyperplasia in Central and South American Indians and Ladinos, ORAL SWRG. 20: 213-217, 1965. 3. Clausen, F. P., Mogeltoft, M., Roed-Petersen, B., and Pindborg, J. J.: Focal Epithelial Hyperplasia of the Oral Mucosa in a South-West Greenlandic Population, Stand. J. Dent. Res. 78: 287-294, 1970. 4. Jarvis, A., and Gorlin, R. J.: Focal Epithelial Hyperplasia in an Eskimo Population, ORAL SURG. 33: 227-228, 1972. 5. Buchner, A., and Ramon, Y.: Focal Epithehal Hyperplasia: Report of Two New Cases from Israel and Review of Literature, Arch. Dermatol. 1W: 97-98, 1973. 6. Perriman, A., and Uthamn, A.: Focal Epithelial Hyperplasia; Report of Seven Cases from Iraq, ORAL SURG.
31:
221-225,
1971.
7. Gomez, A., CaIle, C., Arcila, G., and Pindborg, J. J.: Focal Epithelial Hyperplasia in a Half-Breed Family of Colombians, J. Am. Dent. Assoc. 79: 663-667, 1969. 8. Schock, R. K.,: Familial Focal Epithehal Hyperplasia: Report of a Case, ORAL SURG. 28: 598-602, 1969. 9. Orfanos, C. E., Strunk, V., and Gartmann, H.: Fokale Epitheliale Hyperplasie der Mundschleimhaut: Hecksche Krankheit, Dermatologica 149: 163- 175, 1974.
Volume 46 Number I IO,Starink, T,M,,and Woerdeman, M,J,:Focal Epithelial Hyperplasia oftheOral Mucosa, Br,JoDumatol,
96:375.380, 1977, I I. Buchner, A., and Mass, E.: Focal Epithelial Hyperplasia in an Israeli Family, ORAL SURG. 36: 507-51 I, 1973. 12. Buchner, A., and Ramon, A.: Focal Epithelial Hyperplasia of the Oral Mucosa, Harefuah 90: 221-223, 1976.
13. Buchner, A., Bubis, J. J., and Ramon, Y.: Ultrastructural Study of Focal Epithelial Hyperplasia, SURG.
39: 622-629,
ORAL
1975.
14. Van Wyk, C. W.: Focal Epithelial Hyperplasia of the Mouth: Recently Discovered in South Africa, Br. J. Dermatol. 96: 381-388, 1977. 15. Clausen, F. P., and Willis, M. M. : Papova Virus-Like Particles in Focal Epithelial Hyperplasia, Stand. J. Dent. Res. 79: 362-365, 197 I. 16. Hanks, C. T., Fischman, S. L., and Guzman, M. N.: Focal Epithelial Hyperplasia: A Light and Electron Microscopic Study of One Case, ORAL SURG. 33: 934-943, 1972. Reprint
requests
to:
Prof. Amos Buchner School of Dental Medicine Tel Aviv University Ramat Aviv, Israel