- Email: [email protected]
Laugier-Hunziker-Baran syndrome
Laugier-Hunziker-Baran syndrome Kaori Yago, PhD, DDS,a Yoichi Tanaka, PhD, DDS,b and Soichiro Asanami, PhD, DDS,c Tokyo and Chiba, Japan KEIO UNIVERSITY, TOKYO DENTAL COLLEGE, AND INTERNATIONAL UNIVERSITY OF HEALTH AND WELFARE
Objective. Laugier-Hunziker-Baran syndrome represents a rare acquired pigmentary disorder which has no relevance to internal disorders and has no familial association. There are few reports on histopathologic studies of this syndrome concerning Japanese individuals. The differential diagnosis of oral and pigmented lesions between Laugier-HunzikerBaran syndrome and other disorders, Peutz-Jeghers syndrome in particular, requires our utmost consideration. Study design. Biopsy specimens of 2 cases were taken from pigmented maculae on the lower lips, buccal mucosa, tongue, and palate. Results. Similar histopathologic findings were observed for all locations. The histopathologic examination showed that there was an accumulation of melanin in the basal layer as well as an increase in the number of melanophages in the subepithelial area. Conclusions. Oral scientists and clinicians must be familiar with Laugier-Hunziker-Baran syndrome, because this syndrome is probably more common than is generally recognized. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:e20-e25)
Laugier-Hunziker-Baran syndrome is characterized by acquired melanotic pigmentation of the oral mucosa and palmoplantar area, which is frequently associated with longitudinal melanonychia.1-3 It appears that there is no association between the development of LaugierHunziker-Baran syndrome and internal disorders such as gastrointestinal polyposis; nor is there a familial association. Because the syndrome is a very rare condition,4,5 there are few reports on the histopathologic observations of the oral mucosa regarding this disease in the oral science fields.4 We present a histopathologic analysis of the syndrome in the present report of 2 cases. The specimens were obtained from the lip, buccal mucosa, tongue, and palate of the patients. We also discuss the disorders which present with similar pigmentary changes, including Peutz-Jeghers syndrome, from which it be distinguished. CASE 1 A 39-year-old Japanese man came to our hospital with a chief complaint of a fractured upper left incisal tooth due to a traffic accident. He had multia
Staff Doctor, Department of Dentistry and Oral Surgery, School of Medicine, Keio University. b Professor, Clinical Laboratory, Division of Surgical Pathology, Ichikawa General Hospital, Tokyo Dental College. c Professor, Department of Oral Surgery, Mita Hospital, International University of Health and Welfare. 1079-2104/$ - see front matter © 2008 Mosby, Inc. All rights reserved. doi:10.1016/j.tripleo.2008.03.037
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ple pigmented maculae in his mouth and on his fingers. He said that they appeared when he was 20 years old. Physical examination revealed that there were multiple pigmented maculae of up to 5 mm in diameter, irregular in shape, on his lips, buccal mucosa (bilaterally), tongue, and palate (Fig. 1). Well defined brownish maculae, oval in shape, measuring 2-3 mm in diameter, were present on the palmarplantar areas of his fingers and toes. A single longitudinal pigmented band measuring 2 mm was present on 2 toenails (Fig. 2), but otherwise he was in good health and did not take any medication. His renal and hepatic function were normal. The authors suspected that it was a case of Peutz-Jegher syndrome. However, polypoid lesions were not detectable in the gastrointestinal tract by colonoscopy. The authors consulted with a dermatologist. The patient was diagnosed as having Laugier-Hunziker-Baran syndrome because the development of the lesions was irrelevant to internal disorders, such as intestinal polyposis, and no familial association was observed. CASE 2 A 68-year-old Japanese man presented with a 23year history of asymptomatic macular hyperpigmentation on his lips. The patient said that the pigmentation on his lips became gradually progressive and that he did not take any medication which would cause pigmented lesions; otherwise, the patient was in good health. There was no family history of abnormal mucocutaneous pigmentation.
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Fig. 1. Case 1. Multiple hyperpigmented macules in the lower lip (A), buccalmucosa (B), tongue (C), and palate (D).
Fig. 2. Case 1. (A), (B), Multiple hyperpigmented macules in the palmplantararea. (C), A single longitudinal pigmented band presents on the toe nail.
Physical examination revealed multiple well defined diffuse dark brown maculae measuring 2-5 mm in diameter on the lips and buccal mucosa (bilaterally). One pigmented macula was noted on the palate, and pigmentation of the tongue was observed only on the right side (Fig. 3). One pigmented macula measuring 2 mm in diameter was observed on the right thumb (Fig. 4). However, there were none on the feet, and longitudinal pigmented bands were not present on his nails, either.
The number of pigmented maculae was less than that in case 1. There was no family history of acquired macular pigmentary disorders and no association with other systemic conditions. The patient was diagnosed to have Laugier-Hunziker-Baran syndrome. Biopsy specimens for these cases were taken from the pigmented maculae on the lower lip, buccal mucosa, tongue, and palate.
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Fig. 3. Case 2. Multiple hyperpigmented macules in the lower lip (A) and buccal mucosa (B). Pigmentation of his tongue is only on the right side tongue (C), and one pigmented macule was noted on the palate (D).
Fig. 4. One pigmented macule 2 mm in diameter had appeared on the right thumb.
HISTOPATHOLOGIC FINDINGS All specimens of cases 1 and 2 showed almost identical findings. High (lip) or moderate (others) melanin was confined to the basal layer of the stratified squamous epithelium. Melanin also was seen within melanophages in the upper connective tissue (Figs. 5 and 6). Inflammatory changes or malignant features were not noted in any area. DISCUSSION In 1970, Laugier and Hunziker reported 5 cases of an unusual acquired macular hyperpigmentation with no underlying disease.1 In 1979, Baran reported that associated nail pigmentation occurred in 5 out of 9 cases of Laugier-Hunziker syndrome.2 This syndrome is very rare, and since the original description about 50 cases have been reported in the world literature.6 LaugierHunziker-Baran syndrome is a rare condition in the United States7 and United Kingdom,8 and it is slightly
more common in France and Italy.2,3,5 In Japan, this syndrome is not understood very well, and 43 cases, including the present 2 cases, have been reported in the literature.4,9 Almost all of the reports were published in the field of dermatology. In Japanese oral sciences, there is only 1 report besides the present one.4 According to the reports from various foreign countries the pigmentary changes in Laugier-Hunziker-Baran syndrome usually begin in the third to fifth decade of life.6 There is a female preponderance, with an overall female-male ratio of 2:1.8 Nail involvement is seen in about 60% of the patients. The lesions are located most often on the buccal mucosa and on the lips.7 In Japan, Laugier-Hunziker-Baran syndrome affects patients in the range of 27-83 years old, with an average age of 59 years. Women are affected more frequently than men, with an overall female-male ratio of 4:1. Pigmentation is seen on the oral mucosa, on the palmar-plantar areas, fingers, toes, and genital region. Increased pigmentation typically occurs on the lips and buccal mucosa, as well as the tongue and palate area. However, it is extremely rare for pigmentation to be observed on the gingiva or the floor of the mouth. Longitudinal pigmented bands of the nails are observed in 44% of all patients. Pigmented maculae do not disappear naturally; Iitoyo and Miyazawa10 reported a case of a patient who was observed for changes over 8 years after pigmented maculae were first observed in the lips and fingers, and the number of pigmented maculae sharply increased each year, with some of the maculae fusing together and the color becoming slightly darker; pigmentation was also observed in the buccal mucosa approximately 8 years after the initial
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Fig. 5. Histpathologic findings of specimens from the pigmented macules on the lower lip (A), buccal mucosa (B), tongue (C), and palate (D) of case 1 (hematoxylin-eosin stain): an accumulation of melanin in the basal layer and increased number of melanophages in the superficial connective tissues.
consultation, along with linear pigmented bands in the fingernails. So far little information has been reported about treatment methods. Prescribing vitamin C and skinwhitening products is one of the treatment options; however, these treatments are not very effective.11,12 Kon and Takahashi11 gave a 38-year-old female systemic and internal applications of 750 mg/day tranexamic acid (Transamin) and 600 mg/day of a combination drug of vitamin C and pantothenic acid (Cinal) for pigmented maculae on her fingers, lips, and buccal mucosa, along with local and external applications of ointments containing hydroquinone for pigmented maculae on her fingers; they reported that the pigmented maculae on her fingers became less severe after 4 months owing to the efficacy of the external applications of the ointment containing hydroquinone, but no changes were observed in the pigmented maculae of her lips or buccal mucosa. Liquid nitrogen therapy (cryotherapy) is useful.12,13 Niiyama et al.12 reported a case in which liquid nitrogen therapy performed once or twice per week for pigmented maculae of the lips was effective: The color significantly faded in the third month. There are no case reports of pigmented maculae turning into malignant lesions in the Laugier-Hunziker-
Baran syndrome. Therefore, almost all cases were simply followed-up without any specific treatment. In the present cases, we chose to take a wait-and-see approach. As for the differential diagnosis of oral pigmented lesions, it is important to exclude other possibilities, such as Peutz-Jeghers syndrome, Addison disease, Albright syndrome, and the effect of medication. It is particularly important to conduct an appropriate differential diagnosis between Peutz-Jeghers syndrome and Laugier-Hunziker-Baran syndrome. The differences between these 2 syndromes are listed in Table I. Unlike Laugier-Hunziker-Baran syndrome, Peutz-Jeghers syndrome has a genetic background of autosomal dominant inheritance.14 In cases of Peutz-Jeghers syndrome, pigmented maculae may be present at birth and often appear in infancy or early childhood. In the case of Laugier-Hunziker-Baran syndrome, pigmentary changes usually start appearing between the ages of 20 and 50 years. In addition, in cases of Peutz-Jeghers syndrome, there is often a family history and an association with hamartomatous polyposis, mainly colonic. In cases of Laugier-Hunziker-Baran syndrome, gastrointestinal hamartomatous polyposis is not observed, nor is a familial history. In the present 2 cases, the patients had
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Fig. 6. Histpathologic findings of specimens from the pigmented macules on the lower lip (A), buccal mucosa (B), tongue (C), and palate (D) of case 2 (hematoxylin-eosin stain): an accumulation of melanin in the basal layer and increased number of melanophages in the superficial connective tissues, as in case 1.
Table I. Differential diagnosis: Laugier-Hunziker-Baran syndrome and Peutz-Jeghers syndrome Laugier-Hunziker-Baran syndrome
Peutz-Jeghers syndrome
⫺ 20s-50s ⫺ Frequent 44%-60%
Autosomal dominant inheritance Birth-infancy ⫹ Rare Extremely rare
Genetic background Age at onset Gastrointestinal polyposis Pigmented maculae: tongue and palate Pigmented streaks on nail
no previous, personal, or familial history of pigmented lesions or gastric intestinal polyposis, and they had not taken any medication which could lead to pigmentation. The distribution of pigmented lesions is a little bit different between these syndromes. Hyperpigmentation of the lips and buccal mucosa is observed in almost all patients of both syndromes. Maculae of the tongue and palate are rarely observed in cases of Peutz-Jeghers syndrome,15 whereas they are frequently observed in cases of Laugier-Hunziker-Baran syndrome. Iitoyo and Miyazawa stated that the lesions of Laugier-HunzikerBaran syndrome tend to increase as patients get older.10 In one of our cases, we observed an increase in the number of brown maculae on the lips.
The incidence of a pigmented nail band in cases of Laugier-Hunziker-Baran syndrome is 44%-60%.2,6 However, in cases of Peutz-Jeghers syndrome, patients rarely have a pigmented nail band. One patient subsequently developed a malignant melanoma in a case of Peutz-Jeghers syndrome. There are no case reports showing a pigmented macula turning into a malignant lesion in a case of Laugier-Hunziker-Baran syndrome. Besides this report, there are no other reported studies of simultaneous tissue biopsies of the lips, buccal mucosa, tongue, and palate in patients with LaugierHunziker-Baran syndrome. As a result, the histopathologic changes in cases of Laugier-Hunziker-Baran syndrome are not very specific. The histopathologic manifestations were similar for all locations in the
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presented cases. The histologic findings showed an increase of the melanin pigmentation at the basal layer; however, an increase in the number of melanocytes was not seen. This fact suggests that the pigmentation of this syndrome originates from an increase in the production of melanin pigment by the melanocyte. We must be familiar with Laugier-Hunziker-Baran syndrome, because this syndrome is probably more common than is generally recognized. The authors thank Dr. Tanaka, Professor, Department of Dermatology, Tokyo Women’s Medical University, Medical Center East. REFERENCES 1. Laugier P, Hunziker N. Pigmentaion melanique lenticulaire, essentielle, de la muqueuse jugale et des levers. Arch Belg Dermatol Syphiligr 1970;26:391-9. 2. Baran R. Longitudinal melanotic streaks as a clue to LaugierHunziker syndrome. Arch Dermatol 1979;115:1448-9. 3. Baran R, Barriere H. Longitudinal melanonychia with spreading pigmentation in Laugier-Hunziker syndrome: a report of two cases. Br J Dermatol 1986;115:707-10. 4. Fukushima Y, Matsuse Y, Yamamoto M, Sato J, Sakai N, Seto Kanichi. Two cases of Laugier-Hunziker-Baran syndrome. Jpn J Oral Maxillofac Surg 2004;50:620-3. 5. Veraldi S, Cavicchini S, Benelli C, Gasparini G. Laugier-Hunziker syndrome. A clinical, histopathologic, and ultrastructural study of four cases and review of the literature. J Am Acad Dermatol 1991;25:632-636. 6. Kanwar AJ, Kaur S, Kaur C, Thami GP. Laugier-Hunziker syndrome. J Dermatol 2001;28:54-7.
Yago, Tanaka, and Asanami e25 7. Koch SE, LeBoit PE, Odom RB. Laugier-Hunziker syndrome. J Am Acad Dermatol 1987;16:431-4. 8. Kemmett D, Ellis J, Spencer MJ, Hunter JAA. The LaugierHunziker syndrome—a clinical review of six cases. Clin Exp Dermatol 1990;15:111-4. 9. Kondo A, Iizuka M, Nozawa M, Tamiya S, Nuruki H, Umezawa Y, et al. Two cases of Laugier-Hunziker-Baran syndrome. Jpn Dermatol 2003;113:1111-5. 10. Iitoyo M, Miyazawa H. A case of Laugier-Hunziker syndrome with eight years’ observation. Skin Res 1999;41:352-5. 11. Kon A, Takahashi M. A case of Laugier-Hunziker-Baran syndrome. Rinsho Derma 1996;38:171-3. 12. Niiyama S, Okamoto K, Otoyama K. Laugier-Hunziker-Baran syndrome effectively treated with cryotherapy (liquid nitrogen). Jpn J Clin Dermatol 1999;53:56-8. 13. Nakamura T, Fujiwara T, Murata Y, Kumano K. 9 cases of Laugier’s disease (Laugier-Hunziker syndrome). Jpn Dermatol 1997;107:29-34. 14. Jeghers H, Mckusick VA, et al. Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits: a syndrome of diagnostic significance. N Engl J Med 1949;241:993-1005. 15. Yago K, Asanami S, Nagatoshi H, Nakagawa T, Tanaka Y, Kizu H. A case of Peutz-Jeghers syndrome with pigmented spots of the tongue. J Jpn Stomatol Soc 2003;52:200-4. Reprint requests: Kaori Yago, PhD, DDS Department of Dentistry and Oral Surgery, School of Medicine Keio University 35, Shinanomachi, Shinjyuku-ku Tokyo, 160-8582 Japan [email protected]
Objective. Laugier-Hunziker-Baran syndrome represents a rare acquired pigmentary disorder which has no relevance to internal disorders and has no familial association. There are few reports on histopathologic studies of this syndrome concerning Japanese individuals. The differential diagnosis of oral and pigmented lesions between Laugier-HunzikerBaran syndrome and other disorders, Peutz-Jeghers syndrome in particular, requires our utmost consideration. Study design. Biopsy specimens of 2 cases were taken from pigmented maculae on the lower lips, buccal mucosa, tongue, and palate. Results. Similar histopathologic findings were observed for all locations. The histopathologic examination showed that there was an accumulation of melanin in the basal layer as well as an increase in the number of melanophages in the subepithelial area. Conclusions. Oral scientists and clinicians must be familiar with Laugier-Hunziker-Baran syndrome, because this syndrome is probably more common than is generally recognized. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:e20-e25)
Laugier-Hunziker-Baran syndrome is characterized by acquired melanotic pigmentation of the oral mucosa and palmoplantar area, which is frequently associated with longitudinal melanonychia.1-3 It appears that there is no association between the development of LaugierHunziker-Baran syndrome and internal disorders such as gastrointestinal polyposis; nor is there a familial association. Because the syndrome is a very rare condition,4,5 there are few reports on the histopathologic observations of the oral mucosa regarding this disease in the oral science fields.4 We present a histopathologic analysis of the syndrome in the present report of 2 cases. The specimens were obtained from the lip, buccal mucosa, tongue, and palate of the patients. We also discuss the disorders which present with similar pigmentary changes, including Peutz-Jeghers syndrome, from which it be distinguished. CASE 1 A 39-year-old Japanese man came to our hospital with a chief complaint of a fractured upper left incisal tooth due to a traffic accident. He had multia
Staff Doctor, Department of Dentistry and Oral Surgery, School of Medicine, Keio University. b Professor, Clinical Laboratory, Division of Surgical Pathology, Ichikawa General Hospital, Tokyo Dental College. c Professor, Department of Oral Surgery, Mita Hospital, International University of Health and Welfare. 1079-2104/$ - see front matter © 2008 Mosby, Inc. All rights reserved. doi:10.1016/j.tripleo.2008.03.037
e20
ple pigmented maculae in his mouth and on his fingers. He said that they appeared when he was 20 years old. Physical examination revealed that there were multiple pigmented maculae of up to 5 mm in diameter, irregular in shape, on his lips, buccal mucosa (bilaterally), tongue, and palate (Fig. 1). Well defined brownish maculae, oval in shape, measuring 2-3 mm in diameter, were present on the palmarplantar areas of his fingers and toes. A single longitudinal pigmented band measuring 2 mm was present on 2 toenails (Fig. 2), but otherwise he was in good health and did not take any medication. His renal and hepatic function were normal. The authors suspected that it was a case of Peutz-Jegher syndrome. However, polypoid lesions were not detectable in the gastrointestinal tract by colonoscopy. The authors consulted with a dermatologist. The patient was diagnosed as having Laugier-Hunziker-Baran syndrome because the development of the lesions was irrelevant to internal disorders, such as intestinal polyposis, and no familial association was observed. CASE 2 A 68-year-old Japanese man presented with a 23year history of asymptomatic macular hyperpigmentation on his lips. The patient said that the pigmentation on his lips became gradually progressive and that he did not take any medication which would cause pigmented lesions; otherwise, the patient was in good health. There was no family history of abnormal mucocutaneous pigmentation.
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Fig. 1. Case 1. Multiple hyperpigmented macules in the lower lip (A), buccalmucosa (B), tongue (C), and palate (D).
Fig. 2. Case 1. (A), (B), Multiple hyperpigmented macules in the palmplantararea. (C), A single longitudinal pigmented band presents on the toe nail.
Physical examination revealed multiple well defined diffuse dark brown maculae measuring 2-5 mm in diameter on the lips and buccal mucosa (bilaterally). One pigmented macula was noted on the palate, and pigmentation of the tongue was observed only on the right side (Fig. 3). One pigmented macula measuring 2 mm in diameter was observed on the right thumb (Fig. 4). However, there were none on the feet, and longitudinal pigmented bands were not present on his nails, either.
The number of pigmented maculae was less than that in case 1. There was no family history of acquired macular pigmentary disorders and no association with other systemic conditions. The patient was diagnosed to have Laugier-Hunziker-Baran syndrome. Biopsy specimens for these cases were taken from the pigmented maculae on the lower lip, buccal mucosa, tongue, and palate.
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Fig. 3. Case 2. Multiple hyperpigmented macules in the lower lip (A) and buccal mucosa (B). Pigmentation of his tongue is only on the right side tongue (C), and one pigmented macule was noted on the palate (D).
Fig. 4. One pigmented macule 2 mm in diameter had appeared on the right thumb.
HISTOPATHOLOGIC FINDINGS All specimens of cases 1 and 2 showed almost identical findings. High (lip) or moderate (others) melanin was confined to the basal layer of the stratified squamous epithelium. Melanin also was seen within melanophages in the upper connective tissue (Figs. 5 and 6). Inflammatory changes or malignant features were not noted in any area. DISCUSSION In 1970, Laugier and Hunziker reported 5 cases of an unusual acquired macular hyperpigmentation with no underlying disease.1 In 1979, Baran reported that associated nail pigmentation occurred in 5 out of 9 cases of Laugier-Hunziker syndrome.2 This syndrome is very rare, and since the original description about 50 cases have been reported in the world literature.6 LaugierHunziker-Baran syndrome is a rare condition in the United States7 and United Kingdom,8 and it is slightly
more common in France and Italy.2,3,5 In Japan, this syndrome is not understood very well, and 43 cases, including the present 2 cases, have been reported in the literature.4,9 Almost all of the reports were published in the field of dermatology. In Japanese oral sciences, there is only 1 report besides the present one.4 According to the reports from various foreign countries the pigmentary changes in Laugier-Hunziker-Baran syndrome usually begin in the third to fifth decade of life.6 There is a female preponderance, with an overall female-male ratio of 2:1.8 Nail involvement is seen in about 60% of the patients. The lesions are located most often on the buccal mucosa and on the lips.7 In Japan, Laugier-Hunziker-Baran syndrome affects patients in the range of 27-83 years old, with an average age of 59 years. Women are affected more frequently than men, with an overall female-male ratio of 4:1. Pigmentation is seen on the oral mucosa, on the palmar-plantar areas, fingers, toes, and genital region. Increased pigmentation typically occurs on the lips and buccal mucosa, as well as the tongue and palate area. However, it is extremely rare for pigmentation to be observed on the gingiva or the floor of the mouth. Longitudinal pigmented bands of the nails are observed in 44% of all patients. Pigmented maculae do not disappear naturally; Iitoyo and Miyazawa10 reported a case of a patient who was observed for changes over 8 years after pigmented maculae were first observed in the lips and fingers, and the number of pigmented maculae sharply increased each year, with some of the maculae fusing together and the color becoming slightly darker; pigmentation was also observed in the buccal mucosa approximately 8 years after the initial
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Fig. 5. Histpathologic findings of specimens from the pigmented macules on the lower lip (A), buccal mucosa (B), tongue (C), and palate (D) of case 1 (hematoxylin-eosin stain): an accumulation of melanin in the basal layer and increased number of melanophages in the superficial connective tissues.
consultation, along with linear pigmented bands in the fingernails. So far little information has been reported about treatment methods. Prescribing vitamin C and skinwhitening products is one of the treatment options; however, these treatments are not very effective.11,12 Kon and Takahashi11 gave a 38-year-old female systemic and internal applications of 750 mg/day tranexamic acid (Transamin) and 600 mg/day of a combination drug of vitamin C and pantothenic acid (Cinal) for pigmented maculae on her fingers, lips, and buccal mucosa, along with local and external applications of ointments containing hydroquinone for pigmented maculae on her fingers; they reported that the pigmented maculae on her fingers became less severe after 4 months owing to the efficacy of the external applications of the ointment containing hydroquinone, but no changes were observed in the pigmented maculae of her lips or buccal mucosa. Liquid nitrogen therapy (cryotherapy) is useful.12,13 Niiyama et al.12 reported a case in which liquid nitrogen therapy performed once or twice per week for pigmented maculae of the lips was effective: The color significantly faded in the third month. There are no case reports of pigmented maculae turning into malignant lesions in the Laugier-Hunziker-
Baran syndrome. Therefore, almost all cases were simply followed-up without any specific treatment. In the present cases, we chose to take a wait-and-see approach. As for the differential diagnosis of oral pigmented lesions, it is important to exclude other possibilities, such as Peutz-Jeghers syndrome, Addison disease, Albright syndrome, and the effect of medication. It is particularly important to conduct an appropriate differential diagnosis between Peutz-Jeghers syndrome and Laugier-Hunziker-Baran syndrome. The differences between these 2 syndromes are listed in Table I. Unlike Laugier-Hunziker-Baran syndrome, Peutz-Jeghers syndrome has a genetic background of autosomal dominant inheritance.14 In cases of Peutz-Jeghers syndrome, pigmented maculae may be present at birth and often appear in infancy or early childhood. In the case of Laugier-Hunziker-Baran syndrome, pigmentary changes usually start appearing between the ages of 20 and 50 years. In addition, in cases of Peutz-Jeghers syndrome, there is often a family history and an association with hamartomatous polyposis, mainly colonic. In cases of Laugier-Hunziker-Baran syndrome, gastrointestinal hamartomatous polyposis is not observed, nor is a familial history. In the present 2 cases, the patients had
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Fig. 6. Histpathologic findings of specimens from the pigmented macules on the lower lip (A), buccal mucosa (B), tongue (C), and palate (D) of case 2 (hematoxylin-eosin stain): an accumulation of melanin in the basal layer and increased number of melanophages in the superficial connective tissues, as in case 1.
Table I. Differential diagnosis: Laugier-Hunziker-Baran syndrome and Peutz-Jeghers syndrome Laugier-Hunziker-Baran syndrome
Peutz-Jeghers syndrome
⫺ 20s-50s ⫺ Frequent 44%-60%
Autosomal dominant inheritance Birth-infancy ⫹ Rare Extremely rare
Genetic background Age at onset Gastrointestinal polyposis Pigmented maculae: tongue and palate Pigmented streaks on nail
no previous, personal, or familial history of pigmented lesions or gastric intestinal polyposis, and they had not taken any medication which could lead to pigmentation. The distribution of pigmented lesions is a little bit different between these syndromes. Hyperpigmentation of the lips and buccal mucosa is observed in almost all patients of both syndromes. Maculae of the tongue and palate are rarely observed in cases of Peutz-Jeghers syndrome,15 whereas they are frequently observed in cases of Laugier-Hunziker-Baran syndrome. Iitoyo and Miyazawa stated that the lesions of Laugier-HunzikerBaran syndrome tend to increase as patients get older.10 In one of our cases, we observed an increase in the number of brown maculae on the lips.
The incidence of a pigmented nail band in cases of Laugier-Hunziker-Baran syndrome is 44%-60%.2,6 However, in cases of Peutz-Jeghers syndrome, patients rarely have a pigmented nail band. One patient subsequently developed a malignant melanoma in a case of Peutz-Jeghers syndrome. There are no case reports showing a pigmented macula turning into a malignant lesion in a case of Laugier-Hunziker-Baran syndrome. Besides this report, there are no other reported studies of simultaneous tissue biopsies of the lips, buccal mucosa, tongue, and palate in patients with LaugierHunziker-Baran syndrome. As a result, the histopathologic changes in cases of Laugier-Hunziker-Baran syndrome are not very specific. The histopathologic manifestations were similar for all locations in the
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presented cases. The histologic findings showed an increase of the melanin pigmentation at the basal layer; however, an increase in the number of melanocytes was not seen. This fact suggests that the pigmentation of this syndrome originates from an increase in the production of melanin pigment by the melanocyte. We must be familiar with Laugier-Hunziker-Baran syndrome, because this syndrome is probably more common than is generally recognized. The authors thank Dr. Tanaka, Professor, Department of Dermatology, Tokyo Women’s Medical University, Medical Center East. REFERENCES 1. Laugier P, Hunziker N. Pigmentaion melanique lenticulaire, essentielle, de la muqueuse jugale et des levers. Arch Belg Dermatol Syphiligr 1970;26:391-9. 2. Baran R. Longitudinal melanotic streaks as a clue to LaugierHunziker syndrome. Arch Dermatol 1979;115:1448-9. 3. Baran R, Barriere H. Longitudinal melanonychia with spreading pigmentation in Laugier-Hunziker syndrome: a report of two cases. Br J Dermatol 1986;115:707-10. 4. Fukushima Y, Matsuse Y, Yamamoto M, Sato J, Sakai N, Seto Kanichi. Two cases of Laugier-Hunziker-Baran syndrome. Jpn J Oral Maxillofac Surg 2004;50:620-3. 5. Veraldi S, Cavicchini S, Benelli C, Gasparini G. Laugier-Hunziker syndrome. A clinical, histopathologic, and ultrastructural study of four cases and review of the literature. J Am Acad Dermatol 1991;25:632-636. 6. Kanwar AJ, Kaur S, Kaur C, Thami GP. Laugier-Hunziker syndrome. J Dermatol 2001;28:54-7.
Yago, Tanaka, and Asanami e25 7. Koch SE, LeBoit PE, Odom RB. Laugier-Hunziker syndrome. J Am Acad Dermatol 1987;16:431-4. 8. Kemmett D, Ellis J, Spencer MJ, Hunter JAA. The LaugierHunziker syndrome—a clinical review of six cases. Clin Exp Dermatol 1990;15:111-4. 9. Kondo A, Iizuka M, Nozawa M, Tamiya S, Nuruki H, Umezawa Y, et al. Two cases of Laugier-Hunziker-Baran syndrome. Jpn Dermatol 2003;113:1111-5. 10. Iitoyo M, Miyazawa H. A case of Laugier-Hunziker syndrome with eight years’ observation. Skin Res 1999;41:352-5. 11. Kon A, Takahashi M. A case of Laugier-Hunziker-Baran syndrome. Rinsho Derma 1996;38:171-3. 12. Niiyama S, Okamoto K, Otoyama K. Laugier-Hunziker-Baran syndrome effectively treated with cryotherapy (liquid nitrogen). Jpn J Clin Dermatol 1999;53:56-8. 13. Nakamura T, Fujiwara T, Murata Y, Kumano K. 9 cases of Laugier’s disease (Laugier-Hunziker syndrome). Jpn Dermatol 1997;107:29-34. 14. Jeghers H, Mckusick VA, et al. Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits: a syndrome of diagnostic significance. N Engl J Med 1949;241:993-1005. 15. Yago K, Asanami S, Nagatoshi H, Nakagawa T, Tanaka Y, Kizu H. A case of Peutz-Jeghers syndrome with pigmented spots of the tongue. J Jpn Stomatol Soc 2003;52:200-4. Reprint requests: Kaori Yago, PhD, DDS Department of Dentistry and Oral Surgery, School of Medicine Keio University 35, Shinanomachi, Shinjyuku-ku Tokyo, 160-8582 Japan [email protected]