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Juvenile hyaline fibromatosis
Short communications
& case reports
Juvenile hyaline fibromatosis MichaelJ.Aldred, Cardi’, Wales UNIVERSITY
Ph.D.,B.D.S.,F.D.S,*andPeterJ.M.Crawford,
OF WALES
COLLEGE
B.D.S., F.D.S.,M.Sc.D.,**
OF MEDICINE
The literature recording cases of the rare juvenile hyaline fibromatosis is reviewed. Gingival enlargement is a regular feature of this entity. A case report and treatment of the gingival lesions are described, and the differential diagnosis and prognosis are discussed. (ORAL SURG. ORAL MED. ORAL PATHOL. 19876371-7)
J
uvenile hyaline fibromatosis (JHF) is an extremely rare condition, the principal features of which are skin lesions, gingival enlargement, flexural contractures of joints, and osteolytic defects.1-2 Despite significant oral manifestations, no case reports have been published in the dental literature. This article reviews previously documented cases and describes the clinical and histologic features of a case we have seen,with particular emphasis on the oral manifestations. The general features of this casehave previously been described elsewhere.3 CASE REPORT
A.S. was referred to the Department of Children’s Dentistry at the age of 20 months with swelling of the gingivae, which was first noticed 3 weeks previously. This patient was born in the United Kingdom in 1978 of unrelated Kenyan-Asian parents. Neither his parents nor his older brother were similarly affected. The patient was born at term by normal delivery-weighing 2.3 kg-and, except for delayed motor development, was fit and well at presentation. On examination all of the deciduous teeth, with the exception of the second deciduous molars, were erupted and the gingivae of both arches were hyperplastic and erythematous, covering most of the teeth. A provisional diagnosis of hereditary fibromatosis gingivae4was made, and the marked erythema was attributed to
*Lecturer, Department of Oral Medicine and Oral Pathology. **Lecturer, Department of Child Dental Health.
Fig. 1. Clinical appearance at age 30 months, showing marked gingival enlargement.
an inflammatory responseto plaque accumulation. However, intensive oral hygiene measures failed to effect any significant reduction in the gingival erythema. The child was seen again at the age of 30 months, by which time the gingival enlargement had become more marked, producing deep false pockets (Fig. 1). The gingivae were not closely adapted to the teeth and were described (rather appropriately) as “floppy.” They were erythematous and edematous, with loss of the normal stippling. Close examination revealed a fine surface network of dilated capillaries. Extraorally, the nose was bulbous with small elevated pearly plaques around the alae nasi and isolated translucent nodules on the upper lip and in the periorbital region (Fig. 2). Similar nodules were also present in the postauric71
72
Aldred and Crawford
Oral Surg. January, 1987
Fig. 2. At age 30 months. Note bulbous nose with perinasal, periorbital, and lip nodules.
ular region, with coalescenceof similar lesions on the nape of the neck. The perinasal skin lesions had been noted at birth and both the skin lesions and delayed motor development were concurrently under investigation in the Department of Dermatology and Department of Pediatrics of the University of Wales College of Medicine. These investigations-reported previously’-revealed a functional weaknessin certain antagonist muscle groups, which caused the child to walk with hips and knees slightly flexed. In addition, there was a mild flexion deformity of the knees, weaknessand reduced muscle mass in the shoulder girdle and biceps muscles; consequently, he was unable to raise his arms above his head. Hearing and eyesight were normal, and there was no impairment of mental development. Other investigations included electromyogram and nerve-conduction studies, both of which were normal. The combination of the distinctive skin lesions and gingival enlargement suggested a diagnosis of juvenile hyaline fibromatosis. For diagnostic and esthetic reasons, labial and palatal gingivectomies were carried out in both jaws. A muscle biopsy was also performed, which showed minor changes in the size of the muscle fibres. A skeletal survey showed symmetrical medial cortical defects in the proximal ends of the humeri. Similar areas were observed in the tibia, as well as an osteolytic lesion in the distal end of the left humerus.3No abnormalities were detected in the skull, spine, or jaws. With time, the diseaseprogressedand the nose became grossly deformed (Fig. 3). Fleshy growths inside both nostrils, which were surgically removed becauseof blockage of the nasal airway, recurred within 6 months. Firm painless swellings have appeared in relation to the distal right radius and around the medial and lateral malleoli of both ankles, without apparent involvement of the underlying bone. Swellings of a gelatinous consistency have appeared behind the ears, with similar lesions on the right great toe. The postauricular and perinasal nodules have continued to enlarge. Between the agesof 5 and 6 years, the patient was lost to dental recall. At the end of that time, the absenceof the
Fig.
3. Age 3 years, gross nasal deformity.
upper right deciduous second molar was noted, with no history of its extraction. The upper right first permanent molar had moved down into the resulting space (Figs. 4 and 5). There was substantial bone loss associatedwith the remaining deciduous molars. On review when the boy was 7%~years of age, the deciduous incisors had exfoliated uneventfully. Early decalcification at the cervical margins of the deciduous molars, following treatment with topical fluoride in conjunction with the use of fluoride tablets and chlorhexidine mouthwashes, has not progressed. The initial gingivectomy produced only a short-term improvement and, by the time the child was 3% years old, a further gingivectomy was required. This has recently been repeated in association with the permanent incisors. Histopathology
Histologic examination of the gingivectomy material showed marked inflammatory changes in the portion related to the teeth, but the bulk of the specimenconsisted of an accumulation of eosinophilic hyaline material, within which there were many dilated capillaries (Fig. 6). Dispersedthroughout the tissue were round or oval cells with a clear cytoplasm-resembling chondrocytes--either solitary or arranged in groups and, at high power, a fine fibrillar pattern was seen within the matrix (Fig. 7). The hyaline material was PAS positive, diastase resistant, and stained with Alcian blue. This material did not appear to be amyloid, when judged by examination of Congo-
Juvenile hyaline jibromatosis
Volume 63
Number 1
Fig.
73
4. Orthopantomograph of child at age 6 years 8 months, showing mesial migration of upper right first
molar.
Fig. 5. Bitewing radiographs at age 6 years 8 months, showing alveolar bone loss and interproximal caries.
red-stained sections under polarized light. No metachromasia was observed after staining with toluidine blue. The hyaline appearance and pseudocartilaginous cells were characteristic of the histologic features of juvenile hyaline fibromatosis.5,6 A biopsy specimen from a skin nodule showed a similar appearance, with a patchy perivascular mononuclear infiltrate in the upper and middle parts of the dermis and thinning of the overlying epidermis.’
Fig. 6. Hyaline matrix with dilated capillaries. (Hematoxylin and eosin stain. Magnification, X50.)
DISCUSSION
To date, twenty-three cases1-3~5-‘a (including the present case) have been documented as occurring in seventeenfamilies, to our knowledge, with no obvious sex predilection (male:female ratio 1.3:1). In two families, other siblings who were probably
74
Aldred and Crawford
Oral Surg. January, 1987
is universally reported, but nodular6,‘*.2’ or papillomatous varieties may occur.’ Some reports have described dilated capillaries5 others have reported both a soft, vascular, spongy swelling and firm, fibrous enlargements in the same subject.’ Many reports have documented flexural contractures of joints-usually painful-that have caused progressive disability and deformity.z*3.5-7,lo.I’, 13-” Physica12* 3,5,6,lo.13-’5,” and sexua12’development may be impaired, but intellectual growth appears to remain normal. Osteolytic defects, particularly involving the long bones, skull, and terminal phalanges of the extremities, are a further notable feature,2,3.6.8.lo,‘I. 13,15-”but no osteolytic lesions of the jaws have been described. Generalized osteoporosis may also be evident.*, ‘3-‘5The importance of osteolytic lesions (as part of the condition) has been emphasized.6 Hypochromic, microcytic anemia has been discovered in a number of subjects2,5,7,‘o.‘swith occasional instances of hypoproteinemia2,‘O and hypoglycemia. 2oAn elevated erythrocyte sedimentation rate has been recorded2~‘0,‘3-‘5.20~2’ and is suggested to reflect ulceration and infection of the skin tumors. 7. Clear cells embedded within hyaline material featuring a fine fibrillar pattern, (Hematoxylin and eosin stain. Magnification, X 160.) Fig.
similarly affected died in infancy.2.7 A substantial number of reports have originated in Japan5-‘0 with sporadic casesappearing throughout the rest of the world’-3l ‘L’~ (Fig. 8). The first report of JHF is generally attributed to Murray,’ who reported on peculiar cases of molluscum fibrosum. He described three affected children in one family and illustrated the salient clinical manifestations of the condition with a drawing (Fig. 9). However, the gingival swelling in the oldest child had been previously described by Heath.19A variety of terms have been used, but the term JHF is now almost uniformly accepted, although whether this name is strictly correct has been questioned.5,‘7 The principal features are skin lesions and gingival enlargement.‘,2 The skin lesions may appear as plaques, papules, or nodules, particularly affecting the perinasal and postauricular areas-or as larger tumors which progressively enlarge” and may eventually ulcerate’, *,5*6.12.I3 or undergo calcification.2*20 Some skin lesions may regress spontaneously.’ 5,‘*,I3 In one family, the condition was limited to tumors involving the scalp,9 but all other reports describe gingival enlargement. The appearance of the gingival lesions is poorly described in the literature. Generalized enlargement
Parental consanguinity has been reported’*6-8,‘O and, in other cases, both sets of parents came from the same close communities.5,9The latter factor may be implicated in the case of the Kenya+Asian child in this report, and similarly in the case reported by Atherton et al.” Treatment remains unsatisfactory. The primary treatment of the larger skin lesions is excision, although these lesions may recur after such treatment.‘39,“3 “322Other approaches have included the ineffective use of hyaluronidase injections and radiotherapy.* ACTH, cortisone, or prednisolone**14.20.2’ and anabolic2’ steroids have been used with variable results, while capsulotomy or orthopedic surgery5-’ may be of benefit with regard to the flexural contractures of joints. Gingivectomy may have to be repeated as necessary, as in the present case. Oral mucosal involvement has been referred to without further details,2 and in most casesthe teeth appear to be unaffected, although hypodontia,15 ridged incisors,‘3 irregular occlusion,6 and delayed eruption’6 have been reported. Caries6,‘5 may be a secondary feature, resulting from plaque accumulation. Involvement of the tongue and internal organs has been revealed at postmortem examination.5, I33I4 Perianal involvement516,*,‘Ox 13*” and hypertrichosis’3*‘5have been described in some reports. Recurrent suppurative infections, affecting skin, eyes,nose, and ears, have been reported.* Histologically, both the skin and gingival lesions of JHF show features similar to the present case.The
Juvenile hyaline fibromatosis
Volume63 Number 1
75
Fig. 8. Geographic distribution of reported casesof juvenile hyaline fibromatosis. Closed circles represent affected subjects; open circles unaffected siblings. Half-closed circles denote other siblings with probable JHF.
hyaline
material
tive,2,5.6.9,I2.13.17s
20-22
is diastase
consistently resistant,Z
PAS 5s 6 17.21
posiand
Congo red negative,5s6*9’ “321 whereas results of Alcian blue staining and metachromsia with toluidine blue staining are more variable.2s5*6*9*lo*12* 2o The cellular component may be chondroid in appearance or there may be spindle cells resembling fibroblasts.‘* 2,6,8-‘o,12* I33~5.I7320* 22A frothy or granular cytoplasm may be seen, with finely stippled chromatin within the nucleus.5*6*9,lo*I23I33I772o Dilated blood vessels and lymphatics are common findings.2v5-9v 13-15* I7920-22 Mitoses are extremely rare. Small lesions tend to be more cellular than larger lesions.9*I23I7 The periphery of the lesion may be well defined in some areas or merge into the adjacent tissue elsewhere. Joint infiltration by this tissue has been described. In two cases, opening of the mouth was limited,2slopresumably as a result of involvement of the temporomandibular joint.‘O Irregularities in muscle fiber size2,3*7and loss of striations7 are further features of the condition. Electronmicroscopy has demonstrated the presence of fibrils within the hyaline material and intracytoplasmic granules containing similar fibrils, and it has been suggested that these granules (or their contents) are transferred into the extracellular space.5*lo,I3916.17* 20,21 Ruthenium red staining indicates that these fibrils are glycosaminoglycans.23 Histochemical techniques have demonstrated the presence of chondroitin sulfate, hyaluronic acid, dermatan sulfate within the cells, and hyaline substance 12,13.15.20 Manifestations of JHF in the form of pearly skin nodules may be present at birth3115,17* 2o and most subjects have skin lesions by the age of 2
Fig. 9. Drawings of the eldest of the three affected children described by Murray,’ showing gingival enlargement, skin lesions on the forehead and nose and in the perinasal area, as well as deformity of the fingers. (Reproduced by permission of the editor of the Journal of the Royal Society of Medicine.)
years.l-3-5-8,‘O-l8Gingival enlargement may precede the eruption of teeth,l or it may not be apparent until the end of the first decade,2 but has not been recorded as preceding the skin lesions. The severity
76
Aldred and Crawford
of the condition may vary in different members of the same family, but tends to increase with age,’ while the gingival enlargement appears to be limited by masticatory action. Iwata and co-workers24have suggested that the basic defect is a connective tissue disorder characterized by synthesis of abnormal glycosaminoglycans by fibroblasts, and the condition is regarded as being genetically determined, with an autosomal recessive mode of inheritance.5,25 Several reports have documented the subsequent progress of patients, with new skin lesions developing periodically and the flexural contractures of the joints resulting in severe immobility.20-23Life expectancy is uncertain, particularly since the oldest patient reported this century can currently be only 35 years old.2 Of the three cases reported by Murray,’ only one (aged 36) was still alive, severely disfigured and disabled, at the time of the further report of Whitfield and Robinson.26 Of the conditions appearing as gingival enlargement, this is perhaps the most distinctive becauseof its associated skin lesions. However, some thought should be given to alternative diagnoses, such as hereditary fibromatosis gingivae,4 from which it can be distinguished by the absenceof skin lesions in that condition; Rutherfurd’s syndrome, which in addition shows cornea1 opacities but does not feature skin lesions; Laband’s syndrome, in which nails are hypoplastic or absent although the nose and pinnae of the ears may be large and poorly structured; Cross’s syndrome, in which the gingival enlargement is also associated with microphthalmia and hypopigmentation; tuberous sclerosis, which shows epilepsy and mental retardation; and hyalinosis cutis et mucosae, in which all the oral tissues-including the tonguebecome involved. These latter conditions were reviewed by Gorlin and co-workers.27 Because of the gingival hyperplasia, the dental surgeon plays a large part in the care of these patients. From earliest diagnosis, the full preventive armamentarium of dietary counseling, fluoride replacement therapy, and oral hygiene instruction should be implemented. As with any genetically determined disorder, genetic counseling is an important part of the management. We thank Mrs. A&on Crawford, Miss Jane Woodhouse, and Miss Gabrielle Tschoepe, for translation of articles from the Spanish, French, and German literature. We are grateful to Dr. P.J.A. Holt and his colleagues for permission to publish this case.
(hi Surg. January, 1987 REFERENCE6
1. Murray J: On three peculiar casesof molluscum fibrosum in children. Medico-Chirurgical Transactions 56: 235-254, 1873. 2. Puretic S, Puretic B, Fiser-Herman M, Adamcic, M: A unique form of mesenchymal dysplasia. Br J Dermatol 74: 8-19, 1962. 3. Finlay AY, Ferguson SD, Holt PJA: Juvenile hyaline fibromatosis. Br J Dermatol 108: 609-616, 1983. 4. Rushton MA: Hereditary or idiopathic hyperplasia of the gums. Dent Pratt 7: 136-146, 1957. 5. Kitano Y, Horiki M, Aoki T, Sagami S: Two casesof Juvenile hyalin fibromatosis. Arch Dermatol 106: 877-883, 1972. 6. Kitano Y: Juvenile hyalin fibromatosis. Arch Dermatol 112: 86-88, 1976. I. Ishikawa H, Hori Y: Systematisierte hyalinose im zusammenhang mit epidermolysis bullosa dystrophica und hyalinosis cutis et mucosae. Arch J Klin Experiment Dermatol 218: 30-51, 1964. 8. Horio T, Hiramoto M, Yamada M: An atypical case of hyalinosis cutis et mucosae. Arch Dermatol (Kyoto) 63: 171-180, 1968. 9 Enjoji M, Kato N, Kamikozuru K, Arimi E: Juvenile fibromatosis of the scalp in siblings. Acta Med Kagoshima 18: 145-151, 1968. IO Hamada K, Ohdu S, Hayakawa K, Kikuchi I, Koono M: Puretic syndrome--(?ingival fibromatosis with hyaline fibromas. Jinrui Indennaku Zasshi 25: 249-255. 1980. 11 Atherton DJ, Lak; BD, Wells RS: Juvenile hyaline fibromatosis. Br J Dermatol 105: 61-63, 1981. 12 Drescher E, Woyke S, Markiewicz C, Tegi S: Juvenile fibromatosis in siblings (Fibromatosis hyalinica multiplex juvenilis). J Pediatr Surg 2: 427-430, 1967. 13. Costa OG, Costa PU, Guimaraos RC, Tafuri WL, Boglioli L: Fibromatosis hialina juvenil. Med Cutan Ibero Lat Am 5: 331-340, 1975. 14. Schmidt BJ, de Tomasi, Farhat CK, Neves JC, Cavalhal S, Carvalho AA, Furlaneto J, Souto RSC: Hemangiomatose sclerosante atypique. Arch Fr Pediatr 26: 213-219, 1969. 15. Suschke J, Kunze D: Ein Neuer MucopolysaccharidoseTyp. Deutsch Medizinische Wochenschrift 96: 1941-1943, 1971. 16. Gutierrez Cl, Zambrano V, Garcia F, Martin F, Ospina J, Camargo H: Fibromatosis hialinica multiple juvenil. Medicina Cutanea 7: 283-286, 1973. 17. Gianotti F, Ermacora E, Magrini U: Fibromatose hyaline juvenile. Ann Dermatol Venereol 104: 152-153, 1977. 18. Guilhou JJ, Meynadier J: Juvenile hyalin Bbromatosis. In: Kukita A, Seiji M (editors): Case presentations. XVI Congressus Internationalis Dermatologiae, Tokyo, 1982, University of Tokyo Press, p. 839. 19. Heath C: Injuries and diseasesof the jaws. The Jacksonian Prize essay of the Royal College of Surgeons of England 1867; ed. 2, London, 1872, J. & A Churchill, p. 194. 20. Ishikawa H, Mori S: Systemic hyalinosis or fibromatosis hyalinica multiplex juvenilis as a congenital syndrome. Acta Derm Venereol (Stockh) 53: 185-191, 1973. 21. Puretic S, Puretic B: Clinical and histopathological observations on systemic familial mesenchymosis.Proceedings of the 13th International Congress of Pediatrics 5: 373-381, 1971. 22. Woyke S, Domagala W, Olszewski W: Ultrastructure of a fibromatosis hyalinica multiplex juvenilis. Cancer 26: 11571168, 1970. 23. Ishikawa H, Maeda H, Takamatsu H, Saito Y: Systemic hyalinosis (juvenile hyaline fibromatosis): Ultrastructure of the hyaline with particular reference to the cross-banded structure. Arch Dermatol Res 265: 195-206, 1979. 24. Iwata S, Horiuchi R, Maeda H, Ishikawa H: Systemic hyalinosis or juvenile hyaline fibromatosis: Ultrastructural
Juvenile hyaline jibromatosis
Volume 63 Number 1 and biochemical study of cultured skin fibroblasts. Arch Dermatol Res 267: 115-121, 1980. 25. Witkop CJ: Heterogeneity in gingival fibromatosis: Birth defects original article series. New York, National Foundation March of Dimes 7: 210-221, 1971. 26. Whitfield A, Robinson AH: A further report on the remarkable series of cases of molluscum fibrosum in children communicated to the Society by Dr. John Murray in 1873. Medico-Chirurgical Transactions 86: 293-302, 1903. 27. Gorlin RJ, Pindborg JJ, Cohen MM: Syndromes of the head
and neck, ed. 2, New York, 1976, Mc-Graw-Hill Company, pp. 329-336, 366-370, 704-708. -
Keprint
requests
to:
Dr. Michael J. Aldred Department of Oral Medicine and Oral Pathology Dental School University of Wales College of Medicine Heath Park Cardiff CF4 4XY, Wales
77 Book
& case reports
Juvenile hyaline fibromatosis MichaelJ.Aldred, Cardi’, Wales UNIVERSITY
Ph.D.,B.D.S.,F.D.S,*andPeterJ.M.Crawford,
OF WALES
COLLEGE
B.D.S., F.D.S.,M.Sc.D.,**
OF MEDICINE
The literature recording cases of the rare juvenile hyaline fibromatosis is reviewed. Gingival enlargement is a regular feature of this entity. A case report and treatment of the gingival lesions are described, and the differential diagnosis and prognosis are discussed. (ORAL SURG. ORAL MED. ORAL PATHOL. 19876371-7)
J
uvenile hyaline fibromatosis (JHF) is an extremely rare condition, the principal features of which are skin lesions, gingival enlargement, flexural contractures of joints, and osteolytic defects.1-2 Despite significant oral manifestations, no case reports have been published in the dental literature. This article reviews previously documented cases and describes the clinical and histologic features of a case we have seen,with particular emphasis on the oral manifestations. The general features of this casehave previously been described elsewhere.3 CASE REPORT
A.S. was referred to the Department of Children’s Dentistry at the age of 20 months with swelling of the gingivae, which was first noticed 3 weeks previously. This patient was born in the United Kingdom in 1978 of unrelated Kenyan-Asian parents. Neither his parents nor his older brother were similarly affected. The patient was born at term by normal delivery-weighing 2.3 kg-and, except for delayed motor development, was fit and well at presentation. On examination all of the deciduous teeth, with the exception of the second deciduous molars, were erupted and the gingivae of both arches were hyperplastic and erythematous, covering most of the teeth. A provisional diagnosis of hereditary fibromatosis gingivae4was made, and the marked erythema was attributed to
*Lecturer, Department of Oral Medicine and Oral Pathology. **Lecturer, Department of Child Dental Health.
Fig. 1. Clinical appearance at age 30 months, showing marked gingival enlargement.
an inflammatory responseto plaque accumulation. However, intensive oral hygiene measures failed to effect any significant reduction in the gingival erythema. The child was seen again at the age of 30 months, by which time the gingival enlargement had become more marked, producing deep false pockets (Fig. 1). The gingivae were not closely adapted to the teeth and were described (rather appropriately) as “floppy.” They were erythematous and edematous, with loss of the normal stippling. Close examination revealed a fine surface network of dilated capillaries. Extraorally, the nose was bulbous with small elevated pearly plaques around the alae nasi and isolated translucent nodules on the upper lip and in the periorbital region (Fig. 2). Similar nodules were also present in the postauric71
72
Aldred and Crawford
Oral Surg. January, 1987
Fig. 2. At age 30 months. Note bulbous nose with perinasal, periorbital, and lip nodules.
ular region, with coalescenceof similar lesions on the nape of the neck. The perinasal skin lesions had been noted at birth and both the skin lesions and delayed motor development were concurrently under investigation in the Department of Dermatology and Department of Pediatrics of the University of Wales College of Medicine. These investigations-reported previously’-revealed a functional weaknessin certain antagonist muscle groups, which caused the child to walk with hips and knees slightly flexed. In addition, there was a mild flexion deformity of the knees, weaknessand reduced muscle mass in the shoulder girdle and biceps muscles; consequently, he was unable to raise his arms above his head. Hearing and eyesight were normal, and there was no impairment of mental development. Other investigations included electromyogram and nerve-conduction studies, both of which were normal. The combination of the distinctive skin lesions and gingival enlargement suggested a diagnosis of juvenile hyaline fibromatosis. For diagnostic and esthetic reasons, labial and palatal gingivectomies were carried out in both jaws. A muscle biopsy was also performed, which showed minor changes in the size of the muscle fibres. A skeletal survey showed symmetrical medial cortical defects in the proximal ends of the humeri. Similar areas were observed in the tibia, as well as an osteolytic lesion in the distal end of the left humerus.3No abnormalities were detected in the skull, spine, or jaws. With time, the diseaseprogressedand the nose became grossly deformed (Fig. 3). Fleshy growths inside both nostrils, which were surgically removed becauseof blockage of the nasal airway, recurred within 6 months. Firm painless swellings have appeared in relation to the distal right radius and around the medial and lateral malleoli of both ankles, without apparent involvement of the underlying bone. Swellings of a gelatinous consistency have appeared behind the ears, with similar lesions on the right great toe. The postauricular and perinasal nodules have continued to enlarge. Between the agesof 5 and 6 years, the patient was lost to dental recall. At the end of that time, the absenceof the
Fig.
3. Age 3 years, gross nasal deformity.
upper right deciduous second molar was noted, with no history of its extraction. The upper right first permanent molar had moved down into the resulting space (Figs. 4 and 5). There was substantial bone loss associatedwith the remaining deciduous molars. On review when the boy was 7%~years of age, the deciduous incisors had exfoliated uneventfully. Early decalcification at the cervical margins of the deciduous molars, following treatment with topical fluoride in conjunction with the use of fluoride tablets and chlorhexidine mouthwashes, has not progressed. The initial gingivectomy produced only a short-term improvement and, by the time the child was 3% years old, a further gingivectomy was required. This has recently been repeated in association with the permanent incisors. Histopathology
Histologic examination of the gingivectomy material showed marked inflammatory changes in the portion related to the teeth, but the bulk of the specimenconsisted of an accumulation of eosinophilic hyaline material, within which there were many dilated capillaries (Fig. 6). Dispersedthroughout the tissue were round or oval cells with a clear cytoplasm-resembling chondrocytes--either solitary or arranged in groups and, at high power, a fine fibrillar pattern was seen within the matrix (Fig. 7). The hyaline material was PAS positive, diastase resistant, and stained with Alcian blue. This material did not appear to be amyloid, when judged by examination of Congo-
Juvenile hyaline jibromatosis
Volume 63
Number 1
Fig.
73
4. Orthopantomograph of child at age 6 years 8 months, showing mesial migration of upper right first
molar.
Fig. 5. Bitewing radiographs at age 6 years 8 months, showing alveolar bone loss and interproximal caries.
red-stained sections under polarized light. No metachromasia was observed after staining with toluidine blue. The hyaline appearance and pseudocartilaginous cells were characteristic of the histologic features of juvenile hyaline fibromatosis.5,6 A biopsy specimen from a skin nodule showed a similar appearance, with a patchy perivascular mononuclear infiltrate in the upper and middle parts of the dermis and thinning of the overlying epidermis.’
Fig. 6. Hyaline matrix with dilated capillaries. (Hematoxylin and eosin stain. Magnification, X50.)
DISCUSSION
To date, twenty-three cases1-3~5-‘a (including the present case) have been documented as occurring in seventeenfamilies, to our knowledge, with no obvious sex predilection (male:female ratio 1.3:1). In two families, other siblings who were probably
74
Aldred and Crawford
Oral Surg. January, 1987
is universally reported, but nodular6,‘*.2’ or papillomatous varieties may occur.’ Some reports have described dilated capillaries5 others have reported both a soft, vascular, spongy swelling and firm, fibrous enlargements in the same subject.’ Many reports have documented flexural contractures of joints-usually painful-that have caused progressive disability and deformity.z*3.5-7,lo.I’, 13-” Physica12* 3,5,6,lo.13-’5,” and sexua12’development may be impaired, but intellectual growth appears to remain normal. Osteolytic defects, particularly involving the long bones, skull, and terminal phalanges of the extremities, are a further notable feature,2,3.6.8.lo,‘I. 13,15-”but no osteolytic lesions of the jaws have been described. Generalized osteoporosis may also be evident.*, ‘3-‘5The importance of osteolytic lesions (as part of the condition) has been emphasized.6 Hypochromic, microcytic anemia has been discovered in a number of subjects2,5,7,‘o.‘swith occasional instances of hypoproteinemia2,‘O and hypoglycemia. 2oAn elevated erythrocyte sedimentation rate has been recorded2~‘0,‘3-‘5.20~2’ and is suggested to reflect ulceration and infection of the skin tumors. 7. Clear cells embedded within hyaline material featuring a fine fibrillar pattern, (Hematoxylin and eosin stain. Magnification, X 160.) Fig.
similarly affected died in infancy.2.7 A substantial number of reports have originated in Japan5-‘0 with sporadic casesappearing throughout the rest of the world’-3l ‘L’~ (Fig. 8). The first report of JHF is generally attributed to Murray,’ who reported on peculiar cases of molluscum fibrosum. He described three affected children in one family and illustrated the salient clinical manifestations of the condition with a drawing (Fig. 9). However, the gingival swelling in the oldest child had been previously described by Heath.19A variety of terms have been used, but the term JHF is now almost uniformly accepted, although whether this name is strictly correct has been questioned.5,‘7 The principal features are skin lesions and gingival enlargement.‘,2 The skin lesions may appear as plaques, papules, or nodules, particularly affecting the perinasal and postauricular areas-or as larger tumors which progressively enlarge” and may eventually ulcerate’, *,5*6.12.I3 or undergo calcification.2*20 Some skin lesions may regress spontaneously.’ 5,‘*,I3 In one family, the condition was limited to tumors involving the scalp,9 but all other reports describe gingival enlargement. The appearance of the gingival lesions is poorly described in the literature. Generalized enlargement
Parental consanguinity has been reported’*6-8,‘O and, in other cases, both sets of parents came from the same close communities.5,9The latter factor may be implicated in the case of the Kenya+Asian child in this report, and similarly in the case reported by Atherton et al.” Treatment remains unsatisfactory. The primary treatment of the larger skin lesions is excision, although these lesions may recur after such treatment.‘39,“3 “322Other approaches have included the ineffective use of hyaluronidase injections and radiotherapy.* ACTH, cortisone, or prednisolone**14.20.2’ and anabolic2’ steroids have been used with variable results, while capsulotomy or orthopedic surgery5-’ may be of benefit with regard to the flexural contractures of joints. Gingivectomy may have to be repeated as necessary, as in the present case. Oral mucosal involvement has been referred to without further details,2 and in most casesthe teeth appear to be unaffected, although hypodontia,15 ridged incisors,‘3 irregular occlusion,6 and delayed eruption’6 have been reported. Caries6,‘5 may be a secondary feature, resulting from plaque accumulation. Involvement of the tongue and internal organs has been revealed at postmortem examination.5, I33I4 Perianal involvement516,*,‘Ox 13*” and hypertrichosis’3*‘5have been described in some reports. Recurrent suppurative infections, affecting skin, eyes,nose, and ears, have been reported.* Histologically, both the skin and gingival lesions of JHF show features similar to the present case.The
Juvenile hyaline fibromatosis
Volume63 Number 1
75
Fig. 8. Geographic distribution of reported casesof juvenile hyaline fibromatosis. Closed circles represent affected subjects; open circles unaffected siblings. Half-closed circles denote other siblings with probable JHF.
hyaline
material
tive,2,5.6.9,I2.13.17s
20-22
is diastase
consistently resistant,Z
PAS 5s 6 17.21
posiand
Congo red negative,5s6*9’ “321 whereas results of Alcian blue staining and metachromsia with toluidine blue staining are more variable.2s5*6*9*lo*12* 2o The cellular component may be chondroid in appearance or there may be spindle cells resembling fibroblasts.‘* 2,6,8-‘o,12* I33~5.I7320* 22A frothy or granular cytoplasm may be seen, with finely stippled chromatin within the nucleus.5*6*9,lo*I23I33I772o Dilated blood vessels and lymphatics are common findings.2v5-9v 13-15* I7920-22 Mitoses are extremely rare. Small lesions tend to be more cellular than larger lesions.9*I23I7 The periphery of the lesion may be well defined in some areas or merge into the adjacent tissue elsewhere. Joint infiltration by this tissue has been described. In two cases, opening of the mouth was limited,2slopresumably as a result of involvement of the temporomandibular joint.‘O Irregularities in muscle fiber size2,3*7and loss of striations7 are further features of the condition. Electronmicroscopy has demonstrated the presence of fibrils within the hyaline material and intracytoplasmic granules containing similar fibrils, and it has been suggested that these granules (or their contents) are transferred into the extracellular space.5*lo,I3916.17* 20,21 Ruthenium red staining indicates that these fibrils are glycosaminoglycans.23 Histochemical techniques have demonstrated the presence of chondroitin sulfate, hyaluronic acid, dermatan sulfate within the cells, and hyaline substance 12,13.15.20 Manifestations of JHF in the form of pearly skin nodules may be present at birth3115,17* 2o and most subjects have skin lesions by the age of 2
Fig. 9. Drawings of the eldest of the three affected children described by Murray,’ showing gingival enlargement, skin lesions on the forehead and nose and in the perinasal area, as well as deformity of the fingers. (Reproduced by permission of the editor of the Journal of the Royal Society of Medicine.)
years.l-3-5-8,‘O-l8Gingival enlargement may precede the eruption of teeth,l or it may not be apparent until the end of the first decade,2 but has not been recorded as preceding the skin lesions. The severity
76
Aldred and Crawford
of the condition may vary in different members of the same family, but tends to increase with age,’ while the gingival enlargement appears to be limited by masticatory action. Iwata and co-workers24have suggested that the basic defect is a connective tissue disorder characterized by synthesis of abnormal glycosaminoglycans by fibroblasts, and the condition is regarded as being genetically determined, with an autosomal recessive mode of inheritance.5,25 Several reports have documented the subsequent progress of patients, with new skin lesions developing periodically and the flexural contractures of the joints resulting in severe immobility.20-23Life expectancy is uncertain, particularly since the oldest patient reported this century can currently be only 35 years old.2 Of the three cases reported by Murray,’ only one (aged 36) was still alive, severely disfigured and disabled, at the time of the further report of Whitfield and Robinson.26 Of the conditions appearing as gingival enlargement, this is perhaps the most distinctive becauseof its associated skin lesions. However, some thought should be given to alternative diagnoses, such as hereditary fibromatosis gingivae,4 from which it can be distinguished by the absenceof skin lesions in that condition; Rutherfurd’s syndrome, which in addition shows cornea1 opacities but does not feature skin lesions; Laband’s syndrome, in which nails are hypoplastic or absent although the nose and pinnae of the ears may be large and poorly structured; Cross’s syndrome, in which the gingival enlargement is also associated with microphthalmia and hypopigmentation; tuberous sclerosis, which shows epilepsy and mental retardation; and hyalinosis cutis et mucosae, in which all the oral tissues-including the tonguebecome involved. These latter conditions were reviewed by Gorlin and co-workers.27 Because of the gingival hyperplasia, the dental surgeon plays a large part in the care of these patients. From earliest diagnosis, the full preventive armamentarium of dietary counseling, fluoride replacement therapy, and oral hygiene instruction should be implemented. As with any genetically determined disorder, genetic counseling is an important part of the management. We thank Mrs. A&on Crawford, Miss Jane Woodhouse, and Miss Gabrielle Tschoepe, for translation of articles from the Spanish, French, and German literature. We are grateful to Dr. P.J.A. Holt and his colleagues for permission to publish this case.
(hi Surg. January, 1987 REFERENCE6
1. Murray J: On three peculiar casesof molluscum fibrosum in children. Medico-Chirurgical Transactions 56: 235-254, 1873. 2. Puretic S, Puretic B, Fiser-Herman M, Adamcic, M: A unique form of mesenchymal dysplasia. Br J Dermatol 74: 8-19, 1962. 3. Finlay AY, Ferguson SD, Holt PJA: Juvenile hyaline fibromatosis. Br J Dermatol 108: 609-616, 1983. 4. Rushton MA: Hereditary or idiopathic hyperplasia of the gums. Dent Pratt 7: 136-146, 1957. 5. Kitano Y, Horiki M, Aoki T, Sagami S: Two casesof Juvenile hyalin fibromatosis. Arch Dermatol 106: 877-883, 1972. 6. Kitano Y: Juvenile hyalin fibromatosis. Arch Dermatol 112: 86-88, 1976. I. Ishikawa H, Hori Y: Systematisierte hyalinose im zusammenhang mit epidermolysis bullosa dystrophica und hyalinosis cutis et mucosae. Arch J Klin Experiment Dermatol 218: 30-51, 1964. 8. Horio T, Hiramoto M, Yamada M: An atypical case of hyalinosis cutis et mucosae. Arch Dermatol (Kyoto) 63: 171-180, 1968. 9 Enjoji M, Kato N, Kamikozuru K, Arimi E: Juvenile fibromatosis of the scalp in siblings. Acta Med Kagoshima 18: 145-151, 1968. IO Hamada K, Ohdu S, Hayakawa K, Kikuchi I, Koono M: Puretic syndrome--(?ingival fibromatosis with hyaline fibromas. Jinrui Indennaku Zasshi 25: 249-255. 1980. 11 Atherton DJ, Lak; BD, Wells RS: Juvenile hyaline fibromatosis. Br J Dermatol 105: 61-63, 1981. 12 Drescher E, Woyke S, Markiewicz C, Tegi S: Juvenile fibromatosis in siblings (Fibromatosis hyalinica multiplex juvenilis). J Pediatr Surg 2: 427-430, 1967. 13. Costa OG, Costa PU, Guimaraos RC, Tafuri WL, Boglioli L: Fibromatosis hialina juvenil. Med Cutan Ibero Lat Am 5: 331-340, 1975. 14. Schmidt BJ, de Tomasi, Farhat CK, Neves JC, Cavalhal S, Carvalho AA, Furlaneto J, Souto RSC: Hemangiomatose sclerosante atypique. Arch Fr Pediatr 26: 213-219, 1969. 15. Suschke J, Kunze D: Ein Neuer MucopolysaccharidoseTyp. Deutsch Medizinische Wochenschrift 96: 1941-1943, 1971. 16. Gutierrez Cl, Zambrano V, Garcia F, Martin F, Ospina J, Camargo H: Fibromatosis hialinica multiple juvenil. Medicina Cutanea 7: 283-286, 1973. 17. Gianotti F, Ermacora E, Magrini U: Fibromatose hyaline juvenile. Ann Dermatol Venereol 104: 152-153, 1977. 18. Guilhou JJ, Meynadier J: Juvenile hyalin Bbromatosis. In: Kukita A, Seiji M (editors): Case presentations. XVI Congressus Internationalis Dermatologiae, Tokyo, 1982, University of Tokyo Press, p. 839. 19. Heath C: Injuries and diseasesof the jaws. The Jacksonian Prize essay of the Royal College of Surgeons of England 1867; ed. 2, London, 1872, J. & A Churchill, p. 194. 20. Ishikawa H, Mori S: Systemic hyalinosis or fibromatosis hyalinica multiplex juvenilis as a congenital syndrome. Acta Derm Venereol (Stockh) 53: 185-191, 1973. 21. Puretic S, Puretic B: Clinical and histopathological observations on systemic familial mesenchymosis.Proceedings of the 13th International Congress of Pediatrics 5: 373-381, 1971. 22. Woyke S, Domagala W, Olszewski W: Ultrastructure of a fibromatosis hyalinica multiplex juvenilis. Cancer 26: 11571168, 1970. 23. Ishikawa H, Maeda H, Takamatsu H, Saito Y: Systemic hyalinosis (juvenile hyaline fibromatosis): Ultrastructure of the hyaline with particular reference to the cross-banded structure. Arch Dermatol Res 265: 195-206, 1979. 24. Iwata S, Horiuchi R, Maeda H, Ishikawa H: Systemic hyalinosis or juvenile hyaline fibromatosis: Ultrastructural
Juvenile hyaline jibromatosis
Volume 63 Number 1 and biochemical study of cultured skin fibroblasts. Arch Dermatol Res 267: 115-121, 1980. 25. Witkop CJ: Heterogeneity in gingival fibromatosis: Birth defects original article series. New York, National Foundation March of Dimes 7: 210-221, 1971. 26. Whitfield A, Robinson AH: A further report on the remarkable series of cases of molluscum fibrosum in children communicated to the Society by Dr. John Murray in 1873. Medico-Chirurgical Transactions 86: 293-302, 1903. 27. Gorlin RJ, Pindborg JJ, Cohen MM: Syndromes of the head
and neck, ed. 2, New York, 1976, Mc-Graw-Hill Company, pp. 329-336, 366-370, 704-708. -
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