Juvenile hyaline fibromatosis.

Juvenile hyaline fibromatosis is a rare, autosomal-recessive disease characterized by papular and nodular skin lesions, gingival hyperplasia, joint contractures and bone involvement in variable degrees. It is a connective tissue disorder with aberrant synthesis of glycosaminoglycans by fibroblasts. We report a 5-year-old female born of first-degree consanguineous marriage who presented with multiple, recurrent, painless, variable-sized nodules. Fine needle aspiration cytology smears and the subsequent histopathological examination from the nodules showed benign spindle cells in a Periodic acid Schiff-positive myxoid background. The disease has a relentlessly progressive course, with most patients surviving only up to the 4(th) decade. As of now, there is no specific treatment for this disorder. Genetic counseling is essential to explain to parents about a 25% chance of having a diseased baby in any pregnancy. With the gene being mapped recently, techniques for antenatal diagnosis are likely to be established.

Introduction

Juvenile hyaline fibromatosis (JHF) is a rare, autosomal-recessive hereditary disease with distinct clinical and histopathological features. A scan of the world literature revealed that less than 70 cases have been reported so far.[1-3] The clinical onset is usually noted from birth up to 5 years of age. Boys are affected slightly more commonly than girls.[4] It is characterized by papular and nodular skin lesions, gingival hyperplasia, joint contractures and bone involvement in variable degrees.[2]

Case Report

We report a 5-year-old female born of first-degree consanguineous marriage who presented with multiple, recurrent, painless, variable-sized nodules over the scalp, back, ear lobules and lower lip [Figure 1]. The lesions were first noticed when the child was 6 months old and, since then, the nodules gradually increased in size. Two of the nodules on the scalp were excised when the child was 2 years old. But, there was recurrence at the same site. The child has normal developmental milestones. The only other older sibling in the family and the parents are normal.

Figure 1

Multiple nodules over the back and lower lip

On examination, the lesions consisted of multiple papules and nodules of varying sizes. They were soft to firm in consistency and nontender. There was no gingival hyperplasia or flexion contracture deformities of the limbs. There was no significant lymphadenopathy or hepatosplenomegaly. Hematological and biochemical investigations were within normal limits.

Fine needle aspiration Cytology (FNAC) smears from the nodules showed sparse spindle cells in a Periodic acid Schiff (PAS)-positive background, the features of which were suggestive of fibromatosis [Figure 2].

Figure 2

FNAC smears showing few spindle cells in a PAS +ve myxoid background

The nodules over the back, scalp, ear lobule and lower lip were excised in multiple sittings and sent for histopathological examination.

Pathological findings

Grossly, the nodules were of variable sizes and grayish-white, and the cut surface showed a gelatinous grey-white appearance [Figure 3].

Figure 3

Variable-sized grey-white nodular masses with gelatinous cut surface

Microscopically, there were poorly circumscribed lesions in the dermis and subcutis composed of a sparse population of uniform spindle cells embedded in an abundant homogenous eosinophilic fibrillary matrix [Figure 4]. The matrix was PAS positive [Figure 5]. These findings were diagnostic of JHF.

Figure 4

Sparse population of uniform spindle cells (hematoxylin and eosin stain, 100×)

Figure 5

Matrix showing PAS positivity (100×)

The patient was lost to follow-up for the past 7 years and now she has presented with many more new nodules over the forehead, chest and abdomen. The lesions on the cheek and ear lobule have increased in size [Figure 6]. Excision in multiple sittings has been planned.

Figure 6

Recurrent lesions after 7 years

Discussion

JHF is a rare, crippling autosomal-recessive disorder, first described by Mc Murray in 1873 as molluscum fibrosum and renamed by Kitano as JHF in 1972.[1-2] The etiology of JHF is unknown. The gene that causes JHF has been mapped to 4q21. Mutations in the capillary morphogenesis factor -2 gene have also been described.[2] It has been hypothesized that JHF is a connective tissue disorder characterized by aberrant synthesis of glycosaminoglycans by fibroblasts.[4] Glycosaminoglycans in the tumor tissue comprised dermatan sulfate, chondroitin sulfate and hyaluronan, with the dermatan sulfate predominating. In contrast, hyaluronan is the most abundant in normal skin.[5] It usually affects one or more siblings and, as in the present case, it initially presents in children between 2 and 5 years of age.[2] The condition is characterized by multiple cutaneous papules, nodules or tumor masses, gingival hypertrophy, joint contractures and osteolytic defects.[4] Skin lesions may be the most outstanding symptoms of JHF, but joint contracture and gingival hypertrophy precede the skin manifestation.[6] Joint contractures cripple the patients and retard normal motor development if it occurs in infancy.[2] Severe gingival hyperplasia can interfere with eating and delay dentition too.[1] The present case has only cutaneous lesions, but there is no gingival hypertrophy, joint or bone involvement till date. The tumor masses vary in size from 1 mm to about 5 cm. They are slow growing and painless and have a tendency to recur following excision,[4] as was seen in the present case. Woyke et al. reported a patient who underwent successful surgical removal of more than 100 tumors over a period of 19 years with good cosmetic results.[7] Quintal and Jackson reported a patient who had numerous surgical excisions over a period of 34 years and found that the therapy was as mutilating as the disease.[8] The diagnosis is confirmed by histology.[2] The tumors are poorly circumscribed and consist of cords of spindle-shaped cells embedded in a homogeneous eosinophilic matrix. They are often found in the dermis, subcutis and gingiva, although the bone and joints may also be involved. Early lesions show increased cellularity and less-prominent stroma, whereas the large, older lesions are less cellular and contain more ground substance. The matrix stains positively with PAS and alcian blue but does not stain with toluidine blue or congo red. Elastic tissue is completely absent. Occasional nodules reveal marked calcification.[4] The differential diagnosis of JHF includes neurofibromatosis, gingival fibromatosis, nodular amyloidosis, infantile systemic hyalinosis, congenital generalized fibromatosis, lipoid proteinosis and Winchester syndrome.[2] The disease has a relentlessly progressive course, with most patients surviving only up to the 4th decade.[1-2] As of now, there is no specific treatment for this disorder.[1] The treatment is only aesthetic and its aim is to limit orthopedic disability. Early tumorectomy may help, but relapses are not infrequent. Joint contractures may respond to intralesional systemic steroids and physiotherapy.[2] Physiotherapy, as emphasized in the present case, avoids flexion contractures.

Genetic counseling is essential to explain to parents about a 25% chance of having a diseased baby in any pregnancy. With the gene for the disease being mapped recently, techniques or antenatal diagnosis are likely to be established.[1]