| Abstract|| |
Background: Juvenile Hyaline Fibromatosis is a rare autosomal recessive connective tissue disorder. Case Characteristics: Three year old girl with multiple facial nodules, gingival hypertrophy and multiple joint contractures. Her sibling, male child also had similar findings which was progressive and he died at 2 years. Outcome: Nodule biopsy showed extensively hyalinised dermis with PAS positivity. Message: Juvenile Hyaline Fibromatosis is a differential diagnosis for children presenting with multiple nodular lesions.
Keywords: Facial nodules, gingival hypertrophy, joint contracture, juvenile hyaline fibromatosis, juvenile systemic hyalinosis
|How to cite this article:|
Ravikumar VR, Veerappan Ramamoorthi RG, Manisankar S. Juvenile hyaline fibromatosis in siblings. Indian J Pathol Microbiol 2019;62:300-2
| Introduction|| |
Juvenile hyaline fibromatosis (JHF) is a rare and progressive autosomal recessive connective tissue disorder. Worldwide, <70 such cases have been reported, and those from India are rare with only 5 published. It occurs due to mutation in the capillary morphogenesis gene 2 (CMG2) on chromosome 4q21. It usually presents between the ages of 2 and 5 years with multiple nodular skin lesions (which may also be confluent), gingival hypertrophy, joint contractures, and osteolytic lesions on skiagram. It may be associated with feeding problems, malnutrition, and recurrent infections. Diagnostic confirmation requires histological examination of the nodule biopsy specimen which shows oval to spindle-shaped cells with abundant, extensively hyalinized stroma with periodic acid–Schiff (PAS) positivity. We present a child with JHF with sibling also diagnosed with JHF.
| Case Report|| |
A 3-year-old girl child, third born to nonconsanguineous parents, was brought with multiple facial swellings, which started from 1½ years of age and progressively increased in size. She also had feeding difficulty. Her elder sibling (first born), a boy, had similar swellings in the face, which started at 7 months of age. Her sibling had developed progressive dysphagia and respiratory distress and was diagnosed with systemic JHF and had expired at 2½ years of age.
On examination, she had wide nasal bridge and multiple facial nodules, involving the upper lip, chin, forehead, nose, and both ears [Figure 1]a. The one in the left ear was very large with skin discoloration [Figure 1]b. There were multiple pin head nodules in the forehead and root of the nose [Figure 1]a. The nodules were firm in consistency and nontender. She had mild gingival hypertrophy. She had contractures of all metacarpophalangeal joints of her left hand with restriction of movement. She also had contractures of both knees and was able to walk with support.
|Figure 1: (a) Multiple facial nodules, involving the upper lip, chin, forehead, nose, and both ears; (b) large nodule in the left ear with skin discolouration; (c) microscopic examination of nodule biopsy specimen showing extensive hyaline deposition in the dermis; (d) cords and clusters of oval to spindle-shaped cells, separated by abundant hyalinized stroma|
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The large ear nodule was biopsied. Cut surface of the biopsy specimen was homogenous gray-black with focal areas of hemorrhage and fibrous band traversing through the specimen. Microscopic examination showed that dermis was expanded by extensive deposits of homogenous eosinophilic hyaline material interspersed with fibroblasts [Figure 1]c. The lesion was composed of cords and clusters of oval to spindle-shaped cells, separated by abundant hyalinized stroma [Figure 1]d. The cells showed bland nuclear morphology. Mitotic figures were not detected. PAS staining was positive (hyaline deposits). Alcian blue and Congo-red staining was negative. A clinical and histological diagnosis of JHF was made. Immunohistochemistry which will identify the morphology of spindle-shaped cells, hyaline deposits, and collagen were not done due to want of funds from the parents.
| Discussion|| |
JHF is an extremely rare and progressive autosomal recessive connective tissue disorder. There are only five published Indian reports of this disease and <70 reports worldwide. Family history of similar condition is usually present in most children presenting with JHF, as with our child. Consanguinity of parents is variable. There is no gender difference. JHF is thought to be a severe form of infantile systemic hyalinosis, with comparatively later initial presentation and less progressive course. It is associated with aberrant fibroblast synthesis of glycosaminoglycans, leading to predominance of dermatan sulfate in the skin, in contrast to hyaluronan in the normal skin. Basement membrane formation is disrupted, leading to leak of hyaline substance through it, which gets built up in skin, joints, bones, and other body tissues, thus causing characteristic clinical features.
Children with JHF usually present between the ages of 2 and 5 years with varying combinations of papulonodular skin lesions, gingival hypertrophy, joint contractures, and osteolytic bony lesions. Nodules predominantly occur in the head-and-neck region, involving scalp, nose, ears, and cheek, as present in our child. They may also occur in the back and perianal region. They may vary from 1 mm to 5 cm in size, are non-tender, slow growing and typically recur after excision. Gingival hypertrophy may be mild, as with our child, or may be severe, interfering with dentition and feeding, leading to malnutrition. Flexion contractures may involve small joints of hands or large joints such as knee, elbow and hip, as present in our child.
Blood and other biochemical investigations are usually within normal limits or nonspecific. These children may have hypochromic anemia related to malnutrition. Diagnosis is confirmed by histological examination of the biopsy specimen. Grossly, the nodules have a grey-white gelatinous appearance on the cut surface. Characteristic histologic findings include cords of oval to spindle-shaped cells within the PAS-positive amorphous eosinophilic matrix, containing abundant hyaline material. Elastic tissue is rarely observed or may be completely absent. Mitotic figures are absent. The child reported above had similar histological features on nodule biopsy specimen. The differential diagnoses include infantile systemic hyalinosis, neurofibromatosis, congenital generalized fibromatosis, nodular amyloidosis, and Winchester syndrome.
Treatment largely relies on early tumor removal for nodular lesions, gingivectomy, and nutritional supplementation for gingival hypertrophy and resulting malnutrition, physiotherapy to prevent or delay flexion contractures and capsulotomy and intralesional corticosteroid therapy for established joint contractures. Recurrence of nodules is common and Woyke et al. have reported successful removal of more than 100 nodules in a patient over a period of 19 years. JHF is a progressive disorder with most patients surviving up to 4th decade only. Genetic counseling is an important aspect of management and parents need to be explained about the 25% chance of recurrence in the next sibling. With the genetic defect being identified, antenatal diagnostic methods are likely to be invented in near future.
JHF should be considered in a child presenting with multiple nodular lesions especially involving face. It should also be considered in differential diagnosis of gingival hypertrophy and joint contractures, particularly if associated with a positive family history. Early diagnosis and interventions are needed for the betterment of prognosis.
Obtained from father of the child.
Declaration of patient consent
These authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given/her consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal patient's identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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Valkodai Ramanathan Ravikumar
Department of Pediatrics, G. Kuppuswamy Naidu Memorial Hospital, P. B No. 6327, Nethaji Road, Pappanaickenpalayam, Coimbatore - 641 037, Tamil Nadu
Source of Support: None, Conflict of Interest: None