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  Table of Contents    
CASE REPORT  
Year : 2019  |  Volume : 62  |  Issue : 2  |  Page : 300-302
Juvenile hyaline fibromatosis in siblings


Department of Pediatrics, G. Kuppuswamy Naidu Memorial Hospital, Coimbatore, Tamil Nadu, India

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Date of Web Publication10-Apr-2019
 

   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

How to cite this URL:
Ravikumar VR, Veerappan Ramamoorthi RG, Manisankar S. Juvenile hyaline fibromatosis in siblings. Indian J Pathol Microbiol [serial online] 2019 [cited 2019 Jul 22];62:300-2. Available from: http://www.ijpmonline.org/text.asp?2019/62/2/300/255844





   Introduction Top


Juvenile hyaline fibromatosis (JHF) is a rare and progressive autosomal recessive connective tissue disorder.[1] Worldwide, <70 such cases have been reported, and those from India are rare[2] with only 5 published. It occurs due to mutation in the capillary morphogenesis gene 2 (CMG2) on chromosome 4q21.[3] 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.[2] 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.[4] We present a child with JHF with sibling also diagnosed with JHF.


   Case Report Top


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 Top


JHF is an extremely rare and progressive autosomal recessive connective tissue disorder.[1] There are only five published Indian reports of this disease and <70 reports worldwide.[2] 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.[2] JHF is thought to be a severe form of infantile systemic hyalinosis, with comparatively later initial presentation and less progressive course.[5] 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.[6] 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.[7]

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.[8] 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.[8]

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.[9] 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.[4] 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.[2]

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.[9] 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.[10] JHF is a progressive disorder with most patients surviving up to 4th decade only.[1] 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.

Consent

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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Nischal KC, Sachdev D, Kharkar V, Mahajan S. Juvenile hyaline fibromatosis. J Postgrad Med 2004;50:125-6.  Back to cited text no. 1
[PUBMED]  [Full text]  
2.
Rashmi MV, Geetha JP, Srinivas Arava NM, Kodandaswamy CR. Juvenile Hyaline Fibromatosis (JHF): A rare case with recurrence. J Clin Diagn Res 2014 8:161.  Back to cited text no. 2
    
3.
Dowling O, Difeo A, Ramirez MC, Tukel T, Narla G, Bonafe L, et al. Mutations in capillary morphogenesis gene-2 result in the allelic disorders juvenile hyaline fibromatosis and infantile systemic hyalinosis. Am J Hum Genet 2003;73:957-66.  Back to cited text no. 3
    
4.
Geethamani V, Ravindra S, Reddy VV. Fine needle aspiration cytology of juvenile hyaline fibromatosis: A case report. Acta Cytol 2007;51:624-6.  Back to cited text no. 4
    
5.
Nofal A, Sanad M, Assaf M, Nofal E, Nassar A, Almokadem S, et al. Juvenile hyaline fibromatosis and infantile systemic hyalinosis: A unifying term and a proposed grading system. J Am Acad Dermatol 2009;61:695-700.  Back to cited text no. 5
    
6.
Katagiri K, Takasaki S, Fujiwara S, Kayashima K, Ono T, Shinkai H, et al. Purification and structural analysis of extracellular matrix of a skin tumor from a patient with juvenile hyaline fibromatosis. J Dermatol Sci 1996;13:37-48.  Back to cited text no. 6
    
7.
Raja K, Khan MA, Mubarak M, Abbas Z, Luck NH, Hassan SM, et al. Three years old child with juvenile hyaline fibromatosis presenting with rectal bleeding. J Pak Med Assoc 2013;63:396-8.  Back to cited text no. 7
    
8.
Gupta LK, Singhi MK, Bansal M, Khullar R, Jain V, Kachhawa D, et al. Juvenile hyaline fibromatosis in siblings. Indian J Dermatol Venereol Leprol 2005;71:115-8.  Back to cited text no. 8
[PUBMED]  [Full text]  
9.
Krishnamurthy J, Dalal BS, Sunila MV. Juvenile hyaline fibromatosis. Indian J Dermatol 2011 6:731.  Back to cited text no. 9
    
10.
Woyke S, Domagala W, Markiewicz C. A 19-year follow-up of multiple juvenile hyaline fibromatosis. J Pediatr Surg 1984;19:302-4.  Back to cited text no. 10
    

Top
Correspondence Address:
Valkodai Ramanathan Ravikumar
Department of Pediatrics, G. Kuppuswamy Naidu Memorial Hospital, P. B No. 6327, Nethaji Road, Pappanaickenpalayam, Coimbatore - 641 037, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_76_17

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