Path Quiz Case- 78

                              Case history and images:

This is a rare disorder which was first described in 1873 as molluscum fibrosum and later named Juvenile hyaline fibromatosis (JHF) by Drescher et al in 1969.  This autosomal recessive disorder is characterized by aberrant collagen synthesis with deposition of hyaline material in the supporting tissues of the skin, gingiva, bone and joints. Usually more than one sibling in the same family is affected. Spontaneous regression of the lesions has been reported only rarely.

There are two distinct forms of juvenile hyaline fibromatosis - a localized form with very slow growth and a diffuse form with large and rapidly growing tumours .

Typical diagnostic criteria are multiple hyaline subcutaneous fibroma, painless papulonodular skin lesions (vary in size from a millimeter to about 5 cm), gingival hypertrophy, muscle contractures of the extremities and multiple osteolytic bone destructions.

Age: Commonly occurs in infancy and childhood (usually between 2 to 5 years). Some cases have been reported in adults.

Site: The nose, chin, ears, scalp, back, and knees are the most commonly affected sites.

Microscopic features: Image Link1 ; Image Link2 ;Image Link3 ; Image Link4 .

The tumour is poorly circumscribed and is characterized by eosinophilic homogeneous ground substance containing bland fibroblast-like cells with abundant granular cytoplasm. The substance is present in the extracellular spaces of the dermis and soft tissues.

In the skin lesion the skin appendages are reduced in number. A few thin-walled vessels are present and these are often surrounded by concentrically arranged collagen bundles.

The smaller and younger lesions tend to be more cellular. The large and older lesions contain abundant ground substance  The ground substance is PAS-positive and diastase resistant. The substance is alcian blue negative.  The ground substance consist mainly of acid mucopolysaccharides of cartilaginous type.

Immunohistochemistry: Immunohistochemically, the spindle-shaped cells are vimentin-positive but negative for alpha-smooth muscle actin and S-100 protein, and the hyaline ground substance are positive for type I and type III collagen but negative for type II and type IV collagen and tenascin.

Differential diagnosis:

Infantile systemic hyalinosis :

This is a specific, presumably autosomal recessive, genetic disease.

Clinical features included  stiff skin and painful joint contractures in the first few months of life together with small papules, particularly on the face and trunk, perianal nodules, hyperpigmentation over the metacarpophalangeal joints and over the malleoli, gingival hyperplasia and persistent diarrhea.

Hyaline (glassy) material is deposited in many tissues including the skin, muscle, the heart, gastrointestinal tract, lymph nodes, spleen, thyroid, and adrenal glands. There are overlapping features with JHF and are probably part of the same disease spectrum.

The gene for the disease is on chromosome 4q21. This gene encodes capillary morphogenesis protein 2 (CMG2), a transmembrane protein that is induced during capillary morphogenesis. The same gene is mutated in juvenile hyaline fibromatosis, a similar but milder disease.