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Juvenile Hyaline Fibromatosis

      A 27-year-old African American man presented to an orthopedic surgeon with a painful mass on his left fourth toe, which impaired ambulation and the wearing of closed footwear. His medical history was notable for juvenile hyaline fibromatosis diagnosed at age 4 years and for multiple prior operations to remove symptomatic masses on his face and extremities. Physical examination revealed multiple masses of varying size on his face and all extremities (Figure A ), with a large mass on the distal aspect of the fourth toe on the right foot that had eroded into the distal phalanx and another painful mass on his medial hallux (Figure B). A right fourth toe partial amputation and excision of the hallux mass were performed. Histologic examination of the amputation specimen revealed extensive replacement of the subepidermal connective tissue by amorphous, partially calcified hyaline material with an associated proliferation of bland, epithelioid fibroblastic cells, diagnostic of juvenile hyaline fibromatosis (Figure C). This process extended into and destroyed the underlying bony phalanx (Figure D).
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      FigurePatient with juvenile hyaline fibromatosis. A, Multiple masses on hands. B, Large mass on the distal aspect of the fourth toe on the right foot that had eroded into the distal phalanx and another painful mass on the medial hallux. C, Photomicrgraph showing extensive replacement of the subepidermal connective tissue by amorphous, partially calcified hyaline material with an associated proliferation of bland, epithelioid fibroblastic cells (stain, original magnification ×100). D, Photomicrograph showing the disease process extended into and destroyed the underlying bony phalanx (stain, original magnification ×100).
      Juvenile hyaline fibromatosis is a very rare genetic disorder with an autosomal recessive pattern of inheritance, first described by Murray in 1873 as “molluscum fibrosum.”
      • Murray J.
      On three peculiar cases of molluscum fibrosum in children in which one or more of the following conditions were observed: hypertrophy of the gums, enlargement of the ends of the fingers and toes, numerous connective-tissue tumours on the scalp and other parts of the surface of the body, with various superficial affections of the skin.
      It is genetically related to a similar (but not identical) condition termed infantile systemic hyalinosis.
      • Liu L.
      • Ren F.
      • Tan Q.
      Infantile systemic hyalinosis.
      Patients with juvenile hyaline fibromatosis present in childhood with joint contractures, gingival hyperplasia, osteopenia, osteolytic bone lesions, and papular and nodular skin lesions.
      • Karande V.
      • Andrade N.N.
      Juvenile hyaline fibromatosis.
      The skin lesions vary widely in number and size, are slow growing and usually painless, and tend to recur following excision. Both juvenile hyaline fibromatosis and infantile systemic hyalinosis are caused by sequence variations in the ANTXR2 gene (ANTXR cell adhesion molecule 2; gene name alias, capillary morphogenesis gene 2 [CMG2]), which codes for a protein involved in basement membrane matrix assembly, in particular collagen type VI homeostasis, and morphogenesis of endothelial cells.
      • El-Kamah G.Y.
      • Fong K.
      • El-Ruby M.
      • et al.
      Spectrum of mutations in the ANTXR2 (CMG2) gene in infantile systemic hyalinosis and juvenile hyaline fibromatosis.
      Distinct mutations are seen in juvenile hyaline fibromatosis and infantile systemic hyalinosis, suggesting a genotypic-phenotypic correlation. The prognosis for these diseases is variable, with survival into adulthood for patients with juvenile hyaline fibromatosis and early death from intractable diarrhea and recurrent infections in infantile systemic hyalinosis.

      References

        • Murray J.
        On three peculiar cases of molluscum fibrosum in children in which one or more of the following conditions were observed: hypertrophy of the gums, enlargement of the ends of the fingers and toes, numerous connective-tissue tumours on the scalp and other parts of the surface of the body, with various superficial affections of the skin.
        Med Chir Trans. 1873; 56: 235-254.1
        • Liu L.
        • Ren F.
        • Tan Q.
        Infantile systemic hyalinosis.
        JAMA Dermatol. 2019; 155: 1306
        • Karande V.
        • Andrade N.N.
        Juvenile hyaline fibromatosis.
        Contemp Clin Dent. 2018; 9: 484-487
        • El-Kamah G.Y.
        • Fong K.
        • El-Ruby M.
        • et al.
        Spectrum of mutations in the ANTXR2 (CMG2) gene in infantile systemic hyalinosis and juvenile hyaline fibromatosis.
        Br J Dermatol. 2010; 163: 213-215