Multiple Scalp Tumors in Juvenile Hyaline Fibromatosis with Antxr-2 Mutation in a Family

Sir,

Hyaline fibromatosis syndrome is a rare autosomal recessive disorder associated with deposition of amorphous, hyaline material in skin, and visceral organs.[1] Dermatological opinion was sought for a 4-year-old female, born of consanguineous marriage delivered as normal, vaginal delivery. Her mother noticed multiple boggy, progressively increasing swellings over scalp, retroauricular, and perianal region, since 2 years of age and reddish swellings over tips of some toes and middle fingers, upper and lower gingival mucosa, and multiple skin colored raised lesions in nasolabial fold since six months. The 2-year-old female sibling had similar multiple boggy swellings over scalp, upper and lower gingival mucosae, and skin colored lesions were noted over retroauricular area and the nasolabial fold. There was no history of diarrhea, recurrent infections, joint contracture, or seizure in either of siblings. Antenatal and postnatal periods were uneventful. General physical examination was normal in both the siblings. Cutaneous findings of elder sibling comprised of multiple subcutaneous, soft to firm, noncompressible, nontender nodules over scalp, and behind both ears [Figure 1a]. Multiple skin colored papules were seen on nasolabial fold [Figure 1b]. A fleshy, skin colored plaque was present in the perianal region [Figure 1c]. Nails showed multiple skin colored papules over nail folds. Multiple erythematous swellings and whitish crusting were noted on tips of fingers. Oral mucosa showed upper and lower gingival redness and hypertrophy in both siblings [Figures 1b and 2b]. Multiple subcutaneous, soft to firm, noncompressible, and nontender nodules were present over scalp [Figure 2a]. Multiple skin colored papules were present over nasolabial folds.

Figure 1.

Multiple subcutaneous nodules over scalp (a); multiple skin-colored papules were seen on nasolabial fold and upper and lower gingival redness and hypertrophy (b); and fleshy, skin-colored plaque was present in the perianal region (1c)

Figure 2.

(a) and upper and lower gingival redness and hypertrophy (b)

Both the siblings had anemia (hemoglobin – 9 g/dL). Skeletal survey in both the patients showed osteolytic lesions in bilateral medial aspect of proximal tibial metaphyses, medial, and humeral shaft. Dental and ophthalmological evaluations were normal. Gingival biopsy and biopsy of the retroauricular nodule showed unencapsulated ill-circumscribed lesion in the dermis composed of spindle shaped cells in a homogenous eosinophilic matrix in both the siblings [Figure 3a and b]. Alcian blue stain was positive [Figure 3c]. USG abdomen was normal except mild hepatomegaly in younger sibling. Genetic analysis of older sibling was found to have Antxr-2 on exon 14 variant C.1156 G>T (homozygous) mutation, which was pathogenic in nature. We could not do genetic analysis of the other patient and parents because of financial constraints. Final diagnosis of juvenile hyaline fibromatosis was made on the basis of cutaneous findings, histopathology, and genetic mutation. Parents were counseled about the disease and prognosis was explained. Perianal swelling and scalp tumors were excised in pediatric surgery department under general anesthesia.

Figure 3.

Histopathology from retroauricular nodule on hematoxylin and eosin staining showed unencapsulated ill-circumscribed lesion in the dermis composed of spindle shaped cells in a homogenous eosinophilic matrix at 4× (a) and spindleshaped cells in homogenous eosinophilic matrix at 10× (b). Alcian blue stain positivity was seen in (c)

In 1873, juvenile hyaline fibromatosis (JHF) was first reported by Murray as molluscum fibrosum; however, the term was given by Kitano in 1976.[2] JHF is common in consanguineous marriage as autosomal recessive mode of inheritance is the most common mode of inheritance (affecting siblings); however, sporadic cases are known to occur. Exact prevalence of juvenile hyaline fibromatosis is not known, approximately 70 cases have been reported worldwide and only few case reports are from India.[1] Mutation in CMG2/ANTXR2 gene has been described in ISH and JHF. JHF is believed to be a milder phenotype of ISH. Clinical manifestations begin in the first few months of the life.[3] The main manifestations of ISH and JHF are papular and nodular skin lesions around the nostrils and ears, and large subcutaneous nodules, mostly on the scalp, gingival hyperplasia, joint contracture, and various degrees of bone involvement. Osteolytic bone lesions are commonly observed in the distal phalanges, skull, and long bones. However, ISH is distinguished from JHF by the presence of visceral (intestinal, cardiac, hepatic, splenic, thyroid) involvement and a rapid fatal outcome.[3,4,5] The characteristic histological features of JHF include the presence of increased number of fibroblasts embedded in a hyalinized connective tissue stroma. The hyaline material is positive with special stains such as alcian blue.[1] Treatment is unsatisfactory. Therapeutic trials have been attempted with dimethylsulphoxide, and ketotifen for JHF without much improvement. Surgical excision of swellings remains the only treatment available in juvenile hyaline fibromatosis although recurrences are common.

Determination of the specific underlying mutation by genetics studies (CMG2/ANTXR2 in majority of cases) is important for family planning and counseling.

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Conflicts of interest

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