USP6 Gene Rearrangement by FISH Analysis in Cranial Fasciitis: A Report of Three Cases

Abstract

Cranial fasciitis (CF) is an uncommon benign myofibroblastic proliferation involving the soft and hard tissues of the cranium. It typically occurs in the pediatric population with a male predilection (male-to-female ratio 1.5:1). The clinical presentation is usually a rapidly expanding, painless nodule. Bone erosion may be appreciated radiographically. Histopathologic sections of CF show plump, fibroblast-like cells with pale, oval shaped nuclei and prominent nucleoli in a fibrous or myxoid background. Growth is self-limited and surgical excision is considered curative. Due to these features, CF is thought to be a variant of nodular fasciitis (NF). As with NF, CF may mimic a sarcomatous process and pose a diagnostic challenge to clinicians and pathologists alike. Erickson-Johnson et al. identified rearrangements of the ubiquitin-specific protease 6 (USP6) gene in 44 of 48 cases of NF. MYH9 was the fusion partner in 12 of these cases. To date, the molecular profile of CF has not been studied. Here we present the molecular findings in three cases of CF identified at our institution. Each case was subjected to fluorescence in-situ hybridization with appropriate negative controls. Two of three cases were positive for the USP6 gene rearrangement. The third case failed to hybridize, likely related to nucleic acid damage secondary to decalcification. Negative controls did not demonstrate the genetic rearrangement. These findings warrant further investigation of the USP6 gene rearrangement in CF, as it may prove helpful as a diagnostic adjunct in challenging cases.

USP6-Associated Neoplasms: A Rapidly Expanding Family of Lesions

“…Several subtypes of NF are recognized, the most important being intravascular fasciitis and cranial fasciitis, the latter predominantly reported in infants under 2 years of age. 34 Morphologically, NF is usually a circumscribed lesion, often presenting with focal infiltrative growth and composed of plump myofibroblastic cells that may show slight cytonuclear atypia without hyperchromasia or pleomorphism. A worrisome feature may be the presence of brisk mitotic activity.…”

“…Since detection of the rearranged USP6 in NF, this entity has been reported at several extraordinary sites, such as the breast parenchyma, 44 the placenta, 45 the periosteum of the mandible, 46 the soft tissue of the orbit, 47 the vulva, 48 the parotid gland, 49 intra-articular in the knee, 50 the soft tissue of the cranium (eg, cranial fasciitis), 34,40 and the skin. 51,52 The differential diagnosis of NF includes benign as well as malignant mesenchymal lesions.…”

A NovelCOL1A1-CAMTA1Rearrangement in Cranial Fasciitis

“…25 USP6 gene rearrangement was reported in 2 cases of cranial fasciitis. 26 Our case suggests that COL1A1-CAMTA1 translocation is present in a subset of cranial fasciitis and may be helpful in the differential diagnosis.…”

Fusion of the Lumican (LUM) Gene With the Ubiquitin Specific Peptidase 6 (USP6) Gene in an Aneurysmal Bone Cyst Carrying a t(12;17)(q21;p13) Chromosome Translocation

“…Apart from aneurysmal bone cyst, USP6 activation by promoter-swapping gene fusion has also been found in nodular fasciitis, cranial fasciitis, and myositis ossificans (38)(39)(40)(41)(42)(43)(44)(45). Furthermore, USP6 rearrangements were detected in a subset of cellular fibromas of tendon sheath which share similar histological features with nodular fasciitis (46).…”