Fibrous hamartoma of infancy: a clinicopathologic study of 145 cases, including 2 with sarcomatous features

Fibrous hamartoma of infancy is a rare soft tissue lesion of infants and young children with characteristic triphasic morphology, which typically occurs in the axilla and less commonly in other locations. We reviewed 145 cases of fibrous hamartoma of infancy from our consultation archives. Cases occurred in 106 males and 39 females (mean age-15 months; range birth to 14 years), and involved both typical sites (eg, axilla/back/upper arm) (n=69) and unusual locations (n = 76). Six were congenital. The tumors presented as subcutaneous masses and ranged from 0.4 to 17 cm (mean 3 cm). All displayed triphasic morphology, but varied widely in the relative percentages of fat, fibroblastic fascicles, and primitive mesenchyme. Hyalinized zones with cracking artifact, mimicking giant cell fibroblastoma, were present in a 44 (30%) of cases; however FISH for PDGFB gene rearrangement was negative in five tested cases. In addition to classical fibrous hamartoma of infancy, two lesions contained large sarcomatous-appearing foci with high cellularity, high nuclear grade, and brisk mitotic activity. One occurred in a 10-month-old female as a new mass in a congenital fibrous hamartoma of infancy; the other occurred as a leg mass in a 6-year-old male. ETV6 gene rearrangement was negative in the tumor from the 10-month-old female. Genomic microarray (OncoScan) showed normal molecular karyotype in eight tested cases, whereas the two tumors with sarcomatous features showed a hyperdiploid/near tetraploid molecular karyotype with copy neutral loss of heterozygosity of chromosomes 1p and 11p, and loss of 10p, chromosome 14, and a large portion of chromosome 22q (22q11.23q13.33), respectively. Follow-up (52 patients; range: 1-208 months, median: 8 months) showed only two local recurrences and no metastases. Extensive local disease in the 10-month-old female with sarcomatous-appearing fibrous hamartoma of infancy necessitated forequarter amputation. In summary, our study confirms the classic clinicopathologic features, including the triphasic morphologic appearance of most cases. In contrast to earlier studies, our series illustrates a broader histologic spectrum than previously appreciated, including its close resemblance to giant cell fibroblastoma in one quarter of cases and the rare presence of 'sarcomatous' areas, the latter providing evidence that these are complex neoplasms rather than hamartomas.