Osteoblastoma

Not clinically relevant

Rearrangement of FOS has been identified in both osteoblastomas and osteoid osteomas, further strengthening the link between these two lesions. The rearrangement is present in 87% of the cases. The breakpoints in FOS cluster to exon 4, which is fused to introns of other genes or intergenic regions. The resulting transcript lacks regulatory elements, similar to the v-Fos retroviral oncogene. FOS is a member of the AP-1 family of transcription factors, increased levels of which can promote cell growth. FOS rearrangements can be detected at the protein level using an antibody against the FOS N-terminus, which results in nuclear immunoreactivity in the osteoblastic cells. In a smaller percentage of cases, FOSB rearrangement has been detected. Whole-genome DNA sequencing analysis performed in osteoblastomas shows diploid tumor cells with few other somatic alterations. Previously, karyotypic abnormalities such as rearrangement of chromosome 13 and deletions on chromosome 22 have been reported; these activate the WNT/β-catenin signaling pathway.

Macroscopically, osteoblastomas are usually red to tan lesions, reflecting their intense vascularity. Bone expansion with marked cortical thinning or surrounding areas of sclerosis may be seen. The borders are usually well defined. Blood-filled cystic spaces (aneurysmal bone cyst change) may be present.

Osteoblastomas are microscopically similar to osteoid osteomas. Osteoblastomas are characterized by interconnecting, delicate, woven bone trabeculae, usually rimmed by a single layer of polygonal osteoblasts. The trabeculae may show different levels of mineralization, from osteoid to densely mineralized woven bone that shows multiple cement lines (pagetoid appearance). The stroma is loose and usually richly vascularized, with dilated capillary-type blood vessels. Osteoclast-like giant cells are scattered throughout the tumor. Lace-like osteoid deposition, although uncommon, can be present, as can cartilaginous differentiation. The borders are usually well defined, often showing peripheral bone maturation towards lamellar bone. Destructive host bone permeation should not be seen, and it is possibly the most reliable histological feature in differentiating osteoblastoma from osteoblastoma-like osteosarcoma. Atypical mitotic figures should be absent. The diagnosis of so-called aggressive osteoblastoma is controversial and not recommended. This entity was initially reported with a more aggressive clinical course and morphologically characterized by the presence of large, epithelioid osteoblasts (twice the size of normal osteoblasts) that are frequently mitotically active. However, the presence of epithelioid osteoblasts does not seem to predict an aggressive clinical course in osteoblastoma; therefore, the term “epithelioid osteoblastoma” is preferred. Rarely osteoblastomas may show degenerative atypia, which should not be mistaken for malignancy.

Not clinically relevant

The prognosis is good, but recurrences are described in as many as 23% of the cases, more frequently in patients treated with curettage than with en bloc resection, with which a 14% recurrence rate is reported. Although osteoid osteoma and osteoblastoma may be morphologically indistinguishable, and they may in fact be different clinical manifestations of the same disease, an attempt to differentiate these tumor types is justified by the tendency for clinical progression and recurrence seen in the latter. Epithelioid osteoblastoma was initially reported with a more aggressive clinical course and morphologically characterized by the presence of large, epithelioid osteoblasts that are frequently mitotically active. The presence of epithelioid osteoblasts does not consistently predict an aggressive clinical course in osteoblastoma. Conversely, some osteoblastomas > 4 cm with locally destructive features and repeated recurrences may lack epithelioid cytomorphology. Rare cases of malignant transformation are described.

FOS gene rearrangement or rarely FOSB gene rearrangement is found in the majority of osteoblastomas.

Essential: bone tumor with compatible imaging; radiological demonstration of a > 2 cm lesion; well-defined tumor borders, absence of host bone permeation; bone-forming tumor composed of trabeculae of woven bone rimmed by plump osteoblasts in a vascularized stroma.