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Main differential diagnosis
Juxtacortical myositis ossificans is composed by a spindle-cell proliferation admixed with woven bone
that exhibits a zonation pattern of progressive maturation toward the periphery of the lesion. The spindle
cell component is similar to that seen in nodular fasciitis, characterized by non-cohesive, plump, spindle-
shaped cells reminiscent of tissue culture; instead of the long fascicles present in parosteal osteosarcoma.
[37]
MDM2 amplification is absent in myositis ossificans, while rearrangement of USP6 can be detected .
Desmoplastic fibroma and fibrous dysplasia are also characterized by hypocellular fascicles of bland
spindle cells in a collagenous background but lack the bone trabecula seen in parosteal osteosarcoma. In
ambiguous situations, they can be confidently separated from parosteal osteosarcoma by the absence of
MDM2 amplification or MDM2 nuclear immunostaining.

Osteoma affects almost exclusively bones formed by membranous ossification, thus locations outside the
craniofacial bones and jaws, where this entity might constitute a diagnostic differential, are extremely rare.
Osteoma contains cortical-type bone and lacks the fascicles of spindle cells seen in parosteal osteosarcoma.

Up to a fourth of bizarre parosteal osteochondromatous proliferation (BPOP) may arise in long tubular
bones [38-40] , a location where it must be distinguished from parosteal osteosarcoma. The latter is exceedingly
rare in small tubular bones of hands and feet, which are the sites of predilection of BPOP.

BPOP are smaller lesions measuring from a few millimeters up to 3 cm. BPOP has a zonal architecture,
absent in parosteal osteosarcoma, comprised by an admixture of cancellous bone, aggregates of cartilage
and fibrous tissue. Characteristically in BPOP, an irregular zone of endochondral ossification and
calcification, characterized by the presence of so-called “blue bone” is present in the interface between
cartilage and bone.

Dedifferentiated parosteal osteosarcoma can be distinguished from periosteal and high-grade surface
osteosarcoma by the presence of a low-grade spindle-cell component and MDM2 amplification in
dedifferentiated parosteal osteosarcoma.

Treatment and prognosis
Parosteal osteosarcoma is a locally aggressive tumor with limited potential for distant spread. Hence,
surgical resection with adequate margins is the treatment of choice. Chemotherapy is reserved for
dedifferentiated paraosteal osteosarcomas. The incidence of local recurrences has been demonstrated to be
[41]
strictly related to the adequacy of surgical margins .
The prognosis of parosteal osteosarcoma is excellent. Long-term survival rate for this entity is at least
90%. Nevertheless, it possesses a risk of transformation into an intermediate or high-grade sarcoma
[42]
(dedifferentiation), either at first diagnosis or after recurrences, estimated to occur in between 14% and
24% of cases [29,30] . Dedifferentiation confers a significantly worse prognosis to parosteal osteosarcomas,
diminishing overall survival and equating it to that of conventional high-grade osteosarcomas [29,43] .

Periosteal osteosarcoma
Definition and clinical features
Periosteal osteosarcoma is an intermediate grade, mainly chondroblastic, bone-producing sarcoma that
[2]
arises on the surface of bone beneath the periosteal layer . It is rare, accounting for less than 2% of all
osteosarcomas [1,27,44,45] . It mostly affects children, adolescents and young adults with a peak incidence in
the second decade of life . The most common sites of involvement are the diaphysis of the tibia and the
[1]
femur [1,27,44,46] , but other long bones of extremities and much less frequently, flat bones, can be involved [1,44] .