Published Works: Malignant
Tumors Arising in Pre-existing
Malignant Tumors Arising in Pre-existing Conditions
of Bone
The majority of primary malignant bone tumors originate in normal-appearing
bone. Malignant tumors arising in benign preexisting lesions of bone are rare.
The association of certain conditions with sarcomatous transformation has been
well documented.
Malignant transformation describes a process whereby the cells have lost their
histologic differentiation, resulting in increased anapalsia and increased mitotic
rate to become a malignant tumor. Such malignant processes have been noted in
bone, Paget’s disease, infarct, radiation osteitis, osteochondromatosis,
enchondromatosis, and less frequently in chronic osteomyelitis, fibrous dysplasia,
synovial chondromatosis, osteoblastoma, giant cell tumor, and chondroblastoma.
In a long-standing indolent process such as bone infarct, the primary lesion
is surrounded by a reparative process and it is possible that malignant transformation
occurs in these areas of reparative activity.
Malignant transformation is seen in adult patients who have a long-standing
history of preexisting conditions. Adult patients who have one of the above
underlying conditions and who present with a change in the clinical course with
a rapid onset of pain, swelling, and constant change in the appearance of the
radiographic features should be suspected of having malignant transformation.
Early recognition and treatment are of vital importance.
Sarcomatous
Transformation
Bone Infarct
Sarcomas arising in bone infarcts are extremely rare. Such events are seen in
middle-aged patients in whom the bone infarct has been present for many years.
Such cases have been reported in patients with idiopathic bone infarct, sickle
cell disease, and in caisson workers. Histologically, the sarcomatous process
in most of the cases is malignant fibrous histiocytoma followed by osteosarcoma
and fibroscarcoma.
Paget's Disease
The most serious and devastating complication of Padget’s disease is the
development of sarcomatous transformation. The incidence of sarocomatous change
varies in different reports. It is estimated to be under 1 percent. Osteosarcoma
is the most common histological type. Paget’s sarcoma is very rare in
patients under the age of 50 years. The majority of the patients are in their
sixth and seventh decades. Males are affected more often than females. Sarcomatous
change is more commonly seen in patients with polyostotic Paget’s disease.
The most common anatomical sites are the femur, humerus, pelvis, and cranium.
Radiographically, the sarcomatous change could be lytic, blastic, or mixed type.
The average duration of symptoms before diagnosis is about 6 months. The presenting
symptoms are pain and swelling. The overall prognosis of Paget’s sarcoma
is poor with a short life expectancy. In most cases, surgical extirpation is
only palliative, and radiotherapy and chemotherapy do not change the clinical
course.
Radiation Induced
Sarcoma
Radiation is associated with a variety of skeletal complications. The most devastating
complication is radiation-induced sarcoma. Malignant fibrous histiocytoma is
the most common histologic type. The criteria for radiation-induced sarcoma
are: (1) the involved bone should be included in the radiation field; (2) there
should be a latent period of several years, at least 3 to 4 years; and (3) histologic
verification of sarcoma.The mean latent period until sarcomatous change in adults
is about 16 years. A shorter mean latent period of 9.6 has been reported in
children. Postradiation sarcomas are very aggressive with high rates of metastases
and shorter life expectancy.
Chronic
Osteomyelitis
Squamous cell carcinoma is known to occur in chronic draining sinuses of osteomyelitis.
This complication is reported to occur in less than 0.5 percent of cases of
chronic osteomyelitis. Pain and swelling with progressive radiographic changes
should alert the clinician to the possibility of malignant change.
Osteochondroma
and Osteochondromatosis
It appears that the risk of malignant change in osteochondroma has been grossly
overestimated. The wide range of incidence reported is probably related to the
different age group distribution and different histologic criteria. A realistic
incidence of malignant change for solitary osteochondroma is less than 1 percent
and for multiple osteochondromatosis is less than 5 percent. The risk of malignant
change increases with larger lesions and with lesions which are localized closer
to the axial skeleton such as the pelvis and spine. The average age of sarcomatous
change is usually beyond the third decade of life. Malignant change should be
suspected whenever one of the following criteria is present: (1) osteochondroma
that continues to grow after the second decade of life; (2) large cartilage
cap over 2 cm in patients beyond the second decade of life; (3) scattered peripheral
calcification embedded within the cartilaginous cap; and (4) permeation of adjacent
bone. Histologically, most chondrosarcomas arising in osteochondromas are low-grade
malignancy and have a favorable prognosis and low metastatic rates.
Enchondroma
and Enchondromatosis
The rate of transformation of enchondroma to chondrosarcoma varies from center
to center. Unni from the Mayo Clinic is very skeptical about such a possibility
of sarcomatous change. Huvos maintained that occasionally a chondrosarcoma may
arise in a preexisting enchondroma. Mirra speculated that about half of all
central chondrosarcomas originated from preexisting enchondroma. In our experience
the rate of malignant transformation is very low. The distinction between cellular
enchondroma and low-grade chondrosarcoma presents a significant diagnostic problem
to the bone pathologist. Clinically, insidious pain with progressive radiographic
change such as endosteal scalloping raises the possibility of malignant transformation.
Histologically, permeation of tumor into the marrow spaces and preexisting bone
is the most important criterion to establish the diagnosis for chondrosarcoma.The
incidence of chondrosarcoma arising in enchondromatosis (Ollier’s disease)
is much higher and is estimated to be 10 to 30 percent during a lifetime. The
average age of these patients is 40 years. In most cases, the chondrosarcoma
is of low-grade malignancy. The prognosis for chondrosarcoma is directly related
to the histologic grade; low grade tumors have a good prognosis.
Fibrous Dysplasia
Sarcoma arising in fibrous dysplasia is extremely rare. So far, over 100 cases
have been reported. Approximately, one-third of these patients received radiation
therapy prior to the development of the sarcoma. The diagnosis of low-grade
central osteosarcoma always should be ruled out before making the diagnosis
of sarcomatous transformation. The histologic type in most cases is osteosarcoma
followed by fibrosarcoma. The prognosis is poor.
Synovial
Chondromatosis
Chondrosarcoma arising in synovial chondromatosis is extremely rare. So far,
only 20 cases have been reported. Most patients had a prolonged history of synovial
chondromatosis with an interval of at least 10 years and multiple surgical procedures.
In both conditions (synovial chondromatosis and chondrosarcoma arising in synovial
chondromatosis) the clinical presentation is similar, namely pain, swelling,
loss of range of motion, and multiple previous surgical procedures. The diagnosis
should be based on the histologic findings. Histologically, chondrosarcoma arising
in synovial chondromatolosis should demonstrate chondrocytes which have lost
their clustering pattern, myxoid changes of the matrix, necrosis, and spindling
of the cells.
Giant Cell Tumor
Lung metastases in histologically benign giant cell tumor is seen in less than
2 percent of the cases. Those metastatic lesions should not be confused with
malignancy and should be described as deposits of benign tumor cells in the
lung. They are self-limited in their growth potential and in most cases remain
static and may even regress spontaneously. Malignant giant cell tumor without
an antecedent history of radiation is extremely rare. The tumor can be malignant
at the initial presentation, or malignancy may occur at the side of a previously
documented benign giant cell tumor.
Chondroblastoma
Sarcoma arising in chondroblastoma is extremely rare. Only rare cases have been
reported without previous irradiation. Lung metastases have been reported in
histologically benign chondroblastoma. Those should not be confused with malignancy.
They are self-limited in growth and carry and excellent prognosis.
Osteoblastoma
Osteoblastoma is rare, benign bone-forming tumor. It is estimated that local
recurrence following intralesional curettage occurs in 10 percent of the cases.
Cases of aggressive osteoblastoma have been reported. Aggressive osteoblastoma
histologically demonstrates increased cellularity with large epithelioid osteoblasts,
but the presence of these cells does not necessarily indicate aggressive behavior.
The distinction between aggressive osteoblastoma and osteoblastoma-like osteosarcoma
is very difficult even for an experienced bone pathologist. There are a few
well-documented cases of osteoblastoma that after multiple local recurrences
transformed to osteosarcoma.
