10. Pathology and Oncology MCQs

Which of the following describes the histopathology of tumoral calcinosis:

There have been no characteristic gene translocations or rearrangements noted in osteosarcoma, chondrosarcoma, neurofibrosarcoma, or epithelioid sarcoma. In contrast, Ewing’s sarcoma has been noted to have a consistent genetic translocation t(11:22).

This patient has widespread metastatic disease based on bone scan findings. Biopsy before intervention for pathologic lower-extremity fracture likely is not needed in a scenario with numerous bone lesions and pulmonary metastases. The absence of a clear primary tumor of origin suggests this is unlikely to be a renal cell carcinoma for which preoperative embolization would be considered before an intralesional procedure. Tissue should be obtained at the time of surgery. Although an SUV greater than 3 is suspicious for malignancy, activity on PET scan should not influence the need for biopsy in this scenario.

The imaging studies reveal an expansile lesion with the classic soap bubble appearance that involves most of the calcaneus. The bone scan reveals a very active lesion with intense uptake, and the MRI scans show the classic, loculated appearance of the lesion with multiple fluid-fluid levels. While it is important to rule out telangiectatic osteosarcoma, the most likely diagnosis is an aneurysmal bone cyst. While giant cell tumor might have a similar appearance, the multiple fluid levels in an expansile lesion strongly favor an aneurysmal bone cyst.

Transient osteoporosis is a self-limited painful but reversible disorder. Although first described in pregnant women, it is more common in young to middle-aged men. The radiograph shows loss of mineralization in the right hip relative to the left side. There is no osseous destruction or cortical expansion typical of metastasis or giant cell tumor. The process is confined to the femoral side of the joint unlike rheumatoid arthritis, which would be centered in the joint. Osteonecrosis is better defined with sharp but irregularly shaped margins, and there is no double-line sign. The MRI scans reveal diffuse edema in the femoral head and neck that is atypical for osteonecrosis. Transient osteoporosis may recur in the same or opposite hip.

DISCUSSION: The radiographs show a bone-producing lesion in the distal femoral metaphysis in this case of classic osteosarcoma presenting in the most common location, the distal femur. The coronal MRI scan reveals a marrow-occupying lesion with extension into the soft tissues. The histology shows osteoid production by pleomorphic cells consistent with an osteosarcoma. Ewing’s sarcoma is a bone tumor characterized by uniform small blue cells on histology. Rhabdomyosarcoma is the most common childhood soft-tissue sarcoma. Osteomyelitis has an inflammatory appearance on histology. Malignant fibrous histiocytoma of bone has a lytic radiographic appearance and a pleomorphic storiform pattern without osteoid on histology.

DISCUSSION: If the patient’s medical condition and prognosis remain good in the presence of significant and progressive neurologic deficit from cord compression, then the most reliable means of restoring function is via surgical decompression and fusion. Decompression should be directed toward the compressing structure (e.g., anteriorly if the compression is from the anterior side). This procedure can be done via a posterolateral technique, such as costotransversectomy in some cases.

Chemotherapy has no role in the treatment of which of the following tumors:

Findings in patients with McCune-Albright syndrome include polyostotic fibrous dysplasia, multiple cafe-au-lait spots, and precocious puberty. The bone changes in NF-1 resemble nonossifying fibromas, not fibrous dysplasia. NF-2 has little bony change with typical ocular abnormalities. Paget’s disease occurs in older individuals and does not present with cafe-au-lait spots. Ollier’s disease (multiple enchondromatosis) may show bone changes but not the other findings.

DISCUSSION: The use of multiagent chemotherapy has been shown to be associated with a survival benefit in patients with osteosarcoma. The use of chemotherapy in adults with soft-tissue sarcoma remains somewhat controversial. It has not been associated with improved survival rates in patients with renal carcinoma, dedifferentiated chondrosarcoma, or melanoma.

The radiographs show increased density and reactive bone formation. A faint nidus can be seen on the radiograph but is obvious on the CT scan. The initial therapy for an osteoid osteoma should be oral anti-inflammatory drugs. A biopsy or SPECT bone scan is not indicated because the osteoid osteoma is clearly seen on the CT scan. If the patient fails to respond to nonsurgical therapy, CT-guided radiofrequency ablation or surgical excision is indicated depending on the anatomic location.

A positive margin is most closely related to subsequent local recurrence. The other factors cited, including the size and site of the tumor, may be related to local recurrence; however, they are more commonly prognostic because of the difficulty in obtaining wide surgical margins about large or proximal tumors. Radiation therapy has been noted to decrease the incidence of recurrence but is not felt to be as important as the surgical margin. The grade of the tumor has more influence on the prevalence of metastatic disease than the incidence of local recurrence.

The lesion is a chondroblastoma. The plain radiographs show a well-defined radiolucent lesion in the distal femoral epiphysis of a skeletally immature patient. The margins are well defined, suggesting a benign growth. The epiphysis is an unusual location for bone tumors, except for chondroblastomas. Of all chondroblastomas, 95% are located within the epiphysis. The MRI scans show a punctate appearance that is commonly seen in cartilage lesions. The biopsy specimen shows a chondroid lesion with polygonal chondrocytes. These findings are consistent with a chondroblastoma. The natural history of chondroblastomas is for continued growth and bone destruction if left untreated. Treatment should consist of curettage, with or without the use of physical or chemical adjuvants, and bone grafting.

The findings are consistent with Ewing’s sarcoma. The radiographs reveal a lytic lesion in the diaphysis of the right fibula. There is elevation of the periosteum and evidence of a surrounding soft-tissue mass. The biopsy specimen shows diffuse small round blue cells surrounding the lamellar bone. It is the second most common malignant bone tumor in children. The most common treatment regimen consists of chemotherapy followed by surgical resection and/or radiation therapy. Surgical resection is employed when the lesion can be removed with wide margins and causes less morbidity than radiation therapy.

DISCUSSION: The plain radiographs show an eccentric metaphyseal lesion involving a long bone in a skeletally immature patient. The lesion is longer than it is wide, with distinctly lobular outer edges that are sclerotic. These findings are characteristic of a nonossifying fibroma. Small asymptomatic lesions may be followed clinically. Larger lesions that occupy greater than two thirds of the width of the shaft and are located in areas of high mechanical stress such as the femur are more prone to fracture than smaller lesions. Pain is often a sign of impending fracture or the presence of a small fracture that may not be apparent on radiographs. The natural history of the lesion is to resolve over a period of years. The procedure that would allow the patient to return to contact sports is curettage and bone grafting. Intralesional steroid injection has been advocated in the treatment of unicameral bone cysts and eosinophilic granuloma but not nonossifying fibromas. En bloc resection is not indicated for a benign lesion. Low-dose radiation therapy has been used for eosinophilic granuloma but not for nonossifying fibromas. REFERENCES: Walker RN, Green NE, Spindler KP: Stress fractures in skeletally immature patients. J Pediatr Orthop 1996;16:578-584. Arata MA, Peterson HA, Dahlin DC: Pathological fractures through non-ossifying fibromas: Review of the Mayo Clinic experience. J Bone Joint Surg Am 1981;63:980-988.

DISCUSSION: This is a case of synovial sarcoma. The radiograph shows some soft-tissue swelling in the upper arm. The MRI scans show a lesion that has increased signal on T2-weighted images and low signal on T1-weighted images. There is a suggestion of a large cystic component to this lesion. The pathology shows a biphasic population of cells, a spindle cell component, and an epithelioid component. Up to 20% of synovial cell sarcomas have areas of cyst formation. The most common cytogenetic translocation with synovial cell sarcoma is X; 18. The 11; 22 translocation is most commonly associated with Ewing’s sarcomas; the 12; 22 translocation is most commonly associated with clear cell sarcomas; the 2; 13 translocation is most commonly associated with alveolar rhabdomyosarcomas, and the 12; 16 translocation is most commonly associated with myxoid liposarcomas. REFERENCES: Kawai A, Woodruff J, Healey JH, et al: SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma. New Engl J Med 1998;338:153-160. Sandberg AA: Cytogenetics and molecular genetics of bone and soft tissue tumors. Am J Med Genet 2002;115:189-193.

Giant-cell tumor is the most common lesion involving the epiphysis, although its epicenter is usually in the metaphysis, and in the rare case of giant-cell tumor occurring in a skeletally immature patient, giant-cell tumor is located in the metaphysis. It also can involve the flat bone of the pelvis and sacrum. Chondroblastoma exclusively occurs in the epiphysis of skeletally immature patients. It is more common than the other responses. Although conventional chondrosarcoma does not involve the epiphysis, clear-cell chondrosarcoma involves the epiphysis as well; however, it is rare and less common than chondroblastoma. Aneurysmal bone cyst may occur in the epiphysis; however, it is often seen with other benign tumors such as chondroblastoma or giant-cell tumor. It is less common in this location than chondroblastoma. Osteoblastoma does not classically appear at the epiphysis. It is more commonly seen in the spine or the diaphysis of long bones.

In the initial assessment of acute low back pain in adults, no diagnostic testing is indicated during the first 4 weeks in the absence of “red flags” for a serious underlying condition. This patient has five “red flags” for a spinal tumor as a possible etiology of his low back pain, including age older than 50 years, constitutional symptoms (recent weight loss), pain worse when supine, severe nighttime pain, and a history of cancer. In the presence of “red flags” for tumor or infection, it is recommended that the clinician obtain a CBC count, ESR, and a urinalysis. If these are within normal limits and suspicions still remain, consider consultation or seek further evidence with a bone scan, radiographs, or additional laboratory studies.

This patient has a dedifferentiated liposarcoma within a preexisting atypical lipomatous tumor. The imaging demonstrates a large fatty mass with increased internal septations proximally (the atypical lipomatous tumor) and a solid enhancing mass distally (the dedifferentiated portion). A biopsy reveals a high-grade liposarcoma. Surgical treatment of a high-grade sarcoma involves wide surgical resection. Radiation decreases local recurrence but does not clearly influence overall survival. The role of chemotherapy in high-grade soft-tissue sarcomas remains investigational; there is a modest (8%-15%) associated improvement in overall survival.