10. Pathology and Oncology MCQs

Current treatment regimens for Ewing’s sarcoma typically involve induction chemotherapy followed by local control and further chemotherapy. Local control consists of surgery alone, radiation therapy alone, or a combination of the two. In bones that are easily resectable (or expendable) with wide margins, surgery alone is usually recommended. For areas that are unresectable (i.e., large, bulky pelvic tumors), radiation therapy alone is sometimes the preferred method of local control. If surgery is chosen and margins are close, radiation therapy can be used as an adjuvant. Amputation is rarely required for an isolated fibular lesion. Observation without adequate local therapy results in local recurrence.

Plasmacytoma is very sensitive to radiation therapy and given the complexity of the resection and complications of surgery in the given location, radiation therapy is preferred. However, the patient has clear loss of bony structural integrity, and resultant instability would persist even with tumor irradiation; therefore, posterior stabilization is warranted. Chemotherapy and bone marrow transplant are reserved for systemic disease with multiple myeloma.

The radiograph shows an aggressive destructive lesion. In this age group, and based on the anatomic location, a primary malignant tumor (osteosarcoma) is likely. Additional staging studies to identify metastatic disease are imperative prior to any biopsy. MRI of the femur helps to reveal skip metastasis and provides information regarding the anatomic location of the lesion. CT of the chest and a bone scan evaluate for distant metastatic spread. A bone scan is also useful in evaluating the extent of local bone activity about the lesion.

The patient has a solitary lesion that is at high risk for fracture. While metastatic lesions are most common in this age group, a stabilization procedure is contraindicated until results of a biopsy confirm the presence of a metastasis. Because of the lytic lesion and the associated calcification shown on the radiograph, the most likely diagnosis is a chondrosarcoma. Therefore, any type of stabilization procedure with a rod or plate would compromise a wide surgical excision to remove the entire proximal femur. Radiation therapy and chemotherapy are also contraindicated until biopsy results are obtained. Because of these factors, obtaining a frozen section biopsy specimen is considered the next most appropriate step in management. If a metastatic lesion is confirmed on the frozen section, a stabilization procedure could then be performed under the same anesthetic.

Which of the following soft tissue lesions has a characteristic reciprocal transformation between chromosomes 12 and 16:

Whereas chondrosarcoma is the most frequently occurring malignant bone tumor of the foot and synovial sarcoma is the most common soft-tissue foot malignancy, the most common malignant tumor overall is melanoma. It constitutes approximately 25% of lesions found on the lower extremity. Furthermore, 31% of all melanomas arise in the foot.

The finding of a unilateral absent pedicle is often referred to as a winking owl sign and is a manifestation of pedicle destruction from metastatic disease. As the vertebral body is destroyed from the neoplastic process, it extends into the pedicle and destroys the cortical rim that normally creates the oval ring of the pedicle on an AP image.

DISCUSSION: Soft-tissue sarcomas generally are treated with radiation therapy and wide surgical resection. In this patient, involvement of most of the posterior calf compartment and circumferential involvement of the posterior tibial and peroneal neurovascular bundle makes limb salvage impractical. Any attempt at wide surgical resection would leave a poorly functioning limb with questionable surgical margins. A high below-knee amputation would be the best option. Radiation therapy alone is contraindicated.

The radiograph and MR images show an osteoblastic lesion in the T9 and T8 vertebral bodies. In an older man, this finding most likely reveals metastatic prostate cancer. The first and least invasive diagnostic step is to order a PSA level. Gleave and associates found in a retrospective review of patients with prostate cancer that isolated levels of PSA lower than 10 to 20 micrograms per liter are rarely associated with bone metastasis. In a neurologically intact patient with no evidence of neural compression or instability, surgery is not indicated. Fine-needle aspiration may be performed, but the diagnostic yield in a blastic lesion is low. A bone scan may be indicated to complete the metastatic workup, but it will not aid in the diagnosis of tissue source.

The history, examination, and MRI scan findings are consistent with a midsubstance partial rupture of the rectus femoris muscle. This is an injury masquerading as a “pseudo tumor.” The lack of an appreciable mass effect on the T1-weighted MRI scan, the defined fluid signal on the T2-weighted scans, and the lack of significant contrast enhancement after gadolinium are all most consistent with injury rather than a neoplasm. Most of these injuries respond to nonsurgical management; a few will benefit from late debridement and repair if symptoms fail to resolve in 3 to 6 months. The treatment of choice is nonsurgical management with a follow-up MRI scan to verify that the findings are resolving.

It is important to remember that this condition is autosomal dominant. The putative tumor suppressor gene mutations are EXT1 or EXT2. The risk of low-grade chondrosarcoma occurring in this condition is approximately 10%.

DISCUSSION: The five most common primary carcinomas that metastasize to bone are breast, prostate, lung, renal, and thyroid in decreasing order of incidence. REFERENCES: Frassica FJ, Gitelis S, Sim FH: Metastatic bone disease: General principles, pathophysiology, evaluation, and biopsy. Instr Course Lect 1992;41:293-300. CA, January/February 2000, vol 50, no. 1 (Cancer Statistics).

Cytogenetics best demonstrates the 11;22 translocation characteristic of Ewing’s sarcoma. The translocation also can be detected with polymerase chain reaction and fluorescent in situ hybridization. The Ewing antibody is used for immunostaining to check for cell membrane (surface) staining of a marker unrelated to the translocation; this could also help distinguish Ewing’s sarcoma from small cell osteosarcoma. A bone scan will show increased uptake with both types of tumors. Although most Ewing’s sarcoma tumors are diploid, some are polyploid as are most osteosarcomas. Flow cytometry is used to sort cells, sometimes based on antibody binding. LDH can be elevated in both Ewing’s sarcoma and osteosarcoma and is a poor prognostic indicator when elevated. Lymph node metastases are uncommon in both of these tumors.

The radiographs show the characteristic features of osteopetrosis. The condition results from defective resorption of immature bone by osteoclasts. There are three distinct clinical forms: (1) infantile-malignant, which is autosomal recessive and fatal in the first few years of life if untreated; (2) intermediate autosomal recessive; and (3) autosomal dominant. These conditions do not follow a malignant course, and patients have normal life expectancy with orthopaedic problems and anemia. In the malignant form, the clinical features include frequent fractures, macrocephaly, progressive deafness and blindness, hepatosplenomegaly, and severe anemia beginning in early infancy or in utero. The anemia is caused by encroachment of bone on marrow, resulting in obliteration, and the hepatosplenomegaly is caused by compensatory extramedullary hematopoiesis. Dental caries and abscesses, as well as osteomyelitis of the mandible, are also seen. Most patients have normal intelligence. Treatment of the malignant form includes high dose 1,25 dihydroxy vitamin D with a low-calcium diet to stimulate bone resorption, not because there are vitamin deficiencies.

The imaging studies show a permeative lytic destructive lesion in the proximal radius with “hair-on-end” periosteal reaction and a large soft-tissue mass most consistent with Ewing’s sarcoma. The pathology reveals monotonous sheets of “round blue” cells. This limits the differential diagnosis to primary lymphoma of bone versus Ewing’s sarcoma. These are best differentiated by immunohistochemistry, cytogenetics, and flow cytometry. Lymphoma of bone is typically CD34 positive and CD99 negative; whereas, the reverse is true of Ewing’s sarcoma, CD34 negative and CD99 positive. The most common cytogenetic translocation with Ewing’s sarcoma is (11; 22) (q24; q12).

Discussion: Squamous cell carcinoma is the most common type of malignant tumor deriving from chronic osteomyelitis. The most frequently affected site is the tibia, followed by the femur. When the neoplasm invades the bone, there is either osteolytic erosion or a pathological fracture. Diagnosis is confirmed by biopsy at all suspicious wound sites. The malignant transformation most often results in squamous cell carcinoma and much more rarely in fibrosarcoma, osteosarcoma, reticulosarcoma, malignant fibrous histiocytoma or angiosarcoma. Many experts accept amputation as the best treatment option for carcinomatous transformation of chronic bone infections.

For the fibula (or any bone) to bow, a long-standing process needs to be present. Pressure from a rapid process would cause erosion, not allowing the bone to remodel. The other features are helpful confirmatory findings but also may be associated with aggressive processes. In this patient, the fibular deformity is caused by a sessile osteochondroma of the tibia.

Nonsurgical modalities remain the mainstay for treatment of herniated disks. Spontaneous resorption of herniated disks frequently is detected by MRI. Marked infiltration by macrophages and neovascularization are observed on histologic examination of herniated disks, and the resorption is believed to be related to this process.

DISCUSSION: The imaging studies reveal a predominantly blastic lesion in the distal femur with posterolateral periosteal changes. The bone scan shows increased uptake in the distal femur, beyond that expected with radiography. Cross-sectional imaging confirms the presence of a soft-tissue mass extending from the lateral aspect of the femur, with diffuse intramedullary signal changes. This aggressive presentation, particularly in this location and in a patient of this age, is most consistent with osteosarcoma. The mineralization in the soft tissue strongly suggests neoplasm, not the reactive bony changes seen in an infectious process.