10. Pathology and Oncology MCQs

DISCUSSION: The biopsy specimens reveal a high-grade spindle cell lesion adjacent to an area of benign cartilage. This is consistent with a dedifferentiated chondrosarcoma. The radiograph shows a pathologic fracture through a lesion characterized by calcification within the left greater trochanter. Distal to the area of calcification, there is a more osteolytic, destructive appearance. Synovial sarcoma has a biphasic appearance histologically with areas of glandular differentiation that stain positive with keratin. Metastatic prostate cancer, although osteoblastic in appearance, would have a glandular histologic appearance. There is no cartilage in these lesions. Classic low-grade chondrosarcoma does not have an area of high-grade pleomorphic spindle cells within the lesion. A periosteal osteosarcoma is a surface-based lesion with a sunburst radiographic pattern. Although there may be cartilage in the lesion histologically, there are also malignant cells producing osteoid. Dedifferentiated chondrosarcoma is an aggressive, high-grade variant of chondrosarcoma.

DISCUSSION: Angiosarcoma is a locally aggressive sarcoma. The radiograph shows extensive multiple discontinuous lesions throughout the entire tibia. The extent of bone involvement precludes resection; therefore, the treatment of choice is amputation, either above the knee or through the knee. Radiation therapy is not needed after amputation, and chemotherapy remains investigational for soft-tissue sarcoma. REFERENCE: Simon MA, Springfield DA: Surgery for Bone and Soft Tissue Tumors. Philadelphia, PA, Lippincott-Raven, 1998, ch 29.

The radiographic appearance of the lesion emanating from the posterior cortex of the left distal femur is consistent with a surface bone-producing lesion; therefore, the most likely diagnosis is a parosteal osteosarcoma. In an osteochondroma, the cortex and medullary cavity of the lesion are in continuity with that of the native bone. A dedifferentiated chondrosarcoma has histologic components of a high-grade sarcoma plus a benign or low-grade malignant cartilage tumor. Tumoral calcinosis is characterized by amorphous calcium in the soft tissues and does not emanate from the bone itself. While often confused with parosteal osteosarcoma, myositis ossificans is usually more mature at the periphery of the lesion rather than the center. In addition, myositis ossificans does not involve the underlying cortex but remains separate from the bone.

Idiopathic osteonecrosis of the medial femoral condyle occurs predominantly in women older than age 60 years. It is characterized by pain centered in the medial anterior aspect of the knee, and onset is sudden. Flattening, sclerosis, and the radiolucent crescent sign are radiographic indicators of osteonecrosis. The radiographs show no narrowing of the joint space or osteophyte formation to indicate osteoarthritis, and there are no loose bodies to indicate synovial osteochondromatosis. A meniscal tear is not consistent with the radiographic findings shown here. Meniscal tears can coexist with osteonecrosis, but the pain is not eliminated merely by partial meniscectomy. Metastatic lesions to the distal femoral epiphysis are exceedingly rare.

Also known as Nora’s lesion, BPOP is a benign osteocartilaginous tumor that almost always occurs in the hands and feet; one occurrence each in the femur and tibia has been reported. Although local recurrence is common after excision, metastases have not been reported.

The incidental finding in the posterior intercondylar notch of the knee in this patient represents a benign synovial hemangioma. No intralesional calcifications are shown either on the plain radiographs or CT scan. The MRI scans reveal a hypervascular lesion with multiple filling defects, with hyperintensity on T2-weighted images and low to intermediate signal intensity on T1-weighted images. Histologically, vascular lakes within fine capillaries with a synovium on the surface of the lesion are characteristic of this condition. Many patients with synovial hemangioma present with pain, swelling, stiffness, or mechanical symptoms. As with PVNS, the disease can be localized or diffuse in nature. Surgical excision, either open or arthroscopic, is the recommended treatment.

Osteofibrous dysplasia frequently presents at a very young age, usually less than 10 years. In most patients, it involves the anterior cortex of the tibial shaft and minor anterior bowing of the tibia is frequently seen. The lesion is unpredictable in nature, but local recurrence is very high in patients who undergo surgery before 15 years of age.

The figure shows a supracondylar process, which is a normal anatomic variant. An osteochondroma tends to occur more toward the end of bones, and the medullary space of the underlying bone extends into the base of the osteochondroma. The presence of a supracondylar process is usually asymptomatic.

To date, only the percent of necrosis after induction chemotherapy in high-grade osteosarcomas seems to be of prognostic value. The value in soft-tissue sarcoma and rhabdomyosarcoma is being evaluated but has not been substantiated. Chondrosarcomas and parosteal osteosarcomas are not treated with chemotherapy.

The use of bisphosphonates has been recently associated with the development of osteonecrosis of the jaw. Length of exposure seems to be the most important risk factor for this complication. The type of bisphosphonate may play a role and previous dental procedures may be a precipitating factor. Bisphosphonates are a class of therapeutic agents originally designed to treat loss of bone density (ie, alendronate). The primary mechanism of action of these drugs is inhibition of osteoclastic activity, and it has been shown that these drugs are useful in diseases with propensities toward osseous metastases. In particular, they are effective in diseases in which there is clear upregulation of osteoclastic or osteolytic activity, such as breast cancer and multiple myeloma, and have developed into a mainstay of treatment for individuals with these diseases. Although shown to reduce skeletal events, there has been no improvement in patient survival.

This patient has a septic distal interphalangeal joint, which was treated with antibiotics alone. As a result, the patient developed osteomyelitis with bone destruction and abscess. The best way to treat this problem is to perform surgical débridement of bone and soft tissue, along with abscess drainage and an appropriate antibiotic regimen. Antibiotic treatment without surgery would not be successful in eliminating this particular infection. Bone scan with biopsy is not the correct option, because this problem is an infection and not a tumor, and MRI already has provided enough diagnostic information.

Histologic grade, the presence or absence of metastatic disease, and tumor size are important prognostic factors. Of the available choices, however, the size of the sarcoma is the most important prognostic indicator. A tumor size of greater than 5 cm is a more important prognostic factor than tumor location. Patients with sarcomas that measure 5 cm or less have nearly identical 3-year survival rates regardless of whether the tumor is subcutaneous or deep.

DISCUSSION: The radiographs reveal a geographic, diaphyseal lesion with very subtle cortical expansion, cortical thinning, relatively sharp demarcation, and angular rather than rounded borders, suggesting a fibrous bone lesion. This lesion demonstrates the classic ground glass appearance of fibrous dysplasia. Ewing’s sarcoma, metastases, and aneurysmal bone cyst all typically have a more aggressive appearance.

DISCUSSION: A core needle biopsy can easily be performed in an outpatient setting or with image guidance to aid in the diagnosis. Core needle biopsies preserve the architectural relationship of cells, which is important in the diagnosis of mesenchymal lesions. A core needle biopsy is appropriate for soft-tissue lesions and osseous lesions and should be performed in a multidisciplinary setting with a surgeon performing the resection so unnecessary compartmental contamination is not introduced into the needle tract.

siRNA functions by causing mRNA to be broken down after transcriptions, resulting in an inability to undergo translation.siRNA are short (usually 20 to 24-bp) double-stranded RNA (dsRNA) sequences with phosphorylated 5' ends and hydroxylated 3' ends. Because of their ability to block a gene of interest, they have been generating interest in the treatment of disease processes that involve gene expression.Noh et al. study the affects of PD98059, an extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor, on osteosarcoma. They found that blocking the ERK1/2 pathway with PD98059 induces osteosarcoma cell death by inhibiting a potential drug-resistance mechanism.Illustration A shows how siRNA works to block translation of mRNA. Incorrect Answers:

Based on the epiphyseal location and sharp, well-defined borders, the radiograph suggests chondroblastoma. Histologically, multinucleated giant cells are scattered among mononuclear cells. The nuclei are homogenous and contain a characteristic longitudinal groove. Although not seen here, “chicken-wire calcification” with a bland giant cell-rich matrix is also typical for chondroblastoma. Clear cell chondrosarcoma occurs in epiphyseal locations but has a more aggressive histologic pattern and occurs in an older age group. Giant cell tumors occur in the epiphysis but have a more uniform giant cell population histologically. Aneurysmal bone cyst often results in bone remodeling and has a different pathologic appearance. Osteonecrosis has a typical histologic pattern of empty lacunae and necrotic bone.

DISCUSSION: Pigmented villonodular synovitis often presents with intermittent swelling and minimal pain. It often occurs around joints but may be found around tendon sheaths and bursal linings. Periarticular erosions involving both sides of joints are typical, and multiple joint involvement has been described. Portions of low-signal intensity on T1- and T2-weighted images are characteristic of hemosiderin-laden processes. High-signal content is suggestive of high water content. The combination of low-signal intensity areas in intra-articular lesions with or without osseous destruction is diagnostic of pigmented villonodular synovitis. Aspiration reveals bloody or brownish fluid. The treatment of choice is synovectomy performed arthroscopically or open. Recurrence is common.

DISCUSSION: Ewing’s sarcoma typically occurs in the major long tubular bones, with the femur the most common location. The flat bones of the pelvis are the second most common location. Ewing’s sarcoma occurs in the fibula but with a lower incidence than that seen in the major tubular bones. Ewing’s sarcoma infrequently occurs in the metacarpals or the vertebral bodies.