10. Pathology and Oncology MCQs

The radiographs show a bone-producing lesion in the femoral diaphysis. The radiographic appearance of small round cell tumors is more permeative with an elevated periosteum and no matrix production. The appearance of this lesion is most consistent with osteosarcoma. Patients who carry the Rb gene are predisposed to osteosarcoma.

The histology shows eosinophils with a background of larger cells (Langerhans’ cells). This is consistent with eosinophilic granuloma. Localized sites are best treated with curettage, steroid injection, or observation. Chemotherapy is used only if there is systemic involvement.

The histologic appearance of the soft-tissue lesion reveals compact nests of cells with a clear cytoplasm surrounded by a delicate border of fibrocollagenous tissue. There can be scattered multinucleated giant cells. This is consistent with a clear cell sarcoma, also called malignant melanoma of soft parts. This tumor is usually positive for S-100 and HMB45 (a melanoma-associated antigen). These tumors are frequently found around the foot and ankle. Similar to epithelioid sarcoma, it is usually intimately bound to tendons or tendon sheaths. Often the tumors are present for many years. The classic histologic appearance of this lesion differentiates it from the other choices.

This classic case of osteosarcoma illustrates the typical radiographic and histologic characteristics of this disease. The radiographs show an aggressive-appearing lesion of the distal femur. The lesion has both lytic and blastic areas. Periosteal reaction is present in the form of a Codman’s triangle. The radiographs are highly suggestive of osteosarcoma. The photomicrographs show malignant spindle cells that produce osteoid, thus confirming the diagnosis of osteosarcoma. Treatment of osteosarcoma is multimodal including multi-agent chemotherapy and surgery (wide resection or amputation).

The patient has rhabdomyosarcoma. Axillary node and bone marrow biopsy are part of the staging because about 12% of patients with rhabdomyosarcoma of the extremity have evidence of lymph nodes metastases at presentation. Bone marrow metastases have been shown to portend a worse prognosis.

Multiple Myeloma lesions are cold on bone scan and because of this a skeletal survey is more useful.

DISCUSSION: Heterotopic ossification may occur spontaneously or following trauma. The imaging studies and histology reveal mature fatty bone marrow and trabecular bone. Osteochondromas are cortically based with the medullary canal extending into the lesion. This is not evident in this patient. Also, no obvious cartilage cap is present. Parosteal osteosarcoma commonly occurs in the posterior distal femoral cortex but is ruled out by the lack of the typical fibrous stromal cells forming the low-grade malignant osteoid. The histology and clinical presentation eliminate osteomyelitis and osteoblastoma.

In 95% of patients with Ewing’s sarcoma, there is a translocation, t(11;22). This results in EWS/FLI-1 transcription factor that results in tumor cell proliferation. Other mechanisms causing tumor cell proliferation include inactivation of tumor suppressor genes, or activation of proto-oncogenes.

The images reveal a large mass in the posterior thigh arising from the sciatic nerve. The lesion is edematous, and the gadolinium image reveals rim enhancement, suggesting necrosis, given that the STIR image is not uniformly bright as would be seen in a cystic lesion. The PET scan has increased uptake, in this case a standard unit value (SUV) of greater than 2.0. These findings are all very suggestive of a malignant process. The history of neurofibromatosis makes a malignant peripheral nerve sheath tumor, or neurofibrosarcoma, the most likely diagnosis. The term “peripheral nerve sheath tumor” has replaced neurolemmoma and schwannoma.

DISCUSSION: The obturator vessels and nerve pass along the lateral pelvic wall along the true pelvic brim (nerve lies anterior to the vessels and lies on the obturator internus muscle) and descend into the obturator groove at the upper portion of the obturator foramen.

DISCUSSION: The patient’s history and laboratory studies are very suspicious for a postoperative diskitis. The predominant symptom often is back pain. An ESR of 90 mm/h is considered significantly elevated and normally would be expected to return to near baseline by 2 weeks postoperatively. A normal WBC result is not unusual with postoperative diskitis. Management should consist of an MRI with gadolinium to confirm the diagnosis, followed by a biopsy percutaneously to obtain tissues for pathology and microbiology. Surgical debridement is reserved for patients whose percutaneous biopsy results are negative and a high index of suspicion for diskitis remains, or when management consisting of IV antibiotics, bed rest, and spinal immobilization fails to provide relief. REFERENCES: Garfin SR, Vaccaro AR (eds): Orthopaedic Knowledge Update: Spine. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1997, pp 257-271. Beaty JH (ed): Orthopaedic Knowledge Update 6. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1999, pp 713-721.

DISCUSSION: The radiographic appearance shows a slightly expansile lesion in the proximal phalanx of the fifth digit typical of an enchondroma. There is a stippled appearance within the bone and no evidence of cortical destruction. The biopsy reveals a cartilage lesion with basophilic cytoplasm. There are some hypercellular areas but no evidence of pleomorphism. Enchondromas in the tubular bones of the hand are usually more cellular than their counterparts in the femur and humerus and should not be considered malignant. No other lesions are noted in the radiograph, so a diagnosis of Ollier’s disease cannot be made. An osteochondroma is a benign surface cartilage tumor. Brown tumor and osteomyelitis can be differentiated from enchondroma based on the histology. REFERENCES: Wold LE, Adler CP, Sim FH, et al: Atlas of Orthopedic Pathology, ed 2. Philadelphia, PA, WB Saunders, 2003, p 225. McCarthy EF, Frassica FJ: Pathology of Bone and Joint Disorders with Clinical and Radiographic Correlation. Philadelphia, PA, WB Saunders, 1998, p 227.

The widening, bowing, and cupping of the physes indicate some form of metabolic bone disease; therefore, the most likely diagnosis is renal osteodystrophy. The age of onset makes X-linked hypophosphatemic rickets less likely. The ground glass lesions and widening of the medullary canal characteristic of fibrous dysplasia are not present. There are no fractures creating the deformities indicating osteogenesis imperfecta. There is an asymmetry of the deformities that makes diastrophic dysplasia less likely.

DISCUSSION: Solitary bone lesions require biopsy, for there is the possibility that the lesion may represent a primary bone sarcoma, which will necessitate a different treatment plan. This is especially true in patients with remote histories of cancer. The most likely cause of a lytic bone lesion in a patient older than age 40 years is a metastatic lesion. REFERENCES: Rougraff BT, Kneisl JS, Simon MA: Skeletal metastases of unknown origin: A prospective study of a diagnostic strategy. J Bone Joint Surg Am 1993;75:1276-1281. Simon MA, Karluk MB: Skeletal metastases of unknown origin: Diagnostic strategy for orthopedic surgeons. Clin Orthop Relat Res 1982;166:96-103.

Tenosynovial giant-cell tumors are widely known as pigmented villonodular synovitis (PVNS), although this term is misleading because this tumor type is a clonal neoplasm and does not involve an inflammatory process. It often is shown to have a t(1:2)(p13q37) karyotype resulting in CSF1-COL6A3 gene fusion. There are various amounts of mononuclear cells, osteoclastlike giant cells, foamy histiocytes, hemosiderophages, and chronic inflammatory cells. Local recurrences are common, but CSF1R inhibitors are being investigated in studies involving local control improvement and disease regression. Targeted therapy trials to assist in control of the diffuse-type tenosynovial giant-cell tumor (formerly called PVNS) involve the use of monoclonal antibodies that inhibit CSF1R activation. CSF1R-expressing mononuclear phagocytes are affected by these monoclonal antibodies. Tenosynovial giant-cell tumor is characterized by an overexpression of CSF1. CSF1R activation leads to recruitment of CSF1R-expressing cells of the mononuclear phagocyte lineage.

Placing cement over a bone biopsy site prevents tumor contamination by controlling hematoma. Even though the use of cement may impart some strength, the femur is still at significant risk for fracture. The use of bone cement in this manner has not been cleared by the FDA, but many physicians feel that it is appropriate when the patient’s health status has been given careful consideration, and the physician has the necessary knowledge and training. The other options are not important reasons to use methylmethacrylate in biopsies.

Metastatic disease of the spine occurs in as many as 70% of patients with disseminated cancer and may result in vertebral collapse, spinal instability, and progressive neurologic compromise. Three fourths of these originate from breast, prostate, kidney, or lung carcinoma or myeloma or lymphoma. The vertebral body is affected due to a rich blood supply and sinusoidal vascular distribution. Cord compression is the extrusion of tumor tissue and detritus of bone or disk in the spinal canal following the partial collapse of a vertebral body that has been infiltrated and weakened by a metastatic deposit.

Curettage and bone grafting typically are the preferred treatment of chondroblastoma, yielding acceptable local recurrence rates of less than 10%. Some surgeons advocate adjuvant therapies such as phenol, liquid nitrogen, or argon beam coagulation. Untreated, these lesions can destroy bone and invade the joint to a significant degree. Large intra-articular lesions may require major joint reconstruction. Wide local excision is rarely required to control the tumor. Radiation therapy is indicated only in unresectable lesions.

DISCUSSION: The radiograph reveals a metaphyseal lesion with some stippled mineralization suggesting a chondroid tumor. The bone scan shows increased uptake, beyond what is expected for a simple enchondroma, and beyond the limits of the lesion. The MRI sequences shows a lobular lesion on the T1- and T2-weighted (bright on the T2 sequence) images with inhomogeneous uptake of gadolinium; both findings are typical for a chondroid lesion. The history of pain, the positive bone scan, the age of the patient, the size of the lesion, and the central location (enostotic) of the lesion all suggest a malignant cartilage tumor. The images are not consistent with the other diagnoses. In particular, plasmacytoma is more uniformly bright on T2-weighted images and often has a negative bone scan. REFERENCES: Menendez LR (ed): Orthopaedic Knowledge Update: Musculoskeletal Tumors. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 187-194. Resnick D (ed): Diagnosis of Bone and Joint Disorders. Philadelphia, PA, WB Saunders, 2002, pp 3897-3904.