10. Pathology and Oncology MCQs

DISCUSSION: Local control of osteosarcoma consists of wide resection and reconstruction. Radiation therapy is not recommended except in unresectable lesions or for palliation. Curettage and bone grafting result in intralesional resection with an unacceptable high rate of local recurrence. Chemotherapy alone is not adequate for local control. REFERENCES: Simon M, Springfield D, et al: Osteogenic Sarcoma: Surgery for Bone and Soft Tissue. Philadelphia, PA, Lippincott Raven, 1998, p 274. Wold LA, et al: Osteogenic Sarcoma: Atlas of Orthopaedic Pathology. Philadelphia, PA, WB Saunders, 1990, pp 14-15.

DISCUSSION: Resection and reconstruction of this very proximal lesion provides the best chance to avoid hardware complications that may be associated with stabilization procedures. Wide resection of isolated renal cell carcinoma metastasis, which presents distant to the nephrectomy, may improve long-term survival. REFERENCES: Fuchs B, Trousdale RT, Rock MG: Solitary bony metastasis from renal cell carcinoma: Significance of surgical treatment. Clin Orthop Relat Res 2005;431:187-192. Jung ST, Ghert MA, Harrelson JM, et al: Treatment of osseous metastases in patients with renal cell carcinoma. Clin Orthop Relat Res 2003;409:223-231.

DISCUSSION: Chondroblastomas are benign cartilage lesions frequently seen in adolescents or young adults. They are found in the epiphyseal or apophyseal regions of bones. The radiograph shows a radiolucent lesion with mineralization and a well-marginated rim of reactive bone. The lesion is composed of sheets of immature chondroblasts (polygonal cells with a clear, bluish cytoplasm and a small round central nucleus). In some regions, classic “chicken-wire” matrix calcifications and a “cobblestone” pattern of cell arrangement may be seen. Treatment consists of curettage and bone grafting. REFERENCES: Campanacci M: Bone and Soft Tissue Tumors, ed 2. New York, NY, Springer-Verlag, 1999, pp 247-264. Lin PP, Thenappan A, Deavers MT, et al: Treatment and prognosis of chondroblastoma. Clin Orthop Relat Res 2005;438:103-109.

Multiple hints in this history, MRI and pathology section leads to the diagnosis of soft tissue abscess. The sarcomas are slow growing and mostly are asymptomatic. The mass is tender and enlarging over the past week. PVNS would give the patient a painful boggy joint and this mass is supracondyler. Esinophilic granuloma would give a punched-out lesion in the long bones on the plain radiographs. The best clue is the slide given which shows inflammatory cells. PVNS would show hemosiderin stained giant cells, synovial sarcoma would reveal a biphasic pattern of spindle cells, E.G. would show eosinophils and histiocytes, and rhabdomyosarcoma would have cross striation within the tumor cells.

DISCUSSION: In review of 154 patients with nonrhabdomyosarcoma, Rao reported that histologic grade, tumor invasiveness, and adequate surgical margin were the most important prognostic factors. Histologic subtype, use of adjuvant chemotherapy, and patient age were not as important. Size related to degree of invasiveness was not statistically significant. REFERENCES: Rao BN: Nonrhabdomyosarcoma in children: Prognostic factors influencing survival. Semin Surg Oncol 1993;9:524-531. Andrassy R, et al: Non-rhabdomyosarcoma Soft-Tissue Sarcomas: Pediatric Surgical Oncology. Philadelphia, PA, WB Saunders, p 221.

The imaging study demonstrates characteristics of Little Leaguer’s shoulder, including physeal widening. This condition is secondary to overuse (typically throwing) and responds well to rest from the inciting activity. There is no evidence from the patient’s history or examination that he has an impingement syndrome, nor is there any indication of labral pathology on the MRI scan. The changes in the proximal humerus are classic for this condition and are not suggestive of a neoplastic process requiring biopsy for definitive diagnosis.

An aneurysmal bone cyst is a benign, locally destructive lesion of bone. Most are seen in patients in the second decade of life. The clinical presentation varies, but most patients have pain, tenderness, swelling, and/or pathologic fracture. Radiographs show a radiolucent lesion sometimes with expansile remodeling of the cortex. MRI best detects the commonly seen fluid-fluid levels associated with this lesion. Histologic findings include blood-filled spaces with bland fibrous connective tissue septa. The stroma has histiocytes, fibroblasts, scattered giant cells, hemosiderin, and occasional inflammatory cells. Treatment of these lesions consists of extended curettage, plus or minus the use of adjuvants (liquid nitrogen, phenol, argon beam coagulation), and finally filling the bone void (allograft or other bone substitute).

DISCUSSION: Dermatofibrosarcoma protuberans (DFSP) is a rare superficial sarcoma that is frequently misdiagnosed at presentation. It is frequently excised prior to suspecting that the lesion is a sarcoma and if not appropriately treated with tumor bed resection to obtain wide margins, these lesions have a high incidence of local recurrence. It is recommended that the wide excision include the deep fascia and a 2.5- to 3-cm cuff of normal-appearing skin. Distant disease spread is rare and usually occurs in the face of a multiply recurrent lesion. Despite the apparent gross circumscription of these lesions, the tumor diffusely infiltrates the dermis and subcutaneous tissues. A characteristic histologic finding can be seen in the deep margins of the tumor where it intricately interdigitates with normal fat. REFERENCES: Lindner NJ, Scarborough MT, Powell GJ, et al: Revision surgery in dermatofibrosarcoma protuberans of the trunk and extremities. Eur J Surg Oncol 1999;25:392-397. Weiss SW, Goldblum JR, Enzinger FM: Enzinger and Weiss’s Soft Tissue Tumors, ed 4. Philadelphia, PA, Elsevier, 2001, pp 491-505.

DISCUSSION: The venous plexus was described by Batson and helps to explain the common distribution of metastatic cells to the vertebrae, skull, ribs, and proximal long bones. Batson studied the vertebral vein system extensively by using contrast agents in human cadavers and live monkeys. Batson’s plexus is a valveless system that allows retrograde embolism from the major organs such as the breast, prostate, lung, kidney, and thyroid. It is located within the thoracoabdominal cavity and has connections to the proximal long bones and an intercommunicating network of thin-walled veins with a low intraluminal pressure. REFERENCES: Batson OV: Function of vertebral veins and their role in spread of metastases. Ann Surg 1940;112:138-149. Coman DR, de Long RP: Role of vertebral venous system in metastasis of cancer to spinal column: Experiments with tumor-cell suspensions in rats and rabbits. Cancer 1951;4:610-618.

DISCUSSION: The bright signal on the T2-weighted MRI scan suggests fluid. The multiloculated appearance in proximity to the proximal tibiofibular joint suggests that the most likely diagnosis is a ganglion. They typically increase and decrease in size and can be diagnosed by the classic gelatinous fluid obtained through needle aspiration.

DISCUSSION: The findings are consistent with an osteoblastoma. The radiographs show a bone-forming lesion of the distal humerus. The lesion has an osseous component extending out of the native cortex with a thin sclerotic border. The T2-weighted MRI scan shows the lesion extending anteriorly beyond the native cortex. No fluid-fluid levels are seen. Histology shows large osteoblasts producing osteoid and woven bone. The tissue between the spicules of bone and osteoid contains thin fibrous tissue and capillaries. Osteoid osteoma is a smaller lesion usually with sclerotic reactive bone around a small nidus. The histology differentiates osteoblastoma from osteosarcoma because no malignant cells are seen. There is no cartilage production or chondroblasts in the histologic specimen, eliminating chondroblastoma. Giant cell tumors of bone typically occur in an epiphyseal metaphyseal location, most commonly after skeletal maturity, and contain numerous giant cells.

DISCUSSION: The radiograph shown is consistent with Paget disease of the bone. It demonstrates classic findings of widened lamellae and disorganized sclerotic and lytic areas. The cause is not clearly defined, but may be linked to a viral infection and subsequent alterations of osteoblastic and osteoclastic activity. Most patients are asymptomatic, and Paget disease is often found incidentally on radiographs. In this case, the patient’s symptoms likely were caused by hip arthritis, but Paget disease can cause diffuse bone pain in some cases. Considering the patient’s mild and short-term symptoms, observation and NSAID use is most appropriate. An MRI scan or biopsy is indicated if sarcomatous transformation is suspected, but this condition is rare and is associated with a substantial, unrelenting increase in pain. SPEP and UPEP are tests for multiple myeloma, of which the radiographs show no signs.

DISCUSSION: Intravenous fluid administration is the best first step to treat the hypercalcemia of malignancy. Many of these patients are dehydrated, and the increased serum calcium impairs the ability of the kidney to concentrate the urine. The decreased glomerular filtration rate secondary to the hypovolemia also leads to increased tubular resorption of calcium. The establishment of normovolemia will help promote increased urinary excretion of calcium. Lasix can also be used to help promote calciuria. Mithramycin is an antibiotic derived from Streptomyces plicatus. It is part of a group of drugs referred to as chromomycin antibiotics and is the only one of this group used clinically in the United States. It is rarely used in cancer chemotherapy because of its toxicity. A number of drug-related deaths have occurred from the use of mithramycin. Its use is now limited to the treatment of hypercalcemia associated with malignancy where it is used in lower dosage than that used for the treatment of tumors. Methotrexate has no role in the treatment of hypercalcemia of malignancy. While intravenous bisphosphonates are helpful in slowing progression of metastases and may help lower serum calcium, they are not appropriate in the emergent treatment of hypercalcemia in the metastatic cancer patient. REFERENCE: Stewart AF: Clinical practice: Hypercalcemia associated with cancer. N Engl J of Med 2005;352:373-379.

DISCUSSION: Melanoma comprises 25% of lower extremity lesions and is the most common malignant tumor of the foot. The preferred treatment is wide resection. REFERENCES: Hughes LE, Horgan K, Taylor BA, Laidler P: Malignant melanoma of the hand and foot: Diagnosis and management. Br J Surg 1985;72:811-815. Fortin PT, Freiberg AA: Malignant melanoma of the foot and ankle. J Bone Joint Surg Am 1995;77:1396-1403.

The patient has parosteal osteosarcoma. The posterior aspect of the distal femur is the typical location for this variant of osteogenic sarcoma. The imaging studies indicate a surface lesion with no involvement of the adjacent intramedullary canal. The histologic appearance is that of a low-grade fibroblastic osteosarcoma, consisting of relatively mature bone and a bland fibroblastic stroma lacking cytologic atypia and mitotic activity. A cartilaginous component is also frequently seen. Classic osteosarcoma typically has a more aggressive radiologic and histologic appearance.

Etanercept is a biochemically designed tumor necrosis factor receptor immunoglobulin G fusion protein, which binds to TNF-alpha and is thus a TNF-alpha antagonist.TNF-alpha is considered to be one of the major cytokines involved in rheumatoid arthritis pathology. As a result, many biologic agents used to treat rheumatoid arthritis (RA) are manufactured to block TNF-alpha or its receptors. This has been shown to reduce inflammation and stop disease progression. In the USA, Etanercept is approved to treat rheumatoid arthritis, juvenile rheumatoid arthritis and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis. The route of administration is subcutaneous.Bongartz et al. used a randomized control trial to asses the risk of infection and malignancy rates in RA treated with TNF-alpha antagonist. Overall, patients with RA appear to have an approximately 2-fold increased risk of serious infection compared to the general population and non-RA controls, irrespective of TNF-alpha antagonist use. The pooled odds ratio for malignancy was 3.3 (95% confidence interval [CI], 1.2-

DISCUSSION: Elastofibroma is a rare tumor that most commonly occurs in adults who are older than age 55 years. The lesions usually grow between the chest wall and the scapula, and 10% are bilateral. Histologic analysis shows that they are composed of equal amounts of elastin and collagen with occasional fibroblasts.

DISCUSSION: Epithelioid sarcoma is a rare soft-tissue sarcoma that most commonly arises in the hand or upper extremity, and it is frequently misdiagnosed as an infection or granuloma. It tends to have a higher incidence of lymph node metastasis than other soft-tissue sarcomas. The mainstay of treatment is wide surgical excision.

The use of chemotherapy has dramatically improved survival rates of patients with Ewing’s sarcoma. Local disease is best handled with wide resection to decrease local recurrence and to avoid the complications of radiation therapy (i.e., secondary sarcomas). Radiation therapy alone is reserved for unresectable lesions or poor surgical margins. Amputation generally is not necessary.

The figures show a lesion of the proximal humerus consistent with an enchondroma. The lesion is calcified on the radiographs. There is no cortical destruction, significant endosteal scalloping, or soft-tissue mass. The bone scan shows mild uptake in the area of the proximal humerus, and the T2-weighted MRI scan shows a lesion with high uptake, suggesting a lesion with high water content. A CT scan could also be obtained to rule out bone destruction or periosteal reaction. Pain with overhead activities is likely related to the rotator cuff. A biopsy is unlikely to add information because of inherent difficulties interpreting low-grade cartilaginous lesions. Curettage and grafting and en bloc resection are excessive treatments for a benign lesion that is apparently asymptomatic. Observation with a follow-up radiograph in 3 to 6 months is appropriate.