10. Pathology and Oncology MCQs

The laboratory studies and histology are both consistent with myeloma. Infection should show white blood cells other than plasma cells on histology. Lymphoma would show lymphocytes, not plasma cells. The lack of bone formation on the imaging studies and the lack of osteoid on histology rule out osteosarcoma. The cells have too much cytoplasm and nuclear chromatin to be Ewing’s sarcoma cells.

Ewing’s sarcoma is the second most common primary sarcoma of bone in children and young adults. It is a malignant round cell tumor with uncertain histogenesis. Sheets of uniform small round blue cells with a high nuclear-to-cytoplasm ratio and the absence of osteoid formation differentiate this histologic diagnosis from the other conditions.

This patient has a pathologic fracture; in patients older than age 50, the most likely diagnosis is metastatic carcinoma or hematopoietic malignancy. A systemic work-up with staging imaging studies and laboratory tests will identify the primary site of disease in approximately 90% of patients.

Figure 50A: AP pelvis with a 1 cm lucency in the calcar region of the femoral neck and diffuse osteopenia of the proximal femur. Figure 50B: CT scan of the same patient showing a well demarcated lcm lesion in the femoral neck with an obvious nidus. Careful evaluation of the radiographs is critical in this question. First the obvious osteoid osteoma must be recognized. From there answers 2 and 3 can be eliminated. Neither radiograph reveals any sign that treatment has occurred, and the CT scan shows no signs of extensive involvement, thus answer 5 should also be eliminated. The real key is believing that such diffuse osteoporosis could occur in such a young child, as Jones described in his article from 1969.

The history, examination, and surgical findings are most consistent with plantar fibromatosis. Plantar fibromatosis is a benign tumor of the plantar fascia that consists chiefly of fibromyoblasts. These cells produce excessive collagen and are similar to the cells found in the palmar fascia of patients with Dupuytren’s contracture of the hand. The myocyte, synovial cell, and osteocyte all produce their respective individual tissue types but do not contribute to the formation of a plantar fibromatosis. The T-cell is an important immunologic cell that is most affected in patients with HIV.

The most common anatomic location of chondrosarcoma is the pelvis (30%), followed by the proximal femur (20%). Chondrosarcomas appear in the shoulder girdle in 15% of patients but rarely affect the spine or hands.

The MRI scans show a popliteal cyst (Baker’s cyst) in its most common location. The cyst emerges from the knee joint between the medial head of the gastrocnemius muscle and the tendon of the semimembranosus muscle. These images are diagnostic; therefore, no further work-up is indicated. Since the patient is asymptomatic, no treatment is necessary.

The histology shows "lacey" osteoid with minimal cellular atypia. This is consistent with low-grade intramedullary osteogenic sarcoma. Low grade central osteogenic sarcoma is an uncommon form of osteosarcoma that is characterized by a long premorbid history and is compatible with prolonged survival after treatment. Treatment is surgery with wide margins alone and chemotherapy and radiation are not indicated. Good local control is associated with an excellent long term survival.Choong et al. reviewed the long term follow-up of 20 patients diagnosed with low grade osteogenic sarcoma and found the 5 year survival rate was 90% and at 10 years was 85%. Local recurrence is a key feature in most cases and is typically the result of inadequate surgical margins frequently arising from initial misdiagnosis. Although amputation generally is successful for primary and recurrent tumors, limb salvage surgery is a definite option.Kurt et al reviewed 80 well-differentiated osteosarcomas. They found local excision was almost always associated with recurrence. Wide excision wasalmost never followed by recurrence. The recurrent tumor was a high-grade, conventional osteosarcoma in 15% of the patients, and this was associated with a poor prognosis. They recommend wide excision as the treatment of choice for this very rare variant of osteosarcoma.A 32-year-old male sustains a the injury shown in Figure A after a high-speed motor vehicle collision. Which factor has been found to have the highest direct correlation with severe heterotopic ossification after traumatic knee dislocation?Injury Severity Score (ISS )Glascow Coma Scale (GCS )Timing of knee reconstructionNumber of ligaments reconstructedOpen ligament reconstructionFigure A shows a knee dislocation with cruciate ligament avulsion injuries. Development of significant heterotopic ossification (HO) formation has been shown to be most directly correlated to the ISS score.Mills and Tejwani looked at multiple variables including injury severity score( ISS), Glascow coma scale (GCS), closed head injury (CHI), timing of surgery (> or < 3 weeks) and type of surgery (open vs. arthroscopic, number of ligaments reconstructed) in its relation to the formation of HO following knee dislocation. In the final group the sensitivity and specificity of the ISS in relation to HO formation was 100%, while presence of CHI had a specificity of 97 %. Timing, type of surgery and approach did not influence HO formation.A 52-year-old male presents with 6 months of swelling and pain in his leg. He states the lesion has not changed in size for several months and doesn't bother him. He is otherwise healthy and has no other complaints. Representative photograph and MRI are shown in Figures A through C. What is the best initial step in his management?Follow-up in 6 months with repeat radiographsBiopsyMarginal excisionRadiation therapyNeoadjuvant chemotherapy and wide excisionThe initial step in management of a patient presenting with a large soft tissue mass deep to the fascia is to obtain a tissue diagnosis, via biopsy. Initiation of treatment prior to tissue diagnosis is inappropriate and can result in significant patient morbidity and potential mortality. While some soft tissue sarcomas may benefit from chemotherapy, this cannot be initiated prior to diagnosis.Radiation therapy is used in the treatment of soft tissue sarcoma, but again, only after tissue diagnosis. Peabody et al review the appropriate evaluation and staging for musculoskeletal neoplasms and present flow-charts useful in the work-up of bone (Illustration A) and soft tissue (Illustration B) neoplasms. Skrzynski et al performed a comparison of outpatient core-needle biopsy with open surgical biopsy for musculoskeletal tumors. They found the diagnostic accuracy of core-needle biopsy was only 84% with many samples yielding no or different histological samples when compared to final resected specimens. They conclude that while core-needle biopsy is significantly less expensivethan surgical biopsy ($1106 vs. $7234), there is higher concern for sampling error or general diagnostic inaccuracy associated with a core-needle biopsy compared to open biopsy, the "gold standard".What is the appropriate treatment for a 10-year-old boy with Ewing's sarcoma isolated to the proximal femur?Neoadjuvant chemotherapy and surgical excisionNeoadjuvant chemotherapy, surgical excision, and radiation therapyNeoadjuvant chemotherapy, surgical excision, and adjuvant chemotherapyNeoadjuvant radiation therapy and surgical excisionSurgical excision and hormonal therapyEwing's sarcoma is a malignant small round blue cell neoplasm which has a predilection for long tubular bones, pelvis, and ribs. The radiographic appearance of "onion-skinning" seen in illustrations A and B is due to the body's periosteal reaction. Illustration C shows the large soft tissue extraosseous mass characteristic for Ewing's sarcoma. Finally, Illustration D shows the histology where the multiple small round blue neoplastic cells are seen.Ewing's sarcoma is most commonly treated with neoadjuvant chemotherapy, surgical excision, and adjuvant chemotherapy - in particular for tumors located in bones which can be easily resected and reconstructed. For large tumors in areas which either cannot be completely excised or where excision is associated with significant morbidity, some centers consider chemotherapy and radiation therapy without surgical excision. There is a current trend towards surgical resection and away from irradiation for Ewing's sarcoma even though it is radiosensitive, because of the risk of secondary malignancy and growth disturbance due to radiation.Pierz et al review many of the common bone tumors including Ewing's sarcoma and discuss the relevant diagnostic factors as well as specific treatment protocols for each tumor.A 30-year-old female presents with a painful posterior knee mass. The mass gets larger and more painful with activity. Examination reveals a boggy soft tissue mass about her knee. Radiograph and MRI are shown in Figures A and B. What is the most likely diagnosis?Synovial sarcomaHemangiomaLipomaParosteal osteosarcomaPigmented villonodular synovitis (PVNS )This patients history, physical exam, and imaging studies are suggestive of a hemangioma. Pain in hemangiomas is thought to occur due to vascular engorgement secondary to activity and increased blood flow to the lesion. The calcification on the plain radiograph and the fat of the T1 MRI are diagnostic for hemangioma. Current treatment for symptomatic hemangiomas includes some combination of sclerotherapy or vascular coiling, with surgical excisionreserved for few cases. The two attached reviews by Gilbert et al and Damron et al review the history, diagnosis, treatment, and controversial issues in soft tissue sarcomas and benign sarcoma like conditions such as hemangiomas.Current treatment for soft tissue sarcomas includes radiotherapy and surgical excision. While many centers in the world use chemotherapy for soft tissue sarcomas, the data supporting its use is quite limited and likely too controversial to be tested. With regard to the other answer choices, synovial sarcoma and lipoma can show calcification on radiographs, but they are usually not painful and image differently on T1 MRI. Parosteal osteosarcoma typically occurs in this location (posterior distal femur) but occurs as a lesion stuck on the bone. PVNS can have a similar appearance on imaging, but doesn't cause this type of pain.

DISCUSSION: Patients with neurofibromatosis are at risk for development of soft-tissue sarcomas (most commonly malignant peripheral nerve sheath tumors). Clinical indications of development of a neurofibrosarcoma include a rapidly enlarging soft-tissue mass; therefore, this patient should be considered to have a neurofibrosarcoma until proven otherwise. MRI is superior to CT in characterizing the anatomic location of soft-tissue masses and the signal characteristics of the lesion. Areas of necrosis within the tumor may be apparent on MRI that cannot be appreciated on CT, suggesting a malignant tumor. Local imaging studies of suspected malignant tumors should be performed prior to needle or open biopsy so that the biopsy site can be excised at the time of definitive resection. Additionally, postbiopsy changes may lead to MRI artifacts that alter the interpretation of the MRI. REFERENCES: Demas BE, Heelan RT, Lane J, Marcove R, Hajdu S, Brennan MF: Soft-tissue sarcomas of the extremities: Comparison of MR and CT in determining the extent of disease. Am J Roentgenol 1988;150:615-620. Kransdorf MJ, Jelinek JS, Moser RP Jr, et al: Soft-tissue masses: Diagnosis using MR imaging. Am J Roentgenol 1989;153:541-547.

DISCUSSION: Biopsy of the soft-tissue component is often diagnostic. Alternatively, in centers with pathologists familiar with bone tumors, needle biopsy is usually successful. The principles of biopsy of bone tumors include avoiding contamination of uninvolved structures and compartments, taking the most direct path to the tumors, making an excisable biopsy tract, and obtaining diagnostic tissue. Transverse biopsy incisions should be avoided because they hinder the definitive surgical procedure.

DISCUSSION: Forty percent of osteoblastomas occur in the spine, and they can become large and locally aggressive lesions.  They generally occur in the posterior elements but can occur in the ribs and transverse processes.  Microscopic analysis of the lesion will reveal hyperchromatic osteoblasts separated by incompletely mineralized bars of bone.  Recommended treatment is en bloc excision.  Fibrous dysplasia, giant cell tumor, and hemangioma can have similar radiographic appearances; therefore, biopsy may be required to differentiate them from more aggressive lesions.  Osteochondromas are characterized by an osteocartilaginous growth arising from the cortex.REFERENCES: Bridwell KH, Ogilvie JW: Primary tumors of the spine, in Bridwell KH, DeWald RL (eds): The Textbook of Spinal Surgery.  Philadelphia, PA, JB Lippincott, 1991,vol 2, pp 1143-1174.Enneking WF: Musculoskeletal Tumor Surgery.  New York, NY, Churchill Livingstone, 1983, pp 1043-1053.

DISCUSSION: Based on these findings, the most likely diagnosis is fibrous dysplasia.  Twenty percent of patients with fibrous dysplasia have multifocal disease.  The lesions show a typical ground glass appearance.  Fibrous dysplasia frequently involves the diaphysis of the long bones.  There is no associated soft-tissue mass and no periosteal reactions to these lesions, suggesting a benign lesion.  The histology shows proliferating fibroblasts in a dense collagen matrix.  Trabeculae are arranged in an irregular or “Chinese letter” appearance.  Osteogenic sarcoma and Ewing’s sarcoma have a much different radiographic appearance of malignant osteoid and small round blue cells.  Periosteal chondroma does occur in the proximal humerus but is not typically multifocal.  It appears as a surface lesion with saucerization of the underlying bone and a bony buttress adjacent to the lesion.  Some patients with multifocal lesions have associated endocrine abnormalities (McCune-Albright syndrome).REFERENCES: Wold LA, et al: Atlas of Orthopaedic Pathology.  Philadelphia, PA, WB Saunders, 1990, pp 118-119.Simon M, et al: Surgery for Bone and Soft Tissue Tumors.  Philadelphia, PA, Lippincott Raven, 1998, p 197.

DISCUSSION: A bone scan and bone marrow biopsy are part of the staging studies for Ewing’s sarcoma.  Whole body MRI and PET scans are investigational and show promise of greater sensitivity than a bone scan.REFERENCES: Schleiermacher G, Peter M, Oberlin O, Philip T, Rubie H, Mechinaud F, et al: Increased risk of systemic relapses associated with bone marrow micrometastasis and circulating tumor cells in localized ewing tumor.  J Clin Oncol 2003;21:85-91.Daldrup-Link HE, Franzius C, Link TM, Laukamp D, Sciuk J, Jurgens H, et al: Whole-body MR imaging for detection of bone metastases in children and young adults: Comparison with skeletal scintigraphy and FDG PET.  Am J Roentgenol 2001;177:229-236.

DISCUSSION: 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.REFERENCES: Hughes C IV, Hasselman CT, Best TM, et al: Incomplete, intrasubstance strain injuries of the rectus femoris muscle.  Am J Sports Med 1995;23:500-506.Temple HT, Kuklo TR, Sweet DE, et al: Rectus femoris muscle tear appearing as a pseudotumor.  Am J Sports Med 1998;26:544-548.

DISCUSSION: The radiograph and MRI scan reveal a lytic lesion in the left femoral neck region that extends to the lesser trochanter.  Although external beam radiation and radioactive iodine infusion may be helpful in controlling the local disease, the patient is at high risk for femoral neck fracture given the location of the lesion.  Prophylactic surgery is indicated; therefore, the treatment of choice is a cemented bipolar hemiarthroplasty.  The use of a compression hip screw and side plate or an intramedullary nail has a high likelihood of failure with disease progression.  Postoperative treatment with radiation therapy and bisphosphonates is also indicated.REFERENCES: Mirels H: Metastatic disease in long bones: A proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop 1989;249:256-264.Swanson KC, Pritchard DJ, Sim FH: Surgical treatment of metastatic disease of the femur.  J Am Acad Orthop Surg 2000;8:56-65.Clarke HD, Damron TA, Sim FH: Head and neck replacement endoprosthesis for pathologic proximal femoral lesions.  Clin Orthop 1998;353:210-217.

DISCUSSION: Synovial chondromatosis results from chondroid metaplasia within the synovium.  Male to female ratio is 2:1, with a peak incidence in early adult life.  Radiographs can show speckled calcification.  Multiple cartilaginous bodies are found loose in the joint and embedded in the synovium.  These nodules are composed of cartilage with calcification. Treatment includes synovectomy and removal of loose bodies.REFERENCES: Walling AK: Soft tissue and bone tumors, in Coughlin MJ, Mann RA (eds): Surgery of the Foot and Ankle, ed 7.  St Louis, MO, Mosby, 1999, pp 1007-1032.Hocking R, Negrine J: Primary synovial chondromatosis of the subtalar joint affecting two brothers.  Foot Ankle Int 2003;24:865-867.

This case presents a treatment dilemma for most orthopaedic surgeons. However, because lymphomas are very chemo-radiotherapy sensitive, treatment is straightforward. Lymphoma isolated to bone is treated by resection and reconstruction as indicated. In this case, the resection is accomplished with neck osteotomy and the reconstruction with a hemiarthroplasty. Postoperative adjuvant radiotherapy and chemotherapy can be used to treat the local and distant disease as necessary. You wouldn't close the wound without surgical fixation unless the chemotherapy would be used to improve your surgical margin (such as for a osteosarcoma). Radical resection or hip disarticulation are very aggressive and morbid procedures for a tumor that is very sensitive to chemo-radiotherapy. Bone marrow transplantation is not used in the initial treatment of lymphoma, but can be considered for relapsed disease.The clinical and radiographic features specific to lymphoma of bone are outlined by Dürr but on the whole are not diagnostic.Vose describes the current treatment protocols for patients with non-Hodgkin's lymphoma including patients with impending/sustained pathologic fractures.

DISCUSSION: In addition to mild hip dysplasia, the radiograph shows an osteoblastic lesion of the right ilium.  The patient’s symptoms are much more severe than is typical for late hip dysplasia.  MRI can determine the extent of the lesion in the bone and soft tissues.  Following work-up and biopsy, the patient was diagnosed with Ewing’s sarcoma.REFERENCES: Springfield DS, Gebhardt MC: Bone and soft tissue tumors, in Morrissy RT, Weinstein SL (eds): Lovell and Winter’s Pediatric Orthopaedics, ed 5.  Philadelphia, PA, Lippincott Williams and Wilkins, 2001, pp 507-518, 542-544.Herring JA: Tachdjian’s Pediatric Orthopedics, ed 4.  Philadelphia, PA, WB Saunders, 2002,p 2030.

Flow cytometry is a method of quantitating components or structural features of cells primarily by optical means. Ploidy and cell cycle analysis of cancers is the major diagnostic use. Cells are passed single file through a laser beam by continuous flow and several parameters are measured including Cell Diameter, proportional quantity of granular (DNA) within the cell, and using fluorescent probes the total DNA or a specific DNA/mRNA sequence can be counted. In examining tumors the amount of DNA in each cell is important for determining neoplasia.