10. Pathology and Oncology MCQs

DISCUSSION: This is a classic presentation of a giant cell tumor. It is a benign aggressive bone tumor consisting of distinct undifferentiated mononuclear cells. Most occur in patients 30 years to 50 years of age (90% are older than age 20 years) and affect women more than men. Pain and swelling for 2 to 3 months is classic. The most common location is the distal femur. The biopsy specimen shows multinucleated giant cells amid a background of mononuclear cells. This benign tumor may rarely metastasize to the lung (less than 2% of the time). A CT scan of the chest is required to rule out any further lesions. Curettage, with local adjuvants, such as phenol, cryotherapy, or argon beam, and cementation represents the best treatment option at this time.

The epiphyseal location on the radiograph and MRI scan and the histologic findings of polyhedral cells separated by a chondroid matrix with pericellular, lattice-like “chicken wire” calcification all suggest chondroblastoma. Although giant cell tumors of bone typically occupy an epiphyseal location, they are rare in children and when present are often metaphyseal in skeletally immature patients. Enchondromas and osteoblastomas are generally metaphyseal and, along with giant cell tumors, have very different histology than seen here. Chondromyxoid fibromas are typically metaphyseal in location.

The clinical history, CT scan, and histology are most consistent with a lymphoma of bone. An important part of the staging is bone marrow aspiration and biopsy. Lymphoma of bone, when localized, is usually treated with chemotherapy and radiation therapy and has excellent survival rates. Widespread lymphoma has a worse prognosis.

EXPLANATION: This lesion is a pyogenic granuloma, which is a common benign vascular lesion that can occur on skin or mucosa. The etiology is unclear, although this lesion tends to occur in areas of physical trauma. Initial treatment with silver nitrate with an average of 1.6 applications has a success rate of 85%. This patient, however, has failed silver nitrate applications. Wide surgical excision is associated with the lowest recurrence rate and offers the benefit of a single procedure. Other options often necessitate repeated procedures to completely eradicate this lesion.

The history and images show a lytic, malignant solitary bone lesion with a pathologic fracture in an adult patient. In a patient older than age 50 with a lytic bone lesion, metastatic disease is the most likely diagnosis. In the setting of placing an intramedullary nail, the bone will require radiation to eliminate residual disease within the femur.

DISCUSSION: This lytic lesion is in the epiphyseal-metaphyseal region of the distal tibia. The most common lesion in this area is a giant cell tumor. Although these lesions are most commonly seen in adults, they can also occur in the skeletally immature patient. The photomicrograph shows a lesion with multiple giant cells, the nuclei of which are similar to those in the background stroma; this finding is characteristic of giant cell tumors. Giant cells can be seen in many benign lesions, including aneurysmal bone cysts, Brown tumors, and eosinophilic granuloma. These lesions usually have fewer giant cells with less nuclei. The location of this lesion in the epiphyseal-metaphyseal area is not seen in aneurysmal bone cysts, unicameral bone cysts, Ewing’s sarcoma, or eosinophilic granuloma. REFERENCE: Picci P, Manfrini M, Zucchi Z, et al: Giant cell tumor of bone in skeletally immature patients. J Bone Joint Surg Am 1983;65:486-490.

Radiation therapy is the first line of treatment in spinal metastatic disease from lymphoma because it is a highly radiosensitive tumor.

An osteoid osteoma is a benign bone tumor. Osteoid osteomas tend to be small—typically <1.5 cm. Regardless of their size, they cause a large amount of reactive bone to form around them, and they make a new type of abnormal bone material called osteoid bone. This osteoid bone, along with the tumorcells, forms the nidus of the tumor, which is easily identified on CT scans.

DISCUSSION: The laboratory findings are typical for rickets. Oncogenic rickets is a paraneoplastic syndrome that results from a substance secreted by the tumor that interferes with renal tubule reabsorption of phosphate. This substance previously had been called phosphatonin but recently has been identified as fibroblast growth factor 23. Nutritional rickets is rare in developed countries. Delayed onset familial hypophosphatemic rickets is possible, but the likelihood of having two rare diseases is unlikely. Osteosarcoma does not sequester calcium. Alkaline phosphatase levels can be elevated in osteosarcoma but does not cause muscle weakness. Tumor cachexia would occur only with advanced metastatic disease. A unilateral sacral mass would not cause a bilateral L5 neuropathy or the abnormal laboratory findings.

DISCUSSION: Advances in development of new tumor markers and techniques of antigen retrieval have enhanced the sensitivity and reliability of identifying the primary source of metastasis. New markers such as CK7, CK20, CA125, and thyroid transcription factor-1 (TTF-1) can help to determine the origin of an adenocarcinoma or aid in the recognition of other tumors. In patients who do not have an obvious primary site of disease or screening radiographs, these new markers can help focus the search for and guide the treatment of the underlying lesion. CA125 is positive in patients with ovarian cancer, CK7 is positive in patients with breast and lung carcinoma, and CK20 is indicative of colon carcinoma if the CK7 marker is negative. Gastrointestinal stromal tumor (GIST) is positive for CD117 (c-kit) and CD34, whereas 75% of bronchogenic carcinomas are positive for TTF-1. Histochemical staining of the S100 protein family has been used for many years in the diagnosis of malignant melanoma. Recent markers HMB-45, MART-1, and Melan-A have proved to be useful in diagnosis of melanoma. S100B protein has been implicated in downregulation of p53 (oncosuppressor gene). REFERENCES: Harpio R, Einarsson R: S100 proteins as cancer biomarkers with focus on S100B in malignant melanoma. Clin Biochem 2004;37:512-518. Roodman GD: Mechanisms of bone metastasis. N Engl J Med 2004;350:1655-1664.

DISCUSSION: Plexiform neurofibromas are lesions found in patients with NF1. Clinical reports show the prevalence of plexiform neurofibroma to be 20% to 30% but increases to 40% when imaging studies are routinely obtained. The lesions are characterized by diffuse hypertrophy of the involved nerves but with preservation of the nerves’ fascicular organization. The lesions may involve the dermis or may arise in the deeper structures. Palpation of a dermal lesion provokes an image of a “bag of worms.” Plexiform neurofibromas may cause disfigurement and hyperpigmentation of the overlying skin. The lesions also can cause diffuse hypertrophy of the soft tissue and bone, with resultant changes ranging from a relatively minor limb-length discrepancy to gigantism of the entire extremity. Dural ectasia is frequently found in patients with NF1. Therefore, MRI should be obtained prior to planning spinal procedures in these patients; however, dural ectasia is not the cause of limb overgrowth. Lisch nodules are benign hamartomas of the iris. The lesions are uncommon during early childhood but are found in all adults with NF1. Juvenile xanthogranuloma has a low occurrence rate in patients with NF1; its presence is associated with juvenile chronic myeloid leukemia. Malignant peripheral nerve sheath tumors, formally called neurofibrosarcoma, result from malignant degeneration of a plexiform neurofibroma. This condition occurs in up to 4% of patients with NF1. Localized pain, an enlarging mass, or progressive neurologic symptoms suggest a malignant peripheral nerve sheath tumor in a patient with NF1. However, progressive neurologic symptoms also may occur with benign growth of a plexiform neurofibroma. REFERENCES: Alman BA, Goldberg MJ: Syndromes of orthopaedic importance, in Morrissy RT, Weinstein SL (eds): Lovell and Winter’s Pediatric Orthopaedics, ed 5. Philadelphia, PA, Lippincott Williams and Wilkins, 2001, pp 287-338. Greene WB: Neurofibromatosis type I, in Fitzgerald RH, Kaufer H, Malkani AL (eds): Orthopaedics. St Louis, MO, Mosby, 2002, pp 1584-1588.

DISCUSSION: The imaging shows a cartilaginous lesion with destruction and a malignant extraosseous mass most consistent with a dedifferentiated chondrosarcoma. The histology demonstrates a high-grade spindle-cell sarcoma abutting a cartilaginous tumor, confirming this diagnosis. Treatment in this patient would be wide resection. The role of chemotherapy in this tumor is unproven, and an 85-year-old patient is an unlikely candidate for such treatment. Radiofrequency ablation, curettage, and radiation do not play a role in the treatment of this tumor.

The scoring system published by Mirels in 1989 is based on the following characteristics: the location of the lesion, the amount of pain the patient is experiencing, the type of lesion (either lucent, mixed, or blastic), and the lesion size. The tumor is scored from 1 to 3 in each category and a total score is obtained that correlates to fracture risk. Prophylactic fixation is advised for lesions with scores of higher than 8, and consideration for stabilization should be strongly considered for scores of 8. The Mirels scoring system can be useful as an adjunct to clinical decision making.

Osteoid osteomas are painful bone lesions, with radiographs revealing a dense sclerotic cortex surrounding a small radiolucency or nidus. Symptoms often are worse at night but usually are not activity related. While treatment in the past has consisted of open en bloc excision, current means of removal include percutaneous drilling under CT guidance and percutaneous radiofrequency coagulation. Success rates of percutaneous treatment are comparable to those seen following open procedures. The characteristic radiographic appearance of this lesion usually obviates the need for biopsy. Because the lesion is not caused by pyogenic organisms, antibiotics are not indicated.

The radiograph shows a calcified lesion in the medullary canal of the distal femoral diaphysis. The MRI scan shows extensive marrow change distal to the lesion, which is not consistent with an enchondroma. The histology shows a biphasic pattern with low-grade cartilage just apposed to high-grade spindle cell sarcoma. The overall appearance is consistent with dedifferentiated chondrosarcoma. The radiographic appearance is not consistent with enchondroma, and the histologic appearance is not consistent with the other choices.

The obturator internus muscle originates from the internal pelvic wall and passes laterally through the lesser sciatic foramen, banking around the ischium below the sacrospinous ligament before inserting on the medial aspect of the greater trochanter.

Paucytopenia is a common problem in patients with metastatic disease. Causes include chemotherapy, external beam radiation, marrow replacement by tumor, and anemia of chronic disease. There is no correlation with decreased calcium and a decrease in hematopoiesis. Supportive care with granulocyte-colony stimulating factor (G-CSF) and neupogen can stimulate hematopoiesis.

Number four is the correct answer because recurrence is the most likely cause of the lytic zone. Since cement resists invasion by the tumor, lysis of the surrounding bone is inevitably produced in a recurrence. A 1-2 mm lytic zone can be found normally, greater than 5 mm lytic zone is positive for recurrence and the 3 – 5 mm lytic zone is very suspicious and should be followed by MRI and image guided needle biopsy. No other sign of osteomyelitis or stress fractures are noted.

EXPLANATION: The ultrasound shows a homogeneous anechoic mass consistent with a ganglion cyst. As a benign lesion, no further workup or biopsy is required prior to a marginal surgical excision other than age-appropriate laboratory studies. An MRI study with contrast would provide no diagnostic benefit.

DISCUSSION: The photomicrograph shows a synovial cell sarcoma with a characteristic histology of a biphasic pattern of pleomorphic spindle cells and well-differentiated cuboidal to columnar cells forming gland-like spaces. The glandular zones contain mucous-like material that stains positively with periodic acid Schiff. Microscopic calcifications are usually found. Synovial cell sarcoma has a high rate of local recurrence as well as metastases. It is the most common malignancy found in the foot. REFERENCES: Krall RA, Kostianovsky M, Patchefsky AS: Synovial sarcoma: A clinical, pathological and ultrastructural study of 26 cases supporting the recognition of a monophasic variant. Am J Surg Pathol 1981;5:137-151. Wright PH, Sim FH, Soule EH, Taylor WF: Synovial sarcoma. J Bone Joint Surg Am 1982;64:112-122.