Ewing’s Sarcoma The Ewing’s sarcoma is the second most common primarymalignant bone tumor seen in children and is the fourth mostcommon malignant tumor overall. This tumor is a very primitivemesenchymal sarcoma that has a mysterious etiology. However,with the advent of the electron microscope and immunohisto-chemical studies, most experts today feel that this tumor probablyrepresents a poorly differentiated member of a larger family ofneural tumors, distinct from the neuroblastoma. In 90% of cases,cytogeneticists will find reciprocal translocation in chromosome11 and 22. That also is found in patients with the diagnosis ofprimative neuroectodermal tumor (PNET) and Askin’s tumor.Other round cell tumors that have a similar histological appearanceinclude the embryonal rhabdomyosarcoma, the mesenchymalchondrosarcoma, and the metastatic neuroblastoma. It is veryimportant to separate out the large group of histiocytic lymphomas
seen in an older age group that have a similar appearance withH & E staining. With special staining techniques, most lymphomaswill be positive for leukocyte antigen. Likewise with metastaticembryonal rhabdomyosarcoma, specific immunohistochemicalstudies will reveal muscle markers such as actin, desmin, andmyoglobin not found in the Ewing’s sarcoma. Ninety percent of patients with Ewing’s sarcoma will be from 5to 25 years of age, with males being affected slightly more thanfemales. The two most common locations for Ewing’s sarcoma arethe femur and pelvis, followed by the tibia, humerus and scapula,but it can be found in any location in the body that includesmyelogenous tissue, including the spine, rib, foot and hand. Radio-graphically, the Ewing’s tumor will be found typically in a meta-diaphyseal location in the medullary canal with very diffuse,permeative lytic destruction of the surrounding cortical structuresthat looks like hematogenous osteomyelitis. Likewise, the clinicalappearance of Ewing’s sarcoma can mimic infectious disease
with elevated temperature, white count and sed rate. Because of thehigh incidence of necrosis with the Ewing’s sarcoma, it is commonto find liquefied necrotic debris in the tumor site that gives theclinical appearance of osteomyelitis. With early breakthrough intothe subperiosteal tissues, the radiographic finding of a reactiveperiostitis is quite common, creating a multilaminated “onionskin”appearance on a routine radiograph. Another characteristic radio-graphic finding is the “hair-on-end” appearance that is createdby reactive new bone formation along the perpendicular periostealblood vessels running between the periosteum and the subadjacentcortex. Prior to 1970, the prognosis for survival in Ewing’s sarcoma wasextremely poor with approximately 10% of patients surviving theirdisease. Currently with the use of adjuvant systemic chemotherapyin non-metastatic Ewing’s sarcoma, the survival prognosis now runsapproximately 70%. However, in about 20% of patients withEwing’s sarcoma that present with metastatic disease to other bones
or to the lung, the survival rate drops to about 30%. Wheneverpossible, the orthopedic oncologist will attempt a wide resection ofthe primary tumor site, a technique similar to that used for osteo-sarcoma. If wide surgical margins are obtained, the chances forsurvival is probably better than if radiation therapy and chemo-therapy had been used without surgery. However, in cases wherethe surgical margins are positive at the time of surgical resection,postoperative radiation therapy is indicated. The chance for localrecurrence with chemotherapy and radiation therapy alone is 20%or higher. A devastating complication of radiation therapy is path-ological fracture that frequently results in intramedullary fixationthat may fail and can result in amputation. Secondary sarcomas canoccur with the use of radiation therapy for Ewing’s sarcoma in 10%of cases. The primative neuroectodermal tumor accounts for 10%of all Ewing’s-like tumors and carries the same prognosis forsurvival. The clinical management for this entity is essentially thesame as for Ewing’s sarcoma.
CLASSICCase #16913 year femaleEwing’s sarcomadistal femur onion skin periostitis
Lymphoma of Bone Lymphoma of bone accounts for approximately 7% of all primarymalignant tumors of bone and can be divided roughly into twoclinical groups: Hodgkin’s lymphoma of bone and non-Hodgkin’slymphoma of bone. Hodgkin’s lymphoma carries a much betterprognosis for survival. It tends to be localized and presents with aradiographic appearance that frequently includes a dense, scleroticresponse. The non-Hodgkin’s lymphomas can be divided intotwo categories. The systemic form, the most common form withgeneralized involvement of the entire lymphatic system includingsoft tissue and bone, carries a poor prognosis. The less commonform that is found in bone and does not have systemic manifestationscarries a better prognosis for survival. To meet the strict criteria fora primary lymphoma of bone, the disease must be contained withinthe skeletal system for at least six months before becomingdisseminated to other lymphatic organs such as lymph nodes and
spleen, at which time the prognosis for survival becomes muchworse. The age group for primary lymphoma of bone is between25 and 50 years. The most common bones involved are the spineand pelvis in 50% of cases. In the extremities, the most commonlocation is the femur followed next by the humerus and tibia withmultiple skeletal sites involved in approximately 25% of cases. Radiographically, the primary lymphoma takes on a permeativelytic appearance in cortical bone in a metadiaphyseal location,but can also involve epiphyseal bone as well. Because of thepermeative nature of the bone destruction, pathologic fractures arecommon, similar to the situation with Ewing’s sarcoma. In bothprimary lymphoma and Ewing’s sarcoma, large soft tissue massescan be found. With H&E staining, the histological appearanceof lymphoma and Ewing’s sarcoma can be quite similar but withspecific immunohistochemical staining techniques, B cell and T cellsubtypes of lymphoma can be identified and clearly separatedfrom Ewing’s sarcoma. As in the case of Ewing’s sarcoma, the
advent of chemotherapy dramatically improved the prognosis forsurvival that, for a solitary primary lymphoma of bone, is similar toEwing’s sarcoma with a 70% five year survival. However, with moredisseminated involvement of multiple bones or other lymphaticorgans, the prognosis drops dramatically to 10-25%. As with Ewing’ssarcoma, the lymphoma of bone is quite sensitive to external beamradiation therapy. However, the complications (including path-ological fracture) are a problem and the orthopedic oncologist willattempt a wide resection of the tumor if possible or, in more extensiveinvolvement, an intralesional approach with a long stem cementedprosthesis with adjuvant bone cement may be indicated to avoidpathological fracture. In cases of systemic involvement with extensivemetastatic disease, patients can be considered for bone marrowtransplantation. The same holds true for Ewing’s sarcoma.
CLASSICCase #17645 year malelymphoma proximalfemur path fracture
Solitatary Plasmacytoma To fit the strict criteria for the diagnosis of a solitary plasmacytoma,the patient should present with a single bony involvement, asdemonstrated by a bone skeletal survey, and remain free of otherbony site involvement for at least six months after the initialdiagnosis. Unfortunately, in approximately 70% of cases, thesolitary form of the disease will disseminate into the more commonform of multiple myeloma. Likewise, in the case of pure solitaryplasmacytoma, the serum protein electrophoresis study iscompletely normal in 75% of cases with the remaining 25%showing a mild abnormality. The age group for solitary plasma-cytoma is slightly younger than multiple myeloma, typically beforethe age of 40 years. The most common sites of involvementinclude the spine, pelvis and proximal femur with radiographicevidence of a solitary lytic destruction of bone that may take on theappearance of a benign lesion such as a solitary form of fibrous
dysplasia. Because the disease is purely lytic in nature, the boneisotope scan may be negative. Since the disease is considered localized at first, the treatment islocalized with a wide surgical resection and prosthetic replacement,with or without bone cement, followed by local radiation therapyif the margins are positive. No systemic chemotherapy is used untilthe disease becomes more disseminated as demonstrated by increasedlevels of abnormal myeloma protein found by serum electrophoresisstudies. The prognosis for survival is quite good until the diseasebecomes more disseminated which is usually within three yearsafter the initial diagnosis.
CLASSIC Case #182 40 year male with solitary plasmacytoma pelvis
Multiple Myeloma Multiple myeloma is considered to be the most common primarytumor of bone, accounting for approximately 45% of all malignantbone tumors. It is usually seen in patients over 40 years of age andis two times more common in blacks than whites. Radiographically,the lytic lesions seen in multiple myeloma are typically punched-outwith fairly sharp margins but no sclerotic response at the peripheryand thus are not frequently picked up on a total body bone isotopestudy. The diagnosis is usually made by a combination of a bonemarrow biopsy and a serum protein electrophoresis that revealsthe elevated monoclonal immuninoglobulin at either the alpha orgamma spike. Bence-Jones protein is found in the urine examinationsecondary to a light chain immuninoglobulin spillover. Three per cent of patients with myeloma have a sclerotic form(seen on the radiographic examination) associated with a peripheralneuropathy. This type of multiple myeloma has a better prognosis
for survival and is referred to as the Poems syndrome. Skeletallesions are more typically seen in the spine and pelvic area andproximal long bones, but rarely seen distal to the elbow or knee. Inaggressive forms of myeloma with extensive bony destruction byosteoclastic erosion, the patients will develop hypercalcemia thatcan result in a semi-comatose state and sometimes is associatedwith nephrocalcinosis. Renal damage also results from excessiveproteins plugging the renal tubules. Pathological fractures arecommon because of excessive osteoclastic activity (osteoclysis)that can be inhibited by drugs such as Aredia. Even though largeconcentrations of imminoglobulin are produced by the malignantplasma cells, the patient’s resistance to infection is markedlyinhibited and surgical complications resulting from infection shouldbe anticipated when operating on patients with this disease. Systemic chemotherapy has greatly improved the prognosisfor survival in this disease. The drugs used include Malphalan andcortisone which have increased the chance for survival to three years.
Local treatment consists of external beam radiation therapy andintramedullary devices, such as long stem prostheses and inter-locking nails supplemented with bone cement, for pathologicalfractures. Excessive bleeding at the time of surgery is typical withmyeloma patients, similar to the problem faced with patients withmetastatic renal cell disease and thyroid carcinoma. It is importantto radiate the entire long bone involved when considering intra-medullary device fixation because of the potential for newer lesionsarising distal to the fixation device at a later date.
CLASSIC Case #186 fracture 65 year male with multiple myeloma pelvis and hips
Metastatic Neuroblastoma Neuroblastoma is a primitive tumor of childhood taking its originfrom the medullary portion of the adrenal gland or in other parts ofthe sympathetic nervous system and is considered to be the thirdmost common malignancy in childhood. This tumor is usually seenunder the age of five years and typically metastasizes to bonesincluding the vertebra, ribs, skull, femur, pelvis, humerus, tibia, andradius. These patients usually have systemic symptoms includingweight loss, fever, generalized pain and anemia. Radiographically,the lesions in bone have a permeative destructive pattern typicallyin the metaphyseal portion of long bones. Histologically, thecharacteristic feature of the neuroblastoma is a rosette formationwith neurofibrils. However, on routine H&E stains the histology isquite similar to that of rhabdomyosarcoma, non-Hodgkin’slymphoma and Ewing’s sarcoma. Diagnostic studies includecytogenetics that will reveal a chromosomal abnormality in the
number 1 chromosome. A CT scan of the abdomen will frequentlypick up a neoplastic abnormality in the kidneys. Chemotherapy andsometimes bone marrow transplantation is used in the treatmentprotocol for this aggressive, extensive metastatic disease but withonly a a 20-25% chance for survival at five years after diagnosis.
CLASSIC Case #1894 year malemetastatic neuroblastomadistal femur withpathologic fracture