4. Ewing’s Sarcoma
The Ewing’s sarcoma is the second most common primary
malignant bone tumor seen in children and is the fourth most
common malignant tumor overall. This tumor is a very primitive
mesenchymal 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 probably
represents a poorly differentiated member of a larger family of
neural tumors, distinct from the neuroblastoma. In 90% of cases,
cytogeneticists will find reciprocal translocation in chromosome
11 and 22. That also is found in patients with the diagnosis of
primative neuroectodermal tumor (PNET) and Askin’s tumor.
Other round cell tumors that have a similar histological appearance
include the embryonal rhabdomyosarcoma, the mesenchymal
chondrosarcoma, and the metastatic neuroblastoma. It is very
important to separate out the large group of histiocytic lymphomas
5. seen in an older age group that have a similar appearance with
H & E staining. With special staining techniques, most lymphomas
will be positive for leukocyte antigen. Likewise with metastatic
embryonal rhabdomyosarcoma, specific immunohistochemical
studies will reveal muscle markers such as actin, desmin, and
myoglobin not found in the Ewing’s sarcoma.
Ninety percent of patients with Ewing’s sarcoma will be from 5
to 25 years of age, with males being affected slightly more than
females. The two most common locations for Ewing’s sarcoma are
the femur and pelvis, followed by the tibia, humerus and scapula,
but it can be found in any location in the body that includes
myelogenous tissue, including the spine, ribs, 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 structures
that looks like hematogenous osteomyelitis. Likewise, the clinical
appearance of Ewing’s sarcoma can mimic infectious disease
6. with elevated temperature, white count and sed rate. Because of the
high incidence of necrosis with the Ewing’s sarcoma, it is common
to find liquefied necrotic debris in the tumor site that gives the
clinical appearance of osteomyelitis. With early breakthrough into
the subperiosteal tissues, the radiographic finding of a reactive
periostitis 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 created
by reactive new bone formation along the perpendicular periosteal
blood vessels running between the periosteum and the subadjacent
cortex.
Prior to 1970, the prognosis for survival in Ewing’s sarcoma was
extremely poor with approximately 10% of patients surviving their
disease. Currently with the use of adjuvant systemic chemotherapy
in non-metastatic Ewing’s sarcoma, the survival prognosis now runs
approximately 70%. However, in about 20% of patients with
Ewing’s sarcoma that present with metastatic disease to other bones
7. or to the lung, the survival rate drops to about 30%. Whenever
possible, the orthopedic oncologist will attempt a wide resection of
the primary tumor site, a technique similar to that used for osteo-
sarcoma. If wide surgical margins are obtained, the chances for
survival is probably better than if radiation therapy and chemo-
therapy had been used without surgery. However, in cases where
the surgical margins are positive at the time of surgical resection,
postoperative radiation therapy is indicated. The chance for local
recurrence 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 fixation
that may fail and can result in amputation. Secondary sarcomas can
occur 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 for
survival. The clinical management for this entity is essentially the
same as for Ewing’s sarcoma.
209. Lymphoma of Bone
Lymphoma of bone accounts for approximately 7% of all primary
malignant tumors of bone and can be divided roughly into two
clinical groups: Hodgkin’s lymphoma of bone and non-Hodgkin’s
lymphoma of bone. Hodgkin’s lymphoma carries a much better
prognosis for survival. It tends to be localized and presents with a
radiographic appearance that frequently includes a dense, sclerotic
response. The non-Hodgkin’s lymphomas can be divided into
two categories. The systemic form, the most common form with
generalized involvement of the entire lymphatic system including
soft tissue and bone, carries a poor prognosis. The less common
form that is found in bone and does not have systemic manifestations
carries a better prognosis for survival. To meet the strict criteria for
a primary lymphoma of bone, the disease must be contained within
the skeletal system for at least six months before becoming
disseminated to other lymphatic organs such as lymph nodes and
210. spleen, at which time the prognosis for survival becomes much
worse. The age group for primary lymphoma of bone is between
25 and 50 years. The most common bones involved are the spine
and pelvis in 50% of cases. In the extremities, the most common
location is the femur followed next by the humerus and tibia with
multiple skeletal sites involved in approximately 25% of cases.
Radiographically, the primary lymphoma takes on a permeative
lytic appearance in cortical bone in a metadiaphyseal location,
but can also involve epiphyseal bone as well. Because of the
permeative nature of the bone destruction, pathologic fractures are
common, similar to the situation with Ewing’s sarcoma. In both
primary lymphoma and Ewing’s sarcoma, large soft tissue masses
can be found. With H&E staining, the histological appearance
of lymphoma and Ewing’s sarcoma can be quite similar but with
specific immunohistochemical staining techniques, B cell and T cell
subtypes of lymphoma can be identified and clearly separated
from Ewing’s sarcoma. As in the case of Ewing’s sarcoma, the
211. advent of chemotherapy dramatically improved the prognosis for
survival that, for a solitary primary lymphoma of bone, is similar to
Ewing’s sarcoma with a 70% five year survival. However, with more
disseminated involvement of multiple bones or other lymphatic
organs, the prognosis drops dramatically to 10-25%. As with Ewing’s
sarcoma, the lymphoma of bone is quite sensitive to external beam
radiation therapy. However, the complications (including path-
ological fracture) are a problem and the orthopedic oncologist will
attempt a wide resection of the tumor if possible or, in more extensive
involvement, an intralesional approach with a long stem cemented
prosthesis with adjuvant bone cement may be indicated to avoid
pathological fracture. In cases of systemic involvement with extensive
metastatic disease, patients can be considered for bone marrow
transplantation. The same holds true for Ewing’s sarcoma.
268. Case # 906.6 Large cell lymphoma knee
48 year female with medial knee pain 1 year and history of
torn medial meniscus & 18000 WBC & elevated cholesterol
420. Solitatary Plasmacytoma
To fit the strict criteria for the diagnosis of a solitary plasmacytoma,
the patient should present with a single bony involvement, as
demonstrated by a bone skeletal survey, and remain free of other
bony site involvement for at least six months after the initial
diagnosis. Unfortunately, in approximately 70% of cases, the
solitary form of the disease will disseminate into the more common
form of multiple myeloma. Likewise, in the case of pure solitary
plasmacytoma, the serum protein electrophoresis study is
completely 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 before
the age of 40 years. The most common sites of involvement
include the spine, pelvis and proximal femur with radiographic
evidence of a solitary lytic destruction of bone that may take on the
appearance of a benign lesion such as a solitary form of fibrous
421. dysplasia. Because the disease is purely lytic in nature, the bone
isotope scan may be negative.
Since the disease is considered localized at first, the treatment is
localized with a wide surgical resection and prosthetic replacement,
with or without bone cement, followed by local radiation therapy
if the margins are positive. No systemic chemotherapy is used until
the disease becomes more disseminated as demonstrated by increased
levels of abnormal myeloma protein found by serum electrophoresis
studies. The prognosis for survival is quite good until the disease
becomes more disseminated which is usually within three years
after the initial diagnosis.
422. CLASSIC Case #182
40 year male with solitary plasmacytoma pelvis
479. Multiple Myeloma
Multiple myeloma is considered to be the most common primary
tumor of bone, accounting for approximately 45% of all malignant
bone tumors. It is usually seen in patients over 40 years of age and
is two times more common in blacks than whites. Radiographically,
the lytic lesions seen in multiple myeloma are typically punched-out
with fairly sharp margins but no sclerotic response at the periphery
and thus are not frequently picked up on a total body bone isotope
study. The diagnosis is usually made by a combination of a bone
marrow biopsy and a serum protein electrophoresis that reveals
the elevated monoclonal immuninoglobulin at either the alpha or
gamma spike. Bence-Jones protein is found in the urine examination
secondary 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 peripheral
neuropathy. This type of multiple myeloma has a better prognosis
480. for survival and is referred to as the Poems syndrome. Skeletal
lesions are more typically seen in the spine and pelvic area and
proximal long bones, but rarely seen distal to the elbow or knee. In
aggressive forms of myeloma with extensive bony destruction by
osteoclastic erosion, the patients will develop hypercalcemia that
can result in a semi-comatose state and sometimes is associated
with nephrocalcinosis. Renal damage also results from excessive
proteins plugging the renal tubules. Pathological fractures are
common because of excessive osteoclastic activity (osteoclysis)
that can be inhibited by drugs such as Aredia. Even though large
concentrations of imminoglobulin are produced by the malignant
plasma cells, the patient’s resistance to infection is markedly
inhibited and surgical complications resulting from infection should
be anticipated when operating on patients with this disease.
Systemic chemotherapy has greatly improved the prognosis
for survival in this disease. The drugs used include Malphalan and
cortisone which have increased the chance for survival to three years.
481. Local treatment consists of external beam radiation therapy and
intramedullary devices, such as long stem prostheses and inter-
locking nails supplemented with bone cement, for pathological
fractures. Excessive bleeding at the time of surgery is typical with
myeloma patients, similar to the problem faced with patients with
metastatic renal cell disease and thyroid carcinoma. It is important
to radiate the entire long bone involved when considering intra-
medullary device fixation because of the potential for newer lesions
arising distal to the fixation device at a later date.
482. CLASSIC Case #186
fracture
65 year male with multiple myeloma pelvis and hips
549. Metastatic Neuroblastoma
Neuroblastoma is a primitive tumor of childhood taking its origin
from the medullary portion of the adrenal gland or in other parts of
the sympathetic nervous system and is considered to be the third
most common malignancy in childhood. This tumor is usually seen
under the age of five years and typically metastasizes to bones
including the vertebra, ribs, skull, femur, pelvis, humerus, tibia, and
radius. These patients usually have systemic symptoms including
weight loss, fever, generalized pain and anemia. Radiographically,
the lesions in bone have a permeative destructive pattern typically
in the metaphyseal portion of long bones. Histologically, the
characteristic feature of the neuroblastoma is a rosette formation
with neurofibrils. However, on routine H&E stains the histology is
quite similar to that of rhabdomyosarcoma, non-Hodgkin’s
lymphoma and Ewing’s sarcoma. Diagnostic studies include
cytogenetics that will reveal a chromosomal abnormality in the
550. number 1 chromosome. A CT scan of the abdomen will frequently
pick up a neoplastic abnormality in the kidneys. Chemotherapy and
sometimes bone marrow transplantation is used in the treatment
protocol for this aggressive, extensive metastatic disease but with
only a a 20-25% chance for survival at five years after diagnosis.
551. CLASSIC
Case #189
4 year male
metastatic neuroblastoma
distal femur with
pathologic fracture