A 37-year-old male of Eastern European, Jewish ancestry presented to an orthopedic surgeon for pain in his shoulder and neck.
A 37-year-old male of Eastern European, Jewish ancestry
presented to an orthopedic surgeon for pain in his shoulder and
neck. A plain radiograph of the right shoulder (figure 1A) showed
an extensive, well defined bubbly lesion occupying the medullary
cavity of the proximal shaft of the humerus. Expansion of the
humeral shaft and endosteal scalloping was noted. MRI of the
shoulder and proximal humerus (figures 1B,C) showed the lesion to
be confined entirely to the marrow space and to have a mix of low
and intermediate signal on both T1 and gradient echo images.
(A) Radiograph of the right shoulder shows multiple areas of
medullary lucency in the humeral head and proximal shaft. Note
the prominent cortical trabeculations in the shaft and the
endosteal scalloping. (B,C) Coronal T7-weighted MR images of the
right proximal humerus show multiple well defined lesions of low
to intermediate signal of the humeral head and proximal shaft.
The lesions are confined entirely to the marrow space.
Additional history revealed that the onset of shoulder (and
neck) pain occurred acutely while the patient was "rough-housing"
with one of his children. At the request of the radiologist, a
cervical MR examination was performed, and an acute C-6 disc
herniation was encountered. During subsequent anterior discectomy
and cervical fusion, an open biopsy of the humeral lesion was
Pathologically, the lesion consisted of small fragments of
yellowish-brown-to-red soft tissue. Histologic sections
demonstrated a xanthomatous lesion with large, foamy macrophages
interspersed with areas of normal marrow elements (figure 2A). The
iron stain was strongly positive. An electron microscopic study
showed numerous intracytoplasmic twisted tubules consistent with
Gaucher cells (figure 2B).
(A) Histologic section showing the bone marrow space filled with
cells of 20 to 100 microns in diameter with "wrinkled tissue
paper" cytoplasm, characteristic of Gaucher cells (hematoxylin
and eosin, 400X). (B) Electron micrograph of a Gaucher cell
containing intracytoplasmic deposits of twisted membranous
bilayers measuring 60 nanometers (uranyl acetate and lead citrate
The radiologic differential diagnosis suggested a variant of
fibrous dysplasia. The lesions were too well defined for a
malignancy such as leukemia, lymphoma, or metastatic disease to be
considered. A skeletal survey showed numerous well-defined, lytic
lesions within the long bones, identical to those encountered in
the humerus. Despite the multiple skeletal lesions, the patient
remains asymptomatic from his disease.
Gaucher disease is one of the lipid storage disorders that also
includes Niemann-Pick disease and TaySachs disease. It is a rare
familial disorder that is inherited as an autosomal recessive trait
and affects males and females equally. The condition was originally
described by Gaucher in 1882 as a chronic progressive disorder that
The disease is now recognized to be the result of a disorder of
cerebroside metabolism in which a deficiency of the enzyme
glucocerebroside hydrolase produces excess deposits of lipid
materials within the macrophages of the reticuloendothelial system.
The affected cells, referred to as Gaucher cells, are 20 to 100
microns in diameter, are found predominantly in the liver, spleen,
and bone marrow, and have a cytoplasm that stains pale pink with
PAS and pale blue with Mallory analine blue stain.
Characteristically, the cytoplasm either has a foamy appearance or
has the appearance of "crumpled tissue paper" (figure 2A). Iron
deposits also are commonly found in the cells. On electron
microscopy, intracytoplasmic deposits of twisted membranous layers
can be found (figure 2B); these are considered characteristic of
the Gaucher cell.
Proliferation of Gaucher cells within the liver, spleen, and lymph
nodes produces hepatosplenomegaly and lymphadenopathy,
respectively. Other infiltrations occur in the kidneys, lungs,
thyroid, adrenals, and bone marrow. It is the marrow involvement
that produces the characteristic bony lesions.
Three clinical forms of Gaucher disease are recognized: type 1,
termed the "adult" or chronic nonneuropathic form, is most common.
There is a predominance, although not exclusive, among Jews of
Ashkenazic heritage. Patients with this form of the disease often
present in the first decade of life with symptoms referable to
splenomegaly. Occasionally, as in the case we present here, the
symptoms are so mild that diagnosis is delayed until the third or
fourth decade of life. In the more typical case, the replacement of
hematopoietic cells with Gaucher cells produces various degrees of
anemia, leukopenia, and/or thrombocytopenia which often are
relieved by splenectomy.
While 75% of these patients have radiographically demonstrable
skeletal lesions, only about one-third show symptoms.
Type II, the "infantile" or acute neuropathic type, is generally
fatal within two years of onset.
This form has no ethnic predilection and generally presents within
the first six months of life. There are a large number of
neurologic manifestations, including mental retardation,
strabismus, seizures, and spasticity. Hepatosplenomegaly also may
Skeletal manifestations are rare.
Type III, the "juvenile" or subacute neuropathic form, is the
rarest form and is characterized by hepatosplenomegaly and delayed
onset of neurologic and skeletal manifestations.
Radiographically, the long tubular bones (especially the femur),
vertebral column, hip, shoulder, and pelvis are the most frequently
involved sites. Infiltration of the marrow spaces with Gaucher
cells and resorption of bony trabeculae result in osteopenia and
patchy lytic areas, with foci of reparative bony sclerosis (figure
1). Pathologic fractures are known to occur in these areas. Bone
marrow infiltration and endosteal cortical erosion frequently
produce modeling deformities that result in the "Erlenmeyer flask"
appearance of the distal femur, one of the most characteristic bony
manifestations of the disease. The epiphyses in adjacent joints are
usually spared. Findings are often bilateral.
In the vertebral column, infiltration of the central marrow
frequently results in a "fish-type" deformity of the vertebrae
similar to that seen in sickle-cell disease and other
Ischemic necrosis may occur, particularly in the femoral and
Occasionally, the diagnosis of Gaucher disease may be made when
the skeletal manifestations are found as an incidental finding, as
in this case. A careful search of the patient's medical history
should reveal some evidence of hepatosplenomegaly. Our patient
related an episode of blunt abdominal trauma twenty years
previously, during which time hepatosplenomegaly was found. This
reminds us to be cognizant of the old dictum which states that
patients are allowed to have more than one disease at the same
A variety of neoplastic, hematologic, and metabolic disorders,
including metastatic disease, solitary or multiple myeloma,
leukemia, sickle-cell disease, and fibrous dysplasia should be
considered in the differential diagnosis.
Since the radiographic manifestations overlap so many other
disorders, Gaucher disease should be considered in patients who
have hepatosplenomegaly combined with osteopenia with a coarsened
trabecular pattern, focal osteosclerosis, Erlenrneyer flask
deformities of the distal femora, and ischemic necrosis of the
CT-guided biopsy of one or more skeletal lesions may be necessary
to confirm the diagnosis. The histologic features, particularly the
electron microscopic picture, is considered characteristic.