A twenty-nine-year-old man presented with a
four-week history of pain in the right foot. On physical
examination, the plantar surface of the foot was swollen and tender.
Magnetic resonance imaging showed a well-defined, ellipsoid
mass measuring 8 4 3.8 cm, situated between the metatarsal bones
and the plantar aponeurosis (Fig. 1). Computed tomography scans revealed
erosion of the fifth metatarsal. Open biopsy was performed, and
a circumscribed, lobulated nodular mass was found. Histological
examination revealed a uniform pattern consisting of compact nests
of rounded or fusiform cells with a pale or clear cytoplasm. In between
the cells, a network of collagenous tissue was encountered (Fig. 2). Immunohistochemically,
the tumor cells expressed antigens for S-100 protein and
melanoma-associated antigen, reflecting melanin synthesis. Antibodies
reactive to epithelial membrane antigen and cytokeratin were negative.
On the basis of these criteria, the diagnosis of clear-cell
sarcoma was made.
Staging examinations (a technetium-99m bone scan, computed tomography
of the abdomen and thorax, and positron emission tomography) did
not reveal metastatic dissemination (Fig. 3). A transtibial amputation was
performed eighteen days after the biopsy. Examination of the specimen
revealed a grey-whitish tumor measuring 10 ¥ 5 ¥ 3.5
cm, situated in the medial aspect of the sole of the right foot.
The tumor had grown into the subcutaneous fat, but the metatarsal
bones were not affected. At the amputation site, both soft tissue
and bone marrow from the tibia were free of tumor-cell infiltration.
The tumor was classified, according to the revised TNM system4, as pT2b pN0 pM0 G3; this represents
stage III (a stage for which chemotherapy is not indicated), as
defined by the American Joint Committee on Cancer5.
Four weeks after leaving the hospital and two months after the initial
diagnosis, the patient, walking with use of a below-the-knee prosthesis,
fell onto both hands. One week later, when he sought medical help
because of continued pain, examination of the left wrist revealed
a fracture of the capitate with osteolysis (Fig. 4). An open biopsy
of the capitate was performed, and malignant tissue resembling a
clear-cell sarcoma in terms of structure, morphological
characteristics, and immunohistochemical pattern was found, confirming
the highly malignant potential of the primary tumor. Computed tomography
of the thorax and abdomen and a technetium-99m bone scan (Fig. 3) revealed no
further evidence of tumor dissemination.
We performed partial excision of the carpus, with en
bloc removal of the capitate together with the hamate,
the scaphoid, the lunate, parts of the trapezium and trapezoid,
and the proximal parts of the second, third, and fourth metacarpals.
The wrist was fused in 30° of extension and 15° of ulnar deviation.
Stabilization was achieved with interposition of a corticocancellous
autograft harvested from the iliac crest and fixation with a titanium
plate and two Kirschner wires (Fig. 5). Histopathological examination
confirmed the diagnosis. The margins of the resection were tumor-free.
After immobilization in a plaster cast for ten weeks, radiographs
revealed consolidation of the arthrodesis. Following physiotherapy,
the active range of motion of the fingers was not limited, but there
was a 30% reduction in grip strength compared with that
of the contralateral hand. There were no signs of local recurrence
of the tumor at the wrist level. Positron emission tomography, performed
eight days following the operation, revealed multiple metastases
in the left humerus, axilla, and clavicle and within the superior
mediastinum. Three weeks after excision of the carpal metastatic lesion,
the patient presented with a superior vena cava syndrome, dyspnea
and dysphagia due to a soft-tissue mass surrounding the superior
mediastinum, pulmonary metastases, and infiltration of the right
atrium by tumor. Chemotherapy was initiated, and the patient’s
general condition improved. Eventually, additional widespread metastases
developed, and the patient died ten months after the initial presentation.
There are several aspects of this case that reinforce previous findings
reported in the literature. The average age at the time of the first
manifestation of clear-cell sarcoma is about twenty-five years,
and the most frequent site of the primary tumor is the foot1,2,6,7. Clinically, the mass is of
moderate size and grows slowly. Only half of patients report pain.
Therefore, years may elapse between the first occurrence of the
tumor and treatment1,2.
The morphological and immunohistochemical criteria are clear,
but the possibility of a malignant melanoma, especially an amelanotic
lesion, cannot be excluded solely by clinical investigation. To
differentiate clear-cell sarcoma from malignant melanoma, cytogenetic
analysis can be helpful; while the translocation t(12;22)(q13;q13)
seems to be a primary feature of clear-cell sarcoma, this translocation
has not yet been observed in malignant melanoma8,9.
Most authors have emphasized the highly malignant potential of
this entity. Wide local excision is the appropriate surgical treatment.
If wide margins cannot be achieved, radical excision or even amputation
is required1,2. Regional lymphadenectomy
is not obligatory. Primary clear-cell sarcomas of bone have been
reported sporadically, but unequivocal proof of osseous origin will
probably remain impossible10-13.
Therefore, it has been suggested that the term clear-cell
sarcoma should be reserved for tumors arising in soft tissue14. The most common sites of metastatic
spread include the regional lymph nodes, lungs, skeletal system,
liver, and heart1,6. The frequency
of skeletal involvement ranges between 15% and 26%7,15,16. Although there have been rare
reports of primary clear-cell sarcoma arising in the hand, to our
knowledge this is the first description of metastasis to the carpus6,12,17.
A limb-salvage procedure that preserves basic hand function is
justified even in a patient with local recurrence of a clear-cell
sarcoma18. Retrospectively, however,
the indication for an en bloc excision of the capitate
can be reappraised. Because widespread metastases developed in our
patient within a short period of time following this operation,
less radical options, such as curettage followed by use of cement
or grafting of the capitate, are worth considering. However, these
procedures would necessarily have left tumor behind, and the patient chose
the more extensive procedure.
Initial staging had failed to demonstrate the carpal involvement.
Secondary staging had failed to identify further dissemination.
Since the carpus was the site of the initial metastatic manifestation,
we believe that the extremities should be included in the bone scans
of these patients to avoid missing a distal metastasis.
Many authors have proposed the use of positron emission tomography
for the staging of malignant melanoma. The sensitivity of detection
of distant metastasis is higher than 90%, and positron
emission tomography can demonstrate these lesions earlier than can
other conventional imaging techniques19-23.
Since 1997, all patients with a soft-tissue sarcoma of an extremity
treated at our institution have been included in a clinical trial
to evaluate the role of positron emission tomography in the detection
of occult regional nodal or distant metastatic disease at the time
of presentation.
When radiographs demonstrate an osteolytic lesion of the capitate,
the diagnosis is very rarely a primary tumor24.
Metastatic tumors of the hand, from any primary site, are also very
uncommon. In a review of 163 cases reported in the literature, only
five such tumors were located in the capitate25.
Once a metastatic clear-cell sarcoma in the hand or wrist has been
confirmed, further tumor spread is probable. Since the prognosis
is very poor, with a median duration of survival of only five months,
a limb-preserving procedure rather than an amputation through
the forearm should be performed whenever possible26.
The unique feature of the case reported here is the initial metastasis
to the capitate. To our knowledge, this has not been documented
previously in association with soft-tissue sarcoma.