ANATOMIC PATHOLOGY
Original Article
Fine-needle Aspiration Biopsy Cytology of
Giant-cell tumor of Tendon Sheath
PAUL E. WAKELY, J R . , MD, AND WILLIAM J. FRABLE, MD
Localized nodular tenosynovitis, better known as giant-cell tumor of
tendon sheath (GCTTS), is a common neoplasm that has a peak incidence in the fourth to sixth decades of life. Few reports exist elucidating
the cytologic features of this lesion obtained by fine-needle aspiration
biopsy (FNAB). The authors describe five patients, aged 8-50 years, in
whom GCTTS was diagnosed by FNAB cytology. In four of the patients, the lesion was excised, and the FNAB diagnosis of GCTTS was
confirmed; surgical excision is pending in one patient. A diagnosis of
malignancy was not suggested in any of the patients. The tumors were
.7-5 cm in greatest dimension. In two patients, GCTTS affected the
ankle; the hand was affected in the other three. Aspiration smears were
cellular in four cases. All but one case contained several multinucleate
osteoclast-type giant cells; in addition, binucleate cells were common.
The nongiant cell population was dispersed principally as single cells
that had a cytologic appearance mimicking histiocytes and osteoblasts.
Anisonucleosis was minimal, and nuclear pleomorphism was distinctly
absent in both single and multinucleate cells. Mitotic figures were infrequent, except in one case. The diagnosis of GCTTS can be made, or at
least strongly suggested using FNAB when the cytologic and cfinical
features are combined. (Key words: Aspiration cytology; Giant ceil tumor, Soft tissue; Tendon sheath) Am J Clin Pathol 1994; 102:8?290.
Giant-cell tumor of tendon sheath (GCTTS), one among the
many synonyms for the localized form of nodular tenosynovitis, is thought to arise from the synovium of tendon sheath. It is
typically a slowly growing lesion that may occur at any age, but
has a peak incidence between the ages of 30 and 50 years.
Tumor growth may stabilize and remain the same size for a
prolonged period of time. Giant-cell tumor of tendon sheath is
considered to be the most common neoplasms of the hands,
particularly affecting the interphalangeal joints. Other sites of
involvement include the feet, ankles, and knees. In most series,
the local recurrence rate is approximately 10% to 20%.'
The gross and microscopic histopathology of this lesion is
well known and amply described. However, few reports have
delineated the cytologic features of this lesion obtained by fineneedle aspiration biopsy (FNAB). We describe the cytopathology of five cases of GCTTS and discuss the differential diagnosis of this lesion.
were also made. Additionally, in one case, the needle was
rinsed into a balanced salt solution, and alcohol-fixed, Papanicolaou-stained cytocentrifugation smears were made because
of the paucity of cellular material.
RESULTS
CASE 1
An 8-year-old boy was seen in the outpatient clinic with a 3-cm
diameter mass at the right lateral malleolus. The mass was firm and
nontender to palpation. There was no discoloration of the overlying
skin. The clinical impression was probable sarcoma. An FNAB was
performed, and GCTTS was diagnosed. Surgical excision was performed within the following week, and tissue sections confirmed the
FNAB diagnosis. No recurrence has developed in the past 12 years.
MATERIALS A N D METHODS
CASE 2
Fine-needle aspiration was performed by a pathologist in
each instance using 23- or 25-gauge needles and standard techniques. 2 Much of the cellular material smeared onto glass slides
was air-dried and stained with a modified Romanowsky stain
(Diff-Quik, American Scientific Products, Columbia, MD); a
smaller number of alcohol-fixed, Papanicolaou-stained smears
A 38-year-old secretary came to an orthopedic surgeon because of a
small (.7 cm.) nodule on the right indexfingerat the base of the second
interphalangeal joint. The nodule had become somewhat tender and
interfered with her ability to type. The FNAB diagnosis was GCTTS,
confirmed by excision under local anesthesia with tissue histopathology. No recurrence has developed over the past 6 years.
From the Division of Surgical and Cylopathology, Department of
Pathology, Virginia Commonwealth University/Medical College of
Virginia. Richmond. Virginia.
Manuscript received April 9, 1993; revision accepted June 12, 1993.
Address reprint requests to Dr. Wakely: Division of Surgical Pathology and Cytopathology, Medical College of Virginia, P.O. Box 662,
MCV Station, Richmond, VA 23298.
87
CASE 3
A 17-year-old boy had a very firm 5-cm mass over the left ankle that
was present from the age of 6 years. The mass had grown very slowly,
but recently had become somewhat painful. Aspiration of the mass was
performed by an orthopedic surgeon who suspected a ganglion cyst;
however, no fluid was obtained. We performed a repeat FNAB, and a
small amount of material was obtained for smears. The needle was
88
ANATOMIC PATHOLOGY
Original Article
in case 1 and very infrequent in the other cases. Atypical mitoses were not found in any of the smears. Cytoplasms were
finely granular and moderate in amount, with many displaying
a perinuclear zone of cytoplasmic clearing. Vacuolated cells
were unusual. The cytoplasm was elongated and tapered in
many cells, but oval or stellate-shaped in some.
Although easily identified, hemosiderin-laden macrophages
were a minor cellular component of the smears (Fig. 3). Erythrophagocytosis was seen in very few macrophages. Background stromal material, xanthomatous cells, and cell necrosis
were conspicuously absent.
DISCUSSION
FIG. 1. Several osteoclast-type giant cells are clustered in this field.
Because of the low magnification and thickness of the smear in this
field, individual nuclei within each giant cell are difficult to appreciate.
Romanowsky stain, magnification X 175.
rinsed for cytospin preparations. A diagnosis of GCTTS was made.
Surgical confirmation is pending.
CASE 4
An otherwise healthy, 50-year-old white woman had a .7-cm mass on
the volar aspect of the right thumb. The mass had been present and
gradually enlarging for the past 3-4 months. It was slightly tender and
firm. Diagnosis from FNAB was benign mesenchymal cells consistent
with GCTTS. The nodule was excised 5 months later and confirmed
the cytologic diagnosis. There has been no recurrence in the past 10
months.
CASE 5
A 37-year-old policeman developed a 1.5 X 0.5 cm nodule on his
right index (trigger)finger.He gave a history of trauma to this location
7 months earlier. The mass was non-tender and firm to palpation. A
diagnosis of GCTTS was made by aspiration cytopathology. Subsequent surgical excision and tissue histopathology confirmed that diagnosis.
Cytopathology
Aspiration smears were highly cellular in four cases and only
modestly cellular in one (case 4). The pattern mostly appeared
as individually dispersed cells, rather than cohesive aggregates.
Multinucleate osteoclast-type giant cells were obvious in all but
one case (case 4) and were randomly scattered throughout the
smears (Fig. 1). Three to 50 nuclei appeared within these giant
cells. Binucleate cells with mirror image nuclei were common.
The predominate cell, however, was a polygonal-shaped single cell that had an appearance analogous to an osteoblast and/
or histiocyte. Cell nuclei had smooth, round, or oval contours
with fine nuclear chromatin and usually a single small nucleolus that was sometimes indistinct. Nuclei were frequently eccentrically located in cells. Anisonucleosis was minimal, and
nuclear pleomorphism was distinctly absent in both single and
multinucleate cells (Fig. 2). Mitotic figures were only common
Giant-cell tumor of tendon sheath is a relatively frequent soft
tissue tumor whose histopathology has been extensively studied.3"7 The FNAB cytopathology of GCTTS, however, is only
briefly alluded to and sparsely illustrated in the literature.8'9 In
this report, five examples of GCTTS were diagnosed by FNAB
alone. The cytologic diagnosis was confirmed histologically in
four of the cases, which were subsequently treated surgically. In
two patients, we knew the clinical diagnoses before FNAB was
performed (ganglion cyst was diagnosed in case 3, and sarcoma
in case 1); those diagnoses proved to be incorrect. In case 1,
FNAB prevented a more extensive surgical procedure than was
necessary from being done.
Fine-needle aspiration biopsy of soft tissue masses is still in
its infancy, and its role in diagnosis and patient care remains to
be defined for both benign and malignant soft tissue tumors.
The results of our study demonstrate that GCTTS has a characteristic cytologic picture. Except for the hypocellular nature
and lack of multinucleate giant cells in one case, the cytopathology was similar in all smears. These were dominated by single
polygonal cells with rounded, eccentrically located nuclei lacking any pleomorphic features interspersed with multinucleated
osteoclast-like giant cells. Both mononuclear cells and giant
cells from the aspirate smears mirrored their paraffin-embedded histologic counterparts. Some histologic features described
in GCTTS were not found in the cytologic material, including
xanthomatous cells seen histologically but not readily appreciated on smears and histologic stromal hyalinization, which
did not appear as amorphous background material in any of
our cases.
In some cases of GCTTS, a granulomatous-like change has
been described in tissue sections. However, cytologic granulomas were not found in our smears. The mononuclear cells in
the aspirate smears had cytologic features similar to those
ascribed to histiocytes, and the giant cells morphologically imitated normal bone marrow osteoclasts. Previous enzymatic
and immunohistochemical studies of GCTTS have demonstrated that both mononuclear and giant cells are of monocyte/
macrophage lineage and share many of the phenotypic features
of osteoclasts. 34,7
When integrated with the clinical findings, the diagnosis of
GCTTS could be made, or at least strongly suggested, using
FNAB cytology. However, a potentially long list of diagnostic
possibilities should be considered. Because of its location at the
periphery of the extremities, epithelioid sarcoma, synovial sarcoma, clear-cell sarcoma, melanoma, and rhabdomyosarcoma
are malignant neoplasms that may be considered in the differential diagnosis.
A.J.C.P.-July 1994
WAKELY AND FRABLE
89
Giant-cell Tumor of Tendon Sheath
FIG. 2. A and B, Mononuclear cells have
uniform nuclei with bland chromatin
and rounded, stellate, or tapered cytoplasmic boundaries. A mitotic figure is
near the center in A, and an osteoclasttype giant cell is near the bottom of B. A,
Romanowsky stain, magnification X
525; B, Papanicolaou stain, magnification X 525.
Osteoclast-type giant cells are normally absent in each of
these five neoplasms, although frequent in GCTTS. Additionally, the cells of synovial sarcoma are typically spindled, rather
than polygonal, and frequently aggregated in tightly cohesive
groups. Cohesive aggregates (granuloma-like) are also common
in epithelioid sarcoma; however, nucleoli are often much larger
and sometimes pleomorphic in this neoplasm. The nuclei are
larger, and cytoplasm is clear or very pale in clear-cell sarcoma
in contrast to those in GCTTS.
Melanoma displays a greater degree of anisocytosis, pleomorphism, nucleolar enlargement, and atypia than GCTTS,
although the mirror image nuclei, eccentric nuclear position,
and smattering of pigmented cells in GCTTS may superficially
^Jfc^ll
^
FIG. 3. An admixture of mononuclear cells, osteoclast-type giant cell
(left) and pigmented macrophage (right). Romanowsky stain, magnification, X 525.
suggest a diagnosis of melanoma. The multinucleate cells in
rhabdomyosarcoma contain much fewer nuclei than those of
GCTTS. Rhabdomyoblasts are smaller and exhibit much
higher nuclear-to-cytoplasmic ratios than the mononuclear
cells of GCTTS. 1 0 -"
Ancillary immunocytochemistry can be extremely helpful in
separating each of these entities from GCTTS, although none
was performed in these cases. Epithelioid sarcoma and synovial
sarcoma frequently express cytokeratin, clear-cell sarcoma and
melanoma are commonly immunoreactive for S-100, and
rhabdomyosarcoma generally stains with myogenic antibodies
(desmin and actin). None of these antibodies are expressed in
GCTTS.
Proliferative fasciitis and myositis ossificans are nonmalignant entities that may cytologically mimic GCTTS if giant cells
are absent from the smear. The cells of the former are typically
larger with more cytoplasm and huge single nucleoli in contrast
to GCTTS. 12,13 Taken individually, the cells of myositis ossificans are similar to GCTTS; however, in addition to the lack of
giant cells on the smear, densely stained metachromatic material, presumably osteoid, is usually present.14 Some chondroid
lesions that may enter into the clinical differential diagnosis,
such as synovial chondromatosis or soft tissue chondroma, also
typically show a large amount of metachromatic material on
smears.
The uncommon fibroma of tendon sheath is clinically indistinguishable from GCTTS. Age range, lesion size, clinical
symptoms, and anatomic site are nearly identical for each, and
they may represent opposite ends of a morphologic spectrum."
We are unaware of any reports of the aspiration cytology of
fibroma of tendon sheath, but anticipate that, because its histopathology is one of spindle cells embedded in a fibrous or fibromyxoid stroma devoid of giant cells, there would be little difficulty in distinguishing between the two. 1516
Vol. 102-No. I
90
ANATOMIC PATHOLOGY
Original Article
Of the giant-cell lesions that occur in soft tissue, malignant
giant-cell tumor of soft parts, considered a variant of malignant
fibrous histiocytoma, may contain numerous benign-appearing osteoclast-type giant cells. In contrast to GCTTS, however,
the dominant mononuclear cells readily exhibit striking pleomorphism, anisonucleosis, and nucleolar atypia on aspiration
cytology.17
REFERENCES
1. Enzinger FM, Weiss SW. Benign tumors and tumor-like lesions of
synovial tissue. In: Soft Tissue Tumors. 2nd ed. St. Louis: CV
MosbyCo, 1988, p. 638.
2. Frable WJ. Thin-needle aspiration biopsy. A personal experience
with 469 cases. Am J Clin Pathol 1976;65:168-182.
3. Wood GS, Beckstead JH, Medeiros LI, Kempson RL, Warnke
RA. The cells of giant cell tumor of tendon sheath resemble
osteoclasts. Am J Surg Pathol 1988; 12:444-452.
4. Ushijima M, Hashimoto H, Tsuneyoshi M, Enjoji M. Giant cell
tumor of the tendon sheath (nodular tenosynovitis). A study of
207 cases to compare the large joint group with the common
digit group. Cancer 1986;57: 875-884.
5. Myers BW, Masi AT, Feigenbaum SL. Pigmented villonodular
synovitis and tenosynovitis. A clinical epidemiological study of
166 cases and literature review. Medicine 1980;59:223-238.
6. Alguacil-Garcia A, Unni KK, Goellner JR. Giant cell tumor of
tendon sheath and pigmented villonodular synovitis. An ultrastructural study. Am J Clin Pathol 1978;69:6-17.
7. Mizuno K, Ishikura H, Aizawa M. Giant cell tumor of tendon
sheath. An immunohistochemical study of 28 cases. Acta Pathol
Jpn 1986;36:1487-1494.
8. Willems JS: Aspiration biopsy cytology of soft-tissue tumors. In:
Linsk JA, Franzen S, eds. Clinical Aspiration Cytology. 2nd ed.
Philadelphia: JB Lippincott Co, 1989, pp. 365-397.
9. Hajdu SI, Hajdu EO. Cytopathology of soft tissue and bone tumors. Monogr Clin Cytol 1989; 12:47-50.
10. Almeida M, Stastny JF, Wakely PE, Frable WJ. Fine needle aspiration biopsy of childhood rhabdomyosarcoma: Reevaluation of
the cytologic criteria for diagnosis. Acta Cytol 1992; 36:600. Abstract.
11. Akhtar M, Ali MA, Bakry M, Hug M, Sackey K. Fine-needle aspiration biopsy diagnosis of rhabdomyosarcoma: Cytologic, histologic, and ultrastructural correlations. Diagn Cytopathol
1992;8:465-474.
12. Meis JM, Enzinger FM. Proliferative fasciitis and myositis of
childhood. Am J Surg Pathol 1992;16:364-372.
13. Orell SV, Sterrett GF, Walters MN, Whitaker D. Manual and
Atlas of Fine Needle Aspiration Cytology. New York: Churchill
Livingstone, 1992.
14. Wakely PE, Almeida M, Frable WJ. Fine needle aspiration biopsy
cytology of myositis ossificans. Mod Pathol 1994;7:23-25.
15. Satti MB. Tendon sheath tumors: A pathological study of the relationship between giant cell tumour and fibroma of tendon
sheath. Histopathology 1992;20:213-220.
16. Pulitzer DR, Martin PC, Reed RJ. Fibroma of tendon sheath. A
clinicopathologic study of 32 cases. Am J Surg Pathol
1989;13:472-479.
17. Angervall L, Hagmar B, Kindblom L-G. Malignant giant cell tumor of soft tissues. A clinicopathologic, cytologic, ultrastructural, angiographic and microangiographic study. Cancer
1981;47:736-747.
A.J.C.P.-July 1994