Aims and background: Giant cell tumor of tendon sheath (GCTTS) is a co
mmon tumor occurring on the tendon sheaths of the fingers. The nature
of this lesion is still controversial: some researchers consider it a
reactive process arising from chronic inflammation while others regard
it as a tumor of presumed synovial cell or monocytic macrophage syste
m origin. In an effort to clarify the histogenesis we decided to furth
er investigate the immunophenotypic profile of this tumor. Study desig
n: We studied 20 GCTTS of the fingers using a panel of 18 antibodies,
13 monoclonal and 5 polyclonal. Results: The immunohistochemical inves
tigation revealed that the mononuclear cells of this lesion can be div
ided into two groups. The cells of the first and more numerous group w
ere positive for vimentin, PG-M1 and KP1 but also for muscle actin (HH
F35 monoclonal antibody) and neuron-specific enolase. A second populat
ion of mononuclear cells, usually arranged around the giant cells, wer
e positive for PG-M1, KP1, LCA and occasionally for alpha-1-antitrypsi
n and alpha-1-antichymotrypsin, Multinucleated giant cells were also p
ositive for KP1, PG-M1 and LCA monoclonal antibodies. A variable but u
sually weak positivity for alpha-l-antitrypsin, alpha-1-antichymotryps
in and lysozyme was also observed. Conclusions: Our results suggest a
synovial cell origin for GCTTS and do not support the hypothesis that
it could be a neoplasm with a true histiocytic origin. The positivity
of some cells for the HHF35 antibody, together with electron microscop
ic evidence of filament bundles with focal dense bodies, suggests that
at least part of the mononuclear cells may have a myofibroblastic dif
ferentiation.