Cell characterization of mononuclear and giant cells constituting pigmented villonodular synovitis

doi:10.1053/hupa.2003.52

Human Pathology

Volume 34, Issue 1, January 2003, Pages 65-73

https://doi.org/10.1053/hupa.2003.52 Get rights and content

Abstract

The aim of this study was to determine the histologic and cellular characteristics of 2 cell types, mononuclear cells (Mos) and multinuclear giant cells (GCs), that predominantly constitute pigmented villonodular synovitis (PVS). Synovial tissues examined in this study were obtained from 10 patients with PVS. Five methods were used for cell analysis: (1) enzyme-histochemistry for tartrate-resistant acid phosphatase (TRAP); (2) immunohistochemistry using antibodies for CD68, macrophage colony–stimulating factor (M-CSF), MIB-1, p53, p21, p16, and cathepsin-L (cath L); (3) TdT-mediated deoxyuridine triphosphate-biotin terminal end labeling (TUNEL) as a measure of apoptosis; (4) fluorescence-based polymerase chain reaction single-strand conformation polymorphism analyses (FPCR-SSCP) to detect p53 gene mutations; and (5) in situ hybridization using gene-specific oligoprobes for matrix metalloproteinase (MMP)-2, MMP-9, receptor activator of nuclear factor κB ligand (RANKL), and calcitonin receptor (CTR). Both Mos and GCs were shown to express the macrophage/histiocyte marker CD68. In GCs, TRAP and CTR, both of which are known as characteristic phenotype markers of osteoclasts, were expressed. M-CSF and RANKL, which are together essential for osteoclast differentiation, were expressed in both Mos and GCs. Mos were shown to express MIB-1, but GCs were not. Although proliferation-suppressor proteins p53, p21, and p16 were expressed in both Mos and GCs, little apoptotic phenomenon of lining Mos was detected by TUNEL. In our study, p53 gene mutations for exons 5, 7, and 8 in PVS synovial tissues were not detected by FPCR-SSCP analysis. Furthermore, both types of cells demonstrated the proteolytic enzymes MMP-2 and MMP-9 mRNA, and cath L protein. These results suggest that PVS has a hyperplastic property consisting of the CD68-positive monocytic cell lineage with differentiation of osteoclastic giant cells from monocyte and probably controlled against proliferation by wild-type p53, p21, and p16. HUM PATHOL 34:65-73. Copyright 2003, Elsevier Science (USA). All rights reserved.

Section snippets

Materials and methods

Synovial tissues examined in this study were taken from the knee and ankle joints during surgery from 10 patients with PVS (8 from knee joints and 2 from ankle joints). All cases were clinically and histologically diagnosed as diffuse-type PVS without invasion. This study was performed in accordance with the guidelines of the Declaration of Helsinki.

The following methods were used for cell analysis: (1) immunohistochemical staining using antibodies for CD68, M-CSF, MIB-1, p53, p21, p16, and

Results

The results are summarized in Tables 1, 2, 3, and 4.All tables show the ratio of positive cases with respect to each of the markers. We defined the specimen that indicated that immunopositive cells accounted for >30% of the field of view under high-power fields (except in TUNEL, positive cells accounted for >10% of the field of view under high-power fields) as th-e positive case in the light of difference condition in each sample caused by various durations of formalin fixation.

Discussion

Jaffe et al¹ described PVS as an inflammatory and reactive proliferative disease of synovial tissues caused by uncertain trauma of the joint. A study by Young et al²⁵ reported that repeated injections of autologous blood into the joints of dogs produced hypertrophy of the synovia with hemosiderin deposition similar to that of PVS synovial tissue. They suggested that trauma was an important factor in the pathogenesis of PVS.²⁵ Some investigators, however, have suggested that PVS is a neoplasm

Acknowledgements

The authors are very grateful to Dr. Masami Hosaka and Yuji Shibata for providing materials, methods, and helpful discussion.

References (40)

JX O'Connell et al.
Giant cell tumor of tendon sheath and pigmented villonodular synovitis: Immunophenotype suggests a synovial cell origin
Hum Pathol
(1995)
WS El-Deiry et al.
WAF1, a potential mediator of p53 tumor suppression
Cell
(1993)
DE MacCallum et al.
Biochemical characterization of pki67 with the identification of a mitotic-specific form associated with hyperphosphorylation and altered DNA binding
Exp Cell Res
(1999)
T Nishikawa et al.
A novel calcitonin receptor gene in human osteoclasts from normal bone marrow
FEBS Lett
(1999)
DL Lacey et al.
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation
Cell
(1998)
B Vogelstein et al.
p53 function and dysfunction
Cell
(1992)
JM Darling et al.
Expression of metalloproteinases in pigmented villonodular synovitis
Hum Pathol
(1994)
HL Jaffe et al.
Pigmented villonodular synovitis, bursitis, and tenosynovitis
Arch Pathol
(1941)
JM Darling et al.
Multinucleated cells in pigmented villonodular synovitis and giant cell tumor of tendon sheath express features of osteoclasts
Am J Pathol
(1997)
AS Rao et al.
Pigmented villonodular synovitis (giant-cell tumor of tendon sheath and synovial membrane): A review of eighty-one cases
J Bone Joint Surg Am
(1984)

JA Gehweiler et al.

Diffuse biarticular pigmented villonodular synovitis

Radiology

(1969)

JH Smith et al.

Roentgenographic aspects of articular pigmented villonodular synovitis

Am J Roentgenol

(1962)

F Flendry et al.

Pigmented villonodular synovitis

J Bone Joint Surg Am

(1987)

F Flendry et al.

Diagnostic features of diffuse pigmented villonodular synovitis of the knee

Clin Orthop Rel Res

(1994)

WYW Tsang et al.

KP1 (CD68) staining of granular cell neoplasms: Is KP1 a marker of lysosomes rather than the histiocytic lineage?

Histopathology

(1992)

Y Fujukawa et al.

Human osteoclast formation and bone resorption by monocytes and synovial macrophages in rheumatoid arthritis

Ann Rheum Dis

(1996)

EM Gravallese et al.

Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor

Arthritis Rheum

(2000)

A Sabokbar et al.

Human arthroplasty derived macrophages differentiate into osteoclastic bone resorbing cells

Ann Rheum Dis

(1997)

E Romas et al.

Expression of osteoclast differentiation factor at sites of bone erosion in collagen-induced arthritis

Arthritis Rheum

(2000)

F Kullmann et al.

Analysis of the p53 tumor suppressor gene in rheumatoid arthritis synovial fibroblasts

Arthritis Rheum

(1999)

Cited by (35)

Pigmented Villonodular Synovitis: A Retrospective Single-Center Study of 122 Cases and Review of the Literature
2011, Seminars in Arthritis and Rheumatism
Citation Excerpt :
To avoid multiple recurrences, some authors used anti-tumor necrosis factor-alpha (TNFα) therapy as local in some patients with relapsing PVNS (33,34) or general treatment with relative effectiveness (35). The use of anti-TNFα is supported by the fact that macrophages and proinflammatory cytokines such as TNFα are present in the synovium of patients with PVNS (36,37). This treatment could be an option in patients who relapse frequently, but it is not validated.
Pigmented villonodular synovitis (PVNS) is a rare but disabling disease. The objective was to describe the clinical presentation and outcomes of PVNS according to its localization.
Retrospective, systematic study of all cases of biopsy-proven PVNS followed in 1 tertiary-care center specialized in isotopic synoviorthesis. Cases were selected by keyword. Collected data included disease localization, therapeutic modalities, and outcomes.
A total of 122 cases (mean age 33.0 ± 13.1 years, 58% female, 89% diffuse form) of histologically confirmed PVNS were analyzed with a mean follow-up of 5.8 ± 4.3 years (707 patient-years total). The main localizations were the knee (75%) and ankle (16%). Clinical presentation included joint pain (80%) and joint effusion (79%) with hemarthrosis (75% of analyzed articular fluid). The mean delay before diagnosis was 2.9 ± 3.7 years. Magnetic resonance imaging was helpful for diagnosis in 83%. Surgical synovectomy was initially performed in 98% of cases and was often associated with isotopic synoviorthesis (knee: 57%; other localizations: 74%). In patients with a diffuse form treated at first line by surgery followed by isotopic synoviorthesis, the relapse rate was 30% (knee) and 9% (other localizations), respectively, with a mean delay before relapse of 2.6 ± 2.4 and 2.4 ± 0.9 years, respectively.
PVNS occurs in young adults, mainly in the knee joint; joint pain and effusion with hemarthrosis are the most frequent signs. Relapse is frequent, in particular, for diffuse knee PVNS; the usefulness of isotopic synoviorthesis remains to be confirmed.
Molecular pathways involved in synovial cell inflammation and tumoral proliferation in diffuse pigmented villonodular synovitis
2010, Autoimmunity Reviews
Citation Excerpt :
The gene expression pattern detected by genome-wide investigation of PVNS, typical of activated macrophages, along with the high expression levels of IL-6 and Tumor Necrosis Factor-α (TNF-α), was found to be similar to those in proliferative, active RA [7–9]. Moreover, the PVNS-multinucleated giant cells phenotype detected by IHC (tartrate-resistant acid phosphatase — TRAP, calcitonin receptor, RANK, CSF1R, CD33 and CD51), characteristic of osteoclasts, suggests that there is a common autocrine mechanism in osteoclast differentiation underlying the joint destruction process in both diseases [6,10,11]. The neoplastic property of TSGCTs has, instead, been confirmed by the identification of DNA aneuploidy, of clonal karyotypic aberrations [12], and by the finding of up-regulated telomerase activity [13].
Diffuse-type tenosynovial giant cell tumors, also known as pigmented villonodular synovitis, are unique mesenchymal lesions that arise from the synovial tissue of the joints. They are predominantly intraarticular, aggressive, infiltrative processes, characterized by both inflammatory or neoplastic properties and local destructive progression.
The pattern of synovial gene and protein expressions in pigmented villonodular synovitis, similar to those in activated macrophages in rheumatoid arthritis, and the phenotype of multinucleated giant cells, characteristic of osteoclasts, suggest that there is a common autocrine mechanism in osteoclast differentiation in both diseases and indicate the potential utility of tumor necrosis factor (TNF)-α blockade.
High synovial colony stimulating factor 1 (CSF1) messenger RNA (m RNA) expression in pigmented villonodular synovitis, unrelated to a chromosomal translocation involving CSF1 locus, may indicate that there is a synergic paracrine loop mediated by TNF-α and CSF1, as shown in both inflammatory and neoplastic conditions.
The effects of a new therapeutic approach consisting in intraarticular TNF-α blockade were studied in four pigmented villonodular synovitis knees. Knee injections produced a rapid reduction in clinical and sonographic indexes and immunohistological alterations, confirmed by arthroscopic synovectomy. A delayed relapse in one of the four knees and unaltered synovial CSF1 expression were other important findings.
In the light of these observations, CSF1/CSF1R interaction probably represents a more sensible therapeutic target than TNF-α blockade in the diffuse form of pigmented villonodular synovitis.
Pigmented villonodular synovitis
2006, Orthopedic Clinics of North America
Diffuse-Type Giant Cell Tumor of the Paratenon of Achilles Tendon Requiring Reconstruction Using Bilateral Autografts: A Case Report
2020, Journal of Foot and Ankle Surgery
Citation Excerpt :
Although the etiology of the condition is not controversial, an inflammatory or neoplastic process is believed to occur pathologically (11). Researchers have previously compiled a more detailed pathology of D-TPGCT and the osseous phenotype, such as expression of osteoclast characteristics (7) or colony-stimulating factors (15) and production of matrix metalloproteinases (16,17). Ankle joint cyclic loading may contribute to subchondral cysts in both entities (18,19).
Although a diffuse-type giant cell tumor is a rare benign lesion, when it develops it tends to localize to the tendons of the hand and foot. In this study, we report the case of a 41-year-old male patient who was diagnosed with diffuse-type paratenon giant cell tumor involving the Achilles tendon. The duration of the bilateral tumors was 8 years. He visited first affiliated Hospital of Wenzhou Medical University for medical attention. Both his Achilles tendons required removal. The reconstructed Achilles tendon was replaced using tissue derived from the knee and foot. Postoperatively, the patient recovered well and regained full range of motion in the ankle. The use of autografts may shorten patients’ recovery period.
Identification of potential diagnostic biomarkers for tenosynovial giant cell tumour by integrating microarray and single-cell RNA sequencing data
2023, Journal of Orthopaedic Surgery and Research
Multimodal management of tenosynovial giant cell tumors (TGCT) in the landscape of new druggable targets
2023, Journal of Surgical Oncology

View all citing articles on Scopus

^☆: Supported in part by a grant-in-aid for Advanced Medical Science Research by the Ministry of Science, Education, Sports and Culture, Japan.

^☆☆: Address correspondence and reprint requests to Takashi Sawai, MD, PhD, Department of Pathology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan.

View full text

Original ContributionsCell characterization of mononuclear and giant cells constituting pigmented villonodular synovitis☆,☆☆

Abstract

Section snippets

Materials and methods

Results

Discussion

Acknowledgements

Hum Pathol

Cell

Exp Cell Res

FEBS Lett

Cell

Cell

Hum Pathol

Pigmented villonodular synovitis, bursitis, and tenosynovitis

Arch Pathol

Multinucleated cells in pigmented villonodular synovitis and giant cell tumor of tendon sheath express features of osteoclasts

Am J Pathol

Pigmented villonodular synovitis (giant-cell tumor of tendon sheath and synovial membrane): A review of eighty-one cases

J Bone Joint Surg Am

Diffuse biarticular pigmented villonodular synovitis

Radiology

Roentgenographic aspects of articular pigmented villonodular synovitis

Am J Roentgenol

Pigmented villonodular synovitis

J Bone Joint Surg Am

Diagnostic features of diffuse pigmented villonodular synovitis of the knee

Clin Orthop Rel Res

KP1 (CD68) staining of granular cell neoplasms: Is KP1 a marker of lysosomes rather than the histiocytic lineage?

Histopathology

Human osteoclast formation and bone resorption by monocytes and synovial macrophages in rheumatoid arthritis

Ann Rheum Dis

Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor

Arthritis Rheum

Human arthroplasty derived macrophages differentiate into osteoclastic bone resorbing cells

Ann Rheum Dis

Expression of osteoclast differentiation factor at sites of bone erosion in collagen-induced arthritis

Arthritis Rheum

Analysis of the p53 tumor suppressor gene in rheumatoid arthritis synovial fibroblasts

Arthritis Rheum

Original Contributions
Cell characterization of mononuclear and giant cells constituting pigmented villonodular synovitis☆,☆☆