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Rheumatology Advance Access originally published online on October 18, 2005
Rheumatology 2006 45(2):192-195; doi:10.1093/rheumatology/kei117
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Diagnostic value of blind synovial biopsy in clinical practice

E. J. A. Kroot1,2, A. E. A. M. Weel2, J. M. W. Hazes2, P. E. Zondervan3, M. P. Heijboer4, P. L. A. van Daele5 and R. J. E. M. Dolhain2

1 Department of Rheumatology, St Franciscus Hospital and Departments of 2 Rheumatology, 3 Pathology, 4 Orthopaedics and 5 Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.

Correspondence to: R. J. E. M. Dolhain, Erasmus MC, Department of Rheumatology, Z-712, PO Box 2040, 3000 CA Rotterdam, The Netherlands. E-mail: r.dolhain{at}erasmusmc.nl


   Abstract
Top
 Abstract
Introduction
 Materials and methods
 Results
 Discussion
 References
 
Objective. To assess the diagnostic value of blindly performed synovial biopsies in carefully selected patients with unclassified arthritis.

Methods. Synovial tissue was obtained blindly under local anaesthesia. The Arthroforce III take-apart 3.5 mm needle and 1.5 mm grasping forceps were used for this purpose.

Results. Four patients with unclassified arthritis could be diagnosed properly based upon examination of synovial tissue of the knee obtained by an easy-to-perform blind biopsy. The arthritis of the four patients was diagnosed as being part of Erdheim–Chester disease, sarcoidosis, multicentric reticulohistiocytosis and arthritis caused by foreign-body material, respectively.

Conclusions. Analysis of synovial tissue obtained during a blind biopsy procedure has diagnostic potential in carefully selected patients with unclassified arthritis. The common denominator in all the cases presented was a differential diagnosis consisting of a rheumatological disease with characteristic histological features.

KEY WORDS: Blind biopsy, Synovial membrane, Diagnosis, Histology, Arthritis


   Introduction
Top
 Abstract
 Introduction
Materials and methods
 Results
 Discussion
 References
 
Synovial biopsies are seldom used for diagnostic purposes. In general, patient interview, clinical examination, routine laboratory testing, radiographic examination and synovial fluid analysis usually suffice to establish a correct diagnosis. Synovial biopsy analysis is only justified in cases with a high degree of suspicion of atypical infectious agents, evaluation for intra-articular tumours and diseases with characteristic histological features [1, 2]. In these cases, identifying the correct diagnosis is of major importance since it may lead to adjustment of therapy.

Biopsies of synovial tissue for diagnostic purpose are usually performed by the use of orthopaedic arthroscopies requiring specially equipped rooms and partial or total anaesthesia, limiting the value of histology of synovial tissue in daily clinical practice [1–4].

The present case series demonstrates that in selected cases a proper diagnosis can be based upon examination of synovial tissue obtained by the use of an easy-to-perform blind biopsy. This procedure led to adjustment of therapy in all the patients presented here.


   Materials and methods
Top
 Abstract
 Introduction
 Materials and methods
Results
 Discussion
 References
 
Synovial tissue samples were obtained blindly under local anaesthesia. Briefly, after sterile precautions, the suprapatellar pouch was approached laterally and inflated with approximately 30 ml of lidocaine 1% using a 21-gauge needle. Subsequently, when withdrawing the needle from the joint cavity, the subcutaneous tissue and skin overlying the suprapatellar pouch were thoroughly infiltrated with lidocaine 1%. Next, a small incision was made into the skin and a portal (diameter 4.5 mm; 28146 OT; Stöpler, Utrecht, The Netherlands) was inserted into the suprapatellar pouch. Through this portal between 15 and 25 biopsies were taken from different parts of the suprapatellar pouch using a grasping forceps with scoop-tipped ends (Arthroforce III take-apart 3.5 mm needle and 1.5 mm grasping forceps; Stöpler). After this procedure the biopsy specimen was placed in paraformaldehyde 4% and processed for routine histology.


   Results
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 Abstract
 Introduction
 Materials and methods
 Results
Discussion
 References
 
Case 1
An 58-yr-old man known to have Erdheim–Chester disease (ECD), a rare multisystem histiocytic disorder [5, 6], was admitted with a septic arthritis of the left knee caused by Salmonella paratyphi B. The patient was treated with antibiotics and frequent punctures of the infected joint. Despite this treatment, the arthritis of the knee persisted. Several synovial fluid cultures did not reveal an infective agent. However, cultures of synovial fluid are generally less sensitive than cultures of synovial tissue and therefore low-grade persistent arthritis can be missed [1]. Furthermore, although rare, arthritis can be a feature of ECD itself. To distinguish between these two possibilities, blind biopsy of the knee was performed. Cultures of synovial tissue did not reveal an infectious agent. Histological examination of the synovial specimens revealed infiltration of histiocytes and Touton giant cells (Fig. 1A) and the arthritis was diagnosed as a feature of ECD itself. The patient was treated with intra-articular corticosteroids, which resulted in the disappearance of the arthritis.


Figure 1
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  		FIG. 1. Histological examination of synovial tissue. (A) Erdheim–Chester disease: infiltration of histiocytes (a) and Touton giant cells (b). (B) Sarcoidosis: well-defined non-caseating granuloma (c), a collection of epithelioid cells (d) and multinucleated giant cells (e). (C) Multicentric reticulohistiocytosis: infiltrate consisting of histiocytes (f) and foam cells (g). In the cytoplasm of some of these cells a foamy appearance with tiny vacuoles is observed. (D) Arthritis caused by foreign-body material. Foreign-body material (h) is surrounded by giant cells (i).

 
Case 2
A 39-yr-old woman was admitted to our hospital with decreased sense of hearing, vertigo, dry eyes, secondary amenorrhoea and progressive loss of vision. Routine laboratory testing revealed no abnormalities. On a standard chest X-ray bilateral hilar lymphadenopathy was observed. Because of the clinical presentation and these radiological findings, the differential diagnosis consisted of neurosarcoidosis and lymphoma. Because of the high sensitivity of tissue analysis of the liver in sarcoidosis, biopsy of the liver was performed [7]. Unfortunately no diagnosis could be made. Therefore, somatostatin receptor scintigraphy was performed [8]. This technique has the capacity to localize granulomas for eventual subsequent histological examination [8]. Besides the bilateral hilar lymphadenopathy, increased uptake was observed in the glandula parotis, bilateral orbita, nose and right knee. Remarkably, by clinical examination no signs of arthritis of the right knee were observed. Tissue analysis of the glandula parotis and the hilar lymph nodes was not considered primarily, due to the risk of major complications. Since the nose and knee are easily accessible, both were biopsied. Tissue analysis of the mucosa of the nose could not reveal the diagnosis. Only histological examination of biopsy samples of the right knee showed well-defined non-caseating granulomas, including epithelioid cells and multinucleated giant cells (Fig. 1B). The diagnosis of sarcoidosis was established and the patient was successfully treated with prednisolone and antimalarials.

Case 3
This patient, a 47-yr-old man, presented with joint pain, muscle weakness, fatigue and skin abnormalities. Complaints started 1 yr before presentation and were progressive since then. Physical examination revealed several cutaneous papulonodular, but no psoriatic, lesions on the arms and head and arthritis of almost all joints. X-rays of the hands and feet showed erosions in several joints, including the distal interphalangeal joints. On a chest X-ray no abnormalities were observed. Tests for rheumatoid factor and anti-citrullinated protein antibodies, as detected by an anti-cyclic citrullinated peptide 2 enzyme-linked immunosorbent assay, were negative. Although seronegative destructive rheumatoid arthritis (RA) and psoriatic arthritis were considered in the differential diagnosis of this patient, a diagnosis of multicentric reticulohistiocytosis (MR) seemed more likely. Since this latter diagnosis needs histological confirmation, skin biopsy and blind synovial biopsies of the knee were performed. Both biopsy sides revealed infiltrates consisting of histiocytes and foam cells. In the cytoplasm of some of these cells a foamy appearance containing small vacuoles was seen (Fig. 1C). Because of these characteristic histological findings, the patient was diagnosed as having MR [9]. Since therapy with corticosteroids, antimalarials, methotrexate and ciclosporin was not able to stop the progression of joint erosions, treatment with anti-TNF1{alpha} [10] was started. The clinical response to this therapeutic strategy has to be further evaluated, but seems promising.

Case 4
This 27-yr-old patient, known to have the Ehlers–Danlos syndrome, experienced deteriorating instability of the left knee in March 2002. Subsequently, arthroscopic fixation of the lateral meniscus was performed with a polyester suture (Ticron) [11]. The dorsolateral instability was treated by replacing the popliteofibular ligament with synthetic material, localized extra-articularly. The postoperative course was uncomplicated. In February 2003 the patient again experienced a deterioration in the stability of the left knee. Because of the persisting instability in the subsequent months, arthroscopy, followed by a partial meniscectomy of the lateral meniscus, was performed. This procedure was complicated by septic arthritis of the knee, caused by Stenotrophomonas maltophilia, which was treated with intravenous antibiotics for several weeks. Subsequently the patient experienced chronic relapsing arthritis of the operated knee joint, with repeatedly high numbers of leucocytes (range 36–68x109/l). Nevertheless, synovial fluid cultures and blood cultures during this period remained negative. Because of these findings and the recent surgical interventions on the knee, the differential diagnosis consisted of low-grade persisting septic arthritis and arthritis caused by foreign-body material [11]. Blind biopsy of the knee was performed in order to obtain synovial tissue for histology and culture. Cultures of synovial tissue did not reveal an infectious agent. Histological examination of the synovial tissue demonstrated birefringent foreign-body material surrounded by giant cells (Fig. 1D), confirming the diagnosis arthritis caused by foreign-body material. As additional magnetic resonance imaging of the knee could not visualize synthetic materials in the knee joint, an arthroscopic synovectomy of the knee joint was performed and the extra-articularly localized synthetic material was removed. In subsequent months the patient experienced no swelling or tenderness of the knee.


   Discussion
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
References
 
The value of histological examination of synovial tissue for diagnostic purposes in unclassified arthritis is still elusive [1, 2, 12]. The present case series underscores the importance of histology, since in all cases the correct diagnosis was based upon histological examination of synovial tissue. The common denominator of all these cases is that the differential diagnosis includes diseases with specific histological characteristics. The presented cases demonstrate that this additional diagnostic value of histology is of major importance since it led to adjustment of therapy in all patients.

At present, conventional arthroscopies are predominantly used for synovial tissue analysis in unclassified arthritis. Advances of this method include the ability to obtain synovial tissue biopsies under direct vision, the possibility of examination and performing biopsies of other joints than the knee, and the possibility of immediate explorative intervention [13, 14]. Disadvantages of these conventional arthroscopic techniques include the facts that they cannot be performed under local anaesthesia and must be performed in specially equipped rooms.

High-definition, small-bore arthroscopies permitting day-case arthroscopy at out-patient clinics are also being used for this purpose. Compared with conventional arthroscopy, this technique has the advantage of allowing biopsies to be taken under local anaesthesia, i.e. it can be performed by inflating the joint and overlaying skin with lidocaine. In addition, synovial tissue biopsies can be obtained under direct vision and can also be performed on joints other than the knee. A disadvantage is the fact that this procedure needs explicit skills and is therefore not useful in typical out-patient clinics up to now. Additionally, a specially equipped room is required to perform these small-bore arthroscopies.

In the cases presented here, synovial tissue samples were obtained blindly by the use of traditional grasping forceps. This resembles the closed needle (Parker–Pearson) technique, which is the most common technique used to perform blind synovial biopsies from a knee joint [1, 2, 4]. Instead of using grasping forceps, the technique described by Parker and Pearson makes use of a hollow biopsy needle with a hooked notch. Biopsies can be taken by applying suction to this needle using a Luer-Lok syringe. Although comparative studies are not available, we find traditional grasping forceps easier to use, especially if a knee joint is clinically not inflamed. Besides this small difference, in our opinion the two techniques are comparable. In both techniques synovial tissue is obtained from the suprapatellar pouch and both techniques can be performed routinely in the consulting room. Since using either technique several synovial biopsies can be obtained during one procedure, the sampling error can be reduced greatly, giving a variability of less than 10% [15].

A disadvantage of using blind synovial biopsy techniques is that synovial tissue cannot be obtained under visual guidance. When studying RA patients this does not seem to be of major importance [13]. However, for some diseases, such as gouty arthritis, taking biopsies under visual guidance can be an advantage [16].

In the first patient it was possible to diagnose the arthritis as a feature of ECD. This is the first time that synovial tissue analysis has established the diagnosis of arthritis as a feature of ECD. The diagnosis of ECD is usually established by histological examination of bone, retro-orbital or lung tissue, characterized by histiocytes with non-Langerhans cell features [5, 6].

In the second case the diagnosis of sarcoidosis was finally established upon synovial tissue analysis. Remarkably, analysis of synovial tissue of a clinically unaffected joint obtained by blind biopsy led to the correct diagnosis. The finding of histological features of a rheumatic disease in a clinically unaffected joint is in line with current literature [17].

In the third patient MR was suspected, a disease that is sometimes hard to distinguish from RA or psoriatic arthritis. Blind biopsy samples of synovial tissue revealed typical histological features of MR, including infiltration of multinucleated histiocytic giant cells, confirming the diagnosis of MR [9].

The fourth patient was suspected of foreign-body material arthritis or septic arthritis. Histological examination offers the possibility of differentiating between these two disorders as foreign-body material inflammation can be demonstrated by birefringent foreign-body material surrounded by giant cells, in contrast to septic arthritis [11]. The diagnosis was confirmed by finding these disease-characteristic birefringent foreign-body materials and giant cells by analysis of synovial tissue obtained during a blind biopsy procedure.

In conclusion, the present case series demonstrate that blind biopsy can be an effective diagnostic tool with therapeutic consequences in carefully selected patients with unclassified arthritis. This is especially so when the differential diagnosis consists of a rheumatological disease with characteristic histological hallmarks. In our opinion, prospective studies to further confirm the value of analysis of synovial tissue obtained during a blind biopsy procedure for diagnosing unclassified arthritis are clearly warranted in the near future [18, 19].
Figure 2

The authors have declared no conflicts of interest.


   References
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 

  1. Bresnihan B. Are synovial biopsies of diagnostic value? Arthritis Res Ther 2003;5:271–8.[Medline]
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  5. Shamburek RD, Brewer HB Jr, Gochuico BR. Erdheim-Chester disease: a rare multisystem histiocytic disorder associated with interstitial lung disease. Am J Med Sci 2001;321:66–75.[Medline]
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  8. Dalm VA, van Hagen PM, Krenning EP. The role of octreotide scintigraphy in rheumatoid arthritis and sarcoidosis. Q J Nucl Med 2003;47:270–8.[Medline]
  9. Gorman JD, Danning C, Schumacher HR, Klippel JH, Davis JC Jr. Multicentric reticulohistiocytosis: case report with immunohistochemical analysis and literature review. Arthritis Rheum 2000;43:930–8.[CrossRef][ISI][Medline]
  10. Kovach BT, Calamia KT, Walsh JS, Ginsburg WW. Treatment of multicentric reticulohistiocytosis with etanercept. Arch Dermatol 2004;140:919–21.[Free Full Text]
  11. Warme WJ, Burroughs RF, Ferguson T. Late foreign-body reaction to Ticron sutures following inferior capsular shift: a case report. Am J Sports Med 2004;32:232–6.[Free Full Text]
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  13. Youssef PP, Kraan M, Breedveld F et al. Quantitative analysis of inflammation in rheumatoid arthritis synovial membrane samples selected at arthroscopy compared with samples obtained blindly by needle biopsy. Arthritis Rheum 1998;41:663–9.[CrossRef][ISI][Medline]
  14. Baeten D, Van den Bosch F, Elewaut D, Stuer A, Veys EM, De Keyser F. Needle arthroscopy of the knee with synovial biopsy sampling: technical experience in 150 patients. Clin Rheumatol 1999;18:434–41.[CrossRef][Medline]
  15. Dolhain RJ, Ter Haar NT, De Kuiper R et al. Distribution of T cells and signs of T-cell activation in the rheumatoid joint: implications for semiquantitative comparative histology. Br J Rheumatol 1998;37:324–30.[Abstract/Free Full Text]
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Submitted 17 May 2005; revised version accepted 8 August 2005.
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