| Abstract|| |
Introduction: Synovium has been documented as a primary site of inflammation and a major effector organ in a variety of joint diseases. Study of simple technique like synovial biopsy can help in early diagnosis and treatment of diseases significantly improving outcome of patient in cases of rheumatoid arthritis, osteoarthritis, etc., Only limited data exist on utility of synovial biopsies. Aim and Objectives: To analyze the pattern of synovial lesions to differentiate between different kinds of arthritis. Also, to identify early stages of arthritis so as to prevent unnecessary invasive surgical procedure. Materials and Methods: It's a retrospective study to analyze 103 cases of synovial lesions diagnosed in last five years at a tertiary care orthopedic center. All synovial biopsies obtained mainly by open method and few by arthroscopic method, that came to the Dept of Pathology were included. Lesions were classified into four categories that is, inflammatory joint diseases, degenerative joint diseases, tumor-like conditions and tumors. Results: Age group most affected was between 61 and 70 years, with male predominance. Osteoarthritis (OA) was the most common histopathological diagnosis. Early OA tissues showed greater lining layer thickness, vessel proliferation, and inflammation, while surface fibrin deposition along with fibrosis was noted in later stages. Conclusion: The histo-morphological observations made in this study may have important therapeutic implications for some patients during the early evolution of arthritis and could prevent unnecessary operative intervention of later stages.
Keywords: Arthritis, synovial biopsy, synovium
|How to cite this article:|
Tevatia MS, Goyal N, Baranwal AK, Mishra P S, Gupta A, Sharma V, Agarwal M, Gupta PS, Dangwal V. A study to analyze the pattern of synovial lesions from synovial biopsies in a tertiary care centre. Indian J Pathol Microbiol 2021;64:702-6
|How to cite this URL:|
Tevatia MS, Goyal N, Baranwal AK, Mishra P S, Gupta A, Sharma V, Agarwal M, Gupta PS, Dangwal V. A study to analyze the pattern of synovial lesions from synovial biopsies in a tertiary care centre. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 Nov 27];64:702-6. Available from: https://www.ijpmonline.org/text.asp?2021/64/4/702/328563
| Introduction|| |
Synovium is the soft tissue which lines the spaces of diarthrodial joints, tendon sheaths, and bursae. It has continuous surface layer of cells known as intima and the underlying tissue known as subintima. Disease's related to synovial tissue has significant impact on quality of life of patient particularly those involving knee joint. Early and accurate diagnosis can prevent patient from landing into terminally ill state.
Indications for carrying out synovial biopsies include both benign and malignant cases. Benign infectious conditions with pathogens like neisseria, fungi, varicella zoster virus, suspected tuberculous arthritis may require a biopsy for definitive diagnosis. Non-infectious granulomatous states, such as sarcoidosis, affecting a joint can be diagnosed when typical histology of the involved synovia is demonstrated. Other inflammatory benign conditions such as rheumatoid arthritis can generally be diagnosed based on clinical, serological, radiological criteria alone and, routinely there is no requirement of a biopsy., However, the extent of damage to the joints and advancement of the disease, can only be predicted by histo-morphological examination.
Biopsy is also carried out in suspected cases of metastasis as well as the primary tumor of the synovium. Sometime leukemic arthritis may precede systemic onset and malignant cells may not be always visible in joint aspiration, especially if hemarthrosis is present., Pigmented villonodular synovitis is one of the differential diagnosis of mono- or oligoarticular arthritis and biopsy is always required for diagnosis. Deposits of gout and pseudogout can also be detected in synovial tissue and are of diagnostic significance in differentiating some mass lesions due to crystals from malignant causes., Synovial tissue may be obtained using blind needle technique during arthroscopy, or under ultrasonographic guidance. In our study most of the sampling was carried out using blind needle technique.
| Materials and Methods|| |
This study is a retrospective analysis of a total of 103 synovial biopsies received between Jan 2015 to Jan 2020 at a tertiary care center in western India. Relevant clinical and radiological details were obtained from the database. All the biopsies were stained for H and E and wherever necessary special stains like Zeihl-Neelsen stain for AFB and Prussian blue stain for hemosiderin were also done.
Synovial biopsies were obtained mainly by open method and few by arthroscopic method. Biopsy tissue was received in 10% buffered neutral formaldehyde. Sections were cut to 4–6 μ and stained by hematoxylin and eosin (H&E) followed by histopathological examination. Based on histomorphology, lesions were classified under four categories that is inflammatory joint diseases, degenerative joint diseases, tumors, and tumor-like conditions.
| Results|| |
In the present study, synovial lesions range from 2nd to 8th decade of life. Youngest patient was 21 years old and oldest was 80 years. The most common age groups affected was 61–70 years. Male were predominantly affected in our study, except in rheumatoid arthritis in which female predominance was seen.
Most common symptoms were pain and swelling of knee joint which was involved in 99% of cases. Most common histopathological diagnosis in our study was osteoarthritis (OA) followed by chronic nonspecific synovitis, rheumatoid arthritis (RA), and septic arthritis. Cases of benign tumors such as synovial lipoma arborescence, synovial lipoma, and pigmented villonodular synovitis (PVNS), giant cell tumor of tendon sheath, gout, and pseudogout arthritis were also noted in our study. Descriptive analysis of various synovial lesions found in the study is tabulated in [Table 1].
Out of 103 biopsies, 45.6% cases were of osteoarthritis because place of study predominantly being a knee replacement center. These cases on histology showed all stages of osteoarthritis. Early OA changes were seen in 71% of total OA cases compared to 29% cases which were showing late OA changes. Early OA tissues showed greater lining layer thickness along with infiltration of chronic inflammatory infiltrate such as plasma cells and vessel proliferation while surface fibrin deposition and fibrosis were seen in later stages of OA as depicted in [Figure 1]a and [Figure 1]b.
|Figure 1: (a) Synovial biopsy showing early osteoarthritic changes in form of vessel proliferation, presence of inflammation (H&E × 200), (b) Shows fibrin deposition in late stage of osteoarthritis (H&E × 200), (c) Synovial biopsy showing features of chronic non-specific inflammation (H&E × 200)|
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25.2% cases were of chronic non-specific inflammation, showing fibro-collagenous tissue with chronic inflammation in form of predominantly lymphocytes and plasma cells as shown in [Figure 1]c.
Totally, 13.6% cases of rheumatoid arthritis were reported, with female predominance in this sub-group. The histo-morphological features ranged from papillary frond and villi formation with intense inflammation, seen in 71.4% (10/14) cases. In advance stages there is formation of pannus, seen in 28.6% (4/14) cases that is formation of mass of edematous synovium with intense chronic inflammatory cells in form of predominantly plasma cells as shown in [Figure 2]a, lymphoid follicle formation, granulation tissue, macrophages, fibroblasts that grows over articular cartilage and causes erosion. At the same time the inflamed synovium demonstrated prominent blood vessel formation in 57.1% (8/14) cases. Fibrin deposition was seen in 28.6% (4/14) cases. Giant cell was noted in one case.
|Figure 2: (a) Synovial biopsy showing synovial hyperplasia with intense chronic inflammatory infiltrate in form of plasma cells (H&E × 100). (b) Synovial biopsy showing features of pigmented villonodular synovitis in form of giant cells, foamy cells, hemosiderin laden macrophages (H&E × 400)|
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This study reported 02 cases of Pigmented villo-nodular Synovitis (PVNS), one case each in male and female involving knee joint. They had characteristic microscopic features showing PVNS as shown in [Figure 2]b. One case of giant cell tumor of tendon sheath was reported. This was a female patient, aged 50 years. Grossly it was exclusively nodular, microscopically it showed less hemosiderin than PVNS but otherwise histologically similar.
There was one case of tubercular synovitis in a male patient having knee joint involvement. H and E stained section showed granulomas with Langhan's type of giant cells and caseous necrosis as shown in [Figure 3]a. Modified ZN stained showed presence of AFB as shown in [Figure 3]b.
|Figure 3: (a) Synovial biopsy showing features of Tubercular synovitis in form of ill formed granuloma, Langhans giant cells and chronic inflammation (H&E × 200), (b) ZN Stain: Showing acid fast bacilli per 1000 oil emersion field, (c) Synovial biopsy showing features of synovial osteo-chondromatosis, benign chondrocytes with enchondral ossification (H&E × 200|
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Septic arthritis was seen in 03 cases. Ulceration of the synovial lining with neutrophilic infiltration was seen in these cases.
This study had two cases of synovial chondromatosis, also known as synovial chondro-metaplasia or synovial osteo-chondromatosis. Microscopically one case showed characteristic multiple nodules of metaplastic hyaline cartilage, with endochondral ossification and no atypia while other case showed similar features with mild atypia and binucleated forms as seen in [Figure 3]c. One case of cartilaginous loose bodies was reported which showed similar feature as synovial chondromatosis but in setting of advance osteoarthritis.
Lipoma arborescence one of the rarest and a non-neoplastic synovial proliferative lesion. It possibly represents a secondary phenomenon following the degenerative process of the joint. We in our study had one case which grossly showed the entire synovium as bright yellow, nodular and also had papillary appearance. [Figure 4]a depicts characteristically fatty infiltration of the sub-synovial connective tissue seen.
|Figure 4: (a) Synovial biopsy showing features of Lipoma arborescence, fatty infiltration of the sub-synovial connective tissue (H&E × 100), (b) Synovial biopsy showing features of pseudogout showing purple crystals of calcium pyrophosphate (H&E × 200), (c) Synovial biopsy showing features of gout crystals of monosodium urate as amorphous pink tophaceous material surrounded by giant cell reaction (H&E × 200)|
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We reported one case of CPPD and one case of gout. Both CPPD and gout patient presented with pain in the knee joint. H and E stain showed purple crystals of calcium pyrophosphate as shown in [Figure 4]b and case of gout induced crystals showed amorphous pink tophaceous material surrounded by giant cell reaction and histiocytes as shown in [Figure 4]c.
| Discussion|| |
In the present study, the most common age groups affected was 61–70 years. This is similar to study conducted by Jayanthi KJ, et al. and Vijay PM, et al. where maximum cases were also in the age group of 61-70 years and 41-50 years, respectively. In a study by Kulkarni et al. on inflammatory lesions, predominant age group affected was between 11 and 30 year. The higher prevalence of inflammatory lesions in the elderly age group in our study as compared to other studies may be because most patients were referred as terminally ill cases after having conservative treatment and now who could only be managed by replacement surgeries.
Male were predominantly affected population in our study as compared to female, with male to female ratio of 1.5:1, except in rheumatoid arthritis in which female predominance was seen (1:1.8). The results are similar to the other studies conducted on the subject by Jayanthi KJ, et al.; Vijay PM, et al.; Sant MS etc., which show male to female ratio of 1.11:1, 1:0.6, and 1:0.58, respectively.,,
Most common histo-pathological diagnosis in the study was osteoarthritis 43.7%, followed by chronic nonspecific synovitis 25.2%, rheumatoid arthritis 13.6% and septic arthritis 2.9%. Study by Jayanthi KJ, et al. showed chronic non-specific synovitis 73% as the commonest inflammatory synovial lesion, followed by tubercular arthritis 7.0%, septic arthritis 6.5% and rheumatoid arthritis 6.07%. In Vijay PM, et al. study chronic non-specific synovitis was 71%, followed by tubercular synovitis 18.07% and in study by Kulkarni et al. chronic non-specific synovitis 49% was commonest, followed by rheumatoid arthritis 14%, tubercular synovitis 10%. Increase reporting of chronic non-specific synovitis in these studies was may be due to biopsy done at early stages of rheumatoid arthritis or early osteoarthritis which were not showing characteristic histopathological and radiological features required for the specific diagnosis. Hence, these cases, may have been diagnosed as non-specific inflammation rather than specific diagnosis of osteoarthritis or rheumatoid arthritis.
Osteoarthritis was the most common lesion observed in our study being tertiary care knee replacement orthopedic center. We reported 45.6% cases of osteoarthritis. In our study we had features of marked inflammation in early stages compared to later. This finding could help clinicians as deciding factor for conservative treatment or surgery as early cases will respond to anti-inflammatory drugs in view of marked inflammation at early stages (71% cases in our study) as compared to later stages (29% cases in our study) which will show lesser response to drugs and might benefit from surgery only. So early changes could become deciding factor in type of treatment. This study showed concordance rate with M J Benito et al. who also reported the role of inflammation at early and late stages.
Rheumatoid arthritis mainly involves peripheral joints like small joints of hands and feet with female predominance and peak age of 20–40 years. Our study showed, female predominance with male: Female ratio of (1:1.8), this finding is consistent with Archana Panage et al. Predominantly knee (95%) joint is affected in our study and other joints affected were wrist joints (5%) and shoulder joints (2%). A study by Jayanthi KJ had taken into account parameters such as synovial hyperplasia, fibrosis, vascular proliferation, and inflammation. In our study, synovial hyperplasia with lymphoid aggregates were consistently seen in synovial biopsies of all the clinically suspected rheumatoid arthritis.
Tenosynovial giant cell tumors (TSGCT) are a group of benign intra-articular and soft tissue tumors with common histologic features. They can roughly be divided into localized and diffuse type both of which includes giant cell tumors of tendon sheath and pigmented villonodular synovitis. Pigmented villonodular synovitis is a benign proliferative disorder of synovium that occurs most commonly in the third and fourth decades of life and is characterized by the onset of unilateral pain and swelling of a joint, typically the knee (80%); though any synovial joint may be affected. Lesion is best diagnosed by synovial biopsy. In our study, two cases were seen with one case each in male and female involving knee joint. Our findings are in concordance with Jayanthi KJ and Sterling G, et al. West et al. who showed similar histological features as in our study that is marked synovial cell hyperplasia , mononuclear rounded, and epithelioid cells, multinucleated osteoclast like giant cells, lipid-filled macrophages, hemosiderin deposits are between and within cells. Giant cell tumor of tendon sheath is the most common form of TSGCT. As the name implies, it arises from synovial-lined tendon sheaths. Mostly these tumors occur in the digits, especially the fingers, over volar surfaces. It can occur at any age, with peak incidence is in the third to fourth decades. It is an indolent tumor and show female predominance and may represents extra articular analogue. Our study is in concordance with Di Grazia S, Succi G, et al., had only one case in a female patient aged 30 years who presented with wrist joint, painless, slowly growing swelling over years. Histological features were identical to PVNS having multinucleated giant cells, mononuclear cells and macrophages and less hemosiderin than PVNS. However, in a study by Sterling G. West et al., showed more hemosiderin and presence of xanthoma cells which was not found in our study.
There was only one case (0.97%) of tubercular synovitis, in a male patient having knee joint involvement. H and E stained section showed granulomas with Langhan's type of giant cells and caseous necrosis and modified ZN stained showed presence of AFB. However, in a study by Jayanthi KJ, et al. Tubercular synovitis was the second most common lesion constituting 7%.
Lipoma arborescence one of the rarest and a non-neoplastic synovial proliferative lesion. In our study we found one case of Lipoma arborescence, patient aged 40 years this was in concordance with age group of 39–66 years in study by Hallel et al. however our study showed female patient whereas study by Rao et al. and Jayanthi KJ, et al. which had eight and two cases of lipoma arborescence respectively showed male predominance. Characteristic histological features of fatty infiltration of the sub synovial connective tissue was found in our study and also in study by Hallel et al., Rao et al., and Jayanthi KJ et al.
Synovial chondromatosis is a rare condition in which foci of cartilage develop in the synovial membrane of joints, bursae, or tendon sheaths as a result of metaplasia of the sub-synovial connective tissue. These ectopic foci of cartilage can result in painful joint effusions and, on the generation of loose bodies, mechanical symptoms. Anne C. Brower et al. mentioned in the study that synovial chondromatosis is not to be confused with the chondral and osseous fragments seen in a patient with severe osteoarthritis. In this latter situation, not only are there changes of osteoarthritis, but also the calcified fragments seen vary in size and shape. Our study also showed similar case where in loose bodies were formed in background of osteoarthritis.
Crystal arthropathies are systemic disorders and show presence of crystals within synovium, articular cartilage, and periarticular soft tissue. The three endogenously formed crystals that produce disease are monosodium urate (Gout), calcium pyrophosphate dihydrate (Pseudogout), and calcium hydroxyapatite. Synovial biopsy shows characteristic intra articular calcified deposits in synovium, articular cartilage or menisci and affects the knee joint in most of the cases. Our study had two cases of CPPD, both male patient and aged 75 and 83 years which was in concordance with Zhu Y, et al. Characteristic histological features that is purple crystals of calcium pyrophosphate were seen in study by Zhu Y, et al. and Jayanthi KJ, et al. and in our study.
Gout is common in males with prevalence of 3% of the population. Characteristic feature in Synovial biopsy were seen as amorphous pink tophaceous material surrounded by giant cell reaction and histiocytes, as seen by Gupta SJ, et al.
| Conclusion|| |
There are not too many studies carried out on the pattern of synovial lesions in Indian setting. This study brings out that synovial tissues can have a predominant role in histomorphological diagnosis of different kind of arthritis as well as in recognizing early phase of arthritis which may have important therapeutic implications in preventing unnecessary operative intervention of later stages. Histological analysis of synovial biopsies proves to be a valuable tool in establishing an early and specific diagnosis.
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Department of Pathology, Command Hospital Southern Command, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4]