30 Annals of the Rheumatic Diseases 1994; 53: 30-34

Rotator cuff degeneration and lateral epicondylitis: Ann Rheum Dis: first published as 10.1136/ard.53.1.30 on 1 January 1994. Downloaded from a comparative histological study

M D Chard, T E Cawston, G P Riley, G A Gresham, B L Hazleman

Abstract rotator cuff with age would at least give insight Objectives-Rotator cuff tendinitis and into changes that occur which might pre- lateral epicondylitis are common in clini- dispose individuals to symptomatic lesions. cal practice but the underlying pathology Studies on cadavers have described changes is poorly understood. The study examined within the rotator cuff and also at their both normal and biopsy tendon specimens insertion. It is probable that changes within the histologically, to determine the mechan- tendon itself are of most relevance to clinical isms involved in tendon degeneration. symptoms. Rupture of the cuff and calcifi- Methods-Rotator cuff tendons from 83 cation is usually seen within the substance of cadavers aged 11-94 and tendon biopsy the tendon, 1-2 cm from the insertion. As this specimens from 20 patients with lateral area is the 'watershed zone' of blood supply epicondylitis aged 27-56 years were from muscle and bone it is relatively avascular examined histologically. making it prone to ischaemic stress and has Results-The microscopic changes found been called the critical zone. However, a recent in the tendon biopsies from the elbow were qualitative study5 on the number and size of similar to those found in the cadaveric blood vessels in this region suggests that there rotator cufftendons. Abnormalities ranged is little difference between the supraspinatus from minor blood vessel wall changes and and infraspinatus tendons. As most problems loss oftenocytes to calcification. The most occur in the supraspinatus tendon, other frequent abnormality was glycosamino- factors in addition to blood supply most pre- glycan infiltration and fibrocartilaginous dispose this tendon to degenerate. transformation. There appeared to be Rotator cuff degeneration has had limited some sequence in the changes observed study. An early investigation by Lindblom in which were milder in younger patients. 1939,6 was followed by an extensive study on Only 17% of cadaver tendons, below the 125 cases by Wilson and Duff in 19437 who age of39 were abnormal but abnormalities attempted to grade the severity of changes and increase in later life to around 40-50%. looked at the effects of age. A later paper by Conclusions-There was an increasing Brewer on just three tendons8 included some http://ard.bmj.com/ incidence of degenerative changes in ten- electron microscopy studies and most recently dons with age. The changes observed in an investigation by Clark9 emphasised the inter- biopsy samples of common extensor ten- dependance of the individual components of dons were the same as those seen in aged the rotator cuff. These studies are descriptive supraspinatus tendons, but these changes and it is often unclear how frequently changes were not seen in control common extensor were found and at what age. tendons. The region of the tenoperiosteal junction is on September 26, 2021 by guest. Protected copyright. believed to be the usual site of the lesion in (Ann Rheum Dis 1994; 53: 30-34) lateral epicondylitis, although only minor age- related changes have been documented. A variety ofabnormalities have been documented Rotator cuff tendinitis and lateral epicondylitis in operative specimens. Tendon rupture is (tennis elbow) are the principal soft tissue uncommon and the relationship to previous lesions affecting the upper limb and are local steroid injections is uncertain.'° Micro- Rheumatology commonly seen in rheumatological and ortho- fractures, cystic and fibrinoid degeneration Research Unit, paedic practice.' Together they give rise to and round cell infiltrations (often considered Addenbrooke's Hospital, considerable disability within the adult popu- to be inflammatory granulation tissue) and Cambridge, lation, yet the underlying pathology remains attempts at repair have been described in some United Kingdom unclear. Like many soft tissue lesions, biopsy specimens.'13 Macnab reported that some M D Chard T E Cawston is not necessary for diagnosis and surgery is not degenerate cadaver rotator cuff tendons show G P Riley often indicated. Therefore material for patho- changes that might be interpreted as granu- B L Hazleman logical study is rarely available. lation tissue.'4 Department of Age-related or degenerative changes in We proposed that there might be similarities Histopathology, tendon would appear to predispose to lesions, in the pathological changes that occur with age Addenbrooke's Hospital, as rotator cuff tendinitis and tennis elbow in the rotator cuff, and which probably pre- Cambridge, are infrequently seen before middle age.2 3 In dispose to symptomatic lesions, and those seen United Kingdom addition, rotator cuff rupture is a frequent in the condition of lateral epicondylitis. In this G A Gresham finding in elderly cadavers, although the study we investigated the changes with respect Correspondence to: Dr Hazleman. relationship of age-related change to symptoms to age that occur in rotator cuff tendons and Accepted for publication has been thought to be poor.4 In the absence compare them with those seen in tendons IAugust 1993 of operative material, a study of changes in the removed from patients with lateral epicondyli- Rotator cuff degeneration and lateral epicondylitis 31

tis. It was hoped that this study would give thinning, or a small perforation (8 right and insight into the frequency of the changes that 2 left). There were also 7 which had areas of

occur in tendon with age and disease. thickening in the tendon, with calcification in Ann Rheum Dis: first published as 10.1136/ard.53.1.30 on 1 January 1994. Downloaded from 4 cases. Twenty eight rotator cuff tendons had histo- Methods logical abnormalities and these changes are The rotator cuffs were obtained from cadavers listed in table 1. The mild changes included at necropsy within 48 hours of death. For local thickening of the blood vessel walls with the ethical considerations the rotator cuff was formation of collagen in association with them removed without removal of the shoulder (fig 1A). Cell 'fall-out' (that is, a reduction joint itself. A longitudinal incision was made in the number of tenocytes) was the next extending over the lateral aspect of the visible abnormality. Fifteen specimens, showed shoulder to below the deltoid insertion. The the most frequent change, an increase in deltoid was reflected back and the shoulder glycosaminoglycans. This was laid down positioned to reveal the rotator cuff. The between the tendon fibrils. It was pre- conjoined tendons of supraspinatus and infra- dominantly found close to blood vessels, but it spinatus (plus a variable amount of sub- was more diffuse in those with the most scapularis) were removed by incision at the marked changes (fig 1B). In 9 of the 15 cases bony insertion and muscle origin. The bony where glycosaminoglycan infiltration of the insertion could therefore not be examined tendon was found, there was also patches of microscopically and the area of interest for this fibrocartilaginous change. In 7 specimens, how- study was the 'critical area' approximately 1" ever, fibrocartilaginous change was found from the point of insertion.15 16 Specimens alone, without glycosaminoglycan infiltration. were then trimmed to remove all muscle tissue, These occurred either in plaques or as more fat and as far as possible, all remains of the diffuse change. subacromial bursa and shoulder joint lining, Rounded cells with the appearance of chon- without disrupting the tendon which forms drocytes, sometimes arranged in rows between the bonding between the two. No cadaver the collagen fibrils, were found (fig 1 C). These had a known history of shoulder pain as changes were sometimes accompanied by assessed from medical records. Cadavers who areas of fibrocartilage within the tendon sub- had a large rupture of the rotator cuff were stance associated with glycosaminoglycan pro- excluded. duction (fig 1B), but in some cases no increase All specimens from the shoulder and elbow in glycosaminoglycan was seen (fig 1 C). This were preserved in formal saline until processed. could be due to difficulties with reliably Histological examination including staining with staining the glycosaminoglycans in the sections. Haematoxylin and Eosin, Weigert's Resorcin This section (fig 1 C) illustrates the classic Fuchsin, Ponceau S (showing elastic fibres 'glassy' appearance observed in some tendon black and collagen red) and Alcian Blue at biopsy specimens. In its most severe form the Acid pH (to show glycosaminoglycan). Speci- fibrocartilage was undergoing calcification http://ard.bmj.com/ mens were batch processed and microscopic producing poorly formed bone. The most examination was performed by the same florid cases were seen in association with syn- investigator (GAG) and was undertaken with- ovial chondromatosis. Some tendons (fig 1D) out knowledge of specimen details to ensure showed the deposition of calcium in regions blind conditions. that also stained positively with Alcian blue. These calcium deposits did not always stain well with von Kossa stain. This may indicate on September 26, 2021 by guest. Protected copyright. SPECIMENS that hydroxy-apatite may not be the pre- Eighty three rotator cuff tendons were dominant form of calcium deposited. examined with an age range of 11 to 94 years. The numbers of the rotator cuff tendons in There were 48 men, 21 specimens were from each decade and the relative percentage found the left and 27 were from the right shoulder. to be abnormal are listed in table 2. Abnor- Thirty five women were studied, 16 were from malities increase in middle life to remain fairly the left shoulder and 19 from the right. Rotator constant at around 40% and then increase to cuffs were removed from both shoulders in 57% for those of 90 years and over. Perhaps 3 patients (2 men and 1 woman). unexpectedly no abnormal specimens were Common extensor tendon biopsy specimens found in the age range of 40 to 49, although from patients with lateral epicondylitis were around a quarter were abnormal in the pre- taken from 20 patients (9 male, 11 female) ceding decade. Changes were found approxi- with an age range of 27 to 56 years (mean 44 mately twice as frequently in those over 90 years) at the time of a lateral release procedure compared with those under 40. Several very around the site of insertion. Nine control biopsies were taken from cadavers of similar Table 1 Histological changes in the rotator cuff age with no recorded history of elbow pain. Number ofcases Glycosaminoglycan infiltration Results + fibrocartilagenous change 9 ROTATOR CUFF SPECIMENS Fibrocartilagenous change + calcification 7 Blood vessel wall thickening At the time of removal, 10 rotator cuff speci- +/or tenocyte loss alone 6 mens had macroscopic evidence of a partial Glycosaminoglycan infiltration alone 6 rupture, with either marked irregularity and Increased elastic tissue (?normal variant) I 32 Chard, Cawston, Riley, Gresham, Hazleman

I Ann Rheum Dis: first published as 10.1136/ard.53.1.30 on 1 January 1994. Downloaded from

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Figure 1 (A) Thickening ofblood vessel walls with collagen deposition in association with the vessel in a human supraspinatus tendonfrom a 67year old woman. Elastin/Ponceau S stain (Bar = 100 tcM); (B) Increase of glycosaminoglycan deposited between tendonfibrils in a human supraspinatus tendonfrom a 76 year old woman. Alcian blue/periodic acid Schiffstain. (Bar = 100 ,M); (C) Roundedfibroblasts with the appearance ofchondrocytes between the collagenfibrils in a supraspinatus tendonfrom a 93year old woman. Haematoxylin and Eosin stain. (Bar = 100 M)V; (D) Calcium deposit in a human supraspinatus tendonfrom a 94year old ruptured tendon (female). Alcian blue/periodic acid Schiffstain. (Bar = 100 p,M).

elderly subjects had complete massive ruptures Table 3 Histological changes ofcommon extensor tendons which could not be assessed in this study and Abnormalities Number ofspecimens so the true level of tendon abnormality in this showing abnormality group is really higher than that recorded. Glycosaminoglycan infiltration 13 The changes observed did not correlate with New bone formation at site of tendon insertion 6 sex, body weight, manual occupation or side of 4

Fibrofatty change http://ard.bmj.com/ body affected, although macroscopic changes Partial rupture 4 included more partial ruptures in the right Fibrocartilage formation + calcification 2 shoulder. noticeable fibrofatty change, 2 with increased COMMON EXTENSOR TENDON SPECIMENS elastin. There were 4 specimens that showed The microscopic changes found in the com- changes suggesting partial rupture, with ten- mon extensor tendon biopsies showed similar don insertion disorganisation in 3, and cartilage on September 26, 2021 by guest. Protected copyright. changes to that found in the cadaveric rotator dehiscence in another one. One specimen cuff tendons and are detailed in table 3. In 13 showed changes at the tendon attachment specimens there was a moderate or marked suggesting myxoid fibrillar proliferation. increase in glycosaminoglycan within the ten- In 1 case a mild lymphocyte infiltration was don close to the insertion. Six specimens found and in another, giant cells were observed. showed evidence of new bone formation at the These changes were not observed in nine site of tendon insertion (distinct from the specimens taken from cadavers of similar age. normal transitional area of tendon insertion In the control biopsies there was some into bone) (fig 2) with or without increase in patchy glycosaminoglycan between tendon glycosaminoglycan. In a further 2 cases, fibro- fibres but of a very mild nature in 2 cases. Two cartilage was forming within the tendon, specimens had patchy irregular calcification at calcifying in one (fig 3), while in 4 there was the junction of tendon insertion into bone and 1 showed some evidence of arterial thickening Table 2 Number ofpatients in decades with number and of blood vessels in the tendon. percentage ofabnormal specimens in rotator cuffs Age Number in Number % ofdecades decades abnormal Discussion 10-19 5 0 0% Although the association between the changes 20-29 2 0 0% in the rotator cuffs of cadavers and clinical 30-39 1 1 3 27% 40-49 7 0 0% disease is uncertain, it might be expected that 50-59 1 0 4 40% those subjects with an abnormality would have 60-69 1 0 4 40% 70-79 1 9 8 42% a predisposition to tendinitis. None of the 80-89 1 2 5 42% subjects in this study had any hospital record 90-99 7 4 57% of shoulder symptoms, but it is unknown Rotator cuff degeneration and lateral epicondylitis 33

vessels in human supraspinatus and infra- AP spinatus tendons. They concluded that other

factors were important in the development of Ann Rheum Dis: first published as 10.1136/ard.53.1.30 on 1 January 1994. Downloaded from tendon lesions in addition to vascular supply, that predisposed the supraspinatus to rupture. The type of changes found in the cadaveric ^.;,.,.*, i.s. ; rotator cuff specimens were similar to those found in biopsies from tennis elbow lesions but jF- -; *A~ ~ not in control tendon biopsies from a similar area. The similarity of the changes with age in -o _ - * t f X - the rotator cuff and tennis elbow in disease suggests a similar mechanism producing fibro- - - cartilaginous change. j Apart from one case showing minor w aft rotato cuff t b lymphocyte infiltration, inflammation would of tennis Fgre 2Nw bon at *the tendinousjuncio. Nueouscrnciflamtoy appear not to be a histological feature to huma como exteno tenon Havemaoyin n oi ti. (Bar= 1 00P elbow, at least in our patients coming surgery after extensive medical treatment. How .a of-t30iossetw th clinic such changes relate to more acute lesions }- remains unclear. If there is no inflammation Figure 2 New bone at the tendinous junction. Numerous chronicinbfammatoty cells in then there must be an explanation why the human common extensor tendon. Haematoxylin and Eosin stain. (Bar 100nA patients had a chronic painful tennis elbow. A chronic traction phenomenon may occur as has whether presentation to a general praictitionei been previously suggested as a cause of tennis had previously occurred. The absenc,e of any elbow.20 Apart from ischaemia new bone true rotator cuff tendon abnormality boelow the formation would tend to be stimulated at the age of 30 is consistent with the clini cal rarity insertion as was found in six cases and there of rotator cuff tendinitis before that age. No were four patients who had changes suggesting subject in the fifth decade had an abn( Drmality. partial tendon rupture. Both areas are likely to This was unexpected and it is not thought be generously innervated by pain fibres and that this is likely to be representative of this give rise to symptoms with continued traction. age group as a whole. Only 7 sampoles were Some of the changes observed in the tendon examined in this group and future stuidies will were similar to that described by previous be needed to confirm this finding. authors, especially Wilson and Duff.6 These Relative ischaemia of the rotator cuff is authors noted a loss in the intensity of H & E strongly believed to be an important factor in staining, and a hyaline appearance with the loss the 'degenerative' changes that occur. 15 16 The of the wavy lines of collagen fibres. Similar subjects in each age group with an a.bnormal changes were noted in the present study. http://ard.bmj.com/ rotator cuff may be those with poore.r vessels Kannus et al2' examined histological changes in the tendon as a consequence of cc)ngenital in 891 patients with spontaneously ruptured changes and/or atherosclerosis. Me chanical tendons and 445 age and sex matched controls factors, with impingement, may have a role as who had died accidentally. Although neither has been suggested'7 18 but is likely to be a the supraspinatus nor the tendon from lateral secondary aggravating factor.'14 Ho)wever, a epicondylitis were studied, similar changes were recent study by Brooks et al'9 investig;ating the noted. These included hypoxic degenerative on September 26, 2021 by guest. Protected copyright. vascularity of different tendons shc)wed no changes, mucoid degenerative changes, tendo- difference in the size and number of blood lipomatosis, calcifying tendinitis, and vascular changes. The changes observed in control tissues were significantly less frequent. All the ruptured tendon samples had observed abnormalities of which 97% were degenerative whilst 34% of the control tendons had similar degenerative changes. There appeared to be some sequence in the changes observed, suggesting an increasing

MFslk|.>!w!§S-I8F severity of the process. Blood vessel and fibro- blast abnormalities, mainly cell fall-out, were early changes. Areas of glycosaminoglycan infiltration replacing collagen fibres might - indicate that the stressed tendon fibroblasts could no longer maintain their normal function of maintenance and turnover of the tendon collagen. With these changes a rounding up of the cells occurred, proceeding to a trans- formation ofthe fibroblasts to chondrocyte-like cells, with subsequent cartilage formation which then proceeded to calcify to produce bone. It would therefore appear that with increasing Figure 3 Fibrocartilage at thejunction oftendon and mature bone in a human,common severity of the process the tendon fibroblasts extensor tendon. Weigerts Resorcin Fuchsin stain. (Bar = 100 ,uM). undergo a fibrocartilaginous change as though 34 Chard, Cawston, Riley, Gresham, Hazleman

3 Binder A I, Hazleman B L. Lateral humeral epicondylitis- their response to the ischaemia is to ultimately a study of natural history and effect of conservative try to convert areas of tendon to bone. therapy. BrJ Rheum 1983; 22: 73-6. 4 Olsson 0. Degenerative changes in the shoulder joint and Only basic routine histological stains were their connection with shoulder pain. Acta Chir Scand Ann Rheum Dis: first published as 10.1136/ard.53.1.30 on 1 January 1994. Downloaded from used in this study and further work needs to be 1953; (Suppl) 181. 5 Brooks C H, Revell W J, Heatley F W. A quantitative carried out using more specific staining tech- histological study of the vascularity of the rotator cuff niques. These might be used to investigate tendon. J BoneJt Surg 1992; 75B, 1: 151-3. 6 Lindblom K. On pathogenesis of rupture of the tendon the type of glycosaminoglycan present, lipid aponeurosis of the shoulder joint. Acta Radio 1939; 20: content, collagen type, cell density and 563-77. 7 Wilson C L, Duff G L. Pathological study of degeneration relationship to fibrillar elements and interstitial and rupture of the supraspinatus tendon. Arch Surg 1943; material. In addition, electron microscopy 47: 121-35. 8 Brewer R J. Ageing of the rotator cuff. Am J Sports Med could be used to assess collagen fibril size, the 1979; 7:102-10. localisation of collagen types and blood vessel 9 Clark J M, Harryman D T. Tendons, ligaments, and capsule of the rotator cuff. J Bone Jt Surg 1992; 74A 5: distribution. The findings of microscopic 713-25. tendon changes in symptomatic chronic tennis 10 Conrad R W, Hooper W R. Tennis elbow: course, natural history, conservative and surgical management. JT Bone It elbow of the same nature as that found in a Surg 1973; 55A: 1177-87. subgroup of rotator cuffs from normal ageing 11 Nirschl R P, Pettrone F A. Tennis elbow. 7 Bone Jt Surg 1973; 61A: 832-9. individuals, strengthens the belief that such 12 Stack J K. Acute and chronic bursitis in the region of the changes may predispose them to symptomatic elbow. Surg Clin NAm 1949; 29: 155-62. 13 Sarker K, Uhthoff H K. Ultrastructure of the common shoulder disease. With improvements in sur- extensor tendon origin in tennis elbow. Virch Arch Path gical techniques, patients with chronic rotator Anat Histol 1980; 386: 317-30. 14 Macnab I. Rotator cuff tendinitis. Ann Roy Coll Surg Eng cuff lesions are coming to operation earlier, 1973;52:271-87. which will provide biopsies for histological 15 Rathbun J B, Macnab I. The microvascular pattern of the rotator cuff. J BoneJct Surg 1970; 52A: 450-3. assessment and comparison with those changes 16 Rothman R J, Parke W W. The vascular anatomy of the described above. Both the techniques used in rotator cuff. Clin Orthop 1965; 41: 176-86. 17 Neer C S. Anterior acromioplasty for the chronic this study and the more detailed approaches impingement syndrome of the shoulder. J Bone Jt Surg including immunolocalisation of collagen types 1972; 54A: 41-50. 18 Neer C S. Impingement lesions. Clin Orthop 1983; 173: need to be used in the assessment. Such studies 70-7. are at present underway in our departments. 19 Brookes C H, Revell W J, Heatley F W. A quantitative histological study of the vascularity of the rotator cuff tendon. J Bone rt Surgery 1992; 14B: 151-3. 1 Chard M D, Hazleman B L. Shoulder disorders in the 20 Uhthoff H K, Sarker K. A re-appraisal oftennis elbow. Acta elderly. Ann Rheum Dis 1987; 46: 684-7. Orthop Belg 1980; 46: 74-82. 2 Chard M D, Sattelle L M, Hazleman B L. The long-term 21 Kannus P, Jozsa L. Histopathological changes preceding outcome of rotator cuff tendinitis-a review study. Br spontaneous rupture of a tendon. J Bone Jtr Surg 1991 Rheum 1988; 27: 385-9. 73A; 10: 1507-25. http://ard.bmj.com/ on September 26, 2021 by guest. Protected copyright.