The Histopathology of Mycobacterium marinum Synovitis

Transcription

1 The Histopathology of Mycobacterium marinum Synovitis EDWIN N. BECKMAN, M.D., GEORGE A. PANKEY, M.D., AND GORDON B. McFARLAND, M.D. Eight patients with culture-proven Mycobacterium marinum synovitis had synovial specimens with a remarkably similar histologic appearance. There was considerable synovial hyperplasia, and the synovium was thickened by a moderately intense lymphohistiocytic infiltrate, notably devoid of plasma cells. Fibrin covered some synovial surfaces. Giant cells were both of the Langerhans' and foreign body types. Granulomas were noncaseating but varied in frequency and degree of definition. Knowledge of this morphologic picture has proved to be useful in patient care. (Key words: Mycobacterium marinum; Atypical mycobacterium; Granulomatous synovitis) Am J Clin Pathol 1985; 83: THE DIFFERENTIAL DIAGNOSIS of granulomatous synovitis includes sarcoidosis, 23 foreign bodies," Crohn's disease, 8 and brucellae, fungus, Mycobacterium tuberculosis, and "atypical" Mycobacterium infections. 16 ' 24 There has been little emphasis on the histopathology of "atypical" mycobacterial synovitis. Most reports of these synovial infections have only brief mention of the findings.'" 4 ' 6 ' 7 ' 9 ' 112 " 22,24-26 Two clinically oriented case collections do provide more description of the changes. 525 We report our experience with the morphology from eight culture-proven cases of Mycobacterium marinum synovitis. Materials and Methods Our study is of patients with Mycobacterium marinum infections of the synovium seen at the Ochsner Clinic and Ochsner Foundation Hospital from 197 to 1984 but does not include those in which the infection was principally of the skin with only secondary joint involvement. We required that the infectious organisms be substantiated by culture technics for the case to be included in the study. Results Table 1 gives the clinical aspects of our patients. They ranged from 38 to 65 years of age, and all but one were male. All infections involved the hand or wrist. The symptoms were pain and swelling, and in two patients a mass was present. In three patients the site of infection had a known traumatic event involving salt water. Three Received June 4, 1984; received revised manuscript and accepted for publication September 1, Address reprint requests to Dr. Beckman: Ochsner Clinic, 1514 Jefferson Highway, New Orleans, Louisiana Departments of Pathology, Internal Medicine (Section on Infectious Diseases), and Orthopedic Surgery, Ochsner Clinic and Alton Ochsner Medical Foundation, New Orleans, Louisiana additional patients were frequent salt water fishermen and had repeated opportunities for minor hand trauma. Their infections are presumed to also be salt water related. 5,25 One patient injured her hand with steel wool while scrubbing the floor. There is no known or presumed source of infection for the last patient. No patient had known pulmonary disease, which might have served as a source for hematogenous spread of infection. 3,24 No patient had a collagen vascular related arthritis that could have predisposed to an infection. 6,9,1215,26,24,26 None had had prior injection of corticosteroids into the joint. 5,716,24 " 26 There was no evidence for a depressed immune system for any of the patients. 9,24,26 None had sarcoidosis or Crohn's disease. Grossly, the synovium appeared thickened and varied from being edematous to firm. Fibrin covered some synovial surfaces. The color varied from light gray to beefy red to brown. Most of the histopathologic features of the infected synovium were remarkably constant (Table 2). All cases had a considerable degree of synovial proliferation (Fig. 1) with hyperplasia and hypertrophy of lining cells (Fig. 2). Fibrin covered some synovial surfaces. Small numbers of neutrophils were admixed with the fibrin layer. While some areas of the synovium had a mild neutrophilic component to the infiltrate, neutrophils were essentially limited to the fibrin layer. The synovium was thickened by a lymphohistiocytic infiltrate of slight to moderate intensity. A striking feature of this infiltrate was the paucity of plasma cells. In most specimens, none were identified. While the synovium was remarkably similar from specimen to specimen in these previous parameters, granulomas varied in quality, number, and distribution. Usually, the granulomas were moderately well defined and noncaseating (Fig. 3). Some resembled the granulomas of sarcoidosis in their quality of epitheloid histiocytes and sharp circumscription. In two cases granulomas were ill defined (Fig. 4). One specimen included granulomas with central fibrinoid degeneration reminicent of rheumatoid nodules (Fig. 5). Giant cells were both of Downloaded from by guest on 24 September

2 458 BECKMAN, PANKEY, AND McFARLAND Table 1. Patients with Mycobacterium marinum Synovitis A.J.C.P. April 1985 Patient Age, Sex Site Incident Symptoms Gross Synovial Appearance at Surgery y/o male 47 y/o male 6 y/o male 52 y/o male 65 y/o male 54 y/o male 44 y/o female 63 y/o male Index finger Index finger, hand, and wrist Wrist Dorsum of hand Wrist Palm Index finger, palm Middle finger, dorsum of hand Horned by shrimp No specific trauma Frequent fisher Unknown No specific trauma Frequent fisher Fishing hook injury No specific trauma Frequent fisher Stuck finger with steel wool while scrubbing floor Finger injury in brackish water the Langerhans' and foreign body types (Fig. 3). They occurred outside granulomas as well as within them. Many specimens had both types of giant cells. Giant cells and granulomas were not related to polarizable foreign material. Acid-fast stains (modified Ziehl-Neelson method) were performed upon all specimens. In only one specimen were acid-fast organisms visualized in the histologic sections, which emphasizes the importance of culturing the tissue. Over the same time, we also had cases of joint infection by other atypical acid-fast organisms. The morphologic changes were virtually identical in specimens from two patients with Mycobacterium terrae infection, one with Mycobacterium kansasii and one with Mycobacterium avium-intracellulare complex. One Pain, swelling, contraction Edema, pain, tenderness, erythema, decreased range of motion Swollen, tender, carpal tunnel syndrome Swelling, pain Painless mass Swollen, tender, carpal tunnel syndrome Swollen, tender, mass Slow healing wound, satellite lesions Edematous Beige granulomatous tissue with brown flecks Hypertrophic, meaty-brown pannus-like synovium binding tendons Moist, boggy, proliferative, friable Thick, densely adherent, stiff, beefy red Hypertrophic, sticky exudate Boggy, necrotic, discolored Proliferative, tan a few brown flecks of the cases with Mycobacterium terrae infection had a few foci of plasma cells in the inflammatory infiltrate, an unusual finding in Marinum synovitis. The morphology of our cases in which the atypical Mycobacterium infection principally involved the synovium contrasted with cases we saw of skin infection with only secondary joint involvement. The latter specimens had minimal synovial hyperplasia and had intense acute inflammation, chronic inflammation including large numbers of plasma cells, and major areas of necrosis in the connective tissue adjacent to the joint and in the subcutaneous tissue. Our eight patients were treated by synovectomy and appropriate antibiotic therapy. All patients responded well to therapy, with resolution of their symptoms within 3-11 months. Table 2. Histopathologic Findings in Mycobacterium marinum Synovitis Granulomas Patient Frequency Quality Lymphocytes Histiocytes NC moderately defined, some sarcoid-like NC moderately defined, a few sarcoid-like NC ill-defined nodules NC moderately defined Many well defined but some with fibrinoid necrosis NC ill-defined nodules NC moderately defined NC moderately defined Plasma Cells A rare focus Extremely rare Synovial Hyperplasia Fibrin-related Acute Inflammation Rare Fibrin Downloaded from by guest on 24 September 218 NC noncascaling. Grading system: to subjectively determined.

3 ' 'ft. V?!&?<<: ',.P. l 4 -* ' %ii^^^" f%-7; ^ f ^'v* 'm" ;<! jfsj&w 1 * # '$&> ggp'l if N * : * ^. * '/ ^t^/ *- J I ' '* ^ *&',&*»' W * y -'~/ 'Jflfe ^ Downloaded from by guest on 24 September 218 FIG. 1 (upper). Proliferative synovium with chronic inflammatory infiltrate. Typical of the spotty distribution of granulomas with this infection, this synovial region lacks granulomas, while other areas had a moderate number. Hematoxylin and eosin (X4). FlG. 2 (lower). Deep to the hyperplastic cells of the synovial lining is a moderately intense infiltrate of lymphocytes and histiocytes. Note the absence of plasma cells. Hematoxylin and eosin (X32).

4 Downloaded from by guest on 24 September 218

5 Vol. 83 No. 4 MYCOBACTERIUM MARINVM SYNOVITIS 461 FIG. 3 (upper). Moderately defined noncaseating granulomas with giant cells of both the foreign body and Langerhans' types. Hematoxylin and eosin (X2). FIG. 4 (lower). Two ill-defined, noncaseating granulomas of the synovium. Hematoxylin and eosin (X32). Discussion Our cases of M. marinum synovitis had a relatively similar histologic appearance. This morphologic picture is in the range of that mentioned in prior reports of atypical Mycobacterium synovitis. 1 ' 2 ' 4 " 7 ' 9, ' 24 " 26 The variation in appearance of granulomas is similar to that previously reported. Most frequently, they merely have been described as noncaseating without being otherwise specified. 615 ' 22 Some reports have described or portrayed the noncaseating granulomas as being discrete. 6 ' 15,18 ' 19 ' 21 ' 22 They sometimes have been found specifically to be ill defined, 1 and Williams and Riordan's cases of M. marinum synovitis had that appearance. 25 Only one study of M. marinum synovitis has mentioned the presence of caseating granulomas, and it reported "There was very little caseation, even in the center of some tuberculoid granulomas." 5 In addition, we have found only four reports of caseating granulomas in synovitis caused by atypical mycobacterial organisms one with a M.fortuitum infection, 1 one with M. terrae, n one with M. kansasii, 1 and one with a group III organism of a type not otherwise specified. 3 Areas of fibrinoid necrosis of the synovium have been reported with atypical Mycobacterium synovitis. 17,25 Central microabscesses were reported in one case with involvement by M. fortuitum. 26 Finally, not all specimens of cultureproven atypical Mycobacterium synovitis have even had granulomas mentioned in the microscopic description. 2 ' 4-21 As with our cases, the infectious organism often has not been seen in the tissue and has only been identified by culture. 2 ' ' 17 ' 22 The paucity of plasma cells in the inflammatory infiltrate has not been stressed in the literature, but this finding is consistent with the morphologic pictures re- Downloaded from by guest on 24 September 218 FIG. 5. One of the unusual granulomas with central fibrinoid degeneration from patient 5. Hematoxylin and eosin (X1).

6 462 BECKMAN, PANKEY, AND McFARLAND A.J.C.P. April 1985 ported. We have found only three references of the occurrence of plasma cells in the inflammatory infiltrate in atypical Mycobacterium synovitis. 12 ' 22 ' 24 In conclusion, our cases of M. marinum synovitis had a histologic appearance that, although not pathognomonic, was characteristic. Recognition of this typical morphologic picture is important for two reasons. First, it could lead to suspicion of this disease in a case where Mycobacterium cultures inadvertently were not performed or where the culture was handled inappropriately. For example, the specimen from a patient at our institution had the typical histopathologic appearance for M. marinum synovitis, a consistent gross appearance of the synovium, and a history of salt water related trauma to the hand. Though the specimen had multiple cultures, culture for Mycobacterium organisms inadvertently was not performed. Based upon the pathologic appearance and the patient's history, he was treated successfully for atypical Mycobacterium synovitis and cured. A second reason for knowledge of the morphologic appearance of atypical Mycobacterium synovitis is to allow institution of antibiotic therapy while cultures are in progress. Acknowledgment. The authors gratefully acknowledge technical assistance for this project provided by Betty Petersen, MT (ASCP), SM. References 1. Ariel I, Haas H, Weinberg H, Rousso M, Rosenmann E: Mycobacterium fortuitum granulomatous synovitis caused by a dog bite. J Hand Surg 1983; 8: Booth JE, Jacobson JA, Kurrus TA, Edwards TW: Infection of prosthetic arthroplasty by Mycobacterium fortuitum. Two case reports. J Bone Joint Surg 1979; 61A: Chapman JS: Atypical mycobacterial infections. Pathogenesis, clinical manifestations, and treatments. Med Clin North Am 1967;51: Cheatum DE, Hudman V, Jones SR: Chronic arthritis due to Mycobacterium intracellulare sacroiliac, knee, and carpal tunnel involvement in a young man and response to chemotherapy. Arthritis Rheum 1976; 19: Chow SP, Stroebel AB, Lau JHK, Collins RJ: Mycobacterium marinum infections of the hand involving deep structures. J Hand Surg 1983; 8: DeMerieux P, Keystone EC, Hutcheon M, Laskin C: Polyarthritis due to Mycobacterium kansasii in a patient with rheumatoid arthritis. Ann Rheum Dis 198; 39: Feyen J, Martens M, Mulier JC: Infection of the knee joint with Mycobacterium xenopi. Clin Orthop 1983; 179: Frayha R, Stevens MB, Bayless TM: Destructive monoarthritis and granulomatous synovitis as the presenting manifestation of Crohn's Disease. Johns Hopkins Med J 1975; 137: Girard DE, Bagby GC, Walsh JR: Destructive polyarthritis secondary to Mycobacterium kansasii. Arthritis Rheum 1973; 16: Godwin MC: Infection of knee joint by Mycobacterium kansasii. JAMA 1965; 194: Goodnough CP, Frymoyer JW: Synovitis secondary to non-metallic foreign bodies. J Trauma 1975; 15: Gunther SF, Elliott RC: Mycobacterium kansasii infection in the deep structures of the hand. Report of two cases. J Bone Joint Surg 1976; 58A: Halla JT, Gould JS, Hardin JG: Chronic tenosynovial hand infection from Mycobacterium terrae. Arthritis Rheum 1979; 22: Hemdon JH, Dantzker DR, Lanoue AM: Mycobacterium fortuitum infection involving the extremities. J Bone Joint Surg 1972; 54A: Hoffman GS, Myers RL, Stark FR, Thoen CO: Septic arthritis associated with mycobacterium avium: A case report and literature review. J Rheumatol 1978; 5: Kelly PK, Weed LA, Lipscomb PR: Infection of tendon sheaths, bursae, joints, and soft tissues by acid-fast bacilli other than tubercle bacilli. J Bone Joint Surg 1963; 45A: , Klinenberg JR, Grimley PM, Seegmiller JE: Destructive polyarthritis due to a photochromogenic mycobacterium. N Engl J Med 1965;272: May DC, Kutz JE, Howell RS, RaffMJ, Melo JC: Mycobacterium terrae tenosynovitis: Chronic infection in a previously healthy individual. South Med J 1983; 76: Mehta JB, Hovis WM: Tenosynovitis of the forearm due to Mycobacterium terrae (radish bacillus). South Med J 1983; 76: Moore M, Frerichs JB: An unusual acid-fast infection of the knee with subcutaneous, abscess-like lesions of the gluteal region. Report of a case with a study of the organism, Mycobacterium abscessus. J Invest Dermatol 1953; 2: Owen DS, Toone E: Soft tissue infection by Group I atypical mycobacteria. South Med J 197; Saphyakhajon P, Mukhopaohyay D, Speigel P, Grossman BJ: Mycobacterium kansasii arthritis of the knee joint. Am J Dis Child 1977; 131: Siltzbach LE, Duberstein JL: Arthritis in sarcoidosis. Clin Orthop 1968;57: Sutker WL, Lankford LL, Tompsett R: Granulomatous synovitis: The role of atypical mycobacteria. Rev Infect Dis 1979; 1: Williams CS, Riordan DC: Mycobacterium marinum (atypical acid-fast bacillus) infections of the hand. A report of six cases. J Bone Joint Surg 1973; 55A: Williams GV: Mycobacterium Fortuitum: An unsuspected cause of synovitis and osteomyelitis. Aust NZ J Med 198; 1: Downloaded from by guest on 24 September 218