Metastatic carcinoma presenting as monarticular arthritisa case report and review of the literature.код для вставкиСкачать
95 METASTATIC CARCINOMA PRESENTING AS MONARTICULAR ARTHRITIS: A CASE REPORT AND REVIEW OF THE LITERATURE GARVIN C. MURRAY and ROBERT H. PERSELLIN Arthritis resulting from metastatic carcinoma involving juxtaarticular bone or synovial tissue is a poorly recognized and rarely reported occurrence. It has received only brief mention in the current standard tests of rheumatology (1,2). Consequently, when it occurs, it usually presents a diagnostic dilemma leading to unfortunate delays and errors in medical management. We present here an unusual case of the heretofore unreported occurrence of sternoclavicular arthritis as the presenting manifestation of metastatic carcinoma. The pertinent literature is reviewed, and the clinical characteristics of this form of arthritis are discussed. Case Report. In December 1977, a 69-year-old Mexican-American man presented to the Bexar County Hospital emergency room with a 3-week history of painful swelling of the right sternoclavicular joint. An anteroposterior radiograph of the right clavicle and sternoclavicular joint revealed only soft tissue swelling without bony abnormalities; however, a small infiltrate was noted in the apex of the right lung associated with pleural thickening. Because of this finding, he was admitted for further evaluation. He had an 80-pack a year smoking history but From the Division of Rheumatology, Department of Medicine, The University of Texas Health Science Center at San Antonio. Supported in part by an Arthritis Clinical Research Center grant from the Arthritis Foundation and by grants from the South Central Texas Chapter of the Arthritis Foundation and the Ruth and Vernon Taylor Foundation. Garvin C. Murray, MD: Fellow in Rheumatology; Robert H. Persellin, MD: Professor of Medicine, Head, Division of RheumatolOgY. Address reprint requests to Robert H. Persellin, MD, Department of Medicine, Division of Rheumatology, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284. Submitted for publication June 14, 1979; accepted July 31, 1979. Arthritis and Rheumatism, Vol. 23, No. 1 (January 1980) denied chronic cough or hemoptysis. There was no history of fever, chills, night sweats, weight loss, or exposure to tuberculosis. The sternoclavicular symptoms were first noted 3 weeks prior to admission and had gradually become more severe. There was no history of trauma associated with the onset of the joint pain. No other arthritic complaints were elicited. The patient had been hospitalized in 1971 for medical problems associated with chronic alcoholism, including Wernicke’s syndrome, Korsakoff s psychosis, peripheral neuropathy, muscle atrophy, and hepatic cirrhosis. On examination the patient appeared chronically ill and debilitated with clinical features of an organic brain syndrome. His vital signs and cardiorespiratory findings were normal. The liver was slightly enlarged but nontender. No lymphadenopathy or prostatic nodules were present. Prominent clubbing of the fingers was noted, but other manifestations of hypertrophic pulmonary osteoarthropathy were not apparent. Overlying the right sternoclavicular joint was a 3 x 4 cm area of swelling which was mildly erythematous, warm, and tender to palpation. There were no other signs of arthritis. Laboratory studies revealed a hematocrit of 42% and a leukocyte count of 5,100/mm3 with a normal differential. The alkaline phosphatase was moderately elevated at 196 units/liter (normal, 35-125 units/liter) and a Westergren erythrocyte sedimentation rate was 30 =/hour. Normal values were obtained for serum electrolytes, urea nitrogen, glucose, bilirubin, creatinine, SGOT, LDH, and urinalysis. Tomography of the right lung revealed multiple thick and thin-walled cavitary lesions involving the greater portion of the right apex associated with irregular pleural thickening. Sputum cytology was negative; however, fluorochrome smears for Mycobacterium tuberculosis documented active infection. In view of the finding of pulmonary tuberculosis, 96 CASE REPORTS the possibility of tuberculous arthritis was considered, and an evaluation of the sternoclavicular lesion was undertaken. Except for soft tissue swelling, results of tomograms of the right clavicle and sternoclavicular joint were normal. Arthrocentesis of the involved joint yielded only 0.3 ml of serosanguinous fluid, which subsequently proved to be culture-negative for aerobic bacteria and M tuberculosis. In addition to occasional polymorphonuclear leukocytes, a Wright's stain of the joint aspirate surprisingly revealed clumps of darkly staining neoplastic cells (Figure 1). An open biopsy provided additional tissue which was histologically consistent with metastatic clear cell carcinoma infiltrating the sternal head of the right clavicle. A search for the primary carcinoma, including bronchoscopy, intravenous pyelogram, upper gastrointestinal series, barium enema, and a liver-spleen scan, was negative. A 99"technetiumpyrophosphate bone scan demonstrated areas of increased uptake in the regions of the right sternoclavicular joint and proximal femur, left shoulder, and iliac crest (Figure 2). In view of the re- sults of the clinical evaluation, it was thought that the neoplasm had probably originated in the bronchioles. Although the patient was treated with a chemotherapeutic regimen, as well as with isoniazid and ethambutol, he died 4 weeks later. An autopsy was not performed. Discussion. A broad spectrum of rheumatologic disorders is known to occur in association with malignant diseases. These are listed in Table 1 and include such diverse syndromes as hypertrophic osteoarthropathy (3), gout (4), dermatomyositis (5), Sjogren's syndrome (6), carcinomatous polyarthritis (7), and arthritis associated with lymphoproliferative and myeloproliferative diseases (8,9). Although less well recognized, arthritis due to metastatic carcinoma involving juxtaarticular structures or synovium can also occur (10-19) and on rare occasions may be the presenting manifestation of the malignant process. Diagnosis in these cases can be difficult, often resulting in unfortunate delays and errors in medical management. Figure 1. A cluster of poorly differentiated malignant cells seen in the sternoclavicular joint aspirate. (Wright's stain, original magnification X 1200.) CASE REPORTS Figure 2. 99"Technetium pyrophosphate scan of the patient demonstrating areas of increased uptake in the regions of the right sternoclavicularjoint and proximal femur, left shoulder, and iliac crest. 97 case was there a polyarticular onset (case 2). Importantly, inflammation of the affected joints was observed in all 11 patients in which physical findings were reported. Effusions were present in six. The knee was most commonly involved with the hip being the second most likely site. Involvement of the ankle, wrist, and the joints of the hands and feet was less frequent. No previous cases of sternoclavicular involvement have been reported. This distribution of arthritis parallels the incidence of osseous metastases involving the appendicular skeleton which diminishes with increasing distance from the central axis of the body (20,21). Not surprisingly, carcinoma of the breast and lung were the primary neoplasms in the majority of cases (64%). These malignancies are the most common to occur in women and men, respectively, and both commonly metastasize to bone (22). Although metastases to distant peripheral sites are rare, this review concurs with previous observations that metastatic osseous invasion distal to the knee or elbow most frequently results from bronchogenic carcinoma (23,24). Arthrocentesis, performed on 6 patients, was often valuable in establishing the appropriate diagnosis. In the majority (83%) the synovial fluid was bloody or serosanguinous and usually noninflammatory. Cytologic evaluation utilizing either Papanicolaou or Wright's staining revealed neoplastic epithelial cells in four instances. As illustrated by the present case, an evaluation of even a seemingly insignificant quantity of aspirated fluid may prove fruitful. Based on observations in four synovial fluid aspirates with characteristics similar to those reported above, Naib suggested that the presence of an hemorrhagic, noninflammatory effusion should arouse suspicion of a primary or secondary neoplasm (25). Percutaneous or surgical synovial biopsies were performed in 5 instances and proved diagnostic in 4 patients. Bone biopsy was diagnostic in 4 others, whereas the diagnosis was made at autopsy in 2. The presence of neoplastic epithelial cells was the most striking feature of the synovial histology in the majority of patients. La- Table 1. Rheumatic disorders associated with malignant diseases Our experience with the patient presented here was in many ways comparable to other reported cases of arthritis resulting from metastatic carcinoma (10-19). A summary of the clinical features of these patients together with the Dresent case is presented in Table 2. The arthritis associated with metastatic carcinoma was most commonly monarticular. In only one Y Hypertrophic osteoarthropathy Gout Dermatomyositis Sjogren's syndrome Carcinomatous polyarthritis Arthritis associated with lymphoproliferativeand myeloproliferative diseases Arthritis associated with metastatic carcinoma CASE REPORTS Table 2. Summary of the clinical features of 14 cases of arthritis caused by metastatic carcinoma Case no. Age/ (Ref.) sex Initial diagnosis* History of previous Joint malignancy involved Duration of symptoms to final diagnosis Initial radiologic findings Radiologic findings at final diagnosis Procedure diagnostic of articular lesiont Final diagnosis l(l0) 66/F RA Yes Ankle 24 months Mild deminerali- Diffuse deminerzation alization BBx Breast carcinoma 2(11) 59/M RA No Knee, PIP joints 5 weeks Numerous osteolytic lesions AUT Squamous cell carcinoma, lung 3(12) 66/M MA Yes Knee 4 weeks Demineralization Extensive lysis of patella ARCT, SBx Squamous cell carcinoma, lung 4(13) 63/M TA or TbA No Knee 3 months Not reported Lysis, lower pole of patella AUT Epidermoid carcinoma, lung 5 (14) 62/F OA Yes Knee 4 weeks Not reported Degenerative changes ARCT, SBx Adenocarcinoma, colon 6 (15) 54/F MA Yes Knee 12 months Mild degenerative Osteolytic changes and blastic lesions ARCT Breast carcinoma 7 (16) 52/F MA Yes wrist 4 months Demineralization Osteoblastic lesions SBx Bronchogenic carcinoma (presumed) 8 (17) 67/M Gout Yes Ankle 6 weeks Soft tissue swelling Extensive demineralization with fracture BBx Transitional cell carcinoma, urinary bladder 9 (18) 48/M Gout Yes IP joint, great toe Not reported Lytic lesion Unchanged X-ray Squamous cell carcinoma, lung IO(19) 89/M MA Yes Hip 10 weeks Not reported Blastic lesions in pelvis X-ray, BSc Prostatic carcinoma 11 (19) 63/F RA Yes Hip 16 months Not reported Abnormal (details not given) X-ray, BSc Breast carcinoma 12(19) 51/F TbA No Hip 3 months Normal Normal SBx Lung carcinoma 13(19) 34/M INB No Hip 2 weeks Mottling of femoral head Abnormal (details not given) BBx Carcinoma, primary unknown Present case 69/M TbA No Sternoclavicular joint 3 weeks Normal Normal Unchanged ARCT, BBx Bronchogenic carcinoma (presumed) * RA = rheumatoid arthritis; MA = monarthritis; TA = traumatic arthritis; TbA = tuberculous arthritis; OA = osteoarthritis; INB = ischemic necrosis of bone. t BBx = bone biopsy; AUT = autopsy; ARCT = arthrocentesis; SBx = synovial biopsy; BSc = bone scan. gier (16) described a patient in which an open synovial biopsy initially demonstrated non-specific inflammation consisting of mild synovial hyperplasia, capillary congestion, and plasma cell and lymphocyte infiltrates. Deeper sectioning revealed undifferentiated epidermoid carcinoma in underlying connective tissue. Similar find- ings were reported in synovial tissue obtained from a patient with metastatic bronchogenic carcinoma (1 1). No neoplastic cells were detected however, radiographs revealed extensive osteolytic changes in adjacent bone. These observations suggest that malignant metastatic deposits in tissues adjacent to a joint may cause non- CASE REPORTS specific synovial inflammation without directly involving the synovial membrane itself. The mechanism by which this occurs is unknown. In the majority of cases the pre-existence of a malignancy was known and provided an important clue to the etiology of the joint complaint. Nevertheless, an underlying malignancy was not usually suspected as the cause of arthritis. This was reflected by the original diagnoses which included rheumatoid and infectious arthritis in 3, gout in 2, and ischemic necrosis of bone, osteoarthritis, and traumatic arthritis in 1 patient each. As a consequence, delays were incurred in making the appropriate diagnosis. The duration of joint symptoms from onset to final diagnosis ranged from 2 weeks to 24 months. The median duration was 2 months. Two additional factors appear to have contributed to this difficulty with early diagnosis. Physical findings often did not suggest the presence of an initial or recurrent malignancy, and laboratory data were usually not helpful. Furthermore, the initial radiographic studies of the involved joints were frequently normal or revealed only minimal non-specific changes, such as mild demineralization or soft tissue swelling (Table 2). The paucity of radiographic abnormalities associated with metastatic invasion in these patients can be explained on the basis of the site of initial metastasis. Since 0sseous metastases begin their proliferation in the marrow cavity, they can reach macroscopic size without altering bony architecture or becoming radiographically apparent (24). The exact physiologic mechanisms of bone resorption remain unclear; however, neoplastic activation of osteoclasts or production of osteolytic substances, such as prostaglandins, are probably important (26). Osteolytic changes appear to occur only after the marrow space has been extensively infiltrated by tumor cells. The mechanism by which carcinoma metastasizes to synovial tissue remains unclear. Direct hematogenous dissemination of tumor cells to synovium probably occurs, but it appears to be extremely rare. Goldenberg (14) and Meals (19) have each reported a case of biopsy-documented synovial membrane involvement by carcinoma in which this mode of metastasis may have occurred. However, in neither case was a postmortem dissection of the involved joint performed. It appears more likely that metastasis to juxtaarticular bone occurs first, with synovial involvement following secondarily. This could occur by subsequent direct tumor invasion of synovial tissue or by secondary hematogenous metastasis through intercommunicating vascular channels (27,28) analogous to the way suggested for the 99 development of joint infection following juxtaarticular osteomyelitis in the adult (29,30). Secondary lymphatic spread from bone to joint probably does not occur since the presence of lymphatic vessels in bone marrow where osseous metastases occur has not been conclusively demonstrated (3 1). Furthermore, once established in bone, subsequent tumor spread occurs via established anatomic channels, namely the medullary cavity and the haversian and Volkmann’s canals (31). Of the 14 cases reviewed, all but 2 (cases 5 and 12) had evidence of juxtaarticular osseous involvement. Why synovial tissue with its large total surface area and generous blood supply is not involved more frequently by metastatic neoplasms remains to be answered. That this type of involvement can and does occur, albeit rarely, needs to be more fully appreciated and considered as a potential cause of monarticular arthritis. REFERENCES 1. Cohen AS: Tumors of synovial joints, bursae, and tendon sheaths, Arthritis and Allied Conditions. Eighth edition. Edited by JL Hollander, DJ McCarty. Philadelphia, Lea and Febiger, 1972, p 1385 2. Barnes CG: Miscellaneous and uncommon rheumatic conditions, Copeman’s Textbook of the Rheumatic Diseases. Fifth edition. Edited by JT Scott. Edinburgh, Churchill Livingstone, 1978, pp 859-860 3. Hammarsten JF, OLeary 3: The features and significance of hypertropic osteoarthropathy. Arch Intern Med 99:43141, 1957 4. Yu T, Weinreb N, Wittman R, Wasserman LR: Secondary gout associated with chronic myeloproliferative disorders. Semin Arthritis Rheum 5:247-256, 1976 5. Barnes BE: Dermatomyositis and malignancy: a review of the literature. Ann Intern Med 84:68-76, 1976 6. Tala1 N, Sokoloff L, Barth WF: Extrasalivary lymphoid abnormalities in Sjogren’s syndrome (reticulum cell sarcoma, “pseudolymphoma,” macroglobulinemia). Am J Med 43:5O-65, 1967 7. MacKenzie AH, Scherbel AL: Connective tissue syndromes associated with carcinoma. Geriatrics 18:745-753, 1963 8. Spilberg I, Meyer GJ: The arthritis of leukemia. Arthritis Rheum 15:63O-635, 1972 9. Davis JS, Weber FC, Bartfeld H: Conditions involving the hemopoietic system resulting in a pseudorheumatoid arthritis: similarity of multiple myeloma and rheumatoid arthritis. Ann Intern Med 47:1O-17, 1957 10. Jacox RF, Tristan TA: Carcinoma of the breast metastatic to the bones of the foot: a case report. Arthritis Rheum 3:170-177, 1960 11. Karten I, Bartfeld H: Bronchogenic carcinoma simulating 100 CASE REPORTS early rheumatoid arthritis: metastasis to the fingers. JAMA 179~162-164,1962 12. Benedek TG: Lysis of the patella due to metastatic carcinoma. Arthritis Rheum 8560-566, 1965 13. Gall EP, Didizian NA, Park Y: Acute monarticular arthritis following patellar metastasis: a manifestation of carcinoma of the lung. JAMA 229:188-189, 1974 14. Goldenberg DL, Kelley W, Gibbons RB: Metastatic adenocarcinoma of synovium presenting as an acute arthritis: diagnosis by closed synovial biopsy. Arthritis Rheum 18:107-110, 1975 15. Moutsopoulos HM, Fye KH, Pugay PI, Shearn MA: Monarthric arthritis caused by metastatic breast carcinoma: value of cytologic study of synovial fluid. JAMA 234:75-76, 1975 16. Lagier R: Synovial reaction caused by adjacent malignant tumors: anatomicopathologic study of three cases. J Rheumatol4:65-72, 1977 17. Bevan DA, Ehrlich GE, Gupta VP: Metastatic carcinoma simulating gout. JAMA 237:2746-2747, 1977 18. Vaezy A, Budson DC: Phalangeal metastases from bronchogenic carcinoma. JAMA 239:226-227, 1978 19. Meals RA, Hungerford DS, Stevens MB: Malignant disease mimicking arthritis of the hip. JAMA 239:1070-107 1, 1978 20. Mulvey RB: Peripheral bone metastases. J Roentgen01 Radium Ther Nucl Med 91:155-160, 1964 2 1. Wirth CR: Metastatic bone tumors, Clinical Oncology. Edited by J Horton, GJ Hill. Philadelphia, WB Saunders Company, 1977, pp 636-644 22. Silverberg E: Cancer statistics, 1979. CA 29:6-21, 1979 23. K e r b R: Metastatic tumors of the hand. J Bone Joint Surg 40A:263-277, 1958 24. Shackman R, Harrison CV: Occult bone metastases. Br J Surg 35:385-389, 1948 25. Naib ZM: Cytology of synovial fluids. Acta Cytol 17:299309, 1973 26. Editorial: Osteolytic metastases. Lancet 2: 1063-1064, 1976 27. Gardner E: Blood and nerve supply of joints. Stanford Med Bull 11:203-209, 1953 28. Trueta J, Harrison MHM: The normal vascular anatomy of the femoral head in adult man. J Bone Joint Surg 35B:442461, 1953 29. Trueta J: The three types of acute haematogenous osteomyelitis: a clinical and vascular study. J Bone Joint Surg 41B1671-680, 1959 30. Atcheson SG, Ward JR: Acute hematogenous osteomyelitis progressing to septic synovitis and eventual pyarthrosis: the vascular pathway. Arthritis Rheum 2 11968-971, 1978 31. Milch RA, Changus GW: Response of bone to tumor invasion. Cancer 9:340-351, 1956 Tissue Grafts in Reconstructive Surgery An international conference will be held in Athens, Greece, May 25-30, 1980, t o commemorate the tenth anniversary of the Greek Human Tissue Bank. Symposia will deal with problems of tissue banking and tissue transplantation, and poster sessions will be included. The official languages of the conference will be Greek and English; proceedings of the conference will be published in both languages. For further information, contact Dr. Paul Karatzas, General Secretary t o the Conference, N.R.C. Democritos, Human Tissue Bank, Aghia Paraskevi, Athens, Greece.