Renal cell carcinoma and vasculitis: Report of two cases
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Journal of Surgical Oncology 3535-38 (1987) Renal Cell Carcinoma and Vasculitis: Report of Two Cases GORDON N. HOAG, MD, PhD From the Department of Pathology, Health Sciences Centre, Winnipeg, Manitoba, Canada A 63-year-old Caucasian male with systemic leukocytoclastic vasculitis involving the skin, lungs, and gastrointestinal tract was found to have a renal cell carcinoma at autopsy. A 77-year-old-woman with a history of hypertension was felt to have temporal arteritis that was confirmed by biopsy. The autopsy revealed a renal cell carcinoma in association with widespread giant cell arteritis. The possible association of renal cell carcinoma with vasculitis and an assessment of the possible clinical use- fulness are presented and cases of vasculitis with renal neoplasms are briefly reviewed. KEY WORDS: renal neoplasms INTRODUCTION Various neoplastic syndromes have been associated with 50-75% of patients with renal cell carcinoma [l]. These syndromes have been divided into those of endo- crine and nonendocrine origin. Recently, the production of specific hormones by tumour tissue has been identified as the mechanism of such syndromes [2,3]. There have been few reports of possible nonendocrine associations with renal cell carcinoma . There have been few pre- vious descriptions of vasculitis in association with renal cell carcinoma. leukocytoclastic vasculitis (Fig. la). The immunoperox- idase studies indicated the presence of IgM antibody and complement (C3) in association with small vessels. The patient died on the fifth hospital day after transfer. Postmortem examination revealed systemic vasculitis involving the lungs, gastrointestinal tract, and skin with secondary pneumonia. A 4-cm renal cell carcinoma of typical histology (Fig. lb) was present in the lower pole of the left kidney with metastasis to the thyroid gland. There was no evidence of kidney involvement by the vasculitis. Accessory findings included a duodenal li- poma and a pleomokhic adenoma of the parotid gland. Case 1 Case 2 A 63-year-old male came to his physician with a 2-day onset of dyspnea, diarrhea, and a palpable red purpuric A 77-year-old woman with hypertension controlled by rash on his forearms. The admission laboratory investi- Chlorthalidone came to a physicians office with malaise gations showed the erythrocyte sedimentation rate was and tender nodules along the distribution of the temporal 45 mm/hr and the Direct Coombs test was positive. arteries. The erythrocyte sedimentation rate was 16; these Urinalyses indicated a 2 + protein and microscopy re- lesions were not biopsied, and there was spontaneous vealed 20 abnormal wbc, 2-3 rbc, and 25-30 granular improvement without therapy. She remained well until 8 casts per high-power field. The rash continued to spread, months later, when she noted a queer clutching feeling involving the upper and lower limbs and mucous mem- in the neck, shoulders, and arms, associated with a basal branes, and his dyspnea became progressively worse. He systolic murmur and bilateral carotid and subclavian was transferred on the seventh hospital day to the Health bruits. The blood pressure was unobtainable in the right Sciences Centre, Winnipeg. On admission he was noted to have a generalized purpuric purple-red rash, sparing the palms of his hands and the soles of his feet, and to be severely dyspneic. A skin biopsy showed a pobmorpho- nuclear cell infiltration of small vessels consistent with 0 1987 Alan R. Liss, Inc. Accepted for publication October 11, ,985. Address reprint requests to Dr. G.N. Hoag, Island Medical Labora- tories, 4489 Viewrnont Avenue, Victoria, BC, Canada, VSZ 5KS. 36 Hoag Fig. 1. a: The presence of a perivascular infiltrate in the epidermis is seen. X 150. b: Typical granular cell type renal cell carcinoma. X60. arm. On admission to the hospital, temporal artery bi- opsy showed intimal fibrosis and mononuclear cell infil- tration compatible with resolving temporal arteritis. Prednisone therapy was instituted but she died suddenly on the tenth hospital day. Autopsy revealed giant cell arteritis (Fig. 2a) involving the retinal, cerebral, carotid, coronary, and mesenteric arteries, as well as aortitis with ruptured dissecting aneu- rysm (Fig. 2b) and hemopericardium. A 4-cm renal cell carcinoma of typical histology was present in the upper pole of the right kidney (Fig. 2c). DISCUSSION The criteria for the diagnosis of paraneoplastic syn- dromes have been considered and reviews of nonendo- crine paraneoplastic syndromes associated with renal cell carcinoma have been presented [3,4]. As no cases of vasculitis were presented in association with renal cell carcinoma, one would conclude this to be a rare occur- rence. In our first case there were no apparent skin lesions. However, a case of renal carcinoma with skin manifestations has recently been described. Andrash et Renal Cell Carcinoma and Vasculitis 37 Fig. 2. a: cell. ~ 6 0 0 . b: type renal cell carcinoma. X60. Giant cell arteritis in cerebral artery. x 150. Insert shows enlarged view of giant Typical clear cell Dissecting aortic aneurysm (probe shows dissection). c: a1 [ S ] reported cold-induced ischemia, hypergamma- the left kidney, a left radical nephrectomy was performed globulinemia, and gangrene of the distal phalanges of the and a renal adenocarcinoma was identified.There was fingers in a 63-year-old woman. A skin biopsy showed marked improvement in the digital ischemia and hyper- mild leukocytoclastic vasculitis. Following the demon- gammaglobulinemia postoperatively. The second case of stration of an avascular cystic mass in the upper pole of vasculitis in association with a renal neoplasm  was in 38 Hoag a 72-year-old man with a 3-month history of progressive myalgias, ischemic necrosis with Raynauds phenomena, fevers, fatigue, and profuse diarrhea. Following the dem- onstration of a large intrarenal mass of the left kidney, a left radical nephrectomy was performed, and a renal oncocytoma was diagnosed. A necrotizing vasculitis was seen in the perinephric adipose tissue. Postoperatively the patient showed a diffuse erythematous macular and urticaria1 eruption which subsequently improved and the patient was free of any symptoms 16 months later. The first case in this study of systemic leukocytoclastic vasculitis had a very rapid course with gastrointestinal and pulmonary involvement in addition to the skin. Leu- kocytoclastic vasculitis has been found to occur with various malignancies other than the two reported cases associated with renal neoplasm; these have included Hodgkins disease, reticuloendothelial disease, lympho- sarcoma, and carcinoma [7,8]. In these instances, when other precipitating factors have been investigated and found to be negative, it has been suggested that endoge- nous antigens, such as tumour antigens or serum pro- teins, can induce the formation of the immune complexes . This phenomenon has been demonstrated in animal models [S]. The immunoperoxidase study of the skin biopsy, in the first case we reported, indicated a single IgM antibody with complement present. These findings are consistent with those of Schroeter et a1 [lo], who demonstrated immunoglobulins in 50 % of patients with the cutaneous form of leukocytoclastic vasculitis. The second case of giant cell arteritis also had a very rapid course and systemic manifestations were seen. This pattern of involvement has previously been described . No specific factors were demonstrable in our case to account for the giant cell arteritis. The hypothesis to account for leukocytoclastic vasculitis may also be appli- cable to giant cell arteritis (81. Although these two cases of vasculitis were associated with renal cell carcinoma, the cause-and-effect relationship cannot be enunciated because the neoplasm was not recognized before the patients died. Both of the renal cell carcinomas were of similar size and may have been amendable to surgical intervention had the natural history been slower. As other patients with resectable lesions [5,6] have done well postoperatively with symptomatic improvement, there would be no reason to anticipate that patients who have recognizable and resectable renal cell carcinomas in as- sociation with vasculitis may not have the same prognosis. Recognition of the many paraneoplastic syndromes as- sociated with renal cell neoplasms continues to increase. Whereas endocrine manifestations account for the major- ity of symptoms, nonendocrine manifestations are also of importance. The finding of widespread vasculitis in as- sociation with renal cell carcinoma indicates the impor- tance of evaluating kidney function in patients with vasculitis where the etiologic agent is unknown. CONCLUSION Paraneoplastic syndromes associated with renal cell carcinomas are widely recognized. Two patients with documented vasculitis of unknown etiology were found to have renal cell carcinomas at autopsy. Previously doc- umented cases have established that resolution of the vasculitis upon surgical removal of the renal neoplasm occurs. ACKNOWLEDGMENTS The secretarial assistance of K. Curtis in the typing of this manuscript is appreciated. REFERENCES 1. 2. 3. 4. 5 . 6. 7. 8. 9. 10. Hall TC, Nathanson L: The paraneoplastic syndromes. CA Samaan NA: Hormone production in non-endocrine tumors. CA Altaffer LF, Chenault OW, Jr. : Paraneoplastic endocrinopathies associated with renaI tumors. J Urol 122573-577, 1979. Tveter KJ: Unusual manifestations of renal carcinoma. A review of the literature. Acta Chir Scand 139:401-409, 1973. Andrasch RH, Bardana EJ, Jr., Porter JM, Pirofsky B: Digital ischemia and gangrene preceding renal neoplasm. Arch Intern Med 136:486-488, 1976. Susman BR, Levin FC, Barland P, Fromowitz F: Vasculitis: associated with renal oncocytoma. NYSMJ 81: 1501-1503, 1981. Sams WM, Jr., Thorne EG, Small P, Mass MF, McIntosh RM, Stanford RE: Leukocytoclastic vasculitis. Arch Derrnatol Fauci AS, Haynes BF, Katz P: The spectrum of vasculitis. Clin- ical, pathologic, immunologic and therapeutic considerations. Ann Intern Med 89:660-676, 1978. Cochrane CG: Mechanisms involved in the deposition of immune complexes in tissues. J Exp Med 134:75~-89s, 1971. Schroeter AL, Copeman PWM, Jordon RE, Sams WM, Jr., Winkleniann RK: Irnrnunofluorescence of cutaneous vasculitis associated with systemic disease. Arch Dermatol 104:254-259, 1971. 18:322-329, 1968. 27: 148-159, 1977. 112~219-226, 1976.
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