Testicular vasculitis: Implications for systemic disease

Testicular Vasculitis: Implications for Systemic Disease MUHAMMAD S. SHURBAJI, MD, AND JONATHAN I. EPSTEIN, MD Nine cases of testicular vaseulitis were identified from the surgical pathology and autopsy files of the Johns Hopkins Hospital. In three cases this was the initial manifestation of polyarteritis nodosa. Two of these men presented with recurrent testicular pain and fever, with orchiectomy samples showing focal infarcts and necrotizing vasculitis. The third man presented with epididymitis, with his biopsy specimen showing vasculitis. In two cases, men presented with systemic and testicular signs of polyarteritis nodosa, and the diagnosis was made on testicular biopsy and later studied at autopsy. In another case, the testicular lesions were seen with Goodpasture's syndrome; the patient was thoroughly studied at autopsy, and no evidence of polyarteritis nodosa was found. In the remaining three cases, testicular vasculitis was identified incidentally without diseases associated with vasculitis, one at orchiectomy for prostate adenocarcinoma and the other two at autopsy. Polyarteritis nodosa is the most common cause of necrotizing vasculitis of the testes, and pathologists should recognize the rare testicular presentation of this disease. However, testicular vasculitis also may be seen with other systemic diseases associated with vasculitis. Three of our cases were seen without systemic vasculitis, suggesting that testicular vasculitis may occur as an isolated finding without being a manifestation of systemic disease. HUM PATHOL 19:186--189, 1988.

T h e testes are frequently involved in polyarteritis nodosa, with the reported incidence varying from 60 to 86% in autopsy studies. 1,2 This involvement is infrequently diagnosed before death, because only 2 to 18% of patients are symptomatic.2,~ Only three cases of what is described as polyarteritis nodosa presenting predominantly with testicular signs and symptoms have been reported. 4-6 Although in all three patients, histopathologic lesions typical of polyarteritis nodosa were present in the testis or epididymis, systemic symptoms or other organ involvement was not present, except in the case of Mowad et al. 4 Moreover, Womack and AnselF have reported two cases of isolated arteritis of the epididymis with no evidence of systemic disease at 2.5 years and 6 months follow-up. We undertook this study to evaluate the significance of the histopathologic diagnosis of necrotizing vasculitis in the testes or epididymis and its relation to systemic vasculitis.

From the Department of Pathology,the Johns Hopkins Hospital, Bahimore, Maryland. Accepted for publication 27 April 1987. Address correspondenceand reprint requests to Dr. Shurbaji: Department of Pathology, the Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore,MD 21205. Keywords: epididymitis,Goodpasture'ssyndrome,polyarteritis nodosa, testicularvasculitis. © 1988 W.B. Saunders Company 0046-8177/88 $0.00 + .25 186

MATERIAL AND METHODS

Seven cases in which the diagnosis of vasculitis was first made on a testicular or epididymal specimen were identified in a review of the surgical pathology files of the Johns Hopkins Hospital from 1950 to 1986. All available clinical records and, when applicable, other surgical specimens, autopsy reports, and slides were reviewed. In addition, we searched the autopsy files from May 1889 to July 1986, during which time 45,180 autopsies were performed, and we identified two cases of isolated testicular vasculitis discovered at autopsy. All available clinical records and, when applicable, surgical specimens were reviewed. RESULTS

The clinical and pathologic characteristics of the nine cases included are summarized in table 1. Patients with testicular vasculitis were divided into three broad groups on the basis of the clinical outcome of their disease. T h e first g r o u p consisted of five patients in whom testicular vasculitis was either the initial or an early manifestation of polyarteritis nodosa. Testicular symptoms were the presenting complaints of three patients in whom there was no clinical suspicion of polyarteritis nodosa (cases 1 to 3). Two of these patients had a history of recurrent testicular pain, swelling, and fever, with orchiectomy specImens showing focal infarcts and necrotizing vasculitis. The third man presented with fever and signs and symptoms of epididymitis. Partial epididymectomy was performed and revealed necrotizing vasculids. The remaining two patients in this group presented with systemic symptoms suggestive of polyarteritis nodosa and had testicular signs (tenderness in case 4 and atrophy in case 5) that directed biopsy toward the testes. Testicular biopsy samples revealed necrotizing vasculitis in case 4 and resolving vasculitis in case 5. These five patients were shown to have polyarteritis nodosa by either subsequent clinical, surgical, or autopsy evaluation (table 1). Group II consisted of one patient who had testicular vasculitis and a syndrome known to be associated with systemic vasculitis. This patient (case 6) presented with hypertension, azotemia, and nose bleeds. Polyarteritis nodosa was suspected; and because tenderness was noted on testicular examination, a biopsy was done of the testes, revealing necrotizing vasculitis. The patient then developed massive hemoptysis and died 1 month later. At autopsy, severe fresh and organizing pulmonary hemorrhage

TESTICULARVASCULITIS[Shurbaji & Epstein]

¥.I~LE t.

Case

Age (yr)/Race

Clinical and Pathologic Characteristics of Nine Cases of Testicular Vasculitis

Clinical Presentation

Testicular Signs and Symptoms

Diagnostic Procedure and Pathologic Finding

Group I: Testicular vasculitis as an early or initial manifestation of PAN Orchiectomy: 1 29/W Fever, testicular Recent pain, necrotizing symptoms swelling, ? mass vasculitis Recurrent pain and Orchiectomy: 2 56/W Fever, testicular swelling necrotizing symptoms vasculitis 3 48/B Fever, testicular Testicular pain, Epididymectolny: ? epididymitis necrotizing symptoms vasculitis 4 66/W Neurologic Tenderness Testicular biopsy: necrotizing symptoms, vasculitis azotemia Atrophy Testicular biopsy: 5 51/W Fever, proteinuria resolving vasculitis Group II: Testicular vasculitis occurring in diseases associated with systemic vasculitis 6 73/B Hypertension, Tenderness Testicular biopsy: azotemia, nose necrotizing vasculitis bleeds Group III: Isolated testicular vasculitis 7 75/B Orchiectomy for None Orchiectomy: metastatic necrotizing prostate vasculitis adenocarcinoma 8 70/B Sudden cardiac None Autopsy: death necrotizing vasculitis 9 53/B Acute myelogenous None Autopsy: leukemia necrotizing vasculitis

Final Diagnosis* PAN: systemic symptoms noted clinically

(2 mo)

PAN: vasculitis on temporal biopsy (9 too), ileal resection (10 mo), and autopsy (21 mo) PAN: vasculitis on prostate biopsy (7 yr) PAN: systemic symptoms of PAN confirmed by initial testicular biopsy and autopsy (137 mo) PAN: systemic symptoms of PAN confirmed by initial testicular biopsy and autopsy (11 mo) Goodpasture's syndrome: diagnosed at autopsy (1 mo) Isolated testicular vasculitis: no evidence of systemic vasculitis at 12 mo follow-up Isolated testicular vasculitis: no evidence of systemic vasculitis at autopsy Isolated testicular vasculitis: no evidence of systemic vasculitis at autopsy

* In parentheses are listed the intervals from testicular biopsy or orchiectomy to the diagnosis or event. PAN, polyarteritis nodosa.

and a crescentic glomerulonephritis with an immunofluorescence pattern consistent with the diagnosis of Goodpasture's syndrome were found. No evidence of active or inactive vasculitis was seen in any organ, although the testes showed multifocal tubular atrophy and scarring. The third group comprised three patients in whom necrotizing vasculitis, histopathologically indistinguishable from polyarteritis nodosa, was incidentally discovered. None of these patients had any testicular or systemic symptoms suggestive of vasculitis. In one patient (case 7), the lesions were discovered incidentally in both testes removed because of metastatic adenocarcinoma of the prostate. The patient lived for 12 months after the procedure without evidence of systemic vasculitis despite close followup. Isolated necrotizing testicular vasculitis was discovered incidentally at autopsy in two patients (cases 8 and 9). The first was a patient with sudden cardiac death, and the other died of acute myelogenous leukemia. In both, thorough study at autopsy revealed no vasculitis in any other organ. PATHOLOGIC FINDINGS

In group I, comprising the three patients who presented with testicular signs of polyarteritis no187

dosa, the two orchiectomy specimens showed active and resolving vasculitis involving the medium-sized and small arteries within the testicular parenchyma and tunica albuginea (fig. 1). One of these patients (case 2) had, in addition, vasculitis involving arteries of the spermatic cord. Both orchiectomy specimens showed recent testicular infarcts (fig. 1B). The third patient, who presented with testicular signs of polyarteritis nodosa, had only an epididymectomy perf o r m e d which revealed a similar vasculitis. T h e remaining two men in group I, who were clinically suspected to have polyarteritis nodosa, had limited testicular biopsies performed, one showing an active vasculitis and the other a resolving arteritis involving only a single vessel in each case. In group II, the biopsy specimen from the single patient showed only active vasculitis in small and medium-sized arteries (fig. 2). The patients in group III with isolated testicular vasculitis all had orchiectomy specimens for review. All three had some vasculitic lesions that were indistinguishable from those seen in the active phases of polyarteritis nodosa, with panarteritis, periarteritis, acute and chronic inflammation, and fibrinoid necrosis of the vessel wall often affecting only a localized segment of the wall (fig. 3). One of these cases also had lesions of resolving vasculitis. Multiple such

HUMAN PATHOLOGY

Volume 19, No. 2 [February 1988]

FIGURE 1. A, Typical lesion of active polyarteritis nodosa [case I] showing fibrinoid necrosis with transmural acute inflammation in a medium-sized artery in the testicular parenchyma. B, Recent testicular infarct [case I] with hemorrhage [bottom]. A medium-sized artery with resolving arteritis is shown in the adjacent viable testicular parenchyma [top]. [Both, hematoxylin-eosin stain. A, × 130; B, x 50.]

lesions were identified in two patients, and only a single artery was involved in the third. In addition to the p a r e n c h y m a l vasculitis, one m a n had involvem e n t of vessels in the tunica albuginea. No evidence of recent or remote testicular infarcts was noted. In summary, the vasculitic lesions of isolated testicular vasculitis a p p e a r e d histologically indistinguishable f r o m those seen in polyarteritis nodosa. A m o n g the orchiectomy and autopsy specimens, in which sampling e r r o r was not a factor, there was o v e r l a p a m o n g all t h r e e g r o u p s in terms o f the n u m b e r o f vessels involved, location o f affected vessels, and the presence of active and resolving vasculitis, although there was a greater p r e p o n d e r a n c e o f vasculitic lesions o f variable ages in the polyarteritis nodosa group. T h e only feature seen exclusively in the polyarteritis nodosa group was that of recent testicular infarcts, which may have accounted for these patients' testicular symptoms, in contrast to the asymptomatic patients with isolated testicular vasculitis who were discovered incidentally.

DISCUSSION Vasculitis affecting the testis is most commonly seen as a manifestation of polyarteritis nodosa. Autopsy studies have shown a high incidence of testicular involvement by polyarteritis nodosa at autopsy,

ranging from 60 to 86%. 1,2 This involvement is infrequently diagnosed before d e a t h because only 2 to 18% o f t h e s e p a t i e n t s s h o w t e s t i c u l a r signs or symptoms. 2,3 In only one previously r e p o r t e d case was testicular vasculitis the presenting manifestation of subsequently proven polyarteritis nodosa. 4 In our series, the most c o m m o n cause of necrotizing vasculitis involving the testis was polyarteritis nodosa, which was seen in five men. T h r e e of these patients presented initially with signs and symptoms confined to the testes or epididymis, but on follow-up they developed evidence of systemic involvement by polyarteritis nodosa. T h e pathologist should be aware that testicular vasculitis, t h o u g h rare, may be the first manifestation of polyarteritis nodosa. However, testicular vasculitis histologically indistinguishable from polyarteritis nodosa may also be seen with other systemic diseases associated with vasculitis. In our series, one patient had Goodpasture's syndrome, a disease known to be associated with a polyarteritis nodosalike vasculitis, s W h e n groups I and II were combined, six of the nine patients with testicular vasculifts (67%) ultimately were shown to have serious systemic illnesses. T h e existence of polyarteritis nodosa-like lesions confined to one organ, as seen in three of our cases, is now well recognized and has been reported in the a p p e n d i x , 9 gallbladder, 1° uterine cervix, 11 uterine corpus, a2 a n d breasts. 13 W o m a c k a n d AnselF have

188

TESTICULARVASCULITIS[Shurbaji & Epstein

FIGURE 2 [left]. Testicular biopsy sample from a patient with Goodpasture's syndrome [case 6] showing active necrotizing vasculitis involving a small parenchymal artery, Note the fibrinoid necrosis and segmental involvement of vessel wall, {Hematoxylin-eosin stain, × 210.] FIGURE 3 [right], Isolated testicuar vasculitis [case 7] showing active polyarteritis nodosa-like lesions involving a small parenchymal artery. Note the similarity with lesions shown in figures IA and 2, [Hematoxylin-eosin stain. × 210.]

reported two cases of isolated arteritis of the epididymis. This study shows that testicular vasculitis need not be a manifestation of systemic disease, but may occur as an isolated, incidental finding. It is important to distinguish cases of isolated testicular vasculitis from polyarteritis nodosa, given the latter diagnosis' p o o r p r o g n o s i s and n e e d for aggressive therapy. All three of our patients with isolated testicular vasculitis were asymptomatic, in contrast to those patients with systemic vasculitis. Although the vasculitis lesions of isolated testicular vasculitis appeared histologically indistinguishable from those seen in polyarteritis nodosa, recent testicular infarcts were only seen in the polyarteritis nodosa group, possibly accounting for these patients' testicular symptoms. The presence of recent testicular infarcts may be a poor prognostic sign when evaluating necrotizing vasculitis that is apparently confined to the testis.

2. Dahl EV, Baggenstoss AH, DeWeerd JH: Testicular lesions of periarteritis nodosa, with special reference to diagnosis. Am J Med 28:222, 1960 3. Frohnert PP, Shepps SG: Long-term follow-up study of periarteritis nodosa. Am J Med 43:8, 1967 4. Mowad J J, Baldwin BJ, Young JD Jr: Periarteritis nodosa presenting as mass in testis. J Urol 105:109, 1971 5. Roy JB, Hamblin DW, Brown CH: Periarteritis nodosa of epididymis. Urol 10:62, 1977 6. Lee LM, Moloney PJ, Wong HCG, et ah Testicular pain: an unusual presentation of polyarteritis nodosa. J Urol 129:1243, 1983 7. Womack C, Ansell ID: Isolated arteritis of the epididymis. J Clin Pathol 38:797, 1985 8. Heptinstall RH: Schonlein-Henoch syndrome: tung hemorrhage and glomerulonephritis or Goodpasture's syndrome. In Heptinstall RH (ed): Pathology of the Kidney, vol II, ed 3. Boston, Little Brown & Co., 1983, p 761 9. Plaut A: Asymptomatic focal arteritis of the appendix. Am J Pathol 27:247, 1951 10. Bohrod MG, Bodon GR: Isolated polyarteritis nodosa of the gallbladder. Am Surg 36:681, 1970 11. Ansell ID, Evans DJ, Wight DGD: Asymptomatic arteritis of the uterine cervix. J Clin Pathol 27:664, 1974 12. Lin CS, Braza F: Focal arteritis of the uterus: a case report. Mt Sinai J Med 45:402, 1978 13. Chaitin B, Kohout ND, Goldman RL: Focal arteritis of the breast. Angiology 32:334, 1981

REFERENCES 1. McCall M, Pennock JW: Periarteritis nodosa: our present knowledge of the disease. Ann Intern Med 21:628, 1944

189