Idiopathic retroperitoneal fibrosis: a report of 3 cases.P Vaideeswar, AS Shenoy, A Sivaraman, JR Deshpande, AA Pandit
Dept of Pathology, Seth GS Medical College, Bombay, Maharashtra.
Case histories of three male patients diagnosed as idiopathic retroperitoneal fibrosis either on autopsy or following intra-operative biopsy are reported. Two of them were in the 5th decade and one aged 22 yrs. All of them presented with features of urinary tract obstruction and renal failure. The obstruction was detected either by ultrasonography or following ascending pyelogram. One of them underwent peritoneal dialysis but later on died of sudden cardiac arrest. The remaining two underwent surgery, during which a biopsy was taken. Histological examination in all the three patients revealed fibroblastic proliferation and mononuclear cell infiltration. Features of chronic periaortitis were also found in the autopsy specimen of descending aorta of the first patient. Both the elderly patients had aortic atherosclerosis which is suspected to be the etiological factor for fibrosis. However in the young male patient intense eosinophilic infiltrate was observed in biopsy material pointing towards 'hypersensitivity' reaction as a cause for fibrosis.
Keywords: Adult, Case Report, Human, Kidney Failure, Chronic, etiology,Male, Middle Age, Retroperitoneal Fibrosis, complications,diagnosis,Ureteral Obstruction, etiology,
Idiopathic retroperitoneal fibrosis is a rare disease of unknown aetiology, characterized by fibroblastic proliferation, collagen deposition and a variable infiltration of inflammatory cells. It typically affects middle aged and elderly patients, especially males; they usually present with features of chronic renal failure produced by fibrous constriction and final obliteration of the ureters.
Most cases of retroperitoneal fibrosis are idiopathic and the rest are associated with ingestion of drugs or some form of retroperitoneal injury. We are reporting three cases of retroperitoneal fibrosis, two in elderly males and one in a 22-year-old male who presented with urinary tract obstruction/chronic renal failure.
Case 1: A 54-year-old male was admitted for acute and intermittent abdominal pain and oedema feet since 8 months. There was a previous history of chest pain, vomiting and loose motions. He was a known hypertensive on irregular drug therapy.
On examination, there was mild pallor. The blood pressure was 130/90 mm Hg and there was a pericardial rub on auscultation. Other systems were normal. The BUN was 130 mg% and serum creatinine 10.6 mg%. The electrocardiogram was suggestive of an antero-septal ischaemia. Ultrasonography showed bilateral renal enlargement with grade 1 and grade 2 hydronephrosis of the right and left kidneys respectively. In view of the azotaemia, peritoneal dialysis was done. However, the patient did not improve and later had sudden cardiac arrest.
A complete autopsy was performed. There was an ill defined, irregular, grey white, extremely firm/hard mid-line retroperitoneal mass. This encased the proximal descending abdominal aorta, inferior vena cava and their branches, as well as the middle third of the right ureter and the proximal third of the left ureter. It extended into the hilum of the left kidney [Figure:1], and was firmly adherent to the head and part of the body of the pancreas and duodenum. The posterior part of the diaphragm on the right side was greyish white and fibrotic. Microscopically, the mass was composed of hyaline fibrous tissue with an infiltrate of lymphocytes, plasma cells and few histiocytes. At places, there were lymphocytic aggregates with palest germinal centres [Figure:2]. Entrapped nerve bundles and lymph nodes were also seen. The veins showed evidence of phlebitis with organizing thrombi. Small arteries showed circumferential fibrous intimal thickening.
The perirenal fat and renal capsule were markedly thickened and fibrotic. The left kidney (55 gm) was smaller than the right (100 gm), Both showed features of benign nephrosclerosis and chronic pyelonephritis with mild hydronephrosis.
The heart was moderately enlarged (500 gm), with fibrinous pericarditis. The coronaries showed mild atheromatous narrowing. There was no evidence of recent or healed myocardial infarction. The entire descending thoracic aorta and the abdominal aorta (not encased) in the retroperitoneal mass) showed marked thickening of its wall, measuring 9 mm at the site of maximum thickness. Intima showed severe atherosclerosis. On microscopy, there was marked periadventitial and adventitial fibrosis [Figure:3], represented by bands of hyalinised fibrocollagenous tissue with vascularization. Aggregates of lymphocytes and plasma cells were also present.
The other findings were mild cerebral oedema, tuberculous bronchopneumonia in the left upper lobe with associated tuberculous lymphadenitis. A diagnosis of idiopathic retroperitoneal fibrosis, chronic periaortitis with chronic renal failure was made.
Case 2: A 55-year-old male presented with left loin pain since many days. The blood pressure was 160/120 mm Hg. The BUN was 14 mg% and creatinine 1.1 mg %. Urine culture showed no growth. The ascending pyelogram showed a left pyelo-ureteral obstruction.
Per-operatively, there was a hard mass, densely adherent to the left kidney and surrounding the left ureter and the aorta. In view of suspected renal malignancy, the left kidney and upper one third of the ureter were excised along with the mass. Part of the mass around the aorta was left behind.
The tissue representing the excised mass showed fibrous tissue with diffuse infiltrate of lymphocytes, plasma cells, neutrophils and occasional eosinophils. A few lymphoid aggregates were also present. The veins showed mural infiltration of neutrophils and lymphocytes with luminal organizing thrombi [Figure:4]. The excised kidney showed hydronephrosis and features of chronic pyelonephritis
Case 3: A 22-year-old male came with a history of progressive oliguria and occasional dysuria, pain in the left abdomen and back and fever with chills since 6-8 months. There was no previous history of tuberculosis or tuberculous contact and of urethral instrumentation.
Systemic examination revealed only left loin tenderness and bilateral small hydrocoeles. Haemogram was normal. Routine urine examination showed mild degree of proteinuria with 4-6 pus cells and 3-5 red blood cells per high power field. The BUN and creatinine were 128 mg % and 9.7 mg % respectively. The other biochemical investigations were within normal limits.
Ultrasonography showed bilateral renal enlargement with grade 2 hydronephrosis and hydroureter. Cystoscopy showed a bulge in the posterior of the urinary bladder, suggesting an extrinsic mass. The computed. tomographic scan was suggestive of a soft tissue tumour in the region of the seminal lymphoma vesicles, infiltrating the posterior wall of the bladder and the anterior wall of the rectum.
Exploratory laparotomy was performed. There was a hard, irregular and ill circumscribed mass at the base of the bladder, engulfing both ureters. The left ureter was thick walled with a narrow lumen. There were nodular deposits at the internal inguinal ring. Mass biopsy, internal inguinal ring deposits and lower segment of the left ureter were submitted for histopathology. Left ureteric implantation to the lateral bladder wall was performed.
The biopsy from the mass was represented by four brown, soft to firm bits, aggregating 2 cm. Microscopically, it was composed of mainly fibrous tissue with collagenization and collections and infiltrations of lymphocytes, plasma cells, few histiocytes, neutrophils and eosinophils. There was phlebitis with recanalising thrombi. Grey white nodules from the internal ring showed features similar to the retrovesical mass. Sections from the ureter showed intact normal epithelium with marked eosinophilic infiltration in the lamina propria forming in abscess. The muscle and perimuscular tissue had dense eosinophilic infiltration with fibrosis and vascularization. Careful search did not reveal any micro-organisms or parasites.
Idiopathic retroperitoneal fibrosis is a disease of infrequent occurrence with well-defined and distinct clinical and pathological features. Although an earlier description of this condition existed in the French literature (Albarran in 1905), it was not until Ormond's reports, that it became a well-established entity. Since retroperitoneal fibrosis shares its obscure aetiology and non-specific morphologic characteristics with a variety of lesions like mediastinal fibrosis, orbital sclerosis, Reidel's thyroiditis and sclerosing cholangitis, these conditions are grouped under the term, idiopathic systemic fibrosis or multifocal fibro-sclerosis.
The process usually occurs in elderly patients. But, it has also been reported in patients in the third and fourth decades of life and even in children. Males are affected more commonly than females. All three in our series are males - two in the fifth decade and the third was 22-year-old.
The cause of retroperitoneal fibrosis is poorly understood. About three-fourths of the cases are idiopathic while other cases may be related to retroperitoneal injury, drug therapy with methysergide, beta-blockers and haloperidol or genetic factors. In a recent report, Dent et al have demonstrated a T cell receptor gene re-arrangement and suggested that the fibrotic process probably represented a low grade T cell lymphoma.
It is also proposed that the fibrosis results from a hypersensitivity reaction directed against certain substances released from atherosclerotic plaques. Autopsy and computed tomographic studies show that the fibrotic process occurs usually around the aorta, which has severe atherosclerosis. This results in medial thinning and/or breaching. When this occurs, insoluble lipid, ceroid, leaks into the periaortic tissue to elicit an immunologic reaction. The active immunological phenomenon is indicated by the presence of circulating anti-ceroid antibodies and the nature of inflammatory cells, as studied by cell markers. The inflammatory cell infiltrates are accompanied by varied amount of peri-aortic fibrosis and varying degrees of wall thickening and the term 'chronic peri-aortitis' was proposed by Mitchinson in 1984.
Aortic atheroscierosis may have been the aetiolgic factor in two cases of retroperitoneal fibrosis, seen in the elderly. In fact, the autopsied case also showed chronic peri-aortitis, proximal and distal to the area of retroperitoneal fibrosis. The aetiology of the third case remains obscure.
The primary pathologic change is involvement of the fat of the Gerota's fascia of the retroperitoneum by the inflammatory process, which is rapidly converted to dense fibrous scar. Occlusive phlebitis is an important feature and was seen in all the cases. The cell infiltrate consists mainly of aggregates of lymphocytes and plasma cells, often accompanied by macrophages and eosinophils. This was the histologic picture in the first two cases of retroperitoneal fibrosis, where an atheroscierotic aetiology was suspected. However, the young male with a pelvic mass (Case 3), showed a striking infiltrate of eosinophils, suggesting the possibility of a hypersensitivity aetiology, unrelated to atheroscierosis.
Most frequently, the patients present with features of chronic renal failure, hypertension, pain, backache, weight loss and abdominal mass. In all the cases reported, the patients presented with features of urinary tract obstruction and renal failure.
The mode of treatment is excision of the mass with ureterolysis and corticosteroid therapy. However, some patients do not respond to therapy; the underlying fibrosis/inflammation continues and they present with recurrence of symptoms. Unfortunately, both our surgical cases were lost to follow-up.
We are grateful to the Dean, Seth GS Medical College and King Edward Memorial Hospital, Mumbai for granting us the permission to publish the article.