Clin J Gastroenterol (2010) 3:296–300 DOI 10.1007/s12328-010-0184-7
A case of polyarteritis nodosa complicated by rectal cancer Takatomi Oku • Tetsuro Okamoto • Takashi Sakai • Tetsuya Miseki • Yasunori Kubo Atsushi Yamakawa • Hideaki Sugata
Received: 7 April 2010 / Accepted: 3 October 2010 / Published online: 3 November 2010 Ó Springer 2010
Abstract Solid cancers are rarely complicated by the occurrence of polyarteritis nodosa (PN), and most cases diagnosed as PN are, in fact, cases of paraneoplastic vasculitis. Paraneoplastic vasculitis is usually resolved after tumor removal. We present a rare case of a 69-year-old man with PN complicated by rectal cancer, without the occurrence of paraneoplastic vasculitis. Microscopic examination of the resected cancer lesion revealed inflammation of some arteries and neutrophil and lymphocyte infiltration, fibrin deposition, stenosis, and vasodilatation of capillaries caused by congestion in the submucosal layer. It was unclear how these findings exerted influence on the rectal cancer. Although the symptoms of PN did not improve after the patient’s tumor was removed surgically, the symptoms improved rapidly after oral treatment with prednisolone and cyclophosphamide. Keywords
Rectal cancer Polyarteritis nodosa
Introduction Polyarteritis nodosa (PN) is an autoimmune disease characterized by systemic angiitis. Collagen diseases are often complicated by the occurrence of various cancers, as is typically seen in dermatomyositis. Although patients with PN sometimes have hematologic neoplasms, solid cancers T. Oku (&) T. Sakai T. Miseki Y. Kubo A. Yamakawa H. Sugata Internal Medicine, Obihiro Daiichi Hospital, West-4, South-15, Obihiro 080-0014, Japan e-mail: [email protected]
T. Okamoto Internal Medicine, Gorinbashi Naika Hospital, Sapporo, Japan
are rarely found in such patients . Moreover, all the reported cases of PN with malignancy have features of paraneoplastic vasculitis. We report a case of a patient with rectal cancer who had a long history of PN that was not paraneoplastic vasculitis. Herein, we describe the unique histopathologic features of blood vessels present at the cancer site.
Case report A 69-year-old man was referred to our hospital in February 2003 for further evaluation of a fever and polyarthralgia that had persisted since 1994. His private medical doctor had treated him with low-dose prednisolone and non-steroidal anti-inflammatory drugs; however, his symptoms (body temperature exceeding 38°C) that had exacerbated from December 2002 failed to improve even with the administration of prednisolone at 20 mg/day and several different antibiotics. He lost 7 kg of body weight in 2 months. He was a non-smoker and his family history was unremarkable. The following findings were obtained on physical examination: height, 167 cm; body weight, 57 kg; blood pressure, 120/84 mmHg; pulse, 72/min; and body temperature, 38.2°C. Mild pallor was observed in the palpebral conjunctiva. No lymphoadenopathy was detected by palpation in accessible nodal sites. There were no abnormal findings in the chest or abdomen. He had edema in the right leg and myalgia in his right calf. Neurologic examination revealed sensory impairment in the right ulnar nerve area and dorsum of the right foot. The deep tendon reflexes were diminished in both distal extremities, with bilateral foot drop. The patient had a highly elevated serum level of C-reactive protein (CRP) value (14.5 mg/dl), but his
Clin J Gastroenterol (2010) 3:296–300
mononeuritis, and polyarthralgia and polymyalgia. Since the patient had elevated levels of MPO-ANCA, microscopic polyangiitis (MPA) was considered in the differential diagnosis of this case; however, this antibody test has
peripheral blood leukocyte count (8600/ll) was not elevated (Table 1). Normocytic and normochromic anemia was also found. The anti-nuclear antibody test was positive, and myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) was positive, at over 640 EU. In addition, the plasma level of thrombomodulin (TM)—a marker of endothelial cell damage—was high. The fecal occult blood test was repeatedly positive. Nerve conduction velocity tests showed normal velocity in the peroneal nerves of both sides, with reduced potential amplitudes on the right side, implying axonal degeneration in the right peroneal nerve. Similar findings were obtained for the right ulnar nerve. These neurologic findings were indicative of mononeuritis multiplex. Magnetic resonance imaging (MRI) with T2-weighted images of the patient’s calf revealed that the signal intensity of the right soleus muscle was higher than that of the left; this finding was believed to reflect inflammatory edema. Histologic examination of the biopsy specimens from the right soleus muscle revealed extensive inflammatory cell infiltration, with fibrinoid necrosis of arterial walls (Fig. 1). These findings showed that the patient fulfilled the Japanese diagnostic criteria of classical PN proposed by the Research Committee in 1998, including the characteristic tissue findings and 3 major manifestations, namely, continuous fever with a temperature exceeding 38°C, multiple
Fig. 1 Histologic examination of biopsy specimens from the right soleus muscle. Remarkable inflammatory cell invasion, laceration and fibrinoid necrosis of elastic fiber in periarterial area were found (H&E, 9200)
Table 1 Laboratory data on admission Peripheral blood WBC RBC Hb
Blood chemistry 8600/ll 4
379 9 10 /ll 9.6 g/dl
3.0 g/dl 0.3 mg/dl
69 IU/ml 80 9 (nucleolar type)
29.1 9 10 /ll
Coagulation tests PT
Stool occult blood
Tumor markers CEA CA19-9
1.7 ng/ml 7.6 IU/ml
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Fig. 2 Colonoscopic findings of rectal cancer. a 0-IIa ? IIc type lesion of approximately 15 mm diameter was found in the rectum. b The margin of the lesion showed clearly after indigo carmine spraying (H&E, 9200)
low specificity and may also be elevated in PN . In addition, in our case, we did not find any characteristic features of MPA, i.e., the patient did not have renal dysfunction, lung hemorrhage, or intestinal pneumonia. Muscle biopsy findings revealed medium- and small-sized muscular arteries with a leukocytic infiltrate. On the basis of the above findings, PN was diagnosed in our patient. Colonoscopy was also performed because of repeatedly positive fecal occult blood tests and also because PN may be complicated by gastrointestinal tract bleeding, which is considered as a prognostic factor in PN . Colonoscopy revealed an elevated rectal lesion with a central depression which was classified as the 0-IIa ? IIc type according to the Japanese macroscopic classification  (Fig. 2a, b). The histologic characteristics of the biopsy specimens were also compatible with a well-differentiated adenocarcinoma. Because the submucosal layer showed narrowing at irregular intervals on endoscopic ultrasonography, the lesion was considered to have extensively invaded the submucosal layer. Computed tomography and ultrasonography showed no metastasis in the liver, lymph nodes, or other sites, and no signs of ascites. Laparoscopically-assisted low anterior resection of the rectum was performed on March 20, 2003; on the basis of its macroscopic appearance, the lesion was classified as 0-IIa ? IIc rectal cancer of approximately 15 mm diameter macroscopically. The histopathologic diagnosis was sm ly1 v1 N (-) P0 H0 M (-) stage I, according to Japanese criteria . Pathologic examination of the resected cancerous tissue also revealed signs of angiitis. Microscopic examination of the lesion revealed inflammation of some arteries and neutrophil and lymphocyte infiltration, fibrin deposition, stenosis, and vasodilatation of capillaries caused by congestion in the submucosal layer (Fig. 3). These findings were thought to be typical of PN; however, neither ulcerations nor ischemic changes were found. The clinical course in this case is illustrated in Fig. 4. Resection of the rectal cancer failed to improve the patient’s symptoms, including high-grade fever, polyarthralgia, and
Fig. 3 Histopathologic findings of the resected rectal cancer tissue. Microscopic findings revealed angiitis in some arteries with neutrophil and lymphocyte infiltration, fibrin deposition, occlusions (arrow) and vasodilatation of capillaries caused by congestion in the submucosal layer in rectal cancer (arrowhead) (H&E, 9200)
polyneuritis. High serum levels of CRP, TM, and MPOANCA also persisted. First, intravenous methylprednisolone at 1.0 g/day was administered for 3 consecutive days and then the patient was started on oral prednisolone at 60 mg/day (1 mg/kg day-1) and oral cyclophosphamide at 50 mg/day (0.8 mg/kg day-1). Subjective symptoms, including the high-grade fever, improved immediately, and the serum levels of CRP and TM and the titer of MPO-ANCA also decreased.
Discussion According to the Annual of Pathological Autopsy Cases in Japan (Nippon Boken Shuho), the incidence of solid cancer as a complication of PN (0.5%) is lower than that of systemic lupus erythematosus (1.2%), systemic sclerosis
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Fig. 4 Clinical course of the patient. PSL Prednisolone, mPSL methylprednisolone, CP cyclophosphamide, CRP C-reactive protein, TM thrombomodulin, MPO-ANCA myeloperoxidase antineutrophil cytoplasmic antibody
20mg PSL 10mg
PSL CP 50mg
(9.2–9.6%), and dermato- and polymyositis (25.9–53.5%) . Angiitis, including PN, tends to be complicated by hematologic neoplasms, including hairy-cell leukemia, rather than by solid cancers [1, 6, 7]. To the best of our knowledge, the first case of vasculitis associated with solid tumor was reported in 1968 , and since then, only 51 such cases have been described. The most frequently observed solid cancers in patients with vasculitis were those of the lung, colon, kidney, prostate, and head and neck . Different subtypes of inflammatory blood vessel disease have been documented in patients with solid tumors and include cutaneous leukocytoclastic vasculitis, peripheral nerve and muscle microvasculitis, Henoch–Scho¨nlein purpura, temporal arteritis, PN, Churg–Strauss syndrome, etc.; cutaneous leukocytoclastic vasculitis is the most frequent type noted. To date, only 3 cases of PN-associated solid cancer have been reported [10–12]. Interestingly, almost all the PN patients developing complicated solid tumors had paraneoplastic vasculitis, which is usually resolved if the tumor is removed, so it is included in the criteria proposed by Curth . Several mechanisms have been proposed to explain paraneoplastic vasculitis: (a) direct invasion of the cancer cells , (b) infectious complication of the tumor , and (c) an immunologic link between vasculitis and the neoplasm [15, 16]. On the other hand, it was hard to diagnose our patient’s angiitis as a paraneoplastic vasculitis because his clinical symptoms of PN had been present since 1994 and had not improved even after tumor resection. Therefore, we believe that the present case is very important and is the first report of cancer complicated with PN rather than paraneoplastic
vasculitis. The mechanism underlying the development of both rectal cancer and PN in the same person has yet to be clarified. Since there is no similar report, we consider that the carcinogenesis in this case was not related to PN. If vasculitis does not improve after removing the tumor, immunosuppressive treatment should be administered immediately because the vasculitis is not paraneoplastic. Approximately two-thirds of patients with PN experience abdominal pain, nausea, vomiting, or other gastrointestinal signs and symptoms associated with organ damage due to ischemia and infarction ; among all cases of PN, gastrointestinal hemorrhage occurs in roughly 6% of cases, bowel perforation in 5%, and bowel infarction in 1.4% [18, 19]. Pathologic characteristics in the bowel walls of PN are essentially the same as in ischemic enterocolitis including ulcer, erosion, necrosis, hematomas and congestions etc. . In most patients with PN, ischemia is present in the small bowel, but it is rare in the colon  due to vascular network complexity. Although the arteriole in the submucosal layer of the colon in the presented case had fibrinoid necrosis with inflammatory cell infiltration, no findings of ishchemic change were seen histologically. As it was unclear how these findings exerted influence on the rectal cancer, it will be necessary to investigate similar cases and further investigate angiitis within cancer tissues with PN.
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