54歳女性.患者は超音波検査にて膀胱に異常腫瘤を指摘され, 著者らの泌尿器科へ受診となった.膀胱鏡検査では膀胱後壁に小指頭大の非乳頭状広基性腫瘍が確認され, 経尿道的膀胱腫瘍切除術を施行となった.しかし, 切除開始時, 収縮期血圧が240mmHgまで急激に上昇し, 切除続行は困難と判断し手術を中止に, することとなった.術後は血清ノルアドレナリン濃度の上昇がみられた.病理組織学的診断では悪性褐色細胞腫であった.その後, 膀胱部分切除術および骨盤内リンパ節郭清術を施行したところ術後1年経過現在, 再発の徴候は認められていないA case of malignant pheochromocytoma of the urinary bladder is presented. A 54-year-old woman visited our hospital for screening and was found to have an abnormal mass in the bladder on ultrasonography. The patient was not hypertensive. Cystoscopy revealed a broad-based, small fingertip-sized, nonpapillary tumor on the posterior wall of the urinary bladder. Transurethral resection (TUR) was performed without suspicion of pheochromocytoma because of her well-controlled blood pressure and lack of characteristic symptoms. Transient elevation of systolic blood pressure to 240 mmHg occurred during resection of the tumor. Radical resection was therefore not possible. The serum norepinephrine level was elevated postoperatively. Pathologic examination revealed a malignant pheochromocytoma. On January 30, 2003, partial cystectomy of the residual tumor and pelvic lymphadenectomy were performed. She has had no clinical sign of recurrence for 1 year after the second operation

Osafune, Takashi

Segawa, Naoki

Kyoto University Research Information Repository

Title Malignant pheochromocytoma of the urinary bladderAuthor(s)Segawa, Naoki; Osafune, TakashiCitation泌尿器科紀要 (2005), 51(4): 291-296Issue Date2005-04URL http://hdl.handle.net/2433/113586RightType Departmental Bulletin PaperTextversionpublisherKyoto UniversityActa Urol. Jpn. 51: 291-296, 2005 291 MALIGNANT PHEOCHROMOCYTOMA OF THE URINARY BLADDER Naoki SEGAWA and Takashi OSAFUNE The Department of Urology, Otsu Red Cross Hospital A case of malignant pheochromocytoma of the urinary bladder is presented. A 54-year-old woman visited our hospital for screening and was found to have an abnormal mass in the bladder on ultrasonography. The patient was not hypertensive. Cystoscopy revealed a broad-based, small fingertip-sized, non papillary tumor on the posterior wall of the urinary bladder. Transurethral resection (TUR) was performed without suspicion of pheochromocytoma because of her well-controlled blood pressure and lack of characteristic symptoms. Transient elevation of systolic blood pressure to 240 mmHg occurred during resection of the tumor. Radical resection was therefore not possible. The serum norepinephrine level was elevated postoperatively. Pathologic examination revealed a malignant pheochromocytoma. On January 30, 2003, partial cystectomy of the residual tumor and pelvic lymphadenectomy were performed. She has had no clinical sign of recurrence for I year after the second operation. (Hinyokika Kiyo 51: 291-296, 2005) Key words: Pheochromocytoma, Bladder tumor, Urinary bladder INTRODUCTION Pheochromocytomas are neoplasms ansmg from chromaffin tissues of the sympathetic nervous system. Primary involvement of the urinary bladder is rare, and accounts for less than 0.06% of all vesical neoplasms I) and less than I % of all pheochro-mocytomas2) Pheochromocytomas are rarely ma-lignant. We present a case of malignant pheochro-mocytoma of the urinary bladder CASE REPORT A 54-year-old woman was admitted to the Department of Internal Medicine in our hospital for screening on December 10, 2002. A urinary bladder tumor was incidentally detected on abdominal ultrasonography. It was a 1.0 X 1.0 cm well-defined, solid echogenic mass. She was referred to the Department of Urology. She was 160 cm tall and weighed 57.5 kg. Her pulse was 72 beats/min. Her blood pressure was 120/80 mmHg. Findings of physical examination were unremarkable. She had no history of hypertension, and was taking no medications. Laboratory data, including complete blood count, blood urea nitrogen, creatinine, electrolytes and urinalysis, were normal. Urine cytology yielded a class II result. Blood norad-renaline and adrenaline levels were not measured since the tumor had not been diagnosed as a pheochromocytoma of the urinary bladder prior to surgery. Cystoscopic examination revealed a I cm broad-based, non-papillary submucosal tumor in the posterior wall of the bladder. The surface was covered by nearly normal mucosa. Pelvic magnetic resonance imaging (MRI) revealed a demarcated Fig. I. MRI (saggital plane) showed a demar-cated mass with a high signal intensity on TI-weighted images. mass with high signal intensity on both TI- and T2-weighted images (Fig. I). The tumor had clear margins. No extravesicular invasion was observed . Transurethral resection (TUR) was performed for differential diagnosis on December 17, 2002. The patient's systolic blood pressure abruptly increased to 240 mmHg at the beginning of TUR. Complete TUR was considered impossible and biopsy alone ·was performed. On the day after operation, the serum noradrenaline level was elevated (I, 165 pg/ml, normal range: 100-450 pg/ml) . Adrenaline and dopamine levels were normal. 131I-meta-iodo-benzylguanidine scintigraphy revealed no uptake of 292 Acta Urol. Jpn. Vol. 51, No.4, 2005 a b • . , • & • .. " • .. • c d Fig. 2. Histopathological findings of the tumor. (a) HE stain (X400), (b) HE stain (X200), (c) Immunohistochemical staining is positive to chromogranin A (X400), (d) Positive reactivity for MIB-l is found in 7% of the tumor cells (X400). isotope In the urinary bladder. No extravesical uptake was noted. A technetium bone scan was negative for metastasis Histopathologically, the tumor cells had granular cytoplasm with a moderately pleomorphic nucleus and were proliferating abundantly to form a spindle-like shape in a piriform honeycomb form (Fig. 2a). They presented the characteristic features of pheochromocytoma. The major portion of the tumor was invading the muscular layer (Fig. 2b) . Immunohistologically, the tumor cells were positive for chromogranin A and MIB-l (Fig. 2c, d). Based on these findings, the tumor was diagnosed as a primary malignant pheochromocytoma of the urinary bladder. The amount of tumor remaining in the deep muscle layer suggested that additional surgical treatment was needed. In preparation for removal of the pheochromocytoma, the patient was treated with a lO-day course of a blockade and intravenous hydration in the hospital. She had no cardiac aberrations and no f3 blockade was necessary. Partial cystectomy including the mass and limited bilateral pelvic lymphadenectomy were performed under general anesthesia. The InCISIOn was circumscribed with a I-cm margin. Since no extravesicular invasion was observed, separation of the bladder was relatively easy. The surgical margin was free of tumor. No pelvic lymphadenopathy was observed. No fluctuation of blood pressure was noted during the surgical procedures. Postoper-atively, her blood pressure was maintained with intravascular volume expansion. Gross-pathologic examination revealed a well-circumscribed, white-yellowish, homogeneous mass within the bladder wall. Final pathologic examination also revealed malignant pheochromocytoma. The surgical mar-gins were free of tumor, as were the lymph nodes. The serum noradrenaline level was normalized and remained normal a month after operation. Her course has remained uneventful up to one year postoperatively without any signs of recurrence or metastasis. DISCUSSION It is difficult to judge preoperatively whether a pheochromocytoma is malignant or not based on preoperative morphological features, but the grounds for malignancy include metastasis to the associated lymph nodes and distant metastasis. Histological findings of malignancy include tumor cell necrosis and vascular invasion, absence of hyaline globes within the tumor cells, mitotic figures and cytological Table 1. Characteristics of patients with malignant pheochromocytoma of the urinary bladder in Japan Case Authors Age/ Macro- Secondary Miction- Location of tumor Preop. Surgical method Prognosis Length of follow- Source no. gender hematuria hypertension attack diag. up (months) r:Fl Katsume 49/F Dead of distant Gan no rinsho 7: 395-398 t'l + + Dome + Partial cystectomy 7 Q (1961) metastasis ~ 2 Tazaki 66/M + Dome Partial cystectomy Nihon hinyokika gakkai zassi ? (1963) 54: 561 ~ 3 Shinbo 17/F + Partial cystectomy AN ED 24 Nihon rinsho 28: 2507-2516 ~ (1970) 4 Imanaka 15/F + Posterior, lateral wall + Partial cystectomy ANED 8 Nishinihon J Urol 44: 315- '"d (1982) 320 ::r '" Namima Igaku no ayumi 142: 387-391 0 5 22/M + Trigone, lateral wall Partial cystectomy (') (1987) ::r .., 0 6 Na~ata 63/M + Total cystectomy ANED Nihon hinyokika gakkai zassi S (19 8) 79: 573 0 (') '< Mizuzeki r+ 7 29/M + Posterior wall + Partial cystectomy ANED 12 Gan no rinsho 37: 377-384 0 (1991) S I» 8 Takeda 27/M + + Vesical neck, lateral + Total cystectomy Distant metastasis 35 Nihon hin~okika gakkai zassi 0 (1991) wall 82: 826-89 ...., Makino ;-9 31/M + + Vesical neck Total cystectomy ANED 16 Acta Urol Jpn 37: 537-540 '" (1991) ~ Kawai Dead of distant Nishinihon J U rol 55: 1726- ::J. 10 47/F + + Posterior wall Partial cystectomy 6 ::l (1993) metastasis 1729 I» ~ II Katabami 28/F + Trigone, vesical neck + Total cystectomy Dead of distant Nihon naika gakkai zassi 83 : 0-(1994) metastasis 110-112 Pi" Hiromoto Nishinihon J U rol 60: 772- 0-12 63/M + Lateral wall Total cystectomy Distant metastasis 120 0-(1998) 775 '" .., 13 Present case 54/F Posterior wall Partial cystectomy ANED 12 ANED: alive with no evidence of disease. 294 Acta Urol. Jpn. Vol. 51, No.4, 2005 anomalies3) Immunohistochemical markers of cell proliferation have been used to evaluate tumor cell populations. Our case did not demonstrate any clinical data that suggested malignancy. The MIB-I labeling index may be a reliable indicator of malignant behavior. The most commonly studied proliferative marker is Ki-67. MIB-l, a monoclonal antibody to Ki-67, used in formalin-fixed, paraffin embedded sections, recognizes a nuclear antigen present in all phases of the cell cycle except G04) Recently, several studies on prognostic markers of pheochromocytoma and paraganglioma suggested that MIB-Ilabeling index was useful for evaluation of malignant potentiaI5,6) Van-der-Harst et al. re-ported that in their 110 cases, 50% of which were malignant, none of the benign pheochromocytomas exhibited MIB-I indices >2.5%. In half of the metastatic pheochromocytomas, MIB-l indices were >5%5) In other words, MIB-I expression, when present, was indicative of malignant behavior4) We diagnosed the present case as malignant based on the existence of muscular invasion and MIB-I expression. Similar histologic findings have been obtained in other cases ofmalignancy7) The expression ofMIB-I was relatively high (7%) compared with other cases of malignancy4--6) Histologic criteria in malignant pheochromocytoma of the bladder has not been proposed. However, we thought that cases with distant metastasis were clinically malignant and this case was histologically malignant. In adults, pheochromocytomas are extraadrenal in 15% and multicentric in 15-24% of cases8) Das et al. reviewed 100 cases of bladder pheochromocytoma reported up to 19839) Of these, pheochromocytoma was nonfunctional in 17% and malignant in about 15% of the cases. The characteristic clinical_symp-toms included hypertension in 65%, macroscQpic hematuria in 58% and micturitional attack in 46% of the cases. Resection of an unsuspected pheochro-mocytoma sometimes produced a sudden rise in blood pressure, as occurred in our case. The most common sites of occurrence are the apex and lateral wall. The tumors are mostly solitary. As they arise in the submucosal muscle layer, it is difficult to obtain complete resection with TUR. The MRI of bladder pheochromocytomas shows an intramural tumor with intermediate signal intensity on TI-weighted images and high signal intensity on T2-weighted images, but this is nonspecific and overlaps with the findings of other intramural bladder tumors lO) In our case, MRI showed an almost characteristic appearance. Our patient with pheo-chromocytoma of the urinary bladder had no history of hypertension and no characteristic symptoms related to micturition. Thus, pheochromocytoma was not suspected until a serious hypertensive crisis occurred during the TUR procedure. Pheochro-mocytoma should be suspected in cases of intramural bladder tumor. We do not recommend TUR alone for treatment of pheochromocytoma of the urinary bladder, because of the possibility of serious hypertensive crisis and the difficulty of complete resection with TUR alone. The treatment of pheochromocytoma of the bladder is surgical excision. Open surgery permits complete resection and a more thorough examination of the surrounding structures and regional lymph nodes. Most of the reported cases were removed by partial cystectomy. Total cystectomy with lymph node dissection is performed when the lesion is clearly malignant. In a review of 100 cases of pheochro-mocytoma of the urinary bladder, Das et al. also recommended pelvic lymph node dissection in all cases of bladder pheochromocytoma to exclude metastatic disease. While most cases were treated with partial cystectomy, 7 were treated with radical cystectomy because of confirmed metastatic lympho-adenopathy, and 7 with TUR9) Fifteen patients were reported to have malignant pheochromocytoma. The pathological evidence of malignancy remains unconfirmed. Only a few more than 20 malignant cases excluding those in Japan have been previously reported ll ) We calculated the number of Japanese cases of malignant pheochromocytoma of the urinary bladder. Since Katsume et al. described the first case of malignant pheochromocytoma in Japan, the patient described in the present report is, we believe, the 13th malignant case in Japan (Table I). This disease occurs over a wide range of ages extending from 15 to 66 years. The characteristic clinical symptoms are secondary hypertension in 31 %, macrohematuria in 54% and miction-attack in 38% of cases. The mortality rate has not been particularly high, with 3 deaths among 13 cases. In conclusion, pheochromocytoma of the urinary bladder is rare. Long-term follow-up with moni-toring of blood pressure and signs and symptoms as well as catecholamine assays is essential since it is not possible histologically to differentiate benign and malignant pheochromocytomas9) We maintain an expectant attitude by performing catecholamine determinations monthly and imaging and scinti-graphic studies every 6 months to avoid any delay in the case of relapse REFERENCES I) Leestma JE and Price EB J r: Paraganglioma of the urinary bladder. Cancer 28: 1063-1073, 1971 2) Heiken JP, McClennan BL and Distantis DJ: Nontransitional cell tumors of the bladder. In: Radiology. Edited by Taveras JM and Ferrucci JT, pp 1-7, Lippincott, Philadelphia, 1994 3) Linnolla RI, Keiser HR, Steinberg SM, et al.: SEGAWA, et al.: Pheochromocytoma of the urinary bladder 295 Histopathology of benign versus malignant sympa-thoadrenal paragangliomas: clinicopathological study of 120 cases including unusual histologic features. Hum Pathol 21: 1168-1180, 1990 4) Brown HM, Komorowski RA, Wilson SD, et al.: Predicting metastasis of pheochromocytomas using DNA flow cytometry and immnohistochemical markers of cell proliferation. Cancer 86: 1583-1589, 1999 5) Van-der-Harst E, Bruining HA, Jaap-Bonjer H, et al.: Proliferative index In pheochromocytomas: does it predict the occurrence of metastases? J Pathol 191: 175-180, 2000 6) Nagura S, Katoh R, Kawaoi A, et al. : Immunohis-tochemical estimations of growth activity to predict biological behavior of pheochromocytomas. Mod Pathol 12: 1107-1111, 1999 7) Hiromoto Y, Fuji K, Inoue K, et al.: Malignant pheochromocytoma of the urinary bladder associ-ated with renal cell cancer: a case report. Nishinihon J Urol 60: 772-775, 1998 8) Whalen RK, Althausen AF and Daniels GH : Extra-adrenal pheochromocytoma. Urology 147: 1-10, 1992 9) Das S, Bulusa NV and Lowe P: Primary vesical pheochromocytoma. Urology 21: 20-25, 1983 10) Warshawsky R, Bow SN, Waldbaum RS, et al.: Bladder pheochromocytoma with MR correlation. J Comput Assist Tomogr 13: 714--716, 1989 11) Piedrola G, Lopez E, Rueda MD, et al.: Malignant pheochromocytoma of the bladder: current controversies. Eur Urol 31: 122-125, 1997 (Received on August 16, 2004) Accepted on December 10, 2004 296 Acta Urol. Jpn. Vol. 51， No.4， 2005 和文抄録腸脱悪性褐色細胞腫の l例瀬川直樹*長船 崇大津赤十字病院I必尿器科症例は54歳，女性.当院の検診を受け，超音波検査にて跨統に異常腹痛を指摘され，泌尿器科を受診した.時脱鏡検査で腸脱後壁に小指頭大の非乳頭状広基性腫蕩を確認し，経尿道的勝脱腫蕩切除術を施行した.切除開始時，収縮期血圧が 240mmHgまで急激に上昇し，切除続行は閤難と判断し手術を中止した.術後，血清ノルアドレナリン濃度の上昇がみられた.*現静岡済生会総合病院泌尿器科病理組織学的診断は悪性褐色細胞腫であった.術前，血圧は安定しており褐色細胞腫を疑わせる症状はなかった.2003年 l月30日，跨脱部分切除術および骨盤内リンパ節郭清術を施行した.術後 l年を経過し，再発の徴候はない.(泌尿器科紀要 51・291-296，2005) 

膀胱悪性褐色細胞腫の1例

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膀胱悪性褐色細胞腫の1例

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