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Journal of Clinical Oncology, Vol 25, No 18 (June 20), 2007: pp. 2621-2623 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.11.5600
Paraneoplastic Polyarthritis From Non–Small-Cell Lung Cancer Metastatic to the BladderBrady Urological Institute, Johns Hopkins Hospital, Baltimore, MD
Hematology and Oncology P.C., Fairfax Northern Virginia, Alexandria, VA
Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD A 52-year-old white man presented with a 1-month history of glands penis pain and tenderness to palpitation, as well as microscopic hematuria, dysuria, and urgency. In addition, he had a 3-month history of pain and weakness in the shoulders and elbows. Past medical history was unremarkable and social history was positive for 30 pack-years of smoking. Six months prior, the patient presented to his medical oncologist with 4 months of gradually worsening pain involving the ankles, knees, hands, elbows, and shoulders. Around the same time he developed shortness of breath and wheezing. Chest x-ray showed a right upper lobe mass. This was confirmed with subsequent axial fused fluorodeoxyglucose positron emission tomography computed tomography (FDG-PET/CT) imaging of the chest, abdomen, and pelvis that demonstrated a single focus of increased FDG uptake in the lung. Right upper lobectomy with mediastinal lymphadenectomy was performed; and 1 day after surgery, the patient reported complete resolution of the pain. Histology of the tumor demonstrated poorly differentiated non–small-cell adenocarcinoma of the lung with no evidence of tumor in the hilar or mediastinal lymph nodes (T2N0Mx). Six months after resection of his primary lung non–small-cell adenocarcinoma, the patient was referred to a urologist because of microscopic hematuria and penile pain. There was also pain and weakness in the shoulders and elbows reminiscent of his presentation before lung surgery. There was no flank pain, gross hematuria, fever, or chills, and no evidence of recurrent infections. Radiographic studies were repeated and demonstrated no evidence of progression of his lung cancer with no lymphadenopathy; however, a new bladder mass was found on CT imaging of the abdomen and pelvis (Fig 1; arrow) associated with increased uptake by FDG-PET/CT imaging. Cystoscopy confirmed presence of a mass in the dome of the bladder. Biopsy of the bladder mass showed poorly differentiated carcinoma with no associated intestinal-type metaplasia or cystitis glandularis. Random biopsies were negative for tumor. The patient underwent partial cystectomy. The tumor from the patient's previous lung resection specimen was concurrently reviewed and was found to be morphologically similar to the bladder mass (Figs 2A and 2B). Immunohistochemical stains showed that the neoplasm was positive for cytokeratin-7 (Fig 2C) and TTF-1 (Fig 2D), and negative for cytokeratin 20 (Fig 2E) and thrombomodulin (Fig 2F), consistent with immunostaining patterns of non–small-cell adenocarcinoma of the lung suggesting that this tumor was nonurothelial in nature. Overall, the immunohistochemical profile as well as the tumor morphology was most consistent with a metastasis from the patient's primary lung carcinoma. One day after surgery, patient again reported complete resolution of both musculoskeletal and penile pain.
Secondary neoplasms of the genitourinary tract are rare.1,2 The kidney is the most likely genitourinary site for secondary tumor, followed by the bladder.2 It is estimated that approximately 3% to 33% of bladder tumors are secondary in nature, with larger numbers coming from autopsy studies and smaller numbers coming from studies of surgical specimens.1,2 While most secondary neoplasm's represent direct invasion of tumors from adjacent sites (eg, cervix, prostate, colon and rectum), the most common primary sites of secondary metastases to the bladder include gastric carcinoma,3-5 breast carcinoma,6 malignant melanoma,7 and lung carcinoma.1,2 Other primary sites metastatic to the bladder reported in the literature include the cecum,8,9 pancreas,10 and thyroid.11 Interestingly, the incidence of secondary tumors of the bladder is estimated to be approximately the same as that of nontransitional cell primary tumors, including adenocarcinomas, squamous cell carcinomas, small cell carcinoma, and other rarer entities.1 Primary adenocarcinomas of the bladder are somewhat less common than secondary ones.1,2 Thus, the distinction between primary and secondary adenocarcinomas is a common diagnostic problem. In general, histomorphology remains the best diagnostic test to assess the origin and prognosis of a bladder tumor. Histological evidence of concomitant intestinal-type metaplasia or cystitis glandularis is suggestive of primary adenocarcinoma. Immunohistochemistry can also be helpful when the primary lesion is known. Herein we report a case of secondary adenocarcinoma to the bladder presenting with an array of signs and symptoms which included a paraneoplastic syndrome consistent with initial presentation of the patient's known history of lung cancer. To our knowledge, this is the first report of a secondary bladder cancer presenting as a paraneoplastic syndrome. Paraneoplastic syndromes are a constellation of signs and symptoms that are unrelated to the local effect of the primary tumor or its metastases. Unusual presentation, lack of response to treatment, and parallel course with an underlying neoplasm are consistent with the diagnosis of a paraneoplastic syndrome. Diagnosis of a paraneoplastic syndrome is largely determined by clinical symptoms. A variety of musculoskeletal syndromes, including the inflammatory myopathies and polyarthritis, are known to be associated with malignancy.12-15 Certain tumor types, including cancer of the lung, are more commonly associated with paraneoplastic myopathies.12,13 Most recently, a study of dermatomyositis and polymyositis patients identified cancer in a respective 30% and 15% of patients.13 Of note, cancer developed most commonly within 1 year after the onset of myositis and the most common cancer histology reported was adenocarcinoma.13 Recent research in the field supports a model for paraneoplastic myositis pathogenesis whereby myositis-specific autoantigens, which have been found to be specifically increased in several cancer types including lung, lead to both specific T and B cells against those antigens. Subsequent muscle damage leading to elevated levels of MSAs is then thought to reactivate immune responses previously generated in the initial antitumor response. Motorsensory neuropathy, arthritis, and arthralgias to the knees as well as periarthritis to the shoulder are early signs of polyarthritis syndrome associated with paraneoplastic syndrome.14,15 Musculoskeletal symptoms may precede neoplastic manifestations by many months and may improve with appropriate treatment. As with the case described herein, marked improvement of signs and symptoms of paraneoplastic polyarthritis/myositis has been described after removal of the tumor, suggesting that it is the tumor burden that mitigates suprathreshold autoantigen burden. We describe a case of secondary adenocarcinoma to the bladder metastatic from the lung presenting with a symptoms consistent with paraneoplastic polyarthritis. Clinical history is the most important factor in correctly diagnosing secondary neoplasms of the bladder. While hematuria and/or pelvic pain are the most frequent symptoms of secondary bladder involvement, other more subtle symptoms which provide clues to the origin of the primary may be present as is described herein. Furthermore, once an association between a malignancy and a paraneoplastic syndrome has been identified, reappearance of those symptoms can be used to help monitor the patient for early signs of cancer recurrence. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
ACKNOWLEDGMENTS T.J.B. and H.A. contributed equally to this manuscript. REFERENCES 1. Bates AW, Baithun SI: Secondary neoplasms of the bladder are histological mimics of nontransitional cell primary tumours: Clinicopathological and histological features of 282 cases. Histopathology 36:32-40, 2000[CrossRef][Medline] 2. Bates AW, Baithun SI: The significance of secondary neoplasms of the urinary and male genital tract. Virchows Arch 440:640-647, 2002[CrossRef][Medline] 3. Lamontagne AE Jr, Breiter JR, Heimann WG, et al: Gastric carcinoma with bladder metastases presenting with urinary frequency. Conn Med 51:426-427, 1987[Medline] 4. Leddy FF, Peterson NE, Ning TC: Urogenital linitis plastica metastatic from stomach. Urology 39:464-467, 1992[CrossRef][Medline] 5. van Driel MF, Ypma AF, van Gelder B: Gastric carcinoma metastatic to the bladder. Br J Urol 59:193-194, 1987[Medline] 6. Ryan PD, Harisinghani M, Lerwill MF, et al: Case records of the Massachusetts General Hospital: Case 6-2006: A 71-year-old woman with urinary incontinence and a mass in the bladder. N Engl J Med 354:850-856, 2006 7. Demirkesen O, Yaycioglu O, Uygun N, et al: A case of metastatic malignant melanoma presenting with hematuria. Urol Int 64:118-120, 2000[CrossRef][Medline] 8. Grey BR, Clarke L, Maddineni SB, et al: Adenocarcinoma of the caecum metastatic to the bladder: An unusual cause of haematuria. BMC Urol 6:29, 2006[CrossRef][Medline] 9. Arai E, Ueda M, Sanada S: Hematuria: An initial sign of cecal carcinoma [Japanese]. Hinyokika Kiyo 36:347-349, 1990[Medline] 10. Chiang KS, Lamki N, Athey PA: Metastasis to the bladder from pancreatic adenocarcinoma presenting with hematuria. Urol Radiol 13:187-189, 1992[Medline] 11. Kaplan AS, van Heerden JA, McMahon MM, et al: Follicular carcinoma of the thyroid presenting with hematuria: A case report. Surgery 100:572-575, 1986[Medline] 12. Levine SM: Cancer and myositis: New insights into an old association. Curr Opin Rheumatol 18:620-624, 2006[Medline] 13. Hill CL, Zhang Y, Sigurgeirsson B, et al: Frequency of specific cancer types in dermatomyositis and polymyositis: A population-based study. Lancet 357:96-100, 2001[CrossRef][Medline] 14. Campanella N, Moraca A, Pergolini M, et al: Paraneoplastic syndromes in 68 cases of resectable non-small cell lung carcinoma: Can they help in early detection? Med Oncol 16:129-133, 1999[Medline] 15. Sheehy C, Ryan JG, Kelly M, et al: Palmar fasciitis and polyarthritis syndrome associated with non-small-cell lung carcinoma. Clin Rheumatol 2007 [Epub ahead of print]
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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