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CASE REPORT
Ahead of print publication  

Nonmetastatic renal cell carcinoma presenting with persistent cough: Case report with literature review


1 Hospital Medicine/Department of Internal Medicine, The Miriam Hospital, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA; Internal Medicine, TriHealth Cancer Institute, Good Samaritan Hospital, TriHealth, Cincinnati, Ohio, USA
2 Department of Hematology Oncology, TriHealth Cancer Institute, Good Samaritan Hospital, TriHealth, Cincinnati, Ohio, USA

Correspondence Address:
Mohd Amer Alsamman,
Division of Hospital Medicine, The Miriam Hospital, The Warren Alpert Medical School of Brown University, 164 Summit Avenue, Providence, Rhode Island
USA
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/AJM.AJM_47_19

   Abstract 

Renal cell carcinomas (RCC), constitute 80– 85% of primary renal neoplasms. The classic triad of RCC (flank pain, hematuria, and a palpable abdominal renal mass) occurs in approximately 9% of patients; it strongly suggests locally advanced disease. RCC may also be associated with a number of paraneoplastic syndromes. These are typically due to ectopic production of various hormones. We present a 69-year-old male patient previously healthy presented to the emergency department with recurrent persistent cough. A non-metastatic RCC was incidentally discovered. Eventually, he underwent left radical nephrectomy. One year has passed with no cough. This is a rare and unusual presentation of RCC that falls under the category of paraneoplastic syndrome with review of similar reported cases and summary of all paraneoplastic syndromes associated with RCC in literature.

Keywords: Cough, paraneoplastic syndrome, prostaglandins, renal cell carcinoma



How to cite this URL:
Alsamman MA, Draper D. Nonmetastatic renal cell carcinoma presenting with persistent cough: Case report with literature review. Avicenna J Med [Epub ahead of print] [cited 2019 Jul 19]. Available from: http://www.avicennajmed.com/preprintarticle.asp?id=260254




   Introduction Top


Renal cell carcinomas (RCCs), which originate within the renal cortex, constitute 80–85% of primary renal neoplasms. The classic triad of RCC (flank pain, hematuria, and a palpable abdominal renal mass) occurs in approximately 9% of patients; when present, it strongly suggests locally advanced disease. Other symptoms and signs are related to invasion of adjacent structures or distant metastases.[1]

RCC may also be associated with a number of paraneoplastic syndromes. These are typically due to ectopic production of various hormones (erythropoietin, parathyroid hormone–related protein, gonadotropins, human chorionic somatomammotropin, renin, glucagon, and insulin).[2]

Very few cases have been reported as nonmetastatic RCC presenting with persistent cough.


   Case report Top


A 69-year-old male presented to the emergency department with new onset persistent dry cough. He denied any fever, chills, rhinorrhea, and myalgias. He has no significant past medical history and takes no chronic medications. He has no known drug or environmental allergies. Vitals signs showed heart rate of 88 beats per minute, respiratory rate of 16 breaths per minute, and blood pressure of 135/85mm Hg. His physical exam was unremarkable except for mild diffuse expiratory wheezes on lung auscultation. A chest X-ray was clear. Laboratory values including a complete blood count and comprehensive metabolic panel were also normal. He was given dextromethorphan liquid and inhalational albuterol with complete resolution of symptoms, and he was discharged home with instructions to follow-up with his primary care physician. Two weeks later, his cough recurred, however, associated with left-sided chest pain. He re-presented to the emergency department. A computed tomography (CT) angiography of the chest was performed to rule out pulmonary embolism. No pulmonary pathology was found; however, he did have a 4.3-cm left renal mass most compatible with RCC [Figure 1].
Figure 1: Axial lower section of computed tomography scan of the chest with intravenous contrast showing an incidental left renal mass suggestive of renal cell carcinoma

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He was admitted to the hospital and CT of the abdomen and pelvis showed no evidence of metastasis. An magnetic resonance imaging of the abdomen showed irregular enhancing 5-cm mass on the left kidney [Figure 2] and [Figure 3] most consistent with RCC.
Figure 2: Coronal section of magnetic resonance imaging of the abdomen demonstrating irregular enhancing 5-cm mass on the left kidney most consistent with renal cell carcinoma

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,
Figure 3: Axial section of magnetic resonance imaging of the abdomen demonstrating irregular enhancing mass on the left kidney most consistent with renal cell carcinoma

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He was scheduled for laparoscopic nephrectomy. Prior to his nephrectomy, he had several exacerbations of cough with asthma-like episodes including wheezing and dyspnea. These responded well to corticosteroids. He underwent left radical nephrectomy. Surgical pathology confirmed clear cell RCC, Fuhrman nuclear grade 2. The margins of resection are free of tumor. No lymph node identified. Postoperatively his cough resolved. One year has passed and he is cough free.


   Discussion Top


This patient had very unusual presentation of nonmetastatic RCC with cough. It has been suggested that RCC secretes prostaglandins (mainly E2) that can cause cough reflex through the prostaglandin E receptor 3 pathway.[3]

There are a number of reasons why we believe the patient’s cough was directly related to his RCC. The patient never had asthma or cough previously. His symptoms coincided with his RCC. Imaging showed no metastasis to lung or extension of tumor to the diaphragm, which in some cases can cause cough through direct irritation. Symptoms were resolved after nephrectomy, which supports the theory that RCC induced cough via secretion of prostaglandins. Cough receptors are situated in the larynx and the tracheobronchial tree; C-fiber receptors may contribute. Postnasal drip, asthma, and gastroesophageal reflux disease are the underlying causes of chronic cough in almost 90% of cases.[3],[4] Angiotensin-converting enzyme inhibitors can cause cough through accumulation of bradykinin.[5]

Okubo et al.[6] reported a case where a patient had weight loss and intractable cough, and was found to have RCC that was surgically removed and cough symptoms were resolved for 7 months. The patient’s cough recurred and patient was found to have metastatic recurrence of RCC. Mastectomy was performed with complete removal of the tumor and after 18 months patient remains cough free.

Benzodiazepines has been suggested to alleviate severe cough symptoms in those patients as Estfan and Walsh[7] reported a case of intractable cough in a patient with metastatic RCC that only responded to diazepam. Fujikawa et al.[8] reported a case of a patient with RCC who developed a refractory cough, which was immediately resolved after tumor embolization. Similarly, Roberts et al.[9] reported a case of chronic cough, fever, and weight loss and incidental discovery of RCC; his symptoms were completely resolved within 24h after nephrectomy.

Unlike other reported cases, our patient did not have other signs or symptoms suggestive of malignancy or RCC, such as weight loss, fever, anemia, or hematuria that warrants further workup. He solely presented with cough prior to RCC diagnosis contrary to other cases that had a diagnosis of RCC prior to presenting with cough.

Unfortunately neither our case, nor other reported cases demonstrated an increase in the levels of serum prostaglandins or bradykinins. However, all developed persistent cough, which was refractory to usual treatment, and a diagnosis of RCC was made. Following nephrectomy a complete resolution of cough was noted.

This case report details the importance of thorough evaluation of refractory cough and physician should consider occult RCC as a possible etiology, in the absence of more common suggestive signs or symptoms such as anemia. RCC can present in various ways; some are common and some are extremely rare. All are linked to paraneoplastic etiology. We searched literature and summarized all of those presentations [Table 1][16].
Table 1: Summary of all paraneoplastic syndromes in renal cell carcinoma from available literature

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Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest. Consent was obtained from the patient.



 
   References Top

1.
Skinner DG, Colvin RB, Vermillion CD, Pfister RC, Leadbetter WF. Diagnosis and management of renal cell carcinoma. A clinical and pathologic study of 309 cases. Cancer 1971;28:1165-77.  Back to cited text no. 1
    
2.
Gold PJ, Fefer A, Thompson JA. Paraneoplastic manifestations of renal cell carcinoma. Semin Urol Oncol 1996;14:216-22.  Back to cited text no. 2
    
3.
Maher SA, Birrell MA, Belvisi MG. Prostaglandin E2 mediates cough via the EP3 receptor: implications for future disease therapy. Am J Respir Crit Care Med 2009;180:923-8.  Back to cited text no. 3
    
4.
Chung KF, Pavord ID. Prevalence, pathogenesis, and causes of chronic cough. Lancet 2008;371:1364-74.  Back to cited text no. 4
    
5.
Mukae S, Itoh S, Aoki S, Iwata T, Nishio K, Sato R, et al. Association of polymorphisms of the renin-angiotensin system and bradykinin B2 receptor with ACE-inhibitor-related cough. J Hum Hypertens 2002;16:857-63.  Back to cited text no. 5
    
6.
Okubo Y, Yonese J, Kawakami S, Yamamoto S, Komai Y, Takeshita H, et al. Obstinate cough as a sole presenting symptom of non-metastatic renal cell carcinoma. Int J Urol 2007;14:854-5.  Back to cited text no. 6
    
7.
Estfan B, Walsh D. The cough from hell: diazepam for intractable cough in a patient with renal cell carcinoma. J Pain Symptom Manage 2008;36:553-8.  Back to cited text no. 7
    
8.
Fujikawa, A, Daidoh, Y, Taoka Y, Nakamura S. Immediate improvement of a persistent cough after tumor embolization for renal cell carcinoma–a rare manifestation of paraneoplastic syndrome. Scand J Urol Nephrol 2002;36:393-5.  Back to cited text no. 8
    
9.
Roberts L, Wood G, Whitby M, Heathcote P. An unusual case of chronic cough. Aust N Z J Med 1991;21:780.  Back to cited text no. 9
    
10.
Sandhu DP, Munson KW, Harrop JS, Hopton MR, Ratcliffe WA. Humoral hypercalcaemia in renal carcinoma due to parathyroid hormone related protein. Br J Urol 1993;72:848-50.  Back to cited text no. 10
    
11.
Palapattu GS, Kristo B, Rajfer J. Paraneoplastic syndromes in urologic malignancy: the many faces of renal cell carcinoma. Rev Urol 2002;4:163-70.  Back to cited text no. 11
    
12.
Walsh PN, Kissane JM. Nonmetastatic hypernephroma with reversible hepatic dysfunction. Arch Intern Med 1968;122:214-22.  Back to cited text no. 12
    
13.
Pras, M, Franklin EC, Shibolet S, Frangione B. Amyloidosis associated with renal cell carcinoma of the AA type. Am J Med 1982;73:426-8.  Back to cited text no. 13
    
14.
O’keefe SC, Marshall FF, Issa MM, Harmon MP, Petros JA. Thrombocytosis is Associated with a significant increase in the cancer specific death rate after radical nephrectomy. J Urol 2002;168:1378-80.  Back to cited text no. 14
    
15.
Sidhom OA, Basalaev M, Sigal LH. Renal cell carcinoma presenting as polymyalgia rheumatica. Resolution after nephrectomy. Arch Intern Med 1993;153:2043-5.  Back to cited text no. 15
    
16.
Turk HM, Ozet A, Kuzhan O, Komurcu F, Arpaci F, Ozturk B, et al. Paraneoplastic motor neuron disease resembling amyotrophic lateral sclerosis in a patient with renal cell carcinoma. Med Princ Pract 2009;18:73-5.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]



 

 
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