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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT  
Year : 2011  |  Volume : 22  |  Issue : 6  |  Page : 1211-1214
Renal cell carcinoma associated with granulomatous reaction


1 Department of General Pathology, Christian Medical College, Vellore, Tamil Nadu State, India
2 Department of Urology, Christian Medical College, Vellore, Tamil Nadu State, India

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Date of Web Publication8-Nov-2011
 

   Abstract 

Granulomatous inflammation is a distinctive pattern of chronic inflammatory reaction characterized by accumulation of epithelioid histiocytes and multinucleate giant cells. The cause of granulomas can be infectious or non-infectious. Granulomas have been described within the stroma of malignancies like carcinomas of the breast and colon, seminoma and Hodgkin's lymphoma, where they represent T-cell-mediated reaction of the tumor stroma to antigens expressed by the tumor. Granulomatous reaction in association with renal cell carcinoma (RCC) is uncommon, with only few published reports in the literature. We describe three cases of conventional (clear cell) RCC associated with epithelioid granulomas within the tumor parenchyma.

How to cite this article:
Narasimhaiah DA, Manipadam MT, Aswathaman K, Krishnamoorthy S. Renal cell carcinoma associated with granulomatous reaction. Saudi J Kidney Dis Transpl 2011;22:1211-4

How to cite this URL:
Narasimhaiah DA, Manipadam MT, Aswathaman K, Krishnamoorthy S. Renal cell carcinoma associated with granulomatous reaction. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2019 Nov 22];22:1211-4. Available from: http://www.sjkdt.org/text.asp?2011/22/6/1211/87236

   Introduction Top


Granulomatous inflammation is a distinctive pattern of chronic inflammatory reaction characterized by focal accumulation of activated macrophages that often develop an epithelioid appearance. Granulomas may develop in a number of immunologically mediated infectious and non-infectious conditions. [1] Granulomas may also occur within malignancies like carcinomas of the breast, kidney, colon and Hodgkin's lymphoma. [2],[3],[4] Granulomatous reaction in association with renal cell carcinoma (RCC) is uncommon, with only few published reports in the literature. We describe three cases of conventional (clear cell) RCC associated with epithelioid granulomas within the tumor parenchyma. Also, in regions with a high incidence of tuberculosis, it is difficult to differentiate tumor-related granulomatous reactions from that that are due to concomitant tuberculosis. This difficulty could have implications on the modalities of treatment that can be offered to the patient.


   Case Report Top


All three patients were male, with the age ranging from 44 to 65 years. Two of the patients presented with gross, painless hematuria of 15 days to one month duration, whereas in one patient the tumor was discovered incidentally. None of the patients had associated co-morbidities. The erythrocyte sedimentation rate in one of the patients was 80 mm/hour; all other hematological and biochemical parameters were normal in all the patients. Serology for human immunodeficiency virus (HIV), hepatitis B surface antigen and antibody for hepatitis C virus (HCV Ab) were negative. None of the patients had past or present history suggestive of tuberculosis or any history of contact with tuberculosis. The computed tomography (CT) scan of the abdomen revealed a tumor in the right kidney in all three patients with normal left kidney and absence of intra-abdominal lymphadenopathy. The chest X-rays were normal in all patients. The patients underwent right radical nephrectomy.

Pathology

On gross examination, the tumors ranged in size from 3 cm × 2.5 cm to 7 cm × 5.5 cm × 5 cm, with yellow, soft and variegated cut surfaces. The adjacent renal parenchyma was grossly normal. The histopathology showed conventional (clear cell) RCC, with the Fuhrman's nuclear grade ranging from I to III. There were foci of intra-tumoral necrosis in one case. The adjacent renal parenchyma showed focal interstitial chronic inflammation in two of the cases and chronic pyelonephritis in one case.

An uncommon feature observed in all three tumors was the presence of epithelioid granulomas within the tumor parenchyma. The granulomas were well formed, discrete, as well as confluent with associated multinucleate giant cells of both Langhans' and foreign body type [Figure 1], with the granulomas measuring 200 microns to 1200 microns in diameter. The granulomata were within the viable tumoral parenchyma as well as in the fibrous septa intercepting the tumor. Only one case showed foci of coagulative necrosis within some granulomas [Figure 2]. The special stains for acid fast bacilli (Ziehl-Nielsen) and fungi (Gomori's methenamine silver and Periodic acid Schiff with diastase) did not reveal any microorganisms. There were no Schaumann or asteroid bodies. Mycobacterial cultures and polymerase chain reaction (PCR) for Mycobacterium tuberculosis could not be performed.

The granulomas were confined to the tumor, except in one case where one small granuloma was present in the perinephric adipose tissue. In view of the absence of granulomas in the non-tumorous renal parenchyma, lack of clinical features suggestive of tuberculosis and normal chest X-ray, these granulomas were considered to be tumor related and the patients were not treated with anti-tuberculous drugs.
Figure 1: Scattered epithelioid granulomas within the parenchyma of clear cell renal cell carcinoma (Hematoxylin and Eosin, 50×).

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Figure 2: Intra-tumoral epithelioid granuloma with a central focus of necrosis (Hematoxylin and Eosin, 200×).

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   Discussion Top


There are few published reports of association of RCC with granulomatous reaction in the literature. [4],[5],[6],[7],[8] The types of RCC associated with granulomas are variable. In the present report, all RCCs were of the conventional (clear cell) type, which is similar to that described in other reports. [5],[6],[7] The RCC had sarcomatoid features in the report by Piscioli et al, [4] and was of papillary type in the case described by Marinides et al. [8] The Fuhrman's nuclear grade ranged from I to III in our cases, whereas all tumors were grade I in the report by Hes et al. [5] All the granulomas were of the epithelioid type. The location of granulomas is variable, with granulomas being described within the tumor parenchyma, tumoral stroma as well as at the periphery of the tumor. [4],[5],[6],[7] In our study, the granulomas were present within the tumoral parenchyma as well as in the fibrous septa intercepting the tumor, except in one case that showed a small granuloma in the perinephric adipose tissue away from the tumor. The other reports describe granulomas confined to the tumor, except the study by Hes et al, where one case showed granulomas within the normal kidney in the vicinity of the tumor. [4],[5],[6],[7] In the previously published reports, the granulomas were non-necrotizing. [4],[5],[6],[7] These granulomas have been described as "sarcoid like reaction"/"sarcoid like granulomas." [4],[6],[7] Hes et al, describe RCC with non-caseating granulomas. [5] There is also a case report of renal sarcoidosis coexisting with hypernephroma. [9] In comparison, in our study, the granulomas were necrotizing in one of the cases, but no acid fast bacilli or fungal microorganisms were detected on performing the special stains. In view of lack of clinical features to suggest tuberculosis as well as normal chest radiographs, none of our patients were treated with anti-tuberculous therapy. However, it was not possible to completely exclude tuberculosis as mycobacterial culture and PCR were not performed. In a study from Pakistan, the PCR for Mycobacterium tuberculosis (MTB-PCR) was positive in the axillary lymph nodes, showing metastatic tumor in association with granulomatous reaction in cases of invasive carcinoma of breast. [10] MTB-PCR detects the presence or absence of Mycobacterium DNA, without a clue as to whether the disease is active or dormant (only showing a healed focus). [10] Hence, clinical correlation is required and it is not sufficient if the MTB-PCR is positive. In a country like India, with a high prevalence of tuberculosis, a positive PCR may not necessarily indicate an active infection.

Tumor-associated granulomas represent an immune response of the tumor stroma to antigens expressed by the tumor, and manifests as a local T-cell-mediated reaction. [5],[6],[7],[10] The possibilities to be considered in any tumor associated with granulomatous reaction are: (a) the granulomas are a reaction to tumor-related antigens and (b) there is co-existence of chronic granulomatous process like tuberculosis/sarcoidosis and tumor.

In conclusion, we report three cases of RCC associated with necrotizing and non-necrotizing granulomas. Based on the morphological features of granulomas, it is not possible to entirely exclude concomitant tuberculosis, especially in a country like India with a high incidence of tuberculosis. However, the lack of granulomas in the adjoining parenchyma along with the absence of supportive clinical and radiological features tipped the balance in favor of tumorrelated granulomatous reaction. Nevertheless, this is a difficult, but important, distinction to be made with major therapeutic implications.

 
   References Top

1.Kumar V, Abbas AK, Fausto N. Acute and Chronic inflammation. In: Pathologic Basis of Disease. Saunders, seventh edition, 2006;47-86.  Back to cited text no. 1
    
2.Coyne JD. Colonic carcinoma with granulomatous (sarcoid) reaction. J Clin Pathol 2002;55: 708-9.  Back to cited text no. 2
    
3.Santini D, Pasquinelli G, Alberghini M, Martinelli GN, Taffurelli M. Invasive breast carcinoma with granulomatous response and deposition of unusual amyloid. J Clin Pathol 1992; 45:885-8.  Back to cited text no. 3
    
4.Piscioli I, Donato S, Morelli L, Del Nonno F, Licci S. Renal cell carcinoma with sarcomatoid features and peritumoral sarcoid-like granulomatous reaction: Report of a case and review of the literature. Int J Surg Pathol 2008;16(3):345-8.  Back to cited text no. 4
    
5.Hes O, Hora M, Vanecek T, et al. Conventional renal cell carcinoma with granulomatous reaction: a report of three cases. Virchows Arch 2003;443:220-1.  Back to cited text no. 5
    
6.Campbell F, Douglas-Jones AG. Sarcoid-like granulomas in primary renal cell carcinoma. Sarcoidosis 1993;10:128-31.  Back to cited text no. 6
    
7.Kovacs J, Varga A, Bessenyei M, Gomba S. Renal cell cancer associated with sarcoid-like reaction. Pathol Oncol Res 2004;10:169-71.  Back to cited text no. 7
    
8.Marinides GN, Hajdu I, Gans RO. A unique association of renal cell carcinoma with sarcoid reaction in the kidney. Nephron 1994;67:477-80.  Back to cited text no. 8
    
9.Bottone AC, Labarbera M, Asadourian A, Barman A, Richie C. Renal sarcoidosis coexisting with hypernephroma. Urology 1993;41:157-9.  Back to cited text no. 9
    
10.Khurram M, Tariq M, Shahid P. Breast cancer with associated granulomatous axillary lymphadenitis: A diagnostic and clinical dilemma in regions with high prevalence of tuberculosis. Pathol Res Pract 2007;203:699-704.  Back to cited text no. 10
    

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Correspondence Address:
Marie T Manipadam
Department of General Pathology, Christian Medical College, Vellore 632002, Tamil Nadu State
India
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PMID: 22089785

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