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CORRESPONDENCE
Year : 2013  |  Volume : 9  |  Issue : 1  |  Page : 105-107

A review of histopathological and immunohistochemical parameters in diagnosis of metastatic renal cell carcinoma with a case of gingival metastasis


Department of Oral and Maxillofacial Pathology, I.T.S.-Center for Dental Studies and Research Muradnagar, Ghaziabad, Uttar Pradesh, India

Date of Web Publication10-Apr-2013

Correspondence Address:
Seema Sikka
Department of Oral and Maxillofacial Pathology, I.T.S.- C.D.S.R., Muradnagar, Ghaziabad, Uttar Pradesh
India
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DOI: 10.4103/0973-1482.110395

PMID: 23575086

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 > Abstract 

The oral cavity constitutes a site of low prevalence for metastasis of malignant tumors. However, oral metastasis of a renal origin is relatively more common and represents 2% of all cancer deaths. Renal cancer may metastasize to any part of the body, with a 15% risk of metastasis to the head and neck regions, and pose one of the greatest diagnostic challenges in medical sciences. Approximately 25% of patients have a metastatic disease at initial assessment, which is often responsible for initiating the diagnosis in the first place. Here we present a review of literature of renal cell carcinoma along with a case of gingival metastasis.

Keywords: Diagnosis, gingival metastasis, renal cell carcinoma


How to cite this article:
Sikka S, Sikka P, Kaur G, Shetty DC. A review of histopathological and immunohistochemical parameters in diagnosis of metastatic renal cell carcinoma with a case of gingival metastasis . J Can Res Ther 2013;9:105-7

How to cite this URL:
Sikka S, Sikka P, Kaur G, Shetty DC. A review of histopathological and immunohistochemical parameters in diagnosis of metastatic renal cell carcinoma with a case of gingival metastasis . J Can Res Ther [serial online] 2013 [cited 2014 Oct 2];9:105-7. Available from: http://www.cancerjournal.net/text.asp?2013/9/1/105/110395


 > Introduction Top


Metastatic lesions of the oral cavity are extremely rare, and account for approximately 1% of all malignant oral tumors. [1] Renal cell carcinoma (RCC) is the third most common infraclavicular neoplasm that metastasizes to the oral cavity, following of thelung and breast carcinoma. [2] It accounts for nearly 3% of all adult malignancies. [1] RCC typically affects men in the age group of 30 to 60 years, and may metastasize to any part of the body, with a 15% risk of metastasis to the head and neck region when the disease is disseminated, and a 1% risk when it is not. [3] RCC represents 2% of all cancer deaths, and metastasis is usually seen at the time of the initial presentation. [3] The diagnosis of these metastasis constitutes a challenge, especially when there is no history of renal alterations, and histopathologically can be confused with other carcinomas. [3]


 > Case Report Top


A 73 year old male patient presented with multiple painless swellings in the lower gingival region since 7 days, before which the patient's gingivae were apparently normal. There was a history of fever, cough and weight loss since one month.On intraoral examination, three gingival swellings which were reddish brown in color and soft in consistency were seen in the 35-36, 37-38 and 44-46 regions. The sizes of the swellings were 3 × 2.5 cm, 2 × 1 cm and 1 × 1 cm in diameter, respectively [Figure 1], [Figure 2] and [Figure 3]. Histopathology revealed a highly vascular tumor with a trabecular growth pattern. Tumor cells were present in ill-defined nests separated by thin strands of fibrous tissue ([Figure 4]; H/E, 10×). The tumor was highly vascular and the tumor cells showed oval and centrally placed nuclei, with prominent nucleoli. Moderately abundant cytoplasm was present, which was either clear or eosinophilic on staining ([Figure 5]; H/E, 40×). Based on these findings a diagnosis of RCC was suspected. A computed tomography (CT) -scan of the abdomen was carried out, which showed a neoplastic mass in the left kidney [Figure 6], thus confirming the diagnosis of RCC.
Figure 1: Intraoral swelling in the35 region in the patient in the study which is reddish brown in color and 3 × 2.5 cm in diameter

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Figure 2: Intraoral gingival swellings in 37-38 region in the patient in the study which is reddish brown in color and 2 × 1 cm in diameter

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Figure 3: Intraoral gingival swellings in 44-46 region in the patient in the study which is reddish brown in color and 1 × 1 cm in diameter

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Figure 4: Low power (H and E, 10×) photomicrograph of the histopathological section revealing a trabecular growth pattern, with the tumor cells present in ill-defined nests, and separated by thin strands of fibrous tissue

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Figure 5: High power (H and E, 40×) photomicrograph of the histopathological section revealing tumor cells oval and centrally placed nuclei, with prominent nucleoliand moderately abundant cytoplasm was present, either clear or eosinophilic

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Figure 6: Computerized Tomography (CT) scan of abdomen was carried out which showed a neoplastic mass in the left kidney

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 > Discussion Top


RCC poses one of the greatest diagnostic challenges in medicine. Approximately 25% of the patients have metastatic disease at initial assessment, and such involvement may actually initiate the diagnosis, like in our case. [4] RCC is a malignant pathology of a difficult, and many times tardy diagnosis. [3] It is a tumor of low prevalence. [3],[5] It shows a male preponderance, with a male to female ratio of 2:1. Cases have been observed in all age groups, with a predilection for the 5 th and 7 th decade. [5],[6] The classic triad of flank pain, hematuria and palpable mass is seen in about 10% of patients. [7] However, no such symptoms were experienced by our patient.Hematogenous dissemination is by far the most important mechanism of metastasis. [8] About 75% of patients with metastatic renal carcinoma have metastases to the lung, 36% to the soft tissues, 20% to bone, 18% to liver, 8% to cutaneous sites and 8% to the central nervous system. Approximately 15% of RCCs metastasize to the head and neck region. [9] Within the malignant pathologies, RCC provoques the most oral metastasis. [5]

Reports of RCC in the head and neck region involve those in the nose, tongue, paranasal sinuses, larynx, mandible, temporal bone, thyroid gland, and parotid glands. The location of metastasis usually dictates the presenting symptoms. [1] In the oral cavity, the majority of metastases occur to the bones, especially involving the jaw. Only in 33% of the cases are they seated in soft tissues (mainly the gingiva and tongue), and this is usually associated with a bad prognosis. In our case, the gingivae were exclusively involved. The differential diagnosis includes giant cell granuloma, hemangioma and fibroma. [2],[8] The clear cell variants of various tumors represent a metabolic state that the facilitates accumulation of intracytoplasmic macromolecules (lipids and carbohydrates), which are lost to varying degrees during the processing steps for staining the tissue section for microscopic analysis. [4] Gingival inflammation plays an important role in attracting metastatic cells to the gingiva. In these cases, metastasis to the lungs is usually already present, although it is described as metastasis directly to the oral cavity through the vertebral venous plexus. [4]

Histologically differentiating among clear cell tumors with conventional light microscopy can be challenging. It can be especially difficult to distinguish between RCC metastasis and clear cell malignancies of the salivary glands, such as, acinic cell neoplasm, clear cell oncocytoma, mucoepidermoid carcinoma, primary clear-cell carcinoma and epithelial-myoepithelial carcinoma. [10] Immunohistochemical staining helps in this distinction, with RCC metastasis exhibiting focal cytokeratin positivity (versus minor salivary gland cancers showing diffuse positivity) and a strong reaction for vimentin. [1] Metastatic tumours with clear cell variants include myoepithelial and glycogen rich clear cell carcinomas of the breast, melanoma, clear cell sarcomas, hemangioblastoma, primary glial and meningeal tumours of brain. Myoepithelial carcinomas stain not only for cytokeratin, but also for S-100 protein and muscle specific actin, an indication of their myoepithelial nature. Melanomas stain positively for S-100 protein and Human Melanoma Black 45 (HMB45) and show more cytological atypia. Rare lesions like clear cell sarcomas are diagnosed on the basis of their clinical features. In case of hemangioblastomas, there is predominance of lipid over glycogen for clear cells. Moreover, they stain negatively for cytokeratin and epithelial membrane antigen. Gliomas are differentiated from metastatic RCC on the basis of reaction to Glial fibrillary acidic protein (GFAP) and S-100 protein. Meningiomas contain a whorled growth pattern of cells absent in metastatic RCC. [4]

Treatment of renal adenocarcinoma metastasis to the head and neck is directed mainly towards palliation. Excision has been performed primarily to control pain and prevent bleeding and infection. Surgical debulking followed by chemotherapy/ radiotherapy or administration of interferon-alpha and interleukin-II have been tried with some reduced morbidity. Finally, newer agents targeting the Vascular endothelial growth factor (VEGF) pathway such as bevacizumab and sorafenib may provide hope for patients with metastatic RCC. Early trials have shown a prolongation of progression-free survival with the use of these targeted molecular therapies in cytokine-refractory patients. [1] The evolution of the patients is poor, with a mortality rate over 90% over5 years of the disease duration. [5]


 > Conclusion Top


conclude, the presentation of RCC as a metastasis can be a diagnostic challenge. The clue to the diagnosis lies in the clinical presentation, such as, thenumber of lesions andduration of spread, and also the histopathological and immunohistochemical features, coupled with special radiological investigations.

 
 > References Top

1.Will TA, Agarwal N, Petruzzelli GJ. Oral cavity metastasis of renal cell carcinoma: A case report. J Med Case Rep 2008;2:313.  Back to cited text no. 1
    
2.Aguirre A, Rinaggio J, Diaz-Ordaz E. Lingual metastasis of renal cellcarcinoma. J Oral Maxillofac Surg 1996;54:344-6.  Back to cited text no. 2
    
3.Maestre-Rodríguez O, González-García R, Mateo-Arias J, Moreno-García C, Serrano-Gil H, Villanueva-Alcojol L, et al. Metastasis of renal clear-cell carcinoma to the oral mucosa, an atypical location.Med Oral Patol Oral Cir Bucal 2009;14:e601-4.  Back to cited text no. 3
    
4.Wahner-Roedler DL, Sebo TJ. Renal cell carcinoma: diagnosis based on metastatic manifestations. Mayo Clin Proc 1997;72:935-41.  Back to cited text no. 4
    
5.Narea-Matamala G, Fernández-Toro Mde L, Villalabeitía-Ugarte E, Landaeta-Mendoza M, Rojas-Alcayaga G. Oral metastasis of renal cell carcinoma, presentation of a case. Med Oral Pathol Oral Cir Bucal 2008;13:E742-4.  Back to cited text no. 5
    
6.Vallalta Morales M, Todolí Parra J, Cervera Miguel JI, Calabuig Alborch JR. Right hemiparesia as presentation of renal cell carcinoma. Ann Med Interna 2004;21:359-60.  Back to cited text no. 6
    
7.Simons J M, Marshall FF. Clinical oncology. Philadelphia: Churchill Livingstone; 1995. p. 1407.  Back to cited text no. 7
    
8.Ellis GL, Jensen JL, Reingold IM, Barr RJ. Malignant neoplasms metastatic to gingivae. Oral Surg Oral Med Oral Pathol 1977;44:238-45.  Back to cited text no. 8
    
9.Azam F, Abubakerr M, Gollins S. Tongue metastasis as an initial presentation of renal cell carcinoma: A case report and literature review. J Med Case Rep 2008;2:249.   Back to cited text no. 9
    
10.Layfield LJ, Glasgow BJ. Aspiration cytology of clear-cell lesions of the parotid gland: morphologic features and differential diagnosis. DiagnCytopathol 1993;9:705-11.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]



 

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