Sinonasal region is an exceptional site for metastatic tumors. Renal cell carcinoma is known to metastasise to the most unusual sites, the sinonasal region being one of them. Clear cell carcinoma is its most common histologic variant. A sixty year old male presented with epistaxis and nasal obstruction. Clinical examination and CT scan revealed a vascular tumor in the right nasal cavity and maxillary sinus. The tumor was resected and sent for histopathological examination. A diagnosis of metastatic clear cell renal cell carcinoma was made and confirmed with immunohistochemistry (IHC). The pathologic diagnosis was made without prior knowledge of the primary tumor in the kidney. Very few cases of metastatic renal cell carcinoma in the sinonasal region have been reported in literature. We present this case to document its occurrence, highlight the rarity and briefly discuss the differential diagnoses of clear cell carcinoma in the sinonasal area, based on morphology and IHC

Mahantachar, V

Raj, JA

Rajaram, T

Cognitive Sciences ePrint Archive

1 
 
  
 
 
Case Report: 
Metastatic Renal Cell Carcinoma in the Sinonasal Region 
Authors 
Jyothi A Raj, Associate Professor of Pathology, 
V Mahantachar, Professor of Pathology, 
T Rajaram, Professor and Head of Department of Pathology, 
Rajarajeswari Medical College and Hospital, Mysore Road, Bangalore - 560074, India. 
Address for Correspondence 
Dr Jyothi A Raj, 
159, 43rd Cross, 2nd main, 
8th block, Jayanagar, 
Bangalore- 560082, 
India.  
E-mail: jyoki255@yahoo.co.in 
Citation 
Raj JA, Mahantachar V, Rajaram T. Metastatic Renal Cell Carcinoma in the Sinonasal Region. Online J Health Allied 
Scs. 2013;12(2):19. Available at URL: http://www.ojhas.org/issue46/2013-2-19.html 
Open Access Archives 
http://cogprints.org/view/subjects/OJHAS.html 
http://openmed.nic.in/view/subjects/ojhas.html 
Submitted: Jan 2, 2013; Accepted: Apr 1, 2013; Published: Aug 15, 2013
Abstract: Sinonasal region is an exceptional site for 
metastatic tumors. Renal cell carcinoma is known to 
metastasise to the most unusual sites, the sinonasal region 
being one of them. Clear cell carcinoma is its most common 
histologic variant. A sixty year old male presented with 
epistaxis and nasal obstruction. Clinical examination and CT 
scan revealed a vascular tumor in the right nasal cavity and 
maxillary sinus. The tumor was resected and sent for 
histopathological examination. A diagnosis of metastatic 
clear cell renal cell carcinoma was made and confirmed with 
immunohistochemistry (IHC). The pathologic diagnosis was 
made without prior knowledge of the primary tumor in the 
kidney. Very few cases of metastatic renal cell carcinoma in 
the sinonasal region have been reported in literature. We 
present this case to document its occurrence, highlight the 
rarity and briefly discuss the differential diagnoses of clear 
cell carcinoma in the sinonasal area, based on morphology 
and IHC.  
Key Words: Sinonasal region; Metastatic renal cell 
carcinoma; Diagnosis 
 
Introduction 
Renal cell carcinoma (RCC) is an aggressive tumor, 
representing approximately 3% of all malignant tumors.(1) 
Metastasis is common, seen in 20-50% of patients, at 
diagnosis or post-nephrectomy. Common sites include lungs, 
liver, bone, brain, and adrenals, although no site is excluded. 
RCC along with malignant melanoma and choriocarcinoma, 
are notorious for metastasising to the most unusual sites such 
as the larynx, parotid, thyroid, heart and pituitary.(2) 
Sinonasal region is an exceptional site, with very few cases 
reported in literature.(1,3) 
Clear cell carcinoma is a rare morphologic pattern with an 
incidence of 9.6 per 100,000. Kidneys constitute the 
commonest primary site of clear cell carcinoma (85%).(1) It 
is rarely seen at other sites. Although primary carcinoma of 
the clear cell type is known to arise in the sinonasal area, 
metastatic RCC should be considered in the differential 
diagnosis of such tumors. Diagnosis of metastatic RCC is 
important as targeted therapies are now an important 
treatment modality. 
Case Report 
A sixty year old male presented with recurrent bleeding from 
the right nostril and history of nasal obstruction. Local 
examination revealed a mass occupying the entire right nasal 
cavity. The left nasal cavity was patent. CT scan reported a 
heterogeneously enhancing mass, occupying the right nasal 
cavity and maxillary sinus, and extending into the 
nasopharynx. There was no obvious bone erosion. A vascular 
tumor was suspected clinically. Due to persistent epistaxis, 
exploration and sphenopalatine artery ligation was done. Two 
biopsies were taken, both of which were inconclusive. 
Subsequently, the mass was excised and sent for 
histopathological examination. 
Gross Findngs: Multiple fragmented grey white tissue bits 
were received, largest measuring 3.0x2.0x1.0cm, and the 
smallest measuring 2.0x1.0x1.0cm. The external surface was 
mucoid, with foci of ulceration. Cut surface was grey white 
with areas of hemorrhage. Chips of bone were also received, 
which were grossly unremarkable. 
The representative tissue was processed and the paraffin 
sections were stained with H&E. 
Microscopy: Benign respiratory epithelium was seen lining 
the surface. The underlying stroma showed a tumor 
composed of cells with abundant clear cytoplasm, arranged in 
nests. The nuclei were small, centrally placed, with dense 
chromatin and inconspicuous nucleoli; mild pleomorphism 
was seen at places, with larger size and open chromatin. The 
cell nests were separated by vascular sinusoids lined by 
endothelial cells. There was very little stroma between the 
 
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2 
 
cells (Fig. 1). The tumor was seen extending upto, but not 
involving the surface lining epithelium or the serous glands 
accompanying the lining mucosa. Adjacent salivary tissue 
and bone were uninvolved. The morphology was strongly 
suspicious of metastatic renal cell carcinoma. The tumor was 
positive for cytokeratin and vimentin; CD10 showed focal 
positivity (Fig. 2). With the above histologic findings and 
IHC profile, a diagnosis of metastatic renal cell carcinoma, of 
clear cell type, in the right sinonasal region was made. 
Further clinical details were sought and the patient disclosed 
having undergone nephrectomy for renal cell carcinoma six 
years back. 
 
Figure 1: Photomicrograph showing nests of clear cells 
surrounded by delicate vascular sinusoids (H&E; Figure 
1A-10x, Fig 1B-40x) 
 
Figure 2: Photomicrographs showing 
immunohistochemical stains in metastatic RCC 
Discussion 
Sinonasal area is an unusual site for metastatic tumors. Renal 
cell carcinoma, in particular, is known to metastasise to the 
sinonasal region, although extremely rare. Nearly 50 cases of 
nasal metastases and about 105 cases of maxillary 
involvement have been reported in literature so far.(4,5) 
Epistaxis is the most common presenting symptom in 
metastatic RCC. It should be included in the differential 
diagnosis of nasal bleeds, as experienced in the present case. 
The tumor is hypervascular due to the presence of abundant 
sinusoids, leading to persistent epistaxis. The high vascularity 
of the tumor can be explained by mutation of the VHL gene, 
which causes upregulation of hypoxia-induced factor 1a, 
which in turn leads to angiogenesis through VEGF 
upregulation.(4) In the case discussed here, sphenopalatine 
artery was ligated prior to biopsy which not only controlled 
the bleed, but also reduced the tumor size considerably. 
The possibility of metastasis should be considered when 
carcinomas of unusual morphology are encountered in the 
sinonasal area.(2) Kaminski et al reported 46 cases of 
metastatic tumors in the head and neck region, of which four 
were in the nasal cavity and paranasal sinuses, with one case 
of RCC involving the maxillary sinus.(6) RCC is the most 
common primary tumor to metastasise to the paranasal 
sinuses, the maxillary sinus being most commonly 
involved.(1) 
About 30% of patients with RCC present with metastasis at 
the time of diagnosis and another 30% develop metastasis 
after initial treatment. Late metastasis is not uncommon. The 
interval between nephrectomy for RCC and nasal metastasis 
was 6 years in the present case. Longer intervals of upto 17 
years have been reported.(7) RCC spreads via the 
hematogenous route, although lymphatic metastasis is also 
known. Microvascular invasion plays an essential role in 
metastasis and is considered an important prognostic marker 
for recurrence. Tumor cells spread either through the inferior 
vena cava or through the Batson’s paravertebral venous 
plexus, which allows the cells to escape the pulmonary 
capillary filter and spread to unusual sites. 
Clear cell carcinoma accounts for 75% of all renal 
neoplasms. It is one of the great mimics in pathology. Tumor 
cells in clear cell RCC have abundant clear cytoplasm due to 
presence of lipid and glycogen. The nuclei are spherical and 
centrally placed. The chromatin could be dense or open, with 
inconspicuous to macronucleoli. The cells are arranged in 
nests and alveolar pattern, surrounded by a regular network 
of small thin walled blood vessels with little supporting 
fibrous tissue, a diagnostic feature of this tumor. Fuhrman 
grading system is a 4-tier grading system for nuclei in RCC. 
It grades tumors based on the size of the nuclei, their shape, 
chromatin pattern and presence and prominence of nucleoli. 
Those with low nuclear grade are less likely to 
metastasise.(8) Clear cell RCCs react positively for 
cytokeratin (CK), AE1, Cam5.2, vimentin, RCC marker, 
CD10 and EMA. MUC1 and MUC3 are consistently 
expressed. The tumor in the present case showed the above 
morphologic features with nuclear grade II. CK, vimentin 
and CD10 were the markers used and were positive. 
The main differential diagnoses include hepatocellular 
carcinoma, clear cell sarcoma, hemangiopericytoma, and 
malignant melanoma.(3) In the present case, CK positivity 
indicates epithelial nature of the tumour. Vimentin was 
positive in the endothelial cells and smooth muscle cells in 
the sinusoids and vascular septae. CD10 positivity indicated 
metastatic RCC. CK and CD10 can be positive in 
hepatocellular carcinoma and melanoma. Co-expression of 
CK and vimentin, common in clear cell RCCs, is not seen in 
other carcinomas and should be taken as suggestive of a renal 
primary when found in metastasis of unknown 
origin.(9) This, considered with history of  nephrectomy for 
RCC, clinched the diagnosis in favour of metastatic renal cell 
carcinoma. 
Salivary gland tumors with clear cell change are excluded by 
the lack of relation between the tumor and salivary 
gland.(10) The salivary tissue in the vicinity of the tumor was 
uninvolved in our case. Rarely, primary clear cell carcinoma 
can arise from the respiratory epithelium in the sinonasal 
tract. Lack of transition from benign respiratory epithelium to 
malignant clear cells excluded this entity in the present case. 
Sinonasal adenocarcinoma is positive for CK and EMA, 
negative for S100, vimentin and CD10. Salivary gland 
tumors are positive for CK and S100, negative for CD10. 
Metastatic RCC is positive for CK, vimentin and CD10. 
Sinonasal renal cell-like adenocarcinoma is an unusual 
neoplasm, described by Zur et al and Hadi et al, that is a 
histologic mimic of RCC. It is diagnosed by exclusion after 
ruling out metastatic RCC. RCC marker and vimentin are 
negative in this entity unlike RCC.(11) Sinonasal renal cell-
like adenocarcinoma and low grade sinonasal 
adenocarcinomas are probably same entities, sharing similar 
morphologic and immunohistochemical profiles. 
3 
 
Clear cell RCCs carry worse prognosis. Nuclear grade, after 
stage, is the most important prognostic feature. Prognosis for 
metastatic carcinoma is poor despite advances in treatment 
like immunotherapy and mTOR kinase inhibitors. Median 
survival is about a year and expected 5-year survival is less 
than 20%.(12) Surgery with radiotherapy is the treatment of 
choice for metastatic deposits in the sinonasal region. It 
reduces the tumor burden and also controls epistaxis. 
Conclusion 
Renal cell carcinoma is an aggressive tumor with a 
propensity for distant metastasis. The patterns of spread are 
not well understood, leading to unusual metastatic sites and 
atypical presenting symptoms. The nasal cavity and paranasal 
sinuses are a rare site for metastatic deposits. Carcinoma in 
the sinonasal area, particularly clear cell variant, is very rare 
and is most often from a metastasising renal cell carcinoma; 
it carries a poor prognosis. Occult RCCs presenting as 
unknown primaries at distant sites or recurring years after 
radical nephrectomy pose unique problems in diagnosis. It 
has to be differentiated from salivary gland carcinomas and 
the rarer sinonasal adenocarcinomas of similar morphology. 
This case was diagnosed based on histopathological findings, 
without the prior knowledge of nephrectomy, which the 
patient had undergone for RCC 6 years back. We report this 
case to highlight an unusual site for metastasis from an RCC, 
6 years after initial diagnosis and also to reinforce the view 
that a detailed history and morphology is as relevant as IHC 
in arriving at a diagnosis. 
References 
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Metastasis to paranasal sinuses as the first presenting 
sign of renal cell carcinoma. Open Journal of 
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2. Nasab MS, Jafari M, Bahar SHM, et al. Endoscopic 
management of unusual metastasis of renal cell 
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3. Terada T. Renal cell carcinoma metastatic to the nasal 
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Metastatic Renal Cell Carcinoma in the Sinonasal Region

Jyothi A Raj

V Mahantachar

T Rajaram

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Metastatic Renal Cell Carcinoma in the Sinonasal Region

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