renal cell carcinoma ( rcc ) can metastasize to any location in the body , and distant metastases are common , being present in 30% to 40% of patients with metastatic disease .
the most common sites affected are the lungs ( 76% ) , regional lymph nodes ( ln ) ( 66% ) , bone ( 42% ) , and liver ( 41% ) .
however , only 1.5 to 3.5% of rcc patients show solitary metastasis , and only 1% have metastasis confined to the head and neck .
moreover , cases of metastatic rcc with a non - identifiable kidney mass are extremely rare . here
, we report a case of metastatic rcc in only a supraclavicular ln with no evidence of a primary kidney lesion .
a 69-year - old man presented with a 2-week history of a progressively enlarging supraclavicular mass in april 2009 .
written consent was obtained from the patient for publication of the study . upon physical examination ,
his body temperature was 37.3 , blood pressure 130/90 mmhg , and pulse rate 75/min . a head and neck examination revealed a palpable firm , fixed , non - tender , 8 cm - sized mass in the right supraclavicular area with no other evident lymphadenopathy , and an abdominal examination revealed no palpable mass . his complete blood cell count , chemistry findings , and renal functionwere normal .
urine dipstick and microscopy tests revealed no hematuria or abnormal cells . computed tomography ( ct ) of
hematoxylin and eosin staining revealed that tumor cells were polygonal with clear cytoplasm and vesicular nuclei with prominent nucleoli ( fig .
immunohistochemical staining showed that tumor cells were positive for pancytokeratin ( 1 : 300 , leica , newcastle upon tyne , uk ) , vimentin ( 1 : 200 , dako , glostrup , demark ) , and cd10 ( 1 : 100 , leica ) ( fig .
2b ) , but negative for thyroid transcription factor 1 ( 1 : 300 , leica ) , cytokeratin 7 ( 1 : 600 , neomarkers , fremont , ca ) , cytokeratin 20 ( 1 : 150 , dako ) and hepatocyte specific antigen ( 1 : 50 , leica ) . based on these findings ,
a diagnosis of metastatic clear cell rcc was made , after which the patient underwent abdominal / pelvic ct ( fig .
3b ) . the results revealed no tumor in either kidney , and no further metastatic lesions ; accordingly , he was diagnosed as having metastatic rcc in a supraclavicular ln only , without an identifiable kidney mass .
the patient was initially treated with radiotherapy ( 4,000 cgy administered in 15 fractions over a period of 3 weeks ) , which induced tumor shrinkage , after which he was administered sunitinib ( 50 mg / day consecutively for four weeks followed by two weeks off per cycle ) .
after two cycles , a follow - up ct scan revealed that the supraclavicular ln had markedly decreased in size ( fig .
the acute toxicity ( grade 3 hand - foot syndrome , asthenia , and grade 2 thrombocytopenia ) led to dose reduction ( 25 mg / day consecutively for four weeks followed by two weeks off ) .
after 20 months of sunitinib under the reduced dose , no tumor progression was observed .
repeated follow - up abdominal / pelvic ct for 20 months has revealed no evidence of a primary renal tumor .
the most common metastatic sites of rcc are the lungs , regional ln , bone , and liver , and it is uncommon for rcc to present a solitary metastasis at an unusual site .
the mechanism of metastasis to unusual sites has not been clearly explained , but the mechanism of solitary metastasis of rcc to the head and neck region ( an unusual site ) is explained as follows .
batson 's paraspinal plexus is a rich , valve - less venous anastomosis with prevertebral , vertebral , and epidural systems , and this rich venous system offers little resistance to the spread of tumor emboli .
accordingly , the vertebral venous plexus offers a means of bypassing the pulmonary venous system and facilitates metastasis in the head and neck region without lung involvement .
metastases that do not follow normal hematogenous flow patterns may also be explained by a right - to - left heart shunt , spontaneous regression of lung disease , or microscopic seeding of lung parenchyma . moreover , non - identifiable kidney lesions are extremely rare in metastatic rcc . in such cases ,
the disease presents as carcinoma of an unknown primary form with a clear cell neoplasm .
however , diagnostic pathology has improved remarkably , and the routine use of electron microscopy and immunohistochemistry and the emerging field of molecular genetics are enabling more precise diagnoses .
differential diagnoses in malignant neoplasms composed of clear cells include hepatocellular carcinoma , adrenal cortical carcinoma and clear rcc .
hepatocellular carcinoma is positive for cytokeratin , epithelial membrane antigen ( epithelial markers ) , and hepatocyte specific antigen , but negative for vimentin , whereas adrenal cortical carcinoma is positive for vimentin , but negative for epithelial markers .
rcc is positive for epithelial markers , vimentin , and cd10 , similar to the neoplastic cells in our case .
a number of previous case reports have also described cases of metastatic clear cell renal carcinoma without a primary renal mass . in the case of metastatic rcc
, no renal tumor was observed initially , but a renal tumor did appear after two years .
bhatia et al .   also reported a case of cutaneous facial rcc with no known primary tumor .
it is not known why the primary lesion remains occult , but it may be involved or too small to be detected .
nevertheless , these lesions could be silent renal tumors ; therefore , close monitoring is essential . as in our case , patients with single site involvement ( brain , liver , subcutaneous tissue , bone , intestine , ln , or others ) should be treated using aggressive local therapy such as resection , radiation therapy , or both , because a minority enjoy long - term , disease - free survival .
in addition to definite local therapy , these patients should also receive systemic therapy based on one of the newer regimens because they seem to confer better survival . in our case of solitary metastasis in a supraclavicular ln ,
radiation therapy was applied and systemic therapy was performed with sunitinib , which is a standard treatment for metastatic rcc . as a result , the patient has been well for the last 20 months without disease progression .
sunitinib is a multitargeting receptor tyrosine kinase inhibitor of vascular endothelial growth factor and of platelet - derived growth factor receptor . in a recent phase iii trial ,
progression - free survival was found to be longer and quality of life to be better for patients with metastatic rcc treated with sunitinib than for those treated with interferon- .
not infrequently , clinicians and pathologists encounter malignant neoplasms composed of clear cells that have sources and natures that can not be determined by conventional morphological studies .
therefore , immunocytochemical staining for cytokeratin , epithelial membrane antigen , vimentin , and fat are of considerable diagnostic help in rcc .
this case report suggests that even in the absence of a primary kidney lesion , clinicians must consider the possibility of metastatic rcc when evaluating patients with clear cell carcinoma from an unknown primary site .
furthermore , if only one metastatic site is present , a local modality such as surgical resection or radiotherapy should be applied , and if necessary , systemic treatment like sunitinib added .
 although metastasis is relatively frequent in cases of renal cell carcinoma ( rcc ) , metastasis in the cervical or supraclavicular lymph node ( ln ) is relatively rare . 
 moreover , cases of metastatic rcc with a non - identifiable kidney mass are extremely rare . here 
 , the authors report a case of metastatic rcc in a supraclavicular ln without a primary kidney lesion . a 69-year - old man presented with a progressively enlarging right supraclavicular mass . 
 incisional biopsy of the affected supraclavicular ln was performed , and histological examination revealed metastatic rcc . 
 however , no tumor was found in either kidney , despite various examinations . 
 the patient was treated with radiotherapy followed by sunitinib . 
 after three months on sunitinib , a follow - up computed tomography scan revealed that the supraclavicular ln had markedly decreased , and after 20 months , the disease had not progressed . 
 this case suggests that , even when there is no primary kidney lesion , clinicians must consider the possibility of metastatic rcc when evaluating patients with clear cell carcinoma with an unknown primary site . 
Introduction
Case Report
Discussion