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hepatocellular carcinoma ( hcc ) shows many pathological features , and it varies architecturally and cytologically .
a variety of cellular products , mimicking normal and pathologic liver cell function , can sometimes be seen by light microscopy or identified by various histochemical and immunohistochemical techniques .
for example , large amounts of cytoplasmic fat or glycogen can cause the cytoplasm to appear white in routine sections , producing the so - called clear cell carcinoma of the liver .
there have been many reports and discussions of the morphological features of hcc , but there have been no reports of a variant of hcc that is characterized by abundant foamy cells with microvesicular cytoplasm .
a case is presented of a patient with a morphologically distinctive pattern of hcc with dominant cytoplasm giving the cells a foamy histiocyte - like appearance , and the histochemical and immunohistochemical characteristics of this tumor are documented .
a 63-year - old man had been followed up for chronic hepatitis c since 1998 at another medical facility . in september 2006 , a tumor was found in liver segment 7 that was diagnosed as hcc .
laboratory findings included : wbc 6,000/l , rbc 488  10/l , hb 15.5 g / dl , ht 45.9% , plt 15.3/10/l , t.bil 1.3 mg / dl , albumin 4.2 g / dl , ast 49 iu / l , alt 57 iu / l , alp 241 iu / l , gt 65
afp was 17.9 ng / ml , and pivka - ii was 202 mau / ml .
abdominal ultrasonography and computed tomography examinations showed a solitary mass 45 mm in diameter in liver segment 7 .
the mass had a regular circumference , a very clear boundary , and a fibrous capsule .
it showed heterogeneous enhancement in the early phase and comparatively low density in the late phase .
t1-weighted magnetic resonance imaging ( mri ) showed irregular and slightly high intensity with arterial enhancement , and nonuniform high - intensity areas with prominent fatty change .
t2-weighted mri showed a high - intensity lesion in the same area . on abdominal dynamic mri , the tumor showed prominent fat deposition inside , and it was heterogeneous , with high intensity on t1-weighted images in the arterial phase ( fig .
these examinations suggested that the preoperative diagnosis was a relatively well - differentiated , nodular type of hcc with fatty change and a clinical stage i according to the tnm classification . a partial resection of liver segment 7 was performed .
the patient 's postoperative course was satisfactory , and he was discharged on postoperative day 9 without complications .
macroscopically , the tumor presented as a single mass measuring 4.5  4.1  3.5 cm .
the cut surface of the tumor was a yellow - white color , with a white part in the central area that was expansive and protruded .
microscopically , the noncancerous lesion showed infiltration of inflammatory cells and rhexis images of the limiting plate at the periportal region ; this was diagnosed as active chronic hepatitis .
the tumor lesion showed a moderately differentiated hcc that consisted mainly of a thick trabecular pattern , with some thin parts and other thick parts .
there was also the lesion with cells with clear cytoplasm corresponding to the white lesion in the face of the cut tumor ( fig .
the white lesion contained rich fatty tissue . despite the fact that it was a moderately differentiated adenocarcinoma , with a diameter of 45 mm
the lesion was mainly composed of foamy histiocyte - like cells , which were negative for cd68 , s-100 , vimentin , and hmb-45 .
cytologically , the lesion contained medium - small fat vacuoles that were negative for pas - alb .
it was interesting that these tumor cells showed a unique , clear , foamy appearance .
there have been no reports of hcc with morphological characteristics that appeared like foamy histiocytes phagocytosing fat .
histiocytes are well known as cells that have a foamy appearance [ 6 , 7 ] ; they are positive on immunohistochemistry for cd68 . however , in the present case , the foamy histiocyte - like cells were negative for cd68 , and they had a clear cytoplasm and a foamy appearance that , at quick glance , appeared to be due to granules . there is a variety of hcc that has clear cytoplasm , and it is known as clear cell hcc .
hcc cells resemble normal liver cells to a variable extent , depending on the degree of differentiation .
a large amount of cytoplasmic glycogen and/or fat can cause the cytoplasm to appear white in routine sections , producing a clear cell appearance .
recently , clear cell carcinoma was reported to occur with a frequency varying from 0.9 to 8.8% in a large series of hccs from many different countries [ 5 , 9 , 10 , 11 , 12 , 13 ] .
microscopically , clear cell hcc shows moderate - to - marked cytoplasmic accumulation of glycogen and/or fat droplets that dissolve during processing , leaving behind a clear area . without immunohistochemistry , it may be difficult to distinguish between morphological differentiation of clear cell hcc and other clear cell carcinomas , such as metastases from renal clear cell carcinoma [ 11 , 13 , 14 ] . in this case
, hepatocyte paraffin 1 ( hep - par 1 ) , which is a monoclonal antibody that reacts with hepatocytes and can be used for differential diagnosis of hepatic tumors , was used to confirm that the foamy histiocyte - like lesion was derived from hepatocytes , because it was positive for hep - par 1 .
the cytoplasm did not contain glycogen or mucin , because pas and sudan stains were negative .
the other immunohistochemical and histopathological findings suggested that this tumor was a hcc ; nevertheless , it was not clear cell hcc .
adsay et al .   reported a morphologically distinctive foamy pattern of pancreatic ductal adenocarcinoma with prominent microvesicular cytoplasm , giving the cells a foamy appearance .
furthermore , these lesions may be confused with hepatic metastases of renal cell carcinoma or clear cell hcc because of the small amount of tissue obtained when biopsies of tumors are performed .
this case was a cytological variant of hcc that had foamy histiocyte - like features . without immunohistological analysis , it is difficult to distinguish hcc with foamy histiocyte - like features from clear cell carcinoma or metastases of renal cell carcinoma .
it is important to recognize this type as a specific cytological variant of hcc that requires confirmation by immunohistochemistry .
nevertheless , it was unclear whether the tumor cells differed from those of normal hcc .
this report describes the case of a patient with a morphologically distinctive pattern of hcc with prominent cell cytoplasm that had a foamy histiocyte - like appearance . to the best of our knowledge ,
hepatocellular carcinoma ( hcc ) shows many pathological features , and it varies architecturally and cytologically . 
 there have been many reports and discussions of the morphological features of hcc . 
 a 63-year - old man was found to have a solitary tumor in liver segment 7 that was diagnosed as hcc . 
 a partial resection of liver segment 7 was performed . 
 microscopically , the tumor lesion showed a moderately differentiated hcc . there was also a lesion with foamy histiocyte - like cells corresponding to the white lesion in the face of the cut tumor . 
 immunohistochemical staining showed that they were negative for cd68 , s-100 , vimentin , and hmb-45 . 
 the cytoplasm itself was negative on periodic acid schiff ( pas ) and sudan staining . without immunohistological analysis , 
 it is difficult to distinguish this hcc variant from clear cell carcinoma or metastases of renal cell carcinoma . 
 it is important to recognize this type as a specific cytological variant of hcc that requires confirmation by immunohistochemistry . 
 this report describes the case of a patient with a morphologically distinctive pattern of hcc with prominent cell cytoplasm that had a foamy histiocyte - like appearance . to the best of our knowledge , 
 this is the first report of this hcc variant .