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tuberous sclerosis is a rare multisystem disorder characterized by widespread hamartomas in several organs including the brain , heart , skin , eyes , lungs , kidneys , liver , and bones .
the most commonly involved abdominal organ is the kidney , which is affected in up to 80% of all cases .
the most common lesion , in these cases , is an angiomyolipoma ( aml ) .
involvement of the liver tends to be less frequent than that of the kidneys and is therefore less well - documented .
an islet cell tumor ( ict ) is a rare neoplasm of the pancreas accounting for 1%-3% of all pancreatic tumors , although an association with tuberous sclerosis is extremely rare it can occur . to our knowledge , only 13 cases of pancreatic ict with tuberous sclerosis have been reported .
we are presenting a case of a 63-year - old - woman with aml of the kidney and liver , calcified subependymal nodules , and a large mass in the pancreas , which was identified histopathologically to be an ict .
a 63-year - old - woman was referred to our department with a complaint of abdominal pain . upon physical examination ,
skin lesions were detected and a firm mass was palpable in the upper quadrant of the abdomen .
she was referred to the radiology department for a computed tomography ( ct ) examination of the abdomen . a biphasic contrast enhanced ct
was also performed on a 16-slice ct system ( somatom sensation , siemens , erlangen , germany ) .
an intravenous injection of 130 ml contrast media ( iopamidol with an iodine concentration of 300 mg / ml ) was given at a rate of 4 ml / s .
scanning was initiated after a delay of 25 s and 70 s after infusion of contrast material for the arterial phase and venous phase images , respectively .
scanning parameters were as follows : slice collimation , 16  1.5 mm ; table feed / rotation , 18.0 mm ; rotation time , 0.5 s ; kv 120 ; effective mas 160 , slice thickness , 2 mm .
ct examination revealed a 9  6 cm mass with discrete nodular calcifications in the head of the pancreas .
the mass showed heterogeneous enhancement in the arterial phase and homogenous enhancement in the venous phase [ figure 1a and b ] .
there were also multiple lesions in the liver ranging in diameter from 3 to 25 mm .
some of the lesions showed homogenous fat - density ; however , others had heterogeneous areas of soft - tissue density and fat - density that were suggestive of aml .
lesions with homogenous fat - density did not show any enhancement in both the arterial and the venous phase images [ figure 2 ] . in lesions containing both a soft tissue component and a fat component ,
the nonfat component was enhanced markedly in the arterial phase and showed isohypodensity in the venous phase .
these lesions had homogenous enhancement in the arterial phase image and became isohypodense in the venous phase image [ figure 3 ] .
there were also multiple fat - containing lesions in both kidneys compatible with aml [ figure 1b ] as well as multiple small discrete sclerotic lesions in the vertebrae .
unfortunately , as the patient was claustrophobic she did not undergo a magnetic resonance imaging ( mri ) investigation .
63-year - old woman with abdominal pain diagnosed with angiomyolipoma ( aml ) of the kidney and liver , and islet cell tumor of the pancreas .
contrast - enhanced computed tomography ( a ) coronal reconstruction image obtained during the arterial phase of enhancement shows a large heterogeneously enhanced mass .
( b ) axial image obtained in the venous phase of enhancement shows that the mass enhanced homogenously and had calcifications ( arrow head ) .
63-year - old woman with abdominal pain diagnosed with angiomyolipoma ( aml ) of the kidney and liver , and islet cell tumor of the pancreas .
axial image obtained in arterial phase shows an aml in segment 2 of the liver containing homogenous fat density without enhancement ( large arrow ) and hyperenhancing small lesion ( small arrow ) .
63-year - old woman with abdominal pain diagnosed with angiomyolipoma of the kidney and liver , and islet cell tumor of the pancreas .
axial image obtained in the arterial phase shows a hyperenhancing lesion in segment 3 of the liver ( arrow ) .
the diagnosis of tuberous sclerosis was established on the basis of radiologic findings of renal and hepatic aml , calcified subependymal nodules , and vertebral sclerotic lesions with a clinical finding of adenoma sebaceum .
ultrasound - guided fine - needle aspiration of the pancreatic mass was performed using a 20-gauge needle .
histological examination of the cell - block preparations of the mass showed solid sheets of neuroendocrine - appearing cells characterized by large eosinophilic cytoplasm with moderate nuclear pleomorphism [ figure 5 ] .
immunochemical staining showed the cells were positive for synaptophysin and a few tumor cells were positive for chromogranin .
on the basis of the morphologic and immunohistochemical findings , the lesion was diagnosed as ict .
since the patient 's serum levels of the pancreatic hormones were within the normal limits , ict was considered as a nonfunctioning lesion .
63-year - old woman with abdominal pain diagnosed with angiomyolipoma of the kidney and liver , and islet cell tumor of the pancreas .
63-year - old woman with abdominal pain diagnosed with angiomyolipoma of the kidney and liver , and islet cell tumor of the pancreas .
h and e , stained specimen ( a ) 200 and ( b ) 400 show neoplastic cells forming solid sheets and also have large eosinophilic cytoplasm with moderate nuclear pleomorphism ( arrows ) .
tuberous sclerosis is a rare autosomal dominant disorder , which can affect almost all body systems .
it is caused by the mutation of two tumor suppressor genes , tsc1 and tsc2 , which encode hamartin and tuberin , respectively .
the tuberin - hamartin complex has been shown to be critical for controlling cell growth and proliferation .
the majority of the legions in tuberous sclerosis are benign hamartomas , which rarely become malignant .
tuberous sclerosis may affect the central nervous system ( cortical tubers , subependymal nodules , and astrocytomas ) , skeletal system ( sclerotic and lucent bone lesions ) , skin ( sebaceous adenomas , and fibromas ) , eyes ( retinal hamartomas ) , lungs ( lymphangioleiomyomatosis ) , heart ( rhabdomyomas ) , and abdominal organs ( amls and cysts ) .
the most commonly affected abdominal organs are the kidneys , which are affected in up to 80% of all reported cases .
cysts may be bilateral or unilateral lesions . initially , the cysts tend to be small in size and fewer in number but over time there is a tendency for the cysts to increase in size and number . renal cell carcinoma or oncocytoma may also be seen .
the involvement of the liver in tuberous sclerosis is much less common and only 13% of patients with tuberous sclerosis were reported as having aml in the liver .
pancreatic involvement in the form of cysts , aml , or ict is very rare in tuberous sclerosis .
icts are rare with an annual incidence of < 0.4 per 100,000 cases and accounts for only 1%-3% of all neoplasm of the pancreas .
genetic syndromes associated with icts include multiple endocrine neoplasia type 1 , von hippel - lindau disease , von recklinghausen disease , and tuberous sclerosis .
icts are very rarely reported with tuberous sclerosis . as noted previously , to our knowledge
, only 13 cases of tuberous sclerosis in patients have been reported where ict was present .
five of these cases had insulinoma , one case had gastrinoma , one case had glucagonoma , one case had somatostatinoma , and the remaining five cases showed the presence of nonfunctional ict .
functional tumors are classified based upon the hormones they produce as well as by the associated endocrine syndrome .
the diagnosis of functioning icts is almost always established biochemically when the tumor is small in size .
nonfunctioning icts , that represent approximately one - half of all documented icts , usually appear at an advanced stage as either benign or malignant .
when benign , the ict shows as a large pancreatic mass and when malignant , extensive hepatic , pulmonary or lymph node metastasis is present .
histological differentiation between benign and malignant tumors is difficult because tumors that metastasize are not necessarily histologically different from nonmetastasizing tumors .
tumors that are larger in size ( > 5 cm ) and show evidence of necrosis , discrete nodular calcification and invasion of retroperitoneal structures can all indicate malignancy .
the presence or absence of metastases is a major predictor of survival of the patient . in the presence of liver metastasis
however , in the presence of tuberous sclerosis , it may not always be possible to differentiate between hepatic metastasis of ict and the hepatic aml .
the classic and most common enhancement feature of nonfunctional icts seen on contrast - enhanced ct is hyperattenuating lesions in the arterial phase , which is evident because of their rich vascular supply .
ct findings of pancreatic ict are similar to hypervascular metastasis , pancreatic hamartoma , acinar cell carcinoma , solid serous adenoma , and solitary fibrous tumors .
it has been suggested that pancreatic hamartomas can be seen with tuberous sclerosis ; however , to our knowledge , a direct association has not been reported in the literature .
liver metastases of icts are also usually hypervascular and appear as hyperattenuating masses in the arterial phase images on ct .
a diagnosis of hepatic aml can be made upon detection of an unenveloped nodule with intratumoral fat , prominent central vessel , and no capsule .
definitive preoperative diagnosis of aml , especially those with lipid deficient characteristics , is a challenge for radiologists . in recent reports
, there has been an increasing frequency of fat - deficient hepatic aml being present along with tuberous sclerosis .
dilated intratumoral vessels are less commonly detected in aml due to their small size in tuberous sclerosis .
fat - deficient hepatic amls have been reported as having homogeneous - heterogeneous enhancement in arterial phase contrast - enhanced ct images .
it is difficult to differentiate fat - efficient hepatic aml from metastasis of ict in tuberous sclerosis because of similar enhancement characteristics of these two lesions .
our patient had four lesions without any fat component in the liver , ranging from 3 to 12 mm that showed homogeneous enhancement in the arterial phase and became isodense in the venous phase .
these four lesions were identified as fat - deficient aml , because the number and size of these lesions had not changed when a ct scan was done 6 months later .
in our case , a diagnosis of tuberous sclerosis was established very late , unlike in most cases reported in the literature that are diagnosed during childhood . after a diagnosis of tuberous
it should be noted that because of the high rate of malignancy , the pancreas should also be evaluated carefully during ultrasonography .
contrast - enhanced ultrasonography or endoscopic ultrasonography may also be performed for increasing the sensitivity and abdominal ct / mri can be added as the next step .
being aware of the association between tuberous sclerosis and ict is particularly important for early diagnosis and a favorable therapeutic outcome .
islet cell tumors ( icts ) are rare tumors of the pancreas . 
 association of this type of tumor with tuberous sclerosis is extremely rare 
 . only 13 cases of pancreatic ict with tuberous sclerosis have so far been documented in the literature 
 . however , awareness of the association of tuberous sclerosis and ict is important for early diagnosis and appropriate treatment of this condition . 
 this article presents the case of a 63-year - old female with angiomyolipoma ( aml ) of the kidney and liver , calcified subependymal nodules and a large mass in the pancreas , which was proven to be an ict on histopathological examination .