pheochromocytomas are rare catecholamine producing tumors arising from chromaffine cells in the sympatho adrenal system .
its prevalence is estimated at 0.1% to 0.6% . they secrete various catecholamines , predominantly norepinephrine , and epinephrine to small extent .
these catecholamines are responsible for the manifestations with sustained or paroxysmal symptoms . diagnosis is established by measuring metanephrines in the urine or blood .
localization of the tumor is done using computed tomography ( ct ) or magnetic resonance imaging ( mri ) scans .
thrombosis of the inferior vena cava ( ivc ) has comparable etiological factors to lower limb deep venous thrombosis .
hypercoagulability related to hematological or neoplastic abnormalities , venous stasis secondary to extraluminal pressure from tumors or inflammatory processes , and vessel injury due to trauma have all been implicated as primary mechanism in the pathophysiology of ivc thrombosis .
however , its association with pheochromocytoma in indian subjects has not been reported till date .
a 48-year - old man was admitted to our hospital with complaints of headache , sweating , anxiety , dizziness , nausea and vomiting .
the patient was 164 cm tall and weighed 57 kg . on physical examination , there were no caf au lait spots or neurofibromas .
hematological analysis confirmed normocytic anemia with hemoglobin 11.3 gm / dl , a raised erythrocyte sedimentation rate ( esr ) ( 130 mm fall in the first hour ) , while the total and differential leukocyte counts were normal .
biochemical parameters such as liver and kidney functions , and serum electrolytes , calcium , phosphorous , alkaline phosphatase and d - dimer were within normal limits .
the endocrinological evaluation revealed increased urine catecholamines and urinary vanillyl mandelic acid ( vma ) [ table 1 ] .
baseline biochemical parameters of the patient abdominal ct revealed a well defined , heterogenous mass lesion of size 7.6  5.3  4.8 cms with attenuation score of 35 hu at the upper pole of right kidney without any calcifications [ figure 1 ] .
there was no involvement of renal vein , hepatic veins and veins of lower limbs demonstrated by doppler ultrasound .
magnetic resonance imaging ( mri ) revealed intraluminal thrombus extending proximally up to the confluence of hepatic veins immediately inferior to the right atrium without distal extension to femoral veins bilaterally [ figure 2 ] .
an ivc venogram via the right jugular vein demonstrated multiple filling defects indicating occlusion of the ivc inferior to the right atrium [ figure 3 ] .
there was simultaneous enlargement of distal part of ivc . computed tomography of the abdomen- showing a well defined , heterogeneously enhancing mass lesion of size 7.6  5.3  4.8 cm at the upper pole of right kidney without any calcifications .
the left adrenal gland appeared to be normal t2-weighted axial magnetic resonance imaging demonstrating the mass ( predominantly high signal ) between the inferior vena cava and right kidney ( black arrow ) compressing the overlying inferior vena cava ( white arrow ) ivc venogram showing multiple filling defects indicating occlusion of the inferior vena cava inferior to the right atrium .
there is distal enlargement of inferior vena cava a diagnosis of ivc thrombosis with pheochromocytoma was established , and surgical treatment was planned .
alpha receptor blocking therapy with prazosin was instituted , followed by  blocker , after testing for adequacy of  blockade .
the patient was treated conservatively with subcutaneous low molecular weight heparin followed by oral warfarin .
after 2 weeks , hypertension was well controlled and the remaining symptoms disappeared . with adequate blood pressure control ,
biopsy of the specimen revealed a typical organoid or zellballen pattern with no cytoplasmatic inclusion , pleomorphism , cytological alterations or necrosis ; and , the mitotic index was low [ figure 4 ] . during the postoperative period ,
the patient 's blood pressure remained normal . a 24-hour urine specimen collected for metanephrine and vma , revealed levels within normal limits . at present , the patient is asymptomatic , requires no medications , and is employed as an engineer .
mri imaging demonstrated resolution of the thrombosis and return of patency of the ivc at 4 months [ figure 5 ] . the typical growth pattern of nests of tumor cells ( zellballen ) surrounded by a discontinuous layer of sustentacular cells and fibrovascular stroma in the biopsy specimen of the patient in the study .
blood vessels surrounding tumor nests are composed of round to oval cells t2-weighted axial magnetic resonance imaging comparable in position and image acquisition to figure 2 demonstrating complete resolution of inferior vena cava thrombosis ( white arrow ) after 4-months of oral anticoagulation therapy
two aspects render our case unusual : 1 ) the coexistence of pheochromocytoma with ivc thrombosis 2 ) though there are case reports citing the association between malignant pheochromocytoma and ivc thrombus , to our sincere belief ; this is the first such report citing this uncommon association from india .
although the lifetime incidence of venous thrombosis is 0.1% , it still remains a rare condition especially in patients below 30 years of age .
predisposing factors include alterations in blood flow [ stasis ] , injury to the vascular endothelium and abnormalities in the constitution of blood hypercoagulability ( virchow 's triad ) .
endothelial damage is invariably an acquired phenomenon , whereas hypercoagulability may result from both congenital and acquired risk factors ( especially in the peri - operative period ) .
the classical presentation of ivc thrombus varies according to the level of the thrombosis with up to 50% of patients presenting with bilateral lower extremity swelling and dilatation of superficial abdominal vessels . whilst some patients remain asymptomatic ,
lower back pain , nephrotic syndrome , hepatic engorgement , cardiac failure and pulmonary embolus have also been described .
tsuji et al . reported a series of 10 patients where 40% were pyrexic at presentation , with an associated elevation in d - dimer levels and inflammatory markers ( white cell count , c - reactive protein ) .
our patient had no lower limb , liver or kidney involvement , and this might be ascribed to the partial occlusion of ivc .
we could not explain normal d - dimer levels in the backdrop of such a large thrombus in our patient .
ct scan with contrast enhanced images and mri scan are used to localize adrenal pheochromocytoma .
meta - iodobenzylguanidine ( mibg ) and positron emission tomography ( pet ) scanning ( gallium- dota - toc / noc and dopa - pet perform better than fdg- pet ) are largely reserved for extraadrenal paraganglioma , or very large tumors to rule out metastasis .
heterogeneity , high hounsfield density on ct ( > hu ) , marked enhancement with intravenous contrast and delayed contrast washout ( < 60 % at 10 minutes ) , high signal intensity on t2 weighted mri , cystic and hemorrhagic changes point to pheochromocytoma , adrenocortical carcinoma or metastasis .
however , pheochromocytoma with lipid degeneration can result in low attenuation scores ( < 10 hu ) and > 60% washout at delayed ct scanning .
benign adrenal incidentalomas are characterized by size < 5 cm , sharp margins , smooth contours , lack of demonstrable growth on serial examinations , attenuation scores < 10 hu , and > 60% washout at delayed ct scanning . in our patient , ct scan revealed nonhomogenous mass of hu 35 without any calcification .
histologically , pheochromocytomas are capsulated and are composed of round or polygonal epithelioid / chief cells arranged in characteristic compact cell nests ( zellballen ) or trabecular patterns .
the chief cells have centrally located nuclei with finely clumped chromatin , and a moderate amount of eosinophilic , granular cytoplasm .
tumors of higher grade are characterized by a progressive loss in the relationship between chief cells and sustentacular cells , and a decrease in the number of sustentacular cells . in our patient , typical zellballen pattern was found .
presence of markers like chromogranin a ( cga ) , neuron specific enloase , synaptophsyin serve as additional tools to confirm the neuroendocrine nature of the chief cells .
the only reliable clue to the presence of a malignant pheochromocytoma is local invasion or distant metastases , which may occur as long as 20 years after resection .
benign  on pathologic examination , long term follow - up is indicated in all patients to confirm that impression .
other markers for malignancy are absent or weak expression of inhibin / activin- beta b subunit , and presence of succinate dehydrogenase b ( sdh b ) subunit is seen . in absence of any invasion , we considered the mass in our patient to be benign . the simultaneous occurrence of pheochromocytoma and ivc thrombosis is reported sporadically .
ivc thrombosis in this case could be because of : 1 ) local compression leading to alteration in blood flow and stasis 2 ) sustained hypertension leading to vascular endothelial injury and hypercoagulability , 3 ) association of pheochromocytoma with systemic lupus erythematous and behcet 's disease might explain the triggering of an autoimmune phenomenon leading to a hypercoagulable state , and 4 ) an underlying anatomic abnormality or coagulation disorder .
it also could be a chance association between these 2 conditions . in our case ,
recent advances in the utilization of ultrasound , ct and mri imaging as well as endovascular procedures have resulted in an increase in detection rates of ivc anomalies , as well as an increase in the incidental discovery of such abnormalities during unrelated investigations , therapeutic endovascular or surgical procedures .
contrast venography remains the standard for diagnosis of ivc thrombosis with a low false - positive rate , and the advantage of access for immediate treatment if required .
however , it is an invasive procedure associated with a 2%-10% incidence of post - procedural deep venous thrombosis ( dvt ) .
duplex ultrasound scanning has become an accurate non - invasive method of diagnosing ivc thrombosis and is often the first - line investigative modality .
however , duplex usg is operator dependant and can be limited by body habitus or the presence of bowel gas and may occasionally fail to identify any ivc anomaly .
ct imaging is a rapid non - invasive method which can accurately diagnose and assess the extent of thrombus as well as delineate any associated abdominal or pelvic abnormality .
mri imaging is now replacing ct as the optimal investigative tool avoiding radiation and giving more accurate delineation of thrombus as well as any ivc anomaly .
mri is also used to follow - up patients to determine morphological changes in the thrombus following therapy .
management of patients with coexisting pheochromocytoma and ivc thrombosis needs operative resection of the adrenal mass and medical / interventional management of ivc thrombosis .
the goals of operation include 1 ) removal of the tumor with postoperative normotension , and 2 ) ivc luminal restoration and anticoagulation .
minimally invasive techniques are being increasingly used for resection of adrenal tumors and to treat renal artery lesions .
our patient was subjected to laparoscopic adrenalectomy after adequate preoperative blood pressure control by  blockers , followed by  blockers .
treatment options in the case of ivc thrombus without anatomical variance include anticoagulation , mechanical thrombectomy , systemic thrombolytic therapy , transcatheter regional thrombolysis , pulse - spray pharmacomechanical thrombolysis and angioplasty .
there is no specific literature describing the ideal duration of anticoagulation in these instances ; however , case evidence identifies a trend toward treatment for a minimum of one year with the interplay of hypercoagulability disorders needing to be factored into any decision .
surgical reconstruction of the ivc and bypass of an aberrant section are both recognized modalities reserved for the most severe cases and are associated with morbidity and mortality risk .
endovascular stent placement in combination with angioplasty is recommended in the cases of residual stenosis and chronic ivc occlusion . in the case of ivc thrombus
associated with an aberrant ivc , with no other predisposing factors , treatment involves anti - coagulation .
the duration of this treatment is widely debated with no extensive literature to provide an evidence based approach .
dean et al . took a view , which is quite similar to that of ours , that a caval anomaly is a permanent risk factor for venous stasis and thrombosis and that anticoagulant treatment should be lifelong . since our patient had no anatomic abnormality or any other predisposing factors , we decided to give the treatment for 4 months only and stopped it then after documenting radiologic luminal restoration .
though cases of renal artery stenosis , renal artery aneurysm and inferior vena cava thrombosis have been described , we found the uncommon association with ivc thrombosis in an indian patient .
ct or preferably mri imaging are required to delineate ivc anatomy and ascertain proximal extent of the thrombus .
although invasive therapeutic modalities exist , long - term and commonly life - long anticoagulation is often required .
pheochromocytoma does not seem to have any effect on the outcome of the coexisting ivc thrombosis .
 pheochromocytomas have been described in association with vascular abnormalities like renal artery stenosis . 
 a 48-year - old man was admitted to our hospital with the complaints of headache , sweating , anxiety , dizziness , nausea , vomiting and hypertension . for last several days , he was having a dull aching abdominal pain . 
 abdominal computed tomography ( ct ) revealed the presence of a left adrenal pheochromocytoma . 
 an inferior vena cava ( ivc ) venogram via the right jugular vein demonstrated occlusion of the ivc inferior to the right atrium . 
 surgical removal of pheochromocytoma was done , followed by anticoagulant treatment for ivc thrombosis , initially with subcutaneous low molecular weight heparin , and then with oral warfarin , resulting in restoration of patency . to the best of our knowledge , 
 the occurrence of pheochromocytoma in ivc thrombosis has not been reported so far from india . 
 possible mechanisms of such an involvement are discussed . 