von hippel  lindau disease is a syndrome of high genetic predisposition towards neoplasms , which shows genealogical traits of autosomal dominant inheritance . the frequency of occurrence of this condition is estimated at 1 per 36 thousand people , which means that in poland there are about 1,000 patients suffering from vhl disease . the diagnosis of vhl disease is established based on genealogical / clinical criteria and an analysis of carrying mutations of the vhl gene . families who are affected by vhl undergo a series of preventive / diagnostic tests and examinations whose aim is early detection and treatment of neoplastic lesions . lindau disease often manifests itself with the following conditions : haemangioblastoma cerebelli , angioma of the brain stem and of the spinal cord , retinal angiomatosis , renal cysts , pancreas cysts , pheochromocytoma or renal carcinoma . they develop within the adrenal medulla , abdominal cavity , chest and occasionally  in the head and the neck . zak and lawson   quote almost 20 sites within the head and the neck where paragangliomas may occur , not only in von hippel the paraganglioma in the head and the neck is connected to the parasympathetic system , while in the adrenal medulla  to the sympathetic system . in von hippel  lindau disease the adrenal medulla is the place where the tumour of the pheochromocytoma type develops . paragangliomas producing catecholamine lead to hypertensive crises and are thought to be the cause of various clinical symptoms of sudden onset . since paragangliomas of the neck occur very rarely in von hippel lindau disease , we decided to discuss the case of a patient with a lesion of this type on the neck and an haemangioblastoma of the spinal cord . the female patient , aged 49 , reported pains in her second and third finger of the right hand that she had had for 2  years . initial diagnosis revealed isthmus carpalis and the patient was operated on without much success  no improvement was noticed . a year later , intensifying root pains of root c5 and c6 on the right side were the reason for performing an mri scan of the cervical spine . the findings from the study showed an intramedullary lesion of 1.5  cm in diameter , localized at the height of c5c6 with accompanying syrinx stretching from c3 to c7 . the patient was consulted neurosurgically several times , but refused to submit to a surgical treatment . gradually , the pains extended to the entire forearm of the upper right limb , and numbness appeared of both lower limbs . sequencing of the vhl gene revealed the presence of the 393c > a ( n131k ) missense mutation ( fig .  1 ) . 2).fig .  1sequencing chromatogram showing the 393c > a ( n131k ) germline mutation in the vhl gene . r hbl retinal haemangioblastoma , cns hbl central nervous system haemangioblastoma , d48 age of death , 49 current age of a patient sequencing chromatogram showing the 393c > a ( n131k ) germline mutation in the vhl gene . the mutation is marked by an arrow pedigree of family with vhl disease caused by the n131k mutation . r hbl retinal haemangioblastoma , cns hbl central nervous system haemangioblastoma , d48 age of death , 49 current age of a patient the patient was treated surgically several times at the ophthalmological department because of gradual deterioration of vision in the left eye . an ophthalmological examination proved the presence of a vast retinal angiomatosis of the left eye . moreover , a ct scan of the abdominal cavity showed renal cysts . in the clinical examination carried out on admission to the department of neurosurgery the following conditions were found : amaurosis oculi sinistri , paraesthesiae to algetic stimuli in the medial part of the right forearm and first , second and third fingers of the right arm increased deep reflexes in the upper right limb along with decreased muscle power of this limb , as well as babiski syndrome on the right side ; rr : 134/85  mmhg ; pulse : 76/min . an mri scan of the cervical spine showed a contrast enhancing image of an intramedullary lesion located near c5/c6 and extending to the dorsal part of the spinal cord on the right side to the subarachnoid space . an mri of the head demonstrated an angioma of 1.5  cm in diameter , localized in the choroid fissure on the right side with a small cyst . then the spinal cord was incised along the sulcus medianus posterior to uncover a lesion of the type of haemangioblastoma and a syrinx filled with yellow liquid . the neoplastic lesion was localized excentrically in the dorsal part of the spinal cord on its right side ; it reached the subarachnoid space and was connected to root c5 originating in the spinal cord . , some paraesthesia and pains in the upper left limb appeared , which gradually subsided within 3  weeks . after the surgery , the upper right limb pain subsided and the right - sided hemiparesis retreated . below we present an mri image of the cervical spine before and after the surgery ( fig . 3a mr of the cervical spine , sagital section : intramedullary tumour at the height of c5/c6 with syrinx reaching as far as c3 and below the lesion to c7 . b mr of the cervical spine , sagital section : total resection of the tumour ; a considerable reduction of the syrinx around the tumour a mr of the cervical spine , sagital section : intramedullary tumour at the height of c5/c6 with syrinx reaching as far as c3 and below the lesion to c7 . b mr of the cervical spine , sagital section : total resection of the tumour ; a considerable reduction of the syrinx around the tumour findings from a histopathological test showed haemangioblastoma . at a follow - up examination estimating how complete the excision had been , a tumour was discerned at the common carotid artery bifurcation on the right side . as a result , a detailed examination of the patient was made at the radiodiagnostics department of the comprehensive cancer centre in gliwice . the radiological examination showed a carotid body paraganglioma of 45    32    24  mm on the right side ( fig . 4a mr of the neck , frontal section : tumour in the carotid bifurcation , of the type of paraganglioma , on the right side . b mr of the neck , axial section : tumour in the parapharyngeal space on the right side , of the type of paraganglioma a mr of the neck , frontal section : tumour in the carotid bifurcation , of the type of paraganglioma , on the right side . b mr of the neck , axial section : tumour in the parapharyngeal space on the right side , of the type of paraganglioma the tumour can be seen in the right carotid space , in the right common carotid artery ( cca ) bifurcation into the internal carotid artery ( ica ) and the external carotid artery . salt and pepper  signal pattern of the tumour is visible in t2-weighted images . time signal intensive curves calculated from the tumour , cca , ica appear to be of the same shape , maximum value of the signal intensity and maximum contrast enhancement at the same time . there are irregular no - signal spots in t2 in the lesion , which may be consistent with haemosiderin . the tumour models and translocates outwards the neighbouring vascular structures without infiltrating them ; it models the parapharyngeal space and the right - sided wall of the pharynx , as well as to some extent the pterygeal muscles . the upper pole of the tumour is adjacent to the cranial basis near the carotid canal inlet , without traces of infiltration . the posterior part of the tumour leans against the i and ii vertebra arches on the space of about 1.5  cm , without traces of infiltration . the lower pole of the tumour is located about 2  cm above the division of the common carotid artery . laboratory testing of the noradrenaline level , adrenaline in blood and hva in the 24-h urine collection failed to give evidence of catecholamine production by the paraganglioma . three weeks after the surgery of the haemangioblastoma of the spinal cord the patient was discharged from hospital in good overall condition . herein we describe a rare case of carotid body paraganglioma in a woman with von hippel  lindau disease , caused by the n131k mutation in the vhl gene . the n131k is a rare missense mutation of the vhl gene . to date , it has been reported only once , in a family affected with vhl type 2 disease ( vhl with pheochromocytoma ) . however , only specific missense mutations are associated with pheochromocytoma  those mutations which map to protein binding sites of pvhl and which are predicted to cause local protein defects . the current case report of carotid body paraganglioma in patient with the 393c > a ( n131k ) missense mutation , further supports association of this mutation and vhl disease type 2 , and suggests its correlation with susceptibility to tumours situated extrarenally . vhl kindreds with pheochromocytoma - associated missense mutations require careful surveillance for pheochromocytoma as this is frequently the first manifestation . therefore , the correlation between the 393c > a ( n131k ) missense mutation and vhl type 2 may be useful in genetic counselling . on admission to the hospital , the patient could not see in her left eye because of retinal angiomatosis ; she suffered from renal cysts , haemangioblastoma near the fissura chorioidea on the right side and she had symptoms of a tumour of spinal cord . the retinal angioma found in the patient occurs in over 50% of vhl patients , often leading to blindness in the eye unless treated with laser therapy or cryocoagulation , preferably in the asymptomatic period . the patient was referred to the department of neurosurgery because of the intramedullary tumour at c5/c6 . the lesion caused pain in the upper right limb and a slight paresis of both right limbs . pain is reported to be the most frequent symptom of haemangioblastoma of the spinal cord . during the operation , it was discovered that the tumour reached the subarachnoid space of the dorsal surface of the spinal cord , and was connected to root c5 on the right side , which may have been the reason for pains in the upper right limb . lindau disease usually reach the dorsal surface of the medulla / spinal cord has already been reported by other authors [ 2 , 15 , 16 ] . the haemangioblastoma was accompanied by the syrinx much larger in size than the tumour itself , which might have been responsible for the numbness of the lower limbs . according to wanebo , the symptoms of vhl disease with haemangioblastoma of the spinal cord are most often caused by the syrinx and not by the tumour itself . haemangioblastomas of the spinal cord , both the ones occurring sporadically and the ones accompanying vhl disease , are usually of small size , and the prognosis in the case of surgical treatment is favourable [ 15 , 18 ] . the tumour was resected totally . after a total resection of heamangioblastoma in vhl patients , one can not exclude , however , the possibility of developing new angiomas in new locations . lindau disease , a tumour of the medullar layer of the adrenal gland of the pheochromocytoma type occurs in 1035% of cases [ 4 , 10 ] . lesions of the type of paraganglioma , localized extrarenally , are extremely rare [ 46 , 19 ] . in the patient , a large lesion was found to originate in the carotid body and situated at the carotid bifurcation , on the right side . according to the radiological findings , the tumour compressed the wall of the pharynx and it displaced the neighbouring vascular structures outwards giving no clinical symptoms . the tumour is hormonally inactive ; it was not joined to the cervical roots and it did not infiltrate the intervertebral foramen . in view of the absence of ailment , the patient currently refuses to submit to surgical treatment of the paraganglioma . report that the frequency of occurrence of surgically treated paragangliomas of the head and the neck in the netherlands comes to one case per one million inhabitants annually . in the autopsy material , therefore , a conclusion can be drawn that paragangliomas of the head and the neck fail to produce clinical symptoms and consequently they are not treated surgically . this is reflected in the case of the patient . unlike the paragangliomas of the adrenal medulla , the paragangliomas of the head and the neck usually do not show endocrinal function . that is why the paragangliomas growing in the neck develop slowly , giving no clinical symptoms for a long time . the current case of carotid body paraganglioma in patient with the 393c > a ( n131k ) missense mutation in the vhl gene , supports association of this specific mutation with vhl disease type 2 , and suggests its correlation with susceptibility to paragangliomas . vhl kindreds with pheochromocytoma - associated missense mutations require careful surveillance for pheochromocytoma as this is frequently the first manifestation . therefore , a correlation between the 393c > a ( n131k ) missense mutation and vhl type 2 may be useful in genetic counselling .
the article describes paraganglioma case in woman with von hippel  lindau disease . 
 she was found to be a carrier of a rare germline mutation in the vhl gene ( 393c > a ; n131k ) . 
 the patient developed large , untypical for von hippel 
 lindau disease , carotid body paraganglioma at the common carotid artery bifurcation . 
 the carotid body paraganglioma coexisted with the haemangioblastoma situated intramedullary in region c5/c6 . 
 the haemangioblastoma reached the right - sided dorsal part of the spinal cord in section c5/c6 . 
 it produced radicular symptoms within c5/c6 , followed by the later paresis of the right limbs . 
 the haemangioblastoma was resected completely . 
 twelve months after the operation , the spinal symptoms receded and the carotid body paraganglioma still was asymptomatic . 
 the current case of carotid body paraganglioma in patient with the 393c > a ( n131k ) missense mutation in the vhl gene , supports association of this specific mutation and vhl disease type 2 , and suggests its correlation with susceptibility to paragangliomas .