Grand Rounds

Carotid Body Tumours

Intro

Tumours

Derived from neural crest cells

Called nonchromaffin paragangliomas

Slow growing tumours

Historical Background

Swiss anatomist Von Haller in 1743

Alfred Kohn coined term paraganglion

Renamed vascular glomus in early 20th century

1941, Guild described “glomic tissue”

Glenner and Grimley distingushed adrenal and extra-adrenal paraganglionma

CURRENTLY, PARAGANGLIOMA BASED ON ANATOMICAL LOCATION IS PROPER TERMINOLOGY (e.g. carotid paraganglioma, jugulotympanic paraganglioma)

Site

90% pheochromocytoma10% extra-adrenal– 85% abdomen– 12% thorax– 3% head and neck

Carotid body most common– Jugulotympanic– Vagal– Other

Shamblin Classification

Shamblin 1971

Type I– Localized easily resected

Type II– Adherent partially

surrounding vessels

Type III– Completely encased

carotids

70% are type II or III

Imaging

MRI / MRA / AngioVascular insight

Occult tumors-0.8 cm

T1, T1 post gad, T2, axial FLAIR, FSE T2

Skull base to thoracic inlet

All well

Patient goes home

Is it cancer ?

Local recurrence

Metastases seen to lungs, lymph nodes, and bones

Malignant nature cannot be predicted by microscopic characteristics, such as nuclear atypia and mitotic rate.

Determined by the presence of local invasion or distant metastasis,

Mets can be late

Zellballen

We don’t know

How quickly will it grow ?

No solid data

Reality is imaging will tell us

Imaging ?

CT

MRI

MRI angiogram

Angiography

U/S

Functional scans

Paragangliomas have somatostatin receptors

Stage disease

Guide therapy

Monitor response

May provide long term palliation

Otolaryngol Head Neck Surg 2000;122:358-62.

Bomanji JB et al. Middlesex

MIBI – I (123 / 131)MIBI similar to NA…..taken into chromaffrin cells….into

storage granulesBut PGL are non chromaffrin ?

They also express somatostatin receptorsThis can be confirmed histologically

Pentetreotide / octreotide – 111 and subsequent labeling with Y 90

How did I get it ?

GeneticsBad luckBad luckBad luck Vs

Hypoxia (10 times higher in high altitude African countries)

Sporadic vs Hereditary

Should we screen patients with sporadic head and neck paragangliomas for hereditary syndromes ?

M.D. Anderson

Jimenez C et al. 2006

The Journal Of Clinical Endocrinology and Metabolism Vol 91; (8) 2851 - 2858

7 genes known to cause hereditary paragangliomas or phaeochromocytomas

NF I VHL

RET MEN II

SDHD SDHC

SDHB

Specific to head and neck paragangliomas – PGL genes

Germline mutations in SDHB, SDHC and SDHD cause hereditary paragangliomas

SDHD (PGL 1) - Chromosome 11q23

SDHB (PGL 4) - Chromosome 1p36

SDHC (PGL 3) - Chromosome 1q21 (single German family ?? )

PGL (PGL 2) locus mapped to 11q13 in an extended Dutch family

These encode 3 subunits of MC II

Succinate dehydrogenase

Some families have hereditary paragangliomas

Mitochondrion

Plasma membrane

Mitochondria complex dysfunction

Mimics chronic hypoxia at a microscopic level

Functional hyperplasia

?? Loss of oncosuppression

What does the carotid body do ?

What will happen when its gone ?

Unilateral – nothing

Bilateral – Something ?

Anecdotal reports

Timmers HJ

Rare but known to occur in neck after RT for NPC

Dutch womanBilateral carotid body tumour (at same time)Immediate onset of hypertension

Reported in Ned Tijdschr 2001

Baroreflex sensitivity was significantly decreased

3 had orthostatic hypotension

When valsalva done vagal tone was down

Normocapnic ventilatory response to hypoxia was absent in all

Conclusion

In bilateral tumour resection we should tell patients about the risks of labile blood pressure

Timmers

Do I need pre operative embolisation ?

Transfemoral under angiographic control

Embolisation

Complications are rare.

Cerebrovascular accident due to rupture of an atheroma with the catheter. The rate is approximately 1 % in most centres.

Prior to using platinum coils for embolisation, polyvinyl alcohol particles were used and this was associated with stroke due to reflux into the internal carotid system during introduction and removal of the catheter.

Facial pain, trisimus and tonsillar ulceration have all been reported.

Type 1 – NO

Types 2 and 3 - Yes

Bakoyiannis KC et al. Int Angiol. 2006 Mar; 25 (1) :40 - 5

AthensPre operative embolisation not necessary10 year retrospective study11 patients 12 tumoursNone embolisedPerioperative mortality zero. Out of 9 grade III tumour, 1 had ICA injured

and vein grafted per op

Radiotherapy

Valdagni et al. Am J Clin Oncol.1990 Feb; 13 (1) :45-8

(Italy)Questioned this theory

13 Carotid body tumours had Rt (mean 52 Gy)

10 - only

3 - In addition

Local control (Subjective and objective ) in all

3/13 complete response

7/13 Some response

3/13 No change

Mayer et al Strahlenther Onkol 2000 Aug; 176 (8): 356 -60

Good as post op in malignant cases – postpone spreading

Eradicating existing nodal diseaseProlong local control

Vascular surgery and complications ?

Smith JJ / Netterville JL et alAnn Vasc Surg. 2006 Jul; 20

(4) : 435 - 9

Retrospective analysis 1990 – 2005Compared all CBR and CBR – vasc.71 tumours 16 needed vasc. Recon. (23 %)Type I – usually CBRType II / III where vasc. Recon neededCranial nerve damage was higher in recon.(x 2)

Thank you