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Intracardiac pheochrornocytoma with dual coronary blood supply: case report and literature review
Cardiovascular
Vol. 3, No. 5, pp. 557-561, 199.5 Copyright @ 1995 Elsevier Science Ltd Printed in Great Britain. All rights reserved O9h7-21OWYS $lO.OO + 0.00 Surgery,
--.-.-_
-
. .._”
Intracardiac pheochromocytomaw&h dual coronary blood supply: casereport and lit;erature review P. J. Fitzgerald, T. A. Ports, M. D. Cheitlin, D. J. Magiiligan* and J. B. Tyrrell+ Department of Medicine, Cardiology Division ‘; Division of Endocrinollogy, and the Department of Surgery, *Division of Cardiovascular Surgery, Unive&ty of California, San Francisco, San Franciscco,iJl 9414.3 USA
An intracardiac pheochromocytoma is extremely rare. This patient first presented postpartum at age 28 with clinical signs, symptoms and biochemical evidence suspicious for the diagnosis of pheochromocytoma. Multiple radiologic studies and laparotomy failed to confirm the diagn&s. Some 20 years later the patient presented with complaints of chest pain, palpitations, and flushing. Cardiac catheterization demonstrated a ‘tumor blush’ superior to the left atrium with a blood supply derived from the coronary arteries. Open-heart surgery was performed and the tumor successfully removed.
Keywords: pheochromocytoma, intracardiac tumor, paraganglioma -
Case report A 29-year-old white woman delivered her first child in the summer of 1968. During the eighth month of pregnancy she noted episodes of shortness of breath and dizziness. These symptoms were associated with a nervous feeling and occasional night sweats. On several subsequent clinic visits her blood pressure was noted to be elevated, and in her ninth month she developed proteinuria and lower-extremity edema. Her delivery was complicated by extremely high blood pressure which persisted postpartum and was treated with methyldopa (Aldomet). Her blood pressure by 1 week postpartum was well controlled and the patient was discharged without antihypertensive medication. She presented 6 months later with complaints of bifrontal headaches, shortness of breath, visual changes, night sweats, facial flushing, palpitations and a feeling of ‘episodes of tension’. The patient noted that these symptoms could occasionally be exacerbated by deepbreathing and/or arm lifting for extended periods of time. Her past medical history was unremarkable. Her family history was significant, her mother having been diagnosed as hypertensive at age 52 and having a tumor (type unknown) removed at age 55. There was no family history of neurofibromatosis and neurocutaneous diseases.
Correspondence to: DC I’. J. Fitzgerald, Center Cardiovascular Interventions, Stanford University Room H.3754, Stanford, CA 94025, USA
for Research in Medical Center,
CARDIOVASCULAR SURGERY OCTOBER 1995 VOL 3 NO 5
Physical examination at that time was normal; electrolyte, hematologic studies and chest radiography and electrocardiography were also normal. Follow-up clinic visits demonstrated episodic hypertension (range 140/90-220/130, equal in all extremities) and mildly elevated catecholamines. The patient had two Regitine tests that were positive. A presumptive diagnosis of pheochromocytoma was made and the patient was started on dibenzyline. One year later she underwent laparotomy and no evidence of tumor was found. The patient, was maintained on alpha-blockade until 1987 (age 47) when she presented again with complaints of episodic headaches, blurry vision, night sweats and flushing. In addition, the patient noted shormess of breath and mild angina1 symptoms on exertion. Her physical examination was unchanged with the exception of an S,; an electrocardiogram was suggestive of left ventricular hypertrophy. At the time her nwepinephrine levels were markedly elevated at 9195plJml and epinephrine levels only slightly elevated at 84pgIml (Table 2). Routine serum studies were notable for an elevated fasting glucose of 12.2 mmolfi and an elevated cholesterol of 8.8 mmolfl. In 1988 a thoracic examination by magnetic resonance imaging showed a 6.0 x 2.0 x 2.8-cm massin the heart, immediately superior to the left atrium and inferior to the markedly displaced right pulmonary artery. A metaiodobenzylguanidine MIBC scan demonstrated abnormal uptake adjacent to the left atrium. The patient underwent cardiac catheterization which showed normal right-sided pressures but increased left-ventricular end-diastolic pressure. ‘fhr coronary ss7
Cardiac case reports Table 1 Summary of the patients catecholamine levels (pg/ml) before and after surgical removal of the pheochromocytoma Time relative to surgery
Catecholamine* Total (120-450) Norepinephrine (110-410) Epinephrine (<50) Dopamine (<30)
8 months preoperative’
1 day preoperative*
5 days postoperative
9419
69144
568
9195
68940
376
84
82
76
139
122
116
ml before surgery but fell rapidly to normal levels by 5 days postoperatively (Table 1). Histologic study confirmed the diagnosis of chromaffin-positive extramedullary paraganglioma (pheochromocytoma). The patient was normotensive and discharged 8 days after surgery. At 1 year she remains symptom-free and normotensive.
*Values in parentheses indicate normal range or level (pg/ml); ‘alphablocker treatment: *no alpha-blocker treatment for 2 months
angiogram showed evidence of extensive tumor vasculatization, represented as a ‘tumor blush’ with the blood supply originating from the right (Figure 1) and left (Figure 2) coronary circulation. There was no evidence of intrinsic coronary obstruction. The patient underwent open-heart surgery in the summer of 1989 with dissection and removal of the tumor from the left atria1 wall and coronary vasculature. Figure 3 shows the tumor (arrowed) being dissected from surrounding cardiac structures. The patient’s norepinephrine levels had risen to > 60 000 pg/
a
Figure 1 Angiogram at a 30” right anterior oblique orientation demonstrating ‘tumor blush’ (solid arrows) arising from the right coronary amly
Figure 2 a 60” left anterior oblique projection depicting the tumor vascular supply derived in part from the left coronary artery (solid arrows). b 30” right anterior oblique projection demonstrating abnormal vessels arising from both the left anterior descending and circumflex arteries (open arrows)
CARDIOVASCULAR SURGERY OCTOBER 199s VOL 3 NO 5
Figure 3 Photograph (cranial view) of the tumor (arrowed) being dissected from the atria1 wall and adjacent tissue structures. The ventricle (V) is being retracted and the forceps points to a large vessel supplying the tumor
Discus&ionand literature review Paraganglioma
Paraganlionic tissue, first described by Kohnl in the year 1900, is a collection of neuroepithelial cells that occur in relationship to the sympathetic nervous system and branchial arch artery. These cells are of neural crest origin and are classified histologically as chromaffin (catecholamine secreting) and non-chromaffin (noncatecholamine secreting). Only in rare instances has non-chromaffin tissue been found to secrete catecholamine2. The highest concentration of chromaffin tissue is located in the adrenal medulla, but the tissue can also be found in other locations such as the thoracolumbar and para-aortic areas. Non-chromaffin tissue is distributed sparsely throughout the body including the carotid body, glomus jugulare, aortic arch and several other areas associated with the parasympathetic nervous system. Tumors arising from this tissue (paragangiomas) of the chromaffin type are referred to as pheochromocytomas and those of non-chromaffin tissue are called chemodectomas. There have been reports in the literature describing pheochromocytomas and chemodectomas in a wide variety of locations throughout the body3, but the heart is one of the rarest locations. Pheochromocytoma
Pheochromocytoma is a catecholamine-producing tumor that is an uncommon yet dramatic cause of secondary hypertension. The incidence of pheochromocytoma is estimated to be O.l-2% of all patients with hypertension. The adrenal medulla accounts for >95% of all reported pheochromocytomas; only 2% of these lesions are located above the diaphragm. Of those located in the mediastinum, 75% are found in the CARDIOVASCULAR SURGERY OCTOBER 1995 VOL 3 NO 5
posterior compartment4. The posterior location may be prevalent because of the association with the large para-aortic sympathetic chain. The middle compartment contains only a few small clusters of chromaffin tissue that could potentially provide a sire for tumor development. The biochemical end-product of chromaffin cell synthesis of catecholamines is norepinephrine. However, most medullary pheochromocytomas secrete high levels of epinephrine5. The enzyme phenylethanolamine-N-methyltransferase (PNMT) is found in large concentrations in the adrenal gland and facilitates methylation of norepinephrine resulting in predominant epinephrine secretion. However, extramedullary tissue contains very little PNMT and as a result these tumors primarily secrete norepinephrine and very rarely epinephrine6. This may in part explain why cardiac pheochromocytomas can often go undiagnosed for many years and exhibit less dramatic clinical features compared with those of adrenal pheochromocytomas. Chemodectoma Chemodectomas are related to the parasympathetic nervous system and have been described in a wide distribution throughout the body. Gopalakrishnan and colleagues’ reported a case of a chemodectoma overlying the left ventricle in a patient who presented with complaints of retrosternal chest discomfort. In this case cardiac angiography revealed a highly vascular tumor which was supplied by the coronary circulation. Hui et al.* reported a chemodectoma within the left atrium in a patient who complained of palpitations and who had a history of benign neck paragangliomas. Catheterization demonstrated that the tumor exclusively received its blood supply from the coronary circulation, Levi and co-workers’ reported a case of chemodectoma in the right ventricular outflow tract that deformed the mitral valve annulus and required surgical debulking and mitral valve replacement. In most cases,chemodectomas cause symptoms related to their size rather than chemical activity. Conversely, pheochromocytomas in the middle mediastinum can not only cause dramatic systemic symptoms by their episodic catecholamine release, but can also cause structural deformities within the pericardium”> ’ *. Intracardiac
pheochromocytomas
To date there have been 45 reported cases of intrathoracic pheochromocytomas’2- .51wrth the earliest casereported in 192412. The majority of these have been located in the posterior mediastinum in association with the paravertebral sympathetic chain. Before 1984 there had only been four reported casesof such a tumor in the middle mediastinum. Two of these were located in association with the left atrium’“, Ia, one in the interatrial groove*’ and another was attached to the posterior aspect of both the right and left atrium ’ ‘. 559
Cardiaccaserepor&Table 2
Summary of reported cases of intracardiac pheochromocytoma
Year
Reference
Location
Diagnosis
Outcome
1988 1970 1974 1982 1984 1985*
Engelman and Hammond’ McNeil etal.14 Wilson eta/.17 Vocci eta/.16 Hodgson eta/.lg Orringer eta/!
1987
Gross eta/”
Left atrium Left atrium lnteratrial groove Posterior left/right atrium lnteratrial septum (i) Left atrium (ii) Left atrium (iii) Left atrium (iv) Inter-ventricular groove and aorbc root Left ventricular wall
Autopsy CXR. pulmonary angiography Venous sampling MIBG Autopsy MIBG MIBG MIBG MIBG MIBG
Dead Survived Survived Survived Dead Survived Survived Dead Survived Dead
*This study included an additional four cases, all occurring in the left atrium, but details concerning diagnosis and outcomes were not reported. CXR. Chest X-ray; MING. metaiodobenzylguanidine
Since 1984, 10 additional cases of intracardiac pheochromocytomas have been published. Orringer and co-workers4 reported the largest series of intracardiac catecholamine-producing tumors. Their series consisted of eight individuals with this cardiac tumor of which six were attached to the left atrium. In addition angiography demonstrated that these tumors derived their blood sup ly exclusively from the coronary arteries. Gross et a1.l I?reported an intracardiac pheochromocytoma within the left ventricular wall between the left anterior descending and left circumflex artery. They postulated that this tumor arose from the chromaffin cells related to the left coronary sympathetic plexus. Hodgson and colleagues”, reported such a lesion located in the atria1 septum found at autopsy that eluded diagnosis for 5 years. Table 2 lists a summary of the 14 cases of intracardiac pheochromocytoma previously described in the literature. The most common location for tumor development is the left atrium, although the explanation for this preferential location is unclear. One possibility may be the close proximity of paraganglionic cell nests to the left atrium. Glenner and Grimley2’ have classified extramedullary paraganglionic tumors on the basis of anatomic distribution, innervation and microscopic structure. Those families include branchiometric, intravagal, aorticosympathetic and visceral autonomic paraganglia. Each of these cell nests is capable of acting as a potential site for pheochromocytoma tumor development. Included in the branchiomeric and intravagal paraganglionic families are the aorticopulmonary and coronary paraganglia that are in close proximity to the left atrium. These cell clusters are at the level of the embryonic fourth and fifth branchial arch. The aorticopulmonary paraganglia are distributed in a region limited by the right pulmonary artery and ductus arteriosus, superior to the pulmonary artery bifurcation and just inferior to the aortic arch. The coronary paraganglia are located in the connective tissue between the ascending aorta and the pulmonary trunk in either s80
dorsal or ventral positions. In adults, the blood supply to these paraganglia is supplied exclusively from the left coronary artery. It is interesting to note that in the present case as well as several others, the blood supply to the cardiac pheochromocytoma was from the coronary vessels. Other potential sites of origin for cardiac-associated pheochromocytoma include the migration from the aorticosympathetic paraganglia or the visceral-autonomic paraganglionic family which occur in association with visceral organs such as the left atrium. These are attractive candidates for possible tumor origin since in most cases the lesions were tightly attached to and in some cases growing within the left atrium. Medical treatment with alpha-blockade in combination with beta-blockade or catecholamine synthesis inhibitors has been shown to work in the short term, especially in preparation for surgical intervention. Because extramedullary pheochromocytomas generally produced high levels of norepinephrine, the direct cardiac effect is minimal compared with .the effect of norepinephrine. This could potentially permit a longer course of medical management for intracardiac pheochromocytomas. Removal of an intracardiac pheochromocytoma is complicated by the need for delicate dissection, since the tumor is usually attached to various intracardiac structures. Cardiopulmonary bypass is mandatory in this situation to avoid life-threatening arrhythmial’ and hemorrhage4. Because pheochromocytomas are extremely vascular, careful dissection is necessary to delineate the coronary circulation. In the case presented here, the angiogram showed that the tumor derived its main blood supply from all three main coronary branches. In two reported cases4’18 coronary bypass was necessary because of coronary compromise during dissection of the dual vascular supply between the tumor and the myocardium. In addition, adherence of the tumor to the myocardium may add complexity to the surgical procedure. Several reported cases required CARDlOVAWJLAt? SURGERY OCTOBER 1BBS VOL 3 NO 5
partial myotomy due to ingrowth of these tumors within the myocardium. In conclusion, the present case demonstrates some of the characteristic features of this rare but intriguing condition of an intracardiac pheochromocytoma. These tumors, like most extramedullary pheochromocytomas, predominantly secrete norepinephrine and can often go undiagnosed for many years. They tend to be located within the left atrium, presumably originating from small clusters of chromaffin tissue located in close proximity to or within the left atrium. Intracardiac pheochromocytomas are highly vascular, their blood supply being derived almost exclusively from the coronary circulation. These tumors can not only cause symptoms related to their size and chemical activity but potentially can also cause angina as the tumor competes with the myocardium for the coronary blood supply. The surgical removal of such a tumor is complex, mandating cardiopulmonary bypass, along with careful dissection of the tumor free of the myocardium and coronary structures.
5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17.
References 1. 2. 3. 4.
Kohn A. Uben den Bau Und doe Entwicklung der Sug. Carotiddruse. Arch fur Mikr Anat 1900; 56: 81-148. Attia A, Golden RL, Ziffer H. Nonchromaffin-staining functional tumor of the organs of Zuckerkandl. N Engl J Med 1961; 264: 2 130-1.-. Ram CVS, Venkata SC. Pheochromocytoma. Cardiology Clinics 1988; 6: 517-35. Orringer MB, Sisson JC, Glazer G et al. Surgical treatment of cardiac pheochromocytomas. .I Thoruc Cardiouasc Surg 1985; 89: 753-7.
CARDIOVASCULAR SURGERY OCTOBER 199s VOL 3 NO S
18. 19. 20.
von Euler US, Strom G. Present status of diagnosis and treatment of pheochromocytoma. Circulation 1957; XV: 5-13. Engelman K, Hammond WG. Adrenaline producrion by an intrathoracic pheochromocytoma. Luncet 1968: I: 609-t 1. GopalakrishnHn R, Ticzbn AR, Crux PA ~?t al. Cardiac Strrg oaraeanelioma ichemodectoma). I Thornr Czdiortzss ‘1978”; 7:: 183-i. Hui G, Mcallister HA, Angelini I’. Left atriai paraganglioma: Report of a case and review of the literature, Am Heurt1 1987; 113: 1230-4. Levi B, Cain AS, Dorab WE. Coronarv paraganglioma. Clin Curdiol 1982; 5: 505-10. Besterman E. Bromlev LL. Peart WS. An mtraper!cardial phaeochromo’qtoma. & He&t J 1974; 36: 318-20. Saad MF. Frazier OH, Hickey RC, Samaan NC. Intraperlcardial pheochromacytoma. Am 1 h&d 1983; 75: 371-6, Miller IW. Ein Paraeamzlioma des Brustsvmpathlcur. Zbl ullg Path 1425; 25: SS-!% ” Peiper Von HJ, Golestan C. Intrathorakaies Phnochromozytom. Thorax Chir 1963; 10: 517-26. McNeil AD, Groden BM, Neville AM. Inrratboracic phcochromocytoma. BY / Surg 1970; 57: 457-62. Shariro B, Sisson J, Kalff V et ~1. The location of middle mediastinal pheochromocytomas. 1 I%nrizc C~rrfiovssc Surg 1984; 87: 814-20. Vocci V, Olsen H, Beilin L. A mahgnant primary cardiac pheochromocytoma. Surgical Rounds 1993; 5” 88.-90. Wilson AC, Bennett RC, Niall JF, Clarebrough JK, Qoyle AE, Louis WJ. An unusual case of intrathoracic pharochromocytoma. Aust NZ J Surg 1974; 44: 27-32. Gross JL, Azenedo MJ, Ludwig EB, Santos A, Pinto JF. Cardiac pheochromocytoma. Am J Med 1987; 83: 1013. Hodgson SF, Sheps SG, Subramanian R, Ix J1’. Carney JA. Catecholamine-secreting paraganglioma of the interatrial septum. Am J Med 1984; 77: 157-61. Glenner GG, Grimley PM. Tumors of extra-medullary paraganglionic system (including chemoreceptorsj. Armed Forces Institute of Pathology/American Cancer Socjety, Washington DC, 1974; 9: 13-38.
Paper accepted 7 September 1994
S61
Vol. 3, No. 5, pp. 557-561, 199.5 Copyright @ 1995 Elsevier Science Ltd Printed in Great Britain. All rights reserved O9h7-21OWYS $lO.OO + 0.00 Surgery,
--.-.-_
-
. .._”
Intracardiac pheochromocytomaw&h dual coronary blood supply: casereport and lit;erature review P. J. Fitzgerald, T. A. Ports, M. D. Cheitlin, D. J. Magiiligan* and J. B. Tyrrell+ Department of Medicine, Cardiology Division ‘; Division of Endocrinollogy, and the Department of Surgery, *Division of Cardiovascular Surgery, Unive&ty of California, San Francisco, San Franciscco,iJl 9414.3 USA
An intracardiac pheochromocytoma is extremely rare. This patient first presented postpartum at age 28 with clinical signs, symptoms and biochemical evidence suspicious for the diagnosis of pheochromocytoma. Multiple radiologic studies and laparotomy failed to confirm the diagn&s. Some 20 years later the patient presented with complaints of chest pain, palpitations, and flushing. Cardiac catheterization demonstrated a ‘tumor blush’ superior to the left atrium with a blood supply derived from the coronary arteries. Open-heart surgery was performed and the tumor successfully removed.
Keywords: pheochromocytoma, intracardiac tumor, paraganglioma -
Case report A 29-year-old white woman delivered her first child in the summer of 1968. During the eighth month of pregnancy she noted episodes of shortness of breath and dizziness. These symptoms were associated with a nervous feeling and occasional night sweats. On several subsequent clinic visits her blood pressure was noted to be elevated, and in her ninth month she developed proteinuria and lower-extremity edema. Her delivery was complicated by extremely high blood pressure which persisted postpartum and was treated with methyldopa (Aldomet). Her blood pressure by 1 week postpartum was well controlled and the patient was discharged without antihypertensive medication. She presented 6 months later with complaints of bifrontal headaches, shortness of breath, visual changes, night sweats, facial flushing, palpitations and a feeling of ‘episodes of tension’. The patient noted that these symptoms could occasionally be exacerbated by deepbreathing and/or arm lifting for extended periods of time. Her past medical history was unremarkable. Her family history was significant, her mother having been diagnosed as hypertensive at age 52 and having a tumor (type unknown) removed at age 55. There was no family history of neurofibromatosis and neurocutaneous diseases.
Correspondence to: DC I’. J. Fitzgerald, Center Cardiovascular Interventions, Stanford University Room H.3754, Stanford, CA 94025, USA
for Research in Medical Center,
CARDIOVASCULAR SURGERY OCTOBER 1995 VOL 3 NO 5
Physical examination at that time was normal; electrolyte, hematologic studies and chest radiography and electrocardiography were also normal. Follow-up clinic visits demonstrated episodic hypertension (range 140/90-220/130, equal in all extremities) and mildly elevated catecholamines. The patient had two Regitine tests that were positive. A presumptive diagnosis of pheochromocytoma was made and the patient was started on dibenzyline. One year later she underwent laparotomy and no evidence of tumor was found. The patient, was maintained on alpha-blockade until 1987 (age 47) when she presented again with complaints of episodic headaches, blurry vision, night sweats and flushing. In addition, the patient noted shormess of breath and mild angina1 symptoms on exertion. Her physical examination was unchanged with the exception of an S,; an electrocardiogram was suggestive of left ventricular hypertrophy. At the time her nwepinephrine levels were markedly elevated at 9195plJml and epinephrine levels only slightly elevated at 84pgIml (Table 2). Routine serum studies were notable for an elevated fasting glucose of 12.2 mmolfi and an elevated cholesterol of 8.8 mmolfl. In 1988 a thoracic examination by magnetic resonance imaging showed a 6.0 x 2.0 x 2.8-cm massin the heart, immediately superior to the left atrium and inferior to the markedly displaced right pulmonary artery. A metaiodobenzylguanidine MIBC scan demonstrated abnormal uptake adjacent to the left atrium. The patient underwent cardiac catheterization which showed normal right-sided pressures but increased left-ventricular end-diastolic pressure. ‘fhr coronary ss7
Cardiac case reports Table 1 Summary of the patients catecholamine levels (pg/ml) before and after surgical removal of the pheochromocytoma Time relative to surgery
Catecholamine* Total (120-450) Norepinephrine (110-410) Epinephrine (<50) Dopamine (<30)
8 months preoperative’
1 day preoperative*
5 days postoperative
9419
69144
568
9195
68940
376
84
82
76
139
122
116
ml before surgery but fell rapidly to normal levels by 5 days postoperatively (Table 1). Histologic study confirmed the diagnosis of chromaffin-positive extramedullary paraganglioma (pheochromocytoma). The patient was normotensive and discharged 8 days after surgery. At 1 year she remains symptom-free and normotensive.
*Values in parentheses indicate normal range or level (pg/ml); ‘alphablocker treatment: *no alpha-blocker treatment for 2 months
angiogram showed evidence of extensive tumor vasculatization, represented as a ‘tumor blush’ with the blood supply originating from the right (Figure 1) and left (Figure 2) coronary circulation. There was no evidence of intrinsic coronary obstruction. The patient underwent open-heart surgery in the summer of 1989 with dissection and removal of the tumor from the left atria1 wall and coronary vasculature. Figure 3 shows the tumor (arrowed) being dissected from surrounding cardiac structures. The patient’s norepinephrine levels had risen to > 60 000 pg/
a
Figure 1 Angiogram at a 30” right anterior oblique orientation demonstrating ‘tumor blush’ (solid arrows) arising from the right coronary amly
Figure 2 a 60” left anterior oblique projection depicting the tumor vascular supply derived in part from the left coronary artery (solid arrows). b 30” right anterior oblique projection demonstrating abnormal vessels arising from both the left anterior descending and circumflex arteries (open arrows)
CARDIOVASCULAR SURGERY OCTOBER 199s VOL 3 NO 5
Figure 3 Photograph (cranial view) of the tumor (arrowed) being dissected from the atria1 wall and adjacent tissue structures. The ventricle (V) is being retracted and the forceps points to a large vessel supplying the tumor
Discus&ionand literature review Paraganglioma
Paraganlionic tissue, first described by Kohnl in the year 1900, is a collection of neuroepithelial cells that occur in relationship to the sympathetic nervous system and branchial arch artery. These cells are of neural crest origin and are classified histologically as chromaffin (catecholamine secreting) and non-chromaffin (noncatecholamine secreting). Only in rare instances has non-chromaffin tissue been found to secrete catecholamine2. The highest concentration of chromaffin tissue is located in the adrenal medulla, but the tissue can also be found in other locations such as the thoracolumbar and para-aortic areas. Non-chromaffin tissue is distributed sparsely throughout the body including the carotid body, glomus jugulare, aortic arch and several other areas associated with the parasympathetic nervous system. Tumors arising from this tissue (paragangiomas) of the chromaffin type are referred to as pheochromocytomas and those of non-chromaffin tissue are called chemodectomas. There have been reports in the literature describing pheochromocytomas and chemodectomas in a wide variety of locations throughout the body3, but the heart is one of the rarest locations. Pheochromocytoma
Pheochromocytoma is a catecholamine-producing tumor that is an uncommon yet dramatic cause of secondary hypertension. The incidence of pheochromocytoma is estimated to be O.l-2% of all patients with hypertension. The adrenal medulla accounts for >95% of all reported pheochromocytomas; only 2% of these lesions are located above the diaphragm. Of those located in the mediastinum, 75% are found in the CARDIOVASCULAR SURGERY OCTOBER 1995 VOL 3 NO 5
posterior compartment4. The posterior location may be prevalent because of the association with the large para-aortic sympathetic chain. The middle compartment contains only a few small clusters of chromaffin tissue that could potentially provide a sire for tumor development. The biochemical end-product of chromaffin cell synthesis of catecholamines is norepinephrine. However, most medullary pheochromocytomas secrete high levels of epinephrine5. The enzyme phenylethanolamine-N-methyltransferase (PNMT) is found in large concentrations in the adrenal gland and facilitates methylation of norepinephrine resulting in predominant epinephrine secretion. However, extramedullary tissue contains very little PNMT and as a result these tumors primarily secrete norepinephrine and very rarely epinephrine6. This may in part explain why cardiac pheochromocytomas can often go undiagnosed for many years and exhibit less dramatic clinical features compared with those of adrenal pheochromocytomas. Chemodectoma Chemodectomas are related to the parasympathetic nervous system and have been described in a wide distribution throughout the body. Gopalakrishnan and colleagues’ reported a case of a chemodectoma overlying the left ventricle in a patient who presented with complaints of retrosternal chest discomfort. In this case cardiac angiography revealed a highly vascular tumor which was supplied by the coronary circulation. Hui et al.* reported a chemodectoma within the left atrium in a patient who complained of palpitations and who had a history of benign neck paragangliomas. Catheterization demonstrated that the tumor exclusively received its blood supply from the coronary circulation, Levi and co-workers’ reported a case of chemodectoma in the right ventricular outflow tract that deformed the mitral valve annulus and required surgical debulking and mitral valve replacement. In most cases,chemodectomas cause symptoms related to their size rather than chemical activity. Conversely, pheochromocytomas in the middle mediastinum can not only cause dramatic systemic symptoms by their episodic catecholamine release, but can also cause structural deformities within the pericardium”> ’ *. Intracardiac
pheochromocytomas
To date there have been 45 reported cases of intrathoracic pheochromocytomas’2- .51wrth the earliest casereported in 192412. The majority of these have been located in the posterior mediastinum in association with the paravertebral sympathetic chain. Before 1984 there had only been four reported casesof such a tumor in the middle mediastinum. Two of these were located in association with the left atrium’“, Ia, one in the interatrial groove*’ and another was attached to the posterior aspect of both the right and left atrium ’ ‘. 559
Cardiaccaserepor&Table 2
Summary of reported cases of intracardiac pheochromocytoma
Year
Reference
Location
Diagnosis
Outcome
1988 1970 1974 1982 1984 1985*
Engelman and Hammond’ McNeil etal.14 Wilson eta/.17 Vocci eta/.16 Hodgson eta/.lg Orringer eta/!
1987
Gross eta/”
Left atrium Left atrium lnteratrial groove Posterior left/right atrium lnteratrial septum (i) Left atrium (ii) Left atrium (iii) Left atrium (iv) Inter-ventricular groove and aorbc root Left ventricular wall
Autopsy CXR. pulmonary angiography Venous sampling MIBG Autopsy MIBG MIBG MIBG MIBG MIBG
Dead Survived Survived Survived Dead Survived Survived Dead Survived Dead
*This study included an additional four cases, all occurring in the left atrium, but details concerning diagnosis and outcomes were not reported. CXR. Chest X-ray; MING. metaiodobenzylguanidine
Since 1984, 10 additional cases of intracardiac pheochromocytomas have been published. Orringer and co-workers4 reported the largest series of intracardiac catecholamine-producing tumors. Their series consisted of eight individuals with this cardiac tumor of which six were attached to the left atrium. In addition angiography demonstrated that these tumors derived their blood sup ly exclusively from the coronary arteries. Gross et a1.l I?reported an intracardiac pheochromocytoma within the left ventricular wall between the left anterior descending and left circumflex artery. They postulated that this tumor arose from the chromaffin cells related to the left coronary sympathetic plexus. Hodgson and colleagues”, reported such a lesion located in the atria1 septum found at autopsy that eluded diagnosis for 5 years. Table 2 lists a summary of the 14 cases of intracardiac pheochromocytoma previously described in the literature. The most common location for tumor development is the left atrium, although the explanation for this preferential location is unclear. One possibility may be the close proximity of paraganglionic cell nests to the left atrium. Glenner and Grimley2’ have classified extramedullary paraganglionic tumors on the basis of anatomic distribution, innervation and microscopic structure. Those families include branchiometric, intravagal, aorticosympathetic and visceral autonomic paraganglia. Each of these cell nests is capable of acting as a potential site for pheochromocytoma tumor development. Included in the branchiomeric and intravagal paraganglionic families are the aorticopulmonary and coronary paraganglia that are in close proximity to the left atrium. These cell clusters are at the level of the embryonic fourth and fifth branchial arch. The aorticopulmonary paraganglia are distributed in a region limited by the right pulmonary artery and ductus arteriosus, superior to the pulmonary artery bifurcation and just inferior to the aortic arch. The coronary paraganglia are located in the connective tissue between the ascending aorta and the pulmonary trunk in either s80
dorsal or ventral positions. In adults, the blood supply to these paraganglia is supplied exclusively from the left coronary artery. It is interesting to note that in the present case as well as several others, the blood supply to the cardiac pheochromocytoma was from the coronary vessels. Other potential sites of origin for cardiac-associated pheochromocytoma include the migration from the aorticosympathetic paraganglia or the visceral-autonomic paraganglionic family which occur in association with visceral organs such as the left atrium. These are attractive candidates for possible tumor origin since in most cases the lesions were tightly attached to and in some cases growing within the left atrium. Medical treatment with alpha-blockade in combination with beta-blockade or catecholamine synthesis inhibitors has been shown to work in the short term, especially in preparation for surgical intervention. Because extramedullary pheochromocytomas generally produced high levels of norepinephrine, the direct cardiac effect is minimal compared with .the effect of norepinephrine. This could potentially permit a longer course of medical management for intracardiac pheochromocytomas. Removal of an intracardiac pheochromocytoma is complicated by the need for delicate dissection, since the tumor is usually attached to various intracardiac structures. Cardiopulmonary bypass is mandatory in this situation to avoid life-threatening arrhythmial’ and hemorrhage4. Because pheochromocytomas are extremely vascular, careful dissection is necessary to delineate the coronary circulation. In the case presented here, the angiogram showed that the tumor derived its main blood supply from all three main coronary branches. In two reported cases4’18 coronary bypass was necessary because of coronary compromise during dissection of the dual vascular supply between the tumor and the myocardium. In addition, adherence of the tumor to the myocardium may add complexity to the surgical procedure. Several reported cases required CARDlOVAWJLAt? SURGERY OCTOBER 1BBS VOL 3 NO 5
partial myotomy due to ingrowth of these tumors within the myocardium. In conclusion, the present case demonstrates some of the characteristic features of this rare but intriguing condition of an intracardiac pheochromocytoma. These tumors, like most extramedullary pheochromocytomas, predominantly secrete norepinephrine and can often go undiagnosed for many years. They tend to be located within the left atrium, presumably originating from small clusters of chromaffin tissue located in close proximity to or within the left atrium. Intracardiac pheochromocytomas are highly vascular, their blood supply being derived almost exclusively from the coronary circulation. These tumors can not only cause symptoms related to their size and chemical activity but potentially can also cause angina as the tumor competes with the myocardium for the coronary blood supply. The surgical removal of such a tumor is complex, mandating cardiopulmonary bypass, along with careful dissection of the tumor free of the myocardium and coronary structures.
5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17.
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Paper accepted 7 September 1994
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