Presentation of a Patient with an Unusual Composite Pheochromocytoma-Ganglioneuroblastoma

Iqra Javeed MD1, Arthur S Tischler MD2, Michael E Tarnoff MD3*, and Ronald M Lechan MD, PhD1

1Division of Endocrinology, Diabetes, and Metabolism, 2Department of Pathology, 3Department of SurgeryTufts Medical Center, Boston, Massachusetts

*Disclosure: Chief Medical Officer and full time employee, Covidien

Most pheochromocytomas are composed of only chromaffin cells. In rare cases, pheochromocytomas (PCCs) are associated with other tumors. These tumors are termed “composite” if they show the same embryologic origin as pheochromocytoma (the neural crest) or “mixed” if the associated tumor has a different embryologic origin from pheochromocytoma. Non-pheochromocytoma components found in the composite pheochromocytoma include ganglioneuroma, ganglioneuroblastoma, neuroblastoma, and malignant schwannoma. The frequency of composite adrenal tumors has been reported as ranging between 1% and 9% of pheochromocytomas. The biologic behavior of these tumors may be as difficult to predict as the more traditional pheochromocytomas.

Here we present the case of a 64 year old woman with hypertrophic cardiomyopathy and frequent episodes of headaches, palpitations, and diaphoresis who was admitted to the hospital with hypertensive urgency with blood pressure of 260/150 mm Hg and heart rate of 140 beats/min. Work up for severe hypertension and her symptoms revealed markedly elevated 24 hour urine epinephrine of 852 mcg/24hrs (normal 2-24), norepinephrine 421mcg/24 hrs (normal 15-100), dopamine 364 mcg/24 hrs (normal 52-480), metanephrine 23994 mcg/24 hrs (normal 58-203), and normetanephrine 5527 mcg/24 hrs (normal 88-649). Computed tomography (CT) imaging of the abdomen and pelvis revealed a 6.5 cm x 7.8 cm x 6.0 cm left adrenal mass (Figure 1). I-123-metaiodobenzylguanidine (MIBG) scan showed uptake of the radiotracer in the left upper quadrant of the abdomen corresponding to the large, left, adrenal mass seen on CT imaging (Figure 2), but no other areas of uptake. Following pretreatment with an alpha blocker and metyrosine, she underwent left adrenalectomy. Histologically, approximately 80% of the tumor consisted of typical PCC and 20% was comprised of neurons and neuropil in a Schwann cell-poor stroma consistent with ganglioneuroblastoma (GNB) (Figure 3). The tumor was immunopositive for succinate dehydrogenase subunit B (SDHB) (Figure 4). However, the tumor was unusual in that the neurons were almost all cytologically mature and Ki-67 immunostaining showed extremely low labeling (<1%) in both the neural and endocrine components. Staining for S100 showed extremely sparse sustentacular cells in the PCC (Figure 5) as well as sparse Schwann cells in the GNB (Figure 6). The GNB tissue was also interesting in that it contained RET negative, RET positive as well as tyrosine hydroxylase (TH) negative and TH positive neurons (Figures 7a, 7b, 8a, and 8b). Post-operatively, her 24 hour urine catecholamines and metanephrine normalized.

There have been only few reported cases of composite PCC+GNB, occurring in patients with ages ranging from 5 to 73 years. Most have been benign, but two cases were malignant. Elevation in dopamine levels along with other catecholamines are more commonly seen in these patients than those with ordinary pheochromocytomas. The GNB component usually shows a typical diagnostic mixture of Schwann cell-rich and Schwann cell-poor stroma containing mature and immature neurons. The overall rarity of composite pheochromocytoma and the paucity of information about the histologenesis and biologic potential of neuroblastic elements make it difficult to predict clinical outcomes. It was of interest that in this particularly unusual composite tumor, both Schwann cells and sustentacular cells were sparse, supporting a possible histogenetic relationship between these cell types.

Figure 1CT abdomen/ pelvis showing large left adrenal mass (red

arrow)

Figure 2MIBG scan showing

radiotracer uptake in left lower quadrant

(red arrow)

INTRODUCTION

CASE PRESENTATION

DISCUSSION

Poster Number: FRI-326

Figure 3Hematoxylin & Eosin staining showing PCC

tissue on left (black arrow) and GNB tissue on right (green arrow) (100x)

Figure 7aRET negative cells in PCC on left (black

arrow), RET positive neurons in GNB on right (green arrow) (100x)

Figure 7bRET negative cells in PCC on left (black arrow)

and Ret negative neurons in GNB on right (green arrow) (100x)

Figure 8aTyrosine hydroxylase (TH) positive PCC

cells on left, TH negative neurons in GNB on right (100x)

Figure 4SDHB staining of PCC (400x)

Figure 8bTH positive neurons in GNB

(100x)

Figure 5Very rare sustentacular cell seen in

PCC (black arrow) (200x)

Figure 6No Schwann cells seen in neural

processes in GNB (200x)