An Unusual Case of a Composite Pheochromocytoma With Neuroblastoma

Abstract

Composite pheochromocytoma (CP) is a rare tumor of the adrenal medulla, consisting of neuroendocrine and neural components. Despite similar neural crest origins, pheochromocytomas and neurogenic tumors are distinct entities. Symptoms may arise from hypersecretion of hormones by either component; however, not all patients present with classic symptoms. Moreover, various medical conditions and substances can confound screening tests and complicate the diagnosis. The patient, a 46-year-old male, was seen in the endocrine clinic regarding a 2-year history of paroxysmal headaches, palpitations and diaphoresis. His medical history was significant for hypothyroidism and substance misuse (nicotine, marijuana and cocaine). Family history was negative for pheochromocytoma, hyperparathyroidism or thyroid malignancies. He was found to be hypertensive in clinic, and two cafe-au-lait spots and bilateral axillary freckles were noted on dermatological examination. Pheochromocytoma was suspected and investigations revealed 24-h urinary catecholamines, metanephrines and vanillylmandelic acid levels that were substantially elevated. He was asked to repeat the urine collection while abstaining from cocaine, given the potential confounding with cocaine-induced elevations of catecholamines and their metabolites; however, the patient did not comply with this. His plasma free metanephrines and chromogranin A were later found to be elevated. Abdominal computed tomography revealed a 5.8 × 5 cm mass in the left adrenal gland, with an attenuation of 40 Hounsfield units. He underwent an uncomplicated laparoscopic left adrenalectomy, after which his blood pressure normalized. Histological features of the tumor revealed findings consistent with a typical pheochromocytoma with neuroblastomatous infiltrates comprising < 5% of the tumor. The mitosis karyorrhexis index was low and there was no ganglioneuromatous infiltrate evident. Medical oncology was consulted in view of the histopathological findings, and no adjuvant therapy was recommended. Unfortunately, he did not fully comply with repeat imaging or biochemical evaluation. Six months postoperatively, the patient remains completely asymptomatic and normotensive. Cocaine-induced catecholamine effects can clinically mimic pheochromocytoma, thereby complicating the diagnosis. In addition, the biologic behavior of CP with neuroblastoma is uncertain and warrants oncologic assessment and surveillance.

Composite tumor with pheochromocytoma and immature neuroblastoma: report of two cases with cytogenetic analysis and discussion of current terminology

“…Tumors with morphologic features of pheochromocytoma and stroma-poor neuroblastoma in the same lesion are rare and are commonly referred to as “composite pheochromocytoma.” Table 1 summarizes the clinical features of published cases [ 2 – 7 ]. We report two additional cases for which we provide further molecular characterization.…”

“…Case 3 represents an outlier, since this 38-year-old patient died with widely metastatic disease within 3 months of diagnosis. With the exception of the case reported by Comstock et al which demonstrated no N-MYC gene amplification in the tumor of their NF1 patient [ 6 ], other studies did not investigate this important prognostic factor [ 2 – 5 , 7 ].…”

“…The most commonly reported cases include components of pheochromocytoma and ganglioneuroma [ 1 ]. However, there are only few reports of tumors with components of pheochromocytoma and stroma-poor neuroblastoma (Table 1 ) [ 2 – 7 ]. We report two distinct cases of composite tumors of the adrenal gland consisting of pheochromocytoma and neuroblastoma.…”

Oncogenic FGFR1 mutation and amplification in common cellular origin in a composite tumor with neuroblastoma and pheochromocytoma

“…Composite pheochromocytoma refers to tumors with morphologic features of PCC and NCC‐derived tumors, such as malignant peripheral nerve sheath tumor and neuroendocrine carcinomas, within the same tumor 4,5 . Composite tumors are rare and most often combined with ganglioneuroma in composite PCC; therefore, composite tumors comprising PCC and NB are even rarer 5‐10 . The genetic mechanism of composite tumors with PCC and NB remains unclear; a single nucleotide polymorphism array analyzed only 1 case 5 .…”

“… 4 , 5 Composite tumors are rare and most often combined with ganglioneuroma in composite PCC; therefore, composite tumors comprising PCC and NB are even rarer. 5 , 6 , 7 , 8 , 9 , 10 The genetic mechanism of composite tumors with PCC and NB remains unclear; a single nucleotide polymorphism array analyzed only 1 case. 5 Here, we applied exome and transcriptome analyses to a patient case with a composite tumor with NB and PCC to investigate whether the NB and PCC lesions arose from a common cellular origin and how this tumor developed.…”