Join Us | Latest Articles | Contact

Journal Home


Editorial Board


Recent Articles


Submit to this journal


Special Issues


Current issue

International Archives of Endocrinology Clinical Research




Adrenal Neuroblastoma Mimicking Pheochromocytoma in an Adult with Neurofibromatosis Type 1

Harbi Khalayleh1, Hilla Knobler2, Vitaly Medvedovsky2, Edit Feldberg3, Judith Diment3, Lena Pinkas4, Guennadi Kouniavsky1 and Taiba Zornitzki2*


1Department of Surgery, Hebrew University Medical School of Jerusalem, Israel
2Endocrinology, Diabetes and Metabolism Institute, Kaplan Medical Center, Hebrew University Medical School of Jerusalem, Israel
3Pathology Institute, Kaplan Medical Center, Israel
4Nuclear Medicine Institute, Kaplan Medical Center, Israel


*Corresponding author: Taiba Zornitzki, MD, Endocrinology, Diabetes and Metabolism Institute, Kaplan Medical Center, Hebrew University Medical School of Jerusalem, Bilu 1, 76100 Rehovot, Israel, Tel: +972-894-41315, Fax: +972-8 944-1912, E-mail: taiba_z@clalit.org.il
Int Arch Endocrinol Clin Res, IAECR-3-008, (Volume 3, Issue 1), Case Report
Received: November 22, 2016 | Accepted: February 18, 2017 | Published: February 21, 2017
Citation: Khalayleh H, Knobler H, Medvedovsky V, Feldberg E, Diment J, et al. (2017) Adrenal Neuroblastoma Mimicking Pheochromocytoma in an Adult with Neurofibromatosis Type 1. Int Arch Endocrinol Clin Res 3:008.
Copyright: © 2017 Khalayleh H, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.



Context

Neurofibromatosis type 1(NF1) is a genetic disorder associated with an increased risk of malignant disorders. Adrenal neuroblastoma is considered an extremely rare tumor in adults and was not previously described in association with NF1.

Case description: A 42-year-old normotensive woman with typical signs of NF1 underwent evaluation for abdominal pain, and a large 14 × 10 × 16 cm left adrenal mass displacing the spleen, pancreas and colon was found. An initial diagnosis of pheochromocytoma was done based on the known strong association between pheochromocytoma, NF1 and increased catecholamine levels. The patient underwent surgery in which a left adrenalectomy, nephrectomy and splenectomy were performed.

The pathology examination revealed an adrenal tumor composed of immature neuronal cells intermixed with fibrillar eosinophilic material (neuropil). These features are compatible with a neuroblastoma. No pheochromocytoma component was found in the tumor. Five months after the operation, a vertebral lesion was detected and biopsied with histological findings of metastatic neuroblastoma.

Conclusion: This is a unique case of an adrenal neuroblastoma mimicking a pheochromocytoma in an adult patient with neurofibromatosis type 1.
Learning points

1. Neurofibromatosis type 1, an autosomal dominant disorder is associated with a known substantial increased risk of developing adrenal pheochromocytomas but not with adrenal neuroblastomas.

2. This is the first reported case of an adrenal neuroblastoma occurring in an adult patient with NF1 presenting as a large adrenal mass with increased catecholamine levels mimicking a pheochromocytoma.

3. This case demonstrates the clinical overlap between pheochromocytoma and neuroblastoma.


Keywords

Adrenal neuroblastoma, Neurofibromatosis type 1, Pheochromocytoma, Neural crest-derived tumors


Background

Neurofibromatosis type 1 (NF1) is a genetic disorder that involves autosomal dominant mutations in the neurofibromin (NF1) gene [1]. These mutations increase the risk of a variety of tumor types, including benign and malignant tumors [1]. Neuroblastoma (NB) is a malignant neoplasm that is embryologically derived from neural crest cells and therefore develops in any organ of the sympathetic nervous system. NB frequently appears in children, and very rarely in adults. Only 190 adolescent and adult cases of neuroblastoma have been described in the literature from 1987 to 2014 [2], and an abdominal primary tumor site was found in only a quarter of the cases. Adult-onset NB is usually classified as a high-risk tumor and is associated with a poor prognosis [2]. The current study presents a case of a giant catecholamine secreting adrenal neuroblastoma in a patient with NF1. Adrenal neuroblastomas are considered an extremely rare tumor in adults and have not been previously described in association with NF1.


Case Presentation

A 42-year-old normotensive woman with neurofibromatosis type 1 (NF1) with typical cutaneous manifestations (multiple neurofibromas, café-au-lait spots and axillary freckling), underwent evaluation for abdominal pain and a large left adrenal mass displacing the spleen pancreas and colon, was found upon a CT scan (Figure 1a). A subsequent fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET-CT) scan showed a 14 × 10 × 16 cm mass with a high and heterogeneous uptake, areas of necrosis and no evidence of distant metastasis (Figure 1b). Laboratory work-up revealed increased urinary levels of normetanephrine (1160 μg/24 hours, normal < 604 μg/24 hours) and dopamine (1481 μg/24 hours, normal < 400 μg/24 hours). An initial diagnosis of pheochromocytoma was made based on the known strong association between pheochromocytoma, NF1 [1] and a positive biochemical work-up, although the discrepancy between the tumor’s large size and the modest catecholamine elevation was puzzling.


Figure 1: a) Coronal contrast enhanced CT of the abdomen showing a large 14.0 cm adrenal mass displacing the spleen, pancreas and colon (black arrow); b) An FDG PET/CT image shows uptake with high heterogeneous uptake and areas of necrosis (black arrow); c) Surgical specimen; d) Adrenal neuroblastoma (HE stainx40), small round blue immature neuronal cells admixed with eosinophilic fibrillar material (neuropil). View Figure 1



.




Despite normal blood pressure levels in ambulatory 24-hour blood pressure monitoring, the patient was treated preoperatively accordingly to a pheochromocytoma diagnosis with alpha- blockers and subsequently underwent an operation in which a left adrenalectomy, nephrectomy and splenectomy was performed as the tumor involved these organs without a true plane of dissection.


Pathological Findings

A 16 × 10 × 9 cm adrenal tumor with areas of hemorrhagic necrosis was present (Figure 1c). The spleen and kidney were adherent to, but not involved with the tumor. On microscopic examination, the tumor was composed of a majority of small immature neuronal cells, and a smaller component of neuronal cells in intermediate and late (ganglion cells) differentiation stages. The neuronal cells were embedded in a rich background of fibrillar eosinophilic material (neuropil) (Figure 1d). Despite performing extensive sampling, no pheochromocytoma components were found in the tumor. Upon immune histochemical staining, the tumor cells were positive for chromogranin, synaptophysin, neurofilament, and vimentin. There was focal S100 positivity in sustentacular cells. These findings were compatible with a neuroblastoma.


Outcome and Follow-Up

The patient's recovery after tumor resection was uneventful. There was no evidence of a metastatic disease on the. 123I-Metaiodobenzylguanidine.(123I-MIBG) single photon emission computed tomography (SPECT) imaging two months after the surgery and according to the INSS system, the tumor was defined as stage 1 Three months later, the patient complained of bone pain and a CT scan detected a single D2 vertebral lesion. The biopsy revealed a metastatic neuroblastoma. The patient was treated by local radiotherapy and the symptoms improved. For the next two years, there was no evidence of metastases on serial total body CT scans performed every six months. At that point the bone pain reoccurred and despite normal serial CT scans, an additional MIBG scintigraphy was performed demonstrating multiple bone and liver metastases. Disease stabilization was achieved by chemotherapy treatment with Etoposide and Carboplatinum. Subsequent serial MIBG scintigraphs showed no further disease progression.


Discussion

Neuroblastoma and pheochromocytoma are both neural crest-derived tumors but current literature describes major differences in their clinical characteristics:

1. Neuroblastomas account for more than 7% of childhood cancers but are considered extremely rare in adults, while pheochromocytomas mostly occur in adulthood [2-4].

2. Only 1-2% of neuroblastoma cases are known to be related to hereditary syndromes, while 15-30% of pheochromocytomas are part of hereditary tumor syndromes [3,5].

3. The most typical presentation of a neuroblastoma is related to its mass effect, while pheochromocytomas are mostly recognized by symptoms and signs caused by excess catecholamines [3]. Despite these differences, recent bioinformatic analyses of genomic data have revealed several similar expression patterns in pheochromocytomas and neuroblastomas [6].

We describe a patient with NF1, an autosomal dominant disorder associated with loss-of-function of the NF1 suppressor gene encoding neurofibromin [1,7]. NF1 patients have a substantially increased risk of developing benign and malignant tumors of neurogenic and non-neurogenic origins [1,7]. Compared with the general population, the prevalence of pheochromocytoma is 1000-to 2000-fold higher in NF1 patients (2% vs. 1-2/100,000) but the age of diagnosis, location and malignancy risk are similar [3,7]. However, according to the existing literature, the association between neuroblastoma and NF1 is rare [7,8], and to the best of our knowledge this is the first reported case of an adrenal neuroblastoma in an adult NF1 patient. Interestingly however, 23% of the rare cases of composite pheochromocytoma that include ganglioneuroblastoma, ganglioneuroma or neuroblastoma, occur in NF1 and a role of neurofibromin in the abnormal proliferation of Schwann cells has been suggested [9].

This is the first report of an adrenal neuroblastoma occurring in an adult patient with NF1 presented as a large adrenal mass with increased catecholamine levels mimicking a pheochromocytoma. This case demonstrates the clinical and possible hereditary overlap between these tumors.


Declaration of Interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the reported research.


Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sectors.


Patient Consent

Written informed consent was obtained from the patient for publication of the submitted article and accompanying images by her signature on the consent form.


Author Contribution

Dr. Harbi Khalayleh researched the data, wrote the manuscript, contributed to the discussion, and reviewed and edited the manuscript. Dr. Hilla Knobler researched the data, wrote the manuscript, contributed to the discussion, reviewed and edited the manuscript. Dr. Vitaly Medvedovsky researched the data, wrote the manuscript and contributed to the discussion. Dr. Edit Feldberg performed the pathology investigation, contributed to the discussion and reviewed and edited the manuscript. Dr. Judith Diment performed the pathology investigation, contributed to the discussion and reviewed and edited the manuscript. Dr. Lena Pinkas reviewed the ¹²³I-MIBG SPECT and FDG PET/CT images Dr. Guennadi Kouniavsky researched the data, wrote the manuscript, contributed to the discussion and reviewed and edited the manuscript. Dr. Taiba Zornitzki researched the data, wrote the manuscript, contributed to the discussion and reviewed and edited the manuscript.


References
  1. Laycock-van Spyk S, Thomas N, Cooper DN, Upadhyaya M (2011) Neurofibromatosis type 1-associated tumours: their somatic mutational spectrum and pathogenesis. Hum Genomics 5: 623-690.

  2. Kurokawa S, Mizuno K, Nakane A, MoritokiY, Nishio H, et al ( 2016) Adrenal Neuroblastoma in an adult: effect of radiotherapy on local progression after surgical removal. Case Reports in Urology 2016: 1-4.

  3. Young WF (2016) Endocrine hypertension. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, Williams textbook of endocrinology. (13th edn), Philadelphia, Elsevier, 556-572.

  4. Castleberry RP (1997) Neuroblastoma. Eur J Cancer 33: 1430-1437.

  5. Mazzaglia PJ (2012) Hereditary pheochromocytoma and paraganglioma. J Surg Oncol 106: 580-585.

  6. Szabó PM, Pintér M, Szabó DR, Zsippai A, Patócs A, et al. (2012) Integrative analysis of neuroblastoma and pheochromocytoma genomics data. BMC Med Genomics 5: 48.

  7. Brems H, Beert E, de Ravel T, Legius E (2009) Mechanisms in the pathogenesis of malignant tumours in neurofibromatosis type 1. Lancet Oncol 10: 508-515.

  8. Cheuk DK, Chiang AK, Ha SY, Chan GC (2013) Malignancies in Chinese patients with neurofibromatosis type 1. Hong Kong Med J 19: 42-49.

  9. Kimura N, Watanabe T, Fukase M, Wakita A, Noshiro T, et al. (2002) Neurofibromin and NF1 gene analysis in composite pheochromocytoma and tumors associated with von Recklinghausen's disease. Mod Pathol 15: 183-188.

International Journal of Anesthetics and Anesthesiology (ISSN: 2377-4630)
International Journal of Blood Research and Disorders   (ISSN: 2469-5696)
International Journal of Brain Disorders and Treatment (ISSN: 2469-5866)
International Journal of Cancer and Clinical Research (ISSN: 2378-3419)
International Journal of Clinical Cardiology (ISSN: 2469-5696)
Journal of Clinical Gastroenterology and Treatment (ISSN: 2469-584X)
Clinical Medical Reviews and Case Reports (ISSN: 2378-3656)
Journal of Dermatology Research and Therapy (ISSN: 2469-5750)
International Journal of Diabetes and Clinical Research (ISSN: 2377-3634)
Journal of Family Medicine and Disease Prevention (ISSN: 2469-5793)
Journal of Genetics and Genome Research (ISSN: 2378-3648)
Journal of Geriatric Medicine and Gerontology (ISSN: 2469-5858)
International Journal of Immunology and Immunotherapy (ISSN: 2378-3672)
International Journal of Medical Nano Research (ISSN: 2378-3664)
International Journal of Neurology and Neurotherapy (ISSN: 2378-3001)
International Archives of Nursing and Health Care (ISSN: 2469-5823)
International Journal of Ophthalmology and Clinical Research (ISSN: 2378-346X)
International Journal of Oral and Dental Health (ISSN: 2469-5734)
International Journal of Pathology and Clinical Research (ISSN: 2469-5807)
International Journal of Pediatric Research (ISSN: 2469-5769)
International Journal of Respiratory and Pulmonary Medicine (ISSN: 2378-3516)
Journal of Rheumatic Diseases and Treatment (ISSN: 2469-5726)
International Journal of Sports and Exercise Medicine (ISSN: 2469-5718)
International Journal of Stem Cell Research & Therapy (ISSN: 2469-570X)
International Journal of Surgery Research and Practice (ISSN: 2378-3397)
Trauma Cases and Reviews (ISSN: 2469-5777)
International Archives of Urology and Complications (ISSN: 2469-5742)
International Journal of Virology and AIDS (ISSN: 2469-567X)
More Journals

Contact Us

ClinMed International Library | Science Resource Online LLC
3511 Silverside Road, Suite 105, Wilmington, DE 19810, USA
Email: contact@clinmedlib.org
 

Feedback

Get Email alerts
 
Creative Commons License
Open Access
by ClinMed International Library is licensed under a Creative Commons Attribution 4.0 International License based on a work at https://clinmedjournals.org/.
Copyright © 2017 ClinMed International Library. All Rights Reserved.