Adrenal neuroblastoma in adult: case report

Abstract

Adult adrenal neuroblastoma is an extremely rare malignancy, accounting for less than 1% of neuroblastoma cases. We report the case of a 27-year-old male with a right adrenal mass, diagnosed as poorly differentiated neuroblastoma. Despite adrenalectomy and adjuvant chemotherapy, the disease metastasized to retroperitoneal lymph-nodes and liver, leading to death from neoplastic progression. This report highlights the rarity, diagnostic complexity and poor prognosis of adult adrenal neuroblastoma.

1. Introduction

Neuroblastoma is a malignant neuroblastic tumour, embryologically derived from the neural crest. This neoplasm can develop in any portion of the sympathetic nervous system, being observed in the adrenals and in the abdomen and retroperitoneum.1, 2, 3 Neuroblastoma is the most common extracranial solid tumour in the paediatric age group; however, it is extremely rare in adults, usually being identified under the age of forty.^2,4,5 Although prognosis depends on a series of characteristics, older age seems to be one of the main aggravating factors.5, 6, 7 In this case report, we present a 27-year-old male patient diagnosed with adrenal neuroblastoma, who underwent adrenalectomy and adjuvant chemotherapy.

2. Case presentation

A 27-year-old male started with insidious right flank pain, with no history of trauma or other associated symptoms. Computed Tomography (CT) showed a 9 cm lesion in the right adrenal (Fig. 1, Fig. 2). The patient did not return for subsequent appointments. After two years, he returned with worsening of the flank pain and performed a new CT, with the lesion progressing to 13.3 cm. Through metabolic evaluation (urinary metanephrines, cortisol after dexamethasone, aldosterone, renin and dehydroepiandrosterone) the lesion was deemed as nonfunctional. The patient underwent open adrenalectomy through a right subcostal anterior incision. The pathology revealed a poorly differentiated right adrenal neuroblastoma (25% of well-differentiated areas), with a low mitotic index (4-14 mitoses per high-power field), with calcification, necrosis and angiolymphatic invasion. There was a positive surgical margin in the medial aspect of the lesion. The histological subtype was classified as unfavourable by INPC, since the system classifies all neuroblastoma cases in patients older than 60 months of age as unfavourable histology. The patient started adjuvant chemotherapy treatment, with a cycle of cyclophosphamide and topotecan in November of the same year, and three cycles of etoposide and cisplatin. Due to aggravating factors, such as age and poor tolerance to treatment, the medical team chose to leave him under observation afterwards.

Fig. 1.

CT Scan showing a 9cm lesion in the right adrenal - coronal view.

Fig. 2.

Computed Tomography (CT) showing a 9cm lesion in the right adrenal - axial view.

One year later, a new CT was performed, showing the appearance of interaortocaval lymph nodes, the largest of which was approximately 1.6 × 1.0 cm, and retroperitoneal lymph node progression in all retroperitoneal chains (Fig. 3, Fig. 4). The largest nodes were situated in the paraaortic and interaortocaval areas. Additionally, there was periportal and peri vesicular oedema. The MYCN amplification test was inconclusive. The patient underwent a salvage retroperitoneal lymphadenectomy, with anatomopathological and immunohistochemical findings compatible with metastatic neuroblastoma, the latter showing a negative reaction for CK (AE1/AE3) and S100 (polyclonal) and positive reactions for chromogranin (polyclonal) and synaptophysin (DAK-SYNAP).

Fig. 3.

Computed Tomography (CT) demonstrating progression of retroperitoneal lymphadenopathy, predominantly in the intercavoaortic and para-aortic regions - axial view.

Fig. 4.

Computed Tomography (CT) demonstrating progression of retroperitoneal lymphadenopathy, predominantly in the intercavoaortic and para-aortic regions - coronal view.

After two months, the patient was hospitalized due to a weight loss of around 6kg, significant prostration and uncontrolled lumbar and abdominal pain, suggesting a probable recurrence. A bone medullogram showed neoplastic invasion, and a CT showed liver metastasis. The patient started a new chemotherapy regime, but seven days after the first treatment cycle, he developed a fever of 39 °C for two days and a sore throat, suggestive of febrile neutropenia.

In the following month, the patient developed episodes of hematemesis over two weeks, in large quantities, requiring four units of red blood cells and six units of platelets (for thrombocytopenia). Due to his desire to spend the next few days at home or in a hospital in his city, and considering that he would not undergo chemotherapy until the following week due to the recent low platelet count, the medical team chose to schedule his hospitalization for the day of his return to the hospital, for a trial of topotecan, vincristine and doxorubicin, but the patient soon evolved with ascites and supraclavicular lymph node enlargement, dying due to neoplastic progression along a few days.

3. Discussion

In general, patients with neuroblastoma do not have clinical symptoms unless there is invasion of other organs or in the setting of metastatic disease.⁶ Symptoms, when present, can range from pain due to local invasion, to flushing, tachycardia and high blood pressure due to high catecholamines production; however, these presenting signs are not the norm.^2,8,9 The patient in our report ended up not presenting any symptoms that by themselves would suggest investigation for neuroblastoma. In addition to the aforementioned factors that cause delayed diagnosis, there is growing evidence that this tumour, in adults, does not have the same classic characteristics found in paediatric patients, such as a low incidence of MYCN amplification and elevated urinary catecholamines and MIBG (iodine avidity-131 metaiodobenzylguanidine, a norepinephrine analogue).^9,10

Although it is difficult to make a specific preoperative diagnosis and considering that the incidence of neuroblastoma in adult patients is extremely low, it is important that this hypothesis be considered in any adult patients with an adrenal mass. The preoperative dosage of urinary catecholamines (homovaline and vanilmandelic acid), elevated in about 50% of adult patients with neuroblastoma, increases the suspicion of neuroblastoma or pheochromocytoma.^5,8,11 Other methods that may suggest the diagnosis include a meta-iodobenzylguanidine scintigraphy, ultrasound and CT of the abdomen with oral and intravenous contrast – these latter assisting in the precise location of the tumour.^8,12 Magnetic resonance imaging can be mor useful in cases of advanced malignancy, with possible venous involvement, renal failure and in cases of allergy to conventional intravenous contrast.^8,12 From then on, confirmation of this tumour will depend on the postoperative pathology, with biopsy of the primary tumour, highlighting the need for a differential diagnosis of small round blue cell tumours, especially when they are found in the sympathetic ganglia.^3,5,9 Neuroblastomas are typically positive for neuronal markers, such as chromogranin, synaptophysin - just like our patient in question -, neurofilament and CD56, and negative for CD99 and myogenic markers in the cytogenetic analysis.^10,13 Patients can be stratified into favourable or unfavourable histology, according to histopathological and clinical characteristics, following the protocol established by the International Neuroblastoma Pathology Classification (INPC).^10,13 The INPC determined three subtypes of neuroblastoma: undifferentiated, differentiated and in differentiation.¹⁰ Our patient had a poorly differentiated tumour, meaning that the cell irregularity is considerable, and it cannot be precisely defined which cell type originated the tumour. Under microscopy, neuroblastoma cells are usually small and rounded, arranged around the neuropil, with an appearance like a chrysanthemum. Lesions present with calcifications, necrosis, haemorrhage and cysts, causing poor density homogeneity.^8,10

Due to its rarity, the treatment of neuroblastoma in adults follows the same protocols as in the paediatric population, with complete surgical resection and adjuvant chemotherapy using alkylating agents (cyclophosphamide/ifosfamide), platinum-based agents (cisplatin, carboplatin), etoposide and adriamycin. In cases of microscopic residual disease, local radiotherapy may be indicated.^13,14 However, the high cost of treatment, the limited availability of centres offering chemotherapy, professionals with adequate surgical experience and radiotherapy, and the lack of access to treatment with immunotherapy, especially in medical centres located in developing countries, makes it even more unfeasible. obtaining success in treatment.⁶ Studies note that the incidence of high-risk patients is higher when compared to patients with low or intermediate risk, which can be explained by the lack of MYCN tests, delaying diagnosis.⁶

Although this scenario was not the case with our patient, another fundamental attribute to be highlighted and which inherently affects all patients with such a diagnosis is the patient's quality of life based on the choice of treatment, since, according to in a report by the St. Jude Lifetime Cohort, published in 2020, 95% of neuroblastoma survivors that outlast more than 10 years after their diagnosis have experienced at least one chronic disease, with radiotherapy provided for local control of paravertebral tumours being one of the contributors to the increase the risk of late endocrine and musculoskeletal effects, as well as patients who used chemotherapy with cisplatin or carboplatin reporting hearing loss. In addition, the sample survivors reported a worsening in their physical quality of life, with difficulty living independently, which allows us to infer about the emotional and social consequences decades after treatment.¹⁴

Recent studies indicate that the use of targeted immunotherapy with anti-GD2 monoclonal antibodies, new and standard treatment in Europe and North America, and T cell-based therapies targeting GD2, both in preclinical development and clinical trials, may use cytotoxic immune cells against primary tumours and residual disease after therapy. Positive results in long-term survival, reduction of long- and short-term toxicity and more effective treatment are expected for the near future.15, 16, 17 More recently, point mutations that lead to the activation of the RAS/MAPK pathway affecting the gene that encodes for anaplastic lymphoma kinase (ALK) were found in 6-17% of cases on sporadic neuroblastomas, suggesting that the use of ALK inhibitors such as crizotinib, ceritinib or lorlatinib may be therapeutic options in selected cases.¹⁸

Despite the numerous adversities that such pathology brings to an individual's life, it is clear that new studies and scientific advances have brought promising results in terms of quality of life and clinical success in the diagnosis of neuroblastoma in adulthood. Recently, an analysis of the database of the SEER program (Surveillance, Epidemiology and End Results) between the years 1975 and 2013, showing that, in the USA, the incidence of neuroblastoma in children increased, but ended up decreasing in adolescents and adults, in addition to an improvement in overall survival in all age groups¹⁹.

4. Conclusion

Adult adrenal neuroblastoma represents an exceptionally rare and aggressive entity, posing diagnostic and therapeutic challenges due to its atypical clinical presentation and biological behaviour compared with paediatric cases. Prognosis for adult neuroblastoma continues to be poor, highlighting the need for multicentre collaboration, molecular research, and tailored therapeutic approaches to ultimately enhance survival and quality of life for these patients.

CRediT authorship contribution statement

Isabela Carvalhal: Writing – review & editing, Writing – original draft, Data curation, Conceptualization. Marcelo Bopp Tesheiner: Writing – review & editing, Writing – original draft, Data curation. Gabriel Teitelbaum Friedman: Writing – review & editing, Writing – original draft, Data curation. Enrico Sousa Villetti: Writing – review & editing, Writing – original draft, Data curation. Mauro Thomé Lopes: Writing – review & editing, Writing – original draft, Data curation. Gustavo Franco Carvalhal: Writing – review & editing, Writing – original draft, Project administration, Methodology, Formal analysis, Data curation, Conceptualization.

Patient consent

Written informed consent was obtained from the patient's family for publication of this case report and associated images.

Funding

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

Conflicts of interest

The authors declare no conflicts of interest.