DIR
Diagn Interv Radiol 2021; 27:811-815
@ Turkish Society of Radiology 2021
PICTORIAL ESSAY
Imaging findings of primary adrenal tumors in pediatric patients
İD H. Nursun Özcan
Aziz Anıl Tan İD Burak Ardıçlı İD Berna Oguz İD Saniye Ekinci İD Tezer Kutluk İD Mithat Haliloglu İD
From the Department of Radiology (H.N.Ö. drhnozcan@yahoo.com, A.A.T., B.O., M.H.), ☒
Department of Pediatric Surgery (B.A., S.E.), Division of Pediatric Oncology, Department of Pediatrics (T.K.), Hacettepe University School of Medicine Ankara, Turkey.
Received 20 August 2020; revision requested 9 September 2020; last revision received 20 October 2020; accepted 10 November 2020.
Published online 18 October 2021.
DOI 10.5152/dir.2021.20701
ABSTRACT
Apart from neuroblastomas, adrenal tumors are rarely seen in children. The most common adrenal tumors are adrenocortical carcinoma and pheochromocytoma. Adrenocortical car- cinoma is usually a large heterogeneous, well-marginated mass with solid/cystic areas and calcifications, with poor prognosis. Most of the pheochromocytomas are benign tumors and usually show intense contrast enhancement, the pattern of which may be diffuse, mottled, or peripheral on computed tomography and magnetic resonance imaging. The purpose of this article is to evaluate primary nonneurogenic adrenal tumors.
I n children, neoplastic and non-neoplastic lesions might be seen in the adrenal region. Pediatric adrenal lesions may be found incidentally, can be suspected in children that suffer endocrine, metabolic, neurological problems or with an abdominal mass. In fetal life, adrenal glands are much larger than in adults because of the existence of a prominent fetal cortex. Their prominent fetal size is also seen in early neonatal life. Ultrasonography (US) is the initial imaging technique to examine the adrenal glands in newborns. In older children, due to the physiologic atrophy of the fetal adrenal cortex, adrenal limbs are thinner than the adjacent crura of the diaphragm. Consequently, they are much more difficult to specify with US, but can be easily identified on computed tomography (CT) or magnetic resonance imaging (MRI). US is the primary modality for imaging the pediatric abdomen. CT or MRI are used as a problem-solving tool for lesion characterization, to de- termine the relationship to adjacent tissues, and to differentiate benign from malignant masses after initial US evaluation (1). In older children MRI should be preferred rather than CT examination. In adults, abdominal CT examinations assess tumor washout of contrast material based upon multi-phase CT, which is necessary to characterize adrenocortical masses (especially adenomas). However, pediatric CT examinations should be done in sin- gle portal venous phase to comply with “Image Gently” and “as low as reasonably achie- vable” (ALARA) principles.
Primary adrenal tumors are classified according to their origin and function. They might originate from the medulla or cortex, and they are hyperfunctioning or nonfunctioning. Primary medullary tumors encompass a spectrum of sympathetic neuroectodermal tumors, which are neuroblastoma, ganglioneuroblastoma, ganglioneuroma, and pheochromocyto- ma, all of which stem from the neural crest and may take place anywhere along the sympa- thetic chain aside from the adrenal gland itself. Neoplasms arising from the adrenal cortex are adrenocortical carcinoma and adenoma.
In the literature, few studies have reported imaging findings of pediatric adrenal tumors, including all types of involvement (i.e., benign, malignant, and metastatic) (1-3). The aim of this article is to describe the imaging findings of primary nonneurogenic adrenal tumors.
Adrenal tumors
Adrenal neoplasms, apart from the neurogenic tumors, are rare in childhood, and they display different histological spectrum and better clinical outcomes compared to the adult patients. Much more has been reported from the clinical and surgical perspectives and less
You may cite this article as: Özcan HN, Tan AA, Ardicli B, et al. Imaging findings of primary adrenal tumors in pediatric patients. Diagn Interv Radiol 2021; 27:811-815.
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about imaging findings (4-6). The most fre- quently detected pediatric primary adrenal tumors are adrenocortical carcinoma and pheochromocytoma.
Adrenocortical carcinoma
Adrenocortical carcinoma constitutes less than 1% of malignancies in the childho- od (7). Patients with adrenocortical carcino-
Main points
· Adrenocortical carcinoma is a heteroge- neous tumor with necrosis and calcifications.
· MRI cannot accurately distinguish the benig- nity of adrenocortical tumors in pediatric pa- tients.
· It is important to differentiate neurogenic tu- mors from other types of adrenal tumors.
ma can manifest with findings linked to hor- monal overproduction (typically virilization in girls), and pseudoprecocious puberty in boys with or without Cushing syndrome. Rarely, patients can present with abdomi- nal pain or a palpable mass. Adrenocortical carcinoma incidence has been estimated at 0.3 per million children annually with two peaks, i.e., below the age of 5 and above the age of 10 years, whereby girls are more frequently involved than boys (8). In our country, Turkish Pediatric Cancer Registry shows that 0.18% of childhood cancers are adrenocortical carcinoma (9). Children with adrenocortical carcinoma can be found in association with two genetic syndromes: Beckwith-Wiedemann and Li-Fraumeni (10). Generally, 5-year survival of adreno- cortical carcinoma is better in children than in adults, at almost 50% (8). Favorable pro-
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gnostic factors are younger age (<4 years), low stage at diagnosis, tumor volume <200 cm3, and virilization alone (11). Radiological findings that suggest the diagnosis of adre- nocortical carcinoma are size of tumor >8.5 cm, volume of tumor >212.5 mL, heteroge- neous structure, and typically heterogene- ous contrast enhancement corresponding to hemorrhage, necrosis, intratumoral cal- cifications, local invasion, and distant me- tastasis (Figs. 1 and 2) (12). However, the shortage of these findings does not rule out carcinoma in the differential diagnosis (2). On MRI, diffusion-weighted images (DWI) have been used with increasing frequency in the abdomen. Miller et al. (13) reported that benign adrenal lesions can not be di- stinguished from malignant lesions using DWI because of considerable overlap in ap- parent diffusion coefficient values.
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The most common sites for adrenocor- tical carcinoma metastases are lungs, liver, and lymph nodes (Fig. 3) (2). Metastatic disease during the diagnosis of adrenocor-
tical carcinoma was reported as an inde- pendent prognostic factor (14). FDG-PET/ CT is used to identify the malignant adrenal tumors, and it may also localize metastases.
Pheochromocytoma
Pheochromocytoma and paraganglioma are unusual neuroendocrine tumors that are derived from the neural crest (15). Phe- ochromocytoma refers to the tumor origi- nating from chromaffin (neuroendocrine) cells in the adrenal gland/medulla; howe- ver, paraganglioma represents the tumor originating apart from the adrenal gland, from sympathetic or parasympathetic gan- glia. In pediatric pheochromocytomas, ne- arly 80% of patients are related to a genetic syndrome, e.g., multiple endocrine neopla- sia type 2 (MEN 2), neurofibromatosis type 1, von Hippel-Lindau disease, and familial paraganglioma syndromes (16). Hence, ge- netic counseling and testing ought to be applied in all patients. In children, 80% of pheochromocytomas occur in the adrenal gland. Bilateral adrenal involvement was seen in 20%-40% of the cases, and pheo- chromocytoma might appear at multiple locations in 30%-70% of cases (17). Less common extra-adrenal locations include the sympathetic chain in a cervical, thora- cic, or pelvic location and rarely they may occur in the urinary bladder, spinal cord, and vagina. Malignant pheochromocytoma is less frequent than in adults, and is deter- mined by imaging-presence of local inva- sion and/or metastasis-rather than histo- pathological analysis. The nuclear imaging is better for patients with familial syndro- mes and those with possible existence of a multifocal/metastatic disease. Evaluation of plasma and/or urine-free metanephrine and normetanephrine levels are the most sensitive diagnostic tests. These catechola- mines are the reason of main tumor manife- stations: hypertension, headache, arrhyth- mia, sweating, and weight loss. They can be seen as a soft-tissue mass in the suprarenal fossa, with various echogenicity on sono- graphy with high vascularity on color Dop- pler US. On contrast-enhanced CT images, they have increased vascularity and strong enhancement, which is mostly homogene- ous in small tumors; however, they might be heterogeneous in larger ones due to cy- stic, necrotic, and/or hemorrhagic parts. On MRI, they have diminished signal intensity on T1-weighted images, increased signal intensity on T2-weighted images and avid enhancement on post-contrast images (Fig. 4). However, up to 30% of them show he- terogeneous or decreased signal intensity on T2-weighted images (18). 68Ga-DOTATA- TE PET/CT is the nuclear imaging of choice
with its higher sensitivity and specificity to detect the lesions that could not be seen on CT and MRI (2).
Adenoma
Adenomas are exceptional pediatric tumors that originate from the adrenal cortex. Pediatric age group adenoma is histopathologically and clinically distinct from adult adenoma. Hallmarks, such as washout thresholds on CT examination and signal loss on out-of-phase MRI can- not reliably distinguish the benignity of these tumors in pediatric patients. Hen- ce, the expression “adrenocortical tumor” rather than adenoma or carcinoma is ge- nerally used to define a primary tumor in
the adrenal cortex in pediatric patients (12, 19). Although not a solid criterion, adrenocortical tumors are much smaller than adrenocortical carcinomas. Never- theless, malignancy cannot be excluded according to the tumor size. On imaging, adenomas are well circumscribed and have mild homogeneous contrast enhan- cement (Fig. 5).
Small round cell tumor with neuroendocrine differentiation
Small round cell tumor with neuroen- docrine differentiation is an uncommon, highly aggressive pediatric malignancy, which rarely occurs in the adrenal gland. On radiological examinations, they are large
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heterogeneous tumors indistinguishable from adrenocortical carcinoma (Fig. 6).
Leiomyosarcoma
Primary adrenal leiomyosarcoma is an uncommon tumor and it is thought to arise from the smooth muscle wall of the central adrenal vein and its branches (20). On ima- ging, they typically show lobulated mass with heterogeneous contrast enhancement (Fig. 7). Their radiological features are analo- gous with other adrenal tumors and there- fore they should be considered in the diffe- rential diagnosis of a suprarenal mass with malignant characteristics.
Malignant rhabdoid tumor
Malignant rhabdoid tumor is an extre- mely malignant pediatric tumor with very poor prognosis. They are mainly present in the kidneys of children and extrarenal presentations are extremely rare. They are large infiltrative masses and the diagnosis depends on histopathology.
Conclusion
In conclusion, apart from neuroblasto- mas, adrenal tumors are exceedingly rare in the pediatric population. Adrenocortical carcinomas are typically heterogeneous tumors with necrosis and calcifications and can behave aggressively by encasement of localized vascular structures and widespre- ad metastasis. Pheochromocytomas are usually benign tumors, and most of them have intense contrast enhancement on CT and MRI. Signal loss on out-of-phase MRI cannot accurately distinguish the benignity of adrenocortical tumors in pediatric pa- tients. Radiological examinations have an important role in recognizing and differen- tiating malignant and benign adrenal neo- plasms. However, radiologists need to err on the side of caution when differentiating
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malignant adrenal tumors, by considering all imaging and clinical findings and labo- ratory tests.
Conflict of interest disclosure
The authors declared no conflicts of interest.
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