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Tumors presenting in both pediatric and adult patients: a case-based review of pathology and imaging features for the radiologist

Laura Magnelli1,2 . Kevin Pierre1 · Priya Sharma 1,2

@ Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract

Various pathologic neoplasms present in both childhood and adulthood. Multiple environmental and genetic factors with different targets at different ages have been implicated in prior literature. These tumors include Multi-Locular Cystic Renal Tumors (MCRT), Adrenocortical Carcinomas, Paragangliomas, Hepatic Hemangiomas, and Medullary Renal Cell Carci- nomas. The pertinent imaging, pathological, and clinical features of these select entities are discussed to assist the General and Pediatric Radiologist in accurate interpretation and treatment planning.

Keywords Tumors . Pediatrics . Adult . Radiology . Pathology . Review

Multi-locular cystic renal tumors (MCRT)

Multi-locular cystic renal tumors (MCRT) exhibit a “bimodal” age distribution. They peak in incidence in chil- dren 3 months to 4 years and adults 40 to 60 years. While MCRTs do not have malignant potential, there is a spectrum of aggressiveness ranging from the benign Cystic Nephroma (CN) to the more aggressive Cystic Partially Differentiated Nephroblastoma. MCRT can be difficult to differentiate from cystic Wilms tumor and cystic renal cell carcinoma and therefore most patients are treated with total or partial nephrectomy with nephron-sparing surgery [1]. Children may present with only a palpable abdominal mass which sometimes is rapidly enlarging. Adults are more likely to present with hematuria, recurrent urinary tract infections, or abdominal pain. [2, 3]. Grossly, MCRTs appear as a well- circumscribed, multiloculated cystic mass with the cysts filled with clear to yellow serous fluid or a myxomatous gel. There is also a thick fibrous capsule and compressed renal parenchyma [2]. Microscopically, the septa are lined

by either cuboidal or flattened epithelia. The more aggres- sive CPDN may be differentiated from the benign CN by the presence of blastemal cells within the translucent septa. Grossly, however, both appear identical [1, 2]. These tumors must be differentiated from a Wilms tumor, where cysts are formed from necrosis of solid tissue, requiring serial sec- tions of the entire specimen to identify solid components. Other entities with a similar presentation may include mul- ticystic dysplastic kidney, which is managed conservatively, and clear cell sarcoma and mesoblastic nephroma which are also managed surgically [2].

Imaging

CN and CPDN are indistinguishable on imaging. Both may cause displacement of bowel and other adjoining struc- tures [2]. Sonography is the main imaging modality used for children in keeping with the principles of ALARA. Features include a mass with cysts of varying echogenici- ties separated by thin echogenic septa. A large soft tis- sue density mass may be detected on radiography [1]. CT also shows a well-circumscribed, encapsulated mass that is hypoattenuating compared to normal renal parenchyma (Fig. 1) [1-3] and thin septations that may or may not enhance [2, 3]. The “claw sign” of renal parenchyma sur- rounding the lesion and movement of both the mass and kidney with respiration on dynamic imaging may help to localize the lesion to the kidney. Herniation into the renal pelvis can occur [2]. Regions of closely packed cysts may

☒ Priya Sharma sharpg@radiology.ufl.edu

1 Divisions of Pediatric and Abdominal Imaging, Department of Radiology, University of Florida College of Medicine, 1600 SW Archer Road, PO Box 100374, Gainesville, FL 32608-0374, USA

2 University of Florida Department of Radiology, Gainesville, FL, USA

Fig. 1 Axial contrast-enhanced CT of a 21-year-old female presenting with hematuria showing a multicystic mass with thin enhancing sep- tations (arrow) in the left kidney

Fig. 2 Axial T2-weighted MRI in the same patient as Fig. 1 showing the T2 hyperintense cystic components of the mass (arrow)

appear solid, making differentiation from RCC and Wilms tumor challenging [1, 2].

The cystic components are hyperintense on T2-weighted imaging (Fig. 2) with variable signal on T1 weighted imaging [2]. The surrounding fibrous capsule and septa- tions may enhance with gadolinium [1, 2].

Adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is a rare, aggressive neoplasm appearing in both children and adults with a median age of diagnosis of 55 years. It is more common in females [4]. It is treated with surgical excision with imag- ing helping in diagnosis, guiding surgery, and in future management. There is an association with syndromes such as Beckwith-Wiedemann Syndrome, Li-Fraumeni Syndrome, Carney Complex, Familial Adenomatous Polyposis Coli (FAP) and Multiple Endocrine Neoplasia Type 1 (MEN1). While often found incidentally, ACC may present with abdominal or flank pain, as a palpable mass, or obstruction from mass effect. Approximately 40-60% of ACCs are functional, and patients may present with symptoms of androgen, estrogen, glucocorticoid and min- eralocorticoid excess; adult patients commonly report with Cushing syndrome and virilization. Females more often present with functional tumors. Patients often present with metastatic disease to the liver, lung, bone, and para-aortic or regional lymph nodes because non-functioning tumors tend to present late in their course. Histology cannot defin- itively determine whether an ACC is benign or malignant; however, features suggestive of malignancy include gross specimen heavier than 500 g or internal necrosis, calcifica- tions, or hemorrhage. Microscopically, malignant features include high nuclear pleomorphism, numerous mitotic cells, nuclear atypia, hyperchromasia, disorganization, and invasion of the capsule, veins, or sinusoid. Adenomas, pheochromocytomas, neuroblastomas, adrenal hemangio- mas, metastases and infections may present similarly, but each have characteristic clinical and imaging features that aid in differentiation [5].

Imaging

ACCs are large tumors ranging from 2 to 25 cm in size and are more common on the left side. However, they may present bilaterally in 2-10% of cases [5]. Other features include irregular margins, central hemorrhage or necrosis (Figs. 3, 4), fat, calcifications, and extension into the renal vein and IVC. There are variable appearances on MRI but typically the lesions are hyperintense to liver parenchyma and show variable degrees of enhancement (Fig. 5). There is typically avid FDG uptake on positron emission tomog- raphy (PET) (Fig. 6) [5]. Tumor size greater than 4 cm and heterogeneous enhancement are the most predictive factors of malignancy in an adrenal mass [6].

Springer

Fig. 3 Transabdominal ultrasound in a 2-year-old female present- ing with virulization shows heterogeneously hypoechoic solid mass (straight arrow) arising from the left adrenal gland superior to the left kidney (curved arrow). Internal hyperechoic regions may represent tumor hemorrhage or necrosis. Final pathology was consistent with ACC

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Fig. 4 Axial contrast-enhanced CT in the same patient as Fig. 4 showing a large, heterogeneously enhancing solid mass of the right adrenal with internal necrosis (arrow)

Paraganglioma

Paragangliomas are rare tumors that are morphologically and functionally identical to pheochromocytomas; how- ever, they differ in that pheochromocytomas are derived from adrenal neural crest cells while paragangliomas are derived from extra-adrenal neural crest cells [7]. Extra- adrenal sympathetic paragangliomas are most com- monly located in the organ of Zuckerkandl, a collection of chromaffin tissue near the aortic bifurcation, but may also arise in the mediastinum, the infra-diaphragmatic para-aortic region, and in the bladder [8]. Extra-adrenal

Fig. 5 Axial fat saturated, post-contrast, subtraction T1-weighted MRI in an adult patient showing a large (17 cm) heterogeneously enhancing mass (arrow) arising from the right adrenal gland

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Fig. 6 Fused FDG-PET/CT in the same patient showing marked FDG-avidity (arrow) in the right adrenal mass

parasympathetic paragangliomas occurring in the head appear similar on imaging and are termed “glomus jugu- lar”, “glomus vagale”, and “glomus tympanicum” depend- ing on their specific locations (Fig. 10). In the neck, they commonly occur in the carotid body as a soft tissue mass splaying the carotid bifurcation [7, 8].

Extra-adrenal paragangliomas are more likely to metas- tasize and have a worse overall prognosis [8]. They are associated with the syndromes of MEN2, VHL, and NF-1 [7-11]. Patients may present from early childhood to late adulthood with a mean age of diagnosis of ~ 40 years. [10, 12]. Many are found incidentally; however, patients may present with episodic sympathetic symptoms due to catecholamine secretion. These include palpitations,

tachycardia, hypertension, perspiration, pallor, hyper- glycemia, and headache [7-11]. Bladder paragangliomas may present with hematuria and micturition syncope [8]. Pheochromocytomas are diagnosed by measuring plasma or urinary metanephrines [7, 9-11]. Tumors average 7 cm in size at resection and are generally lobulated and yellow, red, or brown in color. They can be small and circum- scribed with a rim of compressed adrenal gland. Larger masses may be hemorrhagic or necrotic. Microscopically, they can have an alveolar pattern or appear as small nests (Zellballen). The cells are either granular or basophilic or have an amphophilic cytoplasm. Hyaline globules can be present in the cytoplasm. The cells may have high pleo- morphism, and the nucleoli may be very prominent. How- ever, there are usually no mitotic figures [11]. Treatment includes administration of phenoxybenzamine to control hypertension followed by surgical excision [7, 9, 10].

Imaging findings

Pheochromocytomas characteristically demonstrate low attenuation (<10 HU) on CT with marked enhancement followed by washout on delayed phase. Hemorrhage, necrosis, calcifications, and cystic changes are common [8]. On MRI, pheochromocytomas are hyperintense on T2-weighted imaging (Fig. 7) and enhance with contrast (Figs. 8, 9). However, up to 35% of pheochromocytomas do not enhance. Hemorrhagic and cystic pheochromocyto- mas may appear heterogeneous [8]. Functional imaging is also useful in the diagnosis of pheochromocytoma. [123I] MIBG SPECT, [18F]FDG-PET, [111In]octreotide SPECT, and PET imaging can help to confirm the diagnosis and to aid in staging [8, 9] (Fig. 10).

Fig. 7 Axial T2-weighted MR in a 17-year-old male presenting with abdominal pain showing a heterogeneously hyperintense left adrenal mass (arrow). Final pathology was consistent with pheochromocy- toma

Fig. 8 Axial pre-contrasted T1-weighted MR in the same patient as Fig. 7 showing the left adrenal mass (arrow) demonstrates hypoin- tense signal on T1-weighted imaging

Hepatic hemangioma

Hepatic hemangiomas (HH) are benign tumors that present in the neonates and adults between 30 and 50 years [13]. In children, these present as infantile and congenital hemangio- mas. Infantile hemangiomas are classified as “focal,” which develop in the prenatal period and usually involute just after birth, “multifocal,” which develop in the postnatal period and involute by 6-10 years of age, or “diffuse,” which develop in the postnatal period and replace most of the parenchyma [14, 15]. Congenital hemangiomas are characterized by whether they are rapidly (RICH), partially (PICH), or non-involuting (NICH) [14]. Hepatic hemangiomas usually are found inci- dentally; however, children may present with feeding impair- ment, breathing difficulty or a palpable mass. Complicating features include mild thrombocytopenia and AV shunting

Fig. 9 Axial post-contrast T2-weighted MR in the same patient as Figs. 7 and 8 showing the left adrenal mass (arrow) demonstrates het- erogeneous enhancement

Fig. 10 Axial contrast-enhanced T1 weighted MR in a 44-year-old female shows an enhancing lesion in the left jugular foramen (straight arrow) compatible with a glomus jugulare. There are post-surgical changes in the right jugular fossa (bent arrow) from prior glomus tumor removal

in focal lesions, cardiomegaly, AV shunting, porto-venous shunting, and heart failure in multifocal lesions, and cardiac failure, hypothyroidism, bleeding, abdominal compartment syndrome, high-volume AV shunting, respiratory distress, and heart failure when diffuse [15].

Hepatic hemangiomas in adults represent a separate dis- ease process. They are often found incidentally but may present with upper abdominal pain when larger due to dis- tension of the Glisson’s capsule of the liver. Hepatic heman- giomas are benign tumors composed of dilated blood-filled cavities that are lined by a single layer of endothelial cells. Necrosis, thrombosis, sclerosis, or calcification can also be seen. Histological specimens are usually not obtained due to the risk of hemorrhage considering the vascular nature of the tumor [14].

Imaging

Sonographically, HHs are hyperechoic and homogenous with well-defined margins and posterior acoustic enhance- ment and no internal Doppler flow (Fig. 11). Atypical lesions may appear hypoechoic with a peripheral echogenic ring. Larger lesions may appear heterogeneous due to fibro- sis, necrosis, or hemorrhage [16]. On CT and MR, HHs char- acteristically demonstrate peripheral, discontinuous, nodular enhancement (Figs. 12, 13, 14). T2 weighed imaging also shows a markedly hyperintense lesion, although signal is less intense than simple fluid (Fig. 15) [14, 15]. Red blood cell scintigraphy is the most specific method but has fallen

Fig. 11 Ultrasound in a 3-week-old male undergoing workup for UTI showing a well-defined, hyperechoic solid hepatic lesion (arrow) with mild posterior acoustic enhancement, compatible with a hemangioma

out of favor due to the high cost, length of procedure, higher irradiation, and reduced availability [14].

Medullary renal cell carcinoma

Medullary Renal Cell Carcinoma (MRCC) is a rare but very aggressive subtype of renal cell carcinoma with poor prognosis almost always found in patients of African descent with sickle cell trait. It almost always presents in the advanced stage. It presents from infancy to late adulthood, with a mean age of ~ 26 years old [17]. Other aggressive renal masses include renal lymphoma, rhabdoid

Fig. 12 Axial pre-contrast T1-weighted MR in a 68-year-old male shows a hypointense 6 cm mass in the right hepatic lobe (arrow)

Fig. 13 Axial post-contrast (3 min delay) T1-weighted MR in the same patient as Fig. 12 shows that the right hepatic lobe mass (arrow) demonstrates a discontinuous, nodular peripheral enhancement pat- tern

Fig. 14 Axial post-contrast (20 min delay) T1-weighted MR in the same patient as Figs 12 and 13 shows the right hepatic mass (arrow) demonstrates central filling in of contrast

tumor, mesoblastic nephroma, and transitional cell carci- noma which can often be readily distinguished on imag- ing and histology. MRCC often presents with flank and abdominal pain, or hematuria [18]. Patients may also pre- sent with weight loss, respiratory symptoms, hypertension, scrotal pain, fever, urinary tract infection, and enlarging neck mass [19]. The right kidney is involved 70% of the time. On histology, MRCC shows a yolk sac or reticular growth pattern. It is composed of dense stromal desmo- plasia, inflammatory reaction in the tissue, and positive mucicarmine staining. They can also show eosinophilic cytoplasm, high nuclear grade, and sometimes a tubular formation [20]. Management includes radical nephrec- tomy; however, survival rates are still very low [18].

Fig. 15 Axial post-contrast subtraction MR in the same patient as Figs. 12, 13, 14 shows the right hepatic mass (arrow) demonstrates T2 hyperintense signal

Fig. 16 Axial contrast-enhanced CT in an 8-year-old male with sickle cell trait who presented with hematuria, showing a large, centrally necrotic mass (straight arrow) involving the superior right renal pole. Pathology from ultrasound-guided biopsy consistent with medullary renal cell carcinoma. Hepatic metastases (bent arrow) and retroperi- toneal adenopathy (line arrow) also pictured. Not pictured: metastatic disease also involving the L5 vertebral body and sacroiliac joint

Imaging

MRCC are often imaged in the later stages, and on average are greater than 6 cm in size and appear as a hypodense lesion commonly with invasion into the pelvicalyceal system [19]. The mass may appear cystic or solid and may show internal hemorrhage or necrosis (Fig. 16). Calcification is rare. Retroperitoneal lymphadenopathy, hilar lymphad- enopathy, mediastinal lymphadenopathy, lung metastases with associated pulmonary lymphangitic carcinomatosis, and adrenal gland, IVC and liver metastases may be present (Figs. 16, 17) [18-20].

Fig. 17 Axial contrast-enhanced CT (lung window) in the same patient as Fig. 16 showing numerous pulmonary metastases (arrows)

Author contributions All authors have contributed to the literature search, review, editing, and write-up of this review article. All authors have read and approved the final manuscript.

Funding None.

Compliance with ethical standards

Conflict of interest There are no conflicts of interest for any affiliated authors.

Research involving human and animal rights This article does not contain any studies with human participants or animals performed by any of the authors.

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