Giant non-functioning adrenocortical carcinoma: A rare childhood tumor

Abstract

Adrenocortical carcinoma (ACC) is a rare malignancy, especially in children. The overall incidence is approximately 2 cases per million per year.[1] In children, the incidence is 0.3 cases per million per year, except in southern Brazil where the incidence is 3.4-4.2 cases per million per year.[2] We describe a giant nonfunctioning metastasized ACC in a 6-year-old girl who presented with a history of increasing abdominal girth incidentally noticed by her mother since 1 week. Ultrasound abdomen showed a large right suprarenal tumor with calcifications and necrosis. Empty left renal fossa and compensatory enlarged right kidney were seen. Computed tomography (CT) scan revealed a large heterogenously enhancing right suprarenal mass with calcification and necrosis with pulmonary metastasis. Histopathology report from the right suprarenal mass revealed an ACC. With a stage IV disease, the patient died after 2 months from diagnosis.

Full text

Indian Journal of Medical and Paediatric Oncology | Apr-Jun 2010 | Vol 31 | Issue 2 65
Address for correspondence:
Dr. Viral Patel,
“Radhasoami” Opposite Old
Post Ofce, Karamsad,
Gujarat - 388 325, India.
E-mail: viral_44@yahoo.com
Viral V. Patel, Diva S. Shah,
Chandra R. Raychaudhari,
Keyuri B. Patel
Department of Radiodiagnosis,
PramukhSwami Medical College
and Shree Krishna Hospital,
Karamsad, Gujarat, India
INTRODUCTION
Adrenocortical carcinoma (ACC) is an unusual, and a
highly malignant childhood tumor with grave prognosis.
It accounts for 0.002% of childhood malignancies,
with most of the tumors being functional in children.[3]
Nonfunctioning adrenocortical tumors are exteremly rare
in children.[3] There are many case reports for functional
ACC, but very few reports are available for non-functioning
ACC in children owing to its rarity.[4,5]
The tumor has bimodal age distribution, presenting in
children under 6 years, and in adults 30-40 years old.[6]
Girls are more frequently affected than boys.[6] Functioning
ACC usually draws clinical attention for many hormonal
syndromes, viz., virilization, cushing’s syndrome, cons
syndrome and feminization.
Nonfunctioning adrenal tumors remain a diagnostic
challenge in early diagnosis and successful management
as there are no early signs and symptoms. In a majority
of cases, the tumor has either invaded adjacent organ
or already metastasized to distant organ at the time of
initial diagnosis. In most of the cases, it is mistaken for
neuroblastoma which is the commonest intra-abdominal
childhood tumor.[3] Very rare incidence and unusual mode
of presentation in childhood in our patient with a single
functioning kidney prompted us to make a case report with
its review of literature.
ABSTRACT
Adrenocortical carcinoma (ACC) is a rare malignancy, especially in children. The overall
incidence is approximately 2 cases per million per year.[1] In children, the incidence is
0.3 cases per million per year, except in southern Brazil where the incidence is 3.4–4.2
cases per million per year.[2] We describe a giant nonfunctioning metastasized ACC in a
6-year-old girl who presented with a history of increasing abdominal girth incidentally
noticed by her mother since 1 week. Ultrasound abdomen showed a large right suprarenal
tumor with calcications and necrosis. Empty left renal fossa and compensatory
enlarged right kidney were seen. Computed tomography (CT) scan revealed a large
heterogenously enhancing right suprarenal mass with calcication and necrosis with
pulmonary metastasis. Histopathology report from the right suprarenal mass revealed
an ACC. With a stage IV disease, the patient died after 2 months from diagnosis.
Key words: Adrenocortical carcinoma, adrenocortical tumor, nonfunctioning
DOI: 10.4103/0971-5851.71659
Giant non-functioning adrenocortical carcinoma:
A rare childhood tumor
CASE REPORT
CASE REPORT
A 5-year-old girl presented with complains of abdominal
swelling and low grade fever since few days. No relevant
past history of bowel or urinary complains was present.
There was also no signicant family history of cancer.
Physical examination revealed distended abdomen
with a palpable lump in the right hypochondrium. Her
temperature was mildly raised, blood pressure was 110/72
mm Hg and rest of the vitals were unremarkable.
Ultrasonography of abdomen revealed a large heterogenous
mass of size approximately 11×10.6×9.26 cm in the right
suprarenal region, with calcications, large necrotic and
hemorrhagic areas within and indistinct fat planes from the
superior pole of right kidney. Left kidney was not seen in
left renal fossa or anywhere else in abdomen, suggesting
possible congenital absence. No focal lesion was observed
in liver.
Contrast enhanced CT scan of abdomen conrmed the above
ndings [Figures 1 and 2]. In addition, the lesion was abutting
right lobe of the liver causing mass effect and displacing
the right branch of portal vein and right hepatic vein
[Figures 3 and 4]. Inferiorly, the supero-medial pole of
the right kidney had indistinct fat plane with mass lesion.
However the claw sign and organ embedded sign were negative,
suggestive of extra renal origin [Figure 4]. Medially, the
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66 Indian Journal of Medical and Paediatric Oncology | Apr-Jun 2010 | Vol 31 | Issue 2
Patel, et al.: Non-functioning adrenocortical carcinoma in a child
Figure 1: Non-contrast enhanced CT scan revealed large heterogenous
mass with few chunks of calcications
Figure 3: Multiplanner coronal reformation shows right suprarenal mass
causing displacement and bowing of inferior vena cava and abutting
inferior surface of liver and empty left renal fossa
Figure 2: Contrast-enhanced CT scan showing heterogenously
enhancing suprarenal lesion with areas of necrosis
Figure 4: Sagittal multiplanner reformation of right suprarenal mass
lesion abutting anterosuperior aspect of right kidney
lesion was extending in the midline abutting the caudate lobe,
causing compression and displacement of inferior vena cava
[Figure 3]. It was abutting the renal vessels without any
evidence of invasion/thrombosis. Multiple, moderately
enhancing round to oval shaped, randomly distributed lesions
were observed, involving bilateral lung parenchyma [Figure
5], suggestive of bilateral pulmonary metastatic deposits.
There was no evidence of bone marrow/bone metastasis.
Ultrasound guided biopsy revealed ACC. The tru-cut
biopsy cores showed areas with patternless sheets of
cell interrupted by a ne sinusoidal pattern and broad
trabeculae. Wide expanses of necrosis were seen.
[Figure 6] The individual cells had predominantly
eosinophilic cytoplasm. Less than 25% cells were clear
cells. Significant nuclear atypia and hyperchromatism
were noted. Infrequent but denitive atypical mitotic
gures were seen. [Figure 7] Six out of 9 Weiss criteria
were fullled. The histologic score as per Van Slooten
et al. was 21.
Routine laboratory investigations were unremarkable.
Although there were no clinically evident signs of
virilization or Cushing’s syndrome, plasma cortisol urinary
levels of 17-ketosteroids and 17-hydroxycoticosteroid were
measured and found to be within normal range.
The patient was grouped as stage IV (according to TNM
classication)1 and was planned for palliative chemotherapy.
As it was an advanced stage disease with metastasis and
considering the remote chances of complete cure and the
costly chemotherapy drugs which were not affordable by
the parents, they decided to start ayurvedic treatment. The
patient survived for 2 months after diagnosis.
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Indian Journal of Medical and Paediatric Oncology | Apr-Jun 2010 | Vol 31 | Issue 2 67
Patel, et al.: Non-functioning adrenocortical carcinoma in a child
Figure 5: Bilateral randomly distributed variable sized lung parenchymal
lesions represent metastasis
Figure 7: Signicant nuclear atypia, hyperchromasia and pleomorphism
Figure 6: Area of necrosis with adjacent viable cells
DISCUSSION
ACC is an extremely rare tumor. In children, 90% of the
adrenal tumors are neuroblastomas (adrenal medulla).
Tumors arising from adrenal cortex are rare. Among
them, ACC is most common and it accounts for only
6% of adrenal tumors. Adrenal tumors in children can be
associated with hemihypertrophy and Beckwith Wiedmann
syndrome.[3]
ACC are classied as functional and nonfunctional based on
the hormonal syndromes they produce. Functional tumors
are common and detected earlier than nonfunctioning
tumors due to the production of hormones and associated
clinical signs as well as symptoms.[6] Nonfunctioning tumors
remain undiagnosed till late and mostly present with a large
mass and metastatic disease, as in our case, due to their
silent nature.[4,5] Adrenocortical tumors are associated with
fever for unknown reasons, as seen in our case.[7]
Primary adrenocortical tumors are large tumors usually
measuring more than 5 cm at presentation. The larger
the tumor, more is the chance of it being malignant.
Because they are large, the organ of origin often is
difcult to determine. CT scan plays an important role
in characterizing the organ of origin and in dening the
extent of the primary as well as assessing the presence of
metastatic disease. The common metastatic sites include
lung and liver, with bone and bone marrow being less
common.[3] Neuroblastoma, which is a more common
childhood tumor with similar location, has a tendency
to metastasize to bone and bone marrow, though there
are case reports showing increasing prevalence of lung
metastasis.[8] However, in neuroblastoma, pulmonary
metastasis is usually a terminal event where at least one
other metastatic site apart from lung is present, which
could be bone, bone marrow or liver.[8]
ACC tends to be highly malignant and locally invasive, and
potential curative treatment is complete surgical removal. The
role of tumor debulking in metastatic ACCs is controversial.
According to Allolio et al., stage IV ACC is not amenable
to surgery and mitotane remains the rst-line therapy.[9]
Conversely, Icard et al. reported that debulking surgery along
with mitotane in stage IV patients prolongs survival.[10 ]
The reported median survival of stage IV ACC is less than
12 months. However, there are case reports showing longer
survival in patients with stage IV disease, with surgery and
chemotherapy.[11] Various clinical trials showing varying
effects of different chemotherapy agents like mitotane,
EDP (Etoposide, doxorubicin and cisplatin) and sunitinib
have shown prolonged survivals in individual stage III/IV
patients.[12,13]
Prognosis depends largely on tumor stage. In a study
conducted by Icard P et al. of 253 patients, the overall
survival rate was 38% and the 5-year survival rates were
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68 Indian Journal of Medical and Paediatric Oncology | Apr-Jun 2010 | Vol 31 | Issue 2
as follows: for stage I 60%; stage II 58%; stage III 24%
and stage IV 0%. The overall 5-year survival in different
series ranged between 16 and 38%. Median survival for
metastatic disease (stage IV) at the time of diagnosis is still
consistently less than 12 months.[9,10] The average survival
time for untreated patients is 2.5 months.[14] In our case,
the patient with stage IV disease survived for 2 months
after diagnosis without treatment.
In summary, nonfunctioning ACC is a very rare childhood
tumor. Its early detection and appropriate treatment
remains a continuing challenge. Although neuroblastoma
is the commonest intra-abdominal malignant childhood
tumor, in cases with a large nonfunctioning adrenal lesion
with pulmonary metastasis and no denite evidence of
bone metastasis, a nonfunctioning ACC, though very rare
in children, should be kept in differential diagnosis.
ACKNOWLEDGMENT
Dr. Monica Gupta, Professor, Department of Pathology for
her help in data analysis and Dr. Harshvardhan Khokhar
(R3) is acknowledged for his technical help.
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Patel, et al.: Non-functioning adrenocortical carcinoma in a child
Source of Support: Nil, Conict of Interest: None declared.
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