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Topics

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Introduction

Presentation

Evaluation

Treatment
Introduction
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Adrenocortical neoplasms accounts for 0.2% of all
childhood neoplasms and 1.3% of all carcinomas in patients
<20yrs old*

Single tumors are usually benign unilateral adenomas more
rarely carcinomas
Less commonly patients can present with benign
multinodular hyperplastic lesions
Unlike in adults the differentiation of an adenoma from
carcinoma and its biological behaviour based on morphology
is difficult to predict**.
* Ribeiro etal. European Journal of cancer 2004 ; 40 :1117 - 1126
** Weinke etal. Am J Surg Pathol 2003; 27 (7): 867 - 881
Clinical presentation and outcomes
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<4 years 60%
4 12 yrs
30%
13 20 Yrs 10%
Michalkiewicz Etal. J Clin Oncol. 2004 ;22(5): 838 - 845
Sutter etal. Pediatr Endocrinol Rev. 2006 ; 4(1) : 32 39
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Michalkiewicz Etal. J Clin Oncol. 2004 ;22(5): 838 - 845
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R. C Ribeiro etal. Braz J Med Biol Res 2000; 33(1): 1225 - 1234
Clinical Presentation.
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Virilization is the most common presentation
Common manifestations in males include
Deepening of voice
Acne
Increased facial hair
Increased muscle mass
Proliferation of sebaceous glands with characterstic adult odour
Penile enlargement
Isosexual precocious puberty
In females
Clitoral enlargement
Facial and pubic hair with male escutcheon
Amenorrhoea
Temporal balding
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Cushings Syndrome
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occurred in 1/3 of patients but pure cushing syndrome only
in 5 8%*

Most of them had associated virilization features

Signs and symptoms included moon facies, weight gain,
Centripetal distribution of fat, plethora, hypertension and
striae
Ribeiro etal. Braz J Med Biol Res 2000; 33(1): 1225 1234
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Clinical features..
Feminization, rare and occurred in 2%
of patients the commonest manifestation
being gynaecomazia
Aldosterone producing adenomas are
rare and may comprise up to 1.6%
Head ache, weakness of proximal
muscles, polyuria, tachycardia,
hypocalcemia and hypertension may be
the presenting features
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Ribeiro etal. Braz J Med Biol Res 2000; 33(1): 1225 1234
Ribeiro etal. European Journal of cancer 2004 ; 40 :1117 - 1126
Clinical features
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33% presented with hypertension usually with cushing s
syndrome

In the absence of hypercortisolism hypertension was
rarely caused by excess Mineralocorticoid production
but mostly by mechanical effects of tumor on renal
artery

Distant metastasis found in 5% of patients
Ribeiro etal. European Journal of cancer 2004 ; 40 :1117 - 1126
Clinical presentation.
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Bilateral tumors were seen in upto 1.3%
Rarely ectopic
Has been described in spinal canal, intrathoracic cavity and
renal hilum
Other possible ectopic sites are
Retroperitoneum near coeliac plexus, kidney, genetalia,
Broad ligaments, Epididymis and spermatic cord
Ribeiro etal. Braz J Med Biol Res 2000; 33(1): 1225 1234
To avoid delay in diagnosis
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Consider adrenocortical tumors unless proved otherwise if:
Patient presents with pubarche <4 years
Presence of acne in an infant
Cushings syndrome in children younger than 10 years

Laboratory Evaluation
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Measurement of Urinary 17 Ketosteroid gives a diagnosis in
98% of patients*

Plasma DHEAS is abnormal in 90% of cases

Urinary DHEAS is a poor marker with alteration only in 75% of
patients

The presence of an elevated androgen and cortisol is a strong
predictor of adrenal tumor**
*Sandrini Etal. J Clin Endocrinol Metab 1997 82;2027-2031
**R. C Ribeiro etal. Braz J Med Biol Res 2000; 33(1): 1225 1234
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Routine laboratory investigations include
Serum Cortisol
DHEAS
Testosterone
Aldosterone / Renin activity
Metanephrines..?

These markers will help not only for diagnosis but also for
follow up of these patients

Ribeiro etal. Braz J Med Biol Res 2000; 33(1): 1225 1234
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Adrenarche elevated basal concentrations of DHEA-S and
Androstenodione

CAH increased basal or stimulated peak concentration of 17
OH Progesterone

ACT - A striking Decrease in serum DHEA-S, Androstenodione
and Testosterone on dexamethasone supression in adrenarche
(especially when Imaging study shows a small adrenocortical mass)

Ribeiro etal. European Journal of cancer 2004 ; 40 :1117 - 1126
Pathology
Adenomas represent around 15% of childhood ACT (Almost always functional)


Characteristics Adenoma Carcinoma
Shape Oval to spherical Bosselated
size <10 cms -
Colour Uniform yellow to brown Varigated Yellow to dark
brown
Weight <200grams >400grams
Encapsulation + May be absent
Necrosis absent present
Histology Oval to polygonal cells with
eosinophilic cytoplasm
Medium sized to large cells
with eosinophilic cytoplasm
arranged in alveolar clusters
Haemorrhage and calcification May be present ++
Mitotic figures <2/HPF numerous
Fibrosis and broad bands + ++
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Operative photo
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CRITERIA FOR MALIGNANCY

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Wt - >400g
Size - >10.5 cm
Venacaval invasion
Capsular invasion
Vascular invasion
Extension in to periadrenal tissues
Confluent necrosis
>15 Mitotic figures / 20 HPF
Severe Nuclear Atypia


Weinke etal. Am J Surg Pathol 2003; 27 : 867 881
Imaging
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Imaging studies help for surgical planning and disease
staging

CECT abdomen: diagnostic modality

USG help to identify extend of tumor thrombus

To rule out metastasis: X ray chest & Tc -99 bone scan
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On CT scan well demarcated with an enhancing peripheral capsule
Large tumors may have stellate (hyperintense on T2 weighted MR) appearance
caused by haemorrhage
Calcifications common
CT scans may miss tumor thrombus
US or MR imaging indicated if there is suspicion of tumor thrombus
PET scan may help to identify metastasis not revealed by other
imaging useful in follow up but false negatives can occur
Ribeiro etal. European Journal of cancer 2004 ; 40 :1117 1126
Ribeiro etal. Braz J Med Biol Res 2000; 33(1): 1225 1234
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Treatment
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ACT
SURGICAL
CHEMOTHERAPY
Open Laparoscopic
Mitotane
based
Others
Surgical
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Surgery is the only mode of therapy documented as effective for
treating pediatric ACT

Curative surgical resection considered in every child with ACT

En bloc resection indicated in tumors involving Kidney, Portion of
pancreas / Liver

Tumor should be carefully handled to avoid tumor spillage

IVC should be always palpated before tumor resection cardio
vascular surgeon to be involved if tumor thrombus extending beyond
diaphragm
Ribeiro etal. European Journal of cancer 2004 ; 40 :1117 - 1126
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Steroid replacement therapy is essential in immediate post
operative period

Surgical resection of recurrent disease (local & Distant) may
be warranted even if required multiple times
Ribeiro etal. European Journal of cancer 2004 ; 40 :1117 - 1126
Medical
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Though not validated for use in children Mitotane forms the
main chemotherapeutic agent

Used to treat
Advanced metastatic cancer
As adjuvant therapy in patients with high risk of relapse
To control symptoms from over production of hormone

Most of the recurrence occurs between 6 8 months, continuation of mitotane
therapy for 8 months 1 year is reasonable


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Other chemotherapeutic agents include 5-FU, Etoposide,
Cisplatin, Carboplatin, Cyclophosphamide, Doxorubicin and
streptozocin
Most of these combinations show a response rate of 30%
with very few complete response
The best results reported 53% with cisplatin, Etoposide,
Doxorubicin in conjunction with a small dose of Mitotane

The combination most used in pediatric ACC is Cisplatin +
Etoposide + Mitotane
Ribeiro etal. European Journal of cancer 2004 ; 40 :1117 1126
Ribeiro etal. Braz J Med Biol Res 2000; 33(1): 1225 1234
Follow up
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These hormonal tumor markers allows close monitoring
of tumor recurrence

Hormones fall to normal levels within 7 days of
complete tumor resection

Hormones should be assessed monthly during 1
st
yr of
resection and every 3-4 months in 2
nd
and 3
rd
year

Tumor recurrence to be suspected when hormonal levels
progressively increase (Even if they are normal limits)
Note: assays to be done off mitotane as it can interfere with assay
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