Keywords
adrenal - tumor - oncology - laparoscopy
Introduction
The adrenal gland consists of a medulla and a cortex and may give rise to various
types of tumors. While adenomas and carcinomas may develop in the cortex, the medulla
may be the origin of neuroblastomas, pheochromocytomas, and ganglioneuromas. All of
these lesions may require surgical intervention by an open or a minimally invasive
approach. The risks and benefits of pediatric laparoscopic adrenalectomy for malignant
or semibenign lesions remain a matter of vivid discussion. While simple adrenal cysts
or adenomas are benign lesions and a minimally invasive approach may be considered,
adrenocortical carcinomas and (ganglio)neuroblastomas require careful assessment of
risk factors such as serum biomarkers, hormonal status, and image-defined risk factors
(IDRFs) .[1]
[2]
[3] In the present case series, distinct characteristics of technical feasibility and
oncological safety of laparoscopic approaches for pediatric adrenal masses are discussed.
Case Presentation
Case 1
A 3-year-old boy presented with precocious puberty (tanner stages P2 and G2). X-rays
of the extremities showed an accelerated bone age of ∼6 years. Ultrasound (US) and
magnetic resonance imaging (MRI) of the abdomen revealed a right adrenal mass of approximately
4.0 × 2.5 × 4.0 cm ([Fig. 1]). The laboratory workup of the patient is displayed in [Table 1]. Laparoscopic adrenalectomy was performed. Histopathological examination confirmed
complete resection of an adrenal adenoma with hamartoma components. At the 2-year
follow-up, the patient presented with a normalized hormone status (cortisol, testosterone,
dehydroepiandrostendionsulfate, androstenedione, 17-hydroxyprogesterone, adrenocorticotropic
hormone) and without signs of recurrence in the US.
Fig. 1 Magnetic resonance imaging of all four patients. None of them presented with image-defined
risk factors.
Table 1
Laboratory workup of the patient
|
Parameter
|
Range
|
Case 1
|
Case 2
|
Case 3
|
Case 4
|
|
Age at surgery
|
|
3 years
|
1,5 years
|
15 years
|
7 years
|
|
Body weight (kg)
|
|
18 (90–97th percentile)
|
13 (97th percentile)
|
71 (80th percentile)
|
20 (3rd percentile)
|
|
Height (cm)
|
|
103 (90th percentile)
|
82 (97th percentile)
|
182 (88th percentile)
|
121 (10th percentile)
|
|
Serum LDH (U/L)
|
120–340
|
218
|
367 (+)
|
193
|
248
|
|
Serum NSE (mg/mL)
|
0–26
|
26.0
|
33.1 (+)
|
|
38 (+)
|
|
VMA urine (µg/mg creatinine)
|
<10
|
9.0
|
8.1
|
|
5.0
|
|
HVA urine (µg/mg creatinine)
|
<15
|
15.0
|
11.0
|
|
10.0
|
|
Dopamine urine (µg/mg creatinine)
|
<0.85
|
0.68
|
0.64
|
|
0.52
|
|
Bone marrow aspiration
|
|
|
|
|
Negative
|
|
N-Myc amplification
|
|
|
|
|
Negative
|
|
LH (mU/mL)
|
1.0–14.0
|
0.22 (−)
|
<0.1 (−)
|
1.94
|
|
|
FSH (mU/mL)
|
0.89–11.72
|
0.59 (−)
|
<0.1 (−)
|
1.80
|
|
|
Basal hGH (mU/mL)
|
0.5–3.0
|
6.9 (+)
|
2.1
|
|
|
|
PRL (ng/mL)
|
2.1–29.2
|
|
14.0
|
|
|
|
IGF-1 (mU/mL)
|
30.0–300.0
|
120.6
|
|
|
|
|
Basal ACTH (pg/mL)
|
10–51
|
|
56.6 (+)
|
17.1
|
|
|
Basal cortisol (ng/mL)
|
43–220
|
|
5.8 (−)
|
|
|
|
Androstenedione (ng/mL)
|
1.0–14.0
|
3.3
|
|
2.58
|
|
|
DHEA-S (µg/mL)
|
0.39–4.63
|
8.1 (+)
|
|
1.62
|
|
|
Total Testosterone (ng/mL)
|
2.41–8.30
|
0.4
|
0.77
|
2.88
|
|
|
17OH-Progesterone (ng/mL)
|
0.2–0.9
|
0.88
|
|
0.66
|
|
|
Histology
|
|
Adrenal adenoma
|
Potentially malignant ACT
|
Simple adrenal cyst
|
Ganglioneuroblastoma
|
Abbreviations: ACT, adrenocortical tumor(+)-elevated; (−) - decreased; ACTH, adrenocorticotropic
hormone; DHEA-S, dehydroepiandrostendionsulfate; FSH, follicle stimulating hormone;
hGH, human growth hormone; HVA, homovanillylic acid; IGF, insulin-like growth factor;
LDH, lactate dehydrogenase; LH, luteinizing hormone; NSE, neuron specific enolase;
PRL, prolactin; VMA, vanillylmandelic acid.
Case 2
A one- and half-year-old female presented with a precocious puberty (virilization
with clitoris hypertrophy and pubarche P2–3). Laboratory parameters are shown in [Table 1]. Abdominal US showed a hypoechogenic lesion in the right adrenal gland. MRI ([Fig. 1]) revealed a largely solid, relatively sharply delimited, contrast-enhancing lesion
of the right adrenal gland (4.0 × 3.0 × 3.5 cm) without IDRFs. Thus, a transperitoneal
laparoscopic adrenalectomy was performed. Histopathology revealed a large, encapsulated
adrenocortical tumor (ACT) with a diameter of 5 cm and malignant potential with tumor-free
resection margins. At the 11-month follow-up, there were no signs of recurrence.
Case 3
A 15-year-old male patient presented with exercise-triggered recurrent right abdominal
pain. US and MRI demonstrated an uncomplicated cystic structure in the right adrenal
gland with sharp delineation to the upper renal pole and without pathological contrast
enhancement ([Fig. 1]) giving no indication for surgery. In his routine US checkups, the size of the cyst
increased to 8.0 × 7.6 × 5.8 cm over 2 years indicating surgical removal. Additional
information about laboratory workup is given in [Table 1]. Laparoscopic adrenalectomy was done and histopathology revealed a mesothelial cyst.
At the 12-month follow-up, there were no sonographic signs of recurrence of the cyst.
Case 4
A 7-year-old boy presented due to recurrent abdominal pain. The routine US revealed
an inhomogeneous expansion of approximately 3 × 3 × 2 cm with calcifications in the
right adrenal gland. Laboratory data are displayed in [Table 1]. MRI showed a well circumscribed slightly inhomogeneous mass in the right adrenal
gland of approximately 3.3 × 2.6 × 2.0 cm. Bone marrow biopsy was normal but metaiodobenzylguanidine
(MIBG) scan showed pathologically increased tracer uptake. Anterior laparoscopic adrenalectomy
was done with complete tumor resection. Histopathological examination revealed clinical
stage I maturing ganglioneuroblastoma with free margins. No recurrence was observed
at 2-year follow-up.
Discussion
In this case series, we present four pediatric patients with a broad spectrum of the
adrenal gland masses undergoing laparoscopic resection.
Generally, tumors of the adrenal gland can be malignant (with descending incidence:
neuroblastoma, adrenocortical carcinoma, or sarcoma) or benign (with descending incidence:
adenoma, ganglioneuroma, cysts, or adrenal hyperplasia).[3] In infants, tumors have to be discriminated from postpartum adrenal hematomas as
an important differential diagnosis that has to be considered in the diagnostic workup.
Regarding tumors, pheochromocytomas are rare adrenal masses that can be benignant
or malignant in their behavior. When selecting patients for a minimally invasive approach,
special care has to be taken to identify these children who potentially benefit from
minimally invasive surgery (MIS) (better cosmetic results, less pain, and shorter
hospital stay[4]
[5]) and to exclude those who might be harmed by this procedure (risk of inadequate
resection, tumor recurrence, trocar site metastasis, tumor rupture, and spillage as
well as tumor growth or dissemination in relation to CO2 insufflation[6]
[7]).
Guidelines for adrenalectomy poorly define the indications for MIS in the pediatric
age group. The rarity of adrenal lesions in this age group, a wide pathologic spectrum,
the predominance of malignant lesions, large dimensions of the masses in relation
to small body size of the patients, and technical challenges with miniature instruments
may be hypothesized as the underlying reasons.[8]
After initial suspicion, patients with adrenal masses undergo routine diagnostic workups
usually involve imaging (US, computed tomography and/or MRI) paired with laboratory
analysis (routine blood chemistry, differential blood count, hormone profiles, and
tumor markers). Concerning imaging special emphasis is put on the presence or absence
of IDRFs. Infiltration of the renal pedicle, encasement of major vessels (inferior
vena cava, aorta, superior mesenteric artery, celiac trunk, iliac, and hypogastric
vessels), the porta hepatis, dumbbell tumors, muscular infiltration, and compression
of kidney or ureter have been identified as IDRFs.[1] If present, IDRFs may point to malignant behavior of the tumor. Furthermore, complete
resection could be achieved in only 26% of cases presenting with IDRFs in a study
of Günther et al.[1]
While MIS is the mainstay in benign lesions,[3] it has to be discussed critically in malignant tumors. In selected cases of neuroblastoma
(size ≤ 5 cm diameter and absence of vascular encasement), MIS led to an equal long-term
oncologic outcome compared with open surgery.[9] Similarly, de Lagausie et al state that sizes greater than 6 cm, enlarged veins,
and involved adjacent organs or vessels are relative contraindications for laparoscopic
adrenalectomy for neuroblastomas.[10] Overall, the International Pediatric Endoscopic Group 2010 guidelines state that
there are no absolute contraindications for laparoscopic adrenalectomy as long as
the principles of cancer surgery are maintained.[11]
Special care has to be taken to identify the rare case of a malignant ACT. Suspicion
should be raised in case of adrenal masses presenting with IDRFs and especially in
patients with signs of precocious puberty. ACTs have a high risk of intraoperative
rupture (∼20% of cases) with consecutive tumor spillage.[12] Recent recommendations opted against laparoscopic biopsy or resection of tumors
suspicious for or known to be ACT even when MIS appears feasible and tempting, because
complete resection of the mass is the prerequisite for recurrence-free survival.[13]
[14] However, there are also reports of successful MIS in ACTs.[8]
[15]
[16] These reports are supported by the current German AWMF recommendations that advocate
that a MIS approach in ACTs is feasible as long as the principles of oncological surgery
are maintained.[17] Furthermore, a recent publication of adult ACT cases found evidence that the open
and laparoscopic approach may be comparable in terms of recurrence-free survival for
patients with stage I and II ACT when the principles of surgical oncology are respected.[18]
Taken the recent literature into account, the indication for MIS was clear in cases
1, 3, and 4 presented in this series. Histology of case 2 revealed a potentially malignant
adrenocortical tumor raising the question, if MIS was the optimal therapy for this
patient. As there was no evidence of IDRFs and the tumor size was < 5 cm, MIS was
performed. Although an open procedure may have been beneficial, the tumor could be
removed completely by MIS and the patient is free of recurrences until now (although
the follow-up interval of 11 months is relatively low for an oncologic patient).
In conclusion, MIS is indicated in benign lesions, but has to be discussed critically
in case of potential malignancy. In these cases, a MIS approach may be considered
in selected patients without IDRFs as long as the principles of oncologic surgery
can be maintained.
