Volume 7, Issue 9, September – 2022 International Journal of Innovative Science and Research Technology

ISSN No:-2456-2165

Rare Case of Metastatic Nodular Adrenal

Ganglioneuroblastoma to Bone in a Young Female at
Ibn Rochd University Hospital of Casablanca
in Morocco
Ismael Coulibaly1,
Hanane Rida1,
Xavier Sia1,
Tarik Chékrine1,
Hassan Jouhadi1,
Nezha Tawfiq1,
Souha Sahraoui1,
Abdelatif Bénider1,
Nadia Benchakroun 1,
Zineb Bouchbika1
1
Mohamed VI Center for the Treatment of Cancers, CHU Ibn Rochd, hospital districts, 20360 Casablanca, Morocco

Sara Moukhlis2,
Farida Marnissi2,
2
Central Laboratory of Pathological Anatomy, CHU Ibn Rochd, 20503 Casablanca, Morocco

Mohammed Dakir3,
3
Urology Department, CHU Ibn Rochd, Casablanca, Morocco

Abstract:- Ganglioneuroblastoma is a tumor belonging intermediate malignant potential. Neuroblastoma is the most
to the family of neuroblastic tumours. Those are tumors immature, undifferentiated and malignant tumor of the three
of the sympathetic nervous system. [2]. Ganglioneuroblastoma is very rare in adults. It occurs
Ganglioneuroblastoma is very rare in adults. We report preferentially on 03 sites: the retro-peritoneal, the adrenal
here a case of nodular ganglioneuroblastoma metastatic gland and the posterior mediastinum. The therapeutic
to the bone in a 31-year-old woman who consulted for indications for ganglioneuroblastoma are not well codified
pain in the right flank with, on the CT scan, a due to the rarity of this pathology. We report here a case of
voluminous and heterogeneous tissue formation of metastatic nodular ganglioneuroblastoma to bone in a 31-
lobulated contours. She underwent an adrenalectomy. A year-old woman.
postoperative radiological assessment showed osteolytic
lesions of the neck, left femoral metaphysis and bilateral II. CLINICAL CASE
iliac wings. The patient was put on palliative
chemotherapy. She is currently under surveillance at 16 Our case is that of a young patient aged 31, married
months of survival without new events. and mother of 3 children. She has no particular personal
Ganglioneuroblastomas are considered to have history or notion of cancer in the family. She consulted in
intermediate metastatic potential. September 2019 for an exaggeration of right flank pain
evolving for 2 months. The admission examination found a
Keywords: Ganglioneuroblastoma, Nodular, Metastatic, patient in good general condition with a WHO Performans
Bone, Female. Status of 1 and a painful mass on palpation of the right flank
with no other associated signs. We performed an abdomino-
I. INTRODUCTION pelvic CT scan without and with injection of contrast
product which objectified a voluminous formation of tissue
Ganglioneuroblastoma is a tumor belonging to the density and heterogeneous lobulated contours, visible in the
large family of neuroblastic tumors with two other entities right inter hepatorenal evoking an adrenal origin (Fig 1 and
including neuroblastoma and ganglioneuroma [1]. These are 2). It measured 6.6 cm in height by 12.8 cm in
tumors of the sympathetic nervous system, common in anteroposterior diameter and 10 cm in transverse diameter.
children and rare in adults. The most benign tumor is the The urinary dosages of acid derivatives of catecholamines
ganglioneuroma, which is composed of gangliocytes and (homovanillic acid, vanylmandelic acid) and methoxylated
mature stroma. Ganglioneuroblastoma is composed of both derivatives (metanephrine, normetanephrine) returned high
mature gangliocytes and immature neuroblasts and has an to 12 times normal. She then underwent an adrenalectomy.

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Volume 7, Issue 9, September – 2022 International Journal of Innovative Science and Research Technology
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The pathological examination found an adrenal gland 10]. Some are discovered with symptoms of distant
measuring 13 cm x 8 cm x 6 cm, entirely occupied by a metastases to other organs [11]. He does There are also no
neoplasm of multi-nodular appearance made up of nodules radiological signs specific to ganglioneuroblastoma and it is
0.5 to 2 cm in diameter, often containing significant difficult to make a preoperative diagnosis, although a biopsy
hemorrhagic changes and sometimes d fibro-myxoid aspect. can be performed in some cases before surgery. The ideal
The multinodular tumor proliferation is made of neuroblast imaging for the diagnosis of ganglioneuroblastoma and
cells at different stages of maturation (Fig 3 to 6), ranging metastases in adults is magnetic resonance imaging (MRI)
from small neuroblast to ganglion cell. We noted areas of and meta-iodo-benzylguanidine (MIBG) scintigraphy. PET-
necrosis, the presence of vascular emboli, the presence of FDG and technetium bone scintigraphy are additional means
calcification. The resection was complete R0, no normal that can help in the diagnosis of distant metastasis [12].
adrenal parenchyma is seen, but the adrenal capsule and the Bone is the second most common site of metastasis after
periadrenal fat are preserved. The immunohistochemistry lymph nodes [5, 6, 11, 12, 13]. Ganglioneuroblastoma cells
study showed expression of chromogranin (Fig 7), can activate both osteoclasts and osteoblasts and produce
synaptophysin (Fig 8), neurofilaments (Fig 9) with absence mixed lyticosclerotic bone metastases [11]. Of the 19 cases
of expression of PS 100 (Fig 10) and a Ki 67 at 37% (Fig found in the literature, 9 were metastatic, including 3 to
11). A postoperative thoraco-abdomino-pelvic CT scan was lymph nodes, 2 to bone, 2 to bone marrow and 2 others
performed showing osteolytic lesions of the cervix, left metastatic to the liver (Table 1). In adults the initial
femoral metaphysis and bilateral iliac wings (Fig 13 and 14), extension of the tumor is a fundamental criterion for the
with no residual tumor, no secondary hepatic or pulmonary prognosis, the International Neuroblastoma Staging System
visceral lesions. We completed the assessment with an (INSS) has defined 6 evolutionary stages summarized in
abdomino-pelvic MRI which objectified nodular lesions of table 2.
the right iliac wing, the right sacral fin and the L5 lumbar
vertebra enhanced after injection of gadolinium. The final diagnosis should always be confirmed by
pathological examination and immunohistochemistry for
We concluded that there was a 13 cm multinodular chromogranin-A, neurofilament, synaptophysin and neuron-
ganglioneuroblastoma metastatic to the bone. specific enolase [14, 15]. The usefulness of urinary
catecholamines in the diagnosis of ganglioneuroblastoma is
The patient was put on palliative Etoposide-Cisplatin limited. They cannot be used to differentiate between
type chemotherapy every 21 days, which took place without ganglioneuroblastoma and pheochromocytoma [16]. Urinary
toxicity greater than or equal to grade 2 according to catecholamine derivatives were negative or not searched for
CTCAE V5. After 6 cures, an abdominopelvic MRI and a in some cases in the literature, but they were high in other
bone scintigraphy were performed, reporting stability of the cases. In our case they were high at 12 times normal. The
bone lesions described above (Fig 16 and 17). We opted for International Neuroblastic Pathology Committee (INPC) has
a therapeutic window with close clinical and radiological grouped ganglioneuroblastoma into 2 subtypes: nodular
monitoring. She had 3 years of progression-free survival. ganglioneuroblastoma which is our present case and mixed
Currently she is in bone progression. Analgesic radiotherapy ganglioneuroblastoma [1]
on bone lesions and palliative chemotherapy are planned.
The nodular ganglioneuroblastoma has a poor
III. DISCUSSION prognosis while the mixed one has a good prognosis. The
age, the initial location and the stage of extension at the time
Neuroblastic tumors are apudomes of the neural crest of diagnosis are important prognostic factors.
[3]. They are classified into three histological groups:
neuroblastoma, ganglioneuroblastoma and ganglioneuroma. Treatments for ganglioneuroblastoma include surgery,
The three histological types constitute the different stages of chemotherapy, and radiation therapy. There is no consensus
the development of the same pathology and can be observed on a better treatment. The chemotherapy molecules used are
in the same tumour. Neuroblastoma is the least the combination of etoposide + cisplatin (as in
differentiated form with a high risk of metastasis, neuroendocrine carcinomas) and the combination
ganglioneuroblastoma is an intermediate form, with more (adriamycin, cyclophosphamide and ifosfamide) [23], [26].
neuronal ganglion cells than neuroblasts, and Due to the rarity of ganglioneuroblastomas, a prospective
ganglioneuroma is the most differentiated form with a lower study seems impossible. Survival data are limited. The
risk of metastasis [3, 1] longest follow-up is only 5 years in the localized form
against 2.5 years in the metastatic form. The combination of
We found 50 cases of ganglioneuroblastoma described these 03 therapeutic modalities is beneficial for patients as
in the literature with 19 cases located in the adrenal gland revealed by Schipper et al [5]. Frequent imaging (every 3
(Table 1). Males were predominantly represented. In these months) should also be part of careful follow-up.
19 cases, the mean age at the time of diagnosis was 38 years
with extremes of 20 and 63 years. The average size of the IV. CONCLUSION
tumor was 10.4 cm with extremes of 4.5 cm and 18 cm. No
typical symptoms are present in ganglioneuroblastoma. In Ganglioneuroblastomas are considered to have
some cases, the disease is manifested by symptoms related intermediate metastatic potential between neuroblastoma,
to local mass effect due to tumor expansion [7], as in our which is malignant and therefore highly metastatic, and
present case. Some cases can be found incidentally [4, 8, 9, ganglioneuroma, which is benign and therefore potentially

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Volume 7, Issue 9, September – 2022 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
not very metastatic. The treatment will depend on the stage
of diagnosis and the general condition of the patient at the
time of diagnosis.

Fig 4 Mature Component in Low Magnification

Fig 1 CT Showing Right Adrenal Mass

Fig 5 Immature Component at High Magnification

Fig 2 CT Showing Right Adrenal Mass

Fig 6 Immature Component at Low Magnification

Fig 3 Mature Component at High Magnification Fig 7 Chromogranin Expression

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Fig 12 No Expression PS 100

Fig 8 Synaptophysin Expression

Fig 9 Neurofilament Expression Fig 13 Postoperative CT Scan Showing the Left Bone
Lesion

Fig 10 GFAT
Fig 14 Postoperative CT Scan Showing Iliac Lytic Bone
Lesion

Fig 11 Expression KI 67
Fig 15 Postoperative Bone Scan

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Volume 7, Issue 9, September – 2022 International Journal of Innovative Science and Research Technology
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Fig 16 Bone Scan after Chemotherapy Fig 17 Bone Scan after Chemotherapy
Table 1 Case of Adrenal Ganglioneuroblastoma
Pati Auteur A S Taille Localis Activité Métastases Traitement Survie
ent ge ex (cm) ation sécretoire
1 Butz (1940) 25 M NR NR NR Foie NR NR
[21]
2 Cameron 58 F NR Droite VMA, HVA Aucun Chirurgie 3,5 ans sans
(1967) [22] récidive
3 Takahashi 21 M 8,8 Gauche VMA, HVA Ganglion Chirurgie + 8 mois sans
(1988) [23] RTH + CTH récidive
4 Kishikawa 29 M 11 NR VMA, HVA Os Chirurgie + NR
(1992) CTH
5 Kiozumi 47 F 9 Droite VMA, HVA Moelle osseuse Aucun 3 mois décédé
(1992) [24]
6 Higuchi (1993) 29 M 11 NR Catécholamines Moelle osseuse Chirurgie 10 mois sans
[25] urinaires récidive
7 Hiroshige 35 M 10 Gauche Aucune Aucune Chirurgie 2 ans sans
(1995) [9] récidive
8 Mehta (1997) 22 M 9 Bilatéral NR NR Chirurgie NR
[18]
9 Rousseau N F NR Gauche NR Foie Chirurgie + NR
(1998) [26] R RTH + CTH
10 Fujiwara 25 M 9 Gauche Aucune Aucune Chirurgie 5 ans sans
(2000) [27] récidive
11 Slapa (2002) 20 F 18 NR Aucune Aucune Chirurgie 1 an sans
[19] récidive
12 Koike (2003) 50 M 4,5 Droite Aucune NR Chirurgie 2,5 an sans
[8] récidive
13 Gunlusoy 59 M 12 Droite Aucune Ganglion Chirurgie NR
(2004) [20]
14 Mizuno (2010) 53 M 11 Droite Aucune Os (Vertèbres Chirurgie + 2,5 ans avec
[13] lombaire) RTH récidive
15 Bolzacchini 63 M 5 Gauche Aucune Aucune Chirurgie 6 mois sans
(2015) [17] récidive
16 Qiu (2015) [10] 27 F 11 Gauche Aucune Aucune Chirurgie 5 mois sans
récidive
18 Xiaobo (2015) 27 F 11,5 Gauche NSE Aucune Chirurgie NR
[4]
17 Stefano (2017) 21 F 11 Gauche Aucune Ganglion Chirurgie 21 mois sans
[6] récidive
18 Zahra (2018) 38 M 4,7 Droite Aucune Aucune Chirurgie
[16]
HVA= Homovanillic acid, VMA = Vanylmandelic acid, RTH = Radiotherapy, CTH = Chemotherapy, NR = Not specified

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Table 2 Stage of Extension of Peripheral Neuroblastic Tumors According to the INSS
STADIUM DESCRIPTION
Stage 1 Localized tumour, no local lymph node metastasis, complete surgical excision
Stage 2A Localized tumour, no local lymph node metastasis, incomplete surgical excision
Stage 2B Localized tumour, ipsilateral lymph node metastasis, complete surgical excision
Stage 3 Localized PTN, non-operable And crossing the midline or midline tumor with bilateral extension or localized
tumor with contralateral lymph node metastasis
Stage 4 Metastatic tumor (remote lymph nodes, bone, medullary, etc.)
4S stage Tumors occurring before 1 year, associating a localized primitive site with extensions to the liver, to the skin
and/or bone marrow, excluding bone damage

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