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

ISSN No:-2456-2165

About A Rare Case of Small Neuroendocrine

Carcinoma of the Mandible at the University
Hospital of Casablanca in Morocco
Ismael Coulibaly1, Hanane Rida1, Tarik Chékrine1, Zineb Bouchbika1, Nadia. Benchakroun1, Hassan Jouhadi1,
Nezha. Tawfiq1, Souha Sahraoui1
1
Mohamed VI Center for the Treatment of cancers, CHU Ibn Rochd, Hospital Districts, 20360 Casablanca, Morocco

Abstract :- Neuroendocrine tumors (NETs) arise from II. CLINICAL CASE

neuroendocrine cells and are mostly observed in the
gastrointestinal tract, pancreas, and lungs. NETs in the A 67-year-old Moroccan man, chronic smoker at 15
oral and maxillofacial region are extremely rare. We pack-years, weaned 10 years ago. He is known hypertensive
report a case of a 67-year-old man with an NET in the with cardiac arrhythmia controlled under treatment. He has a
mandible. The patient did not show any symptoms history of eye surgery for cataract in 2009. This patient was
except for remarkable jugular swelling. The lesion seen in consultation for a swelling of the right cheek
appeared as a radiolucent honeycomb abnormality with evolving for 08 months and gradually increasing in size
bone destruction on panoramic radiography. The becoming painful, the starting point of which would be the
histopathologic diagnosis following a biopsy was NET. right mandibular angle. On clinical examination, the patient
Contrast-enhanced computed tomography (CT), 18F- was in good general condition with a WHO Performance
fluorodeoxyglucose positron emission computed Status of 1. There was a voluminous swelling on the right
tomography (18F-FDG PET/CT), showed tumor mass of cheek of about 20 cm in long axis, painful, taking the
the soft parts of the right mandible with bone lysis ascending branch of the mandible with infiltration in endo -
without lymph node, visceral or bone hypermetabolism . buccal (Picture 1). Mouth opening was limited and there was
He had three chemotherapy cures with good clinical and no peripheral clinical lymphadenopathy.
radiological response followed by concomitant radio
chemotherapy 60Gy.The evolution was marked by a A cervico-facial scan was performed showing tumor
febrile grade IV aplasia leading to the death of the mass under and latero mandibular right coming into contact
patient. Neuroendocrine carcinomas of mandible are with the right parotid and encompassing the submaxillary
unusual. Their prognosis is overall bleak. The responsible for mandibular lysis (Image 3)
morphological characteristics, the clinical aspects and
the therapeutic management of these tumors are A biopsy of the mass was performed. The histological
comparable to the neuroendocrine tumors of the lung. study shows a malignant proliferation of undifferentiated
round cells of medium size with an indistinct scanty
Keywords :- Neuroendocrine Small Cell Carcinoma, cytoplasm and a hyperchromic, irregular, sometimes
Mandible, Radiotherapy, Chemotherapy, Surgery. strongly nucleolated nucleus. Immunohistochemical study
showed tumor cells with intense and diffuse synaptophysin
I. INTRODUCTION positivity, but negative for chromogranin A, cytokeratin, CD
20, CD 3, CD 99, desmin and myogenin with a Ki 67 at
Neuroendocrine tumors arise from neuroendocrine 60%.
cells and are mainly seen in the gastrointestinal tract,
pancreas and lungs [1]. Neuroendocrine cells of the oral Positron emission tomography with 18 FDG coupled
mucosa are an underestimated component of the with CT scan showed a hyper metabolic process of the soft
neuroendocrine system whose biological roles are elusive in tissues encompassing the right mandible with bone lysis
the oral cavity [2]. Neuroendocrine carcinoma is a tumor extending submandibularly and ascending along the
that occurs in different places, especially the lungs and the ascending branch of the mandible with a max SUV at 10.22
larynx. The oral cavity is a very rare location for primary for a max liver SUV at 2.2 (Image 5). There was no lymph
neuroendocrine carcinomas [3]. These tumors also have a node, visceral or bone hypermetabolism.
very unfavorable prognosis. The diagnosis is often made at
an advanced stage which further darkens its prognosis. Due Based on these findings, a diagnosis of poorly
to their rarity, there is no standard of care. The treatment is differentiated small cell neuroendocrine carcinoma of the
generally based on the data already known in the right locally advanced gingiva was made. The patient
management of pulmonary localization. However, it is received 3 courses of neoadjuvant chemotherapy based on
necessary to be familiar with the different therapeutic Etoposide + Cisplatin. He developed non-febrile Grade 2
modalities for better management. We report a case of neutropenia after the second course. Post-chemotherapy
neuroendocrine carcinoma of the gum. evaluation by cervico-facial CT scan noted a 90% regression
in size of the mass (Image 4). For surgeons, a surgical

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Volume 7, Issue 9, September – 2022 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
intervention would be very dilapidating with a Diagnosis is based on pathological examination. On
mandibulectomy. We therefore decided on concomitant histological examination, the diagnosis of the
radio-chemotherapy with dose reduction: association of neuroendocrine nature of these tumors is suggested by
homolateral locoregional irradiation at a dose of 60 Gray in morphology and confirmed after an immunohistochemistry
classic fractionation of 30 sessions and two sessions of study. The morphological aspect is similar to what is
etoposide 100 mg and cisplatin 20 mg chemotherapy on D1 observed in the lung: neuroendocrine morphology with a
and at D21. After 15 radiotherapy sessions, the patient high mitotic and necrotic power. The cells are large, with
presented with grade 3 mucositis plus non-febrile grade 4 moderate to abundant cytoplasm [20]. In terms of
neutropenia, which led us to stop radiotherapy and immunohistochemistry, neuroendocrine carcinomas are
hospitalize him. The patient unfortunately died in an array of defined by the presence of neuroendocrine markers,
multi-visceral failure. essentially chromogranin A, synaptophysin, neuron-specific
enolase (NSE) and CD56 [20]. However, the expression of
III. DISCUSSION neuroendocrine markers is inconstant and the absence of
expression of one of these markers does not exclude the
A neuroendocrine tumor is an epithelial tumor whose diagnosis of neuroendocrine carcinoma. In the 04 cases of
cells present structural, phenotypic and functional neuroendocrine carcinoma of the gingiva published in the
characteristics reminiscent of those of normal endocrine literature that we reported, synaptophysin was always
cells secreting peptide hormones [2]. They constitute a expressed whereas chromogranin was positive in only 3
heterogeneous group of tumors arising from cells of the patients [3; 17; 18; 19]. In our observation, only
diffuse neuroendocrine system [4]. They differ in their synaptophysin is expressed. However, to retain the diagnosis
location, embryological origin, degree of differentiation, of a neuroendocrine carcinoma of the gum with certainty,
biological behavior, functional activity and size but share the presence of another primary site must be excluded. In
common morphological, immunohistochemical and the literature, the clinical manifestations are not always
structural characteristics [5]. These are rare tumors but can described, but in most localizations of the oral cavity, we
be found in most locations. There are several classifications find a painful swelling as a reason for consultation [3], as in
of neuroendocrine tumors depending on the primary our case. The general condition is most often preserved at
location. On the head and neck, they are classified as typical the time of diagnosis.
carcinoid, atypical carcinoid, small cell neuroendocrine
carcinoma which can be well, moderately or poorly Computed tomography has been used in the arsenal of
differentiated [6; 7]. the paraclinical assessment in several studies. The place of
PET-FDG is not clearly defined, it is mainly used to search
The predilection site of neuroendocrine carcinomas is for clinically non-noisy secondary localizations
the lung and the digestive tract. But other rare locations are
encountered in the literature, in this case gynecological [8; Therapeutically, there is no therapeutic standard given
9; 10], head and neck [11; 12], bladder [13] and breast [14; the rarity of neuroendocrine carcinomas of the gums.
15]. In terms of ENT and stomatology, the frequent location Radical surgery and adjuvant chemotherapy using cisplatin
is the larynx, gingival neuroendocrine carcinoma is and etoposide seem to be good options for localized forms
exceptional [2]. In an analysis of the National Cancer Center [21]. The rechemoth dieterapie for carcinomaatsmall cells of
database in 2017 in the United States, out of 1042 patients lung origin, which includes genotecisplatin andetoposide is
with small cell carcinoma of the head and neck, only 9% had most often used [11]. In case of non-metastatic disease,
an oral location [12]. Small cell neuroendocrine carcinoma chemotherapy can be used in neoadjuvant or adjuvant
is frequently encountered in the elderly with a history of treatment to reduce tumor burden and reduce the risk of
smoking, as is the case in our patient [16]. ENT and dental distant metastasis. In a series published by Pointer et al in
neuroendocrine carcinomas are very aggressive and have an 2017, 61% of patients had received chemotherapy and
unfavorable prognosis with lymph node, locoregional and radiotherapy combined. Concomitant radiochemotherapy
distant involvement [12; 17]. Small cell forms are rare in the was the most frequent treatment in patients with early and
oral cavity and very few are localized to the gumline. HAS locally advanced disease [12]. Although surgery has an
To our knowledge, we find in the literature a case localized important role in local control, the Pointer et al series
at the level of the retromolar trigone described by Benning showed that adding surgery to radiotherapy and
et al [18], a case reported by Mochizuki Y et al [17] on the chemotherapy in patients with locally advanced disease does
upper gum but combined with squamous cell carcinoma. not did not result in improved survival compared to patients
Zeng M et al [19] reported a case on the lower gingiva and a treated with combined radiotherapy and chemotherapy [12].
case on the lower anterior gingiva was reported by Wu The case reported by Benning et al [18] had been treated
Zhang B. et al in 2014 in a 25-year-old woman with chemotherapy only and the evolution was marked by a
[3].Epidemiologically, the sex ratio is 6/1 for locoregional recurrence and the patient died of his disease
neuroendocrine carcinomas of the oral cavity and 11/1 for 30 months after diagnosis. Overall survival for all patients
localizations of the oral mucosa. Most patients are over 50 with small cell carcinoma of the head and neck was 20.3
years old [2]. months in the National Cancer study [12]. In light of these
data from the literature which highlight the role of systemic
treatment in this disease, neoadjuvant chemotherapy is
recommended before any local treatment in locally

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Volume 7, Issue 9, September – 2022 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
advanced disease. Faced with a locally advanced disease, the IV. CONCLUSION
prognosis is poor from the outset, the trimodal treatment
consisting of chemotherapy, surgery and radiotherapy, Although neuroendocrine carcinomas are well
which is the ideal combination, hardly improves survival described in certain locations, particularly the lungs, they
[12]. In our case the patient responded well to neoadjuvant remain a poorly understood entity, especially in the oral
chemotherapy, the observed toxicity could be related to the location. Due to the lack of knowledge about this type of
concomitant chemotherapy. tumor coupled with their non-specific clinical behavior, the
disease often reaches an advanced stage before the diagnosis
is made, making cure impossible. We have reported a case
of rare neuroendocrine carcinoma occurring in the gingiva.
He had a reserved prognosis from the outset with local
invasion. We consider that for locally advanced forms that
cannot be resected from the outset:

APPENDICES

Picture 1 Photo at the First Day in Consult. Picture 2 Photo After 3 Courses of Chemotherapy

Picture 3 Axial Slice on Diagnostic CT Picture 4 CT Slice After Chemo

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Volume 7, Issue 9, September – 2022 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165

Picture 5 PET Image of Diagnostic

Table 1 Distribution Of Cases Reported In The Literature

Authors Age/Sex Size (Cm) Extension Treatment Survival In Months
Wu Zhang B et 25/F 1.5x2 localized Wide surgery only 13 months progression-free
al survival
38/F 2x3 localized Surgery + Radiotherapy 08 months progression-free
survival
Mochizuki Y et 62/F 2x0.8x0.6 localized Surgery with 23 months progression-free
al [17] maxillectomy only survival
Benning et al 63/M Unspecified localized Chemotherapy + Local recurrence at 08 months
[18] Radiotherapy 60 Gray Distant metastasis at 20
months
Death at 24 months
Zeng M et al 73/M 2.8x2x1.4 localized Large surgery and 14 months progression-free
[19] partial mandibulectomy survival
+ chemo

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