Head-and-Neck Solid Tumors in Children: A Retrospective Review from a Tertiary Care Institute in North India.

OBJECTIVES: The aim of this study was to review the clinical profile, management, and outcome of solid tumors in the head-and-neck region in children at our institute.
METHODS: We retrospectively reviewed children with head-and-neck solid tumors who were treated jointly under the departments of Pediatric Surgery and Otorhinolaryngology at our institute between 2016 and 2019.
RESULTS: In the study period, 10 children (6 males, 4 females) with a median age of 9.5 years (range 5 days-16 years) were treated by our unit. The patients had four tumors arising from the parotid, 2 from nose/naso-pharynx, 1 each from the tongue, submandibular gland, para-pharyngeal space, and infratemporal fossa. A majority (90%) of the patients underwent complete surgical excision of the tumor, preserving the loco-regional neurovascular structures to minimize postoperative morbidity. Malignant lesions were seen in 4 patients (2 rhabdomyosarcoma, 1 primitive neuro-ectodermal tumor, 1 mucoepidermoid carcinoma) and 6 patients had benign pathology (3 pleomorphic adenoma, 2 mature teratoma, 1 schwanomma). Additional therapy with chemotherapy and local radiotherapy was required in 3 out of 4 patients with malignant pathology. The median follow-up duration is 15 months. At last follow-up, all patients are alive and 9 out of 10 patients (90%) are disease-free.
CONCLUSION: Our experience highlights rare and difficult tumors in the head-and-neck region in children. These tumors are not commonly managed by the pediatric surgeon in routine practice. The paper outlines the multi-modality management of these tumors, which is essential for an optimal outcome. Copyright:

INTRODUCTION

Head-and-neck tumors account for approximately 5% of all pediatric tumors.[1] This includes both benign as well as malignant tumors and tumor-like conditions. The management of these tumors in children poses a unique challenge to the treating team owing to the varied anatomical and physiological considerations in the pediatric population. The aim of this study was to review the clinical profile, management, and outcome of solid tumors in the head and neck region in children at our institute.

METHODS

This is a retrospective observational study performed jointly under the departments of Pediatric Surgery and Otorhinolaryngology at our institute for 3 years (2016–2019). The electronic medical records of all patients under 18 years of age with head-and-neck solid tumors who were treated by our unit were reviewed. Patients with hematological (lymphoma/leukemia), endocrine (thyroid/parathyroid), or vascular (hemangioma/lymphangioma) tumors were excluded as these are managed by other units at our center. The medical records of included patients were reviewed and analyzed in detail with regard to demographic features, clinical presentation, site of origin, pathology, surgical procedure, requirement of chemotherapy and/or radiotherapy, follow-up, and outcome.

The diagnostic algorithm for these tumors usually began with a detailed history and physical examination. This was followed by imaging with ultrasonography (USG), computed tomography (CT) and/or magnetic resonance imaging (MRI). Histopathological diagnosis was achieved with a USG guided fine needle aspiration cytology or tru-cut biopsy, incisional or excisional biopsy, as appropriate. Tumor markers like alpha fetoprotein or beta-human chorionic gonadotropin were estimated as indicated.

RESULTS

In the study period, ten children (6 males, 4 females) with a median age of 9.5 years (range 5 days–16 years) were treated by our unit [Table 1]. The patients had 4 tumors arising from parotid, 2 from nose/naso-pharynx, 1 each from the tongue, submandibular gland, para pharyngeal space and infratemporal fossa. A majority (90%) of the patients underwent complete surgical excision of the tumor, preserving the loco-regional neurovascular structures to minimize postoperative morbidity. Malignant lesions were seen in 4 patients (2 rhabdomyosarcoma [RMS], 1 primitive neuro-ectodermal tumor [PNET], 1 mucoepidermoid carcinoma) and 6 patients had benign pathology (3 pleomorphic adenoma, 2 mature teratoma, 1 schwanomma). Additional therapy with chemotherapy and local radiotherapy was required in 3 out of 4 patients with malignant pathology [Table 1]. The median follow-up duration is 15 months. At last follow up, all patients are alive and 9 out of 10 patients (90%) are disease-free.

Table 1

Clinical profile of children with head and neck solid tumors (2016-2019)

Age	Sex	Clinical presentation	Diagnosis	Site of origin	Imaging	Surgery	Histopathology	Benign (B)/malignant (M)	Chemo	RT	FU
5 days	Male	Antenatally diagnosed large neck mass, delivered by exit procedure	Left cervical teratoma	Neck	Fetal MRI: 12 cm × 11 cm × 9 cm, solid - cystic mass in the left cervical regionPost natal CT: Large left cervical mass completely displacing the airway	Excision	Mature teratoma	B	-	-	CR
18 days	Male	Oro-nasal mass with large extra-oral component causing respiratory distress	Nasopharyngeal teratoma	Nasopharynx	CT: Large heterogeneous mass arising from the base of sphenoid and filling the entire nasal and oral cavities	Excision	Mature teratoma	B	-	-	CR
1.5 years	Male	Swelling of nose and upper lip × 5 months. On examination: a palpable mass completely obliterating both nasal cavities on examination	Oro-nasal RMS	Maxilla	MRI: Lobulated sino-nasal mass (5×4.5 cm) involving both nasal cavities and reaching upto the cribriform plate	Excision	RMS	M Stage 3 (Para- meningeal, T2bN0M0)	+	+	CR
5 years	Male	Swelling of the left cheek × 2 months causing difficulty in opening the mouth	Left parotid RMS	Left parotid	CT: Ill defined, heterogenous, soft tissue mass (4.6 cm×3.6 cm×3.7 cm), involving superficial lobe of the left parotid gland and infiltrating the masseter muscle	Left total parotidectomy	RMS	M Stage 1 (nonpara-meningeal, T2bN0M0)	+	+	CR
7 years	Male	Swelling on left side of tongue × 2 years	Lingual schwannoma	Tongue	CT: Well defined lesion (3 cm × 3 cm) on left lateral border of tongue	Excision	Schwannoma	B	-	-	CR
12 years	Female	Swelling of the left parotid region × 2 years	Left parotid pleomorphic adenoma	Left parotid	CT: Well defined lesion (2.5 cm×1.8 cm) in superficial lobe of left parotid gland	Left superficial parotidectomy	Pleomorphic adenoma	B	-	-	CR
13 years	Female	Swelling of left submandibular region × 5 years	Left submandibular gland pleomorphic adenoma	Left submandibular gland	CT: Well defined lesion (2.9 cm × 2.4 cm) from lower border of left submandibular gland	Excision of left submandibular gland	Pleomorphic adenoma	B	-	-	CR
16 years	Male	Swelling of the right parotid region × 2.5 years	Right parotid pleomorphic adenoma	Right parotid	CT: Well defined lesion (3 cm × 3 cm × 4 cm) in superficial lobe of right parotid gland	Right superficial parotidectomy	Pleomorphic adenoma	B	-	-	CR
13 years	Female	Swelling of the right parotid region × 2 years with increase in size of the swelling for past six months	Right parotid muco epidermoid carcinoma	Right parotid	CT: Well defined lesion (3 cm × 3 cm) with cystic component in right parotid gland	Right superficial parotidectomy	Muco epidermoid carcinoma (low grade)	M Stage 1 (T2N0M0)	-	-	CR
16 years	Female	Swelling of right side of neck × 1 yearHoarseness of voice ×1 week	Right para - pharyngeal PNET	Paraphryngeal space	CT: Large heterogeneously enhancing soft tissue mass (7 cm × 7 cm × 8 cm) extending from transverse process of C1 vertebra to C6, into parapharyngeal space with encasement of internal carotid artery	Incisional biopsy	PNET	M Stage 3 (T2bN0M0)	+	+	PR

RMS: Rhabdomyosarcoma, PNET: Primitive neuro-ectodermal tumor, Chemo: Chemotherapy, RT: Radiotherapy, FU: Follow up, CR: Complete response, PR: Partial response, CT: Computed tomography, MRI: Magnetic resonance imaging

Teratoma

Case 1

A 26-year-old primigravida presented to our fetal medicine unit at 38 weeks of gestation with an ultrasonogram (USG) showing a large, heterogeneous neck mass in the fetus. Fetal MRI was done, which revealed a 12 cm × 11 cm × 9 cm, solid–cystic mass in the left cervical region, completely engulfing and displacing the fetal airway [Figure 1a]. A male baby weighing 3.2 kg was delivered by EXIT procedure involving a multi-disciplinary team. The fetal airway was secured by video laryngoscopy guided endotracheal intubation while maintaining the uteroplacental circulation [Figure 1b]. Postnatal CT confirmed the findings of a huge, heterogeneous left cervical mass completely displacing the airway [Figure 1c]. Surgical excision was planned on day 3 of life. Complete surgical excision of the mass, preserving all vital structures of the neck was performed [Figure 1d]. Postoperatively, the baby required prolonged ventilation and ICU care. Histopathology revealed features consistent with mature teratoma.

Figure 1

Left cervical teratoma (a) Fetal magnetic resonance imaging showing mass in the left cervical region (short arrow) compressing the airway (long arrow) (b) Video laryngoscopy image during EXIT procedure showing intra-oral mass (star) compressing the laryngeal inlet (c) Postnatal computed tomography showing a large, heterogenous, left cervical mass (d) Tumor dissected from vital structures in the neck; common carotid artery (white arrow), brachial plexus (black arrow)

Case 2

A 4-day-old male baby presented to us with a huge mass occupying almost the entire oral cavity with a large extra-oral component [Figure 2a]. The baby had mild respiratory distress and was being fed by an oro-gastric tube. CT revealed a heterogeneously enhancing mass arising from the base of sphenoid and filling the entire nasal and oral cavities [Figure 2b]. Surgical excision was planned. Endotracheal intubation was achieved by video laryngoscopy, and airway was secured. Tumor was dissected all around till the base of sphenoid and complete excision was done [Figure 2c and d]. Histopathological examination was suggestive of a mature teratoma. Cleft palate repair was done at around 1 year of age. The baby is asymptomatic at 3-year follow-up.

Figure 2

Nasophayngeal teratoma (a) Clinical photograph showing the extent of the mass (b) computed tomography showing a large heterogeneous mass arising from the base of sphenoid (arrow) (c) Intra-operative position of patient with endotracheal tube in situ (d) Intra-oral view following complete excision of the mass showing cleft palate (black arrow) and site of origin from the base of sphenoid (white arrow)

Rhabdomyosarcoma

Case 3

A 10-month-old boy presented to us with swelling of the nose and upper lip of 5 months. Both nasal cavities were completely obliterated at presentation with a fleshy, palpable mass [Figure 3a]. MRI revealed a lobulated sino-nasal mass (50 mm × 45 mm) involving both nasal cavities and reaching up to the cribriform plate [Figure 3b]. USG guided tru-cut biopsy showed features of RMS. Metastatic workup was negative. The tumor was staged as Stage 3 (Para meningeal, T2bN0M0). As the tumor was unresectable at presentation, neo-adjuvant vincristine, actinomycin D, cyclophosphamide (VAC) chemotherapy was started, Following 10 weeks of chemotherapy, repeat CT showed a significant reduction in size and extent of the lesion [Figure 3c]. Complete surgical excision was performed by a sublabial approach [Figure 3d-f]. Histopathology revealed alveolar RMS with one of the surgical margins positive for tumor cells. The patient was given local radiotherapy and adjuvant chemotherapy. At last follow-up, the child was disease-free.

Figure 3

Oro-nasal rhabdomyosarcoma (a) Location and extent of the tumor at presentation (b) magnetic resonance imaging showing a lobulated mass (arrow) involving both nasal cavities and reaching upto the cribriform plate (c) computed tomography following chemotherapy showing a small residual mass (arrow) (d) Residual nasal mass (arrow) (e) Dissection of the mass by a sub labial approach (f) Complete excision of the tumor with preserved nasal septum and columella

Case 4

A 5-year-old boy presented to us with swelling of the left cheek for the past 2 months [Figure 4a]. He complained of difficulty in opening the mouth. CT revealed an ill-defined heterogeneously enhancing soft tissue mass (46 mm × 36 mm × 37 mm) involving superficial lobe of the left parotid gland and infiltrating the masseter muscle medially [Figure 4b]. USG guided tru-cut biopsy showed findings consistent with embryonal RMS. Metastatic workup was negative. The tumor was staged as Stage 1 (non-para meningeal, T2bN0M0). Neo-adjuvant VAC chemotherapy was started following diagnosis, Following 6 weeks of chemotherapy, clinical examination [Figure 4c], and repeat CT [Figure 4d] showed a significant reduction in size and extent of the lesion. On surgical exploration, the residual left parotid mass was found infiltrating the skin superficially and masseter muscle in the deep plane. The main trunk of the facial nerve and all its branches were dissected carefully and preserved using a nerve stimulator [Figure 4e]. Total left parotidectomy was done; skin infiltrated by the tumor was excised along with masseter muscle with a wide margin. Histopathological examination of the specimen confirmed embryonal RMS with all surgical margins free of tumor. The patient was given local radiotherapy and adjuvant chemotherapy. At 3-year follow-up, the child is disease-free with no evidence of facial nerve palsy or any other morbidity [Figure 4f].

Figure 4

Left parotid rhabdomyosarcoma (a) Site and extent of the tumor at presentation (b) computed tomography showing a heterogenous soft tissue mass involving superficial lobe of the left parotid gland and infiltrating the masseter muscle medially (c) Reduction in size of the mass following chemotherapy (d) computed tomography showing residual mass (arrow) following chemotherapy (e) Dissection of the mass from Facial nerve (arrow) (f) Follow up photograph after 3 years

Schwannoma

Case 5

A 7-year-old boy presented with swelling on the left side of the tongue for the past 2 years. There were no other complaints. On examination, there was a 3 cm × 3 cm, well-defined, firm, nonpulsatile lesion on the left lateral border of the tongue. Cytopathology was positive for spindle cells, suggestive of a benign mesenchymal lesion. Complete extra-capsular excision was done, and the tongue was reconstructed by primary closure. Histopathology of the lesion confirmed schwannoma. Postoperatively, patient did not report any difficulty in swallowing or impaired tongue mobility.

Pleomorphic adenoma

Case 6, 7, 8

There were three cases of pleomorphic adenoma of major salivary glands. Two cases were of parotid gland origin, while one was a submandibular gland pleomorphic adenoma. All patients were subjected to CT with contrast, which revealed a hypo-isointense, well-defined, noninfiltrating lesion. Preoperative cytology in all three patients was suggestive of pleomorphic adenoma. Superficial parotidectomy was performed in patients with parotid lesions, and the tumors were completely excised. On follow-up, there was no evidence of facial palsy or recurrence. The patient with submandibular gland lesion was managed by trans-cervical submandibular salivary gland excision. There were no postoperative complications or recurrence in the follow-up period.

Muco epidermoid carcinoma

Case 9

A 13-year-old female presented with swelling of the right parotid region for 2 years with a progressive increase in the size of the swelling over the past 6 months. Clinical examination revealed a 6 cm × 3 cm, hard swelling of the right parotid gland [Figure 5a]. Cytopathology was negative for malignant cells. CT revealed a 3 cm × 3 cm well-defined lesion in the right parotid with cystic areas. Intraoperatively, tumor was infiltrating the masseter muscle medially. Superficial parotidectomy was done with the excision of infiltrated muscle with the preservation of facial nerve branches [Figure 5 and c]. Histopathology revealed low-grade mucoepidermoid carcinoma. The patient is on regular follow-up and has no evidence of recurrence.

Figure 5

Right parotid muco epidermoid carcinoma (a) Right side modified Blair's incision, (b) superficial musculo-aponeurotic system layer elevated, the solid (^) and cystic (*) portion of the tumour exposed and (c) after near total excision, the masseter muscle (#) and terminal branches of Facial nerve (arrows) exposed

Primitive neuro-ectodermal tumor

Case 10

A 16-year-old girl presented to us with swelling of the right side of the neck for 1 year and hoarseness of voice for the past 1 week. On examination, there was a 10 cm × 8 cm, firm mass extending from the right submandibular region to the mastoid tip. Imaging revealed a large, heterogeneously enhancing soft tissue mass (70 mm × 70 mm × 80 mm), extending from the transverse process of C1 to C6 vertebra into the parapharyngeal space, compressing and displacing the trachea with encasement of the internal carotid artery. An incisional biopsy was done to obtain adequate tissue for histopathology and immunohistochemistry (IHC). Histopathology revealed a round cell tumor of neuro-ectodermal origin. IHC was positive for CD99, focally positive for EMA and CK and negative for synaptophysin, chromogranin, desmin, myogenin, and vimentin. These findings were suggestive of PNET. The patient received chemotherapy, followed by external beam radiotherapy to the neck. The tumor showed partial response with the persistence of a small nonprogressive residual tumor. The patient is symptom-free and under regular follow-up.

DISCUSSION

Pediatric head-and-neck tumors include both benign, malignant, and tumor-like conditions. In our series, there were 6 benign and 4 malignant lesions. The most prevalent benign tumor in this age group is hemangioma affecting almost 10% of the pediatric population,[2] while malignant tumors of lymphoid origin are the most common malignant lesions in this age group.

Major salivary gland neoplasms are rarely seen in the pediatric population. Benign lesions are more common than malignant. The most common benign parotid neoplasm is pleomorphic adenoma.[3] Pleomorphic adenoma, though benign, has a high recurrence rate, and long-term follow-up is mandatory. If left untreated, pleomorphic adenoma progressively enlarges, and malignant degeneration is known.[4] In a study by Rodriguez et al., among 11 pediatric patients with pleomorphic adenoma of the parotid gland, 7 underwent superficial parotidectomy, 3 required total parotidectomy, and in 1 patient excisional biopsy was done. There was 1 postoperative recurrence in this series.[5] Another study by Malone and Baker consisted of 30 patients with pleomorphic adenoma of the salivary gland, all patients were considered for surgical intervention, of which 11 patients developed recurrence.[6] In our series, out of three patients with pleomorphic adenoma, two were parotid lesions, while one affected the submandibular gland. All the cases were managed with complete surgical excision. None of the patients developed neurovascular complications or recurrence.

There was one case of low-grade mucoepidermoid carcinoma of the parotid gland in our series, which was managed by complete surgical excision. Malignant salivary neoplasms are rare in the pediatric age group, with an incidence of 0.4–2.6 cases/100000 populations.[7] Among the malignant lesions, mucoepidermoid carcinoma is the most common malignant salivary gland neoplasm.[8] These lesions should be surgically excised with tumor-free margin to avoid loco-regional recurrence.[9] Low-grade tumors have a more favorable prognosis than high-grade tumors. High-grade tumors should be managed by postoperative radiotherapy.[10] Treatment strategy should be individualized in these rare malignancies.

RMS of head-and-neck accounts for one-third of pediatric RMS.[11] RMS is often associated with various syndromes. Head-and-neck RMS can be sub-classified into orbital, para-meningeal, and nonorbital/non-parameningeal. Nose and nasal cavity RMS are included in parameningeal RMS.[11] We had one case of parameningeal RMS involving the nasal cavity and maxilla. The patient was managed with wide local excision, chemotherapy and local radiotherapy. There was also one case of nonorbital/nonparameningeal RMS of the right parotid gland. Neo-adjuvant chemotherapy was started, and total conservative parotidectomy was done. The patient completed chemotherapy and radiotherapy and showed no signs of residual disease or recurrence on follow-up. RMS should be managed aggressively with multi-modality therapy to achieve complete remission and a disease-free survival. Chemotherapy forms the mainstay of treatment as micro-metastasis are seen even in the initial stages of the disease.[12] Surgical excision should aim at wide local excision with negative margins, which improves the survival rate.[13] However, this is not always feasible in a case of para-meningeal RMS.

Peripheral PNET (pPNET) are family of tumors of neuro-ectodermal origin. pPNET of head and neck are extremely rare lesions that arise from peripheral, nonautonomic neuronal tissue. The most common site of pPNET is orbit followed by neck and parotid.[14] Histopathological and immunohistochemical studies are unable to distinguish between PNET and Ewing's disease.[15] We had one case of parapharyngeal space pPNET in our series which was managed with chemotherapy and radiotherapy. Aggressive multi-modality therapy is the best way to treat these lesions. Early recognition of the disease is important to achieve complete surgical excision with tumor-free margins. Chemotherapy and radiotherapy form the mainstay of treatment in most cases. In our case, tumor was inoperable due to encasement of surrounding neuro-vascular structures and hence, the patient was managed with chemotherapy and radiotherapy.

Teratomas arise from totipotent germ cells and consist of derivatives of all three embryonic germ cell layers-ectoderm, endoderm, and mesoderm. In infancy, they are most commonly encountered in the saccrococcygeal region.[16] Head-and-neck teratomas are rare and account for 2%–9% of all teratomas.[17] These tumors can cause significant morbidity and mortality when seen in the head-and-neck region. Nasopharyngeal teratoma causes significant respiratory obstruction in neonates who are obligate nasal breathers. They may be diagnosed during antenatal ultrasonography. If it appears that the tumor is causing significant compression of the airway, an EXIT procedure can be planned to secure the airway on placental circulation.[18] Further treatment is aimed at complete surgical excision with local reconstruction with preservation of neurovascular structures. In our series, there was 1 case of nasopharyngeal mature teratoma that presented after birth and was managed by complete surgical excision and reconstruction. The second case was a large cervical teratoma that was diagnosed antenatally and was compressing the airway. The baby was delivered and intubated at our center by an EXIT procedure. Subsequently, complete surgical excision was performed, preserving the vital structures of the neck.

Schwannoma is a benign, well-defined, encapsulated tumor, which expands and causes the mass effect. Approximately 25%–40% schwannomas are seen in the head-and-neck region. The most common site of intraoral schwannoma is the tongue and floor of the mouth.[19] Lingual schwannomas are rare in the pediatric age group. There was one patient in our series with schwannoma affecting the lateral border of the tongue. Complete excision of the tumor was done. Since it is a well-defined and encapsulated tumor, primary reconstruction of the tongue is often possible in these cases following excision.

It is important to emphasize through our experience of the above series of cases, the importance of the multidisciplinary approach in the management of head and neck solid tumors in children. A coordinated team effort of pediatric surgeon, otorhinolaryngologist, anesthesiologist, pediatrician, fetal medicine specialist, radiologist, and radiation oncologist is a must for a favorable outcome. Finally, we must ensure that there is regular communication between the treating team and the parents to alleviate their anxiety.

CONCLUSION

Our experience highlights rare and difficult tumors in the head-and-neck region in children. These tumors are not commonly managed by the pediatric surgeon in routine practice. The paper outlines the multi-modality management of these tumors, which is essential for an optimal outcome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published, and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Ethical approval

Was waived by the Ethics Committee of the institute in view of the retrospective nature of the study and all the procedures being performed were part of the routine care.