Carcinoma larynx in a 10-year-old girl : a rare clinical entity

Childhood carcinoma larynx is a very rare clinical entity. A girl of 10 year-old presented with persistent and progressive sore throat with dysphagia, change of voice and respiratory distress with stridor which needed tracheostomy and nasogastric tube feeding. Indirect laryngoscopy revealed exophytic growth involving the epiglottis and ary-epiglottic folds, restricted movement of hemilarynx and compromised airway. Biopsies were positive for squamous cell carcinoma. The malnourished cachectic poor patient was referred for receiving radiotherapy. A high index of suspicion is necessary to make the diagnosis since consequences of late diagnosis are very serious. This report underscores the need for prompt evaluation of children with persistent and progressive sore throat with dysphagia. Key word: Childhood carcinoma larynx, laryngeal carcinoma. 1. Department of Otolaryngology – Head & Neck Surgery, Dhaka Medical College Hospital. Dhaka, Bangladesh. 2. Registrar. Department of Otolaryngology – Head & Neck Surgery, Dhaka Medical College Hospital. Dhaka, Bangladesh. 3. MD (Histopathologypart III), Bangabandhu Sheikh Mujib Medical University. Dhaka, Bangladesh. Address of Correspondence: Dr. Md Zahididul Islam, Department of Otolaryngology – Head & Neck Surgery, Dhaka Medical College Hospital. Dhaka, Bangladesh. Introduction: The first documented case of laryngeal cancer in a child was reported by Rehn in 1868 in a 3 year-old child1. For more than a century thereafter, only 54 cases of laryngeal carcinoma have been reported in children 15 years of age or younger2. Only, before this case is being reported, 22 cases in patients 10 yearold or younger and 63 cases in patients 15 year-old or younger have been reported up to date since 18682 12. Nevertheless, physicians must be aware that a small percentage of cases do occur in the pediatric age group since case reports in patients less than 15 years of age, laryngeal cancers accounts for less than 0.1% of all head and neck malignancies13, 14, 15. In a survey of 98 cases of carcinoma of the larynx in patients less than 20 years of age, have about 20 cases in the 12 and under age group3. However, the incidence of female patients is higher in childhood (40% of childhood cases vs. less than 10% of adult cases) 5, and risk factors, except previous irradiation of papilloma, papillomatosis, malnutrition, are rare. Adolescent carcinomas also appear to be linked to immunologic and genetic factors rather than more common risk factors such as tobacco use, previous radiation, and chemical carcinogens found in adult patients16, 17. Malignant degeneration can take place in juvenile papillomatosis which was found by a study to be more common in children who had had radiotherapy for papillomatosis; consequently the practice of irradiating these children has been abandoned3. Among the other reported risk factors for laryngeal carcinoma are papillomatosis of the larynx, laryngopharyngeal reflux, human immunodeficiency virus (HIV) infection, immunosuppressive therapy, exposure to drug use during pregnancy, both active and passive smoking, exposure to certain chemicals (e.g. asbestos), alcohol use, poor oral hygiene, and a family history of cancer;18 so, attempt for HPV viral subtyping, search for p16 and 15:19 translocation with not neglecting the HIV should be made for aetipathogenesis. Younger patients tend to have a long history of progressive airway obstruction, dysphagia, or dysphonia; but lesions are not recognized until an otolaryngologist is consulted for a fiberoptic airway examination and a delay in diagnosis attributed to the erroneous attribution of some common paediatric respiratory and voice problems and difficult paediatric examination makes the problem more complicated. The scarcity of cases, attempt to preserve anatomy and function of larynx and for avoidance of complications impedes establishment of treatment protocols in children. All authors agree that a primary work up should consist of detailed radiological imaging endoscopy with biopsy, and possible tracheostomy for airway protection and, thereafter, definitive management of squamous cell carcinoma in pediatric patients has varied based on the individual circumstance of the patient19, 20. Prognosis of childhood laryngeal cancer is unclear since the reported survival rates are not tumor stage related. Case report: A 10-year-old malnourished girl had attended in the Deptt. of ENT – Head & Neck Surgery, Sher-e-Bangla Medical College Hospital, Barisal, with sore throat, dysphagia, change The Indirect laryngoscopic examination revealed a globular exophytic growth involving the epiglottis left AE fold and anterior part of the right AE fold. Left vocal cord could not be seen but movement of the left hemilarynx was found restricted with compromised airway. There was no palpable neck node and no systemic metastasis found. The patient was appeared malnourished and cachectic with anemia. Systemic examination did not reveal any noticeable abnormalities. In Direct laryngoscopic examination, the globular exophytic growth in the larynx was assessed and staged as T3NOMO. of voice and respiratory distress. The sore throat was persistent and progressive in nature for about two months, the dysphagia was also persistent and progressive over one month, progressive hoarseness of voice over two weeks and lastly the respiratory distress over one week associated with stridor for 3 days which necessitated tracheostomy and nasogastric tube feeding. Figure 1: A 10-year-old tracheostomized girl with carcinoma larynx 69 Carcinoma larynx in a 10-year-old girl: a rare clinical entity Md Zahidul Islam et al


Introduction:
The first documented case of laryngeal cancer in a child was reported by Rehn in 1868 in a 3 year-old child 1 .For more than a century thereafter, only 54 cases of laryngeal carcinoma have been reported in children 15 years of age or younger 2 .Only, before this case is being reported, 22 cases in patients 10 year-old or younger and 63 cases in patients 15 year-old or younger have been reported up to date since 1868 2 -12 .
Nevertheless, physicians must be aware that a small percentage of cases do occur in the pediatric age group since case reports in patients less than 15 years of age, laryngeal cancers accounts for less than 0.1% of all head and neck malignancies 13,14,15 .In a survey of 98 cases of carcinoma of the larynx in patients less than 20 years of age, have about 20 cases in the 12 and under age group 3 .However, the incidence of female patients is higher in childhood (40% of childhood cases vs. less than 10% of adult cases) 5 , and risk factors, except previous irradiation of papilloma, papillomatosis, malnutrition, are rare.Adolescent carcinomas also appear to be linked to immunologic and genetic factors rather than more common risk factors such as tobacco use, previous radiation, and chemical carcinogens found in adult patients 16,17 .Malignant degeneration can take place in juvenile papillomatosis which was found by a study to be more common in children who had had radiotherapy for papillomatosis; consequently the practice of irradiating these children has been abandoned 3 .Among the other reported risk factors for laryngeal carcinoma are papillomatosis of the larynx, laryngopharyngeal reflux, human immunodeficiency virus (HIV) infection, immunosuppressive therapy, exposure to drug use during pregnancy, both active and passive smoking, exposure to certain chemicals (e.g.asbestos), alcohol use, poor oral hygiene, and a family history of cancer; 18 so, attempt for HPV viral subtyping, search for p16 and 15:19 translocation with not neglecting the HIV should be made for aetipathogenesis.Younger patients tend to have a long history of progressive airway obstruction, dysphagia, or dysphonia; but lesions are not recognized until an otolaryngologist is consulted for a fiberoptic airway examination and a delay in diagnosis attributed to the erroneous attribution of some common paediatric respiratory and voice problems and difficult paediatric examination makes the problem more complicated.The scarcity of cases, attempt to preserve anatomy and function of larynx and for avoidance of complications impedes establishment of treatment protocols in children.All authors agree that a primary work up should consist of detailed radiological imaging endoscopy with biopsy, and possible tracheostomy for airway protection and, thereafter, definitive management of squamous cell carcinoma in pediatric patients has varied based on the individual circumstance of the patient 19,20 .Prognosis of childhood laryngeal cancer is unclear since the reported survival rates are not tumor stage related.

Case report:
A 10-year-old malnourished girl had attended in the Deptt. of ENT -Head & Neck Surgery, Sher-e-Bangla Medical College Hospital, Barisal, with sore throat, dysphagia, change The Indirect laryngoscopic examination revealed a globular exophytic growth involving the epiglottis left AE fold and anterior part of the right AE fold.Left vocal cord could not be seen but movement of the left hemilarynx was found restricted with compromised airway.There was no palpable neck node and no systemic metastasis found.The patient was appeared malnourished and cachectic with anemia.Systemic examination did not reveal any noticeable abnormalities.In Direct laryngoscopic examination, the globular exophytic growth in the larynx was assessed and staged as T 3 N O M O . of voice and respiratory distress.The sore throat was persistent and progressive in nature for about two months, the dysphagia was also persistent and progressive over one month, progressive hoarseness of voice over two weeks and lastly the respiratory distress over one week associated with stridor for 3 days which necessitated tracheostomy and nasogastric tube feeding.

Figure 1: A 10-year-old tracheostomized girl with carcinoma larynx
Tissue was taken from the growth for histopathological examination and that revealed well differentiated squamous cell carcinoma (SCC).The patient was referred to NICRH, Mohakhali, Dhaka, for oncological management.

Discussion:
Carcinoma larynx is an old-age malignancy.In children, the common laryngeal neoplasm is laryngeal papillomatosis.The most common age of carcinoma larynx is around 6 th decade of life 21 .In Bangladesh, mean age at presentation of supraglottic carcinoma is 35-80 years 22,23 .90% of laryngeal carcinoma is squamous cell carcinoma and its different variant 21 .Among the laryngeal carcinoma, supraglottic carcinoma appears earlier in adult population.Supraglottic carcinoma is common laryngeal carcinoma of this subcontinent compared to the western population.This is found more among the younger age group in low socioeconomic group with less male/female ratio in the developing country 22,23 .
Clinical manifestations of laryngeal carcinoma in adolescents may include hoarseness or cough, which may be mistaken for common respiratory infections, pre-pubertal voice change, or other benign childhood conditions 24 .Recurrent respiratory tract infection, or asthma, vocal abuse, difficult examination in children makes the case more aggressive and ultimately fatal 16,17 .Due to its rarity, tendency to mimic benign conditions and the relative difficulty of the pediatric laryngeal examination, SCC is not usually considered in the differential diagnosis of persistent hoarseness or cough, which may lead to a delay in diagnosis.Vocal folds are the most common site of involvement by SCC in adolescents, followed by supraglottic and then subglottic locations 25 .
Etio-pathological basis for childhood and adolescence carcinoma larynx is postulated being irradiation for papillomatosis, HPV infection, HPV induced genome mutation, chromosomal translocation 18 . 21.The relationship of HPV to laryngeal carcinoma is unclear although some studies have attributed laryngeal irradiation as a  predisposing factor in the development of carcinoma.Until the 1970s, malignant degeneration of recurrent respiratory papillomatosis [RRP] was seen in association with patients that underwent radiation therapy for their disease.Spontaneous malignant degeneration of RRP has been reported in the laryngotracheal and bronchioalveolar regions with an incidence rate of 2.3% 26 .Regarding HPV subtyping, HPV 11 had been linked to the malignant transformation of juvenile-onset RRP 27 .Malignant transformations of papillomatosis were 14% (6 of 43 irradiated cases) before 30 years of age whereas no transformation was reported in 58 similar cases treated with surgery alone 28 .Some study relates the risk factors like geographical distribution, malnutrition, and social classes since majority of supraglottic carcinoma cases were from lower socioeconomic group 22,23 .The differential diagnosis of laryngeal neoplasm in children includes: papilloma, subglottic hemangiomas, squamous carcinoma, rhabdomyosarcoma, and adenocarcinoma of minor salivary gland.
In this study 10-year-old female child with carcinoma larynx is so far the first reported case in this country.The postulated causes of our case are HPV infection along with factors like malnutrition and effect of secondary smoking or other environmental oncogenic factors.Due to unfamiliarly of this disease among the physician and pediatricians, she was diagnosed in an advanced stage.Aggressiveness of the disease process, malnutrition, lack of medical support, financial constrain, communication inconvenience, she could not get proper and early intervention which caused her unfortunate fatal outcome.

Conclusion:
Childhood laryngeal carcinoma is very rare malignant condition.

Figure 3 :
Figure 3: Histopathological section displays feature of squamous cell carcinoma in biopsy from laryngeal lesion.
The etiology of this disease is not exactly known.Clinical features are aggressive and the outcome is poor since the diagnosis and the treatment is always late.In any suspected cases where some risk factors are associated should be dignified.Although unusual, one should have a high index of suspicion for any hoarseness, cough, or upper airway disease that does not respond to appropriate medical treatment.By reporting this case and highlighting the difficulties in diagnosis and treatment we hope to increase clinical awareness and thus lead to an improved outcome.Accurate and early diagnosis of the childhood laryngeal carcinoma with prompt aggressive treatment is essential.