- Email: [email protected]
Laryngo-pharyngeal carcinoma in childhood
International Journal of Pediatric Otorhinolaryngology 61 (2001) 83 – 86 www.elsevier.com/locate/ijporl
Case report
Laryngo-pharyngeal carcinoma in childhood Chris Barnes a, Maree Sexton b, Andrew Sizeland c, Karin Tiedemann d, Robert G. Berkowitz e, Keith Waters d,* a
Clinical Fellow in Haematology and Oncology, Royal Children’s Hospital, Melbourne, Australia b Radiation Oncologist, Peter MacCallum Cancer Institute, Melbourne, Australia c Ear Nose and Throat Surgeon, Peter MacCallum Cancer Institute, Melbourne, Australia d Consultant Paediatric Haematologist and Oncologist, Royal Children’s Hospital, Flemington Road, Park6ille 3052 Melbourne, Australia e Department of Otolaryngology, and Paediatrics, Uni6ersity of Melbourne Royal Children’s Hospital, Melbourne, Australia Received 1 April 2001; received in revised form 26 June 2001; accepted 27 June 2001
Abstract Laryngo-pharyngeal carcinoma is rare in children. We present two cases of squamous cell carcinoma of the laryngopharynx in children less than 15 years of age. Both patients presented with a prolonged history of symptoms and extensive disease at diagnosis. Early visualisation the vocal cords with flexible larygnoscopy is important in children presenting with symptoms suggestive of laryngeal pathology. Long-term complications of definitive local therapy for laryngopharyngeal carcinoma are important in young children. Evidence from studies in adult patients suggests that adjuvant chemotherapy may play a role in laryngeal preservation in a select group of patients. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Children; Laryngeal carcinoma; Laryngo-pharyngeal carcinoma
1. Introduction Carcinoma of the laryno-pharynx is rare in children but a common head and neck cancer in adults. We describe two cases of childhood laryngo-pharyngeal cancer managed at the Royal Children’s Hospital, Melbourne. * Corresponding author. Tel.: + 61-9-3455522; fax: + 61-93456524. E-mail address: [email protected] (K. Waters).
We review the literature on laryngeal cancer in children and the use of adjuvant chemotherapy in treating adult patients with laryngeal carcinoma.
2. Case reports
2.1. Patient 1 The patient was a 12-year-old male who presented with an 8-week history of intermittent left
0165-5876/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 1 6 5 - 5 8 7 6 ( 0 1 ) 0 0 5 3 9 - 0
84
C. Barnes et al. / Int. J. Pediatr. Otorhinolaryngol. 61 (2001) 83–86
ear pain and a 2-week history of hoarse voice and progressive dysphagia. There was no significant past medical history. Examination showed a thin boy with a hoarse voice and drooling. There was marked left-sided cervical lymphadenopathy. Flexible laryngoscopy revealed the presence of a large piriform fossa mass extending to the left glottic and supraglottic larynx with fixation of the left vocal cord and critical airway obstruction. A CT scan of the neck showed a lobulated mass arising in the left piriform fossa associated with extensive lymphadenopathy. CT scans of chest and abdomen were normal. Microlaryngoscopy confirmed the findings at flexible laryngoscopy and a biopsy of the mass was consistent with squamous cell carcinoma. The patient was diagnosed as having stage T3N2bM0 hypopharyngeal carcinoma. Three courses of cisplatin (20 mg/m2 per day, day 1 –5) and flurouracil (1 gm/m2 continuous infusion over 5 days) were given at 28 day intervals. There was a marked improvement in the patient’s dysphonia and dysphagia. Repeat CT scan demonstrated reduction in the size of the piriform fossa mass and marked reduction in the associated lymphadenopathy. Frequent grade II gastrointestinal toxicity (mucositis) occurred. The patient received radiotherapy (60 Gy in 30 fractions) to the larynx and involved cervical lymph nodes and 50 Gy in 25 fractions to posterior cervical and supraclavicular nodes. The patient represented 4 weeks later with rapidly increasing dysphagia and stridor. A CT scan showed recurrence of the laryngo-pharyngeal mass with marked upper airway obstruction. A palliative surgical procedure consisting of radical neck dissection and tracheostomy was attempted but not possible because of massive tumour extension. The patient died shortly afterwards.
2.2. Patient 2 A 12-year-old Caucasian boy presented with a 9-month history of progressive hoarseness. Examination showed a well boy with mild dysphonia. Flexible laryngoscopy showed a papillary lesion on the right vocal cord, which was confirmed at microlaryngoscopy. The remainder of the exami-
nation was normal. Excisional biopsy of the lesion was consistent with squamous cell carcinoma in situ. The patient was monitored with monthly surveillance flexible laryngoscopies. Four months later a tumour on the right vocal cord extending into the anterior commissure was found at routine flexible laryngoscopy. Biopsy confirmed a moderately differentiated keratinising squamous cell carcinoma (Stage T1bN0M0). The patient was managed with radiotherapy and received 60 Gy in 30 fractions to the larynx. Microlaryngoscopy 5 months post radiotherapy showed tumour recurrence. A total laryngectomy was performed and showed tumour confined to the larynx. Seventeen months later the patient represented with a single enlarged right upper cervical lymph node. Fine needle aspiration of the node showed metastatic squamous cell carcinoma. A modified radical neck dissection confirmed clusters of tumour in one of 35 lymph nodes There was no extracapsular spread. Postoperatively the patient commenced chemotherapy consisting of 5 courses of cisplatin 20 mg/m2 per day, day 1–5 and flurouracil 1 gm/m2 infused over 5 days at 28 day intervals. Two and one half years following completion of his chemotherapy, the patient remains well with no evidence of tumour recurrence.
3. Discussion Cancer of the laryngo-pharynx is rare in children. There have been 63 cases reported in children less than 15 years of age [1–9]. Carcinoma of the larynx is common in adult patients and is the eleventh most common cancer overall [10]. There are distinct differences between laryngeal carcinoma occurring in children and adults. The sex ratio of childhood cases is 1:1.7, male to female, compared to a sex ratio of 9:1 in adult patients [10]. No recognised risk factors have been identified amongst the cases reported in children, whereas smoking is the most commonly reported risk factors in adults. The majority of cases reported in children presented with prolonged symptoms of hoarseness or upper airways obstruction. Frequently, a delay in
C. Barnes et al. / Int. J. Pediatr. Otorhinolaryngol. 61 (2001) 83–86
the diagnosis was reported with symptoms attributed to vocal changes during puberty, recurrent upper respiratory tract infections or vocal abuse. The majority of these children presented with extensive disease. The delay highlights the importance of adequate visualisation of the larynx in children presenting with dysphonia or other symptoms suggestive of laryngeal pathology. Mirror examination of the larynx by indirect laryngoscopy is often difficult in children. The larynx can usually be adequately assessed by transnasal flexible laryngoscopy under local anaesthetic. Specific treatment details of the cases reported in the literature are incomplete. Twenty-three children were treated with surgery, radiation or both [1,2,6 –9]. Use of chemotherapy in children with laryngeal carcinoma is reported on two previous occasions. Ohlms et al. (1990) described the case of a 13-year-old boy with T3N0M0 laryngeal carcinoma treated with induction therapy of cisplatin and 5-flurouracil followed by involved field radiotherapy [5]. The patient remains well 7 years post treatment (personal correspondence). Laurian et al. (1984) described a case of an 8-year-old boy with T3N0M0 laryngeal carcinoma who was treated with combination chemotherapy of cisplatin, cyclophosphamide, methotrexate and bleomycin [3]. Outcome details are unavailable. Chemotherapy has been used to treat adult patients with carcinoma of the larynx. Squamous cell carcinoma of the head and neck is known to be chemosensitive producing response rates in up to 93% of patients [11–13]. The response to chemotherapy has been shown to select patients who could benefit from more conservative local therapy [14,15]. One study compared patients who were treated with chemotherapy followed by radiation to patients treated with radical surgery and radiation. There was no difference in overall survival with patients who relapse following chemotherapy being salvaged with radical surgery [15]. Thirty one percent of patients in the chemotherapy group were alive with a functioning larynx at 5 years. In a similar study 42% of patients treated with chemotherapy were alive with a functioning larynx at 3 years [14]. Both of the patients we present were treated with chemotherapy. Our patient with a hypopha-
85
ryngeal carcinoma and laryngeal involvement demonstrated initial responsiveness to chemotherapy but rapidly developed massive tumour recurrence. Efficacy of chemotherapy in our patient with laryngeal carcinoma can be implied if he remains disease free following nodal relapse. Overall the management of children with laryngo-pharyngeal carcinoma remains a challenge. Accurate and early diagnosis of children presenting with symptoms suggestive of laryngeal pathology is essential. Long-term complications of local therapy are important in young children but definitive local therapy is essential. Evidence from studies in adult patients suggests that response to chemotherapy may select patients who could benefit from modified local therapy.
Acknowledgements The authors gratefully acknowledge the correspondence from Dr Ohlms and Dr McGill from Harvard Medical School regarding the follow-up a patient with laryngeal carcinoma. The authors also gratefully acknowledge Dr C.W. Chow for his review of the manuscript.
References [1] M.B. de Carvalho, J.A. Sobrinho, A. Rapoport, A. Fava, A. Mendes, J. Kanda, et al., Head and neck squamous cell carcinoma in childhood, Med. Pediatr. Oncol. 31 (1998) 96 – 99. [2] T. Gindhart, W.H. Johnston, S. Chism, H. Dedo, Carcinoma of the larynx in childhood, Cancer 46 (1980) 1683 – 1687. [3] N. Laurian, R. Sadov, E. Kessler, M. Strauss, Laryngeal carcinoma in childhood. A report of a case and review of the literature, Laryngoscope 94 (1984) 684 – 687. [4] W.F. McGuirt, J.P. Little, Laryngeal cancer in children and adolescents, Otolaryngol. Clin. N. Amer. 30 (2) (1997) 207 – 214. [5] L.A. Ohlms, T. McGill, G.B. Healy, Malignant laryngeal tumours in children; A 15 year experience with four patients, Ann. Otol. Rhinol. Laryngol. 103 (9) (1994) 686 – 692. [6] R.H. Ossoff, G.F. Tucker, C.M. Norris, Carcinoma of the larynx in a 11 year old boy…, Otolarygol. Head Neck Surg. March – April 88 (2) (1980) 142 – 145.
86
C. Barnes et al. / Int. J. Pediatr. Otorhinolaryngol. 61 (2001) 83–86
[7] M. Simon, T. Kahn, A. Schneider, W. Pirsig, Laryngeal carcinoma in a 12 year old child, Arch. Otolaryngol. Head Neck Surg. 120 (March) (1994) 277 –282. [8] W. Singh, A. Kaur, Laryngeal carcinoma in a 6 year old with a review of the literature, J. Laryngol. Otol. Sep. 101 (9) (1987) 957 – 958. [9] G.H. Zalzal, R.T. Cotton, K. Bove, Carcinoma of the larynx in a child, Int. J. Pediatr. Otorhinolarygol. 13 (2) (1987) 219 – 225. [10] J. Olofsson, W. VandenBogaert, Tumours of the larynx, in: M. Peckham, H. Pinedo, U. Veronesi (Eds.), Oxford Textbook of Oncology, Oxford Medical Publications, Oxford, 1995, pp. 1040 –1058. [11] H. Pinto, C. Jacobs, Chemotherapy for recurrent and metastatic head and neck cancer, Hematol. Oncol. Clin. N. Amer. 5 (1991) 667 –686. [12] J.M. Richard, H.S. Garnier, J. Pessey, B. Lubonski, J.
Lefebve, D. Dehesdin, et al., Randomised trial of induction chemotherapy in laryngeal carcinoma, Oral Oncol. 34 (3) (1998) 224 – 228. [13] D. Adelstein, Induction chemotherapy in head and neck cancer, Hematol. Oncol. Clin. N. Amer. 14 (4) (1999) 689 – 702. [14] J. Lefebvre, D. Chevalier, B. Luboinski, et al., Larynx preservation in piriform sinus cancer; Preliminary results of a European Organisation for Research and Treatment of Cancer phase III trial. EORTC Head and Neck Cancer Co operative Group, J. Natl. Cancer Inst. 88 (1996) 890 – 899. [15] The department of Veteran Affairs Laryngeal Cancer Study Group. Induction chemotherapy plus radiation compared to surgery plus radiation in patients with advanced laryngeal cancer. The New England Journal of Medicine 1991;324: 1685 – 90.
Case report
Laryngo-pharyngeal carcinoma in childhood Chris Barnes a, Maree Sexton b, Andrew Sizeland c, Karin Tiedemann d, Robert G. Berkowitz e, Keith Waters d,* a
Clinical Fellow in Haematology and Oncology, Royal Children’s Hospital, Melbourne, Australia b Radiation Oncologist, Peter MacCallum Cancer Institute, Melbourne, Australia c Ear Nose and Throat Surgeon, Peter MacCallum Cancer Institute, Melbourne, Australia d Consultant Paediatric Haematologist and Oncologist, Royal Children’s Hospital, Flemington Road, Park6ille 3052 Melbourne, Australia e Department of Otolaryngology, and Paediatrics, Uni6ersity of Melbourne Royal Children’s Hospital, Melbourne, Australia Received 1 April 2001; received in revised form 26 June 2001; accepted 27 June 2001
Abstract Laryngo-pharyngeal carcinoma is rare in children. We present two cases of squamous cell carcinoma of the laryngopharynx in children less than 15 years of age. Both patients presented with a prolonged history of symptoms and extensive disease at diagnosis. Early visualisation the vocal cords with flexible larygnoscopy is important in children presenting with symptoms suggestive of laryngeal pathology. Long-term complications of definitive local therapy for laryngopharyngeal carcinoma are important in young children. Evidence from studies in adult patients suggests that adjuvant chemotherapy may play a role in laryngeal preservation in a select group of patients. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Children; Laryngeal carcinoma; Laryngo-pharyngeal carcinoma
1. Introduction Carcinoma of the laryno-pharynx is rare in children but a common head and neck cancer in adults. We describe two cases of childhood laryngo-pharyngeal cancer managed at the Royal Children’s Hospital, Melbourne. * Corresponding author. Tel.: + 61-9-3455522; fax: + 61-93456524. E-mail address: [email protected] (K. Waters).
We review the literature on laryngeal cancer in children and the use of adjuvant chemotherapy in treating adult patients with laryngeal carcinoma.
2. Case reports
2.1. Patient 1 The patient was a 12-year-old male who presented with an 8-week history of intermittent left
0165-5876/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 1 6 5 - 5 8 7 6 ( 0 1 ) 0 0 5 3 9 - 0
84
C. Barnes et al. / Int. J. Pediatr. Otorhinolaryngol. 61 (2001) 83–86
ear pain and a 2-week history of hoarse voice and progressive dysphagia. There was no significant past medical history. Examination showed a thin boy with a hoarse voice and drooling. There was marked left-sided cervical lymphadenopathy. Flexible laryngoscopy revealed the presence of a large piriform fossa mass extending to the left glottic and supraglottic larynx with fixation of the left vocal cord and critical airway obstruction. A CT scan of the neck showed a lobulated mass arising in the left piriform fossa associated with extensive lymphadenopathy. CT scans of chest and abdomen were normal. Microlaryngoscopy confirmed the findings at flexible laryngoscopy and a biopsy of the mass was consistent with squamous cell carcinoma. The patient was diagnosed as having stage T3N2bM0 hypopharyngeal carcinoma. Three courses of cisplatin (20 mg/m2 per day, day 1 –5) and flurouracil (1 gm/m2 continuous infusion over 5 days) were given at 28 day intervals. There was a marked improvement in the patient’s dysphonia and dysphagia. Repeat CT scan demonstrated reduction in the size of the piriform fossa mass and marked reduction in the associated lymphadenopathy. Frequent grade II gastrointestinal toxicity (mucositis) occurred. The patient received radiotherapy (60 Gy in 30 fractions) to the larynx and involved cervical lymph nodes and 50 Gy in 25 fractions to posterior cervical and supraclavicular nodes. The patient represented 4 weeks later with rapidly increasing dysphagia and stridor. A CT scan showed recurrence of the laryngo-pharyngeal mass with marked upper airway obstruction. A palliative surgical procedure consisting of radical neck dissection and tracheostomy was attempted but not possible because of massive tumour extension. The patient died shortly afterwards.
2.2. Patient 2 A 12-year-old Caucasian boy presented with a 9-month history of progressive hoarseness. Examination showed a well boy with mild dysphonia. Flexible laryngoscopy showed a papillary lesion on the right vocal cord, which was confirmed at microlaryngoscopy. The remainder of the exami-
nation was normal. Excisional biopsy of the lesion was consistent with squamous cell carcinoma in situ. The patient was monitored with monthly surveillance flexible laryngoscopies. Four months later a tumour on the right vocal cord extending into the anterior commissure was found at routine flexible laryngoscopy. Biopsy confirmed a moderately differentiated keratinising squamous cell carcinoma (Stage T1bN0M0). The patient was managed with radiotherapy and received 60 Gy in 30 fractions to the larynx. Microlaryngoscopy 5 months post radiotherapy showed tumour recurrence. A total laryngectomy was performed and showed tumour confined to the larynx. Seventeen months later the patient represented with a single enlarged right upper cervical lymph node. Fine needle aspiration of the node showed metastatic squamous cell carcinoma. A modified radical neck dissection confirmed clusters of tumour in one of 35 lymph nodes There was no extracapsular spread. Postoperatively the patient commenced chemotherapy consisting of 5 courses of cisplatin 20 mg/m2 per day, day 1–5 and flurouracil 1 gm/m2 infused over 5 days at 28 day intervals. Two and one half years following completion of his chemotherapy, the patient remains well with no evidence of tumour recurrence.
3. Discussion Cancer of the laryngo-pharynx is rare in children. There have been 63 cases reported in children less than 15 years of age [1–9]. Carcinoma of the larynx is common in adult patients and is the eleventh most common cancer overall [10]. There are distinct differences between laryngeal carcinoma occurring in children and adults. The sex ratio of childhood cases is 1:1.7, male to female, compared to a sex ratio of 9:1 in adult patients [10]. No recognised risk factors have been identified amongst the cases reported in children, whereas smoking is the most commonly reported risk factors in adults. The majority of cases reported in children presented with prolonged symptoms of hoarseness or upper airways obstruction. Frequently, a delay in
C. Barnes et al. / Int. J. Pediatr. Otorhinolaryngol. 61 (2001) 83–86
the diagnosis was reported with symptoms attributed to vocal changes during puberty, recurrent upper respiratory tract infections or vocal abuse. The majority of these children presented with extensive disease. The delay highlights the importance of adequate visualisation of the larynx in children presenting with dysphonia or other symptoms suggestive of laryngeal pathology. Mirror examination of the larynx by indirect laryngoscopy is often difficult in children. The larynx can usually be adequately assessed by transnasal flexible laryngoscopy under local anaesthetic. Specific treatment details of the cases reported in the literature are incomplete. Twenty-three children were treated with surgery, radiation or both [1,2,6 –9]. Use of chemotherapy in children with laryngeal carcinoma is reported on two previous occasions. Ohlms et al. (1990) described the case of a 13-year-old boy with T3N0M0 laryngeal carcinoma treated with induction therapy of cisplatin and 5-flurouracil followed by involved field radiotherapy [5]. The patient remains well 7 years post treatment (personal correspondence). Laurian et al. (1984) described a case of an 8-year-old boy with T3N0M0 laryngeal carcinoma who was treated with combination chemotherapy of cisplatin, cyclophosphamide, methotrexate and bleomycin [3]. Outcome details are unavailable. Chemotherapy has been used to treat adult patients with carcinoma of the larynx. Squamous cell carcinoma of the head and neck is known to be chemosensitive producing response rates in up to 93% of patients [11–13]. The response to chemotherapy has been shown to select patients who could benefit from more conservative local therapy [14,15]. One study compared patients who were treated with chemotherapy followed by radiation to patients treated with radical surgery and radiation. There was no difference in overall survival with patients who relapse following chemotherapy being salvaged with radical surgery [15]. Thirty one percent of patients in the chemotherapy group were alive with a functioning larynx at 5 years. In a similar study 42% of patients treated with chemotherapy were alive with a functioning larynx at 3 years [14]. Both of the patients we present were treated with chemotherapy. Our patient with a hypopha-
85
ryngeal carcinoma and laryngeal involvement demonstrated initial responsiveness to chemotherapy but rapidly developed massive tumour recurrence. Efficacy of chemotherapy in our patient with laryngeal carcinoma can be implied if he remains disease free following nodal relapse. Overall the management of children with laryngo-pharyngeal carcinoma remains a challenge. Accurate and early diagnosis of children presenting with symptoms suggestive of laryngeal pathology is essential. Long-term complications of local therapy are important in young children but definitive local therapy is essential. Evidence from studies in adult patients suggests that response to chemotherapy may select patients who could benefit from modified local therapy.
Acknowledgements The authors gratefully acknowledge the correspondence from Dr Ohlms and Dr McGill from Harvard Medical School regarding the follow-up a patient with laryngeal carcinoma. The authors also gratefully acknowledge Dr C.W. Chow for his review of the manuscript.
References [1] M.B. de Carvalho, J.A. Sobrinho, A. Rapoport, A. Fava, A. Mendes, J. Kanda, et al., Head and neck squamous cell carcinoma in childhood, Med. Pediatr. Oncol. 31 (1998) 96 – 99. [2] T. Gindhart, W.H. Johnston, S. Chism, H. Dedo, Carcinoma of the larynx in childhood, Cancer 46 (1980) 1683 – 1687. [3] N. Laurian, R. Sadov, E. Kessler, M. Strauss, Laryngeal carcinoma in childhood. A report of a case and review of the literature, Laryngoscope 94 (1984) 684 – 687. [4] W.F. McGuirt, J.P. Little, Laryngeal cancer in children and adolescents, Otolaryngol. Clin. N. Amer. 30 (2) (1997) 207 – 214. [5] L.A. Ohlms, T. McGill, G.B. Healy, Malignant laryngeal tumours in children; A 15 year experience with four patients, Ann. Otol. Rhinol. Laryngol. 103 (9) (1994) 686 – 692. [6] R.H. Ossoff, G.F. Tucker, C.M. Norris, Carcinoma of the larynx in a 11 year old boy…, Otolarygol. Head Neck Surg. March – April 88 (2) (1980) 142 – 145.
86
C. Barnes et al. / Int. J. Pediatr. Otorhinolaryngol. 61 (2001) 83–86
[7] M. Simon, T. Kahn, A. Schneider, W. Pirsig, Laryngeal carcinoma in a 12 year old child, Arch. Otolaryngol. Head Neck Surg. 120 (March) (1994) 277 –282. [8] W. Singh, A. Kaur, Laryngeal carcinoma in a 6 year old with a review of the literature, J. Laryngol. Otol. Sep. 101 (9) (1987) 957 – 958. [9] G.H. Zalzal, R.T. Cotton, K. Bove, Carcinoma of the larynx in a child, Int. J. Pediatr. Otorhinolarygol. 13 (2) (1987) 219 – 225. [10] J. Olofsson, W. VandenBogaert, Tumours of the larynx, in: M. Peckham, H. Pinedo, U. Veronesi (Eds.), Oxford Textbook of Oncology, Oxford Medical Publications, Oxford, 1995, pp. 1040 –1058. [11] H. Pinto, C. Jacobs, Chemotherapy for recurrent and metastatic head and neck cancer, Hematol. Oncol. Clin. N. Amer. 5 (1991) 667 –686. [12] J.M. Richard, H.S. Garnier, J. Pessey, B. Lubonski, J.
Lefebve, D. Dehesdin, et al., Randomised trial of induction chemotherapy in laryngeal carcinoma, Oral Oncol. 34 (3) (1998) 224 – 228. [13] D. Adelstein, Induction chemotherapy in head and neck cancer, Hematol. Oncol. Clin. N. Amer. 14 (4) (1999) 689 – 702. [14] J. Lefebvre, D. Chevalier, B. Luboinski, et al., Larynx preservation in piriform sinus cancer; Preliminary results of a European Organisation for Research and Treatment of Cancer phase III trial. EORTC Head and Neck Cancer Co operative Group, J. Natl. Cancer Inst. 88 (1996) 890 – 899. [15] The department of Veteran Affairs Laryngeal Cancer Study Group. Induction chemotherapy plus radiation compared to surgery plus radiation in patients with advanced laryngeal cancer. The New England Journal of Medicine 1991;324: 1685 – 90.