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Primary malignant melanoma of the larynx: A case report and literature review
Auris Nasus Larynx 34 (2007) 105–110 www.elsevier.com/locate/anl
Primary malignant melanoma of the larynx: A case report and literature review Tomonori Terada *, Nobuo Saeki, Kunichika Toh, Nobuhiro Uwa, Kosuke Sagawa, Takeshi Mouri, Masafumi Sakagami Department of Otolaryngology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya City, Hyogo 663-8501, Japan Received 9 December 2005; accepted 15 September 2006 Available online 27 December 2006
Abstract A 56-year-old Japanese man presented with hoarseness and left sided neck swelling in June 2003. Endoscopy showed an irregular tumor extending from the anterior commissure to the left ventricle with dark pigmentation. A biopsy showed malignant melanoma. A total laryngectomy with left radical neck dissection was performed in July 2003, followed by chemohormonal therapy and radiotherapy to the neck. Multiple bone metastases were diagnosed in May 2004, and the patient died with disseminated disease in April 2005, 21 months after initial treatment. The medical literature on laryngeal malignant melanoma was reviewed, and suggested a very poor prognosis despite therapy with surgery, radiotherapy, and chemotherapy. # 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Malignant melanoma; Larynx; Head and neck
1. Introduction Primary malignant melanoma of the larynx is a rare tumor. To date, there are only about 60 cases of laryngeal melanoma have been reported in the literature. In addition, the reports of adequately documented cases about clinical detailed course are a few cases including our case. This article presents a case of primary malignant melanoma of the larynx and a review of the literature.
2. Case report A 56-year-old Japanese man visited our institution in June 2003 with a primary complaint of hoarseness for the past 2 months, and a 6-month history of swelling on the left side of his neck. The patient had smoked 20 cigarettes a day for 36 years. An irregular tumor was found by endoscopy extending from the anterior commissure to the left ventricle * Corresponding author. Tel.: +81 798 45 6493; fax: +81 798 41 8976. E-mail address: [email protected] (T. Terada).
with partial dark pigment (Fig. 1). Vocal cord mobility was normal on both sides. Multiple lymphadenopathies was detected on the left side of the neck—the lymph nodes were 5.0, 2.2 and 3.0 cm in size in the upper neck, middle neck and lower neck, respectively. A CT scan verified the clinical findings and did not prove any cartilage destruction (Fig. 2). No distant metastases were found on thorax CT, abdomen ultrasound, gallium scintigram, and blood test including liver function test were normal. A biopsy of the laryngeal lesion showed a malignant melanoma (Fig. 3A). The tumor cells had pleomorphic nuclei. Some areas of the tumor consisted of elongated and spindle shaped cells, while other areas showed polygonal epithelial cells. Immunohistochemical staining was positive for S-100 protein and for HMB-45 (Fig. 3B), but was negative for cytokeratin and EMA. Total laryngectomy with a left radical neck dissection was performed in the beginning of July 2003. In the laryngeal specimen the primary lesion was found to arise from the left ventricle and the pigmentation spread into the subglottic area (Fig. 4). Following surgery, chemohormonal therapy (with dacarbazine; 220 mg/(m2 day) from days 1 to
0385-8146/$ – see front matter # 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.anl.2006.09.027
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Fig. 1. Laryngeal endoscopy shows an irregular tumor (arrows). The tumor extends from the anterior commissure to the left ventricle with an area of dark pigment.
3, ranimustine; 60 mg/(m2 day) at only day 1, cisplatin; 25 mg/m2/day from days 1 to 3, and tamoxifen citrate 10 mg 2 per day from days 1 to 28) was given at the end of July 2003 to prevent distant metastasis. Radiotherapy to the neck (60 Gy in 30 fractions, 2 Gy per fraction over 6 weeks) was administered from August 2003 to September 2003. In May 2004, multiple bone metastases were found in the clavicle, pubis, and sternum, and radiotherapy was given to the pubis and sternum (30 Gy in 10 fractions, 3 Gy per fraction over 2 weeks). Chemohormonal therapy was given after radiotherapy. The patient died of dissemination of the disease in April 2005, 21 months after the initial treatment.
3. Discussion Primary mucosal malignant melanoma of the head and neck probably derives from scattered melanocytes in the
Fig. 2. Computer tomography shows the mass arising from the anterior part the vocal cord area, and multiple lymphadenopathy (arrows) is present on the left side of the neck. There is no evidence of cartilage destruction.
mucosa. These cells may be present within the basal layer of the epithelium of the nasal cavity, oral cavity, oropharynx and esophagus. However, melanocytes are rarely detected within the larynx, which could explain the low incidence of primary melanoma in the larynx [1–3]. Mucosal malignant melanoma is rare in the head and neck region, accounting for 8–15% of malignant melanomas at this site [4,5] and less than 1% of all malignant melanomas [6]. The commonest sites in the head and neck are the nasal cavity (69%) and the oral cavity (22%) [7]. Laryngeal malignant melanoma is very rare (1.2–7.4%) [8,9], and about 60 cases have been reported in the literature to date. We found detailed clinical reports were only available for 38 patients, including our patient, as shown in Table 1. Patient characteristics are shown in Table 2. Reviewing the reports in Table 2 of 36 cases where gender was recorded, 29 cases (80.6%) were male, and their ages ranged from 35 to 86 years (mean, 60.5 years). Reuter and Woodruff [2] reported that 58 of 88 patients (66.0%) with malignant melanoma of the head and neck from 1949 to
Fig. 3. (A) There were brown atypical cells at the basal layer of the squamous epithelium. This indicates that the tumor was a primary laryngeal melanoma, and not a metastasis (hematoxylin and eosin staining; 200). (B) In the immunohistochemistry of S-100 protein and HMB-45 (200), brown granules of immunoreactivity were seen in the cytoplasm (arrows). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)
Table 1 Cases of primary malignant melanoma of the larynx reported in the literature
T. Terada et al. / Auris Nasus Larynx 34 (2007) 105–110 A: arytenoid; V: ventricle; E: epiglottis; VC: vocal cord; FC: false vocal cord; Trans: transglottis; AF: aryepiglottic fold; ?: unknown; RT: radiotherapy; TL: total laryngectomy; ND: neck dissection; PL: partial laryngectomy; Immuno: immunotherapy; Chemo: chemotherapy; CH: chemohormonal therapy; *: never rendered free of disease; 0 m: at diagnosis; DOD: died of the disease; AWD: alive with the disease; NED: no evidence of the disease; D-NED: dead with no evidence of the disease (see refs. [2,9,10–12,14,18–38,42,43].
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T. Terada et al. / Auris Nasus Larynx 34 (2007) 105–110 Table 2 Summary of the clinical course of 36 cases in Table 1
Fig. 4. The laryngeal specimen shows the mass arising from the left ventricle to the left anterior vocal cord and the right ventricle; the pigmentation extends into the subglottic area (arrows).
1983 had a history of smoking. Laryngeal melanoma may be due to smoking, as is laryngeal squamous cell carcinoma. The common initial symptom is hoarseness, and other symptoms are irritation in the throat, sore throat, dysphagia and a neck mass [10,11]. In 27 cases where the initial symptom was recorded (Table 2) hoarseness was the initial symptom in 18 cases (66.6%). In 37 cases where the primary site was recorded (Table 2), the primary site was the supraglottic region in 23 cases (62.2%) (epiglottis, 9 cases; aryepiglottic fold, 4 cases; ventricle, 4 cases; arytenoid, 3 cases, and false vocal cord, 3 cases), and the vocal cords in 14 cases (37.8%). The diagnosis of laryngeal melanoma is generally not clinically determined but is dependent on histological evaluation. The histology showed a variety of cells with spindled, polygonal, round or mixed shape. The growth patterns also vary and are similar to other neoplasms. The presence of immunoreactivity of S-100 protein and HMB45 in a pleomorphic or spindle cells is a key to diagnosis [11]. The differential diagnosis of laryngeal melanoma includes squamous cell carcinoma, neuroendocrine carcinoma, non-Hodgkin’s malignant lymphoma, extramedullary plasmacytoma, paraganglioma, sarcomas (malignant fibrous histiocytoma, fibrosarcoma, and malignant Schwannoma) [11]. A mistake is possible in histological examination if the specimen is small and especially if the involvement is an amelanotic melanoma [29]. Some cases were reported that initially histological diagnosis have malignant melanoma confused with poorly differentiated squamous cell carcinoma, with non-Hodgkin’s malignant lymphoma [33], and initially histological diagnosis have confused neuroendocrine carcinoma with malignant melanoma [39]. The traditional primary treatment for malignant melanoma of the head and neck has been radical surgery with or
without adjuvant radiotherapy or chemotherapy. Although radical surgery offers the best choice for local control, local recurrence occurs frequently [2]. Snow et al. [13] reported the recurrence rate of malignant melanoma of the head and neck as 42%, and Shah et al. [5] reported a 64% recurrence rate. In contrast, malignant melanoma of the larynx has a relatively low incidence of local recurrence after surgical removal, even after simple local excision [2]. In 21 cases where the local recurrence was recorded (Table 1), the local recurrence was in 4 cases (19.0%). The reason for the difference in the recurrence rate between malignant melanoma of the head and neck and malignant melanoma of the larynx is unclear, but it may be related to the fact that laryngeal tumors are clinically easily delimited and surgically removed. Melanoma is generally considered to be a radioresistant tumor. However, in vitro studies of cutaneous melanoma cell lines showed that they may not be intrinsically radioresistant and that high dose per fraction therapy is necessary to avoid the cell lines resisting a sublethal radiation dose [11]. Amin et al. [14] also reported that postoperative radiotherapy could be useful
T. Terada et al. / Auris Nasus Larynx 34 (2007) 105–110
in cases of mucosal malignant melanoma of the head and neck. Blatchford et al. [12] reported that chemotherapy should not be used as primary therapy but may be useful as adjunctive treatment. However, McClay et al. [15] used chemotherapy as primary therapy with or without tamoxifen in 65 cases of malignant melanoma, and demonstrated that chemotherapy with tamoxifen increased the mean survival time significantly longer than chemotherapy without tamoxifen. Seo et al. [16] reported six patients with mucosal malignant melanoma of the head and neck treated with chemohormonal therapy: three patients had a complete response, two had a partial response, and one had no response, suggesting that patients showed good responses to chemohormonal therapy. In our patient, chemohormonal therapy was initially performed to prevent distant metastasis after surgery, and later to treat the multiple bone metastasis, although with a poor response. Several studies have reported that the 5-year survival rate was less than 20% [2,14,17,41] and that 80% of the patients had metastatic disease in regional lymph nodes or at distant sites (lung, brain and liver). Prasad et al. [40] reported that the 5-year survival rate and distant metastasis rate of Stage I (N0M0) primary mucosal melanoma of the head and neck were 30.8% and 44%, respectively. As shown in Table 1, cervical metastasis to regional lymph nodes was observed in 19 of 29 cases (65.5%), and distant metastasis in 16 of 27 cases (59.3%); 23 of 29 cases (79.3%) had metastasis either to regional lymph nodes or distant sites. Only 2 of the 28 cases survived for more than 5 years, and the overall 3- and 5-year survival rates were 28.6% and 7.1%, respectively. Despite all therapeutic efforts to control mucosal malignant melanoma of the larynx, the overall 5-year survival rate is very poor.
References [1] Busutill A. Dendritic pigmented cells within human laryngeal mucosa. Arch Otolaryngol 1976;102:43–4. [2] Reuter VE, Woodruff JM. Melanoma of the larynx. Laryngoscope 1986;94:389–93. [3] Goldman JL, Lawson W, Zak FG, Roffman JD. The presence of melanocytes in the human larynx. Laryngoscope 1972;82: 824–35. [4] Anderson LJ, Berthelsen A, Hansen HS. Malignant melanoma of the upper respiratory tract and the nasal cavity. J Otolaryngol 1992;21:180–5. [5] Shah PJ, Huvos AG, Strong WE. Mucosal melanomas of the head and neck. Am J Surg 1977;134:531–5. [6] Trap TK, Fu Y, Calcaterra TC. Melanoma of the nasal and paranasal sinus mucosa. Arch Otolaryngol 1987;113:1086–9. [7] Nandapalan V, Roland NJ, Helliwell TR, Williams EM, Hamilton JW, Jones AS. Mucosal melanoma of the head and neck. Clin Otolaryngol 1998;23:107–16. [8] Buchholz W. Uber Melanoblastome im Bereich der oberen Luft-unt Speisewege. Laryngol Rhinol Otol 1958;37:549–54. [9] Moore E, Martin H. Melanoma of the upper respiratory tract. Cancer 1955;8:1167–76.
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[10] Kim H, Park C. Primary malignant laryngeal melanoma. Yonsei Med J 1982;23:118–22. [11] Wenig BM. Laryngeal mucosal malignant melanoma. A clinicopathologic, immunohistochemical, and ultrastructural study of four patients and review of the literature. Cancer 1995;75:1568–77. [12] Blatchford SJ, Koopman CF, Coulthard SW. Mucosal melanomas of the head and neck. Laryngoscope 1986;96:929–34. [13] Snow GB, VanDer Esch EP, Van Sloaten EA. Mucosal melanomas of the head and neck. Head Neck Surg 1978;1:24–30. [14] Amin HM, Petruzzelli GJ, Husain AN, Nickoloff BJ. Primary malignant melanoma of the larynx. Arch Pathol Lab Med 2001; 125:271–3. [15] McClay EF, Masarangelo MJ, Bread D, Bellet RE. Effective combination chemohormonal therapy for malignant melanoma. Int J Cancer 1992;50:553–6. [16] Seo W, Ogasawara H, Sakagami M. Chemohormonal therapy for malignant melanomas. Nippon Jibiinnkoka Gakkai Kaiho (Tokyo) 1996;99:1004–9 (in Japanese). [17] Karagiannidis K, Noussios G, Sakellariou T, Kontzoglou G, Mantziaris V, Preponis C. Primary laryngeal melanoma. J Otolaryngol 1998;27:104–6. [18] Havens FZ, Parkihill EM. Tumors of the larynx other than squamous cell epithelioma. Arch Otolaryngol 1941;34:1113–22. [19] Curtiss C, Kosinski AA. Primary malignant melanoma of the larynx: report of a case and review of the literature. Cancer 1955; 8:961–3. [20] De Juan P. Melanosarcoma laringeo y otras consideraciones. Acta Otol Rhinol Laryngol Iber-Am 1955;7:296–308. [21] Cremonesi G. Su un eccezionale reperto di sarcoma melanotico primitivo della laringe. Minerva Otorrinolaringo 1956;6:333–40. [22] Welsh LW, Welsh JJ. Malignant melanoma of the larynx. Laryngoscope 1961;71:185–91. [23] Mishima N, Muramatsu H. A case of malignant melanoma of the larynx. Otolaryngology (Tokyo) 1976;34:1173–6 (in Japanese). [24] Pantazopoulos PE. Primary malignant melanoma of the larynx. Laryngoscope 1964;74:95–102. [25] Nsamda C. A case of malignant melanoma of the larynx. J Laryngol Otol 1966;80:1178–81. [26] Catlin D. Mucosal melanoma of the head and neck. Am J Roentgenol 1967;99:809–16. [27] Mu¨ller E. Melanoblastome in kehlkopf und mittelchr. HNO 1968;16:133–6. [28] EL-Barbary AE, Fouad HA, El-Sayed AF. Malignant melanoma involving the larynx: report of two cases. Ann Otol 1968;77: 338–43. [29] Vouri EJ, Hormia M. Primary malignant melanoma of the larynx and pharynx. J Laryngol 1969;83:281–7. [30] Shanon E, Covo J, Loeventhal M. Melanoma of the epiglottis: a case treated by supraglottic larungectomy. Arch Otolaryngol 1970;91:304– 5. [31] Lorenz E. Das maligne melanom des kehlkopfes. HNO 1979;27:275– 7. [32] Maki K. A case of malignant melanoma of the larynx. Pract Otol (Kyoto) 1984;77(Suppl 2):611–7 (in Japanese). [33] Hussain SSM, Whitehead E. Malignant melanoma of the larynx. J Laryngol Otol 1989;103:533–6. [34] Mattavelli F, Di Palma S, Guzzo M. Primary mucosal malignant melanoma of the larynx: case report and review of the literature. Tumori 1995;81:460–3. [35] Szudrowicz Z, Dymek A. Malignant melanoma of the larynx. PAT POL 1995;46:255–6. [36] Duwel V, Michielssen P. Primary mucosal malignant melanoma of the larynx: a case report. Acta Oto-Rhino-Laryngologica Belg 1996;50:47–9. [37] Nakanishi Y, Takeuchi E, Kitano H, Kitajima K. A case of double laryngeal cancer: malignant melanoma and squamous cell carcinoma. Pract Otol (Kyoto) 1996;89:215–20 (in Japanese).
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[38] Asare-Owusu L, Shotton JC, Schofield JB. Adjuvant radiotherapy for primary mucosal malignant melanoma of the larynx. J Laryngol Otol 1999;113:932–4. [39] Trabka-Zawicki P, Skladzien J, Zawilinski J, Wierzchowski W. Diagnostic difficulties in neuroendocrine carcinoma of the larynx. Otolaryngol Pol 2002;56:433–5. [40] Prasad ML, Patel SG, Huvos AG, Shah JP, Busam KJ. Primary mucosal melanoma of the head and neck: a proposal for microstaging localized. Stage I (lymph node-negative) tumors. Cancer 2004;100:1657–64.
[41] Oueslati Z, Touati S, Gritli S, el-May A, Benna F, Boussen H, et al. Mucosal malignant melanoma of the neck and face. Experience at the Salah Azaiz Institute (Tunis). Rev Laryngol Otol Rhinol 2001;122:237–40. [42] Szmeja Z, Kruk-Zagajewska A, Kaczmarek J, Zielinski L, Majewski P. Primary malignant melanoma of the larynx. Otolaryngol Pol 2000;54:173–6. [43] Lin SY, Hsu CY, Jan YJ. Primary laryngeal melanoma. Otolaryngol Head Neck Surg 2001;125:569–70.
Primary malignant melanoma of the larynx: A case report and literature review Tomonori Terada *, Nobuo Saeki, Kunichika Toh, Nobuhiro Uwa, Kosuke Sagawa, Takeshi Mouri, Masafumi Sakagami Department of Otolaryngology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya City, Hyogo 663-8501, Japan Received 9 December 2005; accepted 15 September 2006 Available online 27 December 2006
Abstract A 56-year-old Japanese man presented with hoarseness and left sided neck swelling in June 2003. Endoscopy showed an irregular tumor extending from the anterior commissure to the left ventricle with dark pigmentation. A biopsy showed malignant melanoma. A total laryngectomy with left radical neck dissection was performed in July 2003, followed by chemohormonal therapy and radiotherapy to the neck. Multiple bone metastases were diagnosed in May 2004, and the patient died with disseminated disease in April 2005, 21 months after initial treatment. The medical literature on laryngeal malignant melanoma was reviewed, and suggested a very poor prognosis despite therapy with surgery, radiotherapy, and chemotherapy. # 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Malignant melanoma; Larynx; Head and neck
1. Introduction Primary malignant melanoma of the larynx is a rare tumor. To date, there are only about 60 cases of laryngeal melanoma have been reported in the literature. In addition, the reports of adequately documented cases about clinical detailed course are a few cases including our case. This article presents a case of primary malignant melanoma of the larynx and a review of the literature.
2. Case report A 56-year-old Japanese man visited our institution in June 2003 with a primary complaint of hoarseness for the past 2 months, and a 6-month history of swelling on the left side of his neck. The patient had smoked 20 cigarettes a day for 36 years. An irregular tumor was found by endoscopy extending from the anterior commissure to the left ventricle * Corresponding author. Tel.: +81 798 45 6493; fax: +81 798 41 8976. E-mail address: [email protected] (T. Terada).
with partial dark pigment (Fig. 1). Vocal cord mobility was normal on both sides. Multiple lymphadenopathies was detected on the left side of the neck—the lymph nodes were 5.0, 2.2 and 3.0 cm in size in the upper neck, middle neck and lower neck, respectively. A CT scan verified the clinical findings and did not prove any cartilage destruction (Fig. 2). No distant metastases were found on thorax CT, abdomen ultrasound, gallium scintigram, and blood test including liver function test were normal. A biopsy of the laryngeal lesion showed a malignant melanoma (Fig. 3A). The tumor cells had pleomorphic nuclei. Some areas of the tumor consisted of elongated and spindle shaped cells, while other areas showed polygonal epithelial cells. Immunohistochemical staining was positive for S-100 protein and for HMB-45 (Fig. 3B), but was negative for cytokeratin and EMA. Total laryngectomy with a left radical neck dissection was performed in the beginning of July 2003. In the laryngeal specimen the primary lesion was found to arise from the left ventricle and the pigmentation spread into the subglottic area (Fig. 4). Following surgery, chemohormonal therapy (with dacarbazine; 220 mg/(m2 day) from days 1 to
0385-8146/$ – see front matter # 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.anl.2006.09.027
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Fig. 1. Laryngeal endoscopy shows an irregular tumor (arrows). The tumor extends from the anterior commissure to the left ventricle with an area of dark pigment.
3, ranimustine; 60 mg/(m2 day) at only day 1, cisplatin; 25 mg/m2/day from days 1 to 3, and tamoxifen citrate 10 mg 2 per day from days 1 to 28) was given at the end of July 2003 to prevent distant metastasis. Radiotherapy to the neck (60 Gy in 30 fractions, 2 Gy per fraction over 6 weeks) was administered from August 2003 to September 2003. In May 2004, multiple bone metastases were found in the clavicle, pubis, and sternum, and radiotherapy was given to the pubis and sternum (30 Gy in 10 fractions, 3 Gy per fraction over 2 weeks). Chemohormonal therapy was given after radiotherapy. The patient died of dissemination of the disease in April 2005, 21 months after the initial treatment.
3. Discussion Primary mucosal malignant melanoma of the head and neck probably derives from scattered melanocytes in the
Fig. 2. Computer tomography shows the mass arising from the anterior part the vocal cord area, and multiple lymphadenopathy (arrows) is present on the left side of the neck. There is no evidence of cartilage destruction.
mucosa. These cells may be present within the basal layer of the epithelium of the nasal cavity, oral cavity, oropharynx and esophagus. However, melanocytes are rarely detected within the larynx, which could explain the low incidence of primary melanoma in the larynx [1–3]. Mucosal malignant melanoma is rare in the head and neck region, accounting for 8–15% of malignant melanomas at this site [4,5] and less than 1% of all malignant melanomas [6]. The commonest sites in the head and neck are the nasal cavity (69%) and the oral cavity (22%) [7]. Laryngeal malignant melanoma is very rare (1.2–7.4%) [8,9], and about 60 cases have been reported in the literature to date. We found detailed clinical reports were only available for 38 patients, including our patient, as shown in Table 1. Patient characteristics are shown in Table 2. Reviewing the reports in Table 2 of 36 cases where gender was recorded, 29 cases (80.6%) were male, and their ages ranged from 35 to 86 years (mean, 60.5 years). Reuter and Woodruff [2] reported that 58 of 88 patients (66.0%) with malignant melanoma of the head and neck from 1949 to
Fig. 3. (A) There were brown atypical cells at the basal layer of the squamous epithelium. This indicates that the tumor was a primary laryngeal melanoma, and not a metastasis (hematoxylin and eosin staining; 200). (B) In the immunohistochemistry of S-100 protein and HMB-45 (200), brown granules of immunoreactivity were seen in the cytoplasm (arrows). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)
Table 1 Cases of primary malignant melanoma of the larynx reported in the literature
T. Terada et al. / Auris Nasus Larynx 34 (2007) 105–110 A: arytenoid; V: ventricle; E: epiglottis; VC: vocal cord; FC: false vocal cord; Trans: transglottis; AF: aryepiglottic fold; ?: unknown; RT: radiotherapy; TL: total laryngectomy; ND: neck dissection; PL: partial laryngectomy; Immuno: immunotherapy; Chemo: chemotherapy; CH: chemohormonal therapy; *: never rendered free of disease; 0 m: at diagnosis; DOD: died of the disease; AWD: alive with the disease; NED: no evidence of the disease; D-NED: dead with no evidence of the disease (see refs. [2,9,10–12,14,18–38,42,43].
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T. Terada et al. / Auris Nasus Larynx 34 (2007) 105–110 Table 2 Summary of the clinical course of 36 cases in Table 1
Fig. 4. The laryngeal specimen shows the mass arising from the left ventricle to the left anterior vocal cord and the right ventricle; the pigmentation extends into the subglottic area (arrows).
1983 had a history of smoking. Laryngeal melanoma may be due to smoking, as is laryngeal squamous cell carcinoma. The common initial symptom is hoarseness, and other symptoms are irritation in the throat, sore throat, dysphagia and a neck mass [10,11]. In 27 cases where the initial symptom was recorded (Table 2) hoarseness was the initial symptom in 18 cases (66.6%). In 37 cases where the primary site was recorded (Table 2), the primary site was the supraglottic region in 23 cases (62.2%) (epiglottis, 9 cases; aryepiglottic fold, 4 cases; ventricle, 4 cases; arytenoid, 3 cases, and false vocal cord, 3 cases), and the vocal cords in 14 cases (37.8%). The diagnosis of laryngeal melanoma is generally not clinically determined but is dependent on histological evaluation. The histology showed a variety of cells with spindled, polygonal, round or mixed shape. The growth patterns also vary and are similar to other neoplasms. The presence of immunoreactivity of S-100 protein and HMB45 in a pleomorphic or spindle cells is a key to diagnosis [11]. The differential diagnosis of laryngeal melanoma includes squamous cell carcinoma, neuroendocrine carcinoma, non-Hodgkin’s malignant lymphoma, extramedullary plasmacytoma, paraganglioma, sarcomas (malignant fibrous histiocytoma, fibrosarcoma, and malignant Schwannoma) [11]. A mistake is possible in histological examination if the specimen is small and especially if the involvement is an amelanotic melanoma [29]. Some cases were reported that initially histological diagnosis have malignant melanoma confused with poorly differentiated squamous cell carcinoma, with non-Hodgkin’s malignant lymphoma [33], and initially histological diagnosis have confused neuroendocrine carcinoma with malignant melanoma [39]. The traditional primary treatment for malignant melanoma of the head and neck has been radical surgery with or
without adjuvant radiotherapy or chemotherapy. Although radical surgery offers the best choice for local control, local recurrence occurs frequently [2]. Snow et al. [13] reported the recurrence rate of malignant melanoma of the head and neck as 42%, and Shah et al. [5] reported a 64% recurrence rate. In contrast, malignant melanoma of the larynx has a relatively low incidence of local recurrence after surgical removal, even after simple local excision [2]. In 21 cases where the local recurrence was recorded (Table 1), the local recurrence was in 4 cases (19.0%). The reason for the difference in the recurrence rate between malignant melanoma of the head and neck and malignant melanoma of the larynx is unclear, but it may be related to the fact that laryngeal tumors are clinically easily delimited and surgically removed. Melanoma is generally considered to be a radioresistant tumor. However, in vitro studies of cutaneous melanoma cell lines showed that they may not be intrinsically radioresistant and that high dose per fraction therapy is necessary to avoid the cell lines resisting a sublethal radiation dose [11]. Amin et al. [14] also reported that postoperative radiotherapy could be useful
T. Terada et al. / Auris Nasus Larynx 34 (2007) 105–110
in cases of mucosal malignant melanoma of the head and neck. Blatchford et al. [12] reported that chemotherapy should not be used as primary therapy but may be useful as adjunctive treatment. However, McClay et al. [15] used chemotherapy as primary therapy with or without tamoxifen in 65 cases of malignant melanoma, and demonstrated that chemotherapy with tamoxifen increased the mean survival time significantly longer than chemotherapy without tamoxifen. Seo et al. [16] reported six patients with mucosal malignant melanoma of the head and neck treated with chemohormonal therapy: three patients had a complete response, two had a partial response, and one had no response, suggesting that patients showed good responses to chemohormonal therapy. In our patient, chemohormonal therapy was initially performed to prevent distant metastasis after surgery, and later to treat the multiple bone metastasis, although with a poor response. Several studies have reported that the 5-year survival rate was less than 20% [2,14,17,41] and that 80% of the patients had metastatic disease in regional lymph nodes or at distant sites (lung, brain and liver). Prasad et al. [40] reported that the 5-year survival rate and distant metastasis rate of Stage I (N0M0) primary mucosal melanoma of the head and neck were 30.8% and 44%, respectively. As shown in Table 1, cervical metastasis to regional lymph nodes was observed in 19 of 29 cases (65.5%), and distant metastasis in 16 of 27 cases (59.3%); 23 of 29 cases (79.3%) had metastasis either to regional lymph nodes or distant sites. Only 2 of the 28 cases survived for more than 5 years, and the overall 3- and 5-year survival rates were 28.6% and 7.1%, respectively. Despite all therapeutic efforts to control mucosal malignant melanoma of the larynx, the overall 5-year survival rate is very poor.
References [1] Busutill A. Dendritic pigmented cells within human laryngeal mucosa. Arch Otolaryngol 1976;102:43–4. [2] Reuter VE, Woodruff JM. Melanoma of the larynx. Laryngoscope 1986;94:389–93. [3] Goldman JL, Lawson W, Zak FG, Roffman JD. The presence of melanocytes in the human larynx. Laryngoscope 1972;82: 824–35. [4] Anderson LJ, Berthelsen A, Hansen HS. Malignant melanoma of the upper respiratory tract and the nasal cavity. J Otolaryngol 1992;21:180–5. [5] Shah PJ, Huvos AG, Strong WE. Mucosal melanomas of the head and neck. Am J Surg 1977;134:531–5. [6] Trap TK, Fu Y, Calcaterra TC. Melanoma of the nasal and paranasal sinus mucosa. Arch Otolaryngol 1987;113:1086–9. [7] Nandapalan V, Roland NJ, Helliwell TR, Williams EM, Hamilton JW, Jones AS. Mucosal melanoma of the head and neck. Clin Otolaryngol 1998;23:107–16. [8] Buchholz W. Uber Melanoblastome im Bereich der oberen Luft-unt Speisewege. Laryngol Rhinol Otol 1958;37:549–54. [9] Moore E, Martin H. Melanoma of the upper respiratory tract. Cancer 1955;8:1167–76.
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