ORIGINAL
DURAI,ARTICLE
HASHMI
Primary malignant melanoma of the
epiglottis: A rare presentation
Rajaraman Durai, MS, MRCS; Syed Hashmi, FRCS
Abstract
Primary malignant melanoma of the epiglottis is extremely
rare. Until now, only 4 cases have been reported in the world
literature. We describe a new case of epiglottic primary
malignant melanoma in a 74-year-old man who presented
with hoarseness and a foreign-body sensation. Clinical
examination revealed the presence of a small, whitish,
polypoid tumor on the laryngeal surface of the epiglottis;
no other primary melanoma was detected. Wide excision
of the lesion was performed, and microscopy revealed that
it contained melanin-pigmented tumor cells in both the
mucosa and submucosa. Immunostaining was positive for
S-100 protein. The patient was treated with radiotherapy,
and he remained well 1 year after the diagnosis with no
evidence of recurrence.
new case of primary malignant melanoma of the epiglottis,
and we briefly review the relevant literature.
Introduction
Malignant melanoma is a neoplasm that arises from melanocytes. Melanocytes are derived from the neural crest
and are widely distributed throughout all cutaneous and
mucosal surfaces. They are found in the basal layer of the
epidermis near the dermal-epidermal junction; they have
been reported in the larynx, nasal cavity, and mouth.1 Although melanoma usually arises from the skin, in rare cases
itcanaffecttheeye,meninges,andthemucousmembranes
of the digestive and upper respiratory tract.
Several varieties of epiglottic neoplasms have been
described in the literature. Of these, malignant melanoma
is rare. When malignant melanoma of the epiglottis does
occur, it can be either primary or secondary. Until now,
only 4 cases of primary malignant melanoma of the epiglottis have been reported in the world literature.2-5 None
of them were associated with basal cell carcinoma. A case
of a secondary amelanotic melanoma of the epiglottis was
reported by Ikeda et al in 1991.6 In this article, we report a
Case report
A 74-year-old man presented to the Department of Laryngology and Otology at James Paget Hospital with a
3-month history of hoarseness and an unusual sensation
in his throat. His medical history was significant for several recurrent basal cell carcinomas of the head and neck
(which had been treated with cryotherapy and excision)
and for tuberculous cervical lymphadenitis (for which he
had received a full course of standard antituberculosis
chemotherapy). He was a smoker and had been so for
more than 40 years.
Clinical examination did not reveal any cutaneous
melanomas or palpable cervical lymph nodes. Fiberoptic
laryngoscopydetectedasmall,white,polypoidlesiononthe
posterior aspect of the epiglottis (figure 1). Under general
anesthesia,thepatientunderwentdirectlaryngoscopy,and
the lesion was excised and submitted for histopathologic
examination. A paraffin section stained with hematoxylin
and eosin (H&E) showed tumor cells with clear nuclei
exhibiting pleomorphism and melanin pigmentation in
the cytoplasm (figure 2). These cells had hyperchromatic
nuclei, and they invaded both the mucosa and submucosa.
On immunohistochemistry for S-100 protein, the tumor
cells demonstrated a strong positive staining in both the
nuclei and cytoplasm (figure 3). The lesion was diagnosed
as a primary malignant melanoma because all clinical,
panendoscopic, and ophthalmologic examinations conducted to identify a possible primary lesion elsewhere were
negative. Following surgical excision, the patient opted to
undergo radiotherapy. One year after his diagnosis, he was
well and showed no evidence of recurrence.
From the University Department of Surgery, Royal Free Hospital, London
(Dr. Durai), and the Department of Laryngology and Otology, James
Paget Hospital, Great Yarmouth, U.K. (Dr. Hashmi).
Reprint requests: Rajaraman Durai, MS, University Department of
Surgery, Royal Free Hospital, Pond St., London NW 2QG, UK.
Phone: 44-775-126-5993; fax: 44-207-377-7684; e-mail: dr_
[email protected]
Discussion
No case of malignant melanoma of the epiglottis has been
published since 1991.6 Only 0.6 to 9.3% of patients with
cutaneousmalignantmelanomawillexperienceametastasis
to the mucosa of the upper aerodigestive tract.7 Mucosal
melanomas are usually of the acral lentiginous type,8
and they occur most often in the nasal cavity and sinuses
274
ENT-Ear, Nose & Throat Journal  April 2006
PRIMARY MALIGNANT MELANOMA OF THE EPIGLOTTIS: A RARE PRESENTATION
Figure 1. Fiberoptic laryngoscopy shows the small, white, polypoid lesion (arrow) on the posterior aspect of the epiglottis.
(table 1).9 Among laryngeal melanomas, the supraglottic
region is the most common site of involvement.10 Cases of
metastatic melanoma from an unknown primary may be
attributable to (1) spontaneous regression of the primary,
(2) the location of a primary in a visceral organ, or (3) an
inability to detect a primary in the skin.
The clinical features of laryngeal melanomas include
hoarseness,hemoptysis,dysphagia,airwayobstruction,and
stridor.11-13 Enlarged cervical lymph nodes may be present.
The tumor can spread to the brain, lungs, and spine.12 Our
patientpresentedwithhoarsenessandaforeign-bodysensation. His hoarseness may have been attributable to chronic
laryngitis secondary to his smoking. The foreign-body
sensation disappeared after the tumor was excised.
A diagnosis of melanoma must be confirmed by histologic examination of an excisional biopsy specimen;
obtaining a specimen might require direct laryngoscopy
under anesthesia. Under light microscopy, the tumor will
exhibit a pleomorphic epithelioid cell population of malignant cells. Malignant spindle-shaped cells may also be
identified. Cells often contain dark-brown cytoplasmic and
nuclear melanin.12,14The presence of melanin is identifiable
on H&E staining, Fontana staining, and immunohistochemistry, which will show immunoreactivity with S-100
protein and HMB-45.12 Electron microscopy may identify
the presence of melanosomes or premelanosomes. Although the tumor in our patient appeared to be amelanotic
on clinical examination, melanin pigmentation was seen
in the cytoplasm on microscopy, and immunohistology
was positive for S-100 protein.
Three conditions usually exist that help identify a tumor
as a primary malignant melanoma: (1) the tumor should be
the dominant lesion, (2) there may be local and regional
metastasis, and (3) the patient should have no history of
a primary cutaneous or ocular melanoma or nevus that
regressed spontaneously.8 The hallmark of a primary
malignant melanoma is the presence of junctional activity in the overlying or adjacent mucosa.8 Malignant cells
must be identified in the surface epithelium to establish
a diagnosis of a primary malignant melanoma.14,15 In our
patient, malignant cells were clearly seen in the surface
epithelium (figure 2). Our patient had no other identifiable
malignant lesion, and histology of his previous basal cell
carcinomas did not provide any evidence of pigmentation.
Therefore, his tumor was diagnosed as a primary.
Positron-emissiontomography(PET)andmagneticresonance imaging (MRI) may be used for staging malignant
melanomas.Inaretrospectivestudyoffluorodeoxyglucose
(FDG) PET in 18 patients with mucosal melanoma, Goerres
et al reported that all tumors were visible at staging, but
the FDG uptake was dependent on the size and anatomic
site of the lesion.16 Big nodular lesions were more visible
than the more superficial spreading lesions. Lesions in the
anterior part of the nose were more difficult to detect than
those located elsewhere.
A
B
Figure 2. A: Photomicrograph shows the surface epithelium and underlying stroma, which contains a dense infiltrate of malignant
melanocytes (H&E, original magnification ×100). B: Photomicrograph shows the variability in the size, shape, and staining intensity of the malignant melanocytes (H&E, original magnification ×250).
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DURAI, HASHMI
Table 1. Location of mucosal melanomas of the head
and neck in 259 patients in Merseyside, U.K.9
Site Nasal cavities and sinuses Oral cavity Pharynx, larynx, and upper esophagus %
69
22
9
Table 2. Prognosis of stage I primary mucosal melanomas of the head and neck29
Figure 3. Photomicrograph shows the positive immunostaining for S-100 protein in the nucleus and cytoplasm (original
magnification ×250).
Yoshioka et al analyzed MRI findings in 6 patients with
mucosalmelanomaandfoundthatonT1-weightedimaging,
5 melanomas were hyperintense and 1 was isointense.17
On T2-weighted imaging, 5 were of mixed intensity and
1 was isointense. The mean signal intensity ratios for the
primary melanoma to muscle on T1-weighted imaging
were 1.51 with gadolinium contrast and 1.39 without it;
the difference was not statistically significant. This finding suggests that hyperintensity on T1-weighted imaging
is a common characteristic of mucosal melanoma but not
a universal finding.
The only curative treatment is radical local excision
(total laryngectomy and neck dissection for laryngeal
melanoma).11 Local recurrences are common, even when
surgical margins are wide. A simple local excision is occasionally used. There is 1 report in the literature of a case of
melanoma of the right vocal fold that was managed with a
rightcordectomyandadjuvantradiotherapy.18Thatpatient
remained well without any evidence of local recurrence or
metastasis for more than 3 years. In the case described by
Ikeda et al, a patient with cutaneous amelanotic melanoma
developed a metastatic tumor that involved the epiglottis;
the tumor was successfully excised via an intraoral approach and KTP/532 laser surgery.6
Nonsurgical treatments include radiotherapy, chemotherapy, immunotherapy, and CO2 laser ablation.19 Several
reports published during the past decade on radiotherapy
alone have documented complete response rates of 50 to
75% and enduring long-term control in one-half to twothirds of the complete responders.18,20 These data, taken in
conjunction with the high rate of local failure after surgery
alone, suggest that radiotherapy would have a useful role
as a surgical adjuvant in a combined-modality approach,
as well as being of value in the primary management
of unresectable disease.18,20 Currently, chemotherapy
is principally used for the treatment of disseminated
276
Level I
II III Invasion In situ Lamina propria only Deep tissue Survival
11 yr 6 mo
5 yr 9 mo
1 yr 5 mo
disease and for palliation.21 Immunotherapeutic options
include OK-432, interleukin 2, lymphokine-activated
killer cells, and cyclophosphamide.22 The American Joint
Committee on Cancer conducted a large cohort study of
734 patients with stage I to III melanoma and found that
bacille Calmette-Guérin (BCG) vaccine as an adjuvant
to dacarbazine delayed the progression of disease and
improved survival.23 BCG vaccination usually lowers the
risk of developing melanoma.24
Several reasons explain the poor prognosis associated
with mucosal melanoma: (1) the nonspecific nature of
its symptoms leads to delays in diagnosis, (2) the tumor
affects many older people whose immune function is inefficient, (3) the rich vascular and lymphatic efferents of the
mucosa favor early metastasis, and (4) mucosal melanoma
is histologically aggressive.1,25-27 Even so, overall mortality
for early head and neck melanoma has actually declined
because a higher percentage of patients are seeking treatment when the tumor is at an early stage (table 2).28
Acknowledgment
The authors thank D.A. Harrison, BSc, FRCPath, of the
Department of Pathology at James Paget Hospital in Great
Yarmouth, U.K., for his advice on the pathology section.
References
1. Xavier R, Paiva A, Ribeiro da Silva P, Gameiro dos Santos A.
Primary malignant melanoma of the palatine tonsil: A case report.
J Laryngol Otol 1996;110:163-6.
2. Shanon E, Covo J, Loeventhal M. Melanoma of the epiglottis.
A case treated by supraglottic laryngectomy. Arch Otolaryngol
1970;91:304-5.
3. Welsh LW, Welsh JJ. Malignant melanoma of the larynx. Laryngoscope 1961;71:185-91.
4. Pantazopoulos PE. Primary malignant melanoma of the larynx.
Laryngoscope 1964;74:95-102.
5. Catlin D. Cutaneous melanoma of the head and neck. Am J Surg
1966;112:512-21.
ENT-Ear, Nose & Throat Journal  April 2006
Silverstein Institute
PRIMARY MALIGNANT MELANOMA OF THE EPIGLOTTIS:
A RARE PRESENTATION
6. Ikeda M, Takahashi H, Karaho T, et al. Amelanotic melanoma
metastatic to the epiglottis. J Laryngol Otol 1991;105:776-9.
7. Billings KR, Wang MB, Sercarz JA, Fu YS. Clinical and pathologic
distinction between primary and metastatic mucosal melanoma of
the head and neck. Otolaryngol Head Neck Surg 1995;112:700-6.
8. Ramamurthy L, Nassar WY, Hasleton PS. Metastatic melanoma of
the tonsil and the nasopharynx. J Laryngol Otol 1995;109:236-7.
9. Nandapalan V, Roland NJ, Helliwell TR, et al. Mucosal melanoma of
the head and neck. Clin Otolaryngol Allied Sci 1998;23:107-16.
10. Reuter VE, Woodruff JM. Melanoma of the larynx. Laryngoscope
1986;96:389-93.
11. Szmeja Z, Kruk-Zagajewska A, Kaczmarek J, et al. [Primary malignant melanoma of the larynx]. Otolaryngol Pol 2000;54:173-6.
12. Wenig BM. Laryngeal mucosal malignant melanoma. A clinicopathologic, immunohistochemical, and ultrastructural study of four
patients and a review of the literature. Cancer 1995;75:1568-77.
13. Pau H, De S, Spencer MG, Steele PR. Metastatic malignant melanoma of the larynx. J Laryngol Otol 2001;115:925-7.
14. Amin HH, Petruzzelli GJ, Husain AN, Nickoloff BJ. Primary malignant melanoma of the larynx. Arch Pathol Lab Med 2001;125:
271-3.
15. Allen AC, Spitz S. Malignant melanoma; a clinicopathological
analysis of the criteria for diagnosis and prognosis. Cancer 1953;6:
1-45.
16. Goerres GW, Stoeckli SJ, von Schulthess GK, Steinert HC. FDG
PET for mucosal malignant melanoma of the head and neck. Laryngoscope 2002;112:381-5.
17. Yoshioka H, Kamada T, Kandatsu S, et al. MRI of mucosal malignant melanoma of the head and neck. J Comput Assist Tomogr
1998;22:492-7.
18. Asare-Owusu L, Shotton JC, Schofield JB. Adjuvant radiotherapy
for primary mucosal malignant melanoma of the larynx. J Laryngol
Otol 1999;113:932-4.
19. Hussain SS, Whitehead E. Malignant melanoma of the larynx. J
Laryngol Otol 1989;103:533-6.
20. Trotti A, Peters LJ. Role of radiotherapy in the primary management
of mucosal melanoma of the head and neck. Semin Surg Oncol
1993;9:246-50.
21. Medina JE, Ferlito A, Pellitteri PK, et al. Current management of
mucosal melanoma of the head and neck. J Surg Oncol 2003;83:
116-22.
22. Mochimatsu I, Tsukuda M, Kurihara M, et al. [Case reports of
mucosal melanoma of the head and neck]. Nippon Jibiinkoka
Gakkai Kaiho 1996;99:552-7.
23. Agarwala SS, Neuberg D, Park Y, Kirkwood JM. Mature results
of a phase III randomized trial of bacillus Calmette-Guerin (BCG)
versus observation and BCG plus dacarbazine versus BCG in the
adjuvant therapy of American Joint Committee on Cancer Stage
I-III melanoma (E1673): A trial of the Eastern Oncology Group.
Cancer 2004;100:1692- 8.
24. Pfahlberg A, Kolmel KF, Grange JM, et al. Inverse association
betweenmelanomaandpreviousvaccinationsagainsttuberculosis
and smallpox: Results of the FEBIM study. J Invest Dermatol
2002;119:570-5.
25. Pandey M, Mathew A, Iype EM, et al. Primary malignant mucosal
melanoma of the head and neck region: Pooled analysis of 60
published cases from India and review of literature. Eur J Cancer
Prev 2002;11:3-10.
26. Pandey M, Abraham EK, Mathew A, Ahamed IM. Primary malignant
melanoma of the upper aero-digestive tract. Int J Oral Maxillofac
Surg 1999;28:45-9.
27. Pandey M, Mathew A, Abraham EK, et al. Primary malignant
melanoma of the mucous membranes. Eur J Surg Oncol 1998;24:
303-7.
28. Cowan A, Pou AM. Melanoma of the head and neck. In: Quinn FB
Jr., Ryan MW, eds. Dr. Quinn’s Online Textbook of Otolaryngology.
Galveston, Tex.: University of Texas Medical Branch; 2004. www.
utmb.edu/otoref/grnds/Melanoma-2004-0310/Melanoma-20040310.htm (accessed Feb. 20, 2006)
29. Prasad ML, Patel SG, Huvos AG, et al. Primary mucosal melanoma
of the head and neck: A proposal for microstaging localized, Stage
I (lymph node-negative) tumors. Cancer 2004;100:1657-64.
MINIMALLY INVASIVE OTOLOGICAL SURGERY COURSE
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assisted tympanostomy, otoendoscopy, fat graft myringoplasty, perfusion of
the round window and Eustachian tube, MicroWickTM, permanent aeration
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Silverstein Institute
Ear Research Foundation
1901 Floyd Street
Sarasota, FL 34239
941-365-0367
fax 941-556-4211
www.silversteininstitute.com • [email protected]
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