J Am Board Fam Pract: first published as 10.3122/jabfm.3.4.283 on 1 October 1990. Downloaded from Malignant Presenting As Nasal Obstruction Robert W Martin III, M.D., Charles R. Potter, M.D., W Gerald Klingler, M.D., and Kenneth H. Neldner, M.D.

Abstract: Mucosal arising in the nasal·cavity are rare tumors comprising less than 1 percent of all melanomas. Often, the common clinical symptom is nasal obstruction. Grossly, they mayor may not be pigmented and frequently attain large sizes. Histologic diagnosis of these tumors may be difficult, requiring immunohistochemical or electron microscopic confirmation. Aggressive surgical management is the treatment of choice in clinical stage I disease. Subsequent surveillance for recurrence is mandatory. Markers such as 5·S· cysteinyldopll may prove useful in staging, prognosticating, and postoperative surveillance for early recurrence, but their exact role has yet to be delineated. Ultimate prognosis is poor. (J Am Board Fam Pract 1990; 2:283·7.)

Melanoma of the nasal mucosa represents less It did not decongest, was firm to palpation, and than 1 percent of all melanomas. 1.2 Even though bled readily on contact. There was a 2-cm mass most patients are diagnosed with clinical stage I in the left parotid gland anterior to the left lobule, disease, the disease is usually fatal. Because pri­ and fluid was aspirated from it. There were no mary care physicians evaluate and treat many suspicious cervical nodes. Complete skin exami­ disorders that have nasal obstruction, aware­ nation showed a 2-mm blue on the left ness that melanoma is a possible cause is impor­ midback and a 12 x 7 mm actinic keratosis tant, especially in those patients who do not on the left tip of th.e nose (both proved by bi­ respond to medical management. The histologic opsy). The remainder of the examination was diagnosis may be difficult and often delayed normal. because of anatomic considerati()ns and com­ of the left nasal fossa lesion showed a placency about relatively benign presenting probably malignant melanoma on light micros­ symptoms. Aggressive surgical treatment with copy (Figure 1) and hematoxylin and eosin http://www.jabfm.org/ or without postoperative radiation is the treat­ (H & E) stain. The diagnosis was confirmed by ment of choice despite the dismal pr()gnosis. a strongly positive reaction for 5-100 protein We report our experience with a case of nasal on immunohistochemical staining and by identi­ mucosal melanoma. fication of melanosomes and premelanosomes within the tumor cells on electron microscopy

Case Report . (Figure 2). on 24 September 2021 by guest. Protected copyright. A 66-year-old white man gave a 3-week history of Complete blood count and blood chemistry, nasal congestion and obstructive symptoms de~ urinalysis, and HIV antibody count were within spite the fact that his lesion must have been pres­ normal limits. Nasai culture yielded Staphylococ­ ent much longer. There was no history of cus epidermidis. epistaxis. There was no family history of mela­ A computerized tomography (CT) scan of the or syndrome, although sinuses showed a soft tissue mass that filled most one brother died of a brain tumor ( of the nasal cavity but did not appear to have unknown). infiltrated the lateral nasal wall into the left max­ Physical examination showed a mass in the left illary antrum. The mass filled the entire inferior nasal fossa, visible with use of a nasal speculum. aspect of the left nasal airway and obliterated the inferior turbinate. CT scans of the chest, liver, and spleen were normal as were sinus and chest From the Department of . Texas Tech Univer­ radiographs. Total body bone scan showed in­ sity Health Sciences Center. Lubbock, TX. and Departments of creased accumulation in the 8th rib, 5th lumbar Otolaryngology and Dermatology. Springfield Clinic. Spring­ field. IL. vertebra, right acromioclavicular joint space,

Nasal Melanoma 283 J Am Board Fam Pract: first published as 10.3122/jabfm.3.4.283 on 1 October 1990. Downloaded from

using a microscopically controlled CO2 laser through the left nostril, reflected off manipulated mirrors within the nasal fossa. Beginning 6 weeks postoperatively, the patient was given Echino­ mycin ™ (a clinical trial chemotherapeutic agent) at 1200-mg dose IV at weekly intervals for four doses. The medication was subsequently discon­ tinued because of tumor progression. Four weeks later, alpha interferon and interleukin-2 therapies were initiated. To date, the patient has received two courses of this regimen at intervals of 2 weeks.

Discussion Head and neck melanomas constitute 15 to 20 percent of all melanomas,3-s with nasal mucosa and sinus melanomas comprising 3 percent of this total. 1,2 Since the first nasal melanoma was reported by Lucke in 1869,5 approximately 300 other cases have been reported.2 Mucosal melanoma of the nasal passages is pre­ 6 S dominantly a disease of older whites - (age range

Figure 1. Ught micrographs at 400 times magnification. His­ tology displays sheets of tumor cells under a normal-appear­ ing squamous epithelium. TIle tumor cells have large hy­ perchromatic nuclei containing prominent central nucleoli. Some of the nuclei are eccentrically located within the cells. Subsequent S-100 was positive. http://www.jabfm.org/ and the medial compartment of the right knee, but detailed bone radiographs of these areas failed to confirm metastatic disease. The patient underwent left lateral rhinotomy with left medial maxiIlectomy and total paroti­ on 24 September 2021 by guest. Protected copyright. dectomy with facial nerve preservation (Figure 3). Pathologic evaluation of the surgical speci­ mens showed melanoma in the maxillary bone, the posterior margin of the inferior turbinate, and to one lymph node in the anterior pa­ rotid gland. The 2-cm left parotid gland mass was a Warthin tumor. Ten months postoperatively, a recurrence in the anterior inferior maxillary sinus was discov­ ered during endoscopic examination. A left ster­ nocleidomastoid lymph node was also palpable. CT scan of the lungs showed metastasis to the Figure 2. Electron microscopy showed the presence of melan­ upper lobe of the left lung. The patient under­ osomes and premelanosomes confirming the diagnosis of ma­ went palliative laser destruction of the lesions lignant melanoma.

284 JABFP October-December 1990 Vol. 3 No.4 J Am Board Fam Pract: first published as 10.3122/jabfm.3.4.283 on 1 October 1990. Downloaded from

40 to 70 years9), although a 16-ycar-old patient has been reported. lo In general, a slight prepon­ derance of men is observed.7.H,II,12 Data regard­ ing racial or ethnic patterns arc conflicting.3 The etiology of mucosal melanomas is unknown.9 Ul­ traviolet light exposure cannot be considered etiologic because of the location of occurrence, I Melanosis or mucosal nevi (a rare occurrence in whites) may be precursor lesions, although such lesions are rarely recogn ized. 11,1 3 Presenting symptoms include epistaxis, ob­ struction, discharge, epiphora, facial pain, and swelling.2 Some patients have a history of nasal Figure 3. Melanoma removed at . polyps,6, 14 which may contribute to their ignor­ ing recurrent obstructive symptoms.IO The lesions vary from flat to raised, fleshy to melanoma with clinical outcome,2tl Trapp has black, and have a firm consistencyy,I5 Approxi­ suggested that any mucosal lesion with greater mately 50 percent of nasal melanomas have no than 0.7-mm invasion carries a dismal 3-year 15 obvious pigmentation. prognosis.2 More than 75 percent of the lesions originate in Recently, plasma 5-S-cyst inyldopa has been the nasal cavity/,ll most frequently involving the us d to distinguish cutaneous primary melano­ septum, followed by the inferior and middle tur­ mas without lymph node involvement and to binates.6,H, lo,12, 16 Sites of predilection correspond monitor tumor regression or progression after to the distribution of melanocytes within the mu­ therapy.2 1 The marker's correlation with tumor cosa. 13, 17 Although most patients are first seen mass rather than thickness21 may improve classi­ with clinical stage] disease,2,8 the tumor has a fication of mucosal melanomas and have prog­ high metastatic and recurrence rate. This may be nostic value. due in part to its tendency to compress local Treatment usually advocated is aggressive structu res as It. grows ra dla' II y. 17 surgical resection of the tumor locally (in Histologic misdiagnosis may occur unless the absence of regional or distant m etasta­ clinical suspicion is high and a diligent search for ses). 2,4,6-9, II ,12, 15-17,22,23 Prophylactic lymph nod http://www.jabfm.org/ melanocytes is undertaken. The absenc of read­ dissection, while controversial, is gen rally not ily identifiable melanin by light microscopy in recommended because of the low rate of subse­ one third of the cases IS and the tumor's tendency quent regional nodal recurrence (19 percent in to be more pleomorphic than cutaneous melano­ one series l7) in the abs nce of local or distant mas l7 may contribute to misdiagnosis. Immuno­ metastasis at the time of surgery.H,1 7 histochemical demonstration ofS-1001 Hor HMB- While melanoma is generally considered to be on 24 September 2021 by guest. Protected copyright. 45 proteins are useful markers for malignant p orly responsive to radiotherapy,6-H, II ,16,H it has melanomas, especially the amelanotic type. ; lec­ been u ed in some cases. Tlarwood has suggested tron microscopy is useful in establishing the pres- that the melanoma cell may not be radio-resistant ence of premelanosomes and melanosomes.9 but may have a larg capacity to repair subl thaI While cutaneous melanomas are classified into radiation damage.25 This has led t the use of a four basic clinicopathologic entities (i.e., superfi­ large dose-per-fraction regimen to provide tu­ 25 2H cial spreading, acral, nodular, and malign

Nosal Melanoma 285 J Am Board Fam Pract: first published as 10.3122/jabfm.3.4.283 on 1 October 1990. Downloaded from such as electrodesiccation, II cryotherapy (in se­ sal melanomas of the head and neck. Ilcad Neck lected cases),'2 and stimulation of the immune Surg 19n; 1:24-30. system using bacille Calmette-Gucrin (BCG) 9. Snow (;B, van der Waal I. Mucosal melanomas of the vaccine,!) have shown inconsistent results and head and neck. Otolaryngol C1in North Am 19Hti; are not used. 19:537-47. 10. Lund V. Malignant melanoma of the nasal cavity and The reported 5-year survival rate for head and paranasal sinuses. J Laryngol Owl 19H2; %:H7-5 5. neck mucosal melanomas varies from I to 3H per­ II. Conley j, Pack CT. Melanoma of the mucous mem­ cent,2,6-H,II,12,1.'-17,.l-I,35 even though most patients branes of the head and neck. Arch Otolaryngol 1974; 2 present with elinical stage I disease ,H {Freedman 99:315-9. reported the best results with an overall survival 12. Holdcraft j, Gallagher je. Malignant melanomas of rate of 40.2 percent at 3 years and 3D. <) percent at the nasal and paranasal sinus mucosa. Ann Orol 6 S years ). The poor prognosis suggests that this Rhinol Laryngol 1%9; n:5-20. tumor's biologic behavior may be more aggres­ 13. Zak FG, Lawson W. The presence of mclanocytes in sive than its cutaneous counterpart,'6 probably the nasal cavity. Ann Otol Rhinol Laryngol 1974; because of its mucosal and its anatomic location. H3:515-9. Further, the host-tumor immunologic balance is 14. Ravid JM, Esteves JA. Malignant melanoma of the nose and paranasal sinuses and juvenile melanoma of crucial to the natural history of the disease, 10 the nose. Arch Otolaryngol 1%0; 72:431-44. Because these tumors may remain undetected IS. Blatchford Sj, Koopman CFJr, Coulthard SW. Mu­ for extended periods of time, they are often large cosal melanoma of the head and neck. Laryngoscope when diagnosed; however, age, sex, duration of 19Hti; %:929-H. symptoms, size, and pigmentation do not appear 16. Harrison OF. Malignant melanomata arising in the to correlate with survival. 10 The constant risk of nasal mucous membrane. J Laryngol Otol 1976; fatal metastases is present no matter how long 90:993-1 00.1. after treatment the patient survives.

50:12-H. http://www.jabfm.org/ References 19. Clark WI-I Jr, From L, Bernardino EA, Mihm Me. I. lvloore ES, Martin H. Melanoma of the upper respi­ The histogenesis and biologic behavior of primary ratory tract and oral cavity. Cancer 195.1; H: II ti7 -7ti. human malignant melanomas of the skin. Cancer Res 2. Trapp TK, Fu YS, Calcaterra Te. Melanoma of the 1%9; 29:705-27. nasal and paranasal sinus mucosa. Arch Otolaryngol 20. Breslow A. Thickness, cross-sectional area and depth Head Neck Surg 19H7; 113: IOHti-9. of invasion in the prognosis of cutaneous melanoma .

.1. Batsakis .Ie, Regezi .lA, Solomon AR, et al. The pa­ Ann Surg 1970; 172 :902-H. on 24 September 2021 by guest. Protected copyright. thology of head and neck tumors: mucosal melano­ 21. Peterson LL, Woodward WI{, Fletcher WS, Palm­ mas. Part 13. Head Neck Surg 19H2; 4:404-IH. quist M. Tucker MA, I1ias A. Plasma 5-S-cysteinyl­ 4. Conlcy j, Ilamaker Re. Melanoma of the head and dopa differentiates patients with primary and meta­ neck. Laryngoscope 1977; H7:460-4. static melanoma from patients with dysplastic nevus 5. Uicke A. Die Lehre von den C;eschwlilsten in anato­ syndrome and normal subjects. j Am Acad Damatol miseher und kliniseher Beziehung. In: Handbuch 19HH; 19:509-15. der allgemeinen und speciellen Chirurgie, mit 22. Clark jL, DeVany ji\. Malignant melanoma of the Finschluss der wpographisehen Anatomic, Oper­ nasal cavity and maxillary sinus. Ear Nose Throat j ations. und Verbandlehre. Frlangen, IHti7:244. 19H4; 63:505-H. ti. Freedman HM, DeSanto LW, Devine KD, Weiland 23. Pearman K. Clinical records: malignant melanoma of Lli. Malignant melanoma of the nasal cavity and the nasal mucous membrane. J Laryngol Orol 1979; paranasal sinuses. Arch Otolaryngol 1973; 97: 3 22-5. 93: 1003-9. 7. Shah JP, Huvos AG, Strong EW. Mucosal melano­ 24. Catlin D. Mucosal melanomas of the head and neck. mas of the head and neck. Am .I Surg 1977; I 34: 5 31-5. Am j Roentgenol Radium Ther Nucl Med 1%7; H. Snow GB, van der Fsch FP, van Siooten EA. Muco- 99:H09-lti.

2H6 JABFP October-December I 'NO Vol..l No.4 J Am Board Fam Pract: first published as 10.3122/jabfm.3.4.283 on 1 October 1990. Downloaded from 25. Harwood AR. Melanoma of the head and neck. In: 31. McGuirt WI', ThompsonjN. Surgical approaches to Million RR, Cassisi Nj, eds. Management of head malignant tumors of the nasal septum. Laryngoscope and neck cancer. Philadelphia: jB Lippincott, 1984; 94: 1045-9. 1984:513-28. 32. Barton RT. Mucosal melanomas of the head and 26. Harwood AR, Cummings Bj. Radiotherapy for mu- neck. Laryngoscope 1975; 85:93-9. cosal melanomas. Intj Radiat Oncol BioI Phys 1982; H. Edstrom S, Jacobsson S, Jeppsson PH. Mucosal 8:1121-6. melanoma. Immunological findings in a rare case 27. Harwood AR, Dancuart I', Fitzpatrick Pj, Brown T. treated with BCG vaccine, autologous tumor cells, Radiotherapy in nonlentiginous melanoma of the and cytarabine. Arch Otolaryngol 1979; 105:48- . head and neck. Cancer 1981; 48:2599-605. 50. 28. Kirchner JA, Habermalz H, Fischer JJ. Nasal mela- 34. Eneroth CM, Lundberg C. Mucosal malignant mela- noma. Its treatment by a new technique in radiation nomas of the head and neck with special reference to therapy. Trans Am Acad Ophthalmol Otolaryngol cases having a prolonged clinical course. Acta Oto- 1975; 80:429-30. laryngol (Stockh) 1975; 80:452-8. 29. Berthelsen A, Andersen AP, Jensen TS, Hansen HS. 35. Iverson K, Robbins RE. Mucosal malignant melano- Melanomas of the mucosa in the oral cavity and the mas. Am J Surg 1980; 139:660-4. upper respiratory passages. Cancer 1984; 54:907-12. 36. Kato T, Takematsu H, Tomita Y, Takahasi M, Abe 30. Ghamrawi KA, Glennie JM. The value of radiother- R. Malignant melanoma of mucous membranes. A apy in the management of malignant melanoma of clinicopathologic study of 13 cases in Japanese pa- the nasal cavity. J Laryngol Otol 1974; 88:71-5. tients. Arch Dermatol 1987; 123:216-20. T JABFP You're TheJoumal of the American Board of Family Practice

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Nasal Melanoma 287