Journal of Surgical Oncology 39:29-32 (1988)

Primary Malignant Melanoma of the Nasal Cavity: A Clinicopathologic Study of Nine Cases

~ - _ _

CAKLOS MATIAS, MD, JOSF CORDE, AND JORCE SOARES From the Department of Pathology, lnstrtuto t'ortugucs de Oncologia de

Francisco Gentil, Lisboa, Portugal

.-

Nine cases of primary malignant melanoma of the nasal cavity are pre- sented. All the patients had epistaxis and nasal obstruction at admission. Gross aspect of the neoplasia showed a fungating mass located in the right nasal cavity in six cases and in the left nasal cavity in three. Eight tumors were formed by polygonal cells and one tumor by spindle cells. Melanosis of the adjacent mucosa was found in only 1 case. S-100 protein was demonstrated by indirect immunoperoxidase in all cases. The mean sur- vival rate was 23.8 months. Prognosis was not related to the histologic pattern, cell atypia, necrosis, pigment secretion, or mitotic index. Radio- therapy seemed to have some beneficial influence on the survival but did not influence the local recurrence and metastatic spread of the disease.

KEY WORDS: malignant melanoma, nasal cavity, nasal neoplasia, histology, prognosis

INTRODUCT JON Primary malignant melanoma of the nasal mucosa is

an uncommon neoplasia and constitutes one type of extra- cutaneous melanoma as proposed by the UICC [ 11.

According to several series, malignant melanomas of the nasal cavity and paranasal sinuses represent less than 1 % of the total number of cutaneous and extracutaneous malignant melanomas and 2-9% of head and neck mela- nomas 12-51.

There is little information about the natural history of these tumors, the clinicopathologic factors that influence its prognosis, and the usefulness of therapeutic agents complementary to surgical excision of the neoplasia.

The aim of this study was to reevaluate the pathologic features, therapeutics, and clinical evolution of nine cases of primary malignant melanoma of the nasal cavity.

MATEKIALS AND METHODS On reviewing tumoral lesions of the nasal cavity and

paranasal sinuses from the files of the Department of Pathology of the Instituto Portugues de Oncologia de Francisco Gentil over a 10-year period, we retrieved nine cases of primary malignant melanoma.

Clinical records of all the patients were reviewed for age, sex, presenting symptoms, location, gross aspect, ex-

@ 1988 Alan R. Liss, Inc.

tension of disease, therapy, and clinical evolution. Follow- up information was obtained in all but one case (case 7).

Histologic slides were reviewed, and new sections from available blocks were made when needed. Hematoxylin and eosin, Masson-Fontana, and reticulin staining were used in the study. Immunoreactivity for S-100 protein was investigated in all nine cases using the PAP method (dilution 1 :320, DAKO-immunoglobulins Ltd., Den- mark).

RESULTS Clinical Features

In the present series all the patients were Caucasian. Six were males and 3 females. The mean age at presen- tation was 64 years with a range of 59 to 76 years. None had a personal history of melanoma in other sites. There was no family history of pigmented tumors.

The initial symptom was nasal obstruction in five pa- tients and intermittent epistaxis in four. At the time of diagnosis, seven patients had nasal obstruction, an equal number had epistaxis, and one also complained of facial

Accepted for publication October 15, 1987. Address reprint requests to Carlos Matias, MD, Servico de Anatomia Patol6gica; lnstituto Ponugues dc Oncologia de Francisco Gentil, Rua Prof. Lima Basto, Palhava, 1093 Lisboa codex, Portugal.

30 Matias et al.

TABLE I. Main Histologic Features*

Case No. Pattern Cell atypia Mitosisa Necrosis Melanin

1 M + O +++ 9 ++ ++ 2 M + O + 12 3 M ++ 12 ++ ++ 4 M + O ++ 10 + + + + 5 M + 6 + + 6 M + O + 8 7 M + 8 8 M + O + 12 + + 9 M + 9 + + + + + +

+ -

+ +

- -

*M, medullary; M+O, medullary + organoid areas; (-) absent; (+) mild; (+ +) moderate; (+ + +) severe. 'Per 10 high power fields (HPF).

TABLE 11. Therapy and Clinical Evolution

Case Age No. (yr) Sex Initial therapy Rec Met Evolution

1 61 M S+C DOD, 8 mo 2 64 F S+R+C + + DOD,6yr 3 66 M S + DOD, 11 mo 4 72 M R DOD, 5 mo 5 61 M R + S + + DOD,4yr 6 69 F S+R + AWD, 2 y r 7 59 M S 7

8 76 M S + R DOD, 7 mo 9 61 F S + I DOD, 1 yr

S, surgery; R, radiotherapy; C, chemotherapy; I, immunotherapy; Rec, local recurrence; Met, metastases; DOD, dead of disease; AWD, alive with disease.

pain. The average duration of symptoms before diagnosis was 4 months.

In all nine patients, physical examination revealed a pink to brownish friable fungating mass, almost totally occluding the nasal cavity in six patients. The right nasal cavity was affected in six cases and the left in three. In one case there was also a dark macula on the rnucosa lining the septum on the same side as the tumor. None of the tumors extended to the nasopharynx or to the nose skin.

There was radiographic evidence of maxillary bone invasion in three cases and of ethmoidal invasion in two. Upon surgery one of the latter patients was shown to have meningeal involvement.

One patient had cervical lymph node metastases at pre- sentation (case 5).

Pathologic Findings In the eight surgical specimens the tumor presented as

a uolvuoid fungating mass. There were no macroscoric

changes in adjacent mucosa except in one case that showed a melanotic macula along the septum.

The main histologic features of the neoplasias are de- scribed in Table I.

All the tumors had a solid microscopic aspect. In five cases the reticulin staining showed organoid areas inter- mixed with a medullary pattern of organization of the neoplasia (Fig. 1). Spindle cells were largely predomi- nant in one case (Fig. 2), whereas the other tumors were formed by polygonal cells, mostly of the large cell type (Fig. 3). Giant multinucleated cells were present in cases 1, 3,4, and 8.

The cytoplasm was mostly esinophilic, usually dense. Prominent nucleoli were common, as well as intranuclear cytoplasmic inclusions, observed in all but case 8. There were six to 12 mitotic figures per 10 HPF.

Necrosis was extensive in two cases and absent or presenting as small foci in three.

Melanin pigment could be demonstrated in all nine cases. Five of them, however, showed only scarce cyto- plasmic granules.

Positive immunoreactivity for S- 100 protein was dern- onstrated in all cases, with variable staining intensity.

Vascular proliferation was a constant feature, fre- quently associated with areas of hemorrhage and necrosis of the tumors.

In five cases there was mild lymphoid infiltration.

Therapy and Followup

Table 11 summarizes the types of treatment and the clinical evolution of the nine cases. Surgical treatment was used in all but patient 4 and was the only therapy in cases 3 and 7. Large tumor excision was performed in cases 3, 6, 7, and 8. Patients 1, 2, and 5 were treated by partial maxillectomy and patient 9 by radical max- illectomy .

Patient 4 presented a locally extensive and invasive tumor and was submitted to radiotherapy as the sole treatment. Patient 5 presented with cervical lymph node involvement and was given a 50 Gy radiotherapy course to that area. Five months later he underwent radical cervical lymphadenectomy. Patients 2, 6, and 8 received local radiotherapy postoperatively.

Chemotherapy was used after surgery and radiotherapy in patients 1 and 2 and for metastatic spreading disease 4.5 years later in patient 2.

Adjuvant immunotherapy was used in patient 9 follow- ing radical maxillectomy.

The mean duration of followup was 2 years (range 5 months to 6.4 years). One patient was lost to followup (case 7), and another was alive with disease 2 years after

. -. - - . intial therapy and lost to followup thereafter.

Malignant Melanoma 31

Local recurrence was confirmed in cases 2 and 5 , having occurred 4 years after surgery in case 2 and 3.7 years after surgery in case 5 .

Patient 5 presented with cervical lymph node metas- tases. Three other cases (2,3,6) had lymph node involve- ment within a mean time of 29 months after surgery (range 9-54 months).

Mean survival rate was 23.8 months.

DISCUSSION Primary malignant melanomas of the nasal cavity are

rare neoplasms. In most series they account for less than 4% of all primary nasal tumors [2,6-91.

On reviewing 429 consecutive cases (from 1970 to 1979) of benign and malignant lesions of the nasal cavity

Fig. 1 . Intermixed organoid and medullar areas. H&E. X220. Inset: and paranasal sinuses, we retrieved nine cases of malig- Small and medium type polygonal cells. S = 100 protein. PAP method. x 875. nant melanoma with origin in the nasal cavity (2.1 % of

all lesions, 4.8% of all neoplasms, and 6.9% of all malignant tumors).

We found a significant male prevalence of the disease (two-thirds of our patients), while previous observations found no sexual differences in incidence [ 10,111.

The age at presentation (sixth decade) was similar to other published studies [2,3,11,12]. Thus far melanomas of the mucosae have an age incidence higher than their skin counterpart.

In the present series there was clinical presentation with nasal obstruction and intermittent epistaxis as the most common symptoms. This correlated with the poly- poid gross aspect of the tumors.

Melanomas of the nasal cavity behave as a rapidly growing tumor [7,11,13,14]. In fact the average duration of symptoms before diagnosis was 4 months, shorter than that usually observed in other malignant nasal tumors in our series (8 months) (J. Soares and C. Matias, unpub- lished data). Fig. 2 . Predominant spindle cell area. H&E. X220. Inset X875.

Superficial spreading of the neoplasia, a frequent pat- tern of presentation in cutaneous melanomas, was not observed in the nasal cavity melanomas of the present series.

Several authors have found melanosis of the mucosa adjacent to the tumor to be a common finding and stress that this explains the development of local melanocytic neoplasia [8,11,151. We could not demonstrate this obser- vation in our cases as only one (case 3) had nonmalignant melanocytes at variable distance from the tumor. How- ever, we also find that malignant melanomas originate in occcasional dendritic melanocytes of the nasal mucosa, whose presence in the normal basal epithelium was dem- onstrated by Zak and Lawson [ 161.

Cytologic features of the nasal melanomas showed a predominance of polygonal cells. Pigment deposition was demonstrated in all cases by the Fontana-Masson tech-

Fig. 3. Large, aberrant polygonal cells. H&E. X875. nique.

32 Matias et al.

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