Mucoepidermoid carcinoma ex Pleomorphic adenoma

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CYTOPATHOLOGY

Mucoepidermoid Carcinoma Ex Pleomorphic Adenoma Nonspecific Preoperative Cytologic Findings in Six Cases

Jerzy Klijanienko, M.D.1 Adel K. El-Naggar, M.D., Ph.D.1 Vincent Servois, M.D.2 Joseph Rodriguez, M.D.3 Pierre Validire, M.D.1 Philippe Vielh, M.D., Ph.D.1 1

Department of Pathology, Institut Curie, Paris, France.

2

Department of Radiology, Institut Curie, Paris, France.

3

Department of Head and Neck Surgery, Institut Curie, Paris, France.

BACKGROUND. In contrast to most major salivary gland malignancies, mucoepidermoid carcinoma has been rarely documented and tentatively accepted as carcinoma ex pleomorphic adenoma. The authors present the cytologic and clinical findings for six examples of these rare tumors. METHODS. The six examples were identified during an extensive review of the authors’ salivary gland files, and all were high grade mucoepidermoid carcinomas on histologic evaluation. RESULTS. Overall, mucoepidermoid carcinomas cytologically presented as nonspecific high grade malignancies and consisted of highly malignant cells, in clusters or isolated, that were rarely associated with intracellular and extracellular mucin. In only two cases, a background of cellular and stromal elements consistent with pleomorphic adenoma was identified. CONCLUSIONS. Although it is nearly impossible cytologically to distinguish these lesions from other high grade primary or metastatic carcinomas (such as poorly differentiated squamous cell carcinomas, adenosquamous carcinomas, and salivary duct carcinomas), this limitation is not dramatic, as a cytologic diagnosis of high grade malignancy per se allows for proper preoperative patient management. Cancer (Cancer Cytopathol) 1998;84:231– 4. © 1998 American Cancer Society. KEYWORDS: malignant mixed tumor, carcinoma ex pleomorphic adenoma, mucoepidermoid carcinoma ex mixed tumor, cytology.

C

arcinoma ex pleomorphic adenoma of the salivary gland is a relatively uncommon tumor that accounts for roughly 4% of all malignancies at this location.1 Most primary malignant salivary gland carcinomas have been reported as the malignant component in this setting.2–5 However, the presence of mucoepidermoid carcinoma arising from pleomorphic adenoma, although one of the most frequently occurring primary salivary gland malignancies, has been disputed and rarely reported.2,6 –10 Moreover, of the six cases reported in the literature, some lack convincing illustrations and only two include cytologic findings.6,9,10 We report the cytologic and histologic characteristics of six mucoepidermoid carcinomas arising in pleomorphic adenomas and discuss their differential diagnostic features.

MATERIALS AND METHODS Address for reprints: J. Klijanienko, M.D., De´partement de Pathologie, Institut Curie, 26 rue d’Ulm, 75248 Paris Cedex 05, France. Received March 30, 1998; accepted April 2, 1998. © 1998 American Cancer Society

We reviewed 1648 salivary gland tumors diagnosed at the Institut Curie between 1954 and 1997. Of these, 50 (3%) histologically classified11 as mucoepidermoid carcinoma and 6 (0.3%) as mucoepidermoid carcinoma ex pleomorphic adenoma had preoperative cytology. As already described,12 cytologic samples were performed by a cytopathologist using a 23-gauge (0.6 mm) needle, with aspiration

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TABLE 1 Clinicopathologic Data on Six Patients Who Presented Histologically with High Grade Mucoepidermoid Carcinomas Arising from Pleomorphic Adenomas Case no.

Age (yrs)

Gender

Site

Tumor (cm)

Cytology

Treatment

Follow-up (months)

1 2 3 4 5 6a

57 45 57 75 68 62

M F M M M F

SM P P P P P

232 434 837 635 232 737

MEC ex PA MEC ex PA SCC SCC Ca. NOS Ca. NOS

S S S, RT S, RT, CT S S, RT

ADF (12) Lost (1) Lost (2) DOD (12) ADF (94) Lost (0.5)

SM: submandibular gland; MEC ex PA: mucoepidermoid carcinoma ex pleomorphic adenoma; S: Surgery; ADF: alive, disease free; P: parotid gland; SCC: squamous cell carcinoma; RT: radiotherapy; Ca. NOS: carcinoma not otherwise specified; CT: chemotherapy; DOD: dead of disease. a This patient had a history of recurrent pleomorphic adenoma.

before 1980 and without aspiration after 1980, and evaluated on air-dried smears stained by the May– Gru ¨ nwald–Giemsa method. Demographic, clinicopathologic, and follow-up data were collected from medical charts and pathology reports.

RESULTS Clinicopathologic data on the six patients are presented in Table 1. The cohort comprised four males and two females, with ages ranging from 46 to 75 (mean, 60.8) years. Tumors were located in the parotid gland in five patients and in the submandibular gland in one patient. Tumor sizes ranged from 2 to 8 (mean, 4.8) cm in greatest dimension. Cytologic smears containedhighly malignant epithelial cells, in clusters or isolated, that were consistent with high grade carcinoma. In two tumors, the smears were composed of a variety of cells and mucoid stroma; the cellular component included squamoid and mucous features; and in both tumors, a chondromyxoid background with myoepithelial cells characteristic of pleomorphic adenoma was noted,13 so that a diagnosis of mucoepidermoid carcinoma arising from pleomorphic adenoma was suggested (Fig. 1). In two other tumors, highly atypical squamoid cells were present without any evidence of keratinization or keratin debris, mucous cells and mucoid background were absent, and a diagnosis of primary salivary squamous cell carcinoma was suggested (Fig. 2). The remaining two cases showed no specific distinguishing features other than highly malignant epithelial cells and were diagnosed as high grade carcinoma. All tumors were histologically high grade mucoepidermoid carcinomas (Figs. 3, 4). Three of them were composed of intermediate and squamous cells with focal areas of well-differentiated, foamy, mucous cells lining cystic and ductal structures (Fig. 5); two

FIGURE 1.

Case 1: Fine-needle sampling of high grade mucoepidermoid carcinoma ex pleomorphic adenoma is shown. Typical pleomorphic adenoma is characterized by a red-magenta chondromyxoid stroma and myoepithelial cells (on the left) intermingled with malignant cells of intermediate type. Several cells show clear squamoid features (on the right). Note the mucoid background (May–Gru¨nwald–Giemsa staining, original magnification 340).

were composed of sharply demarcated squamous islands with focal mucin-producing cells, and one case consisted of clear cells intimately associated with intermediate and squamous cells. All tumors showed frequent mitotic figures and an infiltrative pattern. Scant areas of pleomorphic adenoma were seen in five tumors, whereas one patient (Case 6) with a 24-year history of locally recurrent pleomorphic adenoma had a mucoepidermoid carcinoma.

DISCUSSION Carcinoma ex pleomorphic adenoma is an uncommon neoplasm that may present de novo or in recurrent pleomorphic adenoma.1,7 Although most major subtypes of salivary gland carcinoma have been reported in association with pleomorphic adenoma, the existence of mucoepidermoid carcinoma has been

Mucoepidermoid Carcinoma Ex Mixed Tumor/Klijanienko et al.

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FIGURE 2. Case 3: Fine-needle sampling of high grade mucoepidermoid carcinoma is shown. Smears consist of squamous cell carcinoma with keratinizing cells and a necrotic background. Pleomorphic adenoma was not found (May–Gru¨nwald–Giemsa staining, original magnification 340).

FIGURE 4.

FIGURE 3. Case 1: Mucoepidermoid carcinoma, consisting of malignant cells with rare mucus-secreting areas (upper right quadrant), is shown. Pleomorphic adenoma is visible in the lower left corner. Note the keratin metaplasia in the upper left quadrant (hematoxylin– eosin–safranin, original magnification 320).

FIGURE 5. Case 1: Mucus-secreting cells are shown (Alcian blue, original

disputed and rarely reported.2,6 –10 Moreover, only two of the reported cases were diagnosed by fine-needle aspiration.9,10 It seems, therefore, that the occurrence of mucoepidermoid carcinoma is probably underestimated and that, similarly to the salivary duct carcinomas, many adenocarcinomas “not otherwise specified” or squamous cell carcinomas may in fact be high grade mucoepidermoid carcinomas.14 Our retrospective review revealed that only two neoplasms had cytologic features consistent with high grade mucoepidermoid carcinoma, such as mucouscontaining and squamous malignant cells, in a typical background of pleomorphic adenoma. The remaining cases were cytologically diagnosed as squamous cell carcinoma or high grade carcinoma because the peculiar features of pleomorphic adenoma were not identified. Although a high grade carcinoma compo-

Case 3: Mucoepidermoid carcinoma with squamoid features is shown. Underlying pleomorphic adenoma is represented by a hyaline stroma (top) with a few well-preserved myoepithelial cells (hematoxylin– eosin–safranin, original magnification 320).

magnification 340).

nent was always identified on cytologic slides, it was similar to other metastatic or primary high grade malignancies, such as adenocarcinoma not otherwise specified, salivary duct carcinoma, squamous cell carcinoma, and adenosquamous carcinoma.12,14 –16 However, these limitations do not preclude the utility of fine-needle aspiration of such lesions, which makes it possible to watch for metastatic disease and helps to identify patients who may need more aggressive therapy. The transformation of pleomorphic adenoma in mucoepidermoid carcinoma may be not surprising, considering that several phenotypic and submicroscopic features shared by both lesions suggest that there may be a link between these two entities. Moreover, the close phenotypic and ultrastructural resemblance between intermediate cells of mucoepidermoid carcinoma and myoepithelial cells in pleomorphic adenoma,4,17,18 and the putative common

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karyotypic alterations found in both tumors,19 –24 underscore such an association. It is noteworthy that one of the latter studies documented chromosome 11q14 –22 rearrangements and alterations at the short arm of chromosome 3 in both components, indicating an association with early development in some of these tumors.21 In conclusion, mucoepidermoid carcinoma of the salivary gland may present as a high grade malignancy in pleomorphic adenoma and may be confused with poorly differentiated metastatic carcinoma at these sites. The presence of features associating benign pleomorphic adenoma with mucosquamoid cellular features, albeit rare, is helpful in the cytopathologic evaluation of these lesions.

12.

13.

14.

15.

16.

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