Primary Mucoepidermoid Carcinoma and Sclerosing Mucoepidermoid Carcinoma with Eosinophilia of the Thyroid Gland: A Report of Nine Cases Zubair W. Baloch, M.D., Ph.D., Alyson C. Solomon, B.S., Virginia A. LiVolsi, M.D. Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania SMECE were negative. The immunohistochemical Mucoepidermoid carcinoma is a rare primary thy- findings suggest that both MEC and SMECE have roid tumor with indolent biologic potential. Two different histogenesis. types of tumors have been described under this category: mucoepidermoid carcinoma (MEC) and KEY WORDS: Eosinophils, Mucoepidermoid, Scle- sclerosing mucoepidermoid carcinoma with eosin- rosis, Solid cell nests, Thyroid tumors. ophilia (SMECE). The MEC shows both squamous Mod Pathol 2000;13(7):802–807 and glandular differentiation in a background of a noninflamed gland, whereas SMECE is character- Mucoepidermoid carcinoma (MEC) is most com- ized by extensive sclerosis, squamous and glandular monly encountered in salivary glands but can also differentiation, a concomitant inflammatory infil- be seen at other locations, including bronchus, tra- trate rich in eosinophils, and a background of lym- chea, esophagus, breast, pancreas, and thyroid phocytic thyroiditis. gland (1–25). MEC of the thyroid gland is a rare We present nine cases of these entities: five MEC tumor and is characterized by unique histologic and four SMECE. All tumors occurred in women appearance and indolent biologic behavior (10–25). (age 27 to 73 years). Five tumors showed extrathy- Two types of tumors have been described under roidal invasion and multiple lymph node metasta- this heading: MEC (10–18) and sclerosing mucoepi- ses. One case of MEC showed a concomitant tall cell dermoid carcinoma with eosinophilia (SMECE) variant of papillary carcinoma with vascular inva- (19–25). There is interesting debate in the literature sion, and two cases showed intimately associated regarding the histogenesis of these tumors (19–21, areas of usual papillary carcinoma. One of the latter 26–29). Many authors have suggested that these cases also showed areas of transformation to ana- tumors develop from ultimobranchial body rests/ plastic carcinoma. In all cases of SMECE and in only solid cell nests (19, 26–29), whereas some authors one case of MEC, the uninvolved thyroid tissue have reported a follicular origin (14, 16, 17, 20). The showed lymphocytic thyroiditis. Follow-up infor- other suggested sources include C cells, parathy- mation was available in four of the nine cases (3 roid, ectopic salivary gland, and thyroglossal duct months to 7 years). Two patients with SMECE are (10, 11, 16). alive with no evidence of disease. One patient with Fewer than 30 cases of these entities have been MEC and tall cell variant of papillary carcinoma described in the literature. We report clinicopatho- died of disease after 3 months, and the patient with logic features of eight additional cases (five MEC anaplastic carcinoma died after 5 months with lung and four SMECE cases) and discuss various pro- metastasis. posed theories of their cell of origin in light of our Both MEC and SMECE were positive for cytoker- findings. atin and negative for calcitonin. All cases of MEC were positive for thyroglobulin, whereas all cases of MATERIALS AND METHODS Copyright © 2000 by The United States and Canadian Academy of Five cases of primary MEC and three cases of Pathology, Inc. SMECE were retrieved from the consultation files of VOL. 13, NO. 7, P. 802, 2000 Printed in the U.S.A. Date of acceptance: January 27, 2000. one of the authors (VAL), and one additional case of Address reprint requests to: Zubair W. Baloch, M.D., Ph.D., Department of SMECE was retrieved from the surgical pathology Pathology and Laboratory Medicine, 6 Founders Pavilion, University of Pennsylvania Medical Center, 3400 Spruce Street, Philadelphia, PA 19104; files of University of Pennsylvania Medical Center. e-mail: [email protected]; fax: 215-349-8994. Hematoxylin and eosin–stained slides were re- 802 viewed in all cases; unstained paraffin sections By light microscopy, all cases revealed notable were used for immunohistochemical analysis. The areas of both epidermoid and duct-like elements. avidin-biotin-peroxidase complex technique was The epidermoid elements were arranged in solid used for immunostaining. The antibody panel in- sheets with keratin pearl formation. Glandular cluded antithyroglobulin, calcitonin, and cytokera- spaces filled with mucinous material forming mu- tins (AE1/AE3) (Dako, Carpinteria CA). cous cysts were noted in three cases; mucous cells lined the ductal elements (Figs. 1 and 2A). Mucicar- mine stain highlighted the mucinous material RESULTS present in areas of glandular differentiation (Fig. The main clinicopathologic findings are summa- 2B). The background stroma showed varying de- rized in Table 1. For the purposes of this article, we grees of fibrosis and foci of psammomatous calci- divided the tumors into two separate entities, MEC fication. Two cases showed a concomitant aggres- and SMECE, on the basis of pathologic (light mi- sive thyroid tumor; one case showed an associated croscopy and immunohistochemistry) findings. tall cell variant of papillary carcinoma (Fig. 3), and the other showed an anaplastic carcinoma with extensive involvement of the normal thyroid paren- Mucoepidermoid Carcinoma chyma and perithyroidal tissues. One case showed Two patients were men, and three were women, lymphocytic thyroiditis. ranging in age from 27 to 83 years. The clinical By immunohistochemistry, all cases were posi- information was available in four cases, which was tive for thyroglobulin and cytokeratin and negative that of a painless unilateral thyroid mass. Radio- for calcitonin. In a case with a concomitant ana- graphic studies showed a cold nodule. Two patients plastic carcinoma, the MEC showed positive stain- underwent partial thyroidectomy, and two had total ing with thyroglobulin, whereas the anaplastic tu- thyroidectomy. Follow-up information was avail- mor was negative. able in three cases; two patients died of disease and one is alive with no evidence of disease. Sclerosing Mucoepidermoid Carcinoma with Pathologic findings Eosinophilia Gross pathology findings were available in three All patients were women, who ranged in age from cases, which showed a well-circumscribed mass 38 to 73 years. All tumors were in the right thyroid ranging in size from 1.6 to 10 cm. On cut sections, and presented as a solitary mass that was cold on the tumors were tan-brown in color and showed scan. Three patients underwent partial thyroidec- solid and cystic areas. tomy, and one had total thyroidectomy and lymph TABLE 1. Clinicopathologic Features of SMECE and MEC of Thyroid Gland Clinical Tumor Case Age/Sex Gross Findings Histo-Dx LT IH Follow-Up Findings/Treatment Extent/Mets 1 38/F Right neck mass ϫ 1 mo/ Firm, white mass; 6 SMECE ϩ Thyrog Ϫ, calci Ϫ, Extension to NAD3mo Total-thyr and right cm kera ϩ skeletal neck dissection muscle/11 of 13 LN ϩ 2 47/F Right thyroid mass ϫ 2 Circumscribed solid SMECE ϩ Thyrog Ϫ, calci Ϫ, Confined to NAD2y y/Right-thyr mass 5 cm kera ϩ, mucin ϩ thyroid 3 73/F Right thyroid mass/Right- 3-cm solid mass with SMECE ϩ Thyrog Ϫ, calci Ϫ, Confined to NA thyr 1-cm cyst kera ϩ thyroid 4 64/F Right thyroid nodule; Poorly defined gray SMECE ϩ Thyrog Ϫ, calci Ϫ, Confined to NA hypothyroid/Right-thyr area kera ϩ thyroid 5 27/F Cold nodule/Total-thyr 2 cm MEC Ϫ Thyrog ϩ, calci Ϫ, Confined to NAD7y kera ϩ, mucin Ϫ thyroid 6 64/M Right thyroid mass/Right- 10 cm MEC ϩ, Ϫ Thyrog ϩ, calci Ϫ, Extensive DOD After 3 thyr followed by left- tall cell, kera ϩ lymphatic mo thyr pap Ca invasion by tall cell ca 7 83/F Right thyroid mass/ NA MEC ϩ, Ϫ Thyrog ϩ, calci Ϫ, Widely Mets to lung Partial-thyr anaplastic, kera ϩ, mucin ϩ invasive DOD after ca 5mo 8 55/M NA/Total-thyr & neck NA MEC Ϫ Thyrog ϩ, calci Ϫ, NA NA dissection kera ϩ, mucin ϩ 9 36/F Left thyroid mass/Total- 1.6-cm firm discrete MEC ϩ Thyrog ϩ, calci Ϫ, Confined to NA thyr mass mucin ϩ, kera ϩ thyroid Histo-Dx, histologic diagnosis; LT, lymphocytic thyroiditis; IH, immunohistochemistry; Mets, metastases; thyr, thyroidectomy; LN, lymph nodes; SMECE, sclerosing mucoepidermoid carcinoma with eosinophilia; MEC, mucoepidermoid carcinoma; thyrog, thyroglobulin; calci, calcitonin; kera, cytokeratin; NAD, no evidence of disease; DOD, died of disease; pap, papillary; ca, Carcinoma. MEC and SMECE of the Thyroid Gland (Z.W. Baloch et al.) 803 cases the tumors were confined to the thyroid gland. Follow-up information was available in two cases; both are alive without any evidence of dis- ease. Microscopically, in all cases, the non-neoplastic thyroid parenchyma showed lymphocytic thyroid- itis. The tumor cells were arranged in small islands, anastomosing cords, and narrow strands and dis- played prominent squamous differentiation char- acterized by intercellular bridges and keratin pearl formation. Glandular structures resembling mu- cous cysts were noted in two cases (Fig. 4). The background stroma in the main tumor mass re- vealed marked sclerosis and a mixed inflammatory infiltrate with prominent eosinophilia (Fig. 4B). Lymphatic permeation was identified in one case with extensive lymph node involvement. Two cases revealed a separate focus of follicular variant of papillary thyroid carcinoma and papillary micro- carcinoma. Both these lesions were present in the same lobe away from the main tumor mass. The tumor cells stained negative for thyroglobu- lin and calcitonin and positive for cytokeratin (AE1/ AE3) in all cases. Mucin stain was positive in one case with mucous cysts (Fig. 4E). DISCUSSION MEC is most commonly encountered as a tumor of salivary glands; it has been described in the ma- jor salivary glands and in the minor glands, partic- ularly in the oral cavity (1).