Case 4 -

Salivary Gland Type Tumor with Myoeptiehlial Differentiation, Consistent with Ectopic Pleomorphic Adenoma David Chhieng, Yale University School of Medicine, New Haven, CT

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Clinical History A 66 year old man was found to have an incidental thyroid nodule on ultrasound examination. He had no other symptoms. He had history of head and neck irradiation exposure in childhood. There was no other significant medical or surgical history or pertinent family history except for a left facial hemanigoma. On physical examination, a small nodule was palpable in the isthmus of the thyroid gland. The patient had no palpable lymphadenopathy. Thyroid function tests were within normal limits. Thyroid ultrasound revealed a well-circumscribed hypoechoic nodule, measuring 1.5 cm, in the right isthmus. There were also several smaller nodules scattered in both the left and right lobes of the thyroid gland. The patient underwent an ultrasound guided fine needle aspiration biopsy of the isthmic nodule. Case 4 - Figure 1 Low power magnification showing a paucicellular aspirate with several cohesive cellular groups. (Papanicolaou stain, X20) Case 4 - Figure 2 Neoplastic cells in groups and single cells in a myxoid background. (Papnicolaou stain, X100) Case 4 - Figure 3 Magenta stromal fragments with irregular borders. (Diff Quik stain, X400) Case 4 - Figure 4 Individual cells demonstrate round to oval nuclei and moderate amount of cytoplasm which blend with the extracellular materials. The latter appears bluish grey. (Papanicolaou stain, X400) Case 4 - Figure 5 Plasmacytoid cells and scattered spindle cells appear singly in a fibrillary myxoid background. (Papnicolaou stain, X400) Case 4 - Figure 6 Individual cells demonstrate mild nuclear enlargement and fine chromatin. Nuclear pleomorphism is minimal. (Papanicolaou stain, X400) Case 4 - Figure 7 Plasmacytoid cells embedded in a fibrillay myxoid background. (Papanicolaou stain, X400) Case 4 - Figure 8 A cohesive group of bland appearing epithelial cells and stromal fragment which stains magenta. (Diff Quik stain, X200) Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: The aspirate was paucicellular and consisted of singly and loosely cohesive clusters of spindle and plamascytoid epithelioid cell in a myxoid background. The neoplastic cells were also seen embedded within a metachromatic matrix. The latter appeared fibrillary with irregular contours. The tumor cells demonstrated slight nuclear enlargement with fine chromatin. However, no significant nuclear atypia, including nuclear grooves and pseudo-intranuclear inclusions, was noted. No colloid was present. Differential Diagnoses: The cytologic findings present a diagnostic challenge. The presence of spindle and plasmacytoid cells, along with the identification of extracellular materials, in a thyroid FNA should raise the possibility of a medullary thyroid carcinoma. Immunocytochemistry for calcitonin and serum calcitonin level would be helpful in the differential diagnosis. Other entities should be considered in the differential diagnosis included hyalinizing trabecular tumor, papillary thyroid carcinoma with fibromatosis like stroma, anaplastic carcinoma, and spindle epithelial tumor with thymus-like differentiation (SETTLE). Aspirates from hyalinizing trabecular tumors typically demonstrate round to oval epithelial cells with irregular, fibrillary, hyaline globules. The neoplastic cells are usually characterized by the presence of nuclear grooves and pseudo-intranuclear inclusions. [1] Another differential diagnosis is PTC with fibromatosis like stroma. The stromal component is usually inconspicuous in aspirates of PTC of classic and other variants. However, PTC with fibromatosis-like stroma is prominent and made of short, irregular fascicles of fibroblastic spindle cells in a fibromyxoid matrix. [2] The neoplastic follicular cells demonstrate the typical nuclear features of papillary thyroid carcinoma such as nuclear crowding and overlapping, nuclear enlargement, powdery chromatin, and nuclear grooves and pseudoinclusions. SETTLE is a rare tumor which occurs predominantly in children and young adults. The cytology findings of SETTLE include a mixture of epithelioid and spindle cells appearing singly and in aggregates. In addition, deposits of fibrillary extracellular materials surrounded by neoplastic cells are observed. [3, 4] The background usually appears finely granular. Not infrequently, squamous, mucinous, and respiratory epithelial cells are also present. Anaplastic carcinomas present with a mixture of spindle and epithelioid cells which demonstrate marked cytologic pleomorphism. In addition, necrosis, bizarre multinucleated giant cells, and mitotic figures are identified. Chrondroid metaplasia of the stroma in a follicular adenoma is rare and may presented with follicular cells admixed with chondroid extracellular materials in the aspirates. [4] In addition to primary neoplasms of the thyroid gland, metastatic neoplasm such as melanoma and tumors arising from adjacent structures such as chondroid syringoma and myoepithelioma of the soft tissue. Melanoma is a great mimicker and can present with a mixture of epithelioid and spindle neoplastic cells. However, prominent extracellular matrix is usually not characteristic. Both chondroid syringoma and myoepithelioma are characterized by a mixture of epithelial and spindle cells as well as chondromyxoid stroma. Final Diagnosis: A destained ThinPrep slide was immunostained for calcitonin and was negative. The overall cytology was reminiscent of a pleomorphic adenoma of the salivary; however, the thyroid location was uncharacteristic. The cytologic diagnosis was "follicular lesion of undetermined significance". A serum calcitonin assay was advised, which was negative. The patient underwent isthmusectomy as an outpatient under regional anesthesia with sedation. Gross pathologic examination revealed a 1.2 cm well circumscribed soft nodule with a glistening, gray-white lobulated cut surface. Microscopically, the tumor was well circumscribed but unencapsulated with benign thyroid tissue pushed to the periphery. The tumor cells were spindle and epithelioid and were seen in groups or singly within a myxoid chondroid matrix. Focal tubule and trabecula formation by epithelial cells was noted. Individual cells demonstrated hyperchromatic nuclei without distinctive nucleoli. Some of the epithelioid neoplastic cells were plasmacytoid with eccentrically located nuclei and moderate amount of eosinophilic cytoplasm. Cytologic atypia, mitoses, necrosis, or infiltration were not identified. Immunohistochemical findings were summarized as follow: Antibody Results S-100 protein Positive GFAP Positive Cytokeratin 7 Positive Cytokeratin 5/6 Positive c-Kit protein Positive Smooth muscle actin Positive (spindle cell) Epithelial membrane antigen Positive (tubule forming epithelial cells) Thyroglobin Negative Thyroid transcription factor-1 Negative Calcitonin Negative Calponin Negative p63 Negative The histology and the immunophenotypic findings supported a salivary gland type tumor with myoeptiehlial differentiation, consistent with ectopic pleomorphic adenoma. Case Discussion: Embryonically, the thyroid is derived from a median anlage arising in the foramen cecum and 2 lateral anlagen from the forth and fifth brachial pouches (ultimobranchial body), in close association with the parathyroid and thymus. [5] Because of its developmental origin from the ultimobranchial body, intrathyroidal inclusions and their neoplastic counterparts of parathyroid tissue and thymic tissue, as well as solid cell nests can be found in the lateral lobes of the thyroid gland. However, inclusion of salivary gland type tissue within in thyroid gland is rare. To date, there are only 3 reports of intrathyroidal salivary gland tissue, all in lateral lobes, and include one pleomorphic adenoma. The latter was a 7 cm pleomorphic adenoma arising in the right thyroid lobe of a 65- year old woman. [6] Age/Sex Location Ectopic tissue pathology and size Thyroid pathology Ref 65/F Right Lobe Pleomorphic adenoma, 7cm Lymphocytic thyroiditis [6] 66/F NS Mature salivary tissue, size not specified Multinodular goiter [7] 7/F Left Lobe Branchial cleft-like cyst with salivary tissue, 2.4 cm No pathologic change [5] 66/M Isthmus Pleomorphic adenoma, 1.2 cm No pathologic change Current case Ectopic salivary tissue may be seen in the lateral neck, frequently within paraparotid and occasionally in cervical lymph nodes. The is in keeping with the embryogenesis of major and minor salivary glands and their migration from primitive oral epithelium. [8] It has been proposed that aberrant migration of the seromucinous glandular tissue from the branchial pouches could rarely result in heterotopic salivary-type tissue in association with the thyroid glands. [9] We propose that seromucinous salivary-type glandular tissue may have migrated from the foramen cecum in the primitive oral cavity with the median anlage to the isthmus and may have given rise to the isthmic pleomorphic adenoma in this patient. The absence of some of the myoepithelial markers i.e. p63 and calponin and only focal expression of smooth muscle actin in our case is intriguing. Hornick et al. have reported that among the extra-salivary gland myoepithelial tumors, 77% were negative for p63, 64% negative for smooth muscle actin, and 14% negative for calponin. [10] Morphologically, the distinction between pleomorphic adenoma, chondroid syringoma and soft tissue myoepithelioma may be one of semantics and location. This tumor was within the thyroid gland and not in the skin or soft tissue of the next; therefore, chondroid syringoma or soft tissue myoepithelioma did not seem appropriate diagnostic terms. Conclusion(s): In conclusion, this is a rare case of pleomorphic adenoma arising in the thyroid gland and first evaluated by FNA. References: Casey, M.B., T.J. Sebo, and J.A. Carney, Hyalinizing trabecular adenoma of the thyroid gland: cytologic features in 29 cases. The American journal of surgical pathology, 2004. 28(7): p. 859-67. Us-Krasovec, M. and R. Golouh, Papillary thyroid carcinoma with exuberant nodular fasciitis-like stroma in a fine needle aspirate. A case report. Acta cytologica, 1999. 43(6): p. 1101-4. Kirby, P.A., W.A. Ellison, and P.A. Thomas, Spindle epithelial tumor with thymus-like differentiation (SETTLE) of the thyroid with prominent mitotic activity and focal necrosis. The American journal of surgical pathology, 1999. 23(6): p. 712-6. Kloboves-Prevodnik, V., et al., Thyroid spindle epithelial tumor with thymus-like differentiation (SETTLE): is cytopathological diagnosis possible? Diagnostic cytopathology, 2002. 26(5): p. 314-9. Park, J.Y., G.Y. Kim, and Y.L. Suh, Intrathyroidal branchial cleft-like cyst with heterotopic salivary gland-type tissue. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society, 2004. 7(3): p. 262-7. Lange, M.J., Pleomorphic adenoma of the thyroid containing salivary gland cells with pseudocartilage and myoepithelial cells. International surgery, 1974. 59(3): p. 178-9. Cameselle-Teijeiro, J. and J. Varela-Duran, Intrathyroid salivary gland-type tissue in multinodular goiter. Virchows Archiv : an international journal of pathology, 1994. 425(3): p. 331-4. Daniel, E. and W.F. McGuirt, Sr., Neck masses secondary to heterotopic salivary gland tissue: a 25-year experience. American journal of otolaryngology, 2005. 26(2): p. 96-100. Jernstrom, P. and C.A. Prietto, Accessory parotid gland tissue at base of neck. Archives of pathology, 1962. 73: p. 473-80. Hornick, J.L. and C.D. Fletcher, Myoepithelial tumors of soft tissue: a clinicopathologic and immunohistochemical study of 101 cases with evaluation of prognostic parameters. The American journal of surgical pathology, 2003. 27(9): p. 1183-96.