Case 4 -

Oxyphilic Nodule, with Cystic Changes Mary K. Sidawy The George Washington University Washington, DC

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Clinical History A 65-year-old woman referred for FNA of bilateral thyroid nodules which were discovered during a routine physical examination. A thyroid scan showed bilateral cold nodules. The patient had a history of systemic lupus erythematosus, and ductal carcinoma in situ of the right breast that was treated with a mastectomy. Physical examination revealed a firm 1.5 cm left lower pole nodule, and a softer 2.5 cm nodule in right lobe of the thyroid. Both nodules moved up and down with swallowing. Aspirate of the right lobe revealed oxyphilic follicular cells and colloid. The FNA of the left nodule is illustrated (Figures A,B,C). Case 4 - Figure A - Aspiration of the left lower lobe nodule yielded cohesive large sheet of crowded neoplastic cells. The cells smeared poorly and crush artifact is prominent. Colloid is absent from the background. A polymorphous lymphoid infiltrate is focally appreciated, elsewhere in the smear (Diff-Quik stain, low power). Case 4 - Figure B - Higher power image shows neoplastic cells with small, elongated nuclei. Poor preservation due to crush artifact is a prominent finding in this case (Diff-Quik stain, medium power). Case 4 - Figure C - High power image shows focal "nested" appearance reminiscent of a microfollicular or acinar arrangement. No mitotic figures or necrosis present (Diff-Quik stain, high power). Cytologic Findings Aspiration of the left lobe yielded cohesive sheets and clusters of crowded epithelial cells. The cells were small, had bland ovoid nuclei, scant cytoplasm with indistinct cell borders, and were focally arranged in a nesting pattern. Lymphoid tangles (crushed lymphocytes) small lymphocytes , and few activated lymphocytes were seen in the background. Colloid was absent. Immunoperoxidase stains, performed on the Thin-Prep preparations, showed the neoplastic cells to be positive for epithelial markers (CAM-2) and negative for neurone-specific enolase, calcitonin and thyroglobulin. The lymphoid cells were positive for leucocyte common antigen. The left lobe nodule was interpreted as "Thyroid neoplasm not further classified and Hashimoto's thyroiditis." Surgical excision for a definite classification was recommended. The FNA of the right lobe nodule was cellular and composed of oxyphilic follicular cells arranged singly, in groups and sheets. Foamy and hemosiderin-laden histiocytes, and colloid were also noted. A cytologic diagnosis of "Oxyphilic nodule, with cystic changes" was rendered. History and Surgical Follow-up A preoperative chest x-ray showed a 4 cm soft tissue mass in the thoracic inlet with right-sided tracheal deviation, probably representing thyroid enlargement. A total thyroidectomy and excision of the left inferior pole mass were performed. What clinically appeared to be 1.5 cm firm nodule in the left lower pole was found to actually represent the superior tip of a larger substernal mass that extended under the clavicle into the mediastinum. Grossly, the left lobe of thyroid showed multiple colloid cysts, and attached to its inferior pole was a 5 X 3.5 cm encapsulated mass with a tan homogeneous-cut surface. The right lobe showed a 2 X 1.8 cm partially cystic lesion occupying most of the lobe. Microscopic sections of the mass attached to the left inferior pole revealed a neoplasm surrounded by a thick fibrous capsule. Thick fibrous bands dividing the tumor into lobules were also noted. The neoplasm was composed of sheets and whorls of cytologically bland appearing, focally spindled, epithelial cells. Mature lymphocytes were scattered throughout the neoplasm. Fibrosis and few nests of tumor cells were noted in perithyroidal soft tissue and fat. However, no involvement of the thyroid parenchyma was noted. The diagnosis of thymoma with penetration of perithyroidal tissue was made. Microscopic sections of the right lobe of thyroid nodule showed an encapsulated neoplasm composed of large oxyphilic cells with mild nuclear pleomorphism. No vascular invasion or capsular penetration was noted. The diagnosis of a benign Hurthle cell nodule consistent with adenoma was rendered. Discussion Thymoma is the most common primary neoplasm in the anterosuperior mediastinum. The cytopathologic characteristics of thymoma consist of a 'biphasic pattern' or 'dual population' of epithelial cells and lymphocytes. The degree of cellular cohesion of the epithelial cells varies. The epithelial component may consist of spindle cells with elongated regular nuclei and inconspicuous nuclei. The cytoplasm of the epithelial cells is scant to moderate, with indistinct borders. The nuclei are bland with smooth nuclear outline, pale, finely granular chromatin. The proportion of epithelial and lymphoid cells varies and may lead to the erroneous diagnosis of metastatic carcinoma when the lymphoid component is sparse, while the predominance of lymphoid cells may simulate a lymphoma. Preoperative FNA of thymoma mimicking a thyroid lesion has been reported. Most reported cases were misdiagnosed. Lymphocytic thyroiditis, malignant lymphoma, and a neoplasm, not further classified, are the most common rendered diagnoses. The FNA of the left lobe nodule clearly demonstrated a dual population of neoplastic epithelial cells and a polymorphous lymphoid population. The presence of the latter in conjunction with the presence of an oxyphilic nodule in the right lobe led us to conclude that the lymphoid component was part of Hashimoto's thyroiditis. Immunostains were performed in an attempt to classify this unusual epithelial neoplasm characterized by nests of bland, small spindled cells. We excluded follicular neoplasm and papillary carcinoma based on the above cytologic features, the absence of follicular or papillary pattern, the lack of colloid and the negative thyroglobulin immunostain. Medullary carcinoma was considered because of the spindled nature of the neoplastic cells, but was not supported by the negative calcitonin and neurone-specific enolase stains, and lack of amyloid. The small size of the cells and the nesting pattern suggested an insular carcinoma, but evidence of malignancy, such as necrotic background and mitoses, as well as microfollicles, trabeculae and positive staining for thyroglobulin, were not seen. The following summarizes the cytologic criteria and clues of the entities considered in the differential diagnosis of small spindle cell lesion of the thyroid: Hyalinizing trabecular adenoma Smears are cellular, cells occur in aggregates or as single cells. Nuclei are slightly enlarged, oval to spindle with pale chromatin. Intranuclear inclusions. Longitudinal grooving of nuclear membrane. Air-dried smears reveal a distinctive purple stromal deposits. Central core of amorphous hyaline material surrounded by follicular cells. The clue to recognizing hyalinizing trabecular adenoma cytologically, is the combination of features of both papillary and medullary carcinoma. Negative Congo red and calcitonin immunostain should assist in excluding the diagnosis of medullary carcinoma. Medullary carcinoma Smears reveal abundant cellularity. Cells are isolated or in loose fragments. Plasmacytoid, spindle-shaped, or small round cells. Cytoplasm finely granular - Pink cytoplasmic granules is a characteristic feature in air-dried Diff-Quik-stained preparations. Variable degree of nuclear pleomorphism. Bi- or multinucleation very common. Intranuclear cytoplasmic inclusions. Chromatin displays neuroendocrine features. Presence of amyloid (amorphous, acellular material). Positive for calcitonin and chromogranin. Neurosecretory granules by electron microscopy. Anaplastic (undifferentiated) carcinoma The cytologic features reveal a wide variation. Bizarre cells with unequivocal features of malignancy. Cells are isolated or in loose groups. Spindle and polygonal cells. Nuclei hyperchromatic with clumped chromatin. Osteoclast-like giant cells. Mitotic figures. Obtaining diagnostic material is occasionally difficult because of extensive fibrosis or necrosis. Poorly differentiated "insular" carcinoma High cellularity. Scant colloid. Relatively uniform tumor cells in clusters, trabeculae, microfollicular or a single cell pattern. Poorly outlined cytoplasm. Nuclei hyperchromatic with occasional nucleoli. Mitoses and a necrotic background. Non-thyroid malignant tumors may also present as thyroid nodules. The most common neoplasms metastasizing to the thyroid, are carcinomas of the lung, the gastrointestinal tract, breast and melanomas. In these instances, awareness of the history, immunocytochemistry, and comparing the aspirate with the intraoperative smears and/or histological sections of the pervious surgical specimen should aid in reaching the correct diagnosis. In our case, given the history of breast carcinoma, albeit in situ, a metastatic breast carcinoma was considered, but the lack of single cells and significant cytologic atypia milited against this diagnosis. In conclusion, thymoma may present as a palpable neck mass that clinically mimics a thyroid nodule. The possibility of thymoma should be considered when the FNA of a neck mass reveals a dual population of lymphoid and epithelial cells. Awareness of this entity and the constellation of the characteristic cytologic features can prevent a misdiagnosis of this well-recognized pitfall. References Milde P, Sidawy MK. Thymoma presenting as a palpable thyroid nodule: A pitfall in fine needle aspiration of the neck. Cytopathology 10:415-419, 1999. Oertel YC. 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