Bethesda classification.2nd edition(2018) برای بزرگنمایی عکسها کلیک را روی ان نگه دارید..... Fig. 2.1 Nondiagnostic. The smear shows abundant red cells, with rare lymphocytes and mono- cytes. The sample is devoid of thyroid parenchymal elements. Some thyroid nodules are very vascular and with repeated passes yield only blood. Employing a smaller gauge needle (26 or 27 gauge), avoiding negative pressure, and employing a shorter needle dwell time within the nodule may improve cellularity (smear, Diff-Quik stain) Fig. 2.2 Nondiagnostic. The smear shows a large fragment of skeletal muscle and no native thy- roid tissue. This may occur when the needle traverses through the neck muscles. It is important not to confuse skeletal muscle with inspissated colloid (notice the cross striations in the muscle frag- ment, best seen at 7 o'clock) (smear, Papanicolaou stain) Fig. 2.3 Nondiagnostic. This FNA yielded ciliated respiratory epithelium from the trachea. Accidental puncture of the tracheal lumen is uncommon and typically happens in lesions of the thyroid isthmus. Such cases should be carefully evaluated for adequacy since they typically show only rare follicular epithelium (smear, Diff-Quik stain) Fig. 2.4 Nondiagnostic. Extensive air-drying artifact in this alcohol-fixed smear limits cytologic interpretation. Such cases should be carefully evaluated for adequacy and are best managed by a repeat FNA with rapid wet fixation. Liquid-based cytology resolves such issues and may be con- sidered if air-drying artifact is a repeated problem (smear, Papanicolaou stain) Fig. 2.5 Nondiagnostic. Extensive obscuring blood hinders the evaluation of the follicular cells (smear, Papanicolaou stain) Fig. 2.6 Nondiagnostic (cyst fluid only). Abundant hemosiderin-laden macrophages and degener- ated cyst fluid contents. Macrophages do not count toward specimen adequacy. Such cases, when devoid of significant background colloid, are interpreted as nondiagnostic (smear, Papanicolaou stain) Fig. 2.7 Nondiagnostic (cyst fluid only). Macrophages are typically noncohesive, with abundant cytoplasm that often contains golden brown hemosiderin pigment with the Papanicolaou stain (SurePath preparation, Papanicolaou stain) (Case courtesy of Douglas R. Schneider, MD, Department of Pathology, Steward St. Elizabeth's Medical Center, Boston, MA, USA) Fig. 2.8 Benign (satisfactory thyroid FNA). Abundant thin watery colloid coats the smear in this case of a benign follicular nodule ("colloid nodule"). Aspirates with large amounts of colloid are considered adequate for interpretation even when they contain less the six groups of follicular cells (smear Diff-Quik stain) Fig. 2.9 Benign (satisfactory thyroid FNA). There is abundant dense colloid but only scant follicular cells (smear, Papanicolaou stain) Fig. 2.10 Ultrasound gel. Ultrasound gel is recognized by its charateristic purple color with the Papanicolaou stain. It often has a granular texture and, with liquid-based preprations, a weblike structure. When abundant, it can contribute to a "nondiagnostic" interpretation (ThinPrep, Papanicolaou stain) Fig. 3.1 Benign follicular nodule/colloid nodule: watery colloid. (a) Watery colloid is light green or pink with alcohol-fixed, Papanicolaou-stained preparations and has a "thin membrane" or "cel- lophane coating" appearance, often with coalescing "puddles" (smear, Papanicolaou stain). (b) Colloid stains blue-violet with air-dried, Romanowsky-stained preparations and often shows a chicken-wire appearance (smear, Diff-Quik stain) Fig. 3.2 Benign follicular nodule: thick colloid. (a) Colloid demonstrates a "stained glass crack- ing" appearance (smear, Diff-Quik stain). (b) Colloid is orange-pink or green-blue with alcohol- fixed Papanicolaou-stained preparations and can cover a major part of the glass slide surface (smear, Papanicolaou stain) Fig. 3.3 Benign follicular nodule. Monolayered sheets of evenly spaced follicular cells have a honeycomb-like arrangement. (a) Watery colloid is present in the background (smear, Diff-Quik stain). (b) Thick colloid is present (ThinPrep, Papanicolaou stain) Fig. 3.4 Benign follicular nodule. (a) Monolayered sheets of follicular cells are the predominant finding. Stripped follicular cell nuclei are present in the background. When watery colloid is admixed with blood (note the pale-staining red blood cells), it can be difficult to recognize (smear, Papanicolaou stain). (b) Colloid is easier to recognize when it forms characteristic folds and lacu- nae (smear, Papanicolaou stain) Fig. 3.5 Benign follicular nodule. Three-dimensional, variably sized balls/spheres are admixed with flat sheets. Within the spheres there is maintenance of polarity, including a relatively evenly spaced nuclear arrangement (a smear, Diff-Quik stain; b ThinPrep, Papanicolaou stain) Fig. 3.6 Benign follicular nodule. (a) Microtissue fragments are admixed with flat sheets and colloid. There is follicle formation, but these are not microfollicles, because there is maintenance of polarity and the nuclei are evenly spaced (smear, Papanicolaou stain). (b) Hürthle cells (onco- cytes) can be a prominent component of a benign follicular nodule (smear, Diff-Quik stain). (c) The corresponding histologic specimen shows predominantly macrofollicular architecture with compressed Hürthle cells (hematoxylin and eosin stain) Fig. 3.7 Benign follicular nodule. (a) Benign follicular cells have delicate cytoplasm and ill- defined borders. The nuclei are uniformly spaced and approximately the size of red blood cells. Watery colloid is present in the background (smear, Diff-Quik stain). (b) Follicular cells may contain golden-brown cytoplasmic hemosiderin pigment (ThinPrep, Papanicolaou stain) Fig. 3.8 Benign follicular nodule. Benign follicular cells have round to oval, monomorphic nuclei with finely granular chromatin and inconspicuous or absent nucleoli (a smear, Papanicolaou stain; b SurePath preparation, Papanicolaou stain). (Case b courtesy of Douglas R. Schneider, MD, Department of Pathology, Steward St. Elizabeth's Medical Center, Boston, MA, USA.) Fig. 3.9 Benign follicular nodule. (a) Nuclear overlapping and crowding may be observed in some clusters, but there is no significant nuclear enlargement or atypia (smear, Papanicolaou stain). (b) Small flat sheets without significant nuclear overlapping or atypia of follicular cells represent small fragments of macrofollicles, not microfollicles (smear, Diff-Quik stain) Fig. 3.10 Benign follicular nodule. Stripped ("naked") thyroid follicular cell nuclei may be seen in background; care must be taken not to mistake them for lymphocytes (smear, Papanicolaou stain) Fig. 3.11 Benign follicular nodule. Papillary hyperplasia may be seen in association with a hyperplastic nodule or follicular adenoma. The follicular cells usually remain arranged in flat sheets; true papillae are rarely apparent. Nuclear features of papillary thyroid carcinoma are absent (smear, Papanicolaou stain) Fig. 3.12 Benign follicular nodule. Follicular cells suspended in abundant colloid tend to dissociate and may appear shrunken and spindled (a, b: smears, Papanicolaou stain) Fig. 3.13 Benign thyroid cyst. Prominent cystic degeneration often occurs in nodular goiter. Abundant macrophages and few benign thyroid follicular cells are present (smear, Papanicolaou stain) Fig. 3.14 Benign follicular nodule: cyst lining cells. (a, b) Reparative changes are commonly associated with cystic degeneration. Cyst lining cells are usually a small component of the benign aspirate and easily recognized because of their elongated shape and cohesive, flat and/or squamoid appearance, low nuclear/cytoplasmic ratio, and small prominent nucleoli. (a smear, Diff-Quik stain; b Papanicolaou stain). (c) Occasionally, these cells show elongated nuclei with nuclear grooves and powdery chromatin. When the changes are focal and mild, particularly if the back- ground is overwhelmingly benign, they are easily recognized as reactive, but when more advanced and widespread they raise a concern for papillary thyroid carcinoma (smear, Papanicolaou stain) Fig. 3.15 Benign follicular nodule (liquid-based preparations). The follicular cells have pale cytoplasm and small, round, evenly spaced nuclei. (a ThinPrep, Papanicolaou stain; b SurePath, Papanicolaou stain). (Case b courtesy of Douglas R. Schneider, MD, Department of Pathology, Steward St. Elizabeth's Medical Center, Boston, MA, USA) Fig. 3.16 Benign follicular nodule: colloid (liquid-based preparations). (a) Thick colloid on liquid-based preparations resembles its counterpart on smears (SurePath, Papanicolaou stain). (b) Watery colloid has a thin, "folded tissue-paper" appearance (ThinPrep, Papanicolaou stain). (Case a courtesy of Douglas R. Schneider, MD, Department of Pathology, Steward St. Elizabeth's Medical Center, Boston, MA, USA) Fig. 3.17 Squamous cells in thyroid aspirates. (a) Thyroglossal duct cyst. Proteinaceous material, inflammatory cells, and a rare degenerated squamous cell are present (smear, Papanicolaou stain). (b) Thyroglossal duct cyst. The corresponding histopathologic specimen shows cyst contents (as observed in the fine needle aspirate) and a cyst wall lined by mixed squamous and cuboidal/colum- nar epithelium (hematoxylin and eosin stain). (c) Benign squamous cyst of thyroid. The cellular aspirate consists almost entirely of normal-appearing, mature nucleated squamous cells (smear, Papanicolaou stain) Fig. 3.18 Parathyroid cyst. This sparsely cellular specimen has rare groups of small round cells with dark overlapping nuclei and scant cytoplasm, suggestive of follicle formation (smear, Papanicolaou stain) Fig. 3.19 Black thyroid. Follicular cells contain abundant dark brown pigment. Contrast with hemosiderin pigment in Fig. 3.7b (ThinPrep, Papanicolaou stain) Fig. 3.20 Amyloid goiter. (a) Aspiration of abundant thick, glassy, amorphous material that stains pink/orange or purplish (depending on the stain used) is observed. Amyloid deposits are mostly parenchymal and hence often display embedded fibroblasts, a characteristic feature (smear, Papanicolaou stain). (b) A Congo red stain shows characteristic birefringence upon polarization, confirming the diagnosis (cell block section) Fig. 3.21 Benign follicular nodule (patient with Graves' disease). Cells in monolayered sheets have abundant cytoplasm. Flame cells are distinctive for their marginal cytoplasmic vacuoles with red to pink frayed edges (smear, Diff-Quik stain) Fig. 3.22 Benign follicular nodule (patient with Graves' disease). The nuclei are often enlarged, vesicular, and show prominent nucleoli. Anisonucleosis is prominent. The cytoplasm has a granular, "oncocytoid" appearance (smear, Papanicolaou stain) Fig. 3.23 Benign follicular nodule (patient with Graves' disease). (a) The follicular cells may display focal nuclear chromatin clearing and rare grooves. These changes are rarely diffuse, and other diagnostic nuclear features of papillary thyroid carcinoma are absent (smear, Papanicolaou stain). (b) There is marked anisonucleosis (smear, Papanicolaou stain) Fig. 3.24 Lymphocytic thyroiditis. (a) There is a mixed population of Hürthle cells (oncocytes) and polymorphic lymphocytes (smear, Diff-Quik stain). (b) Hürthle cells have abundant granular cytoplasm, large nuclei, and prominent nucleoli. There is mild anisonucleosis (smear, Papanicolaou stain) Fig. 3.25 Lymphocytic thyroiditis. Random nuclear atypia and prominent anisonucleosis of Hürthle cells (oncocytes) is not uncommonly associated with LT (smear, Papanicolaou stain) Fig. 3.26 Lymphocytic thyroiditis, liquid-based preparations. (a) Lymphocytes are dispersed as isolated cells and infiltrate clusters of Hürthle cells (ThinPrep, Papanicolaou stain). (b) Hürthle cells (oncocytes) have abundant granular cytoplasm and prominent nucleoli (SurePath, Papanicolaou stain). (c) Germinal center fragments are often present, comprised of a heteroge- neous mix of polymorphic lymphocytes and larger dendritic cells (ThinPrep, Papanicolaou stain). (Case b courtesy of Douglas R. Schneider, MD, Department of Pathology, Steward St. Elizabeth's Medical Center, Boston, MA, USA) Fig. 3.27 Lymphocytic thyroiditis. (a) Hürthle cells may predominate in any given sample, rais- ing the possibility of a Hürthle cell neoplasm. Rare lymphocytes are present in the background (arrows) (smear, Papanicolaou stain). (b) Lymphoid cells may predominate in an aspirate, raising the possibility of lymphoma. Rare Hürthle cells (oncocytes) are seen in the background (arrows) (smear, H&E stain) Fig. 3.28 Granulomatous thyroiditis. Epithelioid histiocytes, mixed inflammatory cells, and benign thyroid follicular cells (arrow) are present. Inset: Higher magnification of a granuloma (smears, Papanicolaou stain) Fig. 3.29 Acute thyroiditis. There are numerous neutrophils and occasional macrophages (smear, Papanicolaou stain) Fig. 3.30 Riedel thyroiditis/disease. This hypocellular smear contains scattered bland spindle cells and rare chronic inflammatory cells (smear, Diff-Quik stain) Fig.4.1 Atypia of undetermined significance with cytologic atypia. (a) Most of the follicular cells are arranged in benign-appearing macrofollicle fragments. (b) Rare cells have pale nuclei and mildly irregular nuclear membranes. When such cells are very few in number, an atypical interpre- tation is more appropriate than "suspicious for malignancy” (ThinPrep, Papanicolaou stain) Fig. 4.2 Atypia of undetermined significance with cytologic atypia. Follicular cells show mild enlargement of most nuclei and contain hemosiderin pigment. Follow-up was papillary carcinoma. Hemosiderin does not preclude the possibility of papillary carcinoma (smear, Diff-Quik stain) (From Ali et al. [51]. All Rights Reserved) Fig. 4.3 Atypia of undetermined significance with cytologic atypia. (a) In this sparsely cellular specimen, some cells have abundant cytoplasm, enlarged nuclei, and prominent nucleoli. One nucleus has an apparent intranuclear pseudoinclusion (arrow). Such changes may represent atypi- cal but benign cyst-lining cells, but a papillary carcinoma cannot be entirely excluded (ThinPrep, Papanicolaou stain). (b) Reparative-like changes of cyst-lining cells can mimic some cytologic features of papillary carcinoma (smear, Romanowsky stain) Fig. 4.4 Atypia of undetermined significance with cytologic atypia. (a) Cystic papillary carci- noma cells often show degenerative vacuoles; these cells have been termed "histiocytoid." A use- ful feature for recognizing them and distinguishing them from histiocytes is the sharply defined edges of the vacuoles, as opposed to the "fluffy" vacuoles of histiocytes (smear, Papanicolaou stain). (b) In this example, a loose cluster and a microfollicular group exhibit both "hard" cytoplasm and large cytoplasmic vacuoles (ThinPrep, Papanicolaou stain) (A: From Ali et al. [51]. All Rights Reserved) Fig. 4.5 Atypia of undetermined significance with architectural atypia. (a) Scanning magnifica- tion reveals a sparsely cellular specimen with a predominance of microfollicles. (b) High magnifi- cation of a microfollicle (ThinPrep, Papanicolaou stain) Fig. 4.6 Atypia of undetermined significance with architectural atypia. The smear shows cells arranged in a trabecular configuration with associated endothelial cells/blood vessels. Naked nuclei are prominent in the background, and colloid is absent. This proved to be a parathyroid adenoma on resection (smear, Diff-Quik stain) (From Ali et al. [51]. All Rights Reserved) Fig.4.7 Atypia of undetermined significance with architectural and cytologic atypia. Architectural atypia is manifested by a crowded three-dimensional configuration of follicular cells. Cytologic atypia is also evident, with nuclear enlargement, slight chromatin pallor, and a rare nuclear groove. The excised nodule was diagnosed as NIFTP (ThinPrep, Papanicolaou stain) Fig.4.8 Atypia of undetermined significance, Hürthle cell type. The aspirate is sparsely cellular with abundant blood. The few cells present are almost exclusively Hürthle cells (smear, Diff-Quik stain) Fig. 4.9 Atypia of undetermined significance, Hürthle cell type (patient with multinodular goiter). This patient had two nodules, both showing almost exclusively oncocytic follicular cells (smear, Papanicolaou stain) Fig. 4.10 Atypia of undetermined significance, Hürthle cell type (patient with history of Hashimoto thyroiditis). These Hürthle cells show nuclear enlargement and a rare nuclear pseu- doinclusion (arrow) (smear, Diff-Quik stain) Fig. 4.11 Atypia of undetermined significance, not otherwise specified. The nuclear atypia in these specimens does not raise concern for papillary carcinoma. (a) These follicular cells, in a patient with Graves' disease treated with methimazole (Tapazole®), show marked nuclear enlarge- ment and anisonucleosis (ThinPrep, Papanicolaou stain). (b) These atypical follicular cells were obtained from a patient with a history of ionizing radiation to the neck (smear, Romanowsky stain) Fig. 4.12 Atypia of undetermined significance, not otherwise specified. Psammoma bodies are a characteristic feature of papillary carcinoma. They form at the tip of a papilla due to circumferen- tial avascular necrosis, resulting in the concentric lamellations of the classic psammoma body. Psammoma bodies are non-birefringent and composed of calcium phosphate (smear, Diff-Quik stain) (From Ali et al. [51]. All Rights Reserved) Fig. 4.13 Atypia of undetermined significance with atypical lymphoid cells. (a) The sample is composed of a heterogeneous infiltrate of lymphoid cells, including occasional atypical forms. There is a tingible body macrophage in the center of the field. Clonality studies were not available in this case (ThinPrep, Papanicolaou stain). (b) The cell block shows similar features (hematoxylin and eosin stain) Fig. 4.14 Benign (papillary hyperplasia). Papillary projections are seen in papillary carcinoma, but Graves' disease and other hyperplastic thyroid nodules can show benign papillary prolifera- tions. It is critical to carefully examine the cells, especially their nuclear features; a diagnosis of papillary carcinoma should not be rendered on architecture alone. In this case, the patient went to surgery and was found to have papillary hyperplasia in an involuting hyperplastic nodule (smear, Papanicolaou stain) (From Ali et al. [51]. All Rights Reserved) Fig. 4.15 Air-drying artifact. Inadvertent air-drying of alcohol-fixed smears leads to suboptimal nuclear detail (e.g., artifactual pallor, enlargement), including poorly defined, possible nuclear pseudoinclusions (arrows). Except in rare instances, such changes can be recognized as artifactual and not diagnosed as atypia of undetermined significance (smear, Papanicolaou stain) Fig.4.16 Blood and clotting artifact. Extensive blood and clotting can distort the arrangement of follicular cells and make them look artifactually crowded. These findings should be discounted when assessing the architectural arrangement of the follicular cells. Without demonstrable atypia or sufficient benign follicular cells, such cases warrant a nondiagnostic/unsatisfactory interpreta- tion (smear, Papanicolaou stain) Fig. 5.1 Follicular neoplasm/suspicious for a follicular neoplasm. (a, b) Low magnification shows a highly cellular aspirate composed of uniform follicular cells arranged in crowded clusters and microfollicles (a smear, Diff-Quik stain; b smear, Papanicolaou stain) Fig.5.2 Follicular neoplasm/suspicious for a follicular neoplasm. (a) The crowded follicular cells have round nuclei of similar size and faint cytoplasm (smear, Diff-Quik stain). (b) Follicular cells are arranged as microfollicles and have round nuclei, evenly dispersed, granular chromatin, and small nucleoli (smear, Papanicolaou stain) Fig. 5.3 Follicular neoplasm/suspicious for a follicular neoplasm. (a, b) Follicular cells in crowded, microfollicular arrangements show slight size variation, chromatin that is more "open" (less granular), and enlarged nucleoli (a smear, Papanicolaou stain; b ThinPrep, Papanicolaou stain) Fig. 5.4 Follicular neoplasm/suspicious for a follicular neoplasm. (a, b) Microfollicles demon- strate nuclear overlap. Some are loosely cohesive clusters, and there are dispersed, isolated cells (a smear, Diff-Quik stain; b ThinPrep, Papanicolaou stain) Fig. 5.5 Follicular neoplasm/suspicious for a follicular neoplasm. (a, b) Microfollicles may contain small amounts of colloid (a smear, Diff-Quik stain; b smear, Papanicolaou stain) Fig. 5.6 Follicular neoplasm/suspicious for a follicular neoplasm. In some cases, trabeculae of crowded follicular cells are more conspicuous than microfollicles (smear, Papanicolaou stain) Fig. 5.7 Follicular neoplasm/suspicious for a follicular neoplasm. These crowded, uniform cells are arranged in thick trabeculae mimicking neoplastic follicular cells. Lobectomy revealed an unsuspected parathyroid adenoma (smear, hematoxylin, and eosin stain) Fig. 6.1 Follicular neoplasm, Hürthle cell (oncocytic) type/suspicious for a follicular neoplasm, Hürthle cell (oncocytic) type. The aspirate is very cellular and consists of oncocytes (Hürthle cells) of variable size arranged as isolated cells and in crowded groups; colloid is absent. Large-cell dysplasia is present (smear, Diff-Quik stain) Fig. 6.2 Follicular neoplasm, Hürthle cell (oncocytic) type/suspicious for a follicular neoplasm, Hürthle cell (oncocytic) type. The aspirate consists of a pure population of Hürthle cells in crowded groups and as isolated cells. The background lacks colloid and lymphocytes (ThinPrep, Papanicolaou stain) Fig. 6.3 Follicular neoplasm, Hürthle cell (oncocytic) type/suspicious for a follicular neoplasm, Hürthle cell (oncocytic) type. The aspirate is cellular and consists exclusively of Hürthle cells in an isolated-cell pattern simulating medullary thyroid carcinoma (smear, Diff-Quik stain) Fig. 6.4 Follicular neoplasm, Hürthle cell (oncocytic) type/suspicious for a follicular neoplasm, Hürthle cell (oncocytic) type. The aspirate consists of numerous dispersed Hürthle cells. The nuclei are highly variable in size, demonstrating large-cell dysplasia (ThinPrep, Papanicolaou stain) Fig.6.5 Follicular neoplasm, Hürthle cell (oncocytic) type/suspicious for a follicular neoplasm, Hürthle cell (oncocytic) type. This cellular aspirate consists of loosely cohesive, large Hürthle cells with marked anisonucleosis (large-cell dysplasia) and macronucleoli (smear, Papanicolaou stain) Fig. 6.6 Follicular neoplasm, Hürthle cell (oncocytic) type/suspicious for a follicular neoplasm, Hürthle cell (oncocytic) type. The aspirate consists of numerous variably sized groups of crowded Hürthle cells. Although demonstrably oncocytic, they have less cytoplasm than "usual" Hürthle cells, demonstrating small-cell dysplasia (ThinPrep, Papanicolaou stain) Fig. 6.7 Follicular neoplasm, Hürthle cell (oncocytic) type/suspicious for a follicular neoplasm, Hürthle cell (oncocytic) type. The aspirate is comprised almost exclusively of small Hürthle cells ("small-cell dysplasia") (ThinPrep, Papanicolaou stain) Fig. 6.8 Follicular neoplasm, Hürthle cell (oncocytic) type/suspicious for a follicular neoplasm, Hürthle cell (oncocytic) type. This cellular aspirate consists exclusively of Hürthle cells arranged in syncytial-like sheets and as isolated cells. The cells exhibit marked variation in cell and nuclear size (mixed small- and large-cell dysplasia) (ThinPrep, Papanicolaou stain) Fig. 6.9 Follicular neoplasm, Hürthle cell (oncocytic) type/suspicious for a follicular neoplasm, Hürthle cell (oncocytic) type. The aspirate consists of loosely cohesive oncocytes. The cells are highly variable in size and amount of cytoplasm, transitioning from gigantic cells with abundant cytoplasm and macronucleoli to smaller, uniform Hürthle cells with a high nuclear/cytoplasmic ratio. Both large-cell and small-cell dysplasia are present (smear, Diff-Quik stain) Fig. 6.10 Follicular neoplasm, Hürthle cell (oncocytic) type/suspicious for a follicular neoplasm, Hürthle cell (oncocytic) type. This cellular aspirate consists of noncohesive Hürthle cells with both large and small cell dysplasia. Colloid is absent, and transgressing vessels are present (smear, Papanicolaou stain) Fig. 6.11 Follicular neoplasm, Hürthle cell (oncocytic) type/suspicious for a follicular neoplasm, Hürthle cell (oncocytic) type. Transgressing vessels associated with Hürthle cell neoplasms can be seen with liquid-based preparations (ThinPrep, Papanicolaou stain) Fig. 6.12 Benign (multinodular hyperplasia with a prominent oncocytic component). There are benign follicular cells (left) and Hürthle cells (right) in cohesive flat sheets, with a moderate amount of watery ("tissue-paper") colloid. Such cases should not be called "follicular neoplasm, Hürthle cell (oncocytic) type/suspicious for a follicular neoplasm, Hürthle cell (oncocytic) type" (Thin Prep, Papanicolaou stain) Fig. 6.13 Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS). This oncocytic nodule in a patient with lymphocytic (Hashimoto) thyroiditis exhib- its a predominance of Hürthle cells in crowded groups with very few lymphocytes. In a patient with a known clinical diagnosis of lymphocytic (Hashimoto) thyroiditis, such cases can be interpreted as AUS/FLUS (smear, Diff-Quik stain) Fig. 6.14 Follicular neoplasm, Hürthle cell (oncocytic) type/suspicious for a follicular neoplasm, Hürthle cell (oncocytic) type. (a) This cellular aspirate was comprised exclusively of Hürthle cells, without overt nuclear features of papillary thyroid carcinoma (smear, Papanicolaou stain). (b) Histologic examination revealed a Hürthle cell carcinoma with papillary architecture. A subset of Hürthle cell neoplasms exhibits papillary architecture, with occasional cells that have an oval, pale, and grooved nucleus but lacking intranuclear pseudoinclusions. In such cases it can be difficult to distinguish a Hürthle cell neoplasm from an oncocytic papillary thyroid carcinoma, not just cyto- logically but also histologically (hematoxylin and eosin stain) Fig. 6.15 Follicular neoplasm, Hürthle cell (oncocytic) type/suspicious for a follicular neoplasm, Hürthle cell (oncocytic) type. (a) A minority of Hürthle cell neoplasms contain concentrically laminated concretions that are indistinguishable from psammoma bodies (smear, Papanicolaou stain). The correct diagnosis depends on the accompanying cellular features. (b) The histologic specimen revealed a Hürthle cell (oncocytic) adenoma with similar concretions (hematoxylin and eosin stain) Fig. 6.16 Follicular neoplasm, Hürthle cell (oncocytic) type/suspicious for a follicular neoplasm, Hürthle cell (oncocytic) type. (a) Some Hürthle cell neoplasms can be difficult to distinguish from a medullary carcinoma by cytomorphology alone. This case demonstrates a population of cells with abundant cytoplasm and occasional eccentrically placed nuclei (ThinPrep, Papanicolaou stain). (b) Immunohistochemical studies on a cell block preparation are positive for thyroglobulin. (c) The suspicious cells are negative for calcitonin Fig. 6.17 Granular cell tumor of the thyroid. (a) Because they have abundant granular cytoplasm, these neoplasms mimic Hürthle cell (oncocytic) tumors to perfection. (ThinPrep, Papanicolaou stain). (b) Histologic sections revealed nests of neoplastic cells infiltrating collagenized stroma (hematoxylin and eosin stain) Fig. 6.18 Parathyroid carcinoma. Some parathyroid neoplasms have abundant oncocytic cytoplasm (ThinPrep, Papanicolaou stain) Fig. 7.1 Suspicious for papillary thyroid carcinoma. This sheet of follicular cells displays some features of papillary carcinoma, including nuclear enlargement, powdery chromatin, nuclear mem- brane irregularity, nuclear grooves and molding, and small nucleoli. These changes were patchy, however, and other follicular cell sheets looked benign (ThinPrep, Papanicolaou stain) Fig. 7.2 Suspicious for papillary thyroid carcinoma. This loose sheet of follicular cells demon- strates enlarged nuclei, powdery chromatin, nucleoli, and nuclear grooves. There are some ques- tionable (i.e., small, poorly defined) intranuclear pseudoinclusions (arrows) and slight nuclear molding (arrow heads). These changes were patchy, however, and other follicular cells looked entirely benign (ThinPrep, Papanicolaou stain) Fig.7.3 Suspicious for papillary thyroid carcinoma. In this specimen, there were generalized but mild nuclear changes. A loose sheet of follicular cells shows slightly enlarged nuclei, variable chromatin pallor, small but prominent nucleoli, nuclear grooves, and minimal molding (ThinPrep, Papanicolaou stain) Fig. 7.4 Suspicious for papillary thyroid carcinoma. There is a loose sheet of histiocytoid cells with vacuolated cytoplasm, occasional small nucleoli, and small intranuclear pseudoinclusions (smear, Diff-Quik stain) Fig. 7.5 Suspicious for medullary thyroid carcinoma. There is a loose group of cells with rela- tively uniform nuclei; occasional larger nuclei with prominent nucleoli are present. The ill-defined cell borders make it difficult to discern the nature of the cytoplasm, the nuclear/cytoplasmic ratio, and the plasmacytoid contours of these cells. The stripped nuclei resemble small lymphocytes (smear, Diff-Quik stain) Fig. 7.6 Suspicious for medullary thyroid carcinoma. This loose sheet of relatively uniform cells has granular and vacuolated cytoplasm and ill-defined cell borders. The cells appear slightly degenerated, making it difficult to discern their features with certainty (smear, Diff-Quik stain) Fig. 7.7 Suspicious for lymphoma. (a) This hemodilute sample is comprised exclusively of lym- phoid cells, many of which appear poorly preserved. (b) At higher magnification, rare large atypi- cal lymphoid cells are present, but most of the cells are disrupted and appear as bare nuclei. In the absence of immunophenotyping studies that demonstrate clonality, the findings are suspicious but not conclusive for malignant lymphoma (smear, Diff-Quik stain) Fig. 7.8 Suspicious for papillary thyroid carcinoma (patient with Hashimoto thyroiditis). This sheet of unevenly distributed follicular cells shows nuclear enlargement, pale chromatin, nuclear irregularity, and prominent nucleoli (ThinPrep, Papanicolaou stain) Fig. 7.9 Suspicious for papillary thyroid carcinoma. Follicular cells adjacent to areas of infarc- tion, hemorrhage, and cyst formation ("cyst lining cells") can have nuclear changes similar to those of papillary thyroid carcinoma. When nuclear enlargement, pallor, and grooves are widespread throughout the specimen, the diagnosis "suspicious for malignancy" may be unavoidable (smear, Papanicolaou stain) Fig. 7.10 Suspicious for papillary thyroid carcinoma (patient treated with radioiodine for nodular goiter). These follicular cells demonstrate marked anisonucleosis, pale chromatin, and a prominent intranuclear cytoplasmic pseudoinclusion. Although the findings may represent treatment effect, the possibility of papillary thyroid carcinoma cannot be excluded when the atypia is as marked as in this case (smear, Papanicolaou stain) Fig.7.11 Suspicious for papillary thyroid carcinoma. These representative microfollicular groups display nuclear enlargement, variable chromatin pallor, and rare nuclear grooves. Surgical resec- tion of the nodule revealed a NIFTP (smear, Diff-Quik stain) Fig. 7.12 Suspicious for papillary thyroid carcinoma, oncocytic variant. (a) This low- magnification image reveals a hypercellular specimen with many groups of follicular cells with abundant cytoplasm (smear, Diff-Quik stain). (b) High magnification confirms the presence of abundant cytoplasm and reveals an intranuclear cytoplasmic pseudoinclusion. Although the find- ings are suspicious for papillary carcinoma, a Hürthle cell neoplasm cannot be entirely excluded (smear, Diff-Quik stain) Fig. 7.13 Suspicious for papillary thyroid carcinoma. (a) A loose sheet of follicular cells shows nuclear enlargement; pale, powdery chromatin; nuclear grooves; and prominent nucleoli (ThinPrep, Papanicolaou stain). (b) A cell block preparation from the FNA reveals the nested pattern of the atypical cells, along with their pale chromatin and obvious intranuclear cytoplasmic pseudoinclusions. The subsequent thyroidectomy revealed a hyalinizing trabecular tumor (cell block, H&E stain) Fig.7.14 Suspicious for malignancy, cannot classify further. Scattered cells have abundant finely vacuolated cytoplasm, and one cell displays a large intranuclear cytoplasmic pseudoinclusion. The subsequent thyroidectomy showed metastatic renal cell carcinoma (smear, Diff-Quik stain) Fig. 8.1 Papillary thyroid carcinoma. Preparations are often highly cellular and composed of numerous monolayer sheets and occasional papillary-like fragments (smear, Papanicolaou stain) Fig. 8.2 Papillary thyroid carcinoma. Monolayer sheets with a syncytial-like appearance are char- acteristic of papillary thyroid carcinoma. These flat sheets resemble those of benign follicular nodules; attention to the nuclear features is essential for this distinction (smear, Papanicolaou stain) Fig. 8.3 Papillary thyroid carcinoma. This monolayer sheet is comprised of cells with irregular nuclei that show focal molding (arrow) (ThinPrep, Papanicolaou stain) Fig. 8.4 Comparison of benign follicular cells with the cells of papillary thyroid carcinoma. (a) Benign follicular cells (nodular goiter). (b) Compared with those of the benign follicular cells, the nuclei of papillary carcinoma are larger, paler, more crowded, and more irregular in contour (a, b, ThinPrep, Papanicolaou stain) Fig. 8.5 Papillary thyroid carcinoma. True papillary tissue fragments, comprised of fibrovascular cores lined by neoplastic cells, are seen in the conventional type of papillary thyroid carcinoma (smear, Papanicolaou stain) Fig. 8.6 Papillary thyroid carcinoma. The neoplastic cells surround a fibrovascular core (ThinPrep, Papanicoalou stain) Fig. 8.7 Papillary thyroid carcinoma. There is a mixture of flat sheets and rounded, papillary-like fragments without fibrovascular cores (ThinPrep, Papanicoalou stain) Fig. 8.8 Papillary thyroid carcinoma. Cellular swirls are highly characteristic of the conventional (classic) papillary thyroid carcinoma. They are a concentric aggregate of tumor cells in which many of the peripheral cells have ovoid (rather than round) nuclei and are oriented perpendicular to the radius of the swirl (ThinPrep, Papanicolaou stain) Fig. 8.9 Papillary thyroid carcinoma. (a) Intranuclear cytoplasmic pseudoinclusions (INCIs) and micronucleoli are shown. Note that the two INCIS share the same aqua color and granular texture as the surrounding cytoplasm (smear, Papanicolaou stain). (b) A large INCI occupying most of the nucleus is seen in the center. The remaining nuclei show variation in size and shape (smear, Diff- Quik stain) Fig. 8.10 Papillary thyroid carcinoma. Two intranuclear cytoplasmic pseudoinclusions (INCIS) are seen. (ThinPrep, Papanicoalou stain) Fig. 8.11 Papillary thyroid carcinoma. Close inspection at high magnification shows frequent nuclear grooves, finely textured (powdery) chromatin, and micronucleoli (smear, Papanicolaou stain) Fig. 8.12 Papillary thyroid carcinoma. Multinucleated giant cells accompany monolayered sheets of tumor cells. Although multinucleated giant cells are often seen in PTCs, they are a nonspecific finding (smear, Papanicolaou stain) Fig. 8.13 Papillary thyroid carcinoma. Psammoma bodies are concentric rings and are lined here by atypical cells with oval, pale nuclei. Note that the tumor cells surrounding psammoma bodies show hobnail features (ThinPrep, Papanicolaou stain) Fig. 8.14 Papillary thyroid carcinoma, follicular variant. (a) The aspirates show microfollicles with crowded, enlarged clear oval nuclei (smear, Papanicolaou stain). (b) Ultrasound shows solid nodule with blurred margins (c) correlating with infiltrative margin in histology. (d) Histologically, the tumor is composed of microfollicles with "Orphan Annie eye" "clear nuclei (hematoxylin and eosin stain) Fig. 8.15 Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (formerly called encapsulated follicular variant of papillary thyroid carcinoma). (a) The aspirate shows microfollicles with crowded, enlarged, clear, oval nuclei along with microfollicles with small dark nuclei (smear, Papanicolaou stain). (b) Ultrasound shows well-circumscribed solid nodule with a rim, correlating with encapsulation (c). (d) Histologically, the tumor is composed of microfollicles with "Orphan Annie eye" clear nuclei (hematoxylin and eosin stain) Fig. 8.16 Papillary thyroid carcinoma, macrofollicular variant. The neoplastic cells resemble those of a benign thyroid nodule at scanning magnification. In such cases, there can be abundant thin colloid and relatively few sheets of cells. The difference lies in the nuclear features, which are better appreciated at high magnification (smear, Diff-Quik stain) Fig. 8.17 Papillary thyroid carcinoma, macrofollicular variant. Left, There is a large sheet of tumor cells with crowded, "Orphan Annie eye" nuclei; Right, An intranuclear pseudoinclusion is present in the large oval nucleus. Note also the peripheral micronucleoli (smear, Papanicolaou stain) Fig. 8.18 Papillary thyroid carcinoma, cystic variant. There is prominent cystic change with numerous hemosiderin-laden macrophages. A small cluster of neoplastic cells has smooth, dense cytoplasm, and one cell has a large intranuclear cytoplasmic pseudoinclusion (smear, Diff-Quik stain) Fig. 8.19 Papillary thyroid carcinoma, cystic variant. Most of the cells in this image are neoplas- tic. They have abundant granular cytoplasm, hence the descriptor "histiocytoid." Classic nuclear features of papillary thyroid carcinoma are absent, but there is conspicuous nuclear enlargement (ThinPrep, Papanicolaou stain). Fig. 8.20 Papillary thyroid carcinoma, oncocytic variant. The entire neoplasm is composed of oncocytic (Hürthle-like) cells that have abundant granular cytoplasm. The nuclear features of pap- illary carcinoma are not readily apparent in this image; such cases are good mimics of Hürthle cell neoplasms (smear, Diff-Quik stain) Fig. 8.21 Papillary thyroid carcinoma, oncocytic variant. (a) Loosely cohesive polygonal to plas- macytoid oncocytic (Hürthle-like) cells have atypical, clear nuclei with eccentric micronucleoli and rare intranuclear pseudoinclusions without nuclear grooves; such cases are good mimics of medullary thyroid carcinoma. (b) Multiple small and large intranuclear pseudoinclusions are seen in a large oncocytic cell with abundant granular cytoplasm (smears, Papanicolaou stain) Fig. 8.22 Papillary thyroid carcinoma, Warthin-like variant. (a) The aspirate shows papillary fragments in a lymphocytic background (smear, Papanicolaou stain). (b) The fibrovascular cores are engorged with lymphocytes (smear, Papanicolaou stain). (c) The epithelial cells are also inti- mately associated with lymphocytes. The nuclei are enlarged, oval, and clear (smear, Papanicolaou stain). (d) Histologically, the tumor resembles a Warthin tumor of the salivary gland, with tumor epithelium surrounding lymphoid aggregates. Typical nuclear features of papillary carcinoma can be seen at high power (not shown) (hematoxylin and eosin stain) Fig. 8.23 Papillary thyroid carcinoma, tall cell variant. (a) The smear shows elongated cells in loosely cohesive arrangements (smear, Papanicolaou stain). (b) The cytoplasm is elongated, with frequent nuclear pseudoinclusions and rare soap-bubble nuclei (inset) (smear, Papanicolaou stain). (c) Histologically, this variant is comprised of tall rectangular tumor cells with eosinophilic cyto- plasm arranged in parallel rows (hematoxylin and eosin stain) Fig. 8.24 Papillary thyroid carcinoma, tall cell variant. "Soap-bubble-like" intranuclear pseu- doinclusions are often seen in the tall cell variant of papillary thyroid carcinoma (ThinPrep, Papanicolaou stain) Fig. 8.25 Papillary thyroid carcinoma, tall cell variant. The "tallness" of these cells is readily appreciated. When this morphology is seen throughout the sample, one can raise the possibility of a tall cell variant in the FNA report (ThinPrep, Papanicolaou stain) Fig. 8.26 Papillary thyroid carcinoma, columnar cell variant. (a) The aspirate shows loosely cohesive spindle-shaped cells (smear, Papanicolaou stain). (b) The cytoplasm is bipolar and wispy, and cigar-shaped nuclei have few characteristic features of papillary thyroid carcinoma (smear, Papanicolaou stain). (c) Histologic examination shows rows of pseudostratified columnar cells with elongated hyperchromatic nuclei and scanty cytoplasm (hematoxylin and eosin stain) (Courtesy of Dr. Tamar Giorgadze, MD, PhD of Medical College of Wisconsin) Fig. 8.27 Papillary thyroid carcinoma, solid variant. This variant may demonstrate three different cytologic patterns: (a) a cohesive, syncytial tissue fragment pattern, (b) a microfollicular/trabecu- lar pattern, and (c) a noncohesive, single-cell pattern. All three patterns have characteristic nuclear features of papillary carcinoma: convoluted clear nuclei in a2, nuclear clearing and convolution in the inset of b, and nuclear clearing and grooves in c (al, b: smears, Diff-Quik stain; a2, c and insets: smears, Papanicolaou stain) Fig. 8.28 Papillary thyroid carcinoma, diffuse sclerosing variant. (a) The aspirate shows papillary fragments associated with psammoma bodies in a lymphocytic background. The nuclear chroma- tin is darker than in the conventional papillary thyroid carcinoma. (b) On histologic examination, the thyroid gland shows numerous lymphoid follicles and many small "holes." (c) The holes are from popped out psammoma bodies Fig. 8.29 Papillary thyroid carcinoma, diffuse sclerosing variant. The neoplastic cells in this image are "squamoid": they have a flat, polygonal shape with sharply demarcated cell membranes, and they fit together like jigsaw pieces (but there is no overt keratinization.) This squamoid appear- ance is sometimes encountered as a focal finding in conventional (classic) papillary carcinomas, but in the diffuse sclerosing variant, this feature is often widespread. Note that these cells lack the usual nuclear features of papillary carcinoma (ThinPrep, Papanicolaou stain) Fig. 8.30 Papillary thyroid carcinoma, cribriform-morular variant. (a) The aspirate shows large fragments of cohesive epithelium with a complicated arrangement (smear, Papanicolaou stain). The nuclear chromatin is dark, but nuclear pseudoinclusions are present (inset). (b) Histologically, the tumor is characterized by cribriform morula formation ((hematoxylin and eosin stain). (c) Higher magnification shows the characteristic morules (hematoxylin and eosin stain) Fig. 8.31 Papillary thyroid carcinoma, hobnail variant. (a) The tumor cells in this variant are characterized by an eccentric location of the nucleus in elongated cytoplasm (hobnail-like) (smear, Papanicolaou stain). (b) The histologic counterpart shows similar features (hematoxylin and eosin) Fig. 8.32 Hyalinizing trabecular tumor/adenoma. (a) A core of metachromatic hyaline material insinuates among cells with oval nuclei, anisonucleosis, and abundant cytoplasm (smear, Diff- Quik stain). (b) Oval neoplastic nuclei have occasional intranuclear cytoplasmic pseudoinclusions (INCIS, arrows). Note the clear hole in one of the adjacent nuclei (arrowhead), a mimic of INCIS, but recognizable as an artifact because the hole is white rather than the color and texture of cyto- plasm (smear, Papanicolaou stain) Fig. 9.1 Medullary thyroid carcinoma. Predominantly dispersed plasmacytoid or polygonal cells have granular ("salt and pepper") chromatin and small or indistinct nucleoli. A small fragment of amyloid is present (arrow) (smear, Papanicolaou stain) Fig. 9.2 Medullary thyroid carcinoma. (a) In some cases a cohesive, syncytium-like pattern of crowded cells predominates, with few isolated cells. (b) In this example, tumor cells exhibit less abundant cytoplasm, round to ovoid nuclei, and coarse chromatin. Medullary thyroid carcinomas with this pattern mimic a follicular neoplasm, poorly differentiated thyroid carcinoma, and para- thyroid neoplasms (smear, Papanicolaou stain) Fig. 9.3 Medullary thyroid carcinoma. A variety of shapes (round, polygonal, plasmacytoid, and spindled) are noted in this noncohesive population of tumor cells (ThinPrep, Papanicolaou stain) Fig. 9.4 Medullary thyroid carcinoma. (a) The spindle-cell variant can have a syncytium-like arrangement (smear, Diff-Quik stain). (b) The spindle-cell variant has prominent interdigitating cytoplasmic processes with oval nuclei. Smooth nuclear membranes, granular chromatin, and inconspicuous nucleoli are maintained (smear, Papanicolaou stain) Fig. 9.5 Medullary thyroid carcinoma. A large tumor cell with abundant cytoplasm demonstrates red cytoplasmic granules with a Romanowsky-type stain. Note also the presence of amyloid (arrow- head) and a tumor cell with an intranuclear pseudoinclusion (arrow) (smear, Diff-Quik stain) Fig. 9.6 Medullary thyroid carcinoma. Pigmentation and/or melanocytic differentiation can be seen in medullary thyroid carcinoma (arrow), which raises the possibility of a metastatic mela- noma. Even without pigmentation, melanoma is a mimic of medullary thyroid carcinoma because both often demonstrate an isolated-cell pattern, epithelioid or spindled morphology, and binucle- ation. Immunocytochemistry on the cell block in this case confirmed the diagnosis of medullary thyroid carcinoma (ThinPrep, Papanicolaou stain) Fig. 9.7 Medullary thyroid carcinoma. Cytoplasmic vacuoles or lumina are occasionally seen in medullary thyroid carcinoma (smear, Papanicolaou stain) Fig. 9.8 Medullary thyroid carcinoma. Intranuclear cytoplasmic pseudoinclusions can be seen, mimicking papillary thyroid carcinoma (ThinPrep, Papanicolaou stain) Fig. 9.9 Medullary thyroid carcinoma, small-cell variant. (a) Rare cases of medullary thyroid carcinoma exhibit scant cytoplasm and nuclear molding, resembling small cell carcinoma of the lung and other sites (smear, Papanicolaou stain). (b) Immunoreactivity for calcitonin and (c) Congo red staining for amyloid on cell block preparations support the diagnosis of medullary thyroid carcinoma. Nevertheless, because their immunprofiles can overlap and both tumors can contain amyloid, the distinction requires correlation with clinical findings Fig. 9.10 Medullary thyroid carcinoma. In this smear, amyloid is abundant and readily appreciated as a light-green, waxy, amorphous deposit (Papanicolaou stain) Fig. 9.11 Medullary thyroid carcinoma. Amyloid has the same dense, amorphous, and waxy appearance on liquid-based preparations as it does on smears (ThinPrep, Papanicolaou stain) Fig.9.12 Medullary thyroid carcinoma. The tumor cells (on cell block preparations) are immunoreactive for (a) TTF1 (nuclear), (b) calcitonin (cytoplasmic), and (c) chromogranin (cytoplasmic). (d) Tumor cells are negative for thyroglobulin Fig. 9.13 Medullary thyroid carcinoma (left) versus Hürthle-cell neoplasm (right). (a) With Romanowsky-type stains, the cells of some (but not all) medullary thyroid carcinomas are note- worthy for abundant red cytoplasmic granules (smear, Diff-Quik). (b) In contrast, Hürthle cells have blue-gray cytoplasmic granules with Romanowsky-type stains (smear, Diff-Quik) Fig. 9.14 Medullary thyroid carcinoma (left) versus poorly differentiated thyroid carcinoma (right). (a) Medullary thyroid carcinomas often demonstrate an isolated-cell pattern, plasmacytoid cytomorphology, and they occasionally have cytoplasmic lumina (ThinPrep, Papanicolaou stain). (b) Poorly differentiated thyroid carcinomas have similar features, and intracytoplasmic lumina are sometimes seen (ThinPrep, Papanicolaou stain) Fig. 9.15 Medullary thyroid carcinoma (left) versus undifferentiated/anaplastic thyroid carci- noma (right). (a) The giant-cell variant of medullary thyroid carcinoma exhibits markedly enlarged, epithelioid tumor cells with pleomorphic nuclei, often admixed with more conventional-appearing tumor cells (ThinPrep, Papanicolaou stain). Multinucleation may be seen, as in this example. (b) Note the resemblance to undifferentiated (anaplastic) thyroid carcinoma, which can also exhibit an epithelioid cytomorphology and nuclear pleomorphism (ThinPrep, Papanicolaou stain). This rap- idly growing primary thyroid tumor was positive for PAX8 and negative for TTF1, calcitonin, synaptophysin, and chromogranin. Histologic images of medullary thyroid carcinoma (c) and undifferentiated thyroid carcinoma (d) demonstrate similar nuclear and cytoplasmic features (hematoxylin and eosin stain) Fig. 10.1 Poorly differentiated thyroid carcinoma. A low magnification view reveals small fol- licular cells arranged in crowded insulae (smear, Papanicolaou stain) Fig. 10.2 Poorly differentiated thyroid carcinoma. The monomorphic cells are arranged in crowded three-dimensional groups and scattered as isolated cells (ThinPrep, Papanicolaou stain) Fig. 10.3 Poorly differentiated thyroid carcinoma. Endothelium wrapping around cell groups can often be found highlighting the insular arrangements (smear, Papanicolaou stain) Fig. 10.4 Poorly differentiated thyroid carcinoma. This cell block demonstrates the arrangement of cells in insular groups (cell block, H&E stain) Fig. 10.5 Poorly differentiated thyroid carcinoma. In some cases, the malignant cells are arranged predominantly as isolated cells. They can have a plasmacytoid cytomorphology, as seen here (ThinPrep, Papanicolaou stain) Fig. 10.6 Poorly differentiated thyroid carcinoma. In some cases, the cells have oncocytic cytoplasm. Some bare nuclei are also present (smear, Diff-Quik stain) Fig. 10.7 Poorly differentiated thyroid carcinoma. Some tumors demonstrate only mild nuclear atypia, with small nucleoli and delicate chromatin (smear, Papanicolaou stain) Fig. 10.8 Poorly differentiated thyroid carcinoma. Some aspirates exhibit marked nuclear atypia. In this example, there is impressive anisokaryosis (smear, Papanicolaou stain) Fig. 10.9 Poorly differentiated thyroid carcinoma. Aspirates of poorly differentiated carcinomas often contain mitotically active cells (smear, Papanicolaou stain) Fig. 10.10 Poorly differentiated thyroid carcinoma. Necrotic debris (cytoplasmic and nuclear fragments) is seen in some poorly differentiated carcinomas (smear, Papanicolaou stain) Fig. 10.11 Poorly differentiated thyroid carcinoma. The presence of microfollicles does not pre- clude the possibility of a poorly differentiated thyroid carcinoma (smear, Papanicolaou stain) Fig. 10.12 Poorly differentiated thyroid carcinoma. (a) In some cases, tumors show features of papillary carcinoma, including nuclear grooves and pseudoinclusions. (b) There can be significant nuclear pleomorphism (a, b, smears, Papanicolaou stain) Fig. 10.13 Poorly differentiated thyroid carcinoma. Because some aspirates are comprised pre- dominantly of isolated cells with granular chromatin, they mimic both medullary thyroid carci- noma and metastatic neoplasms (smear, Papanicolaou stain) Fig. 10.14 Poorly differentiated thyroid carcinoma. Poorly differentiated thyroid carcinomas are positive for thyroglobulin, which helps to distinguish them from medullary thyroid carcinoma and metastatic tumors (ThinPrep, thyroglobulin immunoperoxidase reaction) Fig. 11.1 Undifferentiated (anaplastic) thyroid carcinoma. Aspiration of tumors with abundant fibrosis can yield low cellularity. If cells lack marked nuclear atypia (arrow), rendering a definitive diagnosis can be difficult. Clinical correlation is important (smear, Papanicolaou stain) Fig. 11.2 Undifferentiated (anaplastic) thyroid carcinoma. Widespread tumor necrosis and asso- ciated inflammation can hinder diagnosis because well-preserved malignant cells are few and far between (arrow) (smear, Papanicolaou stain) Fig. 11.3 Undifferentiated (anaplastic) thyroid carcinoma. Rapid tumor growth and invasion of extrathyroidal tissues is common. Aspiration samples can contain skeletal muscle fragments (cen- ter) as well as anaplastic tumor cells (smear, Papanicolaou stain) Fig. 11.4 Undifferentiated (anaplastic) thyroid carcinoma. Cells are epithelioid (polygonal) in appearance. Variation in cell and nuclear size is evident. Parachromatin clearing and nuclear contour irregularity are prominent (smear, Papanicolaou stain) Fig. 11.5 Undifferentiated (anaplastic) thyroid carcinoma. The neoplastic cells are mostly round, with scant to moderate cytoplasm. There is less pleomorphism of nuclear size and shape than in most cases of UTC, but mitotic figures (arrows) are easily found (smear, Diff-Quik stain) Fig. 11.6 Undifferentiated (anaplastic) thyroid carcinoma. All neoplastic cells are strikingly spindle-shaped, resembling the cells of a sarcoma. Although chromatin is coarse, parachromatin clearing, prominent nucleoli, and nuclear irregularity are not apparent (smear, Papanicolaou stain) Fig. 11.7 Undifferentiated (anaplastic) thyroid carcinoma. Tumor cells are notably spindle-shaped, with long, tapering cytoplasmic processes (smear, Diff-Quik stain) Fig. 11.8 Undifferentiated (anaplastic) thyroid carcinoma. Tumors with a predominantly spindle- cell morphology can appear as microbiopsy fragments. A storiform pattern can be appreciated (smear, Papanicolaou stain) Fig. 11.9 Undifferentiated (anaplastic) thyroid carcinoma. These tumors can be associated with abundant inflammatory cells, typically neutrophils. A multinucleated tumor giant cell with bizarre nuclear features and smaller, isolated, less anaplastic malignant cells are readily identifiable (smear, Papanicolaou stain) Fig. 11.10 Undifferentiated (anaplastic) thyroid carcinoma. Bizarre multinucleated tumor giant cells are found in some aspirations. The size of this tumor giant cell can be fully appreciated when compared to the adjacent neutrophils (arrow) (smear, Diff-Quik stain) Fig. 11.11 Undifferentiated (anaplastic) thyroid carcinoma. Variably pleomorphic tumor giant cells with coarse chromatin are seen in a loosely cohesive cell group (ThinPrep, Papanicolaou stain) Fig. 11.12 Undifferentiated (anaplastic) thyroid carcinoma. In some cases, the epithelioid tumor cells have a conspicuously plasmacytoid appearance (smear, Diff-Quik stain) Fig. 11.13 Undifferentiated (anaplastic) thyroid carcinoma. A giant spindle-shaped tumor cell has a massive intranuclear cytoplasmic pseudoinclusion. Other nuclear features include enlarge- ment, contour irregularity, and a prominent nucleolus (smear, Papanicolaou stain) Fig. 11.14 Undifferentiated (anaplastic) thyroid carcinoma. Epithelioid tumor cells display size variation, mononucleated and binucleated forms, macronucleoli, and clumped chromatin with parachromatin clearing (arrow). Acute inflammatory cells are present in the background (smear, Papanicolaou stain) Fig. 11.15 Undifferentiated (anaplastic) thyroid carcinoma. There is conspicuous infiltration of a multinucleated tumor giant cell by neutrophils (smear, Papanicolaou stain) Fig. 11.16 Undifferentiated (anaplastic) thyroid carcinoma. (a) Some UTCs contain numerous nonneoplastic, osteoclast-like giant cells (smear, Papanicolaou stain). (b) The osteoclast-like giant cells are scattered among the malignant cells (thyroidectomy, hematoxylin and eosin stain) Fig. 11.17 Undifferentiated (anaplastic) thyroid carcinoma. PAX8, one of the most useful immunomarkers in this setting, displays crisp nuclear positivity (cell block, PAX8 immunostain) Fig. 11.18 Squamous cell carcinoma of the thyroid. The sample is composed of large pleomor- phic cells with conspicuous dense orangeophilia of the cytoplasm. There is abundant necrosis, and nuclei show degenerative changes (i.e., dark, smudged, and/or marginated chromatin) (smear, Papanicolaou stain) Fig. 12.1 Metastatic renal cell carcinoma, clear cell type. The malignant cells have finely vacuo- lated cytoplasm (smear, Diff-Quik stain) Fig. 12.2 Metastatic renal carcinoma, clear cell type. Cells in a small cluster have abundant finely granular cytoplasm. Note the adjacent neutrophils for size comparison (ThinPrep, Papanicolaou stain) Fig. 12.3 Metastatic melanoma. The malignant cells are isolated and loosely aggregated. They are large, oval, and plasmacytoid cells with abundant granular cytoplasm, hyperchromatic nuclei, and prominent nucleoli. Foamy histiocytes are present (smear, Diff-Quik stain) Fig. 12.4 Metastatic melanoma. Most of the pigment is engulfed by macrophages ("melano- phages") (smear, Diff-Quik stain) Fig. 12.5 Metastatic ductal carcinoma of the breast. Medium-sized cells have large eccentric nuclei and purple intracytoplasmic vacuolar granules (magenta bodies, arrows) that represent mucin vacuoles (smear, Diff-Quik stain) Fig. 12.6 Metastatic non-small cell lung carcinoma. Irregular cell clusters and spherical groups are composed of polygonal and columnar cells (smear, Diff-Quik stain) Fig. 12.7 Metastatic non-small cell lung carcinoma. Medium-sized cells have large nuclei, prom- inent nucleoli, and ample finely granular cytoplasm. The cells are arranged in spherical clusters (ThinPrep, Papanicolaou stain) Fig. 12.8 Metastatic gastric signet-ring cell carcinoma. Uniform dispersed cells have a high N/C ratio and intracytoplasmic mucinous vacuoles (smear, Diff-Quik stain) (Courtesy of Dr. QK Li, the Johns Hopkins Hospital, Baltimore, MD) Fig. 12.9 Metastatic Merkel cell carcinoma. Dispersed small round blue cells have a high nuclear/ cytoplasmic ratio and frequent mitotic figures (smear Diff-Quik stain) Fig. 12.10 Metastatic colonic adenocarcinoma. Columnar cells with nuclear stratification are associated with granular necrotic debris in the background (smear, Papanicolaou stain) Fig. 12.11 Primary MALT-type lymphoma of the thyroid. There is an abundance of uniform intermediate-sized cells with small nucleoli and granular chromatin (smear, Diff-Quik stain) Fig. 12.12 Diffuse large B-cell lymphoma of the thyroid. The smear is cellular and composed mostly of large lymphoid cells whose nuclei are three to five times larger than those of the smaller lymphocytes (smear, Diff-Quik stain) Fig. 12.13 Hodgkin lymphoma of the thyroid. The cells range widely in size and include scatered very large binucleated and multinucleated cells with features of Reed-Sternberg cells (smear, hematoxylin, and eosin stain) Fig. 12.14 Paraganglioma of the thyroid. FNA of an intrathyroidal paraganglioma is characterized by groups of bland spindle cells with scant wispy cytoplasm (smear, hematoxylin, and eosin stain) Fig. 12.15 Paragangliomas of the thyroid. Higher magnification of Fig. 14. Some aspirates from Paraganglioma of the thyroid contain microfollicle-like structures composed of cells with pale wispy cytoplasm (smear, hematoxylin, and eosin stain) Fig. 12.16 Langerhans cell histiocytosis of the thyroid. The neoplastic cells have variably shaped nuclei, including some that are deeply folded, which mimic the nuclear groove characteristic of papillary carcinoma. Hemosiderin-laden macrophages are also present. Eosinophils were prominent elsewhere on the smear (smear, Papanicolaou stain) Fig.12.17 Sclerosing mucoepidermoid carcinoma with eosinophilia. This neoplasm is comprised mainly of "intermediate cells": nonkeratinizing immature, cuboidal squamous cells. A small squa- mous pearl is also present (ThinPrep, Papanicolaou stain) Fig. 12.18 a Sclerosing mucoepidermoid carcinoma with eosinophilia. The intermediate cells have round nuclei, granular chromatin, and prominent nucleoli. Cytoplasm is thin and granular (ThinPrep, Papanicolaou stain). b Inset: The tumor cells are immunoreactive for TTF-1 Fig. 12.19 Mammary analog secretory carcinoma of the thyroid. The cells are arranged in groups, as seen here, and as isolated cells. Note that some cells have prominent large, solitary cytoplasmic vacuoles (ThinPrep, Papanicolaou stain) Fig. 12.20 Mammary analog secretory carcinoma of the thyroid. The cells have prominent nucleoli (ThinPrep, Papanicolaou stain) Fig. 12.21 Thymoma of the thyroid. Type A thymomas characteristically display variable proportions of lymphocytes and groups of spindle cells, often with scant cytoplasm and spindle-shaped nuclei with finely granular chromatin (smear, Diff-Quik stain) Fig. 12.22 Thymoma of the thyroid. Type B thymomas are characterized by prominent numbers of uniform small lymphocytes and groups of polygonal epithelial cells (smear, Diff-Quik stain)
