Cellient Atlas - Thyroid FNA
INTRODUCTION
Andrew H. Fischer, M.D
Note: The cell block images presented here were generated using a manual method during development of the automated instrument.
The Papanicolaou Society of Cytopathology recently proposed a uniform thyroid FNA classification system to minimize ambiguity between pathologists and clinicians [1]. In this chapter, we will use their proposed classification:
- Unsatisfactory/non-diagnostic
- Benign (includes hyperplastic/adenomatoid nodule and lymphocytic thyroiditis)
- Cellular lesion, cannot rule out follicular neoplasm
- Follicular neoplasm
- Suspicious for malignancy (specify type)
- Malignant (including papillary thyroid carcinoma, medullary carcinoma, anaplastic carcinoma and other tumors)
Conventional thyroid FNA cytology preparations provide the following diagnostic information:
- Nuclear morphology
- Microfollicular vs. macrofollicular arrangement, and amount of colloid.
- Character of colloid (watery vs. dense)
- Presence of macrophages with hemosiderin
- Presence or absence of lymphocytes
- Variation in cell morphology from group to group
As described below, nuclear morphology has to be examined in order to diagnose or exclude papillary thyroid carcinoma. Whether a lesion is microfollicular or macrofollicular relates directly to the amount of colloid and the proportion of follicular cells to colloid. In general, follicular type neoplasms are microfollicular with scant dense colloid [2]. Papillary thyroid carcinomas may be either micro or macrofollicular [2]. Benign follicular nodules are generally macrofollicular and very commonly show cystic degeneration [2, 3]. The cystic degeneration in benign follicular nodules appears as though it has a component of venous stasis, and exhibits edematous, watery colloid together with hemosiderin. Papillary thyroid carcinoma also often shows macrophages with hemosiderin [2]. However, such cystic degeneration is reportedly very uncommon in follicular neoplasms [2, 3], and this has also been our experience. Therefore, once papillary thyroid carcinoma is excluded (based on the absence of the characteristic nuclear features described below), the presence of hemosiderin is very strong evidence in favor of a benign follicular lesion. Lymphocytes, often with plasma cells and fragments of germinal centers, are seen in lymphocytic thyroiditis, but they are rare in follicular neoplasms [2], even follicular neoplasms arising in the setting of lymphocytic thyroiditis. Lymphocytes and plasma cells are, however, relatively common in papillary thyroid carcinoma. Benign follicular lesions will typically show some variation in the cytologic features from group to group, rather than a monomorphic population.
Cell blocks provide all of the diagnostic information listed above, with the exception of very watery colloid. In our experience, the presence of hemosiderin in a follicular-type lesion is virtually always associated with watery colloid. Solid colloid fragments tend to be more abundant in the cell block than in the corresponding ThinPrep®.
Core biopsy can be synergistic with FNA for accurate evaluation of thyroid nodules [4, 5]. Likewise, combining cell blocks with FNA has been found to be useful, disclosing diagnostic patterns that may not be evident in monolayers [6, 7]. Kern found that 1/5 of thyroid FNA’s had diagnostic material only in the cell block sections and not in smears [8]. In the following, the diagnostic synergy between monolayer preparations such as ThinPreps® and cell blocks are illustrated. ThinPrep will present the smaller fragments that are easy to study without histologic sectioning. The remaining largest fragments are captured in the cell block and enhance the ability to see how cell morphology varies over larger-scale distances, useful for the following diagnostic challenges:
- Lymphocytic thyroiditis with Hürthle cell change vs. Hürthle cell neoplasm
- Lymphocytic thyroiditis with reactive follicular cells vs. papillary thyroid carcinoma
- Benign follicular lesion with reactive follicular cells vs. papillary thyroid carcinoma
- Microfollicular groups in a goiter vs. follicular neoplasm.
This chapter illustrates some of these advantages. In general, non-neoplastic Hürthle cell changes, or focal reactive-type nuclear clearing suggestive of papillary thyroid carcinoma, will show a spectrum of changes that blend over the span of a few follicles with normal-appearing follicular cells. In cell blocks, one may have the opportunity to see how the reactive changes are related spatially to areas of lymphocytic destruction of the follicles, or areas in a benign colloid nodule that have become denuded to evoke the reparative reaction resembling papillary thyroid carcinoma. In contrast, neoplastic Hürthle cells or papillary thyroid carcinoma will show an abrupt («clonal-appearing») transition when compared to benign follicular cells, without any apparent relation to a lymphocytic infiltrate.
Cell blocks allow the follicle size to be judged in a manner that complements ThinPrep slides. For a follicle to be considered large, the follicular cells need to be arranged 2-dimensionally over a fairly broad distance; if the follicles are small, the cells will not present in a broad 2-dimensional flat sheet. Surprisingly, it is difficult to find a consensus on the definition of «macrofollicular» [9]. Eight to 10 follicular cell diameters appears to be a reasonable definition for the macrofollicular colloid fragments [9], or for the diameter of flat, 2-dimensional macrofollicular sheets. In tissue sections that cut perpendicular to a macrofollicular group, macrofollicles will appear as a linear arrangement of at least 8 follicular cells. If the section cuts in the plane of a macrofollicular group, one can occasionally encounter a solid-appearing mass of cells analogous to a tissue section that cuts tangentially right through the ductal cell layer in a breast biopsy. Just as surgical pathologists can recognize such tangential sectioning and distinguish this from ductal hyperplasia, one can recognize tangential sectioning through macrofollicular groups. This is illustrated below. Microfollicles by definition have a high proportion of cells to colloid, and the cells cannot lie within a broad 2-dimensional sheet. In cell block sections, microfollicles will not show long linear arrangements of cells. Renshaw et al., found a significant gray zone among experts in the distinction between microfollicular and macrofollicular groupings on cytology preparations [9]. One of the major gray areas relates to the problem of disaggregated follicular cells artifactually piled on top of each other. This artifactual piling up of cells appears easier to diagnose in tissue sections. Another problem area includes those cases in which there are mixtures of microfollicles and macrofollicles. We and others have noted that benign goiterous nodules tend to show flattened cytoplasm in the cells of the microfollicles. The more robust cells of a follicular neoplasm tend to show mostly cuboidal, or even columnar, follicular cells lining the microfollicles [7]. These features are evident in cell block sections and are illustrated below.
Benign follicular nodules tend to show an admixture of cytologically different types of follicular cells. Follicular neoplasms are more likely to be uniform from follicle to follicle. While the appearance of the follicles in a cytology preparation can be compared from group to group, this approach to judging «clonality» may at times be difficult. For example, it can be impossible to know whether the FNA needle sampled areas outside of a neoplasm. Cell blocks can often allow assessment of the morphologic features of truly adjacent follicles over a span of several hundred microns, as illustrated below.
There are some differences in the appearance of nuclei in direct smears, ThinPreps®, and cell blocks. One advantage of cell blocks is that they provide a common platform that can be shared with the surgical pathologists who will ultimately diagnose a resection specimen. We illustrate the utility of this approach for trying to classify the FNAs of problematic follicular-patterned lesions with partially developed nuclear features of papillary thyroid carcinoma [3].
Papillary thyroid carcinoma is an easy diagnosis if the nuclear features are well-developed and the sample is well-preserved. The best diagnostic features of papillary thyroid carcinoma are finely dispersed chromatin, and nuclear envelope irregularity [2]. Interestingly, papillary thyroid carcinoma is the first example of cancer where the diagnostic nuclear features are known to be directly related to the genes that cause it (reviewed in [10]). A spectrum of nuclear envelope irregularity can be present [11]. The chromatin of a papillary thyroid carcinoma is dispersed into very fine particles, and since much of the chromatin is smoothly adherent to the nuclear envelope, even a tiny fold will cause the nuclear envelope-associated chromatin to appear as a linear aggregate or longitudinal groove. Intranuclear cytoplasmic inclusions are particularly characteristic of papillary thyroid carcinoma, but may also be seen in medullary thyroid carcinoma. This intranuclear cytoplasmic inclusion appears as a sharp demarcation which comes from the nuclear envelope-associated heterochromatin, giving it a distinct dark purple border with the cytoplasm. Intranuclear cytoplasmic inclusions are very uncommon in follicular neoplasms [2].
In contrast to papillary thyroid carcinoma, follicular neoplasms tend to show compact aggregates of heterochromatin. As a rough way of distinguishing the papillary carcinoma nuclei from follicular carcinoma nuclei, we have found it useful to note that papillary thyroid carcinomas tend to show more linear aggregates of chromatin (representing very shallow folds of the nuclear envelope) compared to rounded or clumped aggregates of chromatin. These features are illustrated below.
Finally, cell blocks provide a stable platform for immunohistochemistry. Immunohistochemistry for calcitonin is recommended for confirming medullary thyroid carcinoma [1]. Immunohistochemical distinction of papillary thyroid carcinoma from follicular neoplasms has not been widely successful [12]. In general, it appears that when cells develop papillary thyroid carcinoma-like nuclear changes, the cells will show markers of papillary thyroid carcinoma, including cytokeratin 19 and HBME positive staining [13, 14]. The distinction between papillary thyroid carcinoma and reactive changes in such cases is determined by the larger-scale architectural features that are sometimes evident in cell blocks. The future development of markers that can distinguish the diagnostic categories of follicular lesions on FNA will likely require a stable platform for immunohistochemistry or molecular studies. Paraffin-embedded cell blocks provide such a platform. We illustrate one novel application of CD34 immunostaining that suggested the specific diagnosis of an insular-type of poorly differentiated thyroid carcinoma.
for an enlarged view.
Hyperplastic/Adenomatoid Nodule
Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, ThinPrep®.
Macrofollicular groups are arranged in a flat, two-dimensional sheet. Note the round shape and regular, wide spacing of nuclei. As a rough guide, if the nuclei all lie in the same plane over about 8-10 cell diameters (e.g., between the two arrows), the follicle is macrofollicular (see text).
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Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, ThinPrep®.
A macrofollicle with colloid measuring about 10 follicular cells in diameters is present at the left (arrows). A macrofollicular group (broad, flat, 2 dimensional) that has spilled its colloid is present in the upper right (open arrows).
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Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, Cell Block.
A macrofollicular group that has spilled its colloid will show a long linear arrangement of 8-10 follicular cells. Note the basal positioning and regular round shape of the nuclei that are features of benign follicular-type epithelium.
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Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, ThinPrep®.
It is sometimes difficult to characterize whether follicular groups are macro or microfollicular when the follicles are disrupted and clusters overlap in a monolayer preparation. The finding of hemosiderin in macrophages (arrow) in a follicular-type lesion favors a benign nodule.
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Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, Cell Block.
Rarely a macrofollicular group is sectioned parallel to the plane of the nuclei. The clue to the macrofollicular nature of such a group is to recognize the tangential sectioning that leaves only cytoplasm at the edges of the groups (arrows). This particular macrofollicular group shows nuclear overlapping, a feature that should prompt careful examination of the nuclei to rule out papillary thyroid carcinoma (see below).
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Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, ThinPrep®.
The corollary of large sized follicles is the presence of large pieces of colloid, and an increased proportion of colloid compared to follicular cells.
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Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, Cell Block.
Large pieces of colloid that were not deposited on the ThinPrep® slide from the above case are displayed in the cell block sections.
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Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, Cell Block.
Same magnification as Figure 6 shows large pieces of colloid that reflect the macrofollicular architecture of the follicular cells that produced the colloid. Note the linear strips of epithelium (arrow), representing macrofollicular groups.
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Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, Cell Block.
Note the abundant macrofollicular-sized colloid fragments and macrofollicular strips of follicular epithelium (arrow).
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Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, Cell Block.
The mostly large size of the follicles is readily apparent. Note the presence of hemosiderin in macrophages (arrow), a finding that also favors a benign nodule if the nuclear features of papillary thyroid carcinoma are not present (see text).
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Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, ThinPrep®.
The lower right side of the group appears macrofollicular, but the upper and left sides of this fragment could represent microfollicular groups (arrows) because the cells do not lie in a two-dimensional flat sheet. Hemosiderin in a macrophage is helpful in favoring a benign colloid nodule.
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Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, ThinPrep®.
Some definite microfollicular groups are present (arrows) in this same case shown in Figure 11. Note the macrophages with hemosiderin at the lower left.
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Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, Cell Block.
The cell block corresponding to Figures 11-12 shows a clear admixture of micro and macrofollicles. Two features favor a benign nodule. The first is that the microfollicles show a flattened cytoplasm compared to the more robust-appearing macrofollicular cells (compare the height of the cytoplasm at the two arrows). A second feature is the variation in the appearance of the colloid from follicle to follicle. Note the edematous colloid in one follicle adjacent to a follicle with dense colloid (open arrows). Benign hyperplastic/adenomatoid nodules are anticipated to show heterogeneity, while follicular neoplasms are more monotonous.
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Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, Cell Block.
Note the flattened cytoplasm in the microfollicles compared to the cuboidal to columnar cytoplasm of the macrofollicular epithelium at the upper left. Note also the watery colloid in one follicle (arrow) compared to the dense colloid in the microfollicles.
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Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, Cell Block.
Dense fibrous tissue (not actively desmoplastic) containing hemosiderin and markedly atrophic, flattened follicles are seen.
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Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, Cell Block.
Thin colloid at the lower left compared to the denser colloid in the microfollicles together with a flattened, atrophic appearance of the follicular cells in the microfollicles favor a benign hyperplastic/adenomatoid nodule.
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Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, Cell Block.
The tissue architecture evident here illustrates the variability in the cytoplasm between neighboring follicles, with the follicles marked with arrows showing varying degrees of Hürthle cell change compared to the unmarked follicles.
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Follicular neoplasm, Thyroid FNA, Cell Block.
The uniformity of the cytoplasm, the robust cuboidal epithelial cells, the microfollicular arrangement, the absence of hemosiderin, and the uniformity of the colloid favor a follicular neoplasm in this one field.
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Lymphocytic Thyroiditis
Cellular lesion, Cannot rule out follicular neoplasm (lymphocytic thyroiditis vs. Hürthle cell neoplasm), Thyroid FNA, ThinPrep®.
A microfollicular arrangement of Hürthle cells is seen. A few lymphocytes are admixed with the epithelium favoring lymphocytic thyroiditis.
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Benign, Lymphocytic thyroiditis, Thyroid FNA, Cell Block.
This image from the case shown in Figure 19 shows a dense lymphocytic infiltrate with adjacent flattened microfollicles showing Hürthle cell change.
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Benign, Lymphocytic thyroiditis, Thyroid FNA, Cell Block.
At higher magnification, the infiltration of the follicles with lymphocytes can be seen.
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Benign, Lymphocytic thyroiditis, Thyroid FNA, Cell Block.
A lymphoid germinal center is shown.
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Follicular Neoplasm
Cellular lesion, Cannot rule out follicular neoplasm (Hürthle cell neoplasm vs. Lymphocytic thyroiditis), Thyroid, ThinPrep®.
A microfollicular group of Hürthle cells with a few possible lymphocytes is present.
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Follicular neoplasm, Hürthle cell type, Thyroid FNA, Cell Block.
This image from the case in Figure 23 shows the uniformity of the Hürthle cell population which, together with the robust cuboidal cytoplasm in microfollicles, favors a Hürthle cell neoplasm.
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Follicular neoplasm, Hürthle cell type, Thyroid FNA, Cell Block.
The extent of the Hürthle cell change is too broad to be a reaction to any rare admixed lymphoid cells.
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Follicular neoplasm, Hürthle cell type, Thyroid FNA, ThinPrep®.
This case shows a uniform microfollicular arrangement of robust-appearing Hürthle cells without lymphocytes.
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Follicular neoplasm, Hürthle cell type, Thyroid FNA, ThinPrep®.
This crowded group consists of relatively uniform cells with dense, granular cytoplasm.
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Follicular neoplasm, Hürthle cell type, Thyroid FNA, Cell Block.
This image from the same case in Figures 26-27 shows uniform Hürthle cell change, microfollicular arrangement and absence of lymphocytes.
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Follicular neoplasm, Hürthle cell type, Thyroid FNA, Cell Block.
Another area shows larger-sized fragment with a monotonous population spanning several hundred microns and favors the diagnosis of a neoplasm.
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Follicular neoplasm, Hürthle cell type, Thyroid FNA, Cell Block.
Higher magnification shows the round nuclei and distinct chromatin particles of the Hürthle cells.
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Follicular neoplasm, Thyroid FNA, ThinPrep®.
This low power view shows three groups with uniform microfollicles.
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Follicular neoplasm, Thyroid FNA, Cell Block.
This image from the case in Figure 31. Macrofollicles are seen, but no cystic change is present and the intervening abundant microfollicles are uniform.
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Follicular neoplasm, Thyroid FNA, Cell Block.
A higher magnification shows the robust cuboidal follicles and slightly atypical but monotonous population of cells forming microfollicles.
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Follicular neoplasm, Thyroid FNA, Cell Block.
The follicular cells have round nuclei with anisonucleosis and slightly coarse chromatin aggregates.
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Follicular neoplasm, Thyroid FNA, ThinPrep®.
Another case is shown, with uniform microfollicles.
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Follicular neoplasm, Thyroid FNA, ThinPrep®.
Higher power shows round nuclei with slightly coarse chromatin.
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Follicular neoplasm, Thyroid FNA, Cell Block.
A microbiopsy fragment from the same case in Figures 35-36 shows a monotonous microfollicular growth pattern. No hemosiderin or cystic degeneration is apparent.
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Follicular neoplasm, Thyroid FNA, Cell Block.
Note the robust cuboidal cells that form monotonous microfollicles. No colloid is evident.
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Follicular neoplasm, Thyroid FNA, Cell Block.
At higher magnification, the round, regular nuclei with slightly coarse chromatin aggregates are seen.
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Follicular neoplasm, Thyroid FNA, ThinPrep®.
A different case from the preceding shows a monotonous population of follicular cells with a microfollicular arrangement and no hemosiderin.
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Follicular neoplasm, Thyroid FNA, ThinPrep®.
Small, uniform, dense colloid fragments are contained in the microfollicular groups, and the follicular cells have similar morphology from group to group.
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Follicular neoplasm, Thyroid FNA, ThinPrep®.
The nuclei of these follicular cells do not show features of papillary thyroid carcinoma. The nuclei are round, and chromatin is arranged in frequent non-linear aggregates.
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Follicular neoplasm, Thyroid FNA, Cell Block.
This image from the case in Figures 40-42 shows a monotonous population with a microfollicular growth pattern, without hemosiderin or cystic change.
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Follicular neoplasm, Thyroid FNA, Cell Block.
Nuclei are round and uniform, with coarse chromatin. An ominous feature is the back-to-back, solid arrangement of the follicular cells, without an intervening basement membrane.
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Follicular neoplasm, Thyroid FNA, Cell Block.
Our unpublished observations suggest that the back to back growth pattern, reminiscent of cribriform ductal carcinoma in situ, is suggestive of the insular type of poorly differentiated thyroid carcinoma. Indeed, the resection of this specimen showed insular carcinoma with widespread angio-invasion.
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Follicular neoplasm, Thyroid FNA, Cell Block.
A detached cluster of small blood vessels is staining positive for CD34 at the upper left. Note the absence of staining within the back-to-back group of follicular cells (arrow). The large-scale back-to-back growth without an intervening basement membrane/capillary network is essentially the diagnostic insular pattern recognized by surgical pathologists.
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Follicular neoplasm, Thyroid FNA, ThinPrep®.
A solid-appearing growth pattern is seen without colloid.
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Follicular neoplasm, Thyroid FNA, ThinPrep®.
Another similar «clonal-appearing» cluster, with similar nuclear and cytoplasmic features is seen.
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Follicular neoplasm, Thyroid FNA, Cell Block.
This image from the case in Figures 47-48 shows a relatively cohesive, uniform, clonal-appearing population with microfollicular architecture, consistent with a neoplasm.
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Follicular neoplasm, Thyroid FNA, Cell Block.
The nuclei show focal chromatin clearing (arrow). This process is clearly neoplastic, but could it be follicular variant of papillary thyroid carcinoma?
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Follicular neoplasm, Thyroid FNA, Cell Block.
While most of the nuclei are round and show some coarse chromatin aggregates, a few thin nuclear grooves are present and some of the nuclei show fine chromatin (open arrow).
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Follicular neoplasm, Thyroid FNA, Cell Block.
An immunostain for cytokeratin 19 is negative. While there are no definitive markers of papillary thyroid carcinoma, an absence of cytokeratin 19 is somewhat helpful in excluding papillary thyroid carcinoma. Reactive changes that can resemble papillary thyroid carcinoma are often positive for cytokeratin 19, so positive staining has to be interpreted carefully.
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Follicular neoplasm, Thyroid FNA, Cell Block.
A positive thyroglobulin stain can be helpful to exclude medullary thyroid carcinoma in a case that shows no evident colloid.
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Papillary Thyroid Carcinoma
Suspicious for follicular variant of papillary thyroid carcinoma, Thyroid FNA, ThinPrep®.
Multiple small dense colloid fragments are seen consistent with microfollicular architecture. At the edges of the fragment, nuclei show open chromatin, and slight irregularity in shape (arrow).
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Suspicious for Follicular variant of papillary thyroid carcinoma, Thyroid FNA, ThinPrep®.
Compared to the follicular neoplasms shown in previous figures, the chromatin is less coarse in this microfollicular group, and slight anisonucleosis is present.
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Suspicious for Follicular variant of papillary thyroid carcinoma, Thyroid FNA, ThinPrep®.
Pronounced nuclear envelope irregularity is present (arrow).
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Suspicious for Follicular variant of papillary thyroid carcinoma, Thyroid FNA, Cell Block.
Low magnification of the case in Figures 54-56 shows numerous clonal-appearing fragments with a predominantly microfollicular architecture.
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Suspicious for Follicular variant of papillary thyroid carcinoma, Thyroid FNA, Cell Block.
Two of the follicles at this magnification appear to be macrofollicular (at least 10 follicular cell diameters). No papillary structures are evident. Papillary thyroid carcinomas do not need to show papillary architecture and they can be macrofollicular. The defining feature of papillary thyroid carcinoma lies in the nuclear morphology, requiring higher magnification.
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Suspicious for Follicular variant of papillary thyroid carcinoma, Thyroid FNA, Cell Block.
Very fine chromatin and slight nuclear envelope irregularity is present, suspicious for follicular variant of papillary thyroid carcinoma. Note how fine linear arrays of chromatin (nuclei marked with arrows) are more easily seen than rounded aggregates of chromatin. The linear arrays represent very shallow nuclear envelope folds.
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Suspicious for Follicular variant of papillary thyroid carcinoma, Thyroid FNA, Cell Block.
The dividing line between follicular-type and papillary-type epithelium is not yet well-defined. Histolologic sections of thyroid FNAs provide a common platform for surgical pathologists and cytopathologists to define criteria. The resection from this case was diagnosed as follicular variant of papillary thyroid carcinoma.
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Suspicious for papillary thyroid carcinoma, Thyroid FNA, ThinPrep®.
A cluster with a microfollicular architecture and dense colloid shows nuclei with fine chromatin, ovoid shape, and occasional grooves. Hemosiderin is present, a finding that favors papillary thyroid carcinoma over a follicular-type neoplasm.
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Suspicious for papillary thyroid carcinoma, Thyroid FNA, Cell Block.
This high power image from the same case as Figure 61 shows similar features. Note the fine chromatin arranged in thin lines representing shallow folds of the nuclear envelope.
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Suspicious for papillary thyroid carcinoma, Thyroid FNA, Cell Block.
A cytokeratin 19 stain is positive, strongly supporting the suspicion of papillary thyroid carcinoma.
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Papillary thyroid carcinoma, Thyroid FNA, ThinPrep®.
A sharply defined intranuclear cytoplasmic inclusion (arrow), very fine chromatin texture, irregular nuclear contours, and ovoid nuclei are characteristic. Note the broad flat 2 dimensional sheet, indicative of a macrofollicular architecture which is common in papillary thyroid carcinomas.
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Papillary thyroid carcinoma, Thyroid FNA, Cell Block.
The presence of abundant colloid does not exclude papillary thyroid carcinoma.
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Papillary thyroid carcinoma, Thyroid FNA, Cell Block.
The long strip on the right side is a macrofollicular grouping similar to that shown in Figure 64. Note the fine chromatin and nuclear envelope irregularity.
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Papillary thyroid carcinoma, Thyroid FNA, Cell Block.
A sharply demarcated intranuclear cytoplasmic inclusion (arrow), fine chromatin texture, and nuclear envelope irregularity are the most important features for diagnosing papillary thyroid carcinoma.
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Papillary thyroid carcinoma, Thyroid FNA, Cell Block.
Papillary structures may be present in both papillary thyroid carcinomas and benign hyperplastic nodules. The crowding of the nuclei is suggestive of papillary thyroid carcinoma.
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Papillary thyroid carcinoma, Thyroid FNA, Cell Block.
A higher magnification of Figure 68 shows diagnostic features consisting of crowded nuclei with nuclear grooves, very fine chromatin, a rare intranuclear cytoplasmic inclusion (open arrow), and a subtle loss of polarity in areas.
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Benign, Hyperplastic/adenomatoid nodule, Thyroid FNA, Cell Block.
Papillary structures without the nuclear features of papillary thyroid carcinoma strongly favor a benign nodule. Compared to papillary thyroid carcinoma, the nuclei are round, evenly spaced, and have a uniform amount of apical cytoplasm. [6]
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Papillary thyroid carcinoma, Thyroid FNA, ThinPrep®.
Note the abnormal polarity of the nuclei (arrow) that also exhibit nuclear grooves, and fine chromatin.
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Papillary thyroid carcinoma, Thyroid FNA, Cell Block.
Abnormal nuclear polarity in two adjacent cells (arrows) is seen in a papillary fragment, similar to that in Figure 71.
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Papillary thyroid carcinoma, Thyroid FNA, Cell Block.
Bluish calcified psammoma bodies are highly suggestive of papillary thyroid carcinoma but are not sufficient for a diagnosis.
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Papillary thyroid carcinoma, Thyroid FNA, Cell Block.
Open chromatin, rare nuclear grooves, and subtle abnormal nuclear polarity are present. Note the cystic background – a common feature in papillary thyroid carcinoma.
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Papillary thyroid carcinoma, Thyroid FNA, ThinPrep®.
Uniform empty-appearing cytoplasmic vacuoles are sometimes seen in papillary thyroid carcinomas. Typical nuclear features of papillary thyroid carcinoma are present, with a prominent intranuclear inclusion (arrow).
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Papillary thyroid carcinoma, Thyroid FNA, ThinPrep®.
The vacuolated cytoplasm can sometimes give the papillary thyroid carcinoma cells a histiocytoid appearance.
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Papillary thyroid carcinoma, Thyroid FNA, Cell Block.
Histiocytoid carcinoma cells with uniform empty cytoplasmic vacuoles similar to those in Figure 76 are shown.
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Papillary thyroid carcinoma, Thyroid FNA, ThinPrep®.
Squamous metaplasia is another common cytoplasmic change in papillary thyroid carcinoma.
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Papillary thyroid carcinoma, Thyroid FNA, Cell Block.
This group from the same case in Figure 78 shows similar, prominent squamous metaplasia.
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Medullary Carcinoma
Medullary thyroid carcinoma, Thyroid FNA, ThinPrep®.
Mildly pleomorphic cells with eccentric nuclei are present with translucent, dense fragments of amyloid.
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Medullary thyroid carcinoma, Thyroid FNA, ThinPrep®.
Slightly coarse chromatin, eccentric nuclei, and slight cell-to-cell variation in the nuclear morphology is present.
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Medullary thyroid carcinoma, Thyroid FNA, ThinPrep®.
Typical coarse «salt and pepper» chromatin is present.
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Medullary thyroid carcinoma, Thyroid FNA, Cell Block.
A solid growth pattern is present with a fragment of amyloid. Note the eccentric nuclei with a plasmacytoid appearance, and slight nuclear variability.
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Medullary thyroid carcinoma, Thyroid FNA, Cell Block.
Small aggregates of amyloid are present in a mildly pleomorphic population.
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Medullary thyroid carcinoma, Thyroid FNA, Cell Block.
«Salt and pepper» chromatin similar to Figure 82 is shown.
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Medullary thyroid carcinoma, Thyroid FNA, Cell Block.
This congo-red stain performed on the case shown in Figures 80-85 highlights a fragment of amyloid.
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Medullary thyroid carcinoma, Thyroid FNA, Cell Block.
Under polarized light, the congo red-stained amyloid shows the characteristic greenish birefringence.
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Medullary thyroid carcinoma, Thyroid FNA, Cell Block.
These groups from the case in Figures 80-86 stain positive for calcitonin.
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Medullary thyroid carcinoma, Thyroid FNA, Cell Block.
Synaptophysin immunoreactivity is also present in medullary thyroid carcinoma.
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Medullary thyroid carcinoma, Thyroid FNA, ThinPrep®.
A different case from the previous case shows a slightly more pleomorphic population that varies from plasmacytoid to focally spindled.
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Medullary thyroid carcinoma, Thyroid FNA, ThinPrep®.
An intranuclear cytoplasmic inclusion is present in one of the cells of this mildly pleomorphic population.
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Medullary thyroid carcinoma, Thyroid FNA, ThinPrep®.
Spindle shaped tumor cells are also present.
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Medullary thyroid carcinoma, Thyroid FNA, Cell Block.
This same case as Figures 90-92 shows a strong positive immunostain for calcitonin.
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References
- Papanicolaou SoC. Working group recommendations for thyroid fine needle aspiration. http://www.papsociety.org/guidelines.html 2006.
- DeMay RM. The Art and Science of Cytopathology. Chicago: American Society of Clinical Pathologists Press, 1996:1208.
- Baloch ZW, Livolsi VA. Follicular-patterned lesions of the thyroid: the bane of the pathologist. American Journal of Clinical Pathology 2002; 117:143-50.
- Boey J, Hsu C, Collins RJ, Wong J. A prospective controlled study of fine-needle aspiration and Tru-cut needle biopsy of dominant thyroid nodules. World Journal of Surgery 1984; 8:458-65.
- Nishiyama RH, Bigos ST, Goldfarb WB, Flynn SD, Taxiarchis LN. The efficacy of simultaneous fine-needle aspiration and large-needle biopsy of the thyroid gland. Surgery 1986; 100:1133-7.
- Kung IT, Yuen RW. Fine needle aspiration of the thyroid. Distinction between colloid nodules and follicular neoplasms using cell blocks and 21-gauge needles. Acta Cytologica 1989; 33:53-60.
- Kung IT. Distinction between colloid nodules and follicular neoplasms of the thyroid. Further observations on cell blocks. Acta Cytologica 1990; 34:345-51.
- Kern WH, Haber H. Fine needle aspiration minibiopsies. Acta Cytologica 1986; 30:403-8.
- Renshaw AA, Wang E, Wilbur D, et al. Interobserver agreement on microfollicles in thyroid fine-needle aspirates. Archives of Pathology & Laboratory Medicine 2006; 130:148-52.
- Fischer AH, Young KA, DeLellis RA. Incorporating the criteria of malignancy into the evolutionary framework for cancer. J Cellular Biochemistry 2004; 93:28-36.
- Fischer AH, Taysavang P, Weber C, Wilson K. Nuclear envelope organization in papillary thyroid carcinoma. Histology and Histopathology 2001; 16:1-14.
- Rezk S, Khan A. Role of immunohistochemistry in the diagnosis and progression of follicular epithelium-derived thyroid carcinoma. Applied Immunohistochemistry & Molecular Morphology 2005; 13:256-64.
- Prasad ML, Huang Y, Pellegata NS, de la Chapelle A, Kloos RT. Hashimoto’s thyroiditis with papillary thyroid carcinoma (PTC)-like nuclear alterations express molecular markers of PTC. Histopathology 2004; 45:39-46.
- Prasad ML, Pellegata NS, Huang Y, Nagaraja HN, de la Chapelle A, Kloos RT. Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Modern Pathology 2005; 18:48-57.