Fine-needle aspiration study of cystic papillary thyroid carcinoma: Rare cytological findings.

BACKGROUND: Cystic papillary thyroid carcinoma (CPTC) is a variant of papillary carcinoma that has many mimickers in cytological grounds. AIM: To study the cytomorphologic features of CPTC and compare them to those of other cystic thyroid lesions using fine-needle aspiration cytology (FNAC). We also aimed to identify the cytomorphologic features that distinguish CPTC from other cystic thyroid lesions.
MATERIALS AND METHODS: Seventy-three cases of CPTC were included in the study. The cytomorphologic features of these cases were analyzed. The FNA smears of other thyroid lesions with cystic changes (300 colloid goiters, 290 adenomatoid nodules, 11 follicular neoplasms, and 9 hurtle cell neoplasm) were also studied.
RESULTS: The smears in CPTC revealed isolated follicular cells, small groups of cells with scalloped margins, cell swirls, small clusters with a cartwheel pattern, papillary clusters, intranuclear inclusions, nuclear grooves, sticky colloid, intracellular colloids, psammoma bodies, multinucleated giant cells, and foamy and hemosiderin laden macrophages. Small groups of cells with scalloped borders, cellular swirls, and small clusters with a cartwheel pattern were seen in CPTC, but not in other cystic lesions. Interestingly, mesothelial-like cells and hemophagocytic cells were seen in five and three cases of CPTC, respectively, but not in other cystic lesions.
CONCLUSION: Mesothelial-like cells and hemophagocytic cells were observed in five and three cases of CPTC, respectively. Similar finding have not been previously reported in the literature.

Introduction

Papillary carcinoma is the most common malignancy of the thyroid gland. It affects women more frequently than men. Morphologic variants of papillary thyroid carcinoma (PTC) have been described already, some of which have worse prognosis and more recurrence rate than conventional PTC. Interestingly, the first clinical presentation of the tumor may be a metastasis to a lymph node of the neck from a small occult primary tumor.[123]

Cystic change has been identified in many thyroid lesions including PTC but this change is far more common in nonneoplastic thyroid nodules than thyroid neoplasms.[2]

Fine-needle aspiration (FNA) has become a useful, safe, and accurate tool for diagnosis of thyroid lesions.[4] The cytological features of PTC and its variants have been previously described.[156789101112131415] The main purpose of this study was to describe the cytological features of CPTC and compare the findings with other thyroid lesions with cystic change.

Materials and Methods

A 30-year (1980-2013) retrospective review of the cytology slides from our cytology division of pathology department revealed a total of 750 PTCs. Out of these, 73 cases of CPTC, which were confirmed by histologic sections, were retrieved from the files: 55 females and 18 males, with an age range of 28-52 years. There was no pediatric case. The cyst sizes ranged between 2.8 cm and 3 cm. Aspiration was performed from the cysts tissue (42 cases under ultrasound guidance and the remaining without guidance). The cysts yielded 2-3 mL of the fluid that was hemorrhagic in 40 cases and clear yellow in color in the remaining cases. The smears were prepared from the sediment of cytocentrifuged specimens. The air-dried smears were stained with the Wright–Giemsa stain, and alcohol-fixed smears were stained with Papanicolaou stain. Some selected cases were subjected to immunocytochemistry for thyroid transcription factor-1 (TTF-1, Dako, clone 8G7G3/1, Denmark), cytokeratin 19 (CK 19) (Dako, Clone RCK108, Denmark), and cluster of differentiation 68 (CD68) (Dako, clone KP1, Denmark).

The FNA smears of other cystic thyroid lesions were retrieved from the files for the comparative study. These cases included 300 colloid goiters, 290 adenomatoid nodules, 11 follicular neoplasms, and 9 hurtle cell neoplasms.

Medical ethics committee of our university approved the study.

Results

The main cytologic findings of 73 cases of CPTC were as follows: Isolated plasmacytoid cells (71, 97% cases) (which showed deep basophilic dense cytoplasm and dusty chromatin), and some of them showed cytoplasmic vacuolization; signet-ring formation (65 cases, 89%); cytoplasmic blebs (pseudopods); intranuclear cytoplasmic inclusions (42 cases, 57%); and nuclear grooves (46 cases, 63%) [Figure 1a and b]. Small groups of 5-10 cells with scalloped (well-defined) margins and distinct cell borders were frequently seen (72 cases, 98%). Small and large papillary clusters with infiltrative borders were seen after searching many fields in all cases. Some of them showed central cores of hyaline material, nuclear inclusion, and grooves. Small clusters with a radial distribution of cells (cartwheel pattern) were readily observed (61 cases, 83%). Small ball-like cellular clusters with a concentric arrangement of cells (cellular swirls) were also observed in 58 (70%) cases.

Figure 1

Isolated plasmacytoid cell with dense cytoplasm and dusty chromatin. (Wright-Giemsa, ×1000)

Sticky (wispy) colloids (31 cases, 42%) and intracellular colloids (32 cases, 43%) were observed, but colloid balls were not noted. Anisonucleosis (69 cases, 94%), multinucleated giant cells (39 cases, 53%), hemosiderin-laden macrophages (73 cases, 100%), spindle cells (31 cases, 42%), and squamoid cells (30 cases, 41%) were also observed. Atypical follicular cells with mesothelial-like features, such as cytoplasmic blebs (pseudopods) and flat borders or windows (i.e. the cells separated by narrow slit-like spaces), were also seen in five cases [Figure 2a–c].

Figure 2

(a and b) Isolated mesothelial-like cell with cytoplasmic blebs and nuclear groove and pseudo-inclusion. (Wright-Giemsa, ×1000) (c) Mesothelial-like cells separated by narrow slit-like space (window). (Wright-Giemsa, ×1000)

Three cases of CPTC were associated with Hashimoto's thyroiditis and showed erythro- and lymphophagocytosis (follicular cells engulfing mature RBC and lymphocytes). These cells also showed nuclear grooves and inclusions. TTF-1, CK19 immunostaining of these cases, and negativity for CD 68 also showed the follicular epithelial origin of these cells [Figure 3a–c].

Figure 3

(a) Histiocytoid follicular cells show engulfed lymphocytes (lymphophagocytosis). (Wright-Giemsa, ×400). (b) Neoplastic follicular cell with intranuclear inclusion shows engulfed lymphocyte and cytoplasmic vacuole. (Wright-Giemsa, ×1000). (c) Immunoreactivity for TTF-1 of hemophagocytosis of neoplastic follicular cells. (TTF- IHC, ×400)

Figure 4a and b shows corresponding histologic sections of a CPTC.

Figure 4

(a and b) Histologic sections of a case of CPTC with papillary configuration facing a cystic space with optically clear nuclei. (a: H and E, ×250; b: H and E, ×400)

The comparative cytological study results of CPTC with other cystic thyroid lesions are shown in Table 1.

Table 1

Comparative study of cytomorphologic findings in cystic thyroid lesions

Discussion

Thyroid cystic lesions can be caused by neoplastic and nonneoplastic conditions. Adenomatoid (nodular) colloid goiter is the most common cause of a nonneoplastic cystic lesion of the thyroid gland.[2]

It is estimated that about 23% of the thyroid cystic lesions are proved to be malignant.[1]

Among the neoplasms, papillary carcinoma causes cystic changes more frequently than other thyroid neoplasms. The FNA diagnosis of cystic thyroid lesions is very difficult due to low cellularity, presence of nuclear debris, and many hemosiderin-laden macrophages. In FNA smears, the presence of histiocyte/macrophages is a surrogate marker for cystic degeneration but these cells may show nuclear atypia and prominent nucleoli mimicking thyroid malignancy, especially PTC.[1617] Moreover, the presence of squamous cells in benign cysts can lead to a misdiagnosis of a malignant tumor.[2]

On the other hand, follicular epithelial cells in CPTC may show histiocytic morphology;[16] therefore, differential diagnosis of histiocyte from histiocytoid PTC is of great importance. Careful screening of all smears and comprehensive knowledge of the cytologic findings of cystic thyroid lesions may improve the precision of the diagnoses and prevent false-negative and false-positive diagnoses.

Cystic change can be observed in colloid goiters, adenomatous nodules, and neoplasms. The cytological findings of these lesions have been described well in previously published papers and textbooks.[156789101112131415] With minimal effort, the cystic colloid goiter and other cystic neoplasms can be differentiated from CPTC. By contrast, the differentiation of CPTC from cystic adenomatoid nodules is very difficult because the two have many findings in common. Some findings of this study were common to all the cysts and were therefore not useful for differentiation, such as foamy macrophages, atypical histiocytes, spindle cells, squamous cells, anisonucleosis, multinucleated giant cells, and calcification. It has been stated that multinucleated giant cells in PTC are more irregular in shape and have more nuclei and dense cytoplasm, but these cells can be seen in inflammatory thyroiditis as well.[1] Isolated plasmacytoid cells were frequently observed in all cases of CPTC, but not in case of other cystic lesions, with the exception of cystic adenomatoid nodules. The isolated cells in CPTC showed characteristic dense cytoplasm and dusty chromatin, whereas the plasmacytoid cells in cystic adenomatoid nodules showed fine granular cytoplasm and smooth chromatin. Various forms of colloid material (colloid balls, bubble gum, and intracytoplasmic colloid) were frequently seen in adenomatoid nodules, colloid goiter, CPTC, and follicular neoplasms. However, the intracytoplasmic colloid was seen more frequently in CPTC than in other lesions. Nuclear grooves and inclusions were readily observed in a large number of cases of CPTC, but were only rarely seen in a few cases of adenomatoid nodules, follicular neoplasms, and hurtle cell neoplasm. Monolayer sheets and papillary clusters were noted in almost all cases, but the papillary clusters with central hyaline cores were seen only in CPTC. The most important findings of this study specific to CPTC were as follows: Small clusters with scalloped margins, cellular swirls, and clusters with a cartwheel pattern. These findings were not noticed in other cystic lesions and therefore were useful for the differentiation of CPTC from other cystic lesions. In this study, two interesting findings were noticed in CPTC, but not in other cysts:

Hemophagocytic cells were found in three cases, which were associated with Hashimoto's thyroiditis. It is probable that autoimmune mechanisms play a role in hemophagocytosis in CPTC. The immunocytochemical study revealed positive reaction with CK19, and TTF-1 and negative reaction with CD68. So, we believe that these cells are of follicular epithelial origin rather than macrophages.

Mesothelial-like cells with windows and cytoplasmic blebs were found in five cases.

Faquin et al.[2] stated that small cohesive sheets of epithelial cells with windows between cells may be seen in the cytology of benign thyroid cysts but the cells in CPTC are crowded and overlapping.

Conclusion

In conclusion, the cytologic differentiation of CPTC from cystic adenomatoid nodules was very difficult. Small clusters with scalloped margins, cellular swirls, and clusters with a cartwheel pattern were seen only in CPTC, which helped to differentiate CPTC from adenomatoid nodule. Mesothelial-like cells and hemophagocytic cells were seen in a few cases of CPTC.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.