Miyoko Higuchi

Cytological characteristics of papillary thyroid carcinoma on LBC specimens, compared with conventional specimens

The cytological findings in conventional specimens (C‐S) and liquid‐based cytology specimens (LBC‐S) are not quite same. The aim of this article is to clarify the cytological findings of papillary thyroid carcinoma (PTC) characteristic of LBC‐S.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a single-institutional experience in Japan

Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC) was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). To date, no studies on NIFTP have been reported in Japan. This study aimed to evaluate the clinical, cytological, and pathological findings of 54 cases of NIFTP from a single center in Japan, and compare them with those in the western countries. There were no significant differences in age, sex, or tumor size between patients with NIFTP and those with invasive encapsulated follicular variant -PTC. Ultrasound investigation showed a high suspicion lesion in 6.5% of NIFTP and 44.1% of invasive encapsulated follicular variant -PTC (p<0.001). On fine needle aspiration cytology, 75.7% of NIFTP cases were reported as suspicious for malignancy or malignant. Nuclear grooves and irregular-shaped nuclei were observed in 94.6% of cases of NIFTP. Pathologically, 27.8% cases of NIFTP and 13.0% cases of invasive encapsulated follicular variant -PTC had been originally diagnosed as macrofollicular variants of PTC. There were no NIFTP cases with nodal metastasis. We concluded that NIFTP should be renounced noninvasive encapsulated follicular variant -PTC, and should be considered as a malignant tumor with exceeding indolent behavior, and lobectomy alone should be satisfactory for the diagnosis and treatment.

Diagnostic significance of PAX8 in thyroid squamous cell carcinoma

Most types of thyroid carcinomas express PAX8 transcription factor; however, whether thyroid squamous cell carcinoma (SCC) also expresses PAX8, currently remains unknown. We herein examined the immunoreactivity of PAX8 in SCC of thyroidal and extrathyroidal origin, and discussed the diagnostic significance of PAX8. We immunohistochemically examined specimens from 11 SCC, 22 papillary thyroid carcinoma (PTC), 8 anaplastic thyroid carcinoma (ATC), and 2 mucoepidermoid carcinoma (MEC) cases as well as 5 uterine cervical SCC, 5 esophageal SCC, and 5 pulmonary SCC cases. The rates of PAX8-positive SCC, PTC, ATC, and MEC were 90.9%, 90.9%, 75.0%, and 100%, respectively. Two PAX8-negative PTC cases were cribriform variants. No uterine cervical, esophageal, or pulmonary SCC specimen reacted with PAX8 antibody. Thyroid transcription factor-1 (TTF-1) was positive in 9.1% and 95.5% of SCC and PTC cases, respectively, but negative in all ATC and MEC cases. These results demonstrate that PAX8 staining is useful for distinguishing between primary thyroid SCC and invasion or metastasis from extrathyroidal SCC. We recommend using an immunohistochemical panel of antibodies to PAX8 and TTF-1 to confirm a diagnosis of primary thyroid carcinoma.

Cytologic findings and differential diagnoses of primary thyroid MALT lymphoma with striking plasma cell differentiation and amyloid deposition.

We report two cases of thyroid mucosa‐associated lymphoid tissue (MALT) lymphoma with associated amyloid protein deposition. While other primary thyroid neoplasms sush as medullary carcinoma and plasmacytoma with associated amyloid protein are known to occur and have been previously described by fine‐needle aspiration cytology (FNAC), to our knowledge, the current cases are the first of thyroid MALT lymphoma with amyloid deposition to be detailed in the cytopathology literature. Case 1 was a 73‐year‐old female with chronic thyroiditis. FNAC suspected MALT lymphoma. The amyloid material was not noticed, nevertheless it existed. Case 2 was a 71‐year‐old female with a nodule of the thyroid. Malignant lymphoma and medullary carcinoma were suspected by FNAC. The possibility of medullary carcinoma was excluded by a measurement of serum calcitonin and carcinoembryonic antigen. After follow‐up for two years, the nodule was diagnosed as MALT lymphoma associated with plasma cell differentiation and amyloidosis by the fourth FNAC. When we encounter small round cell tumors associated with amyloid in thyroid FNAC, we should consider not only medullary carcinoma but also MALT lymphoma. Diagn. Cytopathol. 2014;42:73–77.

Reappraisal of “cyst fluid only” on thyroid fine-needle aspiration cytology

According to the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), cyst fluid only (CFO) cases are classified in the non-diagnostic category. To date, no large study focusing on CFO has been conducted. To reassess the diagnostic significance of CFO, we compared CFO nodules with non-diagnostic nodules excluding CFO (ND-other). We reviewed the conventional thyroid smears of 715 CFO and 766 ND-other nodules. We compared the timing of and findings at re-aspiration, the histology of resected specimens, and the proportion of malignant nodules between the two groups. Re-aspiration was performed in 9.0% of CFO and 23.8% of ND-other cases. In 12.5% of CFO and 49.4% of ND-other cases, the interval between the first and second aspirations was <3 months. Despite this, there were no cases in which cytological interpretation was complicated by the first aspiration. Overall, 77 CFO nodules (10.8%) were surgically resected; 14 were malignant. In all cases in which re-aspiration cytology revealed malignancy, the initial ultrasound interpretation was a high or intermediate suspicion pattern. The proportion of malignancies subsequently diagnosed in nodules initially classified as CFO and ND-other was 2.0% and 5.6%, respectively (p<0.01). As CFO and ND-other thyroid nodules have different clinical management and malignancy rates, we would like to assert that CFO and ND-other nodules should be separated, and that the former should be considered diagnostic. In terms of clinical management, we recommend that only CFO cases with concerning features on ultrasound undergo re-aspiration.

Cytological Findings for the Diagnosis of Primary Thyroid Mucosa-Associated Lymphoid Tissue Lymphoma by Fine Needle Aspiration

Objective: We examined cytological findings for the diagnosis of primary thyroid mucosa-associated lymphoid tissue (MALT) lymphoma by fine needle aspiration. Study Design: During the study period of 4 years, a total of 101 cases including 51 MALT lymphomas, 20 Hashimotos thyroiditis (HT), and 30 diffuse large-cell B-cell lymphomas were cytologically examined. MALT lymphomas were divided into 44 common MALT and 7 MALT lymphomas with extreme plasmacytic differentiation (MALT-EPCD). Results: (1) Small- to medium-sized cells displaying irregularly shaped nuclei with prominent nucleoli (ISN-PN) were neoplastic cells. (2) In the case of a frequency of plasma cells (PC) below 15%, the accuracy rate for distinguishing common MALT from HT was 97% for ISN-PN cell frequencies above 20% in combination with the presence of lymphoepithelial lesion clusters (LELC) and mountain range-like clusters (MRLC). The frequency of large-sized cells was below 15% in common MALT. (3) In the case of a frequency of PC above 15%, cases with a sum of PC and ISN-PN cells above 30% were MALT-EPCD. (4) MRLC were cell clusters derived from regions of follicular colonization, and LELC were cell clusters from lymphoepithelial lesions of MALT lymphomas. Conclusion: Useful cytological criteria for the diagnosis of thyroid primary MALT lymphoma, such as neoplastic cells and cell clusters, were defined.

Diagnostic value of GATA-3 in cytological identification of parathyroid tissues

Parathyroid and thyroid lesions appear morphologically similar in cytological smears, and their differentiation can be difficult. The purpose of this study was to determine the diagnostic value of T-cell-specific transcription factor GATA-3 as a marker of parathyroid differentiation in cytology specimens, and to examine the utility of liquid-based cytology (LBC). Cytology smears obtained from surgically removed parathyroid and thyroid specimens, including 15 normal parathyroid glands, 12 cases of parathyroid hyperplasia, 55 parathyroid adenomas, 2 follicular thyroid adenomas, and 3 papillary thyroid carcinomas, were examined by immunocytochemistry using antibodies against GATA-3, parathyroid hormone (PTH), chromogranin A, and thyroid transcription factor 1 (TTF-1). All normal and hyperplastic parathyroids and 98.2% of parathyroid adenomas were positive for GATA-3, while 33.3%, 66.7%, and 60.0% of them, respectively, were positive for PTH. The positive rates for chromogranin A among normal parathyroids (80.0%) and parathyroid adenomas (87.3%) were lower than those for GATA-3. At the same time, all thyroid-derived tumours were positive for TTF-1 and negative for GATA-3, PTH, and chromogranin A. LBC smears of 35 parathyroid lesions indicated that the positive rates for GATA-3, PTH, and chromogranin A were 97.1 %, 97.1%, and 100%, respectively, while in conventional smears, those for PTH (25.5%) and chromogranin A (78.7%) were significantly lower (p < 0.01). Our results suggest that GATA-3 is a more reliable biomarker than PTH or chromogranin A in differentiating parathyroid from thyroid lesions in cytology smears and that LBC is useful in detecting cytoplasmic antigens such as PTH and chromogranin A.

Differentiating between benign follicular nodules and follicular neoplasms in thyroid liquid-based cytology preparations

The cytological morphology observed in liquid‐based cytology (LBC) preparations is dissimilar to that of conventional preparations. The aim of this report is to clarify the cytological differences between benign follicular nodules (BFNs) and follicular neoplasms (FNs) in LBC preparations and identify novel diagnostic criteria for LBC preparations.

Stromal tiny black dots, like “sugar-coated”, of von Kossa stain is a diagnostic clue to hyalinizing trabecular tumor of the thyroid gland: Kossa-positive dots of thyroid HTT

Hyalinizing trabecular tumor (HTT) is a rare low‐grade tumor, and a prominent feature is the basement membranous stroma. We assume that such characteristic stromal findings of HTT are related to calcium deposition, and examined HTT samples by von Kossa special staining. There has been no report describing von Kossa special staining for such stroma. We collected 12 cases of HTT and 30 cases of papillary thyroid carcinoma (PTC) that had matched age, gender, tumor size, and surgical procedure characteristics as a control group. We compared the staining pattern and degree of von Kossa positivity between HTT and PTC, and a grading system of von Kossa stain was adopted to highlight differences between them. On von Kossa staining, all HTT revealed many tiny black dots around vessels in the hyalinized stroma, like “sugar‐coated”, and a high degree of calcium deposition in most cases, whereas PTC showed sparse stromal calcification in some cases. The degree of von Kossa staining was significantly different between the two groups. This is the first report describing abundant tiny black dots, like a “sugar‐coated” appearance, of von Kossa stain in HTT. Here, we propose this finding can be a useful diagnostic clue to HTT.

Derivation of thyroid lymphoepithelial cysts from follicular cells

The pathogenesis of thyroid lymphoepithelial cysts is controversial, and two hypotheses have been proposed, namely derivation from branchial-derived remnants or from squamous metaplasia of the follicular cells. The aim of this study was to clarify the pathogenesis of thyroid lymphoepithelial cysts. We performed pathological and immunohistochemical examination of 21 thyroid lymphoepithelial cysts, 13 non-neoplastic squamous metaplasia samples without thyroid carcinoma, 13 solid cell nests, and 14 lateral cervical cysts. On ultrasound, half of thyroid lymphoepithelial cysts were interpreted as calcified nodules regardless of no calcification. Thyroid lymphoepithelial cysts and squamous metaplasia tended to be located in the central and lower portions of the thyroid, while solid cell nests were located in the upper and central portions (p < 0.05). In 95.2% of patients with thyroid lymphoepithelial cysts and all patients with squamous metaplasia, lesions were histologically associated with chronic thyroiditis forming lymph follicles. Hashimotos disease was serologically confirmed in 18 patients with lymphoepithelial cysts (85.7%) and 10 patients with squamous metaplasia (76.9%). Immunohistochemically, lymphoepithelial cysts showed nuclear positivity for PAX8, thyroid transcription factor 1, and p63. One lateral cervical cyst (7.1%) showed positive staining for PAX8, while solid cell nests were PAX8-negative. In three (14.3%) cases of thyroid lymphoepithelial cysts, squamous cells located on the superficial layer were focally and weakly positive for CEA. We concluded that thyroid lymphoepithelial cysts originate from follicular cells and are unrelated to solid cell nests and lateral cervical cysts arising from branchial-derived remnants.