Toshitetsu Hayashi

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.

Comparative histopathological analysis of sporadic pediatric papillary thyroid carcinoma from Japan and Ukraine

This study set out to compare structural and invasive characteristics of sporadic papillary thyroid carcinoma (PTC) in age-matched groups of children and adolescents of Japan and Ukraine to provide detailed histopathological analysis of tumors from different geographical areas with different iodine intake. A total of 348 (160 Japanese and 188 Ukrainian) PTCs from patients without radiation history were analyzed initially as a combined pediatric group and then subdivided into childhood (aged ≤14 years) and adolescent (aged from 15 to ≤18 years) age series. On multivariate comparison, the Japanese pediatric PTC was characterized by a higher sex ratio (p=1.504E-4), and a higher frequency of microcarcinoma (p=0.039), papillary dominant growth pattern (p=0.024), focal oxyphilic cell metaplasia (p=7.644E-6), intrathyroid spread (p=0.010), lymphatic/vascular invasion (p=0.01) and regional lymph node metastases (p=3.540E-6). In the Ukrainian group, multifocal (p=0.004) and non-encapsulated tumors with the solid-trabecular growth pattern (p=0.05) were more frequent. Childhood Japanese PTCs differed from Ukrainian PTCs by more pronounced invasive properties such as lymphatic/vascular invasion and nodal disease, but did not differ by the dominant growth pattern. In adolescents, the differences were detected not only for lymph node metastases, but also for a higher frequency of the papillary dominant pattern in Japanese PTC. Overall, significantly higher frequencies of oxyphilic cell metaplasia and more pronounced invasive features observed in the Japanese PTC in both age-matched series represent the major differences between the tumors from two geographical areas.

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.

Identification of Cytological Features Distinguishing Mucosa-Associated Lymphoid Tissue Lymphoma from Reactive Lymphoid Proliferation Using Thyroid Liquid-Based Cytology

Objective: To identify cytological differences between mucosa-associated lymphoid tissue lymphoma (MALT-L) and nonneoplastic lymphocytes using thyroid liquid-based cytology (LBC). Study Design: We observed LBC and conventional specimens from 35 MALT-L cases, 3 diffuse large B-cell cell lymphoma (DLBCL) cases, and 44 prominent nonneoplastic lymphocytic infiltration cases. Results: In MALT-L cases, the incidence of lymphoglandular bodies in the LBC specimens was lower than that in the conventional specimens (p < 0.001). Moreover, the nuclear sizes in LBC specimens were larger than those in conventional specimens. In 62.9% of the MALT-L and all DLBCL specimens, large nuclei were present in > 10% of the lymphoid cells in LBC specimens. Two cases with prominent nonneoplastic lymphocytic infiltration also exhibited these findings. In LBC specimens, swollen naked nuclei with less punctate chromatin patterns and thin nuclear margins were observed in 92.1% of lymphoma and 20.5% of prominent nonneoplastic lymphocytic infiltration. Elongated nuclei were significantly more apparent in thyroid lymphoma than in prominent nonneoplastic lymphocytic infiltration (p < 0.001), with a significantly higher incidence in LBC specimens than in conventional specimens (p < 0.001). Conclusions: Lymphoglandular bodies are not reliable markers for lymphoma diagnosis using LBC specimens. Large, swollen naked, and elongated nuclei are useful in distinguishing thyroid lymphoma from nonneoplastic lymphocytes in LBC specimens.

Cytoplasmic Lipid Accumulation Characteristic of the Cribriform Variant of Papillary Thyroid Carcinoma

Objective: The purpose of this study was to clarify the diagnostic significance of cytoplasmic lipid accumulation (CLIA) in the cribriform variant of papillary thyroid carcinoma (CV-PTC). Methods: We performed a histological, immunohistochemical, and cytological examination of 35 CV-PTC cases at the Kuma Hospital. CLIA was defined as bubble-like multivacuolation in cytoplasm with distinct cell border. We also examined 100 conventional PTC (con-PTC) cases as controls. Results: Histological analysis showed the presence of carcinoma cells with CLIA in 60.0% of CV-PTC and 5.0% of con-PTC cases. The vacuoles tended to distribute in the subnuclear portion of carcinoma cells showing papillary growth. They were positive for oil red O staining and adipophilin. The carcinoma cells without the vacuoles showed a subnuclear dot-like expression for adipophilin in CV-PTC cases, but not in the con-PTC cases. Cytological analysis showed CLIA in 17 (54.8%) of the 31 CV-PTC cases, but not in the con-PTC cases. Conclusion: This is the first study to report the presence of carcinoma cells with CLIA in CV-PTC. The subnuclear dot-like expression of adipophilin may be characteristic of CV-PTC. These findings might be related to degenerative changes occurring in CV-PTC.

Papillary thyroid carcinoma with desmoid-type fibromatosis: A clinical, pathological, and immunohistochemical study of 14 cases

Papillary thyroid carcinoma (PTC) with desmoid-type fibromatosis (DTF) is characterized by genetic alterations of the fibroblasts. PTC-DTF is extremely rare, and the reports on such cases have been sporadic. Immunohistochemical staining using the antibody for beta-catenin is useful in diagnosing the variant. This report aims to describe the clinical, pathological, and immunohistochemical findings in 14 cases of PTC-DTF and to clarify the diagnostic significance of the variant. The patients included 9 women and 5 men, with a mean age of 49.3 years. PTCs with focal DTF components and with extensive DTF components included 7 cases each. No significant differences were noted in terms of age, gender, and serum thyroglobulin levels between extensive and focal DTF cases. On aspiration cytology, 12 cases were reported as suspicious for malignancy or malignant, and schwannoma or fibroma was suggested in 1 case each. The DTF components were histologically classified into 4 types, namely, central (4 cases), peripheral (1 case), mixed (7 cases), and diffuse type (2 cases). The stromal components were consistent with those of DTF. Immunohistochemically, fibroblasts in the DTF components showed nuclear and cytoplasmic expression for beta-catenin in 12 cases. The features are observed even in cases in which stromal components focally exist. Neither carcinoma cells nor the fibroblasts with Ki-67 labeling index >5% were found in all cases. We agree that PTC with nodular fasciitis-like stroma should be renamed to PTC-DTF.

Fine-needle aspiration cytology for medullary thyroid carcinoma: a single institutional experience in Japan

Many cytological studies on medullary thyroid carcinoma (MTC) have been reported; however, such studies in large series of patients with MTC have not been performed. We investigated MTC at a single institution in Japan using fine-needle aspiration cytology (FNAC), and aimed to establish a preoperative diagnostic algorithm for MTC. FNAC was performed in 119 of 149 patients with MTC (79.9%) who ultimately underwent surgical resection. Moreover, 22 of 56 hereditary MTC (39.3%) were diagnosed preoperatively without FNAC by their high serum calcitonin levels or increased response to calcium stimulation (11 cases each), as well as RET mutation analysis. On FNAC, 76.5% of nodules were categorized as malignancy or suspicious for malignancy. The sensitivity and specificity of calcitonin measurement in aspiration needle wash-out fluid and in immunocytochemical staining for calcitonin were 96.3% and 92.3% respectively. We proposed an algorithm for preoperative diagnosis of MTC utilizing FNAC: When thyroid nodules are highly suspicious for MTC by their clinical and ultrasonographic features, serum calcitonin measurement with or without a calcium stimulation test is required. Furthermore, FNAC should be performed for patients who do not have those findings. When there is a possibility of MTC at the time of FNAC, calcitonin measurement using needle wash-out fluid is a reliable diagnostic tool. When MTC is suspected on cytological examination, immunocytochemical staining for calcitonin is useful for confirming MTC diagnosis.

Warthin-like papillary thyroid carcinoma with immunoglobulin G4-positive plasma cells possibly related to Hashimoto’s thyroiditis

Hashimotos thyroiditis with heavy lymphoplasmacytic infiltration is a common comorbidity of immunoglobulin G4 (IgG4)-related thyroiditis and Warthin-like papillary thyroid carcinoma (WL-PTC). We hypothesized that WL-PTC may have a strong association with IgG4-related thyroiditis. To validate this hypothesis, we clinically and immunohistochemically studied 17 WL-PTC cases. Fourteen patients (82.4%) had anti-thyroglobulin antibody and were confirmed to have Hashimotos thyroiditis through microscopic analysis. Among them, five (29.4%) had disease consistent with IgG4-related thyroiditis but did not exhibit a storiform pattern or obliterative phlebitis. IgG4-related diseases were not found in other organs. No cases with serum IgG4 level of >135 mg/dL were noted. A total of 94.1% of WL-PTC cases had IgG4-positive plasma cells (+PCs) in the stroma, and cases with rich IgG4+PCs were more frequently associated with Hashimotos thyroiditis than those with poor IgG4+PCs. In this study, all three cases without Hashimotos thyroiditis had poor IgG4+PCs, and one of them did not exhibit IgG4+PCs in the stroma of WL-PTC and Hashimotos thyroiditis. Nodal metastatic lesions were seen in eight cases, all of which were not WL-PTC. As such, we should consider that the Hashimotos disease with rich IgG4+PCs seen in our cases is representative of non-IgG4-related disease and not IgG4-related disease involving multiple organs. This study is the first to demonstrate the presence of IgG4+PCs in the stroma of WL-PTC. We concluded that the appearance of IgG4+PCs in the stroma of WL-PTC may be related to Hashimotos thyroiditis with rich IgG4+PC.