• The Korean Journal of Cytopathology
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• v.9 no.1
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• pp.63-68
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• 1998

Fine needle aspiration cytology of "cold" nodules of the thyroid has proved to be of great value in their preoperative diagnosis. Most types of thyroid tumors are readily recognizable from characteristic cellular patterns in the smears of needle aspirates. But follicular neoplasms present some problems because the cytomorphology of the adenomas frequently is same as in carcinoma. For differentiation of benign from malignant follicular neoplasms of the thyroid we tested the usefulness of two objective parameters - nuclear area and perimeter - by morphometry. This study was made on fine needle aspirates from 30 cases with cytologic diagnosis of follicular neoplasm of thyroid. The histologic classification was follicular adenoma in 22 cases and follicular carcinoma in 8 cases. As a reference group we used seven caes with nodular hyperplasia. The smears of aspirates were stained by Papanicolaou method. On each slide 200 randomly selected cells with intact nuclei were measured. The mean value of nuclear area are $25.32{\pm}5.50{\mu}m^2,\;34.08{\pm}7.50{\mu}m^2\;and\;39.97{\pm}6.63{\mu}m^2$ in nodular hyperplasia, follicular adenoma, and follicular carcinoma, respectively. The mean value of perimeter are $19.48{\pm}2.26{\mu}m,\;22.95{\pm}2.65{\mu}m\;and\;24.78{\pm}2.23{\mu}m$ in nodular hyperplasia, follicular adenoma and follicular carcinoma, respectively. The mean nuclear areas and perimeters of cells from follicular adenoma were significantly larger than those from nodular hyperplasia (p<0.05). The mean nuclear areas and perimeters of cells from follicular carcinoma were larger than those from follicular adenoma but the differences are not significant statistically(p>0.05). Therefore, morphometric assessment alone is inadequate to predict malignancy in thyroid aspirates.

• The Korean Journal of Cytopathology
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• v.7 no.2
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• pp.134-137
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• 1996

Monoclonal antibody(TCM-9) against human thyroid cancers have been studied by screening with human thyroid cancers, normal and benign thyroid tissue, and normal human serum protein. A monoclonal antibody(TCM-9) that is known to have strong specificity for human thyroid cancer but not for Graves' disease, adenoma or normal thyroid does not bind to native or mature human thyroglobulin(Tg). We used to TCM-9 antibody by immunohistochemical staining on 5 follicular cancer, 2 follicular adenoma, 1 follicular neoplasm with suspicious invasion, 2 papillary cancer to ascertain being of help in differentiation between follicular carcinoma and adenoma. Reactivity of TCM-9 was observed in follicular carcinoma and papillary carcinoma but not observed in follicular adenoma. Thus TCM-9 is a novel monoclonal antibody against the thyroid cancer.

• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.139-147
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• 2001

Objectives: The most important differential point of follicular carcinoma from adenoma is capsular invasion or angioinvasion of follicular cells. Serial sections for examination of levels of tumor margins are necessary to watch the invasion. However, the interpretation of capsular invasion or angioinvasion is sometimes not feasible on the routine staining of tumor tissue. The aim of this study is to evaluate the clinical significance of expressions of $p27^{KIP1}$, MIB-1, bcl-2 and p53 in differential diagnosis of follicular adenoma and carcinoma. Materials and Methods: 16 cases of follicular carcinoma and 26 cases of follicular adenoma were entered on study of immunohistochemical stains for $p27^{KIP1}$, MIB-1, bcl-2 and p53. In carcinoma cases, correlation between the above markers, patient's age, tumor size, infiltration pattern and metastasis was studied. Results: $p27^{KIP1}$ labelling index (LI) of follicular carcinoma and adenoma was $4.89{\pm}6.92$ and $14.52{\pm}9.17$, respectively, but there was no significant difference between adenoma and carcinoma (p=0.2560). MIB-1 LI of carcinoma and adenoma was $4.11{\pm}3.89$ and $0.80{\pm}0.75$, respectively, and MIB-1 LI was significantly higher in carcinoma (p=0.0000). bcl-2 expression was seen in 2(12.5%) of 16 carcinoma cases and 130(50.0%) of 26 adenoma cases, and bcl-2 expression rate was higher in adenoma than in carcinoma(p=0.014). In one adenoma and one carcinoma case, p53 expression was noted. In follicular adenoma with atypia compared to adenoma without atypia, lower $p27^{KIP1}$ LI, higher MIB-1 LI and lower bcl-2 expression rate were seen. In follicular carcinoma, MIB-1 LI was significantly higher in invasive carcinoma(p=0.045) and was relatively increased in tumors larger than 3.0cm, showing angioinvasion and distant metastasis. But $p27^{KIP1}$ LI was higher in cases over 40 years old(p=0.008) and with conspicuous capsular invasion. There were no positive correlations between expressions of MIB-1, bcl-2 and p53. Conclusion: MIB-1 labelling index and bcl-2 expression could be helpful for differential diagnosis of follicular adenoma and carcinoma, but p53 showed very low expression rate and no significance in differential diagnosis. $p27^{KIP1}$ labelling index reveals decreasing tendency in carcinoma compared with adenoma, MIB-1 LI was considered as a poor prognostic marker in follicular carcinoma, but $p27^{KIP1}$ LI was higher in carcinoma cases over 40 years old with showing conspicuous capsular invasion. Further study for the significance of $p27^{KIP1}$ labelling index in follicular neoplasms is necessary to evaluate diagnostic value of follicular carcinoma.

• The Korean Journal of Cytopathology
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• v.19 no.2
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• pp.152-159
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• 2008

Fine-needle aspiration cytology (FNAC) cannot differentiate follicular adenoma from follicular carcinoma since this distinction can only be based on the presence of capsular or vascular invasion, and this can￢not be detected on a cytologic smear. The goal of this study was to define the diagnostic cytologic findings of follicular neoplasm and the possibility of diagnosing follicular neoplasm by performing FNAC. The cases of histologically diagnosed follicular adenoma and follicular carcinoma on the thyroidectomy specimens were retrieved. Among them, the cases with preoperative FNAC that was done within 3 months of the operation were finally selected. Then we reviewed the FNAC and histologic slides of 19 cases: 9 follicular adenomas and 10 follicular carcinomas. Our results suggest that for cases of follicular neoplasm, the aspirates show high or abundant cellularity, frequent follicle formation and occasional cellular atypism of the follicular cells. However, the atypism is more pronounced and more frequently noticed in the cases of follicular carcinoma, which reveals more higher anisocytosis (7/10, 70%), nuclear pleomorphism (9/10, 90%), coarse clumping of chromatin (8/10, 80%) and cellular overlapping (8/10, 80%).

• Korean Journal of Veterinary Research
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• v.36 no.2
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• pp.429-440
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• 1996

In order to know morphological changes on the female genital organs by Ivermectin(IVM) administration, the histopathological observation was carried out in the organs of rat and mouse treated with the overdose of IVM. In the microscopical findings of the uterus, there were many mitotic figures, epithelial hyperplasia and papillary foldings in the endometrial surface. The increased prevalance of uterine glands, uterine epithelia and glands hyperplasia were markedly presented on diverse patterns adenoma-like structure and single nodular or multiple polyp-like adenoma. In ovary, primary and mature follicles were decreased in number, and hypoplasia of ovarian follicles, atretic follicles, follicular cysts and ovarian atropy were observed. It was considered that IVM administration resulted in follicular hypoplasia and atropy of ovary, and hyperplasia of uterine gland and endometrial surface epithelium might be transformed to neoplasia of glandular structures.

• The Korean Journal of Cytopathology
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• v.4 no.2
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• pp.105-110
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• 1993

The major limitation of fine needle aspiration of the thyroid is in the evaluation of follicular tumors. it may be difficult or occasionally, impossible to distinguish on a cytologic basis, between hyperplastic nodular getter, follicular adenoma and well differentiated follicular carcinoma. We reviewed cytologic presentations of 15 histologically confirmed follicular neoplasms of the thyroid. Aspiration smears of 6 follicular adenomas were cell-rich with ball-like or syncytial aggregates of monotonous follicular cells, in contrast to honeycomb-like flat sheets of adenomatous goiter Mild nuclear pleomorphism and a small visible nucleolus were noted in 2 cases, respectively. Nine cases of follicular carcinoma showed very high cellularity, irregularly shaped cell clusters, and numerous isolated tumor cells. Nuclear pleomorphism and visible nucleoli were noted in 6 and 5 cases, respectively. Another characteristic finding, entrapped endothelial cells within the ceil clusters, was noted in 7 carcinomas and 1 adenoma. The background of the smears of all follicular neoplasms was hemorrhagic, with no or scanty colloid. We confirmed that the cytologic features of follicular adenoma and carcinoma were similar in general, with subtle differences in cell morphology, but the presence of isolated tumor cells and entrapped endothelial cells was suggestive of malignancy.

• The Korean Journal of Cytopathology
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• v.18 no.1
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• pp.74-80
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• 2007

Parathyroid tumors may be difficult to distinguish from thyroid follicular lesions, especially when a tumor is nonfunctioning. We report here two cases of asymptomatic parathyroid carcinoma preoperatively misdiagnosed as thyroid follicular lesions, and one case of parathyroid adenoma showing hyperparathyroidism, and review the cytologic features favoring the diagnosis of parathyroid neoplasm. The cytologic findings that are characterized by clean background, monomorphic small cells, cohesive three-dimensional papillary clusters, small tight clusters with scattered naked nuclei, and well-defined clear cytoplasm favor a diagnosis for the parathyroid lesions. Cytologic findings such as macrofollicular structure, presence of colloid and macrophages, and presence of perivacuolar cytoplasmic granules on May-Grunwald-Giemsa stain support a diagnosis of a thyroid follicular lesion. The cytomorphology of parathyroid tumors is so variable that the distinction from a thyroid lesion cannot be based on the presence or absence of a single feature only but on the cytologic features as a whole.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2175-2178
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• 2012

Purpose: Definite diagnosis of follicular thyroid carcinoma (FTC) is based on the presence of capsular or vascular invasion. To date, no reliable and practical method has been introduced to discriminate this malignant neoplasm from follicular thyroid adenoma (FTA) in fine needle aspiration biopsy material. Matrix metalloproteinase-2 (MMP-2), by degrading extracellular matrix, and caspase-3, by induction of apoptosis, have been shown to play important roles in carcinogenesis and aggressive behavior in many tumor types. The aim of this study was to examine expression of MMP-2 and caspase-3 in thyroid follicular neoplasms and to determine their usefulness for differential diagnosis. Method: Sixty FTAs and 41 FTCs were analysed immunohistochemically for MMP-2 and caspase-3. Result: MMP-2 was positive in 4 FTCs (9.8%), but in none of FTAs, with statistical significance (p= 0.025). Caspase-3 was positive in 30 (50%) of FTAs and in 27 (65.9%) of FTCs. Conclusion: Our results show MMP-2 expression only in FTCs and suggest that this protein may be a useful marker to confirm diagnosis of FTC versus FTA with 100% specificity and 100% predictive value of a positive test. We failed to show any differential diagnostic value for caspase-3 in thyroid follicular neoplasms.

• Korean Journal of Head & Neck Oncology
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• v.13 no.2
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• pp.241-246
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• 1997

It has become evident in recent years that parathyroid adenoma and well differentiated thyroid cancer occur together more than would be expected by chance alone. However, the association between them is not well understood. We have experienced 4 cases of coexistent parathyroid adenoma and well-differentiated thyroid cancer during the past 16 years. None of them had a familial incidence or a history of radiation exposure. Three cases showed symptomatic hypercalcemia(including renal stones, bone pain, joint pain) and in two of them(patient 1 and patient 2), thyroid abnormalities were detected preoperatively by neck ultrasonography or neck CT for evaluation of parathyroid lesions. However, in patient 3, a parathyoid humor was identified and removed incidentally during the course of thyroidectomy. In 3 cases, surgeries for thyroid carcinoma and parathyroid adenoma were performed during the same exploration of the neck, but in patient 4, thyroidectomy preceded parathyroidectomy; The interval between thyroidectomy and subsequent parathyroidectomy was 11 yeras. The thyroid tumors in 3 cases were papillary carcinoma, the sizes of which ranged from 1.0 cm to 1.5 cm in greatest diameter. The remaining case(patient 4) was minimal invasive follicular carcinoma. Total or near-total thyroidectomy with various types of cervical lymphnode dissection and bilateral neck exploration for the parathyroid lesion was performed in 3 cases with papillary carcinoma. Ipsilateral lobectomy and contralateral partial thyroidectomy with consequent unilateral neck exploration for the parathyroid tumor was performed in the case of follicular cancer. In our experience, parathyroid adenoma and well-differentiated thyroid carcinomas can be coexistent and we felt that the attention to the hypercalcemic patients would be needed for detection of this rare condition.

• Korean Journal of Radiology
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• v.23 no.7
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• pp.763-772
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• 2022

Objective: Preoperative differential diagnosis of follicular-patterned lesions is challenging. This multicenter cohort study investigated the clinicoradiological characteristics relevant to the differential diagnosis of such lesions. Materials and Methods: From June to September 2015, 4787 thyroid nodules (≥ 1.0 cm) with a final diagnosis of benign follicular nodule (BN, n = 4461), follicular adenoma (FA, n = 136), follicular carcinoma (FC, n = 62), or follicular variant of papillary thyroid carcinoma (FVPTC, n = 128) collected from 26 institutions were analyzed. The clinicoradiological characteristics of the lesions were compared among the different histological types using multivariable logistic regression analyses. The relative importance of the characteristics that distinguished histological types was determined using a random forest algorithm. Results: Compared to BN (as the control group), the distinguishing features of follicular-patterned neoplasms (FA, FC, and FVPTC) were patient's age (odds ratio [OR], 0.969 per 1-year increase), lesion diameter (OR, 1.054 per 1-mm increase), presence of solid composition (OR, 2.255), presence of hypoechogenicity (OR, 2.181), and presence of halo (OR, 1.761) (all p < 0.05). Compared to FA (as the control), FC differed with respect to lesion diameter (OR, 1.040 per 1-mm increase) and rim calcifications (OR, 17.054), while FVPTC differed with respect to patient age (OR, 0.966 per 1-year increase), lesion diameter (OR, 0.975 per 1-mm increase), macrocalcifications (OR, 3.647), and non-smooth margins (OR, 2.538) (all p < 0.05). The five important features for the differential diagnosis of follicular-patterned neoplasms (FA, FC, and FVPTC) from BN are maximal lesion diameter, composition, echogenicity, orientation, and patient's age. The most important features distinguishing FC and FVPTC from FA are rim calcifications and macrocalcifications, respectively. Conclusion: Although follicular-patterned lesions have overlapping clinical and radiological features, the distinguishing features identified in our large clinical cohort may provide valuable information for preoperative distinction between them and decision-making regarding their management.