Expression of p63 in papillary thyroid carcinoma and in Hashimoto's thyroiditis: a pathobiologic link?

p63 proteins are p53 homologs that are postulated to regulate squamous stem cell commitment. An immunohistochemical survey of p63 expression in normal thyroid and in reactive, neoplastic, and inflammatory thyroid disorders was performed. Sections from routinely fixed and processed archival thyroidectomy specimens were pretreated with citric acid, pH 6.0, for antigen retrieval, then incubated overnight with anti-p63 monoclonal antibody 4A4. Slides were stained using a streptavidin-biotin kit and diaminobenzidine as a chromagen, and then were counterstained with hematoxylin. The results showed that p63 expression was negative in normal thyroid tissue, nodular goiters, and oncocytic follicular adenomas. Positivity was rare and weak in follicular adenomas. p63-positive foci were commonly found in Hashimoto's thyroiditis (1 or more foci in 78.8% of cases), but rare in Graves' disease. Twenty-seven of 33 papillary thyroid carcinomas (81.8%) displayed p63-positive foci. Staining was uncommon in follicular carcinomas and rare in medullary carcinomas. One case of insular carcinoma was p63-positive. All squamoid structures were p63-positive; p63-positive structures morphologically consistent with solid cell nests were also identified. Based on the results of this study, we conclude that p63 is commonly expressed in papillary thyroid carcinoma and in Hashimoto's thyroiditis. Given the debated association of papillary thyroid carcinoma with Hashimoto's thyroiditis, it is possible that p63 expression may be a potential pathobiologic link between the two disorders. The finding of p63 in benign squamoid nests supports a possible interrelationship between these structures and both Hashimoto's thyroiditis and papillary carcinoma. The high percentage of papillary carcinomas with p63-positive foci appears to distinguish papillary carcinoma from other neoplasms originating in the thyroid.     

Nuclear morphometry of primary B cell thyroid lymphoma.

Thyroid lymphoma is usually distinguished from anaplastic thyroid carcinoma and from Hashimoto's thyroiditis by morphological and immunohistochemical assessment of tissue sections. Our objective was to assess the value of nuclear morphometry in the differential diagnosis of these conditions. Nuclear area measurements were performed on 10 cases of thyroid lymphoma using an IBAS 2000 Image Analyser and compared with similar measurements performed on 10 cases of Hashimoto's thyroiditis and 2 of anaplastic thyroid carcinoma. It was found that karyometry demonstrated differences between all three conditions, the cases of thyroiditis being distinguishable from lymphoma on the basis of mean nuclear area alone. Mean nuclear area for lymphomas was greater than for Hashimoto's thyroiditis and lower than for anaplastic carcinomas. The mean nuclear area also reflected the grade of lymphoma, with the exception of one case which had a large reactive T cell population. It is concluded that nuclear morphometry provides valuable information in the diagnosis and assessment of thyroid lymphomas.     

Mixed medullary-follicular carcinoma of the thyroid: diagnostic dilemmas in fine-needle aspiration cytology

Mixed medullary-follicular carcinoma (MMFC) of thyroid is an extremely rare tumor, characterized by coexistence of morphological and immunohistochemical features of both medullary carcinoma and follicular (or papillary) carcinoma. We herein present fine needle aspiration (FNA) findings of a histology-confirmed MMFC along with a review of literature. The patient was a 64-year-old woman who had a history of Hashimoto's thyroiditis and presented with enlargement of preexisting right thyroid nodule. An US-guided FNA of the thyroid nodule was performed and conventional smears were prepared. A cytologic diagnosis of "positive for malignancy, consistent with medullary thyroid carcinoma (MTC)" was rendered based on the presence of features characteristic for MTC, and the absence of components of follicular neoplasm (adenoma and carcinoma) or papillary carcinoma. However, microscopic examination of the follow-up total thyroidectomy specimen with the aid of immunocytochemical study detected minor portion of follicular carcinoma in addition to MTC. A histologic diagnosis of MMFC was then established. While specific identification of MMFC by FNA may be difficult, it should be emphasized that adequate sampling in conjunction with the proper immunostaining panel could have highlighted the different aspects of the mixed tumor.     

Hashimoto's thyroiditis with papillary thyroid carcinoma (PTC)-like nuclear alterations express molecular markers of PTC

AIMS: Focal papillary thyroid carcinoma (PTC)-like nuclear alterations have been documented in Hashimoto's thyroiditis; however, the molecular association between PTC and Hashimoto's thyroiditis is poorly understood. The aim of this study was to determine whether molecular expression patterns of PTC are present in association with PTC-like nuclear alterations in Hashimoto's thyroiditis. METHODS AND RESULTS: The expression of four genes known to be up-regulated in PTC [LGALS3 (galectin3), CITED1, KRT19 (cytokeratin 19) and FN1 (fibronectin-1)] and the human mesothelial cell protein identified by monoclonal antibody HBME1 was evaluated. Immunohistochemistry was performed on 23 cases of Hashimoto's thyroiditis with focal or diffuse Hürthle cell change and PTC-like nuclear alterations, 37 PTC and 18 normal thyroids. Focal expression of galectin3 (GAL3), CITED1, cytokeratin 19 (CK19), HBME1 and fibronectin-1 (FN1) was seen in 87%, 65%, 43%, 26% and 17% of Hashimoto's thyroiditis, respectively, only in thyrocytes showing PTC-like nuclear alterations. In contrast, diffuse expression of GAL3, CITED1, CK19, HBME1 and FN1 was seen in 100%, 95%, 70%, 87% and 89% of PTC, respectively. Normal thyroid tissues did not express any of these proteins. Following immunohistochemistry, four Hashimoto's thyroiditis cases were found to contain foci of PTC. These foci were highlighted by the diffuse and strong expression of PTC-associated proteins, which prompted additional retrospective scrutiny of the haematoxylin and eosin-stained sections leading to appreciation of complete PTC-type nuclear atypia. CONCLUSIONS: Focal PTC-like immunophenotypic changes in Hashimoto's thyroiditis suggest the possibility of early, focal premalignant transformation in some cases of Hashimoto's thyroiditis.     

NTRK3重排甲状腺乳头状癌的临床病理学特征

目的:探讨NTRK3重排甲状腺乳头状癌（PTC）的临床病理学特征、诊断和鉴别诊断。方法:收集2015年1月至2020年1月福建省立医院南院诊断的BRAF V600E阴性的PTC病例174例。对这些病例行免疫组织化学染色和荧光原位杂交（FISH）检测,筛选出NTRK3重排PTC的病例。总结确诊病例的临床资料、病理学特征、...     

Immunohistochemical detection of p53 homolog p63 in solid cell nests, papillary thyroid carcinoma, and hashimoto's thyroiditis: A stem cell hypothesis of papillary carcinoma oncogenesis

Most models suggest that the cell of origin of papillary carcinoma is the mature thyroid follicular epithelial cell. In a recent study, p63 was detected in papillary carcinoma, Hashimoto's thyroiditis, and in squamoid aggregates and solid cell nests (SCNs), embryonic remnants found sporadically in the fully developed thyroid. In the present study, the relationship between solid cell nests and papillary carcinoma was investigated further. Four-micrometer sections from 88 routinely fixed and processed archival thyroidectomy specimens were pretreated with citric acid pH 6.0 for antigen retrieval, then incubated overnight with anti-p63 monoclonal antibody 4A4. Slides were stained with a streptavidin-biotin kit and diaminobenzidine as chromogen and were counterstained with hematoxylin. Squamoid aggregates or SCNs were noted in 21 specimens. Several morphologic variants of SCNs were found, all of which displayed p63 positivity. These included undifferentiated SCNs and those displaying commitment toward squamoid and ciliated glandular differentiation. Small, morphologically inconspicuous aggregates of p63-positive cells were commonly found in Hashimoto's thyroiditis. Commitment of p63-positive undifferentiated cells toward thyroid follicular epithelial differentiation was occasionally noted. One SCN variant, also associated with Hashimoto's thyroiditis, was a floretlike arrangement of p63-positive cells with fusiform nuclei. p63 staining was strong and uniform in some SCNs, but in other SCNs it was compartmentalized and homologous to stem cell-staining patterns in normal squamous or bronchial epithelia. Stem cell-like staining, associated with compartmentalized p63 staining or p63-positive undifferentiated cells, was noted in 7 of 27 papillary carcinomas. p63 immunostaining is a highly sensitive means of detecting SCNs. p63 expression patterns in SCNs and a subset of papillary carcinomas are closely homologous to stem cell-associated p63 staining patterns that have been described elsewhere in squamous and bronchial epithelia. We propose a stem-cell-associated model of papillary carcinoma oncogenesis that suggests that (1) p63-positive embryonal remnants rather than mature follicular cells are the cells of origin of a subset of papillary carcinomas; (2) these p63-positive cells are pluripotent and may stay undifferentiated or undergo benign squamoid or glandular maturation, may undergo thyroid follicular epithelial differentiation, may undergo oncogenic change leading to papillary carcinoma, or may trigger an immune reaction, resulting in lymphoid infiltration and Hashimoto's thyroiditis; and (3) Hashimoto's thyroiditis and papillary carcinoma may therefore be linked etiologically, because both disorders may be initiated by the same population of pluripotent p63-positive embryonal stem cell remnants.     

Immunohistochemical detection of X-linked inhibitor of apoptosis (XIAP) in neoplastic and other thyroid disorders

The X-linked inhibitor of apoptosis (XIAP) is the most potent of the inhibitors of apoptosis, a group of related caspase inhibitors. X-linked inhibitor of apoptosis expression correlates with radio- and chemoresistance and clinical aggressiveness in certain tumors. XIAP expression was examined in 106 specimens from neoplastic and other thyroid disorders, which underwent citrate-based antigen retrieval and staining with monoclonal anti-XIAP. Normal thyroid was XIAP-negative. Of 35 papillary thyroid carcinomas (PTCs), 29 (83%) stained variably in intensity and/or extent. An insular carcinoma was strongly positive and 1 of 4 anaplastic carcinomas moderately positive. Follicular, medullary, and 3 of 4 anaplastic carcinomas, oncocytic neoplasms, and a hyalinizing trabecular tumor were nonstaining. Hashimoto's thyroiditis and adenomatous goiters were either nonstaining or occasionally stained in oncocytic foci. Because XIAP was highly specific for PTC among the thyroid neoplasms, it may be a useful marker for differential diagnosis when used alone or in combination with other markers. XIAP may also be useful in differentiating insular carcinoma from follicular neoplasm in certain difficult cases. In addition, the selective expression of XIAP in PTC and some high-grade thyroid malignancies also provides clues to the role of the apoptotic pathway in the tumorigenesis of these neoplasms.     

The spectrum of papillary thyroid carcinoma variants

Papillary thyroid carcinoma is the most common type of thyroid malignancy. The diagnostic features of these tumors include characteristic nuclear cytology. However, many variants have been reported with different morphology and molecular profiles. Although the vast majority of papillary thyroid carcinomas have an excellent prognosis, some variants of papillary thyroid carcinoma can have a more aggressive course. With this increased attention to papillary thyroid carcinoma variants has come the need to sort out which variants are clinically important and should be recognized by practicing pathologists. The main objectives of this review article are to (1) summarize the gross and histopathologic features of papillary thyroid carcinoma; (2) provide an overview of the subtypes of papillary thyroid carcinoma and their prognosis; (3) discuss established and emerging data on the immunohistochemical findings that are helpful in differential diagnosis; and (4) summarize molecular findings and pathogenesis of these lesions.     

Columnar cell variant of papillary thyroid carcinoma: A diagnostic dilemma in fine‐needle aspiration cytology

Columnar cell variant of papillary thyroid carcinoma (PTC) is an uncommon variant with an aggressive course as compared to classic papillary carcinoma. Cytologic diagnosis of these tumors is difficult due to absence of characteristic nuclear features of classic pattern of papillary carcinoma. We present a case of columnar cell variant in a young female misdiagnosed on aspiration cytology. A 21‐year‐old female presented with solitary nodule in the left aspect of thyroid. A diagnosis of medullary thyroid carcinoma was rendered. The resected thyoroidectomy specimen revealed a columnar cell variant of PTC which was further supported by immunohistochemical staining. Diagn. Cytopathol. 2016;44:816–819. © 2016 Wiley Periodicals, Inc.     

The role of cytokeratin 19 in the differential diagnosis of true papillary carcinoma of thyroid and papillary carcinoma-like changes in Graves’ disease

Graves’ disease is an autoimmune disease predominantly seen in females. All types of thyroid cancers may co-exist with Graves’ disease but papillary carcinoma is the most frequent. Vesicular nuclei, nuclear grooves, and papillary formations that may be seen in Graves’ disease may lead the pathologist to an overdiagnosis of papillary carcinoma. The differential diagnosis between a true papillary carcinoma and foci mimicking papillary carcinoma in Graves’ disease may be challenging by light microscopic features only. This study is designed to determine whether CK19 is effective in the discrimination between the true papillary carcinoma of thyroid and foci resembling papillary carcinoma in Graves’ disease. Twenty-five cases with papillary carcinoma and 25 cases with Graves’ disease containing foci resembling papillary carcinoma were included in the study. All 25 cases with papillary carcinoma stained positive with CK19, whereas only six of 25 cases with Graves’ disease showed weak staining, and the remaining 19 cases were completely negative. It is known that CK19 may show faint staining in benign thyroid lesions such as adenomas. Staining pattern with CK19 together with histopathological findings may be helpful in the differential diagnosis between foci mimicking papillary carcinoma and true papillary carcinoma in Graves’ disease.     

Ultrastructural localization of thyroid peroxidase, hydrogen peroxide-generating sites, and monoamine oxidase in benign and malignant thyroid diseases

Despite thyroid tissue heterogeneity, biochemical and morphological features have been associated with certain thyroid diseases. We analyzed the ultracytochemical localization of thyroperoxidase (TPO), TPO-associated hydrogen peroxide-generating sites (H(2)O(2) sites), and monoamine oxidase (MAO) in terms of morphology and biochemical TPO activity in abnormal thyroids. We examined 11 cases of nontoxic multinodular goiter, 5 cases of Hashimoto's thyroiditis, 1 case of oncocytic (Hürthle or oxyphilic cell) adenoma, 5 cases of Graves' disease, 4 cases of papillary carcinoma, and 4 cases of perinodular normal tissue. In the perinodular tissue, TPO was detected mainly in the nuclear envelope, rough endoplasmic reticulum (RER), and subapical vesicles, but not in the apical surface. In multinodular goiter, heterogeneous TPO reactivity ranging from almost null to strongly positive was detected in similar locations as in the perinodular tissue, and was absent in the microvilli. Follicular cells from Hashimoto's thyroiditis displayed TPO in the nuclear envelope and the scarce RER. Remarkably, oncocytic cells from both Hashimoto's thyroiditis and oncocytic adenoma, typically packed with mitochondria, displayed evident TPO reaction exclusively in mitochondrial cristae. In Graves' disease, the nuclear envelope, enlarged RER, and apical vesicles were strongly TPO positive, and microvilli also exhibited TPO activity. Papillary carcinoma cells were negative for TPO. The localization and characteristics of TPO activity in the H(2)O(2) sites were similar to that of TPO in all tissues. MAO was positive in mitochondria of perinodular tissues, multinodular goiter, and oncocytes and negative in Hashimoto's thyroiditis and Graves' disease. Interestingly, MAO was intensely positive in the nuclear envelope of papillary carcinoma but unreactive in mitochondria. Biochemical TPO activity was increased in multinodular goiter and Graves' disease. In conclusion, several changes in ultracytochemical characteristics of TPO, H(2)O(2) sites, and MAO were associated with thyroid disease. Nonmalignant oncocytic cells exhibited an unusual mitochondrial location of TPO and H(2)O(2) sites. The distribution of MAO in nuclear envelope of papillary carcinoma cells could be a further feature of malignancy.     

Cellular swirls in fine needle aspirates of papillary thyroid carcinoma: a new diagnostic criterion.

No single cytologic feature is specifically diagnostic for papillary thyroid carcinoma. We report herein the presence of swirl-like cellular aggregates in fine needle aspirates of papillary thyroid carcinoma but not in other thyroid entities. Cellular swirls are defined as concentrically organized aggregates of tumor cells in which many of the most peripherally situated cells have ovoid rather than round nuclei that are oriented perpendicular to the radius of the swirl. One hundred Papanicolaou- and/or Diff-Quik-stained FNAs of the thyroid diagnosed as papillary carcinoma, including seven fine needle aspirates of cervical lymph nodes showing metastatic papillary carcinoma, with or without cell blocks, were reviewed for the presence of cellular swirls. An additional 100 thyroid FNAs, similarly stained and prepared, diagnosed as nodular goiter, Hashimoto's thyroiditis and follicular neoplasm were also reviewed for the presence of cellular swirls. Cellular swirls were easily observed at screening magnification and confirmed at high magnification. Seventeen of 100 FNAs (17%) of papillary carcinoma contained cellular swirls. No cases diagnosed as nodular goiter, Hashimoto's thyroiditis or follicular neoplasm contained these structures. Thirteen cases with swirls had histologic follow-up. These comprised seven papillary carcinomas with classical histopathology, two designated 'differentiated papillary carcinoma,' two with follicular variant histopathology; one with a minor component of follicular variant histopathology; one papillary carcinoma metastatic to a cervical lymph node with classic histopathology. Swirls occurred in cases with relatively little pleomorphism, or in well-differentiated regions of papillary carcinoma that also displayed less well-differentiated components. Cellular swirls are a finding that is highly specific to papillary thyroid carcinoma. They are easily seen at screening magnification. Their presence in a FNA specimen may be helpful in cases where classic criteria for papillary thyroid carcinoma are scarce, particularly in well-differentiated papillary thyroid carcinoma. While the size and scope of this study are insufficient to conclude that cellular swirls alone are diagnostic of papillary thyroid carcinoma in the absence of other criteria, we believe these structures should be added to the list of diagnostic criteria.     

Galectin-3, a marker of well-differentiated thyroid carcinoma, is expressed in thyroid nodules with cytological atypia

AIMS: The distribution of galectin-3, a widely recognized marker of well-differentiated thyroid carcinoma, was investigated in 95 thyroid lesions including nodules with foci of cytoarchitectural atypia. METHODS AND RESULTS: Twenty-eight papillary carcinomas, five follicular carcinomas, one Hurthle cell carcinoma, three poorly differentiated carcinomas, one anaplastic carcinoma, 25 nodular hyperplasias and 27 follicular adenomas, including nodules with atypical features, three neoplasms of undetermined malignant potential and two thyroiditis cases were examined. By immunohistochemistry, galectin-3 was consistently found in carcinomas; otherwise benign nodules exhibited galectin-3-positive clusters of cells with poorly developed features of differentiated carcinoma (mainly of papillary type) such as nuclear chromatin clearing, nuclear clefting, pseudoinclusions, which, in each case, were not histologically sufficient to warrant a definitive diagnosis of malignancy. In other nodules galectin-3 staining was negative. The latter were either clearly benign or showed constantly a minor degree of chromatin clearing and of other atypical features when compared with galectin-3-positive cases. CONCLUSIONS: Galectin-3, a reliable marker of differentiated thyroid carcinoma as confirmed in our series of malignant neoplasms, appears expressed in nodules with an overall benign appearance but with focal areas suspicious for malignancy. The significance of such findings needs to be further investigated.     

Warthin-like papillary carcinoma of the thyroid

BACKGROUND: Warthin-like papillary carcinoma of thyroid is characterized by distinct papillary formations lined by tumor cells with oncocytic cytoplasm, nuclear features of papillary carcinoma, and brisk lymphoplasmacytic infiltrates in the papillary stalks. This tumor derives its name from its close resemblance to Warthin tumor of major salivary glands. DESIGN: The clinicopathologic features of 17 patients with Warthin-like papillary carcinoma were studied. RESULTS: Fifteen tumors occurred in women and 2 arose in men (age range, 23-63 years). The lesions ranged in size from 3 mm to 2.5 cm. Fine-needle aspiration biopsies were performed in 7 cases; 4 were diagnosed as papillary carcinoma, 2 as consistent with lymphocytic thyroiditis, and 1 as atypical cells. All 17 tumors were confined to the thyroid; 6 showed prominent cyst formation and the remaining tumors were solid. In each case, the tumor arose in a background of lymphocytic thyroiditis. Nodal metastases were identified in 3 cases; however, none showed distant metastases. In 7 cases, foci of papillary microcarcinoma and follicular variant of papillary carcinoma were found in other areas of the thyroid. CONCLUSIONS: Warthin-like tumors can be mistaken for benign lymphoepithelial lesions of the thyroid, Hürthle cell carcinoma, and tall cell variant of papillary carcinoma in both fine-needle aspiration and histology specimens. Follow-up information on the previously reported cases has suggested that these tumors behave similarly to usual papillary carcinoma. The extensive lymphocytic infiltration in these tumors and their association with chronic lymphocytic thyroiditis may suggest a role for immunological mechanisms in the pathogenesis of thyroid tumors.     

Dipeptidyl aminopeptidase IV staining of cytologic preparations to distinguish benign from malignant thyroid diseases.

Staining for dipeptidyl aminopeptidase IV (DAP IV [EC: 3.4.14.5]) activity was applied to aspiration biopsy specimens or imprint preparations of surgical biopsy specimens from thyroid tumors. Material was obtained from 55 patients with histologically proven thyroid diseases: 9 with papillary carcinoma, 5 with follicular carcinoma, 11 with follicular adenoma, 13 with adenomatous goiter, 8 with Hashimoto's thyroiditis, and 9 with other benign conditions. Most tumor cells, follicular lumina in cell clusters, and intranuclear inclusions were strongly positive for DAP IV in all examples of papillary or follicular carcinoma. In contrast, only a few epithelial cells were labeled for DAP IV in follicular adenoma and adenomatous goiter. Some Hürthle cells in Hashimoto's thyroiditis also were positive for DAP IV. When a DAP IV scoring system based on the percentage of positive cells and staining intensity was used, all benign tissues except one (from a follicular adenoma) were found to have extremely low scores. These results indicate that staining for DAP IV activity is a simple but useful tool to aid in distinguishing benign from malignant thyroid neoplasms.     

Immunohistochemical diagnosis of papillary thyroid carcinoma.

In thyroid, the diagnosis of papillary carcinoma (PC) is based on nuclear features; however, identification of these features is inconsistent and controversial. Proposed markers of PC include HBME-1, specific cytokeratins (CK) such as CK19, and ret, the latter reflecting a ret/PTC rearrangement. We applied immunohistochemical stains to determine the diagnostic accuracy of these three markers. Formalin-fixed, paraffin-embedded tissue from 232 surgically resected thyroid nodules included 40 hyperplastic nodules (NH), 35 follicular adenomas (FA), 138 papillary carcinomas (PC; 54 classical papillary tumors and 84 follicular variant papillary carcinomas [FVPC]), 4 follicular carcinomas (FC), 6 insular carcinomas (IC), 7 Hürthle cell carcinomas (HCC), and 2 anaplastic carcinomas (AC). HBME-1 and ret were negative in all NH and FA; some of these exhibited focal CK19 reactivity in areas of degeneration. Half of the FC and AC exhibited HBME-1 staining but no positivity for CK19 or ret. In PC, 20% of cases stained for all three markers. Classical PC had the highest positivity with staining for HBME-1 in 70%, CK19 in 80%, and ret in 78%. FVPC were positive for HBME-1 in 45%, for CK19 in 57%, and for ret in 63%; only 7 FVPC were negative for all three markers. The six IC exhibited 67% staining for HBME-1 and 50% positivity for CK19 and ret. The seven HCC had 29% positivity for HBME-1 and CK19, and 57% positivity for ret. This panel of three immunohistochemical markers provides a useful means of diagnosing PC. Focal CK19 staining may be found in benign lesions, but diffuse positivity is characteristic of PC. HBME-1 positivity indicates malignancy but not papillary differentiation. Only rarely are all three markers negative in PC; this panel therefore provides an objective and reproducible tool for the analysis of difficult thyroid nodules.     

RET/PTC and CK19 expression in papillary thyroid carcinoma and its clinicopathologic correlation

Recently, the rearrangement of RET proto-oncogene has been reported to be the most common genetic change in papillary thyroid carcinoma (PTC). However, its prevalence has been reported variably and its relation to clinical outcome has been controversial. The characteristic nuclear features of PTC usually render the diagnosis, but problem arises with equivocal cytologic features that are present focally. Although there remains some controversy, CK19 has been reported to be a useful ancillary tool for diagnosis of PTC. To evaluate the expression rate of RET/PTC rearrangement and CK19 in PTCs in a Korean population, we studied 115 papillary thyroid carcinomas in 3 mm-core tissue microarray based immunohistochemical analysis. The prevalence of Ret protein expression was 62.6% and the CK19 immunoreactivity was 80.9%. There was no statistically significant association between the Ret positivity and CK19 immunoreactivity, although the percent agreement of the two was relatively high. The clinicopathological variables did not correlate with the expression of Ret. In conclusion, the prevalence of Ret protein expression and its clinicopathological implications in a Korean population are not much different from those reported in previous studies. However, its detection via immunohistochemistry can be a useful diagnostic tool for diagnosing papillary thyroid carcinoma in conjunction with CK19.     

Investigation of the clonality of lymphocytes in Hashimoto's thyroiditis using immunoglobulin and T-cell receptor gene probes

Southern blotting and DNA hybridization were used for the detection of immunoglobulin and T-cell receptor gene rearrangements in thyroid tissue from six patients with Hashimoto's thyroiditis, three patients with B-cell lymphoma complicating Hashimoto's thyroiditis, and two patients with nonspecific lymphocytic thyroiditis. Immunoglobulin gene rearrangements were detected only in patients with histologic evidence of lymphoma. A single T-cell receptor beta-chain gene rearrangement was detected in one of the patients with uncomplicated Hashimoto's thyroiditis. Based on our knowledge of primary thyroid lymphomas, it is highly unlikely that this case represents an early, histologically occult T-cell lymphoma. The uniform lack of immunoglobulin gene rearrangements in Hashimoto's thyroiditis supports the use of genotypic analysis in differentiating between uncomplicated Hashimoto's thyroiditis and non-Hodgkin's lymphoma. The finding of a T-cell receptor gene rearrangement in a case of Hashimoto's thyroiditis suggests that the immune response in this disease occasionally may be clonally restricted.     

CK19、CK20在甲状腺乳头状癌诊断中的应用价值

目的：探讨甲状腺癌中CK19、CK20蛋白的表达，提高甲状腺的诊断与鉴别诊断水平。方法：应用免疫组化染色对70例甲状腺癌（15例经典型乳头状癌、34例滤泡型乳头状癌、3例Warthin乳头状癌、2例透明细胞型乳头状癌、例柱状细胞型乳头癌、15例滤泡性癌），10例甲状腺腺瘤、10例结节性甲状腺肿和5例标本甲状腺炎中CK19、CK20的表达进行观察。结果:CK19在甲状腺疾病中的表达：55例乳头状癌中，53例为中、强阳性，2例为弱阳性；15例滤泡性癌中，13例为阴性、弱阳性，2例为中、强阳性，两者之间差异存在显著性（P＜0．05）。各癌旁滤泡、10例滤泡性腺瘤、10例结节性甲状腺肿的滤泡、5例桥本甲状腺炎也主要为阴性、弱阳性，个别为中等阳性。对CK20的表达，各型甲状腺乳头状癌、滤泡性癌、癌旁滤泡及滤泡状癌和乳头状增生、多灶性分布的甲状腺泡型乳头状癌和各种滤泡性病变有帮助，可提高甲状腺良恶性病变诊断的准确率及鉴别诊断水平。CK20对鉴别诊断的帮助不大。