Follicular adenoma with papillary architecture: a lesion mimicking papillary thyroid carcinoma

AIMS: The purpose of this study was to investigate the significance of 'benign' encapsulated follicular thyroid nodules with papillary structures. METHODS AND RESULTS: Twenty-one cases of encapsulated neoplastic thyroid nodules with papillary structures and nuclear features not diagnostic of papillary thyroid carcinoma (PTC) were obtained. All cases were reviewed with particular attention to nuclear features (fine chromatin pattern, optical clearing, grooves and inclusions). Representative sections were submitted for measurement of the maximum diameter of 200 round or nearly round nuclei and for immunostaining for MIB1, CK19, HBME and Ret oncogene protein. Nine cases displayed scattered optically clear nuclei or nuclear grooves in less than 30% of total neoplastic cells. They were grouped in the category of thyroid nodules with limited nuclear features of papillary thyroid carcinoma (PTC), but not diagnostic of PTC. The other 12 cases had fine or coarse chromatin, but lacked other features of nuclei in PTC. The diameter of the nuclei ranged from 5.6 to 7.2 microm and were smaller than those of PTC (6.3-10.0 microm). Immunostaining revealed positive reactivity for MIB1 in the papillary structures. Immunostaining for CK19 and HBME varied from negative or focally weak to diffusely moderate reactivity. Ret oncogene protein immunostaining showed focal and weak reactivity in one case and was negative in other cases of the study. Clinical follow-up from 6 months to 15 years revealed no evidence of metastasis. CONCLUSIONS: The papillary structures in the study cases are unlikely to represent degenerative changes due to their proliferative activity. In view of (i) the encapsulation and the uniformity of the constituent cells, (ii) the varying degrees of immunoreactivity for CK19 and HBME and negative immunoreactivity for Ret oncogene protein, and (iii) the absence or insufficiency of nuclear criteria for the diagnosis of PTC and the absence of lymph node metastasis in all study cases, we believe that these lesions represent the papillary variant of follicular adenoma. Recognition of this pathological entity is important to avoid an over-diagnosis of PTC.     

Immunohistochemical markers in diagnosis of papillary thyroid carcinoma: Utility of HBME1 combined with CK19 immunostaining.

Papillary thyroid carcinoma and its variants can be difficult to distinguish from cellular adenomatous nodules. Prior studies have advocated various antibodies to aid in the differential diagnosis, but there is little agreement on their utility. We undertook this study to evaluate immunohistochemical markers in the diagnosis and differential diagnosis of papillary thyroid carcinoma. Ten cases of papillary thyroid carcinoma were initially stained for HBME1, CK19, fibronectin1, Ki-67, Calretinin, p16, SFTPB and CITED1. Additionally, two previously untested antibodies to molecules that have been found to be upregulated in papillary thyroid carcinoma (CST6 and EPS8) were also evaluated. Of these, only HBME1, CK19 and fibronectin1 showed diagnostic utility. These three markers were then further evaluated in 51 papillary thyroid carcinomas and 57 benign thyroids. HBME1 was the most sensitive and specific marker, staining 49/51 papillary thyroid carcinomas and only 4/57 benign thyroids. CK19 was equally sensitive staining all 51 papillary thyroid carcinomas, but it was nonspecific staining 39 of 57 benign thyroids. A negative result, however, was helpful in excluding papillary thyroid carcinoma. Fibronectin1 was positive in 35/51 papillary thyroid carcinomas (69%) and 4/57 (7%) benign thyroids, but its utility was hampered by high background staining. These findings suggest that the combination of HBME1 and CK19 has the greatest diagnostic utility in the differentiation of papillary thyroid carcinoma from its benign mimics.     

Hybrid thyroid carcinoma with a coarse chromatin pattern and nuclear features of papillary thyroid carcinoma

Hybrid follicular carcinoma (FC) and papillary thyroid carcinoma (PTC) have not been previously well described. Consecutive cases of 29 FC, 12 Hurthle cell carcinomas (HC), 247 PTC and 13 Hurthle cell PTC (HPTC) were reviewed with special attention to the coarse (CC) and fine chromatin patterns (FIC), as well as to the presence of nuclear grooves, pseudoinclusions or optically clear appearance. Limited nuclear features of PTC (LNF-PTC) are defined as areas of tumor with FIC in addition to some other nuclear features, but insufficient for the diagnosis of PTC. Tumors with nuclei showing an admixture of CC and PTC or LNFPTC were submitted for immunostaining for cytokeratin 19, HBME and Ret/PTC. FC and HC contained areas of LNFPTC in 25 tumors and focal PTC in 3 tumors. None of these cases was associated with lymph node metastasis. Areas with CC were found in 54 PTC and 3 HPTC. The rates of vascular invasion and distant metastasis tended to be higher for PTC with areas of coarse chromatin pattern than for PTC without such areas; however, the difference was not statistically significant. Immunoreactivity for cytokeratin 19 and HBME was moderate to strong for PTC and focal areas of PTC or LNFPTC in FC without Hurthle cell changes. Ret/PTC immunostaining was positive in areas of LNFPTC or focal PTC in three FC. Focal PTC or areas of LNFPTC are frequently seen in FC. Likewise, areas of CC are often present in PTC. The presence of these focal areas does not appear to change the clinical behavior of the tumor and therefore does not warrant a change of nomenclature.     

HBME‐1 and CD15 immunocytochemistry in the follicular variant of thyroid papillary carcinoma

Papillary carcinoma is the most common thyroid malignancy. As the cytological diagnosis of papillary carcinoma is not difficult in patients with the usual type of lesion, fine‐needle aspiration (FNA) cytology is an effective method for preoperative evaluation. However, this modality is often ineffective in identifying the follicular variant of papillary thyroid carcinoma (FVPTC) due to its similarity to other follicular lesions and the incompleteness of typical nuclear features. Therefore, we investigated the expression of immunocytochemical markers of papillary carcinoma in cytological specimens of FVPTC and evaluated their utilities. The immunoreactivity of HBME‐1 and CD15 was investigated using 50 imprint smear cytological specimens obtained from thyroid lesions, including 13 FVPTC. The sensitivity and specificity of HBME‐1 for FVPTC were 92% and 89%, respectively, while those of CD15 were 23% and 100%, respectively. In conclusion, HBME‐1 is a sensitive marker of papillary carcinoma, including both usual type and FVPTC, in cytological specimens. Therefore, using HBME‐1 immunocytochemistry in FNA cytology will lead to reduction of the incidence of false‐negative diagnoses of FVPTC. Although CD15 is apparently inferior in terms of sensitivity for FVPTC, its excellent specificity will support the definitive diagnosis of thyroid malignancies, including FVPTC, after screening with HBME‐1.     

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.     

Histiocytic aggregates in benign nodular goiters mimicking cytologic features of papillary thyroid carcinoma (PTC)

Macrophages/histiocytes are commonly seen in fine-needle aspiration biopsy (FNAB) specimens of thyroid nodules with varying degrees of cystic change. In some cases the histiocytic component of a cystic thyroid nodule can occur as large tissue fragments with marked nuclear atypia, including elongated nuclei with chromatin clearing, nuclear grooves, and membrane thickening. These nuclear changes mimic cytologic features of papillary thyroid carcinoma (PTC), thus leading to diagnostic difficulty in interpretation of FNAB specimens of benign cystic thyroid nodules. We evaluated ethanol-fixed Papanicolaou-stained smears of 273 cases of FNAB thyroid specimens from goitrous nodules with cystic change. Twenty cases were selected due to the presence of large aggregates of histiocytic cells with the above-mentioned nuclear atypia. An immunostain for histiocytic cells using CD68 was performed on alcohol-fixed slides. Histiocytic cells in tissue fragments with nuclear atypia mimicking PTC nuclei showed strong cytoplasmic staining for CD68; thyroid follicular cells stained negative for CD68. We conclude that histiocytic cells in cystic goitrous nodules can show nuclear features, which appear similar to PTC nuclei. Immunostaining for CD68 may be of value in differentiating between benign cystic thyroid nodules with histiocytic aggregates that mimic cytologic features of papillary carcinoma, and PTC with cystic change.     

Diagnostic usefulness of HBME1, galectin-3, CK19, and CITED1 and evaluation of their expression in encapsulated lesions with questionable features of papillary thyroid carcinoma

We evaluated HBME1, galectin-3 (GAL3), cytokeratin (CK)19, and a new anti-CITED1 antibody in 127 follicular adenoma (FA) and papillary thyroid carcinoma (PTC) cases. The findings were used to evaluate 11 diagnostically challenging encapsulated follicular lesions with questionable features of PTC (FL/QPTC). All 4 markers showed higher expression in PTC than FA. HBME1 was the most specific (96%), whereas CK19 was the most sensitive (96%). In addition, 100% specificity was seen with coexpression of HBME1/CK19. Negative expression of all 4 markers was 97% specific for FA. GAL3 and CITED1, less useful individually, could help in selective cases. FL/QPTC showed heterogeneous, often intermediate, staining patterns, implying that some FL/QPTCs may be biologically borderline lesions or represent a biologic spectrum of PTC. These antibodies can have a confirmatory role in distinguishing the follicular variant of PTC and FA. For FL/QPTC, these antibodies are helpful in some cases, their limitation perhaps suggesting the biologic ambiguity of these lesions.     

Reduced HBME-1 immunoreactivity of papillary thyroid carcinoma and papillary thyroid carcinoma-related neoplastic lesions with Hürthle cell and/or apocrine-like changes

BACKGROUND: We have recently observed that Hürthle cell tumours and papillary thyroid carcinoma with tumour cells showing decapitation of luminal portion of the cytoplasm (apocrine-like changes) display negative or decreased immunoreactivity for HBME. The purpose of this study is to correlate papillary thyroid carcinoma with positive and negative immunoreactivity for HBME with the histopathological features. METHODS AND RESULTS: Two hundred and five thyroid neoplasms including carcinoma and adenomas were grouped into Hürthle cell tumours, tumours with or without some features of Hürthle cells, tumours with apocrine-like changes and adenomas with or without limited nuclear features of papillary thyroid carcinoma but not diagnostic for papillary thyroid carcinoma. All neoplasms were submitted for immunostaining with cytokeratin 19 (CK19) and HBME. Papillary thyroid carcinoma, follicular carcinoma and follicular adenoma that have areas of limited nuclear features but not diagnostic for papillary thyroid carcinoma showed stronger immunostaining for HBME than their respective counterparts with Hürthle cell changes. All Hürthle cell tumours showed negative to focal reactivity. This decrease of reactivity for HBME was proportional to the levels of Hürthle cell changes. In addition, focal to extensive apocrine-like changes were seen in most Hürthle cell neoplasms and rarely seen in non-Hürthle cell neoplasms. Apocrine-like changes abolished or decreased HBME immunoreactivity of papillary thyroid carcinoma and tumours with limited nuclear features. Immunostaining for cytokeratin AE3 was not affected by Hürthle cell or apocrine-like changes. CONCLUSIONS: All papillary thyroid carcinomas without Hürthle cell or apocrine-like differentiation are reactive for HBME. Hürthle cell tumours and tumours with Hürthle cell or apocrine-like changes show negative or focal reactivity for HBME. Except for this limitation, HBME is a sensitive marker for papillary thyroid carcinoma and tumours with limited nuclear features.     

Update on the cytologic features of papillary thyroid carcinoma variants

Papillary thyroid cancer (PTC), which accounts for 85–90% of all thyroid cancers, is generally an indolent tumor with long term survival rates >95%. A reliable definitive diagnosis of PTC is usually straightforward in fine needle aspirates of conventional PTC whenever the characteristic papillary and/or flat honeycomb sheet‐like architecture and the typical nuclear features of chromatin pallor, nuclear enlargement, crowding, grooves and pseudoinclusions are encountered. Conventional PTC, however, has diminished in relative frequency as compared to PTC variants, especially the noninvasive follicular variant of PTC, an indolent tumor which has recently been reclassified as “noninvasive follicular thyroid neoplasm with papillary‐like nuclear features” (NIFTP). These PTC variants are characterized by various architecture, cell type and shape, and stromal features, some of which can be recognized cytologically. Awareness of the cytomorphological spectrum and of the characteristic cytological features of these PTC variants is important to avoid diagnostic pitfalls. In this article, we review the different variants of PTC, including their cytomorphologic features, differential diagnosis, and salient molecular features. Diagn. Cytopathol. 2017;45:714–730. © 2017 Wiley Periodicals, Inc.     

Role of cd56 and e-cadherin expression in the differential diagnosis of papillary thyroid carcinoma and suspected follicular-patterned lesions of the thyroid: the prognostic importance of e-cadherin

Introduction: The pathological diagnosis of papillary thyroid carcinoma (PTC) is generally easy on routine sections stained with hematoxylin and eosin (H&E). However, the differentiation of the follicular variant of PTC (FVPTC) from other suspected follicular-patterned lesions of the thyroid is highly difficult. Among these, the lesions for which FVPTC cannot be excluded are classified as well-differentiated tumors of uncertain malignant potential (WDT-UMP). The most common immunohistochemical (IHC) markers used in the differential diagnosis include HBME-1, galectin-3, and CK19. However, none of these markers provide a 100% differential diagnosis. Objective: The present study compared the diagnostic value of CD56 and E-cadherin for the differentiation of FVPTC from the other benign follicular-patterned lesions, with HBME-1, galectin-3, and CK19. Using these markers, the controversial cases within the WDT-UMP group were reclassified. Additionally, the relationship between the reductions in E-cadherin expression with poor prognostic factors was investigated. Materials and methods: The IHC expressions of CD56, E-cadherin, HBME-1, galectin-3, and CK19 were evaluated in 181 thyroid lesions, including 101 PTCs (45 classical variant PTCs and 56 FVPTCs), 20 WDT-UMPs, 20 follicular adenomas (FAs), 20 hyperplastic nodules (HN), and 20 hyperplastic foci of lymphocytic thyroiditis. The results were statistically compared via SPSS. Results: The expressions of all of the markers were statistically significantly different in PTC and follicular-patterned lesions (P<0.05). It was found that the only marker with both sensitivity and specificity above 90% was CD56 negativity (sensitivity 91.1%, specificity 91.7%). The most sensitive and also the most specific double panel was CD56 negativity and galectin-3 positivity (sensitivity 96%, specificity 85%), and the most sensitive and specific triple panel was CD56 negativity, HBME-1 positivity, and galectin-3 positivity (97% and 70%, respectively).     

CD57 (leu-7) Expression is helpful in diagnosis of the follicular variant of papillary thyroid carcinoma

 CD57 (HNK-1) is a oligosaccharide antigen that is expressed by cells of several lineages. It is present on multipotential neuroepithelial cells during embryogenesis, and tumours of epithelial, neuroectodermal and nerve sheath origin also express CD57. Its role in the diagnosis of thyroid tumours is controversial. We have studied CD57 expression by immunohistochemistry to determine its utility in the classification of thyroid follicular lesions. Study material included 114 normal thyroid sections, 77 benign thyroid lesions (29 colloid nodules, 22 follicular adenomas, 20 cases of Hashimoto’s thyroiditis and 6 of Grave’s disease) and 83 thyroid carcinomas, including 31 follicular variants of papillary carcinoma. We observed CD57 positivity in 95% of thyroid carcinomas, 27% of follicular adenomas and 10% of colloid nodules. It was not expressed in the normal thyroid. CD57 expression in thyroid carcinomas was significantly different from that in normal and benign thyroid lesions (P < 0.0001). The follicular variant of papillary thyroid carcinoma also showed significantly higher CD57 expression than colloid nodules (P < 0.0009) or follicular adenomas (P < 0.0009). No significant difference was seen between colloid nodules and follicular adenomas. We conclude that CD57 immunohistochemistry is valuable in the classification of thyroid follicular lesions into benign and malignant groups and is also helpful in the diagnosis of the follicular variant of papillary thyroid carcinoma. Received: 26 August 1997 / Accepted: 14 October 1997     

Expression of HBME-1 and CD56 in follicular variant of papillary carcinoma in children: An immunohistochemical study and their diagnostic utility

Papillary thyroid carcinoma (PTC) is the most common differentiated thyroid cancer in children; and the follicular variant is the second most common variant after the classic subtype. The histological appearance of follicular variant of papillary thyroid cancer (FVPTC), can be mimicked by benign follicular nodules. Pediatric pathologists encountering such lesions with FVPTC-like appearance may err on diagnosing the benign lesions as malignant. In adult patients, several immunohistochemical markers have emerged recently as a useful adjunct to distinguish differentiated thyroid carcinomas from benign follicular lesions. We undertook an inter-institutional retrospective study to establish the diagnostic utility of immunohistochemical staining for HBME-1, Galectin-3 and CD56 in differentiating FVPTC from its benign mimics, follicular adenoma and adenomatoid nodules, in children. Our specific aim of the project was to define the sensitivity and specificity of the three antibodies in FVPTC. Based on institutional diagnoses, a total of 66 cases were obtained: 32 FVPTC and 34 benign follicular nodules that comprised of 23 follicular adenoma and 11 adenomatoid nodules. Five investigators, who were blinded to the original diagnoses, independently reviewed the slides following pre-determined criteria and semi-quantitatively scoring the immunohistochemical staining. The immunohistochemical staining revealed that a combination of positive HBME-1 and negative CD56 result gave 100% specificity and positive predictive value in distinguishing FVPTC from benign follicular nodules. However, the antibody combination suffered from a lower sensitivity (50%). We used a cutoff of 25% positivity of tumor cells in determining positivity of tumor cells to an antibody. In conclusion, our study found a very high specificity and strong positive predictive value for the combination of HBME-1 and CD56 immunohistochemical stains in distinguishing FVPTC from benign follicular lesions.     

Benign Hürthle cell adenoma with papillary architecture: a benign lesion mimicking oncocytic papillary carcinoma

We studied the significance of encapsulated Hürthle cell thyroid nodules with papillary structures lacking the nuclear features of papillary thyroid carcinoma (PTC); 19 cases fulfilling these criteria were encountered The patients' ages ranged from 22 to 40 years (32+/-6), and the F:M ratio was 3:1 The tumors measured from 0.5-5 cm (2+/-1.1). The diameter of the tumor cell nuclei ranged from 5.6 to 7.2 microns. Many nodules had nuclei displaying a fine chromatin pattern somewhat resembling those of PTC, but these were present in <20% of the tumor cells. Immunohistochemically, there was reactivity for MIB-1 in the papillary structures, negativity to focally weak reactivity for HBME and galectin-3, and negativity to moderate diffuse reactivity for CK19. Clinical follow-up from 1 to 19 years revealed no evidence of metastases in any of the cases. It is unlikely that the papillary structures in the study cases represent degenerative changes in view of the proliferative activity we have demonstrated in them. In view of (1) the encapsulation and the uniformity of the constituent cells, (2) the negative or weak immunoreactivity for galectin-3 and HBME and negative to moderate immunoreactivity for CK19, and (3) the absence or paucity of nuclear criteria for the diagnosis of PTC and the absence of lymph node metastasis in all study cases, we believe that these lesions represent the papillary variant of oncocytic follicular adenoma (Hürthle cell adenoma). Recognition of this entity is important to avoid an overdiagnosis of oncocytic PTC.     

Contribution of immunocytochemical stainings for galectin‐3, CD44, and HBME1 to fine‐needle aspiration cytology diagnosis of papillary thyroid carcinoma

In cytology practice some papillary thyroid carcinoma (PTC) cases have indeterminate diagnoses and overlapping cytological features with benign lesions. This study was undertaken to find out if immunocytochemistry using Galectin‐3, CD‐44 and HBME‐1 could be of help in such situations. Forty‐six cases consisting of 22 malignancy (PTC) cases, 7 suspicious of (S/O) PTC, 1 follicular neoplasm, 5 follicular lesion of undetermined significance (FLUS), and 11 benign (colloid goiter) cases diagnosed by FNA were included in this study. Staining reactions were graded in a sliding scale of –, 1+, 2+, 3+, and 4+. In an assessment of 100 cells, each cell with weak, and moderate to strong positive reaction were assigned a score of 1 and 4, respectively. Staining reaction of ≥+2 and scores >100 were considered positive. Frequency of cases with ≥+2 reaction, and scores >100 for each of Galectin‐3, CD‐44, and HBME‐1 were significantly higher in PTC or combined PTC and S/O PTC cases as compared with FLUS and benign cases taken together (P = 0.01744 to 0.00000). When the cases were compared according to histological malignant and benign diagnoses, the difference was also significant in respect of ≥+2 reaction, and scores >100 for Galectin‐3 and CD44 (P = 0.04923 to 0.00947); however, there was no significant difference, when these parameters for HBME1 were compared. Galectin 3, CD 44, and to some extent HBME 1 are useful immunocytochemical parameters with potential to support FNAC diagnosis of PTC, especially in situations with difficult differential diagnoses. Diagn. Cytopathol. 2014;42:498–505. © 2013 Wiley Periodicals, Inc.     

HBME-1 and CK19 are highly discriminatory in the cytological diagnosis of papillary thyroid carcinoma

The cytologic diagnosis of papillary thyroid carcinoma is straightforward in most instances. However, there are some mimics including goitrous nodules and Hurthle cell neoplasms. Many studies have shown the combination of HBME-1 and CK19 expression to be useful in reaching a correct histologic diagnosis on tissue sections. We aim to assess the value of these markers in the setting of cell blocks prepared from needle aspiration specimens. We performed immunohistochemical staining of HBME-1 and CK19 on cell block material from 22 thyroid nodules that also had follow-up histology. Both CK19 and HBME-1 were strongly positive in all nine cases of papillary thyroid carcinoma, the latter showing distinct luminal accentuation. In the non-papillary carcinomas, none showed positivity for both HBME-1 and CK19. Two of six Hurthle cell neoplasms were positive for CK19, however all were negative for HBME-1. One of nine goitrous nodules was strongly positive for HBME-1 with luminal/membranous staining, but this were negative for CK19. The sensitivity, specificity and positive predictive value of HBME-1 in distinguishing between papillary thyroid carcinoma and goitrous nodules/Hurthle cell neoplasms were found to be 100%, 92.9% and 0.9, respectively; and that of HBME-1 and CK19 combination was 100%, 100% and 1. We thus conclude that the combination of positive HBME-1 (luminal/membranous) and CK 19 (cytoplasmic) staining on cell blocks of thyroid cytologic specimens is highly discriminatory in the diagnostic workup for papillary thyroid carcinoma.     

Sensitive cytologic criteria for the identification of follicular variant of papillary thyroid carcinoma in fine-needle aspiration biopsy

The cytologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC) can be extremely challenging and may be associated with false negative diagnoses. The purpose of this study was to determine the minimal cytologic criteria needed to identify FVPTC. We examined sixty-nine fine-needle aspiration (FNA) cases, processed with Diff-Quik and Papanicolaou stains, that were either diagnostic or suspicious of FVPTC. All cases had histologic confirmation. These cases included 29 FVPTC, 18 classic papillary thyroid carcinoma (PTC), 17 follicular neoplasm (6 adenomas, 10 carcinomas, 1 neoplasm NOS), 2 lymphocytic thyroiditis and 3 nodular goiter. Seven of the most commonly cited cytomorphologic features, including flat syncytial sheets, nuclear enlargement, fine chromatin, nuclear grooves, nuclear pseudoinclusions, and amount of colloid and cytoplasm, were evaluated. A diffuse distribution of fine chromatin, nuclear grooves, and colloid was seen more often in FVPTC than in follicular neoplasm (p<0.01). The combination of flat/syncytial sheets, nuclear enlargement, and fine chromatin was observed in all our cases of FVPTC, and is therefore considered a sensitive marker in detecting FVPTC. Logistic regression analysis revealed colloid to be the only positive predictor in favor of FVPTC over classic PTC.     

甲状腺乳头状癌RET、CK19、TG、Ki-67的表达

目的 研究甲状腺乳头状癌RET、CK19、TG、Ki-67蛋白表达特点及其临床意义。方法 应用免疫组织化学SP法检测RET、CK19、TG、Ki-67蛋白在30例甲状腺乳头状癌、10例结节性甲状腺肿和18例癌旁正常甲状腺中的表达。结果 RET、CK19在乳头状癌的阳性率（66．7％、83．3％）明显高于结节性甲状腺肿和正常甲状腺阳性率（7．1％、25．0％）,两者差异有显著性（P〈0．01）。乳头状癌组及良性病例组TG表达阳性率差异无显著性（P〉0．05）。96．7％的乳头状癌Ki-67阳性细胞数小于10％。结论 RET及CK19在甲状腺乳头状癌表达增加,具有一定的病理诊断价值。     

Diagnostic utility of CD56 immunohistochemistry in papillary carcinoma of the thyroid

Diagnosis of papillary thyroid carcinoma (PTC), in many but not all cases, is an easily achievable diagnosis with almost minimal interobservable variability between pathologists. However, some cases of PTC, particularly the follicular variant, are quite challenging and show wide interobservable variability even among expert thyroid pathologists. Since proper diagnosis of PTC is crucial as it affects patients’ clinical management and prognosis, indications of PTC must be clearly apparent to be an objective rather than a subjective diagnosis. Unfortunately, to date, immunohistochemistry and molecular studies have failed to fully solve this problem. In this study, we assessed the protein expression and loss using antibodies against CD56 in normal follicular thyroid epithelium, follicular thyroid lesions, and follicular thyroid neoplasms in an attempt to evaluate its diagnostic value. A total of 185 cases were studied with tissues from 75 carcinomas (72 papillary, 2 follicular, 1 Hürthle cell) and 35 adenomas (32 follicular and 3 Hürthle cell) evaluated by immunohistochemistry for the expression of this marker. Non-neoplastic thyroids included 65 cases: nodular hyperplasia (n=25), thyrotoxic hyperplasia (Grave's disease) (n=5), lymphocytic thyroiditis (n=19), and Hashimoto's thyroiditis (n=6). Ten cases of normal thyroids from radical laryngectomies for laryngeal squamous cell carcinomas were also studied.     

Immunohistochemical markers in the diagnosis of papillary thyroid carcinomas: The promising role of combined immunostaining using HBME-1 and CD56

We aimed to evaluate the expression and diagnostic value of five immunohistochemical markers (HBME-1, Galectin-3, CK19, CD56 and p63) in a very large series of unequivocal papillary thyroid carcinoma (PTC) cases, including both the classic (CPTC) and the follicular variant (FVPTC).     

Diagnostic utility of galectin-3 and CD26/DPPIV as preoperative diagnostic markers for thyroid nodules

The aim of this study was to search for diagnostic markers that could correctly identify thyroid nodular lesions requiring urgent surgical treatment. We investigated whether galectin-3 and dipeptidyl peptidase IV (CD26/DPPIV) could be potential markers for improving the diagnostic accuracy of conventional cytology. Seventy-nine patients with histologically proven thyroid diseases were analyzed. The immunocytochemical staining results showed galectin-3 expression in neoplastic cells of all 37 papillary carcinomas, five of six follicular carcinomas, all three anaplastic carcinomas, one of three medullary carcinomas, and two of 14 follicular adenomas. All 16 adenomatous goiters were negative for galectin-3 immunostaining. On the other hand, all 37 papillary carcinomas, all six follicular carcinomas, and one of three anaplastic carcinomas revealed CD26/DPPIV expression, whereas all three medullary carcinomas were negative. Among benign thyroid lesions, four of 14 follicular adenomas and two of 16 adenomatous goiters exhibited varying degrees of immunoreactivity for CD26/DPPIV. RT-PCR analysis demonstrated overexpression of galectin-3 and CD26/DPPIV mRNAs in all six papillary and all three follicular carcinomas analyzed, whereas the mRNA expressions of these molecules were barely or not detectable in benign thyroid lesions and normal thyroid tissues, except for one case of follicular adenoma. In conclusion, we demonstrate that galectin-3 and CD26/DPPIV were consistently coexpressed at protein and mRNA levels in differentiated thyroid carcinomas. We propose that combined immunostaining for galectin-3 and CD26/DPPIV in the preoperative evaluation of thyroid nodules may play a role in accurate cytodiagnosis.