Simultaneous immunohistochemical expression of HBME-1 and galectin-3 differentiates papillary carcinomas from hyperfunctioning lesions of the thyroid

AIMS: The histological diagnosis is critical for the postsurgical management and follow-up of thyroid malignancies. The differential diagnosis between papillary carcinoma and hyperfunctioning lesions, either with papillary hyperplasia or with a follicular architecture, can create real diagnostic difficulty. The aim of this study was to evaluate the expression of several antibodies considered to be markers of malignancy in malignant and hyperfunctioning thyroid neoplasms and to include the most effective of them in a diagnostic panel. METHODS AND RESULTS: One hundred resected thyroid nodules--58 hyperfunctioning benign lesions and 42 papillary carcinomas (14 follicular variant, 14 macrofollicular variant and 14 classic type)--were immunohistochemically studied for HBME-1, galectin-3, cytokeratin (CK) 19 and RET-proto-oncogene. HBME-1 and galectin-3 showed 92.8% and 89% sensitivity, respectively, and their coexpression was present in 36 out of 42 papillary carcinomas (85.7%) and absent in non-malignant lesions. Their association increased sensitivity to 94.7% and the diagnostic accuracy to 97.9% and involved the highest number of cases (95%) in comparison with two other panels including, respectively, three (HBME-1, galectin-3, CK19) and all four antibodies. CONCLUSION: An immunohistochemical panel consisting of HBME-1 and galectin-3 can make a correct distinction between malignant and hyperfunctioning thyroid neoplasms with high diagnostic accuracy.     

Immunohistochemical separation of follicular variant of papillary thyroid carcinoma from follicular adenoma

The accurate diagnosis of differentiated thyroid tumors is very important for clinical management of patients. The histopathological distinction between some types of differentiated thyroid tumors can be very difficult even for experienced pathologists. We used immunohistochemical markers from published data obtained from DNA expression profiling, tissue microarray analysis, and immunohistochemistry to analyze a series of 157 thyroid tumors and 5 normal thyroids. These analyses showed that several antibodies were useful in distinguishing follicular adenomas from follicular variant of papillary thyroid carcinomas including HBME-1, CITED 1, galectin-3, cytokeratin 19, and S100A4 (p<0.0001). A combination of markers consisting of a panel of HBME-1, galectin-3, and CK19 or a panel of HBME-1, CITED1, and galectin-3 was usually most effective in distinguishing follicular adenoma from follicular variant of papillary thyroid carcinoma. Because individual tumors may not express some of these markers, the use of a panel of antibodies is recommended. These results indicate that some individual antibodies or a panel of antibodies combined with histopathological analysis can be useful in separating follicular adenoma (FA) from follicular variant of papillary thyroid carcinoma (FVPTC).     

Expression of cytokeratin 19, HBME-1 and galectin-3 in neoplastic and nonneoplastic thyroid lesions

In this study, 105 cases of thyroid lesions were evaluated to assess the role of HBME-1, cytokeratin-19 (CK-19), galectin-3 in distinguishing benign from malignant thyroid lesions. Thirty-seven papillary, 10 follicular, 6 medullary, 1 mixed medullary follicular cell carcinoma, 3 poorly differentiated carcinoma, 18 adenomatous nodular hyperplasia, 30 follicular adenoma cases were included in the study. Immunohistochemical staining was performed with HBME-1, CK-19, galectin-3 on cross-sections derived from selected paraffin blocks. Benign and malignant lesions were compared in terms of intensity, percentage and type of staining with CK-19, HBME-1 and galectin-3, and a statistically significant difference (p < 0.05) was found. The percentage and intensity of staining was higher in malignant lesions. Especially, strong and diffuse expressions of CK19, HBME-1 and galectin-3 were observed in papillary carcinomas. Membranous (luminal) staining was seen more frequently in malignant lesions; cytoplasmic staining in benign lesions. It was concluded that these markers could assist in the diagnosis of thyroid lesions with cellular properties suspicious for the diagnosis of papillary carcinoma and without capsule and vessel invasion. They may be used especially in cases where the follicular variant of papillary carcinoma, follicular adenoma and follicular carcinoma are confused with each other and follicular adenoma cannot be differentiated from follicular carcinoma.     

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.     

Diagnostic value of galectin-3, HBME-1, cytokeratin 19, high molecular weight cytokeratin, cyclin D1 and p27(kip1) in the differential diagnosis of thyroid nodules

The distinction between benign and malignant thyroid tumors is critical for the management of patients with thyroid nodules. We applied immunohistochemical staining for galectin-3, HBME-1, cytokeratin 19 (CK19), high molecular weight cytokeratin (HMWCK), cyclin D1 and p27(kip1) in 295 thyroid lesions to determine their diagnostic accuracy. The expression of all markers was significantly associated with differentiated thyroid carcinoma (DTC).The sensitivity for the diagnosis of DTC was 94.7% with galectin-3, 91.3% with HBME-1, and 90.3% with CK19. The specificities of these markers were 95.5%, 69.7%, and 83.1%, respectively. Combining these markers, co-expression of galectin-3 and CK19 or galectin-3 and HBME-1 was seen in 93.2% of carcinomas but in none of the benign nodules. Comparing follicular variant of papillary carcinoma (FVPC) with follicular carcinoma (FC), the expression of galectin-3, CK19, and HMWCK was significantly higher in FVPC. When comparing FC with FA, the expression of galectin-3 and HBME-1 was significantly higher in FC. These results suggest that 1) galectin-3 is a useful marker in the distinction between benign and malignant thyroid tumors, 2) the combined use of HBME-1 and CK19 can increase the diagnostic accuracy, and 3) the use of CK19 and HMWCK can aid in the differential diagnosis between PC and FC.     

Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy

Aims : To investigate the usefulness of immunohistochemical expression and immunolocalization of a panel of thyroid malignancy markers including HBME-1, cytokeratin (CK) 19 and galectin-3.
Methods and results : We evaluated 170 thyroid lesions including 148 neoplastic lesions [84 papillary carcinomas (PC), 38 follicular carcinomas (FC), 18 follicular adenomas, one hyalinizing trabecular tumour, five medullary carcinomas, two anaplastic carcinomas] and 22 non-neoplastic lesions (12 adenomatous nodules and 10 Hashimoto's thyroiditis). HBME-1, galectin-3 and CK19 were expressed in 94%, 72.6%, 72.6% of PCs and in 63%, 21%, 21% of FCs. The three markers were mostly negative in all normal tissues. Although the most helpful marker in terms of sensitivity and specificity for the follicular variant of PC and for FC diagnosis was HBME-1, when we consider the differentiation between cases of follicular variant of papillary carcinoma (FVPC) and FC or adenoma, in terms of percentage of positive cells, galectin-3 and CK19 were more relevant.
Conclusions : HBME-1 is the most sensitive marker for thyroid malignancy but the three markers may be useful in specific cases. This panel of markers is useful to differentiate the follicular patterned lesions, with special reference to the FVPC.     

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.     

p53, ki-67, galectin-3, HBME-1, 34βE12和CK19在甲状腺乳头状癌中的表达及临床病理意义

 摘要：目的：探讨p53, ki-67, galectin-3, HBME-1, 34βE12和CK-19在甲状腺乳头状癌中的表达及临床病理意义。方法：采用免疫组化检测43例甲状腺乳头状癌、37例结节性甲状腺肿、33例甲状腺腺瘤和17例桥本甲状腺炎中p53, ki-67, galectin-3, HBME-1, 34βE12和CK-19的表达。结果：p53, ki-67, galectin-3, HBME-1, 34βE12和CK-19在甲状腺乳头状癌中的阳性表达例数分别为88.37%、79.07%、88.37%、93.02%、86.05%、95.35%;6种蛋白在甲状腺乳头状癌与结节性甲状腺肿、甲状腺腺瘤和桥本甲状腺炎中的阳性表达率相比较差异均有统计学意义（P<0.01）。结论：联合检测p53, ki-67, galectin-3, HBME-1, 34βE12和CK-19在甲状腺乳头状癌与良性病变的诊断和鉴别诊断中具有重要的价值。     

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).     

Galectin-3 expression in papillary microcarcinoma of the thyroid

AIMS: Galectin-3 is a beta-galactoside binding protein, recently recognized as a promising molecular marker of thyroid malignancy. As reported in several studies, galectin-3 is highly expressed in papillary thyroid carcinoma, but its expression has not been investigated in papillary microcarcinoma, which is a variant of papillary thyroid carcinoma. METHODS AND RESULTS: Using a monoclonal antibody to galectin-3 and the avidin-biotin-peroxidase complex (ABC) immunohistochemical technique, we analysed galectin-3 expression in 63 cases of papillary microcarcinoma. The results showed immunohistochemical reactivity for galectin-3 in 51 (80.9%) cases. Intensity of staining varied from strong or moderate to weak. Galectin-3 localization was mostly cytoplasmic, but also membranous or nuclear in some cells. Immunohistochemical expression of galectin-3 was not found in 12 (19.1%) cases. Most galectin-3 negative microcarcinomas (10/12) were of the non-classical type, i.e. without papillary architecture. Neither the frequency nor the intensity of a positive reaction was related to tumour size. CONCLUSIONS: Galectin-3 gene is expressed at the protein level in most papillary microcarcinomas, although with slightly lower frequency than that reported for clinically evident papillary thyroid carcinoma. The presence of galectin-3 in clinically silent microcarcinomas may indicate that galectin-3 is not related to growth or aggressiveness of papillary thyroid microcarcinomas but rather plays some other role in thyroid tumour biology.     

Expression of papillary thyroid carcinoma-associated molecular markers and their significance in follicular epithelial dysplasia with papillary thyroid carcinoma-like nuclear alterations in Hashimoto’s thyroiditis

The aim of this study was to evaluate the expression of papillary thyroid carcinoma (PTC)-associated tumor markers in follicular epithelial dysplasia showing PTC-like nuclear alterations (FED) in Hashimoto’s thyroiditis (HT) and to explore the relationship between HT and PTC. In this study, 43 PTC, 18 HT with FED and 16 peritumoral benign thyroid tissues were immunohistochemically analyzed for CK19, galectin-3, HBME-1, CD56, claudin-1 and NGAL expression. Our research revealed that in HT, the expression of CK19, galectin-3, HBME-1, claudin-1 and NGAL was focal and limited to FED, while CD56 was strongly positive in FED and most Hürthle cells. The stain intensity of CK19, claudin-1 and NGAL in FED decreased compared with PTC, but were significantly higher than that in peritumoral benign thyroid tissues (all P < 0.0125). For galectin-3, HBME-1 and CD56, no statistically significant difference was detected between HT and peritumoral benign thyroid tissues (all P > 0.05). In conclusion, In HT, FED might be a precancerous condition closely associated with PTC development as they have overlaps in cytological and immunomarker profiles, indicating that in patients with HT, under prolonged stimuli from chronic inflammation, part of follicular epithelia may show regeneration, hyperplasia, Hürthle cell metaplasia and dysplasia, eventually malignant transformation. Hence, long term follow-up and regular inspection would be necessary for Hashimoto’s thyroiditis with FED.     

Combined immunohistochemistry for thyroid peroxidase, galectin-3, CK19 and HBME-1 in differential diagnosis of thyroid tumors

We evaluated some proposed molecular thyroid tumor markers: thyroid peroxidase (TPO), galectin-3, cytokeratin-19, and HBME-1, individually and in combination, by immunohistochemistry in a total of 242 archival thyroid tissue sections. The expression of each individual marker was most helpful for the diagnosis of papillary carcinoma and its follicular variant. However, none of them was sensitive and specific enough to discriminate between Hürthle adenoma and carcinoma. Galectin-3 and HBME-1 could be used as single discriminators between follicular thyroid adenoma and carcinoma, but HBME-1 is the better choice. As a single test, all analyzed tumor markers had sufficient power to predict differentiated thyroid cancer, with sensitivities ranging from 66.5% to 82.2%. The sensitivity was improved by using combinations of some proposed markers. Only two antigens, HBME-1 and TPO, had distinct predictive values for different diagnostic alternatives i.e. a sequential combination improved diagnostic accuracy between follicular thyroid adenoma and the follicular variant of papillary thyroid carcinoma to 92.6% and consequently, between overall benign and malignant thyroid tumors to 89.1%. HBME-1 is the most accurate ancillary stain in discriminating well-differentiated thyroid carcinomas from benign tumors, although the addition of TPO did improve accuracy and served as a useful confirmatory marker.     

Cytokeratin 19 and galectin-3 immunohistochemistry in the differential diagnosis of solitary thyroid nodules

AIMS: The immunohistochemical expression of cytokeratin 19 (CK 19) and galectin-3 was evaluated in 69 thyroid lesions to assess their potential as markers in the diagnosis and classification of thyroid malignancy. The following were studied: 26 cases of papillary carcinoma, 12 of follicular carcinoma, 20 follicular adenomas, two medullary carcinomas, one anaplastic carcinoma and eight multinodular goitres. METHODS AND RESULTS: Formalin-fixed paraffin-embedded thyroid tissues were stained immunohistochemically for both CK 19 and galectin-3. CK 19 expression was found in all 26 papillary carcinomas, five of 12 follicular carcinomas, two of two medullary carcinomas and one case of anaplastic carcinoma. Only five of 20 follicular adenomas were positive for CK 19, and this was in a focal distribution. Two of eight multinodular goitres stained focally positive. Galectin-3 expression was found in 22 of 26 papillary carcinomas, 12 of 12 follicular carcinomas and one of two cases of medullary carcinoma. Only two of 20 follicular adenomas were positive. Three of eight multinodular goitres showed focal galectin-3 expression. CONCLUSIONS: Our findings suggest that the immunohistochemical localization of CK 19 and of galectin-3 is a useful adjunct to the histopathological diagnosis of a solitary thyroid lesion. The expression of CK 19 favours a diagnosis of papillary carcinoma in all its variant patterns. Galectin-3 may serve as a marker for the recognition of follicular carcinoma, particularly the minimally invasive form.     

Diagnosis of necrotic and degenerate thyroid lesions: value of immunohistochemistry

Aims: Classification of necrotic or degenerate thyroid nodules can be difficult. The aim of this study was to investigate the value of cytokeratins, thyroid-specific markers (TTF-1 and thyroglobulin) and HBME-1 antibodies in such thyroid lesions. METHODS AND RESULTS: Twenty-eight necrotic or degenerate thyroid lesions, including four cervical cystic papillary carcinoma (CPC) metastases, were evaluated with immunohistochemistry for TTF-1, thyroglobulin, HBME-1, AE1&3, Cam5.2, MNF116 and cytokeratin (CK)19. There was loss of TTF-1 staining in all necrotic lesions, with positive staining in degenerate tumour cells of all four metastatic CPCs. Thyroglobulin was retained in 18 lesions. Dual CK19 and HBME-1 expression was seen only in six of seven necrotic papillary thyroid carcinomas and the four metastatic CPCs. Retained immunoreactivity for AE1&3 and Cam5.2 was seen in most necrotic papillary carcinomas (n = 11/11 and n = 10/11, respectively), poorly differentiated carcinomas (n = 2/3 and n = 3/3, respectively) and follicular-patterned areas of anaplastic carcinoma (n = 3/5 and n = 4/5, respectively). Cam5.2 showed spurious staining of macrophages in eight lesions. CONCLUSIONS: Thyroglobulin is useful in establishing the thyroid origin of a necrotic lesion. TTF-1 may be useful for highlighting degenerate tumour cells within metastatic CPCs. Retained expression of CK19 and HBME-1 is seen in necrotic papillary carcinomas. AE1&3 is the most specific and Cam5.2 the most sensitive of the CK cocktails in non-viable thyroid lesions.     

Heterotopic intrathymic thyroid tissue

Heterotopic intrathymic thyroid tissue is an extremely rare condition, but it is important to distinguish it from metastases of clinically undetected thyroid carcinoma because metastatic papillary thyroid carcinoma is often so well differentiated, simulating normal thyroid tissue. Described herein are histological findings of heterotopic intrathymic thyroid tissue that was incidentally identified in a woman with papillary thyroid carcinoma during histological examination of a radical neck dissection specimen. These findings emphasize that this rare incidence may occur and should be differentiated from metastatic papillary carcinoma. Histologically, the patient's intrathymic thyroid follicles were identical to the normal thyroid follicles, having flat cuboidal cells with uniformly small nuclei without nuclear grooves or inclusions. The follicular cells had a low Ki-67 labeling index close to zero, and immunonegativity for galectin-3, HBME-1, and RET oncoprotein, in contrast to the tumor cells in primary papillary thyroid carcinoma of the patient. To the authors' knowledge this is the first case report of intrathymic heterotopic thyroid tissue posing a diagnostic difficulty in a patient with papillary thyroid carcinoma.     

Follicular epithelial dysplasia of the thyroid: morphological and immunohistochemical characterization of a putative preneoplastic lesion to papillary thyroid carcinoma in chronic lymphocytic thyroiditis

In chronic lymphocytic thyroiditis (CLT), the follicular epithelial cells display cytological atypia resembling papillary thyroid carcinoma (PTC), and epidemiological studies have suggested an increased risk of PTC in patients with this condition. While reactive atypia is observed diffusely in CLT-affected thyroid parenchyma, it is not unusual to find microscopic foci morphologically distinct from the surrounding parenchyma, exhibiting more pronounced cytological and architectural atypia. These small atypical lesions, which we term “follicular epithelial dysplasia” (FED), are particularly prominent in cases of severe CLT, yet lack invasive growth, papillary architecture, or intranuclear pseudoinclusions. To gain further insight into their biological significance, we constructed a tissue microarray of 70 cases of CLT, comprised of morphologically normal thyroid, thyroid with reactive atypia, FED, follicular nodular disease (nodular hyperplasia or follicular adenoma), and PTC. Immunohistochemical staining was performed for a marker panel including PTC (HBME-1, cytokeratin 19, galectin-3, and cyclin-D1) as well as TTF-1, thyroglobulin, and p63. Slides were digitally scanned and immunohistochemical staining evaluated using automated image analysis software. FED lesions were positive for TTF-1 and thyroglobulin (50/50, 100 %), though some (13/50, 26 %) also expressed p63. Similar to PTC, strong diffuse staining was observed for HBME-1 (43/50, 86 %), cytokeratin 19 (48/50, 96 %), galectin-3 (20/50, 40 %) and cyclin-D1 (38/50, 76 %). In contrast, normal thyroid, reactive atypia, and follicular nodular disease were negative, or at most, exhibited focal weak staining for HBME-1, cytokeratin 19, and galectin-3. The results of this study demonstrate the presence of atypical microscopic lesions in CLT with an immunohistochemical profile similar to PTC, supporting the concept of a premalignant lesion preceding PTC, arising in the context of severe chronic inflammation.     

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 expression of HBME-1 and galectin-3 in the differential diagnosis of follicular-derived thyroid nodules

BackgroundThyroid nodules are common among adults with only a small percentage being malignant and histologically mimic benign nodules. Accurate diagnosis of these thyroid nodules is critical for the proper clinical management. The determination of malignancy in follicular patterned thyroid lesions is based on postoperative histological findings. Therefore, affected patients are referred for surgery, although only 10% will have a final diagnosis of malignancy. The aim of this study was to investigate the ability of two immunohistochemical (IHC) markers; galectin-3 and Hector Battifora mesothelial-1 (HBME-1) individually or in combination, to distinguish between benign (non-neoplastic and neoplastic) and malignant (follicular and papillary carcinomas) thyroid lesions removed by surgical resection.MethodsWe investigated the immunoexpression of galectin-3 and HBME-1 in 50 cases of benign and malignant thyroid nodules. The benign group included 13 cases of thyroid nodular goiter (NG) and 9 cases of follicular adenoma (FA). The malignant group included 5 cases of follicular thyroid carcinomas (FC), 18 cases of classic papillary thyroid carcinoma and 5 cases of follicular variant papillary carcinoma (FVPC).ResultsThe staining results showed that malignant tumors expressed galectin-3 and HBME-1 significantly more than benign nodules. The sensitivity of these markers for the distinction between benign and malignant lesions ranged from 89.3% to 92.9%. Co-expression of galectin-3 and HBME-1 was seen in 82.1% of carcinomas, but in none of the benign nodules. Immunoexpression was usually diffuse in malignant tumors, and focal in the benign lesions.ConclusionOur findings indicate that these immunohistochemical markers are significantly more expressed in malignant tumors compared to benign lesions and may be of additional diagnostic value when combined with routine histology. Galectin-3 has higher sensitivity and specificity of immunoexpression in thyroid malignancy than HBME-1, and the combined use of galectin-3 and HBME-1 can increase the specificity of immunoexpression in malignant tumors.