Does Galectin3 Immunohistochemical Marker Help in Diagnosing the Nature of Benign or Malignant Thyroid Tumor?

Introduction: Galectin-3 has been reported quite accurate to detect or exclude malignancy in nodules with prior indeterminate Fine Needle Aspiration Cytology and per operative findings. Keeping this fact in mind, Galectin-3 can have a pivotal role in separating benign from the malignant thyroid neoplasms. We aim to determine the frequency and intensity of Galectin-3 immunohistochemical expression among benign and malignant thyroid neoplasms confirmed on histopathology. Materials and Methods: We studied 78 thyroid specimens diagnosed with thyroid neoplasms on histopathology. Out of these 39 were benign cases (follicular adenoma and hurthle cell adenoma) and 39 were malignant cases (papillary thyroid carcinomas, follicular carcinoma, medullary carcinoma and poorly differentiated carcinoma). Each specimen was examined grossly and microscopically and checked for immunohistochemical staining pattern of Galectin-3 under the microscope. Results: Age range in this study was from 15 to 65 years with mean age of 44.97 ± 10.78 years. Out of these 78 patients, 17 (21.79%) were male and 61 (78.21%) were female with male to female ratio of 1:3.6. Frequency of positive Galectin-3 immuno histochemical expression among thyroid neoplasms was found in 32 (41.03%) cases with Galectin-3 showing positive staining in 21 (53.85%) of all malignant and 11 (28.21%) of all benign cases .Among the malignant neoplasms, positivity was seen most frequently in papillary thyroid carcinomas as compared to the other malignancies. Conclusion: This study concluded that positive Galectin-3 immunohistochemical expression is more in malignant thyroid neoplasms (53.85%) as compare to the benign lesions (28.21%). Therefore, we recommend that this marker cannot be used alone for the routine diagnosis of malignant lesions as it has shown less sensitivity and specificity. Moreover it also has shown no significant role in differentiating between the benign and the malignant thyroid neoplasms.

Galectin-3 Immunohistochemical Expression in Thyroid Neoplasms – A Study from Kalaburagi, Karnataka

BACKGROUND Thyroid carcinoma is the most common endocrine malignancy. Galectin-3 has been implicated in malignant transformation and metastasis of cancer cells and it has received notable recognition for its usefulness as a diagnostic marker for thyroid cancer. We wanted to evaluate the expression of Galectin-3 on thyroid neoplasms, establish its diagnostic accuracy and also differentiate between benign and malignant thyroid lesions. METHODS A total of 54 thyroidectomy specimens were studied over a period of 3 years (2016 - 2019) which included 20 benign and 34 malignant thyroid neoplasms. Histopathologic evaluation of H & E stained sections was done and immunohistochemistry (IHC) staining for Galectin-3 was performed for all neoplasms with the polymeric method using lyophilized mouse monoclonal antibody. (Path n Situ) and grading based on intensity of Galectin-3 expression were noted. RESULTS Galectin-3 expression was significantly higher (P < 0.001) in malignant thyroid neoplasms in comparison to the benign neoplasms. Galectin-3 expression for malignant neoplasms showed sensitivity of 88.23 %, specificity of 95.0 %, positive predictive value (PPV) of 96.8 % and negative predictive value (NPV) of 82.6 %. Galectin-3 expression in Papillary thyroid carcinoma showed a sensitivity of 95.83 % and PPV of 88.2 %. While comparing the neoplasms showing follicular pattern, Galectin-3 expression was more in the malignant neoplasms (follicular carcinoma and follicular variant of papillary carcinoma thyroid) than benign neoplasms (follicular adenoma). CONCLUSIONS Galectin-3 is a useful marker in differentiating benign and malignant thyroid neoplasms. Galectin-3 is sensitive for Papillary thyroid carcinoma (PTC) and among the follicular patterned lesions, Galectin-3 is sensitive for follicular variant of papillary carcinoma and follicular carcinoma. Thus Galectin-3 protein expression evaluated using immunohistochemistry technique acts as an adjunctive ancillary technique in thyroid cancer diagnosis. KEYWORDS Galectin-3, Immunohistochemistry, Thyroid Carcinoma, Papillary Thyroid Carcinoma

Prevalence of well-characterized and putative marker mutations in benign and malignant thyroid neoplasms

Недостаточная точность дооперационной дифференциальной диагностики путём цитологического исследования материала, полученного при тонкоигольной аспирационной биопсии, и низкая доля случаев злокачественных новообразований, описываемых молекулярно-генетическими маркерами с известной диагностической значимостью, обуславливают актуальность поиска новых молекулярно-генетических маркеров и необходимость оценки их ассоциации с риском рака и клинико-морфологическими характеристиками. Целью работы явилось исследование распространенности расширенного спектра известных и новых предполагаемых драйверных и вторичных мутаций в доброкачественных и злокачественных новообразованиях щитовидной железы. Материал исследования: свежезамороженный хирургический материал злокачественных (64 образца) и доброкачественных (16 образцов) новообразований щитовидной железы. Для поиска точковых вариантов, коротких инсерций/делеций, изменений копийности выполнено таргетное высокопроизводительное секвенирование ДНК по технологии AmpliSeq на платформе NextSeq 550 (Illumina). Поиск перестроек выполнен по наличию транскрипта методом таргетного высокопроизводительного секвенирования по технологии AmpliSeq на платформе MiSeq (Illumina). Мутации в генах BRAF, KRAS, NRAS, HRAS выявлены в 62% случаев рака. В 12% случаев рака выявлены перестройки CCDC6-RET (3 случая) и PAX8-PPARG (2 случая), TPM3-NTRK1, ETV6-NTRK3, STRN-ALK - по одному случаю. Во всех случаях выявленные перестройки были взаимоисключающие с другими известными драйверными мутациями. При доброкачественных новообразованиях перестройки не выявлены. Мутации промотора гена TERT выявлены в 10% случаев рака щитовидной железы и были представлены совместно с известными драйверными мутациями. Известная миссенс мутация EIF1AX выявлена в одном случае доброкачественного новообразования, при злокачественных новообразованиях мутации в гене EIF1AX не выявлены. Предполагаемые драйверные мутации в онкогенах PPM1D, PDGFRA, KDR выявлены в образцах рака щитовидной железы и не выявлены при доброкачественных новообразованиях щитовидной железы. Выводы: дана характеристика распространенности драйверных мутаций с известной диагностической значимостью и мутаций в генах, описанных в литературе без установленной диагностической значимости, при доброкачественных и злокачественных новообразованиях щитовидной железы. Insufficient accuracy of preoperative differential diagnostics by cytological examination of fine-needle aspiration biopsy material and low proportion of cases of malignant neoplasms described by molecular genetic markers with known diagnostic significance determine the relevance of the search for new molecular genetic markers with an assessment of their association with cancer risk and clinical and morphological characteristics. The aim of the work was to study the prevalence of an expanded spectrum of known and new putative driver and secondary mutations in benign and malignant thyroid neoplasms. Material: fresh frozen surgical material of malignant (64 samples) and benign (16 samples) thyroid neoplasms. Methods: search for point variants, short insertions/deletions, and copy number variations was performed via targeted high-throughput sequencing using AmpliSeq technology on the Illumina NextSeq platform. Fusions were by the presence of fused transcript by targeted high-throughput sequencing using AmpliSeq technology on the Illumina MiSeq platform. Results: mutations in genes BRAF, KRAS, NRAS, HRAS were detected in 62% of cancer cases. In 12% of cancers we detected rearrangements of CCDC6-RET (3 cases) and PAX8-PPARG (2 cases), TPM3-NTRK1, ETV6-NTRK3, STRN-ALK - one case each. In all cases, the identified rearrangements were mutually exclusive with other known driver mutations. In benign neoplasms, no rearrangements were found. Mutations in the TERT gene promoter have been identified in 10% of thyroid cancers and have been associated with known driver mutations. The well-known missense mutation EIF1AX was detected in one case of a benign neoplasm of the thyroid gland; in malignant neoplasms, no EIF1AX mutation were detected. Putative driver mutations in the PPM1D, PDGFRA, KDR oncogenes were detected in thyroid cancer samples and were not detected in benign thyroid neoplasms. Conclusions: the work characterize the prevalence of driver mutations with a known diagnostic significance and mutations in genes described in the literature without a known diagnostic significance in benign and malignant thyroid neoplasms.

Role of p27 in differentiating follicular adenoma and follicular carcinoma of the thyroid

Background: Thyroid neoplasms represent a broad spectrum of tumors with different biologic behaviour. Although investigations like thyroid function tests, scintigraphy and ultrasonography were routinely used for the diagnosis of thyroid nodules, they could not discriminate between benign and malignant lesions. The present study is undertaken to assess the expression of cell cycle protein such as p27kip1 (p27) in thyroid neoplasms which might be useful in predicting behaviour of various thyroid neoplasms and aid in their diagnosis. Aim of the study was to assess the expression of p27 and its role in differentiating follicular adenoma and follicular carcinoma of the thyroid.Methods: The present study was undertaken to evaluate the expression of p27 in thyroid neoplasms with the help of immunohistochemical analysis over a period of 1 year. The study was conducted on archival blocks retrieved from the Department of Pathology, SMCH. 19 thyroid neoplasms were diagnosed (7 benign, 12 malignant) and IHC expression of p27 was studied.Results: There was over-expression of p27 staining in case of follicular adenoma whereas malignant lesions showed underexpression on p27 staining. P27 expression was significantly different in follicular adenoma and follicular carcinoma of the thyroid.Conclusions: The role of p27 in differentiating benign and malignant thyroid neoplasms may prove it to be a candidate marker if combined with other additional investigations like radionuclide scan or using a broad panel of IHC markers. This may provide more insight into the behaviour of tumors in a detailed manner.

NEOPLASIA FOLICULAR E CARCINOMA PAPILÍFERO EM UMA MESMA TIREOIDE: UM RELATO DE CASO

RESUMO Neoplasias malignas da tireóide correspondem ao tipo mais comum de câncer endócrino. Dentre os diferentes subtipos histológicos, os mais comuns são os carcinomas papilares, seguidos dos carcinomas foliculares. A ocorrência de “tumores de colisão” na tireoide é rara, e a associação aumenta os riscos de metastatização linfática e hematogênica. A condução de “tumores de colisão” na tireoide é geralmente complexa e a literatura sobre esses casos é escassa, sendo usualmente guiada pelo subtipo mais agressivo. O tratamento cirúrgico com terapia adjuvante guiado pela histologia e pelo estado do paciente é a recomendação. Relatamos o caso de uma paciente com queixa de nódulos tireoidianos palpáveis associado a pigarro recorrente há 1 mês, e que ao exame físico apresentava múltiplos nódulos em toda a topografia da tireoide, com aumento difuso da glândula. O estudo anatomopatológico evidenciou um “tumor de colisão” em tireoide, que apresentou-se histologicamente como carcinoma folicular e papilar. Palavras-chave: Tireoide; carcinoma; tumor de colisão. ABSTRACT Malignant thyroid neoplasms are the most common type of endocrine cancer. Among the different histological subtypes, the most common are papillary carcinomas, followed by follicular carcinomas. The occurrence of thyroid “collision tumors” is rare, and the association increases the risks of lymphatic and hematogenous metastatization. The conduction of “collision tumors” in the thyroid is generally complex and the literature on these cases is scarce and usually guided by the more aggressive subtype. Surgical treatment with adjuvant therapy guided by histology and patient status is the recommendation. We report the case of a patient complaining of palpable thyroid nodules associated with recurrent throat clearing for 1 month, and on physical examination presented multiple nodules throughout the thyroid topography, with diffuse enlargement of the gland. The anatomopathological study showed a “collision tumor” in the thyroid, which presented histologically as follicular and papillary carcinoma. Key-words: Thyroid; carcinoma; collision tumor.

Role of CD10 Marker in Differentiating Malignant Thyroid Neoplasms from Benign Thyroid Lesions (Immunohistochemical & Histopathological Study)

BACKGROUND: CD10 was initially recognised as a cell–surface antigen expressed by acute lymphoblastic leukaemias, and hence it’s early designation as Common Acute Lymphoblastic Leukemia Antigen (CALLA). Also, it has been proven to be reactive in various non-lymphoid cells and tissue and different types of neoplasms. AIM: To evaluate the immunohistochemical expression of CD10 in malignant thyroid neoplasms and different benign lesions and to assess whether CD10 can be used as a malignancy marker in thyroid pathology or not. MATERIAL AND METHODS: A total of 83 archived, formalin fixed, paraffin embedded tissue blocks of 83 cases of malignant thyroid neoplasms and different benign lesions. The samples were immunohistochemically analysed for CD10 expression. A p-value of less than 0.05 was considered statistically significant. RESULTS: CD10 was expressed in 91% of the studied malignant thyroid neoplasms and 58% of benign thyroid lesions. It was expressed in 26 of 28 (92.9%) conventional papillary carcinomas, ten of 10 (100%) follicular variants of papillary carcinoma, seven of nine (77.8%) minimally invasive follicular carcinomas, two of three (66.7%) widely invasive follicular carcinomas, and seven of 7 (100%) undifferentiated carcinomas, seven of 11 (66.7%) adenomatous nodules and eight of 15 (53.3%) follicular adenomas. No statistically significant correlations were detected between CD10 expression and patients’ age, sex, lymph node metastasis, tumour stage and capsular invasion. CONCLUSION: CD10 shows strong sensitivity (91.2%) and moderate specificity (42.3%) in the diagnosis of malignancy overall and shows strong sensitivity (86.4%) and moderate specificity (42.3%) in the diagnosis of malignancy in the follicular-patterned lesions. So, CD10 might be useful in differentiating malignant from benign thyroid lesions (good positive test) and in the diagnosis of follicular variant of papillary carcinoma.