ORIGINAL ARTICLE
The diagnostic utility of INSM1 and GATA3 in discriminating problematic medullary thyroid carcinoma, thyroid and parathyroid lesions
1
Department of Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
Submission date: 2020-12-14
Final revision date: 2021-02-03
Acceptance date: 2021-03-14
Publication date: 2021-05-31
Pol J Pathol 2021;72(1):11-22
KEYWORDS
TOPICS
ABSTRACT
Discriminating thyroid and parathyroid lesions may sometimes pose a diagnostic difficulty. Medullary thyroid carcinomas (MTCs) display various cytologic and architectural features that resemble other thyroid and even rarely some parathyroid neoplasms. Moreover, some MTCs may have negative serum calcitonin, rendering them difficult to diagnose. Hence, to reach an appropriate diagnosis in problematic cases of these three categories – thyroid lesions, MTC and parathyroid lesions – the use of several immunohistochemical panels has been suggested and applied. However, conventional markers are not always conclusive in problematic cases. Thus, in the current study we aim to evaluate the diagnostic utility of using GATA3 and INSM1 (insulinoma-associated protein 1) as novel nuclear markers to be applied as an adjunct in case of histopathologic suspicion.
A retrospective study was carried out on samples of lesions from three groups: group 1: thyroid lesions (27), group 2: medullary thyroid carcinoma (25); 1/25 had negative serum levels of calcitonin, and group 3: parathyroid lesions (36). Biopsies were received at the Pathology Laboratory of Ain Shams University Hospitals.
INSM1 showed 98% diagnostic accuracy in diagnosing MTC and differentiating it from other thyroid lesions. The case of MTC with negative serum calcitonin showed positive INSM1 staining. GATA3 showed 96.8% diagnostic accuracy in diagnosing parathyroid lesions and differentiating them from thyroid lesions.
Using immunohistochemical staining by GATA3 and INSM1, in the appropriate histopathological setting, significantly aids in the differentiation between thyroid lesions, parathyroid lesions and MTCs. INSM1 could serve as a potential diagnostic marker in the rare cases of non-secretory MTC and in metastatic work up.
A retrospective study was carried out on samples of lesions from three groups: group 1: thyroid lesions (27), group 2: medullary thyroid carcinoma (25); 1/25 had negative serum levels of calcitonin, and group 3: parathyroid lesions (36). Biopsies were received at the Pathology Laboratory of Ain Shams University Hospitals.
INSM1 showed 98% diagnostic accuracy in diagnosing MTC and differentiating it from other thyroid lesions. The case of MTC with negative serum calcitonin showed positive INSM1 staining. GATA3 showed 96.8% diagnostic accuracy in diagnosing parathyroid lesions and differentiating them from thyroid lesions.
Using immunohistochemical staining by GATA3 and INSM1, in the appropriate histopathological setting, significantly aids in the differentiation between thyroid lesions, parathyroid lesions and MTCs. INSM1 could serve as a potential diagnostic marker in the rare cases of non-secretory MTC and in metastatic work up.
REFERENCES (48)
1.
Takada N, Hirokawa M, Suzuki A, et al. Diagnostic value of GATA-3 in cytological identification of parathyroid tissues. Endocr J 2016; 63: 621-626.
2.
Ordó¼ez NG .Value of GATA3 immunostaining in the diagnosis of parathyroid tumors. Appl Immunohistochem Mol Morphol 2014; 22: 756-761.
3.
Somnay YR, Schneider D, Mazeh H. Thyroid: medullary carcinoma. Atlas Genet Cytogenet Oncol Haematol 2013; 17: 291-296.
4.
Greco C, Brigante G, Taliani E, et al. Concomitant medullary thyroid carcinoma with paraganglioma-like pattern and papillary thyroid carcinoma. Endocrinol Diabetes Metab Case Rep 2019; 2019: 19-0094.
5.
Ríos A, Rodríguez JM, Febrero B, et al. Histological and immunohistochemical profile of sporadic and familial medullary thyroid carcinoma. Endocrinol Nutr 2011; 58: 521-528.
6.
Vinciguerra GLR, Noccioli N, Cippitelli C, et al. Oncocytic variant of medullary thyroid carcinoma: a rare case of sporadic multifocal and bilateral RET wild-type neoplasm with revision of the literature. Rare Tumors 2016; 8: 6537.
7.
Singh K, Sharma MC, Jain D, Kumar R. Melanotic medullary carcinoma of thyroid – report of a rare case with brief review of literature. Diagn Pathol 2008; 3: 2; doi:10.1186/1746-1596-3-2.
8.
Wang C, Yun T, Wang Z, et al. Pathological characteristics and genetic features of melanin-producing medullary thyroid carcinoma. Diagn Pathol 2018; 13: 86; doi: 10.1186/s13000-018-0764-2.
9.
Tatic S. Histopathological and immunohistochemical features of thyroid carcinoma. Arch Oncol 2003; 11: 173-174.
10.
Gambardella C, Offi C, Patrone R, et al. Clinical challenges with calcitonin-negative medullary thyroid carcinoma. J Cancer Res Clin Oncol 2016; 142: 2023-2029.
11.
Alapat DV, Ain KB, Sloan DA, et al. Disparity between tissue and serum calcitonin and carcinoembryonic antigen in a patient with medullary thyroid carcinoma. Endocrine 2011; 39: 148-152.
12.
Giovanella L, Crippa S, Cariani L. Serum calcitonin-negative medullary thyroid carcinoma: role of CgA and CEA as complementary markers. Int J Biol Markers 2008; 23: 129-131.
13.
Frank-Raue K, Machens A, Leidig-Bruckner G, et al. Prevalence and clinical spectrum of nonsecretory medullary thyroid carcinoma in a series of 839 patients with sporadic medullary thyroid carcinoma. Thyroid 2013; 23: 294-300.
14.
Moo-Young TA, Traugott AL, Moley JF. Sporadic and Familial Medullary Thyroid Carcinoma: State of the Art. Surgical Clinics 2009; 89: 1193-1204.
15.
Scollo C, Baudin E, Travagli JP, et al. Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer. J Clin Endocrinol Metab 2003; 88: 2070-2075.
16.
Liang Y, Heitzman J, Kamat AM, et al. Differential expression of GATA-3 in urothelial carcinoma variants. Hum Pathol 2014; 45: 1466-1472.
17.
Shaoxian T, Baohua Y, Xiaoli X, et al. Characterisation of GATA3 expression in invasive breast cancer: differences in histological subtypes and immunohistochemically defined molecular subtypes. J Clin Pathol 2017; 70: 926-934.
18.
Stolnicu S, Tunde C, Cadar A, Boros M. Differences in GATA3 expression among histological/molecular subtypes and grades in infiltrating breast carcinoma (IBC) are important in the diagnosis of metastatic breast carcinoma. Pol J Pathol 2020; 71: 62-65.
19.
Rooper LM, Bishop JA, Westra WH. INSM1 is a sensitive and specific marker of neuroendocrine differentiation in head and neck tumors. Am J Surg Pathol 2018; 42: 665-671.
20.
Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabelled antibody (PAP) procedures. J Histochem Cytochem 1981; 29: 577-580.
21.
Turchini J, Sioson L, Clarkson A, et al. Utility of GATA-3 expression in the analysis of pituitary neuroendocrine tumour (PitNET) transcription factors. Endocr Pathol 2020; 31: 150-155.
22.
Yu Q, Hardin H, Chu YH, et al. Parathyroid neoplasms: immunohistochemical characterization and long noncoding RNA (lncRNA) expression. Endocr Pathol 2019; 30: 96-105.
23.
Gucer H, Caliskan S, Kefeli M, Mete O. Do you know the details of Your PAX8 antibody? monoclonal PAX8 (MRQ-50) is not expressed in a series of 45 medullary thyroid carcinomas. Endocr Pathol 2020; 31: 33-38.
24.
Patrizia S, Giuseppe S, Francesco P, et al. Cytologic diagnosis of oncocytic neoplasms of the thyroid gland: the importance of the clinical scenario. Appl Immunohistochem Mol Morphol 2019; 27: 726-731.
25.
Srilatha PS, Das J, Monappa V. Oncocytic variant of medullary thyroid carcinoma – a case report. Iran J Pathol 2019; 14: 83-86.
26.
Domagala P, Domagala W. Nuclear CK19-immunopositive pseudoinclusions as a new additional objective diagnostic feature of papillary thyroid carcinoma. Pol J Pathol 2020; 71: 1-6.
27.
Tastekin E, Keskin E, Can N, et al. CD56, CD57, HBME1, CK19, Galectin-3 and p63 immunohistochemical stains in differentiating diagnosis of thyroid benign/malign lesions and NIFTP. Pol J Pathol 2019; 70: 286-294.
28.
Ordó¼ez NG. Thyroid transcription factor-1 is a marker of lung and thyroid carcinomas. Adv Anat Pathol 2000; 7: 123-127.
29.
Saad MF, Ordonez NG, Guido JJ, Samaan NA. The prognostic value of calcitonin immunostaining in medullary carcinoma of the thyroid. J Clin Endocrinol Metab 1984; 59: 850-856.
30.
Erickson LA, Lloyd RV. Practical markers used in the diagnosis of endocrine tumors. Adv Anat Pathol 2004; 11: 175-189.
31.
Zajac JD, Penschow J, Mason T, et al. Identification of calcitonin and calcitonin gene-related peptide messenger ribonucleic acid in medullary thyroid carcinomas by hybridization histochemistry. J Clin Endocrinol Metab 1986; 62: 1037-1043.
32.
Lloyd RV. Use of molecular probes in the study of endocrine diseases. Hum Pathol 1978; 18: 1199-1211.
33.
Yao YZ. CEA in lung cancer: CEA immunohistochemical study of 150 cases. Zhonghua Jie He He Hu Xi Za Zhi 1990; 13: 133-189.
34.
Cheng L, Yin R, Yu Y, et al. Prognostic value of carcinoembryonic antigen level in advanced lung adenocarcinoma. Int J Clin Exp Med 2019; 12: 5812-5819.
35.
Liu H, Lin F. Application of immunohistochemistry in thyroid pathology. Arch Pathol Lab Med 2015; 139: 67-82.
36.
Prameela CG, Ravind R, Sruthi K. Nonthyroidal metastatic lesion in thyroid: A missed diagnosis and a lesson learnt. J Cancer Res Ther 2019; 15: 665-668.
37.
D’Antonio A, Addesso M, De Dominicis G, et al. Mucinous carcinoma of thyroid gland. Report of a primary and a metastatic mucinous tumour from ovarian adenocarcinoma with immunohistochemical study and review of literature. Virchows Arch 2007; 451: 847-851.
38.
Rosenbaum JN, Guo Z, Baus RM, et al. INSM1: a novel immunohistochemical and molecular marker for neuroendocrine and neuroepithelial neoplasms. Am J Clin Pathol 2015; 144: 579-591.
39.
Khan A, Tischler AS, Patwardhan NA, DeLellis RA. Calcitonin immunoreactivity in neoplastic and hyperplastic parathyroid glands: an immunohistochemical study. Endocr Pathol 2003; 14: 249-255.
40.
Li J, Chen W, Liu A. Clinincopathologic features of parathyroid carcinoma: a study of 11 cases with review of literature. Zhonghua Bing Li Xue Za Zhi 2014; 43: 296-300.
41.
Hodgson A, Pakbaz S, Tayyari F, et al. Diagnostic pitfall: parathyroid carcinoma expands the spectrum of calcitonin and calcitonin gene-related peptide expressing neuroendocrine neoplasms. Endocr Pathol 2019; 30: 168-172.
42.
Bauer JL, Toluie S, Thompson LDR. Metastases to the parathyroid glands: a comprehensive literature review of 127 reported cases. Head Neck Pathol 2018; 12: 534-541.
43.
Tomita T. Immunocytochemical staining patterns for parathyroid hormone and chromogranin in parathyroid hyperplasia, adenoma, and carcinoma. Endocr Pathol 1999; 10: 145-156.
44.
Erickson LA, Mete O. Immunohistochemistry in diagnostic parathyroid pathology. Endocr Pathol 2018; 29: 113-129.
45.
Betts G, Beckett E, Nonaka D. GATA3 shows differential immunohistochemical expression across thyroid and parathyroid lesions. Histopathology 2014; 65: 288-290.
46.
Duan K, Mete O. Algorithmic approach to neuroendocrine tumors in targeted biopsies: Practical applications of immunohistochemical markers. Cancer Cytopathol 2016; 124: 871-884.
47.
Miettinen M, Mc. Cue PA, Sarlomo-Rikala M, et al. GATA 3 – A multispecific but potentially useful marker in surgical pathology – a systematic analysis of 2500 epithelial and non-epithelial tumors. Am J Surg Pathol 2014; 38: 13-22.
48.
Mahalakshmi B, Baskaran R, Shanmugavadivu M, et al. Insulinoma-associated protein 1 (INSM1): a potential biomarker and therapeutic target for neuroendocrine tumors. Cell Oncol (Dordr) 2020; 43: 367-376.
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