Carbimazole induced atypia in the thyroid gland


Thyroid nuclear atypia associated with carbimazole is well-known. However, there are rare cases described in literature. We report here a case of thyroid fine needle aspiration cytology (FNAC) of a follicular lesion of undetermined significance or nuclear atypia of undetermined significance (FLUS/AUS) observed in a 56-year-old female presenting with Hashimoto’s thyroiditis on treatment by carbimazole. In conclusion, thyroid nuclear atypia in the form of anisonucleosis, prominent nucleoli, and hyperchromasia associated with carbimazole treatment should be interpreted with caution in differentiating from malignancy.

Keywords: Atypia, carbimazole, cytology, follicular lesion of undetermined significance or nuclear atypia of undetermined significance (FLUS/AUS), thyroid

How to cite this article:
Swami SY, Panchal S, D’Costa G. Carbimazole induced atypia in the thyroid gland. Ann Trop Med Public Health 2016;9:271-2


How to cite this URL:
Swami SY, Panchal S, D’Costa G. Carbimazole induced atypia in the thyroid gland. Ann Trop Med Public Health [serial online] 2016 [cited 2020 Nov 26];9:271-2. Available from:



The first case report concerning this cytostatic effect of carbimazole was published by Smejkal et al. in 1985.[1] Similarly, atypical features in follicular cells such as pseudoinclusions could be seen in other benign thyroid lesions as well. The discussion points out the differential diagnosis of the specificity of nuclear atypia in the diagnosis of thyroid malignancy.

Case Report

A 56-year-old female came with complaints of a swelling in the midline neck, more on the left side, since 4 months and a history of palpitations and tremors. Previous fine needle aspiration cytology (FNAC) showed features of Hashimoto’s thyroiditis with T3; >800 ng/dL, T4; 28 ug/dL, and TSH; 0.02 uIU/mL, after which she was on carbimazole treatment for the last 3 months. Local ultrasonography (USG) showed multiple nodules in the left lobe, the largest of size 1.2 cm × 1 cm. On local examination, a swelling of the left lobe of the thyroid of the size 4 cm × 3 cm, nontender, soft to firm, moving with deglutition was noted.


FNAC [Figure 1] showed clusters, groups, occasional sheets, and individually scattered follicular epithelial cells with moderate anisonucleosis and scanty colloid restricted to follicles. At places, follicular cells were arranged in macrofollicles. Very rarely, a microfollicular pattern of follicular cells was seen. Few atypical follicular cells [Figure 2] with anisonucleosis, hyperchromasia, and prominent nucleoli were seen as well. Occasional Hürthle cells were seen in the background with the absence of lymphocytes. FNAC impression was follicular lesion of undetermined significance or nuclear atypia of undetermined significance (FLUS/AUS).

Figure 1: FNAC thyroid showing groups, sheets, and individually scattered follicular epithelial. At places, macrofollicular arrangement of follicular cells was seen [PAP; 10×]

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Figure 2: FNAC thyroid showing follicular cell atypia in the form of anisonucleosis, hyperchromasia, and at places prominent nucleoli [PAP; 40×]

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As suggested by the Bethesda system for reporting thyroid cytopathology, we report a case of thyroid FLUS/AUS associated with the treatment of Hashimoto’s disease treated with carbimazole.

Cibas et al.[2] suggested the possibility for carbimazole inducing these reactive cellular changes. Treatment with radioactive iodine gives the same nuclear changes such as chromatin clearing, rare nuclear grooves, and rare nuclear pseudoinclusions suggesting papillary carcinoma.[3] A few nuclear pseudoinclusions could be seen as well in other benign thyroid lesions such as benign thyroid cysts, adenomas, Hashimoto’s thyroiditis, and parathyroid neoplasms.[4],[5] In a large series of 245 patients with Graves’ disease, Kim et al.[6] calculated a prevalence of thyroid cancer at 3.3%. Most of them were micropapillary thyroid cancers. In other words, the differential diagnosis between benign nodules and tumors developing in Graves’ disease is often difficult. Fortunately, strict cytological or histological criteria associating nuclear enlargement, nuclear overlapping, pale powdery chromatin, intranuclear grooves, and small nucleoli are enough to give a robust diagnosis of a papillary tumor.[7]

In our case, the atypia was suggestive of a carcinoma but was insufficient to allow a diagnosis of malignancy: The atypical cells were patchy, dispersed, and the nuclei were more often rounded, nuclear overlapping was not obvious, and the chromatin was not pale or powdery. Only few cells showed worrying enlarged nuclei sometimes associated with hyperchromasia and rare nuclear pseudoinclusions. Without clinical information, our diagnosis of FLUS/AUS was justified. In conclusion, in Hashimotovious and the chromatin carbimazole, cells with nuclear atypia even with anisonucleosis, hyperchromasia, and rare prominent nucleoli, should be interpreted with caution and considered more likely as benign nodules.

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Conflicts of interest

There are no conflicts of interest.



Smejkal V, Smejkalová E, Rosa M, Zeman V, Smetana K. Cytologic changes simulating malignancy in thyrotoxic goiters treated with carbimazole. Acta Cytol 1985;29:173-8.
Cibas SE, Syed ZA. The bethesda system for reporting thyroid cytopathology. Thyroid 2009;19:1159-65.
Granter SR, Cibas ES. Cytologic findings in thyroid nodules after 131I treatment of hyperthyroidism. Am J Clin Pathol 1997;107:20-5.
Faquin WC, Cibas ES, Renshaw AA. “Atypical” cells in fine-needle aspiration biopsy specimens of benign thyroid cysts. Cancer 2005;105:71-9.
Goellner JR, Caudill JL. Intranuclear holes (cytoplasmic pseudoinclusion) in parathyroid neoplasms, or “holes happen”. Cancer 2000;90:41-6.
Kim WB, Han SM, Kim TY, Nam-Goong IS, Gong G, Lee HK, et al. Ultrasonographic screening for detection of thyroid cancer in patients with Graves’ disease. Clin Endocrinol (Oxf) 2004;60:719-25.
Anderson SR, Mandel S, LiVolsi VA, Gupta PK, Baloch ZW. Can cytomorphology differentiate between benign nodules and tumors arising in Graves’ disease? Diagn Cytopathol 2004;31:64-7.

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1755-6783.184784


[Figure 1], [Figure 2]

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