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CASE REPORT Table of Contents  
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Carbimazole-induced atypia – A mimicker of malignancy in fine-needle aspiration cytology


 Department of Pathology, Sree Balaji Medical College and Hospital, Chromepet, Chennai, Tamilnadu, India

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Date of Submission26-May-2021
Date of Decision27-Aug-2021
Date of Acceptance28-Aug-2021
Date of Web Publication26-May-2022
 

   Abstract 


A 20-year-old female presented with complaints of thyroid swelling and showed signs and symptoms of thyrotoxicosis and fine-needle aspiration cytology (FNAC) was requested by the surgeon. On examination of FNAC smear, it showed thyroid follicular cells with atypical features like bizarre giant cells, pseudo nuclear inclusions, and mitotic figure. Correlation between clinical history and cytomorphologic features was done and it was reported as atypical changes in thyroid probably due to carbimazole-induced changes. It helped the patient, as radical surgery and its untoward complications were avoided.

Keywords: Carbimazole, complications, cytological atypia


How to cite this URL:
Manikandan M A, Shobana B, Lilly S M, Thanka J. Carbimazole-induced atypia – A mimicker of malignancy in fine-needle aspiration cytology. Indian J Pathol Microbiol [Epub ahead of print] [cited 2022 Nov 27]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=345877





   Introduction Top


FNAC (fine-needle aspiration cytology) is an important investigation in thyroid lesions as it could avert surgery if the lesion presented is benign like nodular goiter or lymphocytic thyroiditis. Even though diagnosing malignant lesions are difficult, FNAC is the mainstay of treatment. We should be careful not to overinterpret a diagnosis and under-interpret a diagnosis. Drug-induced changes are important as some of drugs can simulate a neoplasm with cytological atypia. Carbimazole-induced atypia is a rare finding, which may lead to a misinterpretation of aggressive neoplasm. If misinterpreted or over-diagnosed as thyroid malignancy, it can lead to surgeons choosing surgery as the treatment option and adversely affecting the patient. Correlating the cytological features with clinical history is essential not to misinterpret the diagnosis and choose the correct treatment.


   Case History Top


A 20-year female came with complaints of swelling in anterior aspect of neck for 1 year with progressive increase in size of the swelling. There was no history of pain over the swelling. Patient had increased palpitation, profuse sweating, history of hair loss, and loss of appetite. Patient also had irregular menstrual cycle.

Thyroid function test was done, and T3, T4 and TSH levels were T3 (triiodothyronine) 132.60 ng/dl (normal range 60–180 ng/dl), T4 (thyroxine) 11.75 μg/dl (normal range 5–12 μg/dl), and TSH 0.13 μIU/ml (normal range 0.3–4.50 μIU/ml).

Ultrasonogram findings were given as follows: right lobe measured 4.1 × 2.6 × 2.5 cm and left lobe measured 4.3 × 1.8 × 2.2 cm. Both lobes of thyroid appeared diffusely enlarged with altered echoes with increased vascularity. Final impression was given as diffuse goiter.

On physical examination, the patient had exophthalmos and was thin built. Local examination findings were 6 × 6 cm diffuse swelling in the anterior aspect of the neck, firm in consistency, non-tender, mild warmth felt, moves with deglutition, and was not moving with protrusion of the tongue.

Fine-needle aspiration of the swelling was done, and 0.8 cc of blood mixed aspirate was obtained, and slides were processed and stained with H and E (hematoxylin and eosin) and PAP (papinicolaou) stain.

Smear studied showed normal thyroid follicular cells in sheets and cells in single, admixed with cells showing minimal pleomorphism, presence of Hurthle cells with abundant granular eosinophilic cytoplasm, and prominent nuclei were seen. Some foci showed bizarre nuclei with increased nuclear-cytoplasmic ratio [Figure 1]. Presence of suspicious pseudo nuclear inclusion [Figure 1] and occasional mitotic figure [Figure 2] were noted in a background of scanty colloid with hemorrhage. Few foci showed multinucleate giant cells [Figure 2].
Figure 1: Normal thyroid follicular cells in sheets and microfollicles showing mild pleomorphism admixed with bizarre cells showing enlarged hyperchromatic nuclei. Inset shows pseudo nuclear inclusions (cyto × 400 H and E stain)

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Figure 2: Cells with Hurthle change showing abundant granular eosinophilic cytoplasm and a prominent mitotic figure. Inset shows a multinucleate giant cell (cyto × 400 H and E stain)

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Impression was given as atypia of undetermined significance with nuclear atypia not sufficient to be classified as suspicious for malignancy, probably induced due to carbimazole therapy.


   Discussion Top


Patients presented with thyrotoxicosis, who are taking antithyroid medication, are less likely to present with malignancy. In a study done by Yeo et al.,[1] it was said that patients presented with toxic nodular goiter have less chances of coexisting malignancy.[1]

This patient had prominent exophthalmos and was very thin built, suggesting she had increased metabolic rate due to hyperthyroidism. Her T3 and T4 levels are normal but her TSH levels were low. So, history of drug intake was asked, and patient informed that she was on carbimazole for her treatment for the past 10 years.

The smears showed cohesive clusters and discohesive clusters of thyroid follicular cells with some foci showing normal appearing clusters with microfollicle formation [Figure 1] along with atypical clusters showing minimal pleomorphism, and presence of Hurthle cells with abundant granular eosinophilic cytoplasm and prominent nuclei were seen; some foci showed bizarre nuclei with increased nuclear-cytoplasmic ratio [Figure 2]. According to Bethesda system of reporting thyroid cytopathology, focal cytological atypia with nuclear atypia showing increased nuclear-cytoplasmic ratio and irregular nuclear contour admixed with normal appearing follicular epithelial cells and microfollicles in a scant colloid background should be reported as atypia of undetermined significance, as was in our case report.[2]

Our smear showed pseudo nuclear inclusions [Figure 1]. Nuclear inclusions are present in multiple other conditions and are not specific for papillary thyroid neoplasm. There are three types of nuclear inclusion: true nuclear inclusion, pseudo nuclear inclusion, and pseudo–pseudo nuclear inclusion. True nuclear inclusion is abnormal presence of foreign material in the nucleus. Pseudo nuclear inclusion is due to invagination of cytoplasm into nucleus. Pseudo–pseudo nuclear inclusion is due to artifacts from staining. Etiology varies from infections, metabolic abnormality, malignancy, and drugs, mentioned in a study by You-Tung Ip et al.[3]

Mitotic figures [Figure 2] are usually a sign of aggressive neoplasm like papillary thyroid carcinoma and poorly differentiated carcinoma. In a study done by Anubha Bajaj, presence of mitotic figures was noted in case of goiter with proliferative changes and benign morphology similar to our case report.[4]

In a case reported by Swei H. Tsung, findings with cells showing pleomorphism, Hurthle cell change, and bizarre-looking cells with giant nuclei are noted, which was similar to our case report.[5]


   Conclusion Top


Administration of antithyroid medication (carbimazole) to thyrotoxic patient may induce cytological atypia and simulate malignancy in thyroid, which may require surgery. In our case, proper clinical history obtained along with clinical findings has led to the identification of carbimazole-induced atypia in this thyrotoxic patient and prevented unnecessary surgery and its untoward complications.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Yeo PP, Wang KW, Sinniah R, Aw TC, Chang CH, Sethi VK, et al. Thyrotoxicosis and thyroid cancer. Aust N Z J Med 1982;12(:589-93.  Back to cited text no. 1
    
2.
Ali SZ, Cibas ES. The Bethesda System for Reporting Thyroid Cytopathology: Definitions, Criteria, and Explanatory Notes, Springer International Publishing,New York, U.S.A; 2017.  Back to cited text no. 2
    
3.
Ip YT, Dias Filho MA, Chan JK. Nuclear inclusions and pseudoinclusions: Friends or foes of the surgical pathologist? Int J Surg Pathol 2010;18:465-81.  Back to cited text no. 3
    
4.
Bajaj A. The prosperous goitre: Basedow's bonanza-graves' disease. J Liver Res Disord Ther 2018;4:109-12.  Back to cited text no. 4
    
5.
Tsung SH. Fine needle aspiration cytology of the thyroid gland following methimazole therapy. Ann Clin Cytol Pathol 2018;4:1118.  Back to cited text no. 5
    

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Correspondence Address:
B Shobana,
A8-2A Olympia Grande Apartments, G.S.T Road, Pallavaram, Chennai - 600 043, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_513_21



    Figures

  [Figure 1], [Figure 2]



 

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    -  Manikandan M A
    -  Shobana B
    -  Lilly S M
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