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Quiz Case
2022
:19;
8
doi:
10.25259/Cytojournal_71_2020

Cytologic evaluation of solitary thyroid nodule in a child

Department of Pathology, Sarojini Naidu Medical College, Agra, Uttar Pradesh, India
Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Corresponding author: Anurag Gupta, Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. ganuragdr@gmail.com
Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Rani D, Gupta A, Singh P, Gupta A. Cytologic evaluation of solitary thyroid nodule in a child. CytoJournal 2022;19:8.

HTML of this article is available FREE at: https://dx.doi.org/10.25259/Cytojournal_71_2020

CLINICAL HISTORY

A 8-year-old boy with right sided thyroid lesion (1.5 × 1.5 cm firm, mobile, non-tender which moved with swallowing) since 1 year in addition to 1 × 0.5 cm lesion. Computed tomography scan lesion was heterogeneously enhancing with a few enlarged lymph nodes. Fine-needle aspiration (FNA) showed findings seen in Figure 1.

Figure 1:: a through e: Aspirates revealed dispersed cells with finely granular cytoplasm showing some pink granules in MGG stained smears and with eccentric nuclei, inconspicuous nucleoli, and few binucleate and multinucleated cells (arrow) with loose aggregates showing nuclear pleomorphism. (a: MGG×200, b: PAP×400, c: MGG×400, d: MGGx400, e: PAP×400), with intranuclear cytoplasmic pseudoinclusions (arrow in ‘c’). f and g: The H and E stained smear (×100) showed homogenous, eosinophilic material which demonstrated yellowish to apple green birefringence under polarizing microscopy. h and i: The cells were immunoreactive for calcitonin (h) and chromogranin (i).
Figure 2:: A 8-year-old boy presenting with the right sided thyroid swelling and a separate swelling in the neck (arrows).

QUESTION

What is your interpretation?

  1. Adenomatous nodule with oncocytic features

  2. Hurthle cell neoplasm

  3. Papillary thyroid carcinoma

  4. Medullary thyroid carcinoma.

Answer

The correct cytological interpretation is

d. Medullary thyroid carcinoma (MTC).

EXPLANATION

Cytology smears were cellular, comprising predominantly of dispersed cells and few loose cellular aggregates [Figure 1a]. Cells were oval to polygonal in shape and showed pleomorphism, with presence of anisokaryosis and some binucleate to rare multinucleate cells [Figures 1d and e]. Nuclei were round and placed eccentrically and the simultaneous presence of moderately abundant, and fairly dense cytoplasm with well-defined borders imparted a distinct plasmacytoid aspect [Figures 1b-e]. Intranuclear cytoplasmic inclusions were also noted [Figure 1c]. Nucleoli were inconspicuous. Few of the cells showed pink cytoplasmic granules [Figure 1d]. These appearances were fairly characteristic of MTC. Additional confirmation was forthcoming by way of few dense amorphous clumps of eosinophilic material evident on hematoxylin and eosin staining [Figure 1f], which was verified to be amyloid by virtue of yellow birefringence under the polarizing microscope subsequent to Congo red staining [Figure 1g]. Finally, intense cytoplasmic positivity for calcitonin [Figure 1h] and chromogranin [Figure 1i] was demonstrable on immunocytochemistry.

ADDITIONAL QUESTIONS

  1. Regarding MTC which of the following features is not true

    1. It can occur in sporadic or hereditary forms

    2. In hereditary form, pattern of inheritance is autosomal dominant

    3. It is generally unilateral

    4. Lymph node metastasis may be seen at the time of diagnosis.

  2. Which of the following statements is true regarding MTC –

    1. It is a tumor of parafollicular C-cells

    2. It secretes calcitonin

    3. Amyloid is found in 80–85% of cases

    4. All of the above.

  3. Which of the following is/are cytological feature of MTC?

    1. Dispersed cellular aspirate with anisocytosis

    2. Eccentric nuclei with binucleate and multinucleate forms

    3. Cytoplasmic granularity

    4. All of the above.

  4. Which of the following immunocytochemical stains yield negative results in MTC

    1. Thyroglobulin

    2. Calcitonin

    3. Chromogranin

    4. Synaptophysin.

ANSWERS TO ADDITIONAL QUIZ QUESTIONS

Answers: Q1 – (c), Q2 – (d), Q3 – (d), Q4 – (a).

Q1 (c) – It is generally unilateral. The correct answer is

C. Different clinical forms of MTC are hereditary and sporadic. In hereditary MTC, pattern of inheritance is autosomal dominant. In hereditary MTC, tumor is bilateral in 92–98% of cases and in sporadic MTC, bilaterality is seen in 0–32% of cases. Sporadic MTC shows lymph node metastasis at the time of diagnosis in 40–50% of cases, while in hereditary MTC, it varies from 10% to 38%, in various forms.[1]

Q2 (d) – All of the above. The correct answer is D. MTC is a malignant tumor showing parafollicular C-cell differentiation. It characteristically secretes calcitonin, but can also produce a variety of other peptide products. Histologically, it shows amyloid in 80–85% of cases, which appears as pink staining amorphous material in the form of globules or massive deposits.[1]

Q3 (d) – All of the above. The correct answer is D. Cytologically, in MTC, the aspirates are moderately to highly cellular, comprising dispersed cell population with variability in size and shape. The nuclei are often eccentrically placed with in the cytoplasm, giving a plasmacytoid appearance. Multinucleate cells and nuclear pleomorphism may be present with occasional bizzare giant cells. With MayGrunwald-Giemsa stain, a proportion of cells show typically pink, cytoplasmic granularity.[2]

Q4 (d) – All of the above. The correct answer is A. Immunocytochemically, MTC shows immunoreactivity for calcitonin, chromogranin, and synaptophysin with negativity for thyroglobulin.[2]

BRIEF REVIEW OF THE TOPIC

Thyroid swellings are uncommon in the pediatric age group and the reported incidence, in the age group of 8–18 years, is estimated to be 0.05–1.8%, whereas, in adults, the reported incidence ranges between 3.2% and 8%.[3] Most thyroid nodules developing in childhood are benign and are examples of either follicular adenoma or nodular hyperplasia.[4] However, the proportion of carcinomas is much higher (5–50%) than that seen in adults (5–15%),[5] to the point of surpassing the benign processes in some series. Papillary thyroid carcinoma accounts for 90% of all pediatric thyroid cancers followed by medullary carcinoma (about 5%) and Hurthle cell neoplasms. Follicular carcinoma, poorly differentiated carcinoma, and anaplastic thyroid carcinoma are extremely rare.[4,6] The most frequent cause of goiter in children is autoimmune thyroid disease; although a benign colloid goiter is also a common cause.[7] MTC is a rare tumor arising from parafollicular C-cells.[8] It accounts for <5% of all thyroid cancers.[9] The incidence of pediatric MTC is estimated to be 0.03 cases/100,000 population/year.[10] Due to extremely low incidence of pediatric MTC, we should have awareness of this entity. MTC occurs either sporadically or in an inherited autosomal dominant manner. In adults, sporadic MTC accounts for 65–75% of MTC, but in children, sporadic MTC is very rare; the vast majority of MTC diagnosed in the childhood are hereditary.[10] Hereditary, MTC occurs as familial MTC or as a part of multiple endocrine neoplasia Type 2A and 2B syndromes. MTC diagnosed during childhood almost always results from activating mutations in the RET protooncogene, which encodes the RET receptor tyrosine kinase.[11] The prognosis of pediatric MTC is extremely satisfactory, with a 5-year overall survival (OS) of 95% and 15 year OS of 86%.[10]

The aspirates of MTC are cellular, comprising dispersed cells to loosely cohesive groups of plasmacytoid, spindle, and/or epithelioid cells.[12,13] The characteristic nuclear features include variable nuclear pleomorphism, bi or multinucleated tumor cells, and granular chromatin pattern.[14] The presence of intranuclear inclusions in MTC has been described.[12] These are not diagnostic of MTC, as they are also observed in papillary thyroid carcinoma as well as some benign lesions of the thyroid. The cells have variable amount of cytoplasm ranging from scant to abundant. The cytoplasm is gray or gray-reddish with fine granules, which represents neurosecretory granules. Bose et al. have reported the presence of cytoplasmic granules in 85% of their cases.[12] Amyloid has been demonstrated in 43–81% of MTC cases.[12,13] Congo red staining has been used to highlight the presence of amyloid.[13] The use of immunocytochemistry for calcitonin is sufficient for the diagnosis of MTC, since it is expressed in 80% of the tumors.[15] There is also coexpression of keratin, vimentin, and CEA. Thyroglobulin expression is negative in MTC and is used as negative control marker. If calcitonin expression is negative in suspected MTC, then positive immunostaining using antibodies against chromogranin A or synaptophysin should be sought.[16] The common cytological differential diagnoses of MTC include Hurthle cell neoplasm, papillary thyroid carcinoma and metastatic tumor, particularly melanoma. Hurthle cell neoplasm is a frequent consideration, as it also features dispersed to loosely cohesive cells with moderate to abundant cytoplasm. However, in MTC, chromatin is coarse and macronucleoli are rarely seen. Furthermore, red cytoplasmic granules are observed in MTC with Romanowsky stain.[17] The extremely eccentrically placed nucleus and presence of amyloid can also assist in proper identification of MTC.[16] In both papillary thyroid carcinoma and MTC, intranuclear inclusions are seen, but other nuclear and architectural features help in distinguishing the two.[17] MTC and metastatic melanoma are difficult to distinguish by cytomorphology alone. Immunocytochemistry is helpful in these cases.[17] Furthermore, serum calcitonin levels are elevated in virtually all patients with MTC. In our patient, serum calcitonin level was elevated. He was further investigated and operated at some other center. Hence, the results of genetic studies, and thus, the type of MTC (sporadic vs. familial) is not known. However, none of his family (parents and one elder sibling) gave a prior history of the disease. The patient’s relatives were contacted and the child was well and disease free at 16 months after the surgery.

The cytomorphological features of MTC are quite distinctive and in most of the cases, definitive diagnosis on FNA can be achieved, which can be confirmed with immunocytochemistry.

COMPETING INTERESTS STATEMENT BY ALL AUTHORS

The authors declare no conflicts of interest.

AUTHORSHIP STATEMENT BY ALL AUTHORS

This manuscript has been read and approved by all the authors and represents honest work.

ETHICS STATEMENT BY ALL AUTHORS

As this is a quiz case without identifiers, our institution does not require approval from Institutional Review Board (IRB) (or its equivalent).

LIST OF ABBREVIATIONS (in alphabetic order)

FNA – Fine-needle aspiration

MTC – Medullary thyroid carcinoma.

EDITORIAL/PEER-REVIEW STATEMENT

To ensure the integrity and highest quality of CytoJournal publications, the review process of this manuscript was conducted under a double--blind model (the authors are blinded for reviewers and vice versa) through automatic online system.

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