Cytologic evaluation of solitary thyroid nodule in a child
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.
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.
What is your interpretation?
Adenomatous nodule with oncocytic features
Hurthle cell neoplasm
Papillary thyroid carcinoma
Medullary thyroid carcinoma.
The correct cytological interpretation is
d. Medullary thyroid carcinoma (MTC).
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.
Regarding MTC which of the following features is not true
It can occur in sporadic or hereditary forms
In hereditary form, pattern of inheritance is autosomal dominant
It is generally unilateral
Lymph node metastasis may be seen at the time of diagnosis.
Which of the following statements is true regarding MTC –
It is a tumor of parafollicular C-cells
It secretes calcitonin
Amyloid is found in 80–85% of cases
All of the above.
Which of the following is/are cytological feature of MTC?
Dispersed cellular aspirate with anisocytosis
Eccentric nuclei with binucleate and multinucleate forms
All of the above.
Which of the following immunocytochemical stains yield negative results in MTC
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.
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.
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.
Q4 (d) – All of the above. The correct answer is A. Immunocytochemically, MTC shows immunoreactivity for calcitonin, chromogranin, and synaptophysin with negativity for thyroglobulin.
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%. Most thyroid nodules developing in childhood are benign and are examples of either follicular adenoma or nodular hyperplasia. However, the proportion of carcinomas is much higher (5–50%) than that seen in adults (5–15%), 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. MTC is a rare tumor arising from parafollicular C-cells. It accounts for <5% of all thyroid cancers. The incidence of pediatric MTC is estimated to be 0.03 cases/100,000 population/year. 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. 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. The prognosis of pediatric MTC is extremely satisfactory, with a 5-year overall survival (OS) of 95% and 15 year OS of 86%.
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. The presence of intranuclear inclusions in MTC has been described. 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. Amyloid has been demonstrated in 43–81% of MTC cases.[12,13] Congo red staining has been used to highlight the presence of amyloid. The use of immunocytochemistry for calcitonin is sufficient for the diagnosis of MTC, since it is expressed in 80% of the tumors. 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. 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. The extremely eccentrically placed nucleus and presence of amyloid can also assist in proper identification of MTC. In both papillary thyroid carcinoma and MTC, intranuclear inclusions are seen, but other nuclear and architectural features help in distinguishing the two. MTC and metastatic melanoma are difficult to distinguish by cytomorphology alone. Immunocytochemistry is helpful in these cases. 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.
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