Abstract

A thyroid nodule (TN) is a structurally discrete lesion within the thyroid gland that can be readily distinguished from the adjoining normal thyroid parenchyma. TNs are more frequently detected these days because of the widespread use of high-resolution imaging techniques for various neck pathologies. A well-circumscribed macroscopic lesion measuring 17 mm ×14 mm ×12 mm was observed in the left lobe of the thyroid gland during routine dissection performed on an embalmed elderly female cadaver for undergraduate teaching. It was firm to the touch and greyish brown in color. In the histological examination, the lesion appeared intensely stained and encapsulated by a thick fibrous capsule having various sizes of thyroid follicles lined by cuboidal to low-columnar epithelium with focal areas of calcification and hemorrhages. There was no sign of local tissue or vascular invasion by the lesion. No nuclear atypia was observed. The lesion was identified as a benign follicular adenoma. This report underscores the significance of recognizing that a thyroid gland that appears to be within normal limits may, in fact, harbor a thyroid nodule of considerable size. The identification of such nodules is of paramount importance, as a significant proportion of benign thyroid lesions found in geriatric women have a high propensity to undergo malignant transformation.

benign thyroid nodule, follicular thyroid adenoma, follicular adenocarcinoma

Thyroid nodules (TNs) have been increasingly detected these days on account of the wide use of advanced diagnostic imaging techniques performed for several pathologies in the neck.^[1] TN may be observed incidentally during physical examination of the neck and are referred to as ‘incidentalomas’ of the thyroid. But the terms “TN” and “incidentaloma of the thyroid” are not synonymous. The American Thyroid Association (ATA) defines TNs as “discrete lesions within the thyroid gland, radiologically distinct from surrounding thyroid parenchyma”.^[2,3] On the other hand, a clinically palpable thyroid swelling without classic radiological features of being a distinct entity from the surrounding normal thyroid parenchyma does not qualify to be termed as TN.^[1] A thyroid nodule is usually between a few millimeters and a few centimeters. They can be found alone or in groups, and they may have a complete or incomplete capsule.^[2,3] TNs are at least 4 times more common in females, and their incidence rates have been found to be directly proportional to advanced age and low iodine intake. Development of a new nodule or increase in the size of an existing nodule has been observed in pregnancy, which suggests the probable role of estrogens and progesterone in the pathogenesis.^[1] In this report, the gross anatomic and histological features of an incidentally observed benign solitary TN in an elderly female cadaver are described.

Routine dissection for undergraduate teaching was performed in the front of the neck of a 76-year-old female donated embalmed cadaver as per Cunningham’s Manual of Practical Anatomy, 16th edition. Standard institutional guidelines with regard to the use of human cadavers for medical teaching and research were strictly followed. Relevant written consent was obtained from the family members of the body donor. Observed gross anatomical and histological findings were recorded and photographed. There was neither any visible nor any palpable mass noted in the front of the neck. The dissected thyroid gland was bi-lobed with an intervening isthmus, normal-looking in size and position, weighed 47 g, and measured 4.15 cm × 1.75 cm × 1.12 cm. During grossing of the thyroid gland for tissue processing with a scalpel blade, a gritty sensation was felt on the left lobe, and a single, encapsulated macroscopic lesion was observed (Fig. 1) . The lesion measured 17 mm × 14 mm × 12 mm (Fig. 1A, B) and was firm to the touch and greyish brown in color. The macroscopic lesion was provisionally identified as solitary TN. A portion of the TN with adjoining thyroid parenchyma of the lobe was processed for paraffin embedding and subsequent hematoxylin and eosin (H&E) staining. In the H&E-stained sections, the thyroid gland was seen covered by a thin connective tissue capsule. The lesion within the left lobe was well circumscribed and appeared more intensely stained than the surrounding normal-looking thyroid parenchyma and had thyroid follicles of varying sizes within a thick fibrous capsule filled with colloid. The thyroid follicles within the lesion were lined by cuboidal to low-columnar epithelium, and few of the follicles were degenerated. The fibrous capsule was made up of several lamellae of collagen bundles. Focal areas of calcification were observed in the H&E-stained sections along the periphery of the TN subjacent to the collagen lamellae of the fibrous capsule (Fig. 2A, B, C) . The definitive Von Kossa stain for calcium detection was not performed. The lesion did not have the nuclear features of the papillary thyroid carcinoma, such as nuclear clearing, nuclear grooves, and intranuclear cytoplasmic inclusions. There was no evidence of capsular invasion, but the lesion compressed normal thyroid parenchyma at the periphery. The remainder of the left lobe and the other regions of the thyroid gland were normal in appearance. The available medical record of the deceased revealed that her death was unrelated to the presence of the thyroid lesion.

Figure 1. A, B.

Gross view of the left lobe of the thyroid lobe on a cut section showing the location of the thyroid nodule and its thick fibrous capsule.

Figure 2.

A. Photomicrograph of the hematoxylin- and eosin-stained section of the thyroid nodule with adjoining normal thyroid tissue; B. The nodule is seen well-circumscribed, almost completely by the fibrous capsule in 10× magnification; C. Portion of the thyroid nodule with capsule in 40× magnification. Cap: capsule; Fib: fibrous capsule of the TN; fl: thyroid follicles; black asterisks indicate dense connective tissues, and red asterisks indicate calcification.

The prevalence of TN by mere clinical palpation is reported to be up to 7%, but a prevalence as high as 67% has been observed when screened with high-resolution ultrasonography (hrUSG).^[4] Clinically, it may or may not be palpable depending on the size and location. Several etiological factors have been linked with the occurrence of TN. A significant contributor to the occurrence of TN is believed to be exposure to ionizing radiation. A previously irradiated thyroid gland has more risk for nodule formation. There is a 20%–50% higher chance of encountering a malignant nodule in a previously irradiated thyroid gland. Other factors such as smoking, alcohol use, coexisting metabolic syndrome, etc. are also associated with TN formation. On the other hand, use of oral contraceptive pills and statins might have a protective role. It is estimated that up to 90% of TNs are benign.^[5] However, as up to 5% of all palpable TNs can become malignant, no palpable TN should remain underevaluated.^[6] The other reasons demanding detailed evaluation are the presence of compressive symptoms, hormonal imbalance, or cosmetic reasons.^[7] Irrespective of the size and symptoms, the histological characteristics of a TN can guide the further course of clinical management or even a decision to undertake surgery.^[5] The recommended gold standard diagnostic test for differentiating a benign lesion from a malignant one is fine needle aspiration cytology (FNAC), preferably under ultrasound guidance.^[1] FNAC also can help to decide whether to undertake surgery or not. The general recommendation is that if the lesion is less than 1 cm in dimension and without associated USG features suspicious of malignancy, FNAC is not required.‌^[5] This implies that not all cases of TN are subjected to cytological and histopathological examination. However, in cases of long-standing TN, FNAC is recommended if more than 20% growth is documented in a follow-up examination.^[5]

The most common TN is an adenomatous benign nodule or follicular adenoma of the thyroid, which has minimal risk of malignant transformation. An adenomatous lesion of the thyroid has the cardinal features of nodularity, cystic degeneration, fibrosis, calcification, and hemorrhage as common secondary changes. In the present case, there was no apparent visible or palpable swelling, and there were no discrepancies noted in the sizes of the lobes with loss of glandular architecture. The unilateral solitary TN is separated from the remainder of the normal thyroid parenchyma of the left lobe by a thick fibrous capsule, and the capsule was not infiltrated by the cells of the adenoma within the lesion. The TN was firm to touch, which was probably due to dense inspissations of colloid mimicking calcification. We observed a focal area of calcification in H&E-stained sections located along the periphery of the mass subjacent to the fibrous capsule. Apart from the thick fibrous capsule enclosing the TN, there were no other coarse fibrous trabeculae seen across the parenchyma. Such a lesion has been described by various names, such as ‘adenomatous nodule,’ ‘solitary nodule,’ ‘colloid cyst,’ etc. The other possibility is that it could have resulted from structural remodeling due to cycles of hyperplasia and involution of the thyroid follicles in the elderly female. The nodule is histologically different from the rest of the gland but well circumscribed by a fibrous capsule and thus identified as a follicular adenoma. Inflammatory and neoplastic etiologies are common, known causes for nodule formation in the thyroid gland. The occurrence of nodules increases with advanced age in both genders, but as such, the entity has more predilections to occur in females. A recent Indian study found that 78.92% of females with neoplastic thyroid lesions had peak incidence at a young age among a total of 204 subjects. Follicular adenoma was found to be the most common benign tumor (78.18% of all benign neoplasms), and the present case seems to be of such a benign variety.‌^[8] Goiter belt regions, such as high altitudes and other such places, have a greater tendency to harbor TN. The medical history of the deceased, however, did not provide any clues with regard to the probable etiology of the TN.

The present report highlights that a clinically normal-looking thyroid gland can harbor a macroscopic lesion. Histological findings of an intensely stained, well-encapsulated region of thyroid parenchyma with focal areas of calcification, hemorrhages, absence of capsular or tissue invasion, and atypical nuclear features are indicative of an adenomatous thyroid nodule. Although most such lesions are presumed to be benign, considering the chance of malignant transformation in substantial proportions of the cases and more so in elderly females, their early detection is desirable. Such lesions can be readily detected with hrUSG, and examining the neck for other reasons in susceptible population groups can be a window of opportunity for screening such lesions.

Ethical statement

• Ethical approval from the local institutional ethics committee was not required for this study. The present study was based on the observation of a cadaver. The department received the cadavers used in this study with written informed consent, enabling whole-body dissection for research and educational purposes. All standards pertaining to the use of human cadavers in research and teaching were closely adhered to, in accordance with institutional guidelines.
• The authors declared that no clinical trials were used in the present study.
• The authors declared that no experiments on humans or human tissues were performed for the present study.
• Relevant written consent was obtained from the family members of the body donor.
• The authors declared that no experiments on animals were performed for the present study.
• The authors declared that no commercially available immortalized human and animal cell lines were used in the present study.

Conflict of interest

The authors have declared that no competing interests exist.

Artificial Intelligence (AI) use

The authors accept full responsibility for the content of the manuscript, including the disclosure of any use of AI. No AI tools were used in the preparation of this manuscript.

Funding

No funding was reported.

Author contributions

DB: concept, medical dissection, histological tissue processing, review of literature, analysis and interpretation, writing manuscript; JR: histological tissue processing, review of literature, writing manuscript; SA: histological tissue processing, review of literature, writing manuscript; SS: concept, histological tissue processing, review of literature, analysis and interpretation, writing manuscript, final approval of manuscript.

Author ORCIDs

Dibakar Borthakur https://orcid.org/0000-0001-6044-0743

Jayashree Raja https://orcid.org/0009-0000-9607-9355

Silka Agarwal https://orcid.org/0000-0003-3036-721X

Seema Singh https://orcid.org/0000-0002-9354-7413

Data availability

All of the data that support the findings of this study are available in the main text.