Unifocal Conventional Papillary Thyroid Carcinoma with Coexisting Caseating Granulomatous Inflammation in India

Abstract

Thyroid cancer remains one of the leading endocrine malignancies with Conventional Papillary Thyroid Carcinoma (CVPTC) being the most commonly reported cancer. Caseating granulomatous inflammation is an unusual presentation in the thyroid even in places with high incidence of tuberculosis. The association of CVPTC with caseating granulomatous inflammation is infrequent. It can occur as a result of chronic inflammation which subsequently leads to DNA damage by producing nitric oxide and reactive oxygen species resulting in carcinogenesis. Other than tuberculosis, necrotizing granulomas in the thyroid can also be found in association with fungal diseases, plasma cell granulomas and palpation thyroiditis. We report a case of a 46-year-old lady who presented with neck swelling and dysphagia. Examination of the neck showed a firm, non-tender swelling involving the right lobe of the thyroid that moved with deglutination. The thyroid profile was normal. Ultrasound neck revealed a solitary nodule in the right lobe of the thyroid with heterogeneous architecture and increased vascularity. Fine needle aspiration (FNA) suggested Nodular colloid goitre (Bethesda Category II). Intraoperatively, the gland was stony hard and was found adherent to the underlying muscles with no obvious lymphadenopathy. A gross examination of the right hemithyroidectomy specimen revealed a single nodule with the cavity filled with multiple grey-white papillary excrescences along with an adjacent cystic cavity filled with colloid. Histopathological examination was suggestive of unifocal conventional papillary thyroid carcinoma with surrounding caseating granulomatous inflammation involving the right lobe of the thyroid (pT2 Nx Mx). CVPTC with coexisting caseating granulomatous inflammation is a rare presentation. The exact pathology of caseating granulomatous inflammation in our case is unknown. However, chronic inflammation might have played a role in tumorigenesis.

Introduction

Thyroid carcinoma is the most common endocrine malignancy representing 90 to 95% of all the endocrine tumours [1, 2]. In recent years, there has been a rise in the incidence and prevalence rates of thyroid cancer throughout the universe as a result of more westernisation and changes in the diet and environment [3]. Thyroid cancers are four times more common in women than men [4]. Ultrasonography has greatly improved the early detection and diagnosis of thyroid nodules even of smaller sizes. Fine needle aspiration plays another important role in differentiating and classifying tumours into benign and malignant categories. The risk of malignancy is estimated by using the Bethesda scoring system. However, there can be false negative results due to various errors like the faulty aspiration technique, inadequate sampling or specimen preparation [2].

Histopathological examination is essential for all cases in not only confirming the diagnosis but also in identifying the category, family, tumour type and subtype [5]. In recent decades, molecular pathology of thyroid tumours has emerged to analyse the distinct molecular alterations in various thyroid tumours [6]. Majority of thyroid cancers arise from follicular cells. The most common thyroid cancer arising from follicular cells is CVPTC which has an overall favourable outcome. The tumour is mostly associated with BRAF - V600E mutation. It can also be found in RAS point mutations and fusion oncogenes (RET - PTC). The prognosis of CVPTC depends upon the age, gender, tumour size, multifocal status and lymph node metastasis [3, 6].

Caseating granulomatous inflammation of the thyroid gland is an extremely rare condition seen in association with CVPTC. In the thyroid, caseating necrotizing granulomas are seen predominantly in tuberculosis [7]. However, other conditions like fungal and viral infections, palpation thyroiditis, Wegener’s granulomatosis and subacute thyroiditis can also lead to the formation of granulomas [8, 9]. Chronic inflammation has been suggested as one of the main causes of these granulomatous lesions in the thyroid gland in CVPTC. These granulomas produce persistent inflammation leading to DNA damage and anti-apoptotic properties which have been implicated in the tumorigenesis of CVPTC [10].

We report a rare case of CVPTC with coexisting caseating granulomatous inflammation.

Case Report

A 46-year-old lady, a farmer by occupation presented to the General Surgery Department with complaints of swelling in the right neck for three months which was gradually increasing in size. She also complained of dysphagia for one month. However, there was no history of dyspnoea, hoarseness of voice and loss of appetite. She had no other comorbidities. Examination of the neck showed a firm, non-tender swelling involving the right lobe of the thyroid of size 3 × 2 cm that moved with deglutination. The thyroid stimulating hormone was 1.54 mU/L.

Ultrasound neck revealed the presence of a solitary nodule with heterogeneous architecture in the right lobe of the thyroid measuring 2.5 × 1.5 cm with increased vascularity. Isthmus and the left lobe of the thyroid were normal. Fine needle aspiration from a nodule in the right lobe of the thyroid was suggestive of Nodular colloid goitre (Bethesda Category II). She was further taken up for right hemithyroidectomy. Intraoperatively, the gland was stony hard and was found adherent to the underlying muscles with no obvious lymphadenopathy. and the specimen was sent for histopathological examination.

Gross examination of the right hemithyroidectomy specimen intoto consisted of the right lobe of thyroid and isthmus measuring 4 × 3.2 × 1.8 cm and 2.5 × 1.8 × 1 cm respectively. The outer surface of the right lobe of the thyroid had a capsule and appeared nodular with prominent congested vessels. The cut surface showed a single nodule measuring 3.7 × 3 × 1.8 cm with the cavity filled with multiple grey-white papillary excrescences (Fig. 1). Further serial sectioning of the gland showed a cystic cavity filled with colloid measuring 0.6 × 0.6 × 0.2 cm. No lymph nodes were identified. The cut surface of the isthmus showed a grey-white nodule measuring 1.2 × 1 × 1 cm.

Fig. 1.

Gross image of the right hemithyroidectomy specimen with cut surface showing multiple papillary projections

Histopathological examination of the right lobe of the thyroid showed a well-circumscribed tumour composed of tumour cells arranged in papillary architecture lined by cuboidal epithelium with a prominent fibrovascular core. The tumour cells had a high nuclear-cytoplasmic ratio with ground glass nuclei, membrane irregularity, nuclear grooving, chromatin clearing and occasional cells showing pseudonuclear inclusion (Fig. 2). Few mitotic figures were also evident. However, there was no evidence of lymphovascular and perineural invasion. Adjacent thyroid parenchyma appeared normal in morphology with multiple discrete epithelioid cell granulomas with central caseating necrosis and Langhans giant cells. (Fig. 3). Sections from the isthmus showed hyperplastic nodules with no evidence of papillary carcinoma. Acid Fast Stain [AFS] (Fig. 4) and Periodic Acid Schiff Stain [PAS] (Fig. 5) were non-contributory.

Fig. 2.

Photomicrograph showing Papillary carcinoma thyroid

Fig. 3.

Photomicrograph showing caseating granuloma with Langhans giant cells

Fig. 4.

Periodic Acid Schiff Stain - Negative for Fungal elements

Fig. 5.

Acid Fast Stain - Negative for Tubercle bacillus

Hence, we reported the case as Unifocal conventional papillary thyroid carcinoma with caseating granulomatous inflammation involving the right lobe of the thyroid (pT2 Nx Mx).

Discussion

Caseating granulomatous inflammation of the thyroid gland is an unusual presentation. Various diseases have been implicated in promoting granuloma formation. Thyroid tuberculosis (TT) classically produces caseating granulomas. The other causes of non-caseating granulomas include fungal thyroiditis, palpation thyroiditis, Wegener’s granulomatosis and subacute thyroiditis.

TT is a rare presentation with a prevalence ranging from 0.1–0.6%.⁷ Most of the patients are asymptomatic at the time of presentation but can present with thyromegaly, fever of unknown origin and neck pain. Hence, a postoperative histopathological examination confirms the diagnosis [10, 11].

The occurrence of caseating granulomas in CVPTC may be due to chronic inflammation. These granulomas produce persistent inflammation through DNA damage by producing reactive oxygen species and nitric oxide. Inflammation-related carcinogenesis is mainly due to this DNA damage, inhibition of apoptosis by B cell lymphoma − 2 gene expression and elevated prostaglandin levels as a result of chronic inflammation may result in tumorigenesis [10].

Babu et al. reported a rare case of cervical blastomycosis with left thyroid lobe involvement in an immunocompetent patient that showed the presence of epithelioid granulomas with budding yeasts [8].

Palpation thyroiditis is another condition associated with granulomas. It was first reported by Carney et al. that was assumed to be a result of a traumatic injury caused by vigorous palpation of the gland during examination. In his study, he stated that palpation thyroiditis was noted in 83–100% of thyroid glands with both benign and malignant diseases like papillary carcinoma, medullary carcinoma, Graves’ disease and adenomas. He also reported granulomas in thyroid tissue that were removed in laryngeal cancers and autopsy specimens in hospitalised patients [9]. However, Hwang et al. suggested that apart from mechanical causes, certain types of physiological alterations in the follicular basement membrane can also produce palpation thyroiditis [12].

The granulomas associated with Wegener’s granulomatosis are typically of non-caseating type and exhibit a characteristic irregular geographic shaped necrosis with abundant nuclear debris which was not the finding in our case. So far, only a case of Wegener’s granulomatosis in the thyroid presenting as a mass has been reported by Schmitz et al. [13]

In 1902, Dr. Fritz de Quervain first described the granulomatous disease of the thyroid that commonly presents as Sub-acute (De Quervain) thyroiditis. The cause was presumed to be of viral origin or as a result of post-viral inflammatory conditions along with the strong association of Human Leucocyte Antigen - B 35 antigen. Trivedi et al. reported a case of granulomatous thyroiditis in a patient who had undergone three prior cadaveric renal implants for renal failure due to Alport syndrome. Both fine needle aspiration and lobectomy demonstrated suppurative granulomatous lesions with filamentous micro-organisms that morphologically resembled Actinomyces or Nocardia [14].

After a careful and complete review of the literature, only one case study from the United Arab Emirates done by Rajakumar et al. showed the association of CVPTC with caseating granulomatous inflammation in the gland as well as in the lymph nodes [10]. In our case, right hemithyroidectomy was performed for a solitary thyroid nodule along with suspicion of malignancy. Even though the histopathological findings were suggestive of CVPTC with coexisting caseating granulomatous inflammation, special stains like AFS and PAS were negative. Hence, the cause for granulomas in this case is unknown and could have resulted from chronic inflammation.

Conclusion

CVPTC with coexisting caseating granulomatous inflammation is a rare presentation. The exact pathology of caseating granulomatous inflammation in our case is unknown. However, the role of chronic inflammation in tumorigenesis and the occurrence of granulomas following palpation of the gland is yet debatable. To our knowledge and following a complete literature review, we report the first case of CVPTC with coexisting caseating granulomatous inflammation of non-tuberculous origin.

Abbreviations

AFS

Acid Fast Stain

CVPTC

Conventional Papillary Thyroid Carcinoma

FNA

Fine Needle Aspiration

PAS

Periodic Acid Schiff Stain

TT

Thyroid Tuberculosis

Author Contributions

Dr. MMS performed the surgery Dr. SG grossed the specimen Dr. BCS reported the case and edited the manuscript Dr. UC prepared the manuscript and literature review.

Funding

Nil.

Data Availability

Not applicable.

Declarations

Research Involving Human Participants and / Animals

Human participation involved and consent taken

Informed Consent

Obtained from patient.

Conflict of Interest

All the Authors declare that we do not have any conflict of interests.