Anatomic Pathology #1: Diseases of Thyroid Gland, Mindgrasp Notes

Anatomic Pathology - Diseases of Thyroid Gland

Powered by mindgraspAi Anatomic Pathology #1 - Diseases of Thyroid Gland

• The thyroid gland is formed of two lobes, a right and a left lobe, and a central part consisting of the isthmus and the pyramidal lobe.
• In histological terms, the gland is divided into lobules, with each lobule containing 20 to 40 evenly distributed follicles.
• Each follicle is made up of cuboidal or flat or low columnar follicular cells, which are the functional unit of the thyroid gland.
• The follicles also contain PARAFOLLICULAR cells, which secrete CALCITONIN hormone, promoting absorption of calcium by the skeletal system and inhibiting reabsorption of bone by osteoclast.

Review of Thyroid Gland Histology and Pathology

• The normal histology of the thyroid gland involves follicles of varying shapes and sizes, lined by cuboidal or flat follicular cells, and parafollicular cells in the interstitial part that secrete calcitonin hormone.
• The pathology of the thyroid gland is divided into non-neoplastic and neoplastic diseases, with non-neoplastic diseases further categorized into congenital diseases, hyperplasia, and thyroiditis.
• The classification of neoplastic diseases includes epithelial and non-epithelial neoplasms, further divided into benign and malignant categories.
• The role of the anatomopathologist is crucial in understanding and categorizing different pathologies to define the prognostic risk of the patient.
• Examples of congenital diseases of the thyroid gland include agenesis, aplasia or hypoplasia, thyroglossal duct remnants, thyroglossal duct cysts, and ectopic thyroid tissue in various regions.
• More common pathologies, particularly thyroid hyperplasia, will be further discussed.

Thyroid Gland Diseases

• Common goitre is the most frequent thyroid disease, characterized by an irregular volume increase in the gland with multiple nodules, potentially related to dietary iodine insufficiency in the endemic form.
• Patients with common goitre are typically euthyroid, with TSH levels in the normal range.
• Morphological inspection of nodules differentiates adenomatoid nodules, composed of small follicles lined by cuboidal thyrocytes, from colloid nodules, which are large follicles repleted with pale colloid and lined by flattened thyrocytes.
• Some nodules may contain oncocytic cells, characterized by an oncocytic, eosinophilic pink cytoplasm and irregular nuclei without a prominent nucleolus.

. Granulomatous reactions may occur due to follicle rupture and colloid leakage in the stroma, resulting in variable inflammatory infiltration.

• Dyshormonogenetic goitre is caused by inherited defects in thyroid hormone synthesis, leading to activation of TSH secretion, overstimulation, and hyperplasia of the defective thyroid gland.
• This condition is an important cause of congenital hypothyroidism and is often found during neonatal screening or manifested around a young age, particularly during puberty.
• The essential features include a genetic autosomal recessive enzymatic defect in one of the steps of thyroid hormone synthesis, resulting in congenital hypothyroidism with decreased or absent T3 and T4 levels.

Anatomic Pathology of Thyroid Gland

• Positive feedback of TSH
• Deficiency of thyroid peroxidase (TPO) is a common worldwide cause
• Histological features of marked hypercellular nodules and empty follicles with minimal colloid
• Different nodules are seen separated by fixed septa with fibrosis and mild inflammation
• Characteristically empty follicles
• Diffuse Hyperplasia
• DIFFUSE HYPERPLASIA is observed in the GRAVE'S DISEASE
• Clinical features include follicles that are repleted of colloid, pink colloid, and papillary infoldings
• More fibrosis than inflammation in this type of goiter

Grave's Disease

• Grave's disease is a complex syndrome with different clinical symptoms associated with a diffuse goiter, a diffuse hyperplasia.
• Clinical symptoms in patients with Grave's disease include ophthalmopathy, dermopathy, pretibial myxedema, swelling of the extremities, and clubbing of fingers and toes due to periosteal new bone formation.
• The pathogenesis of Grave's disease is an autoimmune phenomenon, resulting in antibodies that can be stimulatory, inhibitory, or neutral, leading to various clinical presentations of hyperthyroidism or hypothyroidism.
• Macroscopically, the thyroid in Grave's disease is enlarged in volume and appears red at the cut surface.

. Histologically, Grave's disease exhibits hyperplastic follicles with intense lymphocytic infiltration, papillary infoldings, colloids resorption, colloid decrease, dyshormonogenetic goiter, and a dense lymphoid infiltrate.

Thyroid Diseases

• Dyshormonogenetic goiter is more fibrotic and phlogistic than grave's disease
• Atypical cells can build up and be mistaken for a neoplastic malignant process
• Cells with enlarged, atypical nuclei and altered nucleus and cytoplasmic ratio
• Differentiated types of thyroiditis: acute, chronic, subacute
• Most common forms of thyroiditis: acute thyroiditis, granulomatous form, chronic thyroiditis
• Hashimoto thyroiditis is an autoimmune disease with goiter and elevated circulating antibodies
• Different nodules with interspersed follicles in Hashimoto thyroiditis

Diseases of Thyroid Gland

• Germinal T-centers are a defining feature of the thyroiditis, along with massive, diffuse lymphoplasmacytic infiltration and destruction of surrounding thyroid follicles.
• Remaining follicles are small and many are lined by Hurthle cells, which have been defined as oncocytic cells with pink, eosinophilic cytoplasm and a prominent nucleus.
• Hurthle cells are a diagnostic clue for Hashimoto thyroiditis, which is characterized by phlogosis of the follicles and presence of diffuse lymphocytic infiltration and hyperplasia of the oncocytic cells.
• In advanced forms of Hashimoto's thyroiditis, fibrotic septa, interstitial atrophy, and squamous metaplasia can also be observed.
• De Quervain's Thyroiditis is a granulomatous thyroiditis caused by viral infections and is less common than Hashimoto's thyroiditis.
• The gland swells up and is very painful and tender in De Quervain's Thyroiditis, with a characteristic form of phlogistic infiltrate consisting of inflammatory cells, granulomas, and areas of both lymphocytic and neutrophilic infiltration.
• Neoplastic diseases of the thyroid gland have been categorized into different types.

Thyroid Neoplasia

• Thyroglossal duct cyst and other congenital thyroidal abnormalities are developmental abnormalities related to the thyroid gland
• Follicular cell-derived neoplasms include benign tumors such as thyroid follicular nodular disease, follicular adenoma, and follicular adenoma with papillary architecture, as well as low-risk and malignant neoplasms like follicular thyroid carcinoma, papillary thyroid carcinoma, and others
• Thyroid C-cell-derived carcinoma includes medullary thyroid carcinoma
• Salivary gland-type carcinomas of the thyroid consist of mucoepidermoid carcinoma and secretory carcinoma of salivary gland type
• Thyroid tumors of uncertain histogenesis include sclerosing mucoepidermoid carcinoma with eosinophilia and cribriform morular thyroid carcinoma
• Thymic tumors may occur within the thyroid and include various types such as thymoma and thymic carcinoma
• Embryonal thyroid neoplasms like thyroblastoma are also important
• Non-epithelial forms of thyroid neoplasia can include mesenchymal/stromal tissue or the hematolymphoid tissue, as well as germ cell tumors and secondary tumors
• Paraganglioma and mesenchymal/stromal tumors may also occur
• Mesenchymal/stromal tumors include peripheral nerve sheath tumors, benign vascular tumors, angiosarcoma, smooth muscle tumors, and solitary fibrous tumors

Hematolymphoid Tumors and Follicular Cell Derived Neoplasms

• Hematolymphoid tumors include Langerhans cell histiocytosis, Rosai-Dorfman disease, and follicular dendritic cell sarcoma.
• Germ cell tumors consist of benign teratoma (grade 0 or 1), immature teratoma (grade 2), and malignant teratoma (grade 3).
• Follicular cell derived neoplasms are mainly derived from the functional unit of the thyroid, the follicular cells.
• Characteristics of follicular adenoma include an external capsule, follicular cell differentiation, typically seen in euthyroid adults, and a higher occurrence in females.
• Macroscopic histological form of benign follicular adenoma is a circumscribed neoplasia with surrounding parenchyma affected by lymphocytic thyroiditis.

Diagnostic Criteria for Follicular Adenoma

• Criteria for diagnosis of follicular adenoma include:
• Solitary nodule
• Encapsulated, well defined nodule
• Compressed thyroid tissue outside the capsule of thyroid adenoma

. At a microscopical level, back to back arrangement of follicles, decreased colloid, and minimal nuclear atypia can be observed in the cells of follicular adenoma.

• Oncocytic adenoma is a form of adenoma where more than 75% of the neoplastic cells are Hurthle or oncocytic cells, representing a follicular derived neoplasia.

Types of Thyroid Neoplasms

• Follicular adenoma can be recognized by a thick fibrous capsule surrounding the normal thyroid gland.
• Follicular adenoma has a differential diagnosis with follicular carcinoma that involves checking for capsular and/or vascular invasion as well as surrounding parenchyma invasion.
• Papillary adenoma is a variant of follicular adenoma characterized by intrafollicular papillary architecture and hyperplastic follicles.
• The classification of low-risk neoplasms in thyroid pathology includes NIFTP, UMP, and HTT.
• NIFTP, or non-invasive follicular thyroid neoplasm with papillary-like nuclear features, is a new entity that should be completely encapsulated and only exhibit follicular structures.

NIFTP: A Variant of Papillary Thyroid Carcinoma

• NIFTP stands for encapsulated follicular variant of PTC
• It consists of follicular cells and structures without papillary structure
• Nuclei of neoplastic cells resemble those of papillary thyroid carcinoma
• It is non-invasive, encapsulated, and follicular in nature
• Major criteria for defining NIFTP include no BRAF mutation, no papillary structure, and resemblance to papillary like carcinoma in the nuclei
• Scoring a nuclear feature involves a system with a total score of 0 to 3 based on irregular size and shape, membrane, and chromatin characteristics that are similar to papillary thyroid carcinoma

Thyroid Tumors of Uncertain Malignant Potential

• Nuclear atypia is moderate or high and is typical of a PTC (Papillary Thyroid Carcinoma).
• At low magnification, an encapsulated lesion and follicular structures can be observed.
• A nuclear score of 2-3 categorizes the neoplasm as NIFTP (Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features).
• If the neoplasm is infiltrative or shows infiltration of the capsule, it is categorized as a Papillary Thyroid Carcinoma Follicular Variant.