Follicular thyroid carcinoma types, treatment of thyroid tumors, What is minimally invasive FTC?

Follicular Thyroid Carcinoma (FTC) is the second most common type of thyroid cancer after papillary thyroid carcinoma (PTC). It arises from the follicular cells of the thyroid, which are responsible for producing thyroid hormones.

Follicular thyroid carcinoma (FTC)

Incidence

• It is the 2nd common thyroid cancer (10%) and is more frequent in I₂-deficiency areas, suggesting that nodular goiter may predispose to the development of the neoplasm.
• High frequency of RAS mutations in follicular adenomas and carcinomas suggests that the two may be related tumors.
• Age: The mean age is 50 years.
• Gender: (female: male 3:1).

Pathology

• Most FTCs are composed of uniform cells forming small follicles containing colloid appearance of normal thyroid. The following features should be taken into consideration:
• Occasional tumors are dominated by cells with abundant granular, cosinophilic cytoplasm (Hürthle cells).
• Psammoma bodies are not present in the Nuclei and lack the features typical of PTC.
• Follicular lesions with nuclear features typical of PTC should be treated as PTC.
• Nuclear features do not help distinguish follicular adenomas from minimally invasive follicular carcinomas.
• Requires extensive sampling of the tumor-thyroid capsule interface to exclude capsular or vascular invasion.
• Unlike in PTCs, lymphatic spread is distinctly uncommon in follicular cancers.
• Thyrotoxic in 1% of cases.
  
• It has a propensity to spread via the blood stream. Vascular invasion and hematogenous spread in more common in (bone, lung, and liver).

Types

• Minimally invasive tumor: Invasion into, but not through, the tumor capsule.
• Invasive tumors (capsular/vascular).

Diagnosis and Prognosis

FNAC not helpful: lobectomy and isthmectomy, Mortality: 40% (at 10 years).

Scoring and Prognosis of DTC (Differentiated Thyroid Cancer)

AGES and AMES scoring systems: A (Age), G (Grade of tumor), M (Distant metastases), E (Extent of tumor), S (Size of tumor). Both scoring systems have identified 2 distinct subgroups:

Low-risk group:

• Men 40 years or younger, women 50 years or younger, without distant metastasis (bone and lungs).
• Older patients with intra-thyroid follicular/papillary carcinoma, with minor capsular involvement, and with tumors < 4cm in diameter.

High-risk group:

All patients with distant metastasis and older patients with extra-thyroid papillary/follicular carcinoma and tumors >4 cm, regardless of the extent of disease.

Hurthle cell thyroid tumor

• Incidence: 3-5%.
• Gender: Male: Female (2:1).
• Origin: Derived from exyphilic cells of the thyroid gland.
• Possesses TSH receptors.
• Spreads by lymphatics: Only 10% takes up iodine.
• Diagnosis: FNAC (20% malignant) – Often multifocal and bilateral.
• Treatment: Total thyroidectomy + Modified radical neck dissection (if with palpable cervical LNs).
• Thyroid suppression is suggested.
• Prognosis: 5-y-SR (survival rate): 60%.

Medullary thyroid carcinoma (MTC)

• Incidence: 5-7%.
• Age: The peak incidence is at 50-60 years.
• Origin: Arises front parafollicular or C cells of the thyroid (neuroectodermal-ultimobrachial bodies, 4th and 5th branchial pouches).
• Secret calcitonin (95%), 85% secrets carcinoembryonic antigen (CEA).
• Sporadic 90%: Uni-focal, usually at 45y, worse prognosis.
• Familial 10%: Multifocal, usually 35 years, better prognosis, associated with:

1. MEN IIA S (MTC, hyperplastic parathyroid and pheochromocytoma).
2. MEN IIB (MTC, pheochromocytoma, ganglioneuromatosis, and Marfan’s syndrome).

• Does not concentrate ¹³¹I.
• Can secrete: Calcitonin (95%), histamine, serotonin (causes diarrhea), ACTH (2-4%, causing Cushing syndrome), CEA (85%), Prostaglandin E2 and F2 alpha.

Spread:

• Lymphatics: (neck and superior mediastinum).
• Blood: liver, bone (osteoplastic), and lung.
• Local invasion.

Diagnosis:

Serum calcitonin, CEA, FNAC, and histology show a characteristic amyloid stroma.

Treatment

• Total thyroidectomy.
• MRND’s done for palpable cervical LN, tumor > 2cm, as there is a 60% nodal metastasis.
• Tumor debulking in cases of metastatic & local recurrence is done to ameliorate symptoms of flushing & diarrhea & help to decrease the risk of death.
• Radiotherapy and chemotherapy: failure.
• All patients should be screened for pheochromocytoma (MEN II), which should be resected first.
• Selective removal of the parathyroid glands should be done if there is preoperative hypercalcemia.

Follow up: Serum Calcitonin/CEA level.

Prognosis:

• Localized 10-y-SR of 80%. (+) LN 10-y-SR of 45%.
• Best worst prognosis, Familial non-MEN MTC, MEN IIA- sporadic cases, MEN IIB.

Anaplastic thyroid carcinoma (ATC)

• Incidence: An uncommon thyroid malignancy affecting older patients.
• Origin: May arise in a well-differentiated thyroid carcinoma,
  
• 80% of patients have a history of a long-standing goiter with sudden and rapid growth, hoarseness, dysphagia & airway compromise.
• Tracheal invasion and/or bilateral recurrent nerve paralysis can be seen.

Treatment

• Surgical excision is rarely possible without sacrificing essential cervical structures, but tissue diagnosis is needed to differentiate from lymphoma. Tracheostomy and total thyroidectomy are extremely difficult.
• External radiation may temporarily control the local effects of ATC.
• Limited effect of systemic chemotherapy (Adriamycin); no hormonal therapy known.
• Prognosis is extremely poor, with a mean life expectancy of 6-9 months. Death occurs from local invasion of vital cervical structures and airway compression.

Thyroid Lymphoma

• Non-Hodgkin B-cell lymphoma.
• Hashimoto’s thyroiditis is a risk factor.
• Compression manifestations
• Treatment:

1. Chemotherapy / Radiotherapy).
2. Surgery: It is curative when the disease is limited to the thyroid gland only.

• Prognosis: 80% survival if confined to the gland; 40% if it has spread elsewhere.

Metastatic carcinoma

• Rare.
• Hypernephroma is the most common primary site.

When to one suspect a tumor in a goiter?

• Search for hints throughout the history and physical examination:
• Examples of the hints that raise suspicion of a malignant tumor.

History

• Male gender.
• Extremes of age > 12 or > 60.
• History of irradiation to the neck (even repeated X-ray examinations or CT neck.
• Family history of thyroid cancer.
• Short history.
• Rapidly growing goiter or long-standing goiter with recent rapid growth.
• Pain.
• Dysphagia
• Dyspnea.
• Hoarse voice.
• Bone pain.
• Swelling of the lymph node.
• Swelling of the skull.

Examination

• Husky voice.
• Engorged neck veins.
• Weak carotid pulse.
• Single Thyroid nodule.
• Fixed goiter.
• Hard irregular goiter
• Enlarged hard cervical lymph nodes.

How to investigate?

• Ultrasound neck.
• Ultrasound-guided FNAC.

When to refer?

Based on the level of suspicion, GP either:

• Refer on clinical grounds.
• undertake investigations.

Syndromes linked to thyroid tumors

The familial form of medullary thyroid carcinoma (MTC) is usually a component of multiple endocrine neoplasia (MEN) IIA or IIB, or presents as pure FMTC syndrome.

Familial syndromes characterized by a:

Predominance of non-thyroidal tumors, such as:

• Familial adenomatous polyposis.
• PTEN-hamartoma tumor syndrome.

Predominance of papillary thyroid carcinoma (PTC), Such as:

• pure familial PTC (FPTC).
• FPTC is associated with papillary renal cell carcinoma.
• FPTC with multi-nodular goiter.

MEN IIA (Sipple Syndrome)

• It has bilateral medullary carcinoma or C-cell hyperplasia (CC), pheochromocytoma, and hyperparathyroidism.
• This syndrome is inherited in an autosomal dominant manner
• Males and females are equally affected. Peak incidence of medulary carcinoma in these patients is in the 30s. as late adolescence or early adulthood.

MEN IIB

• MENJIB is associated with pheochromocytoma, mucosal ganglioneuromas, and marfanoid habitus.
• This syndrome also has medullary carcinoma and pheochromocytoma, but will only rarely have hyperparathyroidism. Instead, these patients have an unusual appearance, which is characterized by mucosal gangioneuromas and a marfanoid habitus.
• Inheritance is autosomal dominant, as in MEN IIA.
• MEN IB patients usually get medullary carcinoma early in life, diagnosed in infancy or early childhood before their 30s, and males and females are equally affected.

Familial Tumor Syndromes Characterized by a Preponderance of Non-thyroidal Tumors.

Multiple endocrine neoplasia IIA

• The frequency of microscopic PTC is approximately twice as great in thyroid glands of MEN IIA patients if compared with general population.
• These cases usually present with multiple microscopic PTCS.
• These microcarcinomas are likely to carry only modest clinical significance, as microscopic PTCs often remain clinically silent, and affected subjects carrying germline RET mutations undergo thyroidectomy at a young age.

Cowden syndrome

Cowden syndrome is a disorder characterized by multiple noncancerous, tumor-like growths called hamartomas and an increased risk of developing certain cancers.

Almost everyone with Cowden syndrome develops hamartomas. These growths are most commonly found on the skin and mucous membranes (such as the lining of the mouth and nose), but they can also occur in the intestine and other parts of the body. The growth of hamartomas on the skin and mucous membranes typically becomes apparent by a person’s late twenties.

Cowden syndrome is associated with an increased risk of developing several types of cancer, particularly cancers of the breast, a gland in the lower neck called the thyroid, and the lining of the uterus.

Familial adenomatous polyposis

• FAP is an inherited autosomal dominant syndrome caused by germline mutations in the adenomatous polyposis col (APC) gene on chrotansome 5921.
• characterized by hundreds of adenomatous colonic polyps that develop during early adulthood Extracolonic manifestations in FAP include osteomas, epidermal cysts, desmoid tumors, upper gastrointestinal tract polyps hamartomas, (CHRPE) congenital hypertrophy of the retinal pigmented epithelium, hepatoblastomas and thyroid tumors.
• PTCs one of the extracolonic manifestations of FAP and occurs in approximately 2% palients.
• Young women with FAP are at particular risk of developing thyroid cancer and their chance of being affected is approximately 160 times higher than that of normal individuals, PTC Occurs with a frequency of about 10 times greater than that expected for sporadic PTC.

Werner’s syndrome

• Werner’s syndrome is an autosomal recessive connective tissue disease.
• characterized by premature aging, bilateral cataracts, gray hair, and skin atrophy.
• Patients with this syndrome have increased risk of a variety of neoplasias, including benign thyroid lesions and an increased incidence of PTC (only tumor present in white patients), and the most common tumor in Japanese patients (84%), followed by FTC (14%) and anaplastic thyroid carcinomas (2%). This latter neoplasm occurs in this syndrome at a higher frequency as compared with the general population.

Overview of the treatment of thyroid tumors

• Surgery is the main line of treatment whenever feasible.
• Surgery is used to remove the primary tumor, the rest of the thyroid gland, and the regional lymph nodes if indicated.
• Radioactive iodine ablation is used as an adjuvant therapy.
• Radioactive iodine is used as a targeted therapy for iodine-avid distant metastases.
• Postoperative TSH suppression to sub-physiologic levels is maintained through administration of the required dose of l-thyroxine. External beam irradiation is generally used for palliation.

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