Epidemiology and genetic factors
Malignant neoplasms of the thyroid gland are diagnosed at a rate of 5–10 cases per 100,000 population. The main risk group consists of elderly individuals, with this rate being particularly high in industrially developed countries. An important epidemiological feature is gender predilection: women are affected 2–3 times more frequently than men.
The development of various morphological forms of cancer is closely associated with specific genetic abnormalities:
- c-fos: the level of this mutated nuclear protein increases significantly during the development of papillary carcinoma.
- ret and ntrk1: proto-oncogenes encoding tyrosine kinase receptors, mutations in which are frequently detected in thyroid oncology.
- c-myc: mutations of this gene accompany the formation of follicular and medullary carcinomas.
- Anaplastic cancer: characterized by a specific mutation of a gene located on chromosome 5q21 at codon 1346, where an adenine insertion occurs at codon 1556.
Papillary carcinoma
Papillary cancer accounts for up to 60% of all diagnosed cases of malignant thyroid tumors. The disease is most typical for women aged 30 to 50 years and in clinical practice may be accompanied by symptoms of thyrotoxicosis.
Macroscopic appearance Visually, the tumor is a dense, pale gray node up to 10 cm in diameter. Cystic cavities often form within the structure of the neoplasm, and foci of calcification (calcifications) are also detected.
Microscopic appearance and cytology Histologically, the carcinoma is represented by multiple papillary proliferations formed by atypical cubic epithelium. The pathomorphological diagnosis is based on key diagnostic features—specific changes in cell nuclei:
- Presence of hypochromic, "empty" nuclei completely lacking nucleoli.
- Formation of characteristic indentations in the nuclear membrane.
- Appearance of eosinophilic intranuclear inclusions, which represent areas of invaginated cytoplasm.
- Formation of psammoma bodies, which are localized predominantly in the central part of papillary structures.
According to statistical data, metastasis in this form occurs extremely rarely. Involvement of regional cervical lymph nodes is atypical, and hematogenous spread of tumor cells with the formation of lung metastases is recorded only in isolated cases. Therefore, the disease has a favorable prognosis: patient survival exceeds 20 years in 90% of cases.
Diagnosis of medullary cancer within MEN
Medullary thyroid carcinoma (MTC) often develops as a neuroendocrine tumor as part of multiple endocrine neoplasia (MEN) syndromes. Diagnosis requires mandatory confirmation of a hyperfunctional syndrome using a panel of biochemical markers and subsequent morphological verification.
Diagnostic measures:
- Genetic testing: a mandatory stage for diagnosing MEN 2 syndrome, aimed at detecting RET gene mutations.
- Specific markers: if MTC is suspected, the basal plasma calcitonin level is assessed, along with testing the calcitonin level in fine-needle aspiration washout.
- Instrumental methods: ultrasound examination (US) is indicated for absolutely all patients with MEN to detail visualization of the thyroid and parathyroid glands, as well as to assess the status of the cervical and supraclavicular lymph nodes.
- Morphological examination: pathomorphological analysis of surgical or biopsy material must necessarily be supplemented by immunohistochemistry (IHC).
- Assessment of the clinical presentation: the physician searches purposefully for systemic symptoms. Invasion by thyroid cancer can cause voice changes (dysphoria). Hypersecretion of various peptides in MTC sometimes leads to severe diarrhea and Cushing's syndrome. In addition, specific phenotypic features are evaluated: marfanoid habitus and the appearance of tongue neuromas (characteristic of MEN 2B), as well as the presence of cutaneous amyloidosis (typical of MEN 2A).
Key nuclear changes in papillary cancer are easy to remember due to their paradoxical nature: they are "empty, but with a surprise"—lacking nucleoli, yet containing indentations and invaginated cytoplasm (eosinophilic inclusions).
Class and exam questions
What is Plummer's disease and how does it manifest?
This is a toxic follicular adenoma accompanied by the development of mild to moderate thyrotoxicosis in the complete absence of eye signs. Most frequently, the disease affects women aged 40–60 living in regions with severe iodine deficiency, but it can also be detected in children.
What forms belong to rare atypical adenomas?
Such neoplasms include Hürthle cell adenoma, which histologically consists of large granular eosinophilic cells, and papillary adenoma, distinguished by papillary epithelial proliferations directly into the follicular lumen.
What benign thyroid formations exist besides adenomas?
Cysts (containing brownish fluid or blood), lipomas, hemangiomas, teratomas, and dermoid cysts are also encountered in clinical practice. The prognosis for timely treatment of such formations is generally favorable.
What is the purpose of arterial stimulation venous sampling (ASVS) in MEN?
This method is used primarily in diagnosing MEN 1 syndrome. It is essential for detecting topographically unlocalized hormone-active tumors located in the pancreas.
What else to study on this topic
- Morphological characteristics of follicular and medullary carcinomas
- Differential diagnosis of toxic follicular adenoma (Plummer's disease)
- Multiple endocrine neoplasia syndromes (MEN 1, 2A, 2B) and their phenotypes
- Histological features of Hürthle cell adenoma
- Benign non-epithelial tumors (lipomas, hemangiomas, teratomas)
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