Familial non-medullary thyroid carcinoma

Introduction to familial thyroid non-medullary carcinoma Nonmedullarythyroidcarcinoma (NMTC) refers to malignant tumors originating from thyroid follicular cells, including papillary, follicular, and undifferentiated cancers, accounting for the majority of thyroid cancer, while medullary thyroid carcinoma Originated from thyroid C cells. In previous understandings, genetically predisposed thyroid cancer was mainly familial medullary carcinoma, while non-medullary carcinoma was generally sporadic. In 1955, Robinson and Orr of the United Kingdom first reported that a pair of identical twins had thyroid non-medullary carcinoma. In 1975, Nemec et al reported that a mother and child had thyroid non-medullary carcinoma and could definitely exclude radiation exposure and Known familial diseases, which have caused foreign scholars to pay attention to the research on whether the thyroid non-medullary carcinoma has genetic predisposition. In recent years, there have been more and more reports and studies on familial nonmedullary thyroid carcinoma (FNMTC). Available data have shown that familial thyroid non-medullary carcinoma as a part of thyroid non-medullary carcinoma has a genetic predisposition and has its unique etiology, pathology and clinical features. basic knowledge The proportion of illness: 0.001% - 0.002% (with hereditary) Susceptible people: no specific population Mode of infection: non-infectious Complications: thyroid cancer

Familial thyroid non-myeloid carcinoma

(1) Causes of the disease

1. Genetic characteristics

If FNMTC does exist as an independent genetic disease, some large families should be found in a large number of existing patients. The family of patients not only helps to understand the genetic pattern of the disease, but also the understanding of the cause. The cloning of disease genes has been greatly assisted. There are few reports on FNMTC family in the existing literature. In 1980, Lote et al reported two families with 11 patients with papillary thyroid carcinoma. In 1986, Stoffer et al identified 22 thyroid glands. There are 8 families of papillary carcinomas. Later, there are reports of some families. Most of these reports involve fewer patients, and most of them involve only one or two generations. In 1997, Burgess et al reported that two families involved 11 In the case of thyroid papillary carcinoma, the authors believe that its genetic pattern is autosomal dominant, in which one of the 25 members of the family has thyroid papillary carcinoma (6 of which have goiter) and 11 have goiter ( Figure 1), through the study of this family, found that there may be FNMTC pathogenic genes in the chromosome 2q21 region, and some studies have found that FNMTC patients also have breast cancer and kidney cells. The chance increases.

Some families in FNMTC belong to some familial multi-organ susceptibility to tumor diseases, and their thyroid tumors are the main part or component of multi-organ lesions of these diseases. The genetic diseases associated with thyroid non-myeloid tumors are currently known: familial gonads Familial adenomatous polyposis (FAP), Cowden disease, Carney complex, McCune-Albright syndrome and Werner syndrome, clear in FNMTC The proportion of those who belong to the above known genetic diseases is small, and the genetic model and genetic basis of most FNMTCs remain unclear.

(1) Familial adenomatous polyposis: The disease is characterized by the presence of a large number of adenomatous polyps (usually more than 100) in the colon. It is an autosomal dominant genetic disease, and germ cells are generated by the APC gene located on chromosome 5q21. In 1951, Gardner reported on extra-colonary lesions, including skin lesions such as osteoblasts and multiple epidermal cysts in the skull. Later generations will be referred to as "Gardner" with a family-like adenomatous polyposis with extraintestinal lesions. Syndrome, in addition to the above-mentioned bone and skin lesions, common extra-parenteal lesions include dental malformations, upper digestive tract polyps or hamartomas, congenital retinal pigment cell hyperplasia and thyroid lesions, in fact, 1921 Devic and Bussy An extraintestinal lesion of the intestinal adenomatous polyposis was reported, including a case of "goiter." In 1949, Crail reported a case of familial adenomatous polyposis with thyroid non-medullary carcinoma, but until 1968, the thyroid gland The association between cancer and familial adenomatous polyposis is widely accepted. In 1994, Harach et al. showed that familial adenomatous polyposis-associated thyroid cancer is A unique type of thyroid follicular cell tumor, whose genetic basis is different from that of familial adenomatous polyposis and thyroid cancer, and the location of its genetic mutation is different from the latter two.

Familial adenomatous polyposis thyroid cancer is more common in women, about 8 times that of men, and more often within 30 years of age. Studies have shown that women with familial adenomatous polyposis are 100 times more likely to develop thyroid cancer than the general population. The age of 35 years old is up to 160 times. The prognosis of this disease is good. After the diagnosis of thyroid cancer, the 5-year and 10-year survival rates are 90% and 77%, respectively. The treatment failure often shows local recurrence. Usually these patients Most of the primary lesions are multi-centered, and about one-third of the patients present with multiple tumors of the thyroid gland, which are basically female patients.

(2) Cowden disease: also known as "multiple hamartoma syndrome", is an autosomal dominant genetic disease, named after the first patient reported by Lloyd and Dennis in 1963, the disease and Chromosome 10q22-23 is associated with germ cell mutations in the tumor suppressor gene PTEN. Colten's diseased thyroid nodules are often follicular adenomas, adenomatous nodules and microadenomas, and may also be thyroid follicular carcinomas. The nodules that are touched often have a complete capsule. According to the literature, 2/3 of patients with Cowden's disease can have thyroid disease. The average age of onset is 41 years old, female: male is 2.7:1. The average age of onset of malignant tumor patients is higher. Large, tumor diameter is also larger than benign tumors, which also shows the progression of thyroid follicular adenoma to adenocarcinoma in this disease.

(3) Carney complex: also an autosomal dominant genetic disease characterized by pigmentation of the skin mucosa, blue sputum and other pigmented lesions, combined with endocrine or non-endocrine tumors, the disease is located on chromosome 17q24 Protein kinase AR1 regulates subunit PRKAR1 gene mutation in patients with thyroid disease, the patient is younger, showing multiple nodules of the thyroid, 5 cases reported by Stratakis et al, 1 case of papillary carcinoma, 1 case of follicle The other 3 cases were follicular adenomas.

(4) McCune-A1bright syndrome: characterized by multiple fibrous dysplasia, skin lesions and high function of endocrine glands, associated with GNAS1 gene mutation, which has been reported to be associated with thyroid disease, including autonomic thyroid adenoma And follicular adenocarcinoma.

(5) Werner syndrome: due to germ cell mutations in the WRN gene located on chromosome 8p11-21, manifested as premature aging changes in juvenile or adult patients (bilateral cataract, white hair, skin atrophy, etc.), the disease often Combined with epithelial tumors, including thyroid cancer, compared with common thyroid cancer, the age of onset is earlier, the proportion of women in sex is lower, the proportion of undifferentiated cancer is higher, and follicular carcinoma is much more than papillary carcinoma.

2. The basis of molecular genetics

With the exception of a few familial tumor syndromes with thyroid non-medullary carcinoma, little is known about the molecular genetics of FNMTC, which is the best sample of possible pathogenic genes, but is difficult to obtain due to large families. Most of the existing researches have been carried out in small families. The exact pathogenic genes of this disease have not yet been found, but some genetic diseases have been ruled out. Kraimps et al. studied a family (6 cases of goiter). And 3 cases of papillary thyroid carcinoma found that tumor cells showed some eosinophilic changes, and related to TCO (thyroid tumor with cell oxyphilia) gene, which is located on chromosome 19p13.2, and Bevan et al. found in 22 One family has a TCO gene associated with FNMTC. Since many FNMTCs are accompanied by multiple goiters, and familial non-toxic polythyroids are associated with a gene localized to the chromosome 14q region, Bignell et al. Non-medullary carcinoma is not associated with this gene. Another excluded gene is the RET pro-oncogene, which rearranges and sporadic thyroid papilla It is related to the onset of cancer, but it has nothing to do with FNMTC. Although familial adenomatous polyposis can often be combined with thyroid non-medullary carcinoma, the latter is not related to the gene APC that causes familial adenomatoid polyposis. The genes are also MNG1, fPTC, PTEN, TSHR and TRKA.

(two) pathogenesis

FNMTC is mostly papillary thyroid carcinoma, accounting for about 90%. The rest are mainly eosinophilic tumors. A few reports have reported that one of the affected family members is suffering from anaplastic thyroid cancer, while other members are suffering from differentiated thyroid cancer. May suggest the progress of the tumor, pathological features, FNMTC pathological findings and sporadic similar, but more involving the thyroid bilateral, multifocal changes and cell eosinophilic changes, Uchino et al found that FNMTC tumor gland in vivo More scattered loose hair (family 40.7%; loose hair 28.5%), combined with multiple benign goiter is more common, regional lymph node metastasis is relatively less, and distant metastasis is earlier and more common, more special Is a familial adenomatous polyposis-related thyroid cancer, mostly localized lesions, often with intact capsules, local invasion, tumor capsule and interstitial fibrosis, tumor cells showing some and traditional thyroid cancer Different unique cell structure features:

1 a unique growth mode consisting of a sieve-like region, a short bundle of spindle-shaped cells, a non-keratinized squamous cell vortex and a hard tumor-like component;

2 There is no "Glass-glass"-like chromatin in the nucleus;

3 "Fir tree-like" nipple growth patterns of typical papillary thyroid carcinoma are rare.

Familial thyroid non-medullary carcinoma prevention

Family history suggests that patients with FNMTC need to have a physical examination of all family members who may be ill, although it is unclear how long it takes to examine the risk population, but because thyroid cancer is a relatively slow-growing tumor. It is recommended to conduct an annual examination of the dangerous population. If the thyroid mass is found in the physical examination, further examinations must be taken, such as fine needle aspiration cytology, B-ultrasound examination and radionuclide imaging. Property nature.

Familial thyroid non-myeloid carcinoma complications Complications thyroid cancer

Can be complicated by thyroid cancer.

Familial thyroid non-medullary cancer symptoms Common symptoms Dysphagia Difficulty breathing Nodules hoarseness Goiter swelling slow

FNMTC accounts for about 5% of thyroid cancer. Apart from its family history, there is no special clinical feature that can distinguish FNMTC from sporadic. Most of the literature reports that FNMTC is similar to sporadic in age, sex and metastasis. The clinical manifestations are:

1. There are more female patients than males, female: male is about 2:1, and the average age is about 38 years old.

2. Thyroid nodules are gradually enlarged neck painless masses, often found by patients or physicians inadvertently or during B-ultrasound examinations.

3. Patients often have no obvious discomfort and the tumor grows slowly.

4. Late stage may be accompanied by varying degrees of hoarseness, difficulty in pronunciation, difficulty in swallowing and difficulty in breathing, and local aggression.

5. A small number of patients can have a metastatic mass in the neck, and the symptoms of lung metastases are the first manifestations.

6. Patients are generally not associated with changes in thyroid function, but some patients may be associated with hyperthyroidism.

7. It can touch the characteristic thyroid mass. The texture is generally hard, the edges are often blurred, and the surface is uneven. If it is confined to the gland, the tumor can often move with the swallow and move in the gland.

8. Lymph node metastasis is more common in the supraclavicular, jugular vein and paratracheal, and a few cases can also have axillary lymph node metastasis.

Examination of familial thyroid non-medullary carcinoma

Fine needle aspiration and cell examination.

Imaging examinations, such as B-ultrasound, CT, MRI and radionuclide scanning, can confirm the nature of the tumor, and its diagnostic significance is similar to sporadic thyroid cancer.

Diagnosis and diagnosis of familial thyroid non-medullary carcinoma

Family history

The disease is a partially transmitted autosomal dominant inheritance. In some families, the proportion of family members suffering from benign thyroid diseases (such as nodular goiter) is increased, so all patients with thyroid non-medullary carcinoma should pay attention to it. Understanding of family history.

2. Clinical manifestations

In clinical manifestations, FNMTC and differentiated thyroid cancer have no significant difference in age of onset, gender, tumor diameter, local invasion, lymph node metastasis, thyroiditis, etc., but spread in tumor glands, combined with multiple benign lesions and The prognosis and other aspects are obviously different.

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