hrvatski

Clinical characteritics of medullary, poorly differentiated and anaplastic thyroid carcinoma

Medullary thyroid carcinoma (MTG) In 1959, Hazard etal. were the first to describe med¬ ullary thyroid carcinoma (MTC) and its histological char¬ acteristics. In 1961, Sipple reported on the association of thyroid carcinoma and pheochromocytoma in six of his patients. In 1965, Schimke found MTC and bilater pheochromocytoma to be inherited in an autosomal dominant fashion. In 1968, Steiner reported on hyper-parathyroidism associated with MTC and pheochromocytoma, and designated it as MEN (Multiple Endocrine Neoplasia) 2A syndrome, while Williams in 1966 and Sizemore in 1974 identified MTC and pheochromocytoma without parathyroid hyperplasia, associated with a marfanoid body habitus and mucosal ganglioneuromatosis and identified it as MEN 2B syndrome. In 1986, Farndon identified MTC as having a familial association which is not associated with other endocrinopathies and identified it as FMTC. Over time, the following subtypes of MEN 2A syndrome were identified: a) MEN 2A (1): MTC, pheochromocytoma, parathyroid disease, b) MEN 2A (2): MTC and pheochromocytoma with¬ out parathyroid disease, and c) MEN 2A (3): MTC and parathyroid disease without pheochromocytoma. In 1993, routine testing for the RET protooncogene mutation in members of families with MEN 2A syndrome was introduced. MTC ranks 3rd most common thyroid carcinoma and accounts for some 10% of all thyroid carcinomas. It is of a neuroectodermal origin, i.e. it comes from C cells of the thyroid belonging to the APUD system. C cells are characterized by a pluripotent ability to secrete various biological substances such as, first of all, calcitonin, chromogranin and CEA, but also by ectopic production of ACTH, CRF, MSB, VIP, NSE, serotonin, prostaglandin, somatostatin, etc. In 75% of cases MTC occurs in the sporadic and in 25% in the familial form. Sporadic MTC are mainly unifocal, whereas familiar MTC are multicentric and bilateral. Sporadic MTC usually occurs in mature age and develops slowly ; however, at 10-year follow up the survival rate was about 50%. MTC in MEN 2A syndrome is manifested in early thirties and in MEN 2B syndrome in early twenties. MTC in both syndromes and especially in MEN 2B syndrome is considerably more aggressive than spradic MTC and is prone to earlier metastasis. Clinical symptoms of the disease depend on the type of the potential ectopic production of particular hormones or sustances and on associated endrocrinopathies. Some patients complain of diarrhea that occurs with high calcitonin, prostaglandin and serotonin levels. The rate of parathyroid hyperplasia in MEN 2 syndrome is 20% to 40%, of bilateral pheochromocytoma about 50%, however, the incidence rate of pheochromocytoma in MEN 2B syndrome is higher. Since the heritable MTC forms were found to be caused by activation of the RET proto-oncogene mutation, all patients with a familial form of RET proto-oncogene have to undergo testing. Specific type of the familial form of MTC (MEN 2A, MN 2B and FMTC) can be identified by a characteristic mutation of RET proto-oncogene of individual exons (10, 11, 13, 14, 15, 16) as well as by characteristic codons. All newly found MTC have to be tested. In case of positive RET mutation, all relatives have to be tested in order to establish genetic load with this disease and for further treatment and follow up. Recently, prenatal testing for RET mutation on amniocentesis has is also available. Ultrasound-guided cytologic puncture provides a finding that is characteristic of MTC ; calcitonin level can be measured in the aspirate. Histological evidence of MTC is obtained by positive immunohistochemical reaction with calcitonin, chromogranin and CEA. In the early detection and monitoring of patients with MTC, determination of the level of calcitonin as a very selective marker is highly valuable. C cells produce calcitonin that is a very strong inhibitor of osteoclastic activity. Other tumors such as small cell lung carcinoma rarely produce calcitonin. Calcitonin secretion is stimulated by pentagastrin, calcium and alcohol. Measurement of calcitonin is a standard part of the pentagastrin stim¬ ulation test. In newly detected MTC with already formed nodule, high basal calcitonin level is usually measured. Stimulation test (pentagastrin) is highly valuable in the follow up of patients operated on (occurrence of metastases) and in the follow up of newly detected members with familial MTC. Increased CEA level is also a sign of the disease propagation. Increased chromogranin level points to the association of other endocrinopathies (pheochromocytoma). Scintigraphic testing is more or less limited: scintig-raphy of the whole body with Tc"m DMS (V), I131 MIBG and Tc"m octreotide. Scintigraphy with Tc"m sestamibi is useful providing evidence of parathyroid hyperplasia. PET-CT diagnostic technology is important in the detection of existing metastases. The leading treatment method is surgical extirpation of the thyroid with removal of the neck and upper mediastinum lymph nodes. Radioiodine therapy is not indicated, and the effects of x-ray radiation and chemotherapy are poor. The age at which younger family members with MEN 2 syndrome should be exposed to prophylactic thyroidectomy is still a subject for debate. The age range of 6-10 years is considered appropriate. Foci of MTC have been reported in the thyroid of a child operated on at the age of 7 months. Metastases have been reported in a child as young as 6 years. Poorly differentiated thyroid carcinoma (PDTC) According to the WHO classification, PDTC is defined as a tumor originating from follicular thyroid cells and with morphological and biological characteristics between differentiated adenocarcinoma and anaplastic thyroid carcinoma. However, histological definition of PDTC is still controversial and diagnostic criteria have not yet been defined. Histological subtypes of well differentiated adenocarcinoma can be found in the literature: trabecular, nodular, solid and insular growth of follicular adenocarcinoma with presentation of rhabdoid cells, tall columnar cells of papillary carcinoma variant, solid papillary carcinoma variant in children exposed to radioiodine after Chernobyl accident in 1986, and diffuse sclerosing variant of papillary carcinoma in young women associated with lymphocyte infiltration. In PDTC, thyroglobulin can be determined by im-munohistochemical analysis. The possible genetic load such as BRAF mutation in tall cell variant of papillary carcinoma is studied. Expression of various markers of cell proliferation and differentiation is also studied. In the treatment of PTDC, more radical treatment with exploration of the neck and upper mediastinum is suggested. Anaplastic thyroid carcinoma (ATG) ATC is the most aggressive thyroid carcinoma me-tastasizing very quickly with the highest incidence rate in patients aged over 60 years. It is a very rare disease accounting for 1% of all thyroid malignant diseases and is the cause of over 40% of deaths due to thyroid carcinoma. Survival longer than 6 to 12 months of the onset is very rare. ATC occurs in patients with a goiter enlarging for a longer period and with previously diagnosed thyroid adenocarcinoma coming from iodine-poor regions. The main symptoms are abrupt growth of frequently painful nodular goiter with enlarged lymph nodules, with difficulties in respiration and speech. At the time of the disease detection, distant metastases are seen in 20%-50% of patients. Tumor metastasizes to many organs. ATC has easily recognizable cytological and histological characteristics. Treatment is mainly palliative: surgical removal of tumor mass with freeing of the respiratory tract, radiation and chemotherapy.

medullary thyroid carcinoma (MTG); clinical characteritics of MTG

nije evidentirano

engleski

Clinical characteritics of medullary, poorly differentiated and anaplastic thyroid carcinoma

Medullary thyroid carcinoma (MTG) In 1959, Hazard etal. were the first to describe med¬ ullary thyroid carcinoma (MTC) and its histological char¬ acteristics. In 1961, Sipple reported on the association of thyroid carcinoma and pheochromocytoma in six of his patients. In 1965, Schimke found MTC and bilater pheochromocytoma to be inherited in an autosomal dominant fashion. In 1968, Steiner reported on hyper-parathyroidism associated with MTC and pheochromocytoma, and designated it as MEN (Multiple Endocrine Neoplasia) 2A syndrome, while Williams in 1966 and Sizemore in 1974 identified MTC and pheochromocytoma without parathyroid hyperplasia, associated with a marfanoid body habitus and mucosal ganglioneuromatosis and identified it as MEN 2B syndrome. In 1986, Farndon identified MTC as having a familial association which is not associated with other endocrinopathies and identified it as FMTC. Over time, the following subtypes of MEN 2A syndrome were identified: a) MEN 2A (1): MTC, pheochromocytoma, parathyroid disease, b) MEN 2A (2): MTC and pheochromocytoma with¬ out parathyroid disease, and c) MEN 2A (3): MTC and parathyroid disease without pheochromocytoma. In 1993, routine testing for the RET protooncogene mutation in members of families with MEN 2A syndrome was introduced. MTC ranks 3rd most common thyroid carcinoma and accounts for some 10% of all thyroid carcinomas. It is of a neuroectodermal origin, i.e. it comes from C cells of the thyroid belonging to the APUD system. C cells are characterized by a pluripotent ability to secrete various biological substances such as, first of all, calcitonin, chromogranin and CEA, but also by ectopic production of ACTH, CRF, MSB, VIP, NSE, serotonin, prostaglandin, somatostatin, etc. In 75% of cases MTC occurs in the sporadic and in 25% in the familial form. Sporadic MTC are mainly unifocal, whereas familiar MTC are multicentric and bilateral. Sporadic MTC usually occurs in mature age and develops slowly ; however, at 10-year follow up the survival rate was about 50%. MTC in MEN 2A syndrome is manifested in early thirties and in MEN 2B syndrome in early twenties. MTC in both syndromes and especially in MEN 2B syndrome is considerably more aggressive than spradic MTC and is prone to earlier metastasis. Clinical symptoms of the disease depend on the type of the potential ectopic production of particular hormones or sustances and on associated endrocrinopathies. Some patients complain of diarrhea that occurs with high calcitonin, prostaglandin and serotonin levels. The rate of parathyroid hyperplasia in MEN 2 syndrome is 20% to 40%, of bilateral pheochromocytoma about 50%, however, the incidence rate of pheochromocytoma in MEN 2B syndrome is higher. Since the heritable MTC forms were found to be caused by activation of the RET proto-oncogene mutation, all patients with a familial form of RET proto-oncogene have to undergo testing. Specific type of the familial form of MTC (MEN 2A, MN 2B and FMTC) can be identified by a characteristic mutation of RET proto-oncogene of individual exons (10, 11, 13, 14, 15, 16) as well as by characteristic codons. All newly found MTC have to be tested. In case of positive RET mutation, all relatives have to be tested in order to establish genetic load with this disease and for further treatment and follow up. Recently, prenatal testing for RET mutation on amniocentesis has is also available. Ultrasound-guided cytologic puncture provides a finding that is characteristic of MTC ; calcitonin level can be measured in the aspirate. Histological evidence of MTC is obtained by positive immunohistochemical reaction with calcitonin, chromogranin and CEA. In the early detection and monitoring of patients with MTC, determination of the level of calcitonin as a very selective marker is highly valuable. C cells produce calcitonin that is a very strong inhibitor of osteoclastic activity. Other tumors such as small cell lung carcinoma rarely produce calcitonin. Calcitonin secretion is stimulated by pentagastrin, calcium and alcohol. Measurement of calcitonin is a standard part of the pentagastrin stim¬ ulation test. In newly detected MTC with already formed nodule, high basal calcitonin level is usually measured. Stimulation test (pentagastrin) is highly valuable in the follow up of patients operated on (occurrence of metastases) and in the follow up of newly detected members with familial MTC. Increased CEA level is also a sign of the disease propagation. Increased chromogranin level points to the association of other endocrinopathies (pheochromocytoma). Scintigraphic testing is more or less limited: scintig-raphy of the whole body with Tc"m DMS (V), I131 MIBG and Tc"m octreotide. Scintigraphy with Tc"m sestamibi is useful providing evidence of parathyroid hyperplasia. PET-CT diagnostic technology is important in the detection of existing metastases. The leading treatment method is surgical extirpation of the thyroid with removal of the neck and upper mediastinum lymph nodes. Radioiodine therapy is not indicated, and the effects of x-ray radiation and chemotherapy are poor. The age at which younger family members with MEN 2 syndrome should be exposed to prophylactic thyroidectomy is still a subject for debate. The age range of 6-10 years is considered appropriate. Foci of MTC have been reported in the thyroid of a child operated on at the age of 7 months. Metastases have been reported in a child as young as 6 years. Poorly differentiated thyroid carcinoma (PDTC) According to the WHO classification, PDTC is defined as a tumor originating from follicular thyroid cells and with morphological and biological characteristics between differentiated adenocarcinoma and anaplastic thyroid carcinoma. However, histological definition of PDTC is still controversial and diagnostic criteria have not yet been defined. Histological subtypes of well differentiated adenocarcinoma can be found in the literature: trabecular, nodular, solid and insular growth of follicular adenocarcinoma with presentation of rhabdoid cells, tall columnar cells of papillary carcinoma variant, solid papillary carcinoma variant in children exposed to radioiodine after Chernobyl accident in 1986, and diffuse sclerosing variant of papillary carcinoma in young women associated with lymphocyte infiltration. In PDTC, thyroglobulin can be determined by im-munohistochemical analysis. The possible genetic load such as BRAF mutation in tall cell variant of papillary carcinoma is studied. Expression of various markers of cell proliferation and differentiation is also studied. In the treatment of PTDC, more radical treatment with exploration of the neck and upper mediastinum is suggested. Anaplastic thyroid carcinoma (ATG) ATC is the most aggressive thyroid carcinoma me-tastasizing very quickly with the highest incidence rate in patients aged over 60 years. It is a very rare disease accounting for 1% of all thyroid malignant diseases and is the cause of over 40% of deaths due to thyroid carcinoma. Survival longer than 6 to 12 months of the onset is very rare. ATC occurs in patients with a goiter enlarging for a longer period and with previously diagnosed thyroid adenocarcinoma coming from iodine-poor regions. The main symptoms are abrupt growth of frequently painful nodular goiter with enlarged lymph nodules, with difficulties in respiration and speech. At the time of the disease detection, distant metastases are seen in 20%-50% of patients. Tumor metastasizes to many organs. ATC has easily recognizable cytological and histological characteristics. Treatment is mainly palliative: surgical removal of tumor mass with freeing of the respiratory tract, radiation and chemotherapy.

medullary thyroid carcinoma (MTG); clinical characteritics of MTG

nije evidentirano