Mixed medullary-papillary carcinoma of the thyroid: Report of two cases and review of the literature.

Papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) are two distinct types of thyroid carcinoma with considerable difference in terms of cellular origin, histopathological appearance, clinical course and prevalence. The histogenetic origin and possible molecular mechanisms responsible for the development of mixed medullary-papillary carcinoma of the thyroid are still unclear. The most widely accepted hypotheses considering co-occurrence of MTC and PTC are stem cell theory, collision effect theory and hostage theory. Herein we describe two rare cases of mixed medullary-papillary thyroid carcinoma with co-occurrence of MTC and PTC which developed with concomitant MEN 2A and different sites of lymph node metastasis in the fi rst patient, while with atypical clinical presentation in the second patient. In conclusion, co-expression of thyroglobulin, synaptophysin and chromogranin by the papillary component of mixed tumor seems to support stem cell theory in our fi rst case, whereas positive staining for calcitonin but not for thyroglobulin in the medullary component of the tumor along with separation of these two tumors from each other by a normal thyroid tissue seem to indicates the likelihood of collision effect theory in our second case.

RET proto-oncogene mutation analysis in a pedigree with multiple endocrine neoplasia 2A / 中华泌尿外科杂志

ObjectiveTo discuss the clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN ) 2A, and report the mutation of the RET proto-oncogene in a pedigree of three patients with MEN 2A.MethodsBilateral adrenalectomy was performed on two of the three patients with hypertension and bilateral adrenal-conserving adrenal pheochromocytoma resection was performed on the other patient. All three patients were treated by total thyroidectomy and neck lymphadenectomy. Twelve family members were recruited to the study. Peripheral blood was collected and total genomic DNA was prepared for polymerase chain reaction (PCR). PCR products of exon 10 and exon 11 of the RET proto-oncogene were purified and a direct DNA sequence analysis was performed.ResultsThe pathological diagnosis of the specimens was bilateral adrenal pheochromocytoma and medullary thyroid carcinoma in all the three patients. There was no tumor recurrence or distant metastasis after 1.5 - 5 years of follow-up. A missense mutation of TGC (Cys)to CGC (Arg) at codon 634 in exon 11 of the RET proto-oncogene was detected in all three patients. Genetic screening identified two mutation carriers in the other members of this pedigree.ConclusionGenetic mutation screening and surgical intervention may be helpful to the members of high-risk families.

Unpredicted tachycardia and hypotension in a patient with medullary thyroid cancer and undiagnosed pheochromocytoma: A case report / 대한마취과학회지

A 35 year old woman with hypercalcitoninemia was scheduled for an operation to treat her medullary thyroid cancer (MTC). TIVA with propofol and remifentanil was planned, and about 3 minutes after the infusion of anesthetics, her heart rate was suddenly elevated to 180/min and the systolic blood pressure was lowered to nearly 50 mmHg. The blood pressure returned to normal after the injection of phenylephrine 100 microgram and a rapid infusion of 700 ml crystalloid solution. After the operation, bilateral pheochromocytoma and a RET proto-oncogene mutation related with multiple endocrine neoplasia 2A (MEN-2A) were found. Patients with MTC can present with peripheral vasodilation and relative hypovolemia that are related with hypercalcitoninemia. Patients with MEN-2A can be anesthetized for a MTC operation without the appropriate preparation for their pheochromocytoma. Therefore, we suggest that patients with MTC and hypercalcitoninemia should be cautiously anesthetized with TIVA. They also should be screened for pheochromocytoma and the RET proto-oncogene mutation to prevent deleterious hemodynamic events during anesthesia.

Detection of the RET proto-oncogene in a family with multiple endocrine neoplasia type 2A syndrome / 中华内分泌代谢杂志

Objective To detect mutations of the RET proto-oncogene in a family with multiple endocrine neoplasia type 2A (MEN2A). Methods Nineteen family members were recruited in the study. The phenotype of the members with MEN2A were observed. PCR was performed to amplify exans 10 and 11 of the RET proto-oncogene. The PCR products were purified and a direct DNA sequence analysis was performed. Results The Cys (TGC)634Arg(CGC) missense mutation and Gly( GGT)691Ser(AGT) in exon 11 of the RET proto-oncogene were both detected in four members of the family. Only the pelymorphism Gly691Ser in exon 11 of the RET proto-oncogene was detected in one member. The results of the ultrasound examination were shown as follows: two members with bilateral thyroid, one side of parathyroid and adrenal solid lesions; one member with bilateral thyroid and one side of adrenal solid lesions; one member with bilateral thyroid and adrenal and one side of parathyroid solid lesions; and one member with multiple thyroid small nodules. Additionally, another three members with abnormal findings on ultrasound examinations had no gene mutation. Conclusion Analysis of RET gene identifies a TGC to CGC mutation at codan 634 and the polymorphism Gly691 Set in exon 11 in this family with MEN2A. Direct DNA sequencing analysis is useful in diagnosis of MEN2A at gene level.

A Case of Multiple Endocrine Neoplasia 2A with Germ Line Mutation of RET Gene / 대한내분비학회지

Multiple endocrine neoplasia 2A (MEN 2A) is an autosomal dominantly inherited disease, composed of medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism. The activation of germ-line mutations in the RET proto-oncogene are responsible for MEN 2. The analysis of the RET mutations has replaced the measurement of the calcitonin level in the diagnosis of the MEN carrier state. Specific RET codon mutations correlate with the MEN 2 syndromic variant, the age at onset of the medullary thyroid carcinoma (MTC) and the aggressiveness of the MTC. Herein, our experience of a 47-year-old woman, who had a bilateral pheochromocytoma and MTC, and MEN 2A confirmed by the detection of an RET proto-oncogene mutation at axon 10 on codon 618, is reported. Her sister was found to have the same mutant gene. After a total thyroidectomy and bilateral adrenalectomy, the calcitonin and catecholamine levels were normalized, and the patient discharged without problems. This case is reported, with a review of the literature.