Medullary thyroid carcinoma (MTC) accounts for only 3% of all thyroid carcinomas: 75% as sporadic MTC (sMTC) and 25% as hereditary MTC (hMTC) in the context of multiple endocrine neoplasia type 2 (MEN2). Early diagnosis is possible by determining the tumour marker calcitonin (Ctn) when clarifying nodular goitre and by detecting the mutation in the proto-oncogene RET in the MEN2 families. If the Ctn level is only slightly elevated, up to 30 pg/ml in women and up to 60 pg/ml in men, follow-up checks are advisable. At higher levels, surgery should be considered; at a level of > 100 pg/ml, surgery is always advisable. The treatment of choice is total thyroidectomy, possibly with central lymphadenectomy. In the early stage, cure is possible with adequate surgery; in the late stage, treatment with tyrosine kinase inhibitors is an option. RET A mutation analysis should be performed on all patients with MTC. During follow-up, a biochemical distinction is made between: healed (Ctn not measurably low), biochemically incomplete (Ctn increased without tumour detection) and structural tumour detection (metastases on imaging). After MTC surgery, the following results should be available for classification in follow-up care: (i) histology, Ctn immunohistology if necessary, (ii) classification according to the pTNM scheme, (iii) the result of the RET analysis for categorisation into the hereditary or sporadic variant and (iiii) the postoperative Ctn value. Tumour progression is determined by assessing the Ctn doubling time and the RECIST criteria on imaging. In most cases, \"active surveillance\" is possible. In the case of progression and symptoms, the following applies: local (palliative surgery, radiotherapy) before systemic (tyrosine kinase inhibitors).

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor originating from the parafollicular cells (C cells) of the thyroid gland, classified as sporadic and hereditary. Calcitonin (Ctn) secreted by the C cells is a specific serological marker for MTC, which is of great value in diagnosis, treatment and postoperative management of MTC. The effect of chemoradiotherapy and 131I therapy on MTC is limited, with surgery being the primary therapy. Given the aggressive nature and relatively poor prognosis of MTC, the reasonable surgical extent is crucial for improving cure rate and prognosis of patients. However, there are still some controversies regarding the extent of surgery for MTC. This article elaborates on the research progress and controversies of serum Ctn levels in assisting the evaluation of the extent of surgery for MTC.
甲状腺髓样癌（MTC）是一种起源于甲状腺滤泡旁细胞（C细胞）的神经内分泌肿瘤，分为散发性和遗传性。C细胞分泌的降钙素（Ctn）是MTC特异性的血清学标志物，在MTC的诊断、治疗及术后管理中具有重要价值。放化疗及131I对MTC的治疗效果十分有限，手术为目前MTC的主要治疗方式。MTC侵袭性较强、预后相对较差，因此，合理的手术范围对于提高患者的治愈率及改善预后具有重要意义。然而，目前关于MTC的手术范围仍存在部分争议，现就血清Ctn水平在协助评估MTC手术范围的研究进展及争议进行阐述。.

Medullary Carcinoma of the Colon (MCC) is a rare histological subtype of colon cancer, and there is currently no recognized optimal treatment plan for it, with its prognosis remaining unclear. The aim of this study is to analyze the independent prognostic factors for MCC patients and develop and validate nomograms to predict overall survival (OS). A total of 760 patients newly diagnosed with MCC from 2004 to 2020 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. All patients were randomly allocated to a training group and a validation group in a 7:3 ratio. Univariate and multivariable Cox regression analyses were conducted to identify prognostic factors and construct nomograms. The nomogram prediction model was evaluated and validated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The study found that elderly women are more susceptible to MCC, and the ascending colon and cecum are the most common sites of involvement. MCC is poorly differentiated, with stages II and III being the most common. Surgery is the primary treatment for MCC. The prognosis for patients with stage IV MCC is poor, with a median survival time of only 10 months. Independent prognostic factors for MCC include age, N stage, M stage, surgery, chemotherapy, and tumor size. Among them, age < 75 years and completion of chemotherapy were protective factors for colon medullary carcinoma, while N2 (HR = 2.18, 95%CI 1.40-3.38), M1 (HR = 3.31, 95%CI 2.01-5.46), no surgery (HR = 27.94, 95%CI 3.69-211.75), and tumor diameter > 7 cm (HR = 1.66, 95%CI 1.20-2.30) were risk factors for colon medullary carcinoma. The results of ROC, AUC, calibration curves, and DCA demonstrate that the nomogram prediction model exhibits good predictive performance. We have updated the demographic characteristics of colon medullary carcinoma and identified age, N staging, M staging, surgery, chemotherapy and tumor size as independent prognostic factors for colon medullary carcinoma. Additionally, we have established nomograms for prognostic prediction. These nomograms can provide personalized predictions and serve as valuable references for clinical decision-making.

暂无摘要。

A 13-year old Latino male presented with recurrent gross hematuria, 5cm right-sided poorly defined heterogeneous mass, enlarged retrocaval lymph nodes, and 1.2 cm paratracheal lymph node. Given the need for multiple blood transfusions, robot-assisted radical nephrectomy with lymph node dissection was performed. Pathology revealed pT3a high-grade tumor, clear margins, and positive lymph node. Additionally, with multiple sickled RBCs and loss of staining of SMARCB1 in tumor specimen, and hemoglobin electrophoresis suggesting sickle cell trait, diagnosis of metastatic renal medullary carcinoma was confirmed. The patient was enrolled into COG AREN 03B2 trial, and has completed 10 cycles of carboplatin/gemcitabine/bortezomib alternating with cisplatin/gemcitabine/paclitaxel, with no evidence of recurrent disease 9 months post-surgery.

We experienced a case of multiple endocrine neoplasia type 2A(MEN2A)diagnosed with medullary thyroid carcinoma. The patient was a 50s woman who was referred for a thyroid nodule detected in the right lobe during a carotid ultrasound examination. After undergoing a hemithyroidectomy, it was determined that the tumor was medullary carcinoma. RET gene test was performed, confirming a mutation at codon768, leading to the diagnosis of MEN2A. A completion thyroidectomy was performed to remove the remaining thyroid tissue. Postoperatively, the patient is undergoing systemic surveillance.

UNASSIGNED: Standard treatment for patients with medullary thyroid cancer (MTC) consists of total thyroidectomy with central neck dissection, but the rationale for bilateral surgery in patients with unilateral disease on ultrasonography remains unclear.
UNASSIGNED: To determine the presence of occult contralateral disease (lesions not seen on preoperative ultrasonography) in patients with MTC as a rationale for total thyroidectomy.
UNASSIGNED: This multi-institutional, retrospective cohort study was conducted from September 1998 to April 2022 in academic medical centers and included patients with MTC who underwent thyroidectomy with preoperative imaging.
UNASSIGNED: The primary end point was the prevalence of sonographically occult foci of MTC in the contralateral lobe among patients with sporadic MTC.
UNASSIGNED: The cohort comprised 176 patients with a median age at diagnosis of 55 years (range, 2-87 years), 69 (57.6%) of whom were female. Genetic testing was performed in 109 patients (61.9%), 48 (27.5%) of whom carried germline RET variants. Initial surgical management consisted of total thyroidectomy (161 [91.0%]), lobectomy followed by completion thyroidectomy (7 [4.0%]), and lobectomy alone (8 [4.5%]). Central and lateral neck dissections were performed as part of initial therapy for 146 patients (83.1%). In the entire cohort of 176 patients, 46 (26.0%) had contralateral foci disease and 9 (5.1%) had occult contralateral foci that were not identified on preoperative ultrasonography. Among 109 patients who underwent genetic testing, 38 (34.9%) had contralateral disease, 8 (7.3%) of whom had occult contralateral disease not seen on preoperative ultrasonography. Patients with sporadic MTC experienced a 95.7% reduction in the odds of having a focus of MTC in the contralateral lobe compared with patients with a germline RET variant (odds ratio, 0.043; 95% CI, 0.013-0.123). When adjusting for age, sex, tumor size, and lymph node involvement, the odds ratio of having contralateral MTC in patients with sporadic disease was 0.034 (95% CI, 0.007-0.116). Among patients who underwent lobectomy alone with postoperative calcitonin levels, 5 of 12 (41.7%) achieved undetectable calcitonin levels (<2.0 pg/mL; to convert to pmol/L, multiply by 0.292).
UNASSIGNED: The results of this cohort study suggest that a staged approach involving initial thyroid lobectomy could be considered in patients with sporadic MTC and no contralateral ultrasonography findings, with no further surgery if calcitonin levels became undetectable. Further work using prospective randomized clinical trials to evaluate lobectomy as a biochemical cure in patients presenting with unilateral disease is warranted.

Medullary thyroid cancer (MTC) is a prime example for precision medicine in endocrinology and underlines the immediate benefits of basic, translational and healthcare research for patients with a rare disease in clinical . A mutation in the rearranged during transfection (RET) proto-oncogene that codes for a transmembrane receptor protein tyrosine kinase, leads to constitutive activation of the kinase, which is the decisive pathomechanism for the disease. The MTC occurs in a sporadic (somatic RET mutation) or hereditary form (RET germline mutation, multiple endocrine neoplasia types 2 and 3). For germline mutation carriers the timing of preventive thyroidectomy depends on the RET genotype. For advanced metastasized RET-mutant MTC, selective RET kinase inhibitors are available, which are currently considered to be game changers in the treatment. Based on the specific tumor marker calcitonin, MTC can be identified at an early stage during the differential diagnosis of thyroid nodules. The preoperative calcitonin level even enables statements on the degree of dissemination of the disease and on the probability of a cure through surgery. A new development is the consideration of desmoplasia as a histopathological biomarker for the metastatic potential of a MTC, which could possibly modify the operative approach as well as the future MTC nomenclature. Furthermore, the postoperative calcitonin level and the calcitonin doubling time are highly valid prognostic markers for tumor burden and biological aggressiveness of MTC and therefore decisive for patient follow-up. Biochemical, molecular and histological markers enable a risk-adapted surgical treatment and together with new targeted systemic treatments have contributed to a paradigm shift in the diagnostics, prognosis and treatment of MTC in recent years. Endocrine precision medicine for MTC therefore enabled a change from the previous purely symptom-oriented to a modern preventive and individualized treatment.
UNASSIGNED: Das medulläre Schilddrüsenkarzinom („medullary thyroid cancer“ [MTC]) ist ein Paradebeispiel für Präzisionsmedizin in der Endokrinologie und verdeutlicht den unmittelbaren Nutzen von Grundlagen-, translationaler und Versorgungsforschung für Patienten mit einer seltenen Erkrankung im klinischen Alltag. Eine Mutation im Rearranged-during-transfection(RET)-Protoonkogen, das für eine transmembranäre Rezeptortyrosinkinase codiert, führt zur konstitutiven Aktivierung der Kinase; dies ist der entscheidende Pathomechanismus der Erkrankung. Das MTC tritt in einer sporadischen (somatische RET-Mutation) oder hereditären Form (RET-Keimbahnmutation, multiple endokrine Neoplasie Typ 2 und 3) auf. Vom RET-Genotyp wird bei Keimbahnmutationsträgern die Beratung zum Zeitpunkt der präventiven Thyreoidektomie abhängig gemacht. Zur Behandlung von RET-Mutations-positiven MTC stehen selektive RET-Kinase-Inhibitoren zur Verfügung, die aktuell als „game changer“ in der Behandlung des fortgeschrittenen MTC angesehen werden. Anhand des spezifischen Tumormarkers Kalzitonin können MTC bei der Abklärung von Schilddrüsenknoten frühzeitig identifiziert werden. Die Höhe des präoperativen Kalzitoninwerts erlaubt dabei bereits Aussagen zum Ausbreitungsgrad der Erkrankung und zur Wahrscheinlichkeit, diese chirurgisch zu heilen. Eine neuere Entwicklung ist die Berücksichtigung der Desmoplasie als histopathologischer Biomarker für das Metastasierungspotenzial eines MTC, was möglicherweise die operative Vorgehensweise ebenso wie die zukünftige MTC-Nomenklatur modifizieren wird. Ferner sind die postoperativen Kalzitoninspiegel und die Kalzitoninverdopplungszeit hochvalide prognostische Marker für Tumorlast und biologische Aggressivität des MTC und damit entscheidend für den Nachsorgealgorithmus. Biochemische, molekulargenetische und histologische Marker ermöglichen eine risikoadaptierte chirurgische Therapie und haben zusammen mit neuen zielgerichteten Systemtherapien in den vergangenen Jahren zu einem Paradigmenwechsel in der MTC-Diagnostik, -Prognose und -Therapie beigetragen. Endokrine Präzisionsmedizin hat beim MTC somit einen Wandel von der früher lediglich symptomorientierten hin zu einer modernen, präventiven und individualisierten Therapie ermöglicht.

BACKGROUND: Routine preoperative assessment of the tumor marker calcitonin for medullary thyroid cancer (MTC) and the generally improved diagnostics with high-resolution ultrasound, elastography and Doppler function as well as functional imaging, enable the earlier detection of organ-limited, non-metastasized MTC. Thereby, a new treatment option arises for surgical de-escalation in sporadic MTC, moving from routine thyroidectomy with bilateral central lymph node dissection towards unilateral thyroidectomy with ipsilateral central lymph node dissection.
METHODS: A search was carried out in PubMed for surgical approaches and selection of publications with results from limited resection in sporadic MTC.
RESULTS: In selected patient cohorts limited resection surgery can achieve adequate oncological results but requires long-term follow-up.
CONCLUSIONS: When sporadic unifocal primary tumors are identified and intraoperative frozen section pathological investigation is consistently employed for assessing the grade of desmoplasia and breach of the tumor capsule, the extent of resection can be intraoperatively adapted. Pivotal prerequisites for this personalized concept include consideration of preoperative clinical criteria and intraoperative surgical assessment in conjunction with the intraoperative frozen section examination in order to achieve an adequate oncological tumor resection and a biochemical cure.
UNASSIGNED: HINTERGRUND: Die präoperative Routinebestimmung des Tumormarkers Kalzitonin für das medulläre Schilddrüsenkarzinom (MTC) und die allgemein verbesserte Diagnostik mit hochauflösendem Ultraschall, Elastographie und Dopplerfunktion sowie funktioneller Bildgebung ermöglicht es, MTC in früherem, also im organbegrenzten und nichtmetastasierten Stadium zu diagnostizieren. Damit eröffnet sich beim sporadischen MTC die Möglichkeit zur Deeskalation des primären Operationsausmaßes weg von der Thyreoidektomie mit bilateraler zentraler Lymphknotendissektion hin zur limitierten Resektion als Hemithyreoidektomie mit ipsilateraler zentraler Lymphknotendissektion.
METHODS: PubMed-Recherche zum operativen Vorgehen und Auswahl von Publikationen mit Ergebnissen limitierter Operationsverfahren beim sporadischen MTC.
UNASSIGNED: Im selektionierten Patientengut können limitierte Resektionen adäquate onkologische Ergebnisse erzielen, die aber eine Langzeittumornachsorge erfordern.
CONCLUSIONS: Bei Identifikation sporadischer unifokaler Primärtumoren und konsequenter intraoperativer gefrierschnitthistologischer Erfassung des Desmoplasiegrades und des Kapseldurchbruchs kann das Resektionsausmaß intraoperativ der patientenindividuellen Situation angepasst werden. Entscheidende Voraussetzungen hierfür sind die Berücksichtigung der klinischen präoperativen und intraoperativen chirurgischen sowie der gefrierschnitthistologischen Kriterien, die das onkologische adäquate Ergebnis mit R0-Resektion und biochemischer Heilung erreichen.

BACKGROUND: While primary tumor desmoplasia is a powerful biomarker of node metastases in sporadic medullary thyroid cancer (MTC), information for hereditary MTC is sparse.
METHODS: This proof-of-concept study, comprising 3 consecutive children with multiple endocrine neoplasia 2B, evaluated simultaneously the metastatic behavior of multiple primary thyroid tumors of disparate size and extent of desmoplasia within patients.
RESULTS: Altogether, MTC typically involved the ipsilateral central neck before spreading to the ipsilateral lateral and the contralateral neck. Medullary thyroid cancer in the upper thyroid lobe leaped the ipsilateral central neck to invade the ipsilateral lateral neck. Unlike the desmoplasia-positive 6-mm high-grade and 7-mm low-grade primary thyroid tumors, the desmoplasia-negative 8-, 11-, and 16-mm low-grade primary thyroid tumors did not spread to ipsilateral neck nodes. With extranodal growth, the extent of nodal desmoplasia was greater than with intranodal growth.
CONCLUSIONS: This proof-of-concept study suggests that primary tumor desmoplasia is an equally powerful biomarker of node metastasis in hereditary MTC.