[Progress and controversy on the extent of surgery for medullary thyroid carcinoma based on calcitonin levels].

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.

Risk factor analysis and nomogram development and verification for medullary carcinoma of the colon using SEER database.

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.

Extent of Surgery for Medullary Thyroid Cancer and Prevalence of Occult Contralateral Foci.

Importance: 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. Objective: To determine the presence of occult contralateral disease (lesions not seen on preoperative ultrasonography) in patients with MTC as a rationale for total thyroidectomy. Design, Setting, and Participants: 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. Main Outcomes and Measures: The primary end point was the prevalence of sonographically occult foci of MTC in the contralateral lobe among patients with sporadic MTC. Results: 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). Conclusions and Relevance: 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.

[Precision medicine in endocrinology exemplified by medullary thyroid cancer]. / Präzisionsmedizin in der Endokrinologie am Beispiel des medullären Schilddrüsenkarzinoms.

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.

Medullary colon carcinoma with microsatellite instability: case report / Carcinoma medular do cólon com instabilidade de microssatélites: relato de caso

Colorectal cancer is the third most common neoplasm and the second most lethal worldwide. The most common histological type is adenocarcinoma, characterized by its glandular pattern. Medullary colon carcinoma is a rare histological variant of colorectal cancer, characterized by a predominantly solid architecture, poorly di?erentiated or undifferentiated morphology, often associated with an anomalous immunophenotype and microsatellite instability. The present study reports a case in an academic service of general surgery of a 74-year-old patient who presented with a tumor of the ascending colon, histologically with an exuberant lymphocytic in?ltrate, suggestive of large cell lymphoma, but which was revealed by subsequent immunohistochemistry to be medullary carcinoma of the colon with microsatellite instability.

O câncer colorretal é a terceira neoplasia mais comum e a segunda mais letal no mundo. O adenocarcinoma é o tipo histológico mais comum, caracterizado pelo seu padrão glandular. O carcinoma medular do cólon é uma variante histológica rara do câncer colorretal, caracterizada por uma arquitetura predominantemente sólida, morfologia pouco diferenciada ou indiferenciada, frequentemente associada a um imunofenótipo anômalo e instabilidade de microssatélites. O presente estudo relata um caso em um serviço acadêmico de cirurgia geral de um paciente de 74 anos que apresentou tumor de cólon ascendente, histologicamente com infiltrado linfocitário exuberante, sugestivo de linfoma de grandes células, mas que foi revelado através de exame subsequente imunohistoquímico como carcinoma medular do cólon com instabilidade de microssatélites.

[Individualization of treatment in sporadic and hereditary medullary thyroid cancer]. / Therapieindividualisierung beim sporadischen und hereditären medullären Schilddrüsenkarzinom.

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. MATERIAL AND 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. DISCUSSION: 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.

Molecular imaging and related therapeutic options for medullary thyroid carcinoma: state of the art and future opportunities.

Due to its rarity and non-specific clinical presentation, accurate diagnosis, and optimal therapeutic strategy of medullary thyroid carcinoma (MTC) remain challenging. Molecular imaging provides valuable tools for early disease detection, monitoring treatment response, and guiding personalized therapies. By enabling the visualization of molecular and cellular processes, these techniques contribute to a deeper understanding of disease mechanisms and the development of more effective clinical interventions. Different nuclear imaging techniques have been studied for assessing MTC, and among them, PET/CT utilizing multiple radiotracers has emerged as the most effective imaging method in clinical practice. This review aims to provide a comprehensive summary of the current use of advanced molecular imaging modalities, with a particular focus on PET/CT, for the management of patients with MTC. It aims to guide physicians towards a rationale for the use of molecular imaging also including theranostic approaches and novel therapeutical opportunities. Overall, we emphasize the evolving role of nuclear medicine in MTC. The integration of diagnostics and therapeutics by in vivo molecular imaging represents a major opportunity to personalize treatment for individual patients, with targeted radionuclide therapy being one representative example.

Tumor Grade and Molecular Characteristics Associated with Survival in Sporadic Medullary Thyroid Carcinoma.

Background: The International Medullary Thyroid Carcinoma Grading System (IMTCGS) divides medullary thyroid carcinoma (MTC) into two categories, high- and low-grade tumors, which has a profound impact on patient outcomes. The aim of this study was to explore the association between IMTCGS grading, clinical data, and molecular status in sporadic MTC. Methods: A retrospective cohort study was performed on consecutive sporadic MTCs from patients undergoing initial surgery between January 2000 and January 2022 at the Padua Endocrine Surgery Unit. Clinical, pathological, and follow-up data were collected, tumors were graded, and somatic mutations of RET and RAS genes were analyzed. Patient outcomes were based on Ct levels and MTC-related deaths. Survival analyses were carried out employing the Kaplan-Meier method and the log-rank test. A Cox proportional hazard regression model was employed for multivariable survival analysis with the following covariates: somatic RET mutation, MTC stage at diagnosis, sex, age at diagnosis, and IMTCGS grade. Results: We included 141 consecutive sporadic MTCs. The median follow-up was 80.0 months (interquartile ranges: 41.5-122.5 months). Seventeen patients (12.1%) died from disease-related causes. 107/141 (76.9%) were classified as low-grade tumors, 32/141 (23.1%) as high-grade. Patients carrying a RET mutation had more aggressive features and shorter disease-specific survival (DSS) (p = 0.001) and were more frequently classified high-grade than low-grade MTC (p < 0.001). At multivariable survival analysis, only IMTCGS grading was independently associated with DSS (hazard ratio 8.8 [confidence interval: 2.7-28.3], p = 0.005). RET mutations, in particular RET-M918T, were more frequent in high-grade than in low-grade MTC (68.8% vs. 29.4% mutated in RET, 46.9% vs. 12.7% mutated in RET-M918T; p < 0.001). None of the high-grade tumors was mutated in the RAS gene, but the mutation was present in 11.8% of low-grade tumors. Conclusions: IMTCGS grading was associated with DSS independently of other clinical, pathological, and molecular factors. Moreover, MTC grading was associated with RET and RAS patterns, which explains, at least in part, the molecular basis of the aggressive behavior of high-grade MTC.

Update on Selected High-grade Renal Cell Carcinomas of the Kidney: FH-deficient, ALK-rearranged, and Medullary Carcinomas.

High-grade renal cell carcinoma (RCC), often diagnosed at advanced stages, significantly contributes to renal cancer-related mortality. This review explores the progress in understanding specific subtypes of high-grade RCC, namely fumarate hydratase (FH)-deficient RCC, anaplastic lymphoma kinase (ALK)-rearranged RCC, and SMARCB1-deficient renal medullary carcinoma, all of which are now recognized as molecularly defined entities in the WHO classification system (2022). While these entities each exhibit a morphologic spectrum that overlaps with other high-grade RCC, ancillary tools developed based on their distinctive molecular alterations can help establish a specific diagnosis, underscoring the importance of integrating molecular findings into diagnostic paradigms. It is important to exclude these specific tumor types in cases with similar morphologic spectrum before rendering a diagnosis of high-grade papillary RCC, collecting duct carcinoma, or RCC, NOS. Several gray areas exist within the spectrum of high-grade uncommon types of RCC, necessitating continued research to enhance diagnostic precision and therapeutic options.

Canine thyroid carcinomas: A review with emphasis on comparing the compact subtype of follicular thyroid carcinomas and medullary thyroid carcinomas.

Canine thyroid carcinomas are relatively common malignant endocrine neoplasms in dogs derived from either thyroid follicular cells (forming follicular thyroid carcinomas) or medullary cells (parafollicular, C-cells; forming medullary thyroid carcinomas). Older and recent clinical studies often fail to discriminate between compact cellular (solid) follicular thyroid carcinomas and medullary thyroid carcinomas, which may skew conclusions. The compact subtype of follicular thyroid carcinomas appears to be the least differentiated subtype of follicular thyroid carcinomas and needs to be differentiated from medullary thyroid carcinomas. This review includes information on the signalment, presentation, etiopathogenesis, classification, histologic and immunohistochemical diagnosis, clinical management, and biochemical and genetic derangements of canine follicular and medullary carcinomas, and their correlates with human medicine.

Comparing nodal with primary tumor desmoplasia uncovers metastatic patterns in multiple endocrine neoplasia 2B.

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. CONCLUSION: This proof-of-concept study suggests that primary tumor desmoplasia is an equally powerful biomarker of node metastasis in hereditary MTC.

Patterns of Treatment Failure After Selective Rearranged During Transfection (RET) Inhibitors in Patients With Metastatic Medullary Thyroid Carcinoma.

PURPOSE: Medullary thyroid cancer (MTC) harbors frequent mutations in RET oncogene. Selective RET inhibitors (RETi) have emerged as effective treatments. However, resistance almost invariably occurs. METHODS: MTC patients who were initiated on RETi between 2018 and 2022 were included. Baseline characteristics, RET mutational status, RETi response, available tumor tissue and molecular profiles sampled pre- and post-RETi were analyzed. RESULTS: Among 46 MTC patients on RETi during the study period, 26 patients had discontinued at data cut-off because of progression (n = 16), death (n = 4), and toxicity (n = 6). The most frequent RET mutations at baseline were p.M918T (n = 29), and p.C634X (n = 6). Pre- and post-RETi molecular profiles were available in 14 patients. There was no primary resistance on pre-RETi samples. Post-RETi profiles revealed a bypass mechanism of resistance in 75% of the cases including RAS genes mutations (50%), FGFR2 and ALK fusions and and MYC p.P44L. RET solvent from and hinge region mutations was the only resistance mechanisms in 25% of the cases. Tumor samples from initial thyroidectomy, pre- and post-RETi, from six patients, showed an increase of the mean Ki 67-index of 7%, 17% and 40% respectively (P = 0.037) and a more aggressive poorly differentiated histology in three patients. DISCUSSION: Bypass resistance may be the most frequent mechanism of progression under RETi. A more aggressive histology may arise following RETi and warrants further investigation.

Simultaneous Occurrence of Medullary Thyroid Carcinoma and Papillary Thyroid Carcinoma: A Case Series with Literature Review.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of differentiated TC, while medullary TC (MTC) accounts for 4%. The concomitant presence of PTC and MTC is rare. METHODS: This is a retrospective, single-center observational study conducted over 16 years (2001-2017). The data were collected from the clinical records of patients who underwent total thyroidectomy at the Endocrine Unit-Department of Medicine of the University Hospital of Pisa, Italy. RESULTS: Over 690 analyzed cases, 650 (94.2%) were exclusive DTC, 19 exclusive MTC (2.75%) and 5 PTC/MTC (0.7%). No case of mixed medullary/follicular TC or hereditary MTC (familial MTC/multiple endocrine neoplasia type 2) was found. Among the five PTC/MTC cases, there was a male prevalence (M:F = 3:2), and all PTC components were at stage I, whereas 40% of MTC were at stage I and III and 20% of MTC were at stage II; microPTC (mPTC) was prevalent (80%) and also microMTCs were frequent (40%); 60% of MTC patients recovered, while 40% of patients developed metastatic disease. The search for germline mutations of the RET gene resulted in being negative in all cases. CONCLUSIONS: The incidence of PTC/MTC has been increasing over the past 30 years. The etiology of PTC/MTC forms is still unknown, and although this simultaneous occurrence could be only a coincidence, we cannot exclude the hypothesis of a shared genetic origin.

Clinical characteristics of a large familial cohort with Medullary thyroid cancer and germline Cys618Arg RET mutation in an Israeli multicenter study.

Objective: To determine genealogical, clinical and pathological characteristics of a cohort with Cys618Arg mutation from an Israeli multicenter MTC study. Methods: Retrospective database analysis examining RET mutations and comparing Cys618Arg and Cys634Arg/Thr/Tyr subgroups. Results: Genetic testing was performed in 131/275 MTC patients (47.6%). RET mutations were found in 50/131 (38.2%), including Cys618Arg (28/50 cases,56%), and Cys634Arg/Thr/Tyr (15/50,30%). Through genealogical study, 31 MTC patients were found descendants of one family of Jewish Moroccan descent, accounting for 27/28 patients with documented Cys618Arg mutation and 4 patients without available genetic testing. Familial Cys618Arg cases (n=31) and Cys634Arg/Thr/Tyr cases (n=15, from 6 families) were compared. Although surgical age was similar (25.7 vs 31.3 years, p=0.19), the Cys618Arg group had smaller tumors (8.9mm vs 18.5mm, p=0.004) and lower calcitonin levels (33.9 vs 84.5 X/ULN, p=0.03). Youngest ages at MTC diagnosis were 8 and 3 years in Cys618Arg and Cys634Arg/Thr/Tyr cohorts, respectively. Long-term outcome was similar between groups. The Cys618Arg cohort had lower rates of pheochromocytoma (6.5% vs 53.3%, p=0.001) and primary hyperparathyroidism (3.2% vs 33.3%, p=0.01). Conclusion: This is the first description of RET mutation distribution in Israel. Of 131 tested MTC patients, Cys618Arg was the predominant mutation. To the best of our knowledge, this is the largest cohort of Cys618Arg mutation described. For Cys618Arg and Cys634Arg/Thr/Tyr cohorts, MTC was diagnosed earlier than expected, likely due to familial genetic screening, and MTC outcomes were similar between groups. International studies are necessary to further characterize the clinical features of Cys618 mutations due to their relative rarity.

Association of ABCG2 Polymorphisms on Triple Negative Breast Cancer (TNBC) Susceptibility Risk.

OBJECTIVE: The aim of this study was to elucidate the association of ATP-binding cassette super-family G member 2 (ABCG2) gene polymorphisms with individual susceptibility to Triple Negative Breast Cancer (TNBC) as well as clinicopathological variables in TNBC patients. Two common polymorphisms in Asian population, ABCG2 34 G>A and 421 C>A was selected in this study. METHODS: Blood samples were collected from 75 TNBC patients and 83 controls. Genomic DNA was extracted from blood samples and the SNP genotyping was performed by using PCR-RFLP technique. The genotypes were characterized and grouped into homozygous wildtype, heterozygote and homozygous variant based on the band size. The result was subjected to statistical analysis. RESULTS: The A allele and AA genotype of ABCG2 421 C>A had OR of 3.011 (p=0.003, 95% CI: 1.417-6.398) and 9.042 (p=0.011, 95% CI: 1.640-49.837), to develop advanced staging carcinoma respectively. The AA genotype of ABCG2 421 C>A polymorphism was also associated with metaplastic and medullary carcinoma with an OR of 6.429 (p=0.018, 95% CI: 1.373-30.109). A significant association was also found in haplotype 34G/421A of ABCG2 with advanced cancer staging as well as metaplastic and medullary carcinoma with OR of 2.347 (p=0.032, 95% CI: 1.010-5.560) and 2.546 (p=0.008, 95% CI: 1.005-6.447), respectively.  Conclusion: The present study suggests that ABCG2 421 C>A polymorphism was associated with metaplastic and medullary histology and advanced cancer staging in TNBC patients.

Colonic medullary carcinoma: an exceedingly rare type of colorectal malignancy: a case report and review of the literature.

BACKGROUND: Medullary carcinoma of the colon is a rare subtype of colorectal cancer that has a unique, and sometimes varied, clinical and histologic profile. It usually presents in adult patients older than 50 years. Here, we report a unique case of young male patient who initially presented with abdominal pain followed by a large bowel obstruction. CASE PRESENTATION: A 40-year-old SriLankan male presented with right-sided abdominal pain and on examination, there was a palpable right iliac fossa mass. Colonoscopy and a computed tomography scan revealed cecal mass. Later, while waiting for elective resection, the patient developed symptoms and signs of a large bowel obstruction. He underwent a laparoscopic right hemicolectomy with an uneventful postoperative course. The histopathologic evaluation of the resected specimens showed invasive carcinoma with syncytial growth pattern, foci of lymphoid host response, and dirty necrosis, in keeping with a medullary carcinoma pT4a pN2b. Unlike most reported medullary carcinoma cases, this patient was young and caudal-related homeobox transcription factor 2 positive. CONCLUSION: We have reported another case of medullary carcinoma of the colon in a young patient with unique histologic characteristics. Reporting such cases helps in refine understanding of the histologic and genetic, as well as clinical, phenotypes of medullary carcinoma of the colon.

Competing-risks model for predicting the prognostic value of lymph nodes in medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is an infrequent form malignant tumor with a poor prognosis. Because of the influence of competitive risk, there may suffer from bias in the analysis of prognostic factors of MTC. METHODS: By extracting the data of patients diagnosed with MTC registered in the Surveillance, Epidemiology, and End Results (SEER) database from 1998 to 2016, we established the Cox proportional-hazards and competing-risks model to retrospectively analyze the impact of related factors on lymph nodes statistically. RESULTS: A total of 2,435 patients were included in the analysis, of which 198 died of MTC. The results of the multifactor competing-risk model showed that the number of total lymph nodes (19-89), positive lymph nodes (1-10,11-75) and positive lymph node ratio (25%-53%,>54%), age (46-60,>61), chemotherapy, mode of radiotherapy (others), tumor size(2-4cm,>4cm), number of lesions greater than 1 were poor prognostic factors for MTC. For the number of total lymph nodes, unlike the multivariate Cox proportional-hazards model results, we found that it became an independent risk factor after excluding competitive risk factors. Competitive risk factors have little effect on the number of positive lymph nodes. For the proportion of positive lymph nodes, we found that after excluding competitive risk factors, the Cox proportional-hazards model overestimates its impact on prognosis. The competitive risk model is often more accurate in analyzing the effects of prognostic factors. CONCLUSIONS: After excluding the competitive risk, the number of lymph nodes, the number of positive and the positive proportion are the poor prognostic factors of medullary thyroid cancer, which can help clinicians more accurately evaluate the prognosis of patients with medullary thyroid cancer and provide a reference for treatment decision-making.

Both MLH1 deficiency and BRAFV600E mutation are a unique characteristic of colorectal medullary carcinoma: An observational study.

Although immunohistochemistry (IHC) for mismatch repair (MMR) proteins (MMR IHC) is used to identify DNA MMR status, universal screening of all patients with colorectal cancer (CRC) using a combination of both MMR IHC and genetic testing for the BRAFV600E mutation is limited in Japan. This study aimed to better understand the histopathological characteristics of CRCs, which exhibit both deficient mismatch repair (dMMR) and BRAFV600E mutation. MMR IHC of formalin-fixed paraffin-embedded tissues from tumor areas obtained from 651 patients with CRC who underwent surgical resection at Hamamatsu University Hospital (Hamamatsu, Japan) between August 2016 and March 2022 were used to evaluate MMR status, which was determined by staining for the expression of 4 MMR proteins (MLH1, MSH2, PMS2, and MSH6). All dMMR tumors were additionally evaluated for BRAFV600 mutation status via Sanger sequencing. Patient clinical characteristics (age, sex, tumor location, size, and tumor pathology) were then classified using their dMMR and BRAFV600 mutation statuses. Among the 651 patients with CRC, 58 carried tumors with dMMR, of which 52 were deficiency in MLH1 (dMLH1). Interestingly, all 16 medullary carcinomas that were analyzed showed characteristics corresponding to the presence of both dMLH1 and BRAFV600E mutation (P = .01). These results suggest that colorectal medullary carcinomas can be diagnosed based on their unique characteristics of harboring the BRAFV600E mutation and exhibiting dMLH1 expression.