Thymic Neuroendocrine Carcinoma Research Articles

Updated survival follow-up for phase I study of abexinostat with pazopanib in patients with solid tumor malignancies.

3150 Background: Histone deacetylase (HDAC) inhibition downregulates HIF-1a, which may be effective in overcoming resistance to VEGF-targeting tyrosine kinase inhibitors. We report the updated survival follow-up for patients treated with abexinostat and pazopanib in a phase Ib trial. Methods: Patients with solid tumor malignancies were enrolled in this phase Ib, open-label trial (NCT01543763) of abexinostat in combination with pazopanib (3+3 design), with a dose expansion restricted to renal cell carcinoma (RCC). Patients received a 1-week run-in period with abexinostat alone, and then combination abexinostat with pazopanib during a 28-day treatment cycle until disease progression, unacceptable toxicity or study withdrawal. Plasma samples from 29 patients were sent for metabolomics analysis. Results: 51 patients were enrolled: N = 36 patients in dose escalation, N = 15 in dose expansion. At the time of last report in 2017, 5 patients remained on study treatment: N = 4 with RCC, and N = 1 with thymic neuroendocrine carcinoma. 4 of these patients have now had disease progression. Median duration of therapy measured 44.9 months (range 39.8-102.2). One patient with metastatic RCC (patient 1) remains on study treatment, after progression on 5 prior lines of systemic therapy. With updated survival follow-up, median OS measured 12.4 months in the dose escalation arm and 27.65 months in the RCC dose expansion cohort. Overall median duration of therapy in all 51 patients measured 5.6 months (range 1-103 months). Progression-free survival among patients with high PBMC HDAC2 expression (> 0.4) remains longer compared to those with low expression (median 6.3 vs. 3.7 months, p = 0.0041). Metabolomics analysis demonstrated a negative correlation between HDAC2 and N6-acetyllysine, suggesting that baseline HDAC2 may impact efficacy of HDAC inhibition. Conclusions: The combination of abexinostat with pazopanib appears promising, with the potential for long-term responses particularly in patients with metastatic RCC. This has led to an ongoing phase III trial examining this combination in RCC. Clinical trial information: NCT01543763. [Table: see text]

Lymph node dissection in thymic carcinomas and neuroendocrine carcinomas.

Although lymph node (LN) metastases are not uncommon in thymic carcinomas, preoperative LN evaluation, intraoperative lymph node dissection (LND) and postoperative outcomes remain unknown. The aim of this study was to elucidate the characteristics of and outcomes in patients with thymic carcinomas and thymic neuroendocrine carcinomas undergoing LND. A retrospective chart review was performed using our multi-institutional database to identify patients who underwent resection and LND for thymic carcinoma or thymic neuroendocrine carcinoma between 1991 and 2018. An enlarged mediastinal LN was defined as having a short-axis diameter >1 cm. We assessed survival outcomes using the Kaplan-Meier analysis. N1-level LND was performed in 41 patients (54.6%), N2-level LND in 14 patients (18.7%) and both-level LND in 16 patients (21.3%). Pathological LN metastasis was detected in 20 patients (26.7%) among the 75 patients undergoing LND. There was a significant difference in the number of LN stations (P = 0.015) and metastasis factor (P = 0.0042) between pathologically LN-positive and pathologically LN-negative patients. The sensitivity of enlarged LNs on preoperative computed tomography was 18.2%. There was a tendency towards worse overall survival of pathologically N2-positive patients, although the difference was not statistically significant (P = 0.15). Preoperative CT appears to play a limited role in detecting pathological LN metastases. Our findings suggest that the significance of N1- and N2-level LND should be evaluated in prospective studies to optimize the postoperative management of patients with thymic carcinomas and neuroendocrine carcinomas.

The treatment and survival of patients with postoperative recurrent thymic carcinoma and neuroendocrine carcinoma: a multicenter retrospective study.

There are few data available on the outcomes of postoperative recurrent thymic carcinoma (TC) and thymic neuroendocrine carcinoma (TNEC). The aim of this study is to evaluate the treatment and survival in patients with recurrent TC and TNEC after undergoing surgical resection. A retrospective chart review was performed using our multicenter database to identify patients with a postoperative recurrence of TC and TNEC from 1995 to 2018. The clinicopathological factors were reviewed and the survival outcomes were analyzed. Sixty patients were identified among 152 patients who underwent resection of TC and TNEC. The median follow-up period from the first recurrence was 14.8months (range 0-144). The 5-year post-recurrence survival was 23% for the whole cohort. According to a univariable analysis, advanced stage [hazard ratio (HR) 2.81, 95% confidence interval (CI) 1.09-9.54], interval between primary surgery and recurrence (HR 0.97, 95% CI 0.95-0.99), any treatment for recurrence (HR: 0.27, 95% CI 0.13-0.58) and chemotherapy for recurrence (HR: 0.46, 95% CI 0.22-0.95) were significant factors related to post-recurrence survival. Chemotherapy rather than surgery appears to be the mainstay treatment for managing patients with postoperative recurrent TC and TNEC and it may also be considered in multidisciplinary management. Further studies with a larger sample size are required to confirm our findings.

Survival outcomes of patients with high-grade and poorly differentiated thymic neuroendocrine carcinoma.

High-grade and poorly differentiated thymic neuroendocrine carcinoma is the rarest entity in thymic epithelial tumours. The aim of this study is to report survival data in a multi-institutional database in comparison to data in the literature. Retrospective chart review was performed on the basis of our multi-institutional database to identify patients undergoing the resection of poorly differentiated thymic neuroendocrine carcinoma between 1991 and 2018. Relevant factors were extracted, and survival analysis was performed using the Kaplan-Meier method. Twenty-one patients were identified. Five-year overall survival and recurrence-free survival were 64.6% and 51.8%, respectively. Twelve (57.1%) patients had recurrences. Due to the scarcity of data reported in the literature, our data may be used as a standard in high-grade and poorly differentiated thymic neuroendocrine carcinoma.

Sternochondral replacement: use of cadaveric allograft for the reconstruction of anterior chest wall.

Sternum may be involved by different diseases such as trauma, infection after cardiac surgery, tumors (primary and secondary) or chest wall deformities. Surgical excision with a safety margin is the primary goal after sternal resection for tumors, prevention of respiratory impairment due to flail chest and deformity and protection of surrounding organs are other important aims. Various techniques and materials have been used for this operation. We describe the use of cadaveric sternal allograft to reconstruct the chest wall in fourteen patients. Between October 2008 and February 2017, five males and nine females underwent surgical procedure because of primary sternal neoplasm, single-site metastatic disease, neuroendocrine thymic carcinoma and sternal dehiscence after cardiac surgery. Fourteen sternectomy were undertaken. A muscle flap of pectoralis major was prepared to cover the graft in 9 patients. Adjuvant chemotherapy and radiotherapy were performed after surgery in three patients. No postoperative complications happened in 11 cases (84.6%). One (7.1%) patient died 9 days after surgery because of pulmonary embolism. Two patients (15.4%) had complications: one presented fever caused by systemic candidiasis and one had a muscle flap bleeding. Hospitalization median time was 11 days (range, 6-31 days). At follow up, 7 patients were alive in absence of disease, 1 patient is alive with recurrence, 6 patients died but nor infection neither rejection of the graft happened. No respiratory impairment or flail chest were registered in any patients. This technique for sternal replacement in our experience can be considered safe with long term results, providing optimal chest wall stability. The allograft resulted well-tolerated permitting an optimal graft integration in the host.

A unique case of ectopic Cushing's syndrome from a thymic neuroendocrine carcinoma.

SummaryEctopic adrenocorticotropic hormone (ACTH) production leading to ectopic ACTH syndrome accounts for a small proportion of all Cushing’s syndrome (CS) cases. Thymic neuroendocrine tumors are rare neoplasms that may secrete ACTH leading to rapid development of hypercortisolism causing electrolyte and metabolic abnormalities, uncontrolled hypertension and an increased risk for opportunistic infections. We present a unique case of a patient who presented with a mediastinal mass, revealed to be an ACTH-secreting thymic neuroendocrine tumor (NET) causing ectopic CS. As the diagnosis of CS from ectopic ACTH syndrome (EAS) remains challenging, we emphasize the necessity for high clinical suspicion in the appropriate setting, concordance between biochemical, imaging and pathology findings, along with continued vigilant monitoring for recurrence after definitive treatment.Learning points:Functional thymic neuroendocrine tumors are exceedingly rare.Ectopic Cushing’s syndrome secondary to thymic neuroendocrine tumors secreting ACTH present with features of hypercortisolism including electrolyte and metabolic abnormalities, uncontrolled hypertension and hyperglycemia, and opportunistic infections.The ability to undergo surgery and completeness of resection are the strongest prognostic factors for improved overall survival; however, the recurrence rate remains high.A high degree of initial clinical suspicion followed by vigilant monitoring is required for patients with this challenging disease.

Lymph Node Involvement and the Surgical Treatment of Thymic Epithelial and Neuroendocrine Carcinoma

Thymic epithelial and neuroendocrine carcinomas are rare malignancies, and only a few prognosticators are defined. Surgery is the mainstay of treatment, and complete resection contributes to superior outcome. Systematic lymph node dissection is not routinely performed in thymic malignancies. The aim of this study was to assess the impact of histologically confirmed lymph node metastases on the outcome after thymectomy. We identified 53 patients with thymic epithelial or neuroendocrine carcinomas who underwent surgical resection at our center between 1999 and 2016. The clinical follow-up was retrospectively collected, and the impact of clinicopathologic factors on overall survival was analyzed. Ninety-one percent of the patients were treated taking a multimodal approach. Median overall survival was 11.3 years. Lymph node metastases were identified in 16 patients (30.2%; 11 pN1 and 5 pN2). Lymph node metastasis was associated with inferior overall survival (hazard ratio [HR] 3.03, 95% confidence interval [CI]: 1.03 to 8.87, p= 0.044). Masaoka-Koga stage (4 versus 1 to 3) was another significant prognosticator (HR 7.01, 95% CI: 2.52 to 19.50, p= 0.0002). Organ metastases were present in 18 patients at the time of thymectomy and were associated with inferior outcome (HR 5.8, 95% CI: 2.04 to 16.79, p= 0.001). This retrospective, single-center analysis demonstrates a high rate of lymph node metastasis in resectable thymic neuroendocrine tumors or carcinomas. Positive lymph nodes are associated with an inferior outcome. Prospective studies are warranted to explore whether this outcome can be improved by systematic lymphadenectomy and adjuvant therapies. Nevertheless, lymphadenectomy provides optimal staging and should be a routine part of surgery for patients with thymic malignancies.

Resected thymic large cell neuroendocrine carcinoma: report of a case

BackgroundThymic large cell neuroendocrine carcinoma (LCNEC) is extremely rare. The detailed clinical features of thymic LNCECs remain unknown.Case presentationA 90-year-old man with a history of diabetes mellitus, chronic renal failure, and an abdominal aortic aneurysm underwent computed tomography for follow-up, which showed an anterior mediastinal tumor, measuring 31 mm × 28 mm in diameter. Magnetic resonance imaging showed an iso-intensity mass on T1-weighted images and high intensity on T2-weighted images. 18F-Fluorodeoxyglucose-positron emission tomography showed marked uptake in the mass, which was diagnosed as invasive thymoma or thymic carcinoma. Video-assisted thoracic surgery through the left thoracic cavity was converted to median sternotomy due to severe adhesions between the left lung and the chest wall. Partial thymectomy and combined partial resection of left upper lobectomy and the first and the second costal cartilages were performed. The pathologic diagnosis was thymic LCNEC, Masaoka stage III. The patient developed pleural dissemination and left lung metastases in 5 months and died 12 months after surgery.ConclusionsThymic LCNEC has high malignant potential. More cases need to be studied.

Survival outcomes after minimally invasive thymectomy for early-stage thymic carcinoma

Minimally invasive surgery (MIS) has occasionally been used for selected patients with thymoma, but there is little information on the MIS approach for thymic carcinoma. The aim of this study was to evaluate survival outcomes after MIS for early-stage (Masaoka stage I-II) thymic carcinoma and thymic neuroendocrine carcinoma. A retrospective chart review of the cases recorded in our multi-institutional database was performed to identify patients who underwent resection for thymic carcinoma between 1995 and 2017. MIS thymectomy was performed in 17 cases (VATS, n = 14; RATS, n = 3. male, 41%; median age, 72years). The median follow-up period was 32.7 (range 7.4-106) months. The five-year overall survival and relapse-free survival rates were 84.4% and 77.8%, respectively. The present study demonstrated encouraging preliminary results regarding MIS for the treatment of early-stage thymic carcinoma and thymic neuroendocrine carcinoma. Further studies with a larger sample size are required to evaluate the indications for this surgery.

Low incidence of and mortality from a second malignancy after resection of thymic carcinoma†.

Previous studies have suggested that a second malignancy often develops after resection of thymoma; however, it remains unknown whether this is applicable to thymic carcinoma. A retrospective chart review was performed based on our multi-institutional database of resected thymic epithelial tumours between 1991 and 2016. A second malignancy was defined as newly diagnosed after thymic tumour resection. The cumulative incidence of and related death from a second malignancy after thymic and neuroendocrine carcinoma resections were estimated using a competing risk model and were compared to those of patients undergoing a thymoma resection. Two hundred and thirty-eight patients were identified (thymic carcinoma 59; thymoma 179). A second malignancy developed in 1 patient (1.7%) with thymic carcinoma and in 17 patients (9.5%) with thymoma. Deaths from second malignancies were noted in 7 patients with thymoma. There was a tendency towards a lower cumulative incidence of and a lower cumulative death from a second malignancy after thymic carcinoma resection (P = 0.139 and P = 0.20, respectively) than after thymoma resection. The cumulative incidence of a second malignancy in patients with thymic carcinoma was 2.8% at 5 years and at 10 years (8.0% at 5 years and 11.8% at 10 years in patients with thymoma). After resection of thymic and thymic neuroendocrine carcinoma, the probability of developing a second malignancy, as well as mortality from a second malignancy, is very low. A prospective study with a larger sample size is required to validate our results.

A thymic neuroendocrine carcinoma presenting with upper gastrointestinal bleeding: A case report

A thymic neuroendocrine carcinoma presenting with upper gastrointestinal bleeding: A case report

Thymic large cell neuroendocrine carcinoma \u2013 a rare and aggressive tumor: a case report

BackgroundNeuroendocrine tumors are a large group of tumors with a wide spectrum of behavior, affecting mainly the digestive system and the lung. The thymus is very rarely affected.Case presentationA 28-year-old Arab woman presented with chronic chest pain and dyspnea. A computed tomography scan showed a huge anterior mediastinal mass invading neighboring structures. A mediastinotomy was performed with biopsies of the mass. Pathological findings were consistent with a thymic large cell neuroendocrine carcinoma.ConclusionsThe occurrence of a large cell neuroendocrine carcinoma in the thymus, especially in young people, is extremely rare. In this current report, we discuss the clinicopathological issues of this rare tumor according to recent literature data.

Ectopic ACTH-secreting tumor of the thymus revealed by a Cushing’s syndrome: case report and review of literature

Tumors of the thymus are rare. Neuroendocrine tumors are extremely rare. We report a case of a 39-year-old man, referred to our hospital for a paraneoplastic Cushing syndrome with a thymic tumor. Despite bilateral adrenalectomy, the patient still had signs of hypercorticism. A CT scan revealed a 25-mm nodule in the thymic compartment. A resection was indicated and surgery was successful. No adjuvant therapy was administrated. After 10 months, the patient was in good health and his clinical symptoms resolved, with no signs of recurrence. Lung and thymic neuroendocrine carcinomas with Cushing syndrome are aggressive with a high risk of recurrence even after a complete resection. A close follow-up is recommended.

ED15.03 Surgery of Thymic Malignancies

ED15.03 Surgery of Thymic Malignancies

Diagnosis of Churg-Strauss Syndrome Presented With Neuroendocrine Carcinoma: A Case Report.

Churg-Strauss syndrome (CSS) is a rare systemic vasculitis that affect small and medium-sized blood vessels and is accompanied by asthma, eosinophilia, and peripheral neuropathy. This report describes a case of a 52-year-old man who had a history of sinusitis, asthma, and thymus cancer and who had complained of bilateral lower extremity paresthesia and weakness for a month. Peripheral neuropathy was detected by electrodiagnostic studies. Resection of a mediastinal mass, which was diagnosed as thymic neuroendocrine carcinoma, was performed five months before his visit. After thymectomy, peripheral blood tests revealed a gradual increase in eosinophils. Two months after surgery, he was admitted to the hospital for dyspnea, and nodules of focal consolidation were found in his chest X-ray. One month later, pyoderma occurred in the right shin, and the skin biopsy showed extravascular eosinophilic infiltration. He was diagnosed with CSS after thymectomy, and we report a very rare case of CSS presented with thymic neuroendocrine carcinoma.

肺と胸腺に同時期に発生した大細胞神経内分泌癌の1例

肺と胸腺に同時期に発生した大細胞神経内分泌癌の1例

Abstract #944: Multiple Endocrine Neoplasia 1 Presenting with Thymic Neuroendocrine Carcinoma

Abstract #944: Multiple Endocrine Neoplasia 1 Presenting with Thymic Neuroendocrine Carcinoma

Ectopic adrenocorticotropic hormone syndrome caused by neuroendocrine tumors of the thymus: 30-year experience with 16 patients at a single institute in the People's Republic of China.

Background and purposeThymic neuroendocrine carcinomas (TNECs) are extremely uncommon. Certain cases of TNECs can produce the adrenocorticotropic hormone (ACTH) and cause ectopic ACTH syndrome (EAS). The current literature on this topic consists mainly of case reports, and therapeutic guidelines are lacking. The aim of this study was to discuss the diagnosis, surgical management, and prognosis of EAS caused by TNECs to improve clinical experience with this rare disease.MethodsFrom June 1984 to June 2014, at the Peking Union Medical College Hospital, the surgical interventions and follow-up outcomes of 16 consecutive patients (eight men and eight women) with EAS caused by TNECs were retrospectively analyzed.ResultsThe median age was 32.5 years (range: 13–47 years), and the median disease duration was 8.5 months (range: 1–150 months). All patients presented with clinical and biochemical evidence indicating a diagnosis of Cushing’s syndrome. Contrast-enhanced thoracic computed tomography scans were critical to locating the ACTH-producing tumor and evaluating the feasibility of resection. All patients underwent surgery. One patient died of septicemia in the intensive care unit 2 weeks after surgery. No other morbidity or mortality occurred during the perioperative period. The median overall survival (OS) was 41 months (95% CI: 30.3–51.7 months), and the progression-free survival was 28 months (95% CI: 21.6–34.3 months). Both overall survival (P=0.002) and progression-free survival (P=0.030) improved significantly after complete resection.ConclusionTNEC is an extremely aggressive disease that should be considered when treating patients with Cushing’s syndrome due to ectopic ACTH secretion. In particular, all suspected patients should undergo contrast-enhanced thoracic computed tomography scans to facilitate early diagnosis. The current first-line treatment is surgical resection, and complete resection is a favorable prognostic factor. However, additional patients and a longer follow-up will be needed to determine the variables that are predictive of survival and to improve patient prognosis.

Pancreatic metastasis resulting from thymic neuroendocrine carcinoma: A case report.

Thymic neuroendocrine carcinoma (NEC) is a rare type of cancer. Unlike other thymic epithelial tumors and carcinoids originating in other locations, thymic NEC possesses a more aggressive biological behavior, including invasion to proximal structures, local recurrence and distant hematogenous metastasis. Distant metastasis is often observed in the bones, lungs, spleen, liver and adrenal glands. However, pancreatic metastasis resulting from thymic NEC is extremely uncommon, and only a few cases of patients with this disease have been reported. The current study presents the case of a patient with pancreatic metastasis resulting from thymic NEC. The patient was admitted to hospital with an anterior mediastinal neoplasm, which was identified using chest enhanced computed tomography. The patient underwent a monobloc excision of the tumor with resection of involved structures. Subsequently, a pathological diagnosis of atypical thymic carcinoid was provided, according to the morphological characteristics observed and the expression of neuroendocrine markers, as identified by immunohistochemistry. Following surgery, the patient received adjuvant chemotherapy and radiotherapy. However, ~2 years after surgery, metastasis at the pancreatic head was identified. The patient underwent a total pancreatectomy and splenectomy, and did not receive any post-operative therapies; however, the patient succumbed to the disease 9 months following surgery. Overall, the results from the present study demonstrate the clinical features of thymic NEC, which may aid with the diagnosis of this rare disease in other patients.

Spontaneous Rupture of Thymic Neuroendocrine Carcinoma: A Case Report

Thymic neuroendocrine carcinoma (NEC), also known as thymic carcinoid tumors, are uncommon thymic neoplasms with neuroendocrine differentiation. Among primary thymic malignancies, NEC is the least common, accounting for less than 5% of thymic tumors (1). Thymic NEC tends to be locally invasive towards adjacent structures, such as mediastinal fat, lung, pericardium, and great vessels (2). Metastatic spread can occur by either hematogenous or lymphatic routes, and mediastinal lymph node metastasis is found in about 30 percent of patients at presentation (3). Although thymic NEC is typically identified as a large, usually invasive, anterior mediastinal mass with hemorrhage and necrosis (4, 5), it is extremely rare for it to present rupture. Herein, we report a case of the thymic NEC that was initially presented as a potentially fatal hemorrhage by capsular rupture. CASE REPORT