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

PURPOSE: 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. METHODS: 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. RESULTS: Sixty patients were identified among 152 patients who underwent resection of TC and TNEC. The median follow-up period from the first recurrence was 14.8 months (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. CONCLUSIONS: 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.

Immunophenotypic and prognostic analysis of PAX8 and TTF-1 expressions in neuroendocrine carcinomas of thymic origin: A comparative study with their pulmonary counterparts.

OBJECTIVES: To investigate the immunoreactivity of TTF-1 and PAX8 in neuroendocrine carcinoma of thymic (TNEC) and pulmonary origins (PNEC), and whether their immunophenotyping could be used to distinguish between NEC of the two sites, as well as prognosis of patients with TNEC. METHODS: Twenty-two cases of TNEC and 20 cases of PNEC were selected for immunohistochemical analysis using PAX8 and TTF-1. Clinical data and follow-up information were obtained for survival analyses. RESULTS: TTF-1 immunoreactivity was seen in 19 PNEC cases (95%) and 13 TNEC cases (59.1%). PAX8 was negative in all pulmonary tumors while positive in 19 thymic cases (86.4%). TTF-1 positivity was associated with high sensitivity but low specificity for PNEC, and adding PAX8 negativity significantly increased the specificity. PAX8 positivity alone showed essentially 100% specificity and 86.4% sensitivity for TNEC. Survival analysis showed lung metastasis as a significant prognostic factor in TNEC. CONCLUSION: Our study demonstrated that TTF-1/PAX8 immunophenotyping may be helpful for differential diagnosis of NECs of pulmonary and thymic origins. TTF-1+/PAX8- immunophenotyping showed high specificity for PNECs, while PAX8+ alone showed a good diagnostic accuracy for TNEC. Lung metastasis was a predictive factor that associated with survival of TNEC patients. J. Surg. Oncol. 2016;114:697-702. © 2016 Wiley Periodicals, Inc.

Generalised hyperpigmentation caused by ectopic adrenocorticotropic hormone syndrome with recurrent thymic neuroendocrine carcinoma.

Ectopic adrenocorticotropic hormone (ACTH) syndrome is a rare cause of generalised hyperpigmentation. The clinical features are due to the excessive ectopic secretion of adenocorticotropin by diverse neuroendocrine or non-endocrine tumours. Here, we describe a rare case of ectopic ACTH syndrome developing from recurring thymic neuroendocrine carcinoma, which first presented as generalised hyperpigmentation.

Case report: A challenging case of severe Cushing's syndrome in the course of metastatic thymic neuroendocrine carcinoma with a synchronous adrenal tumor.

Ectopic ACTH syndrome (EAS) remains one of the most demanding diagnostic and therapeutic challenges for endocrinologists. Thymic neuroendocrine tumors account for 5%-10% of all EAS cases. We report a unique case of a 31-year-old woman with severe EAS caused by primary metastatic combined large-cell neuroendocrine carcinoma and atypical carcinoid of the thymus. The patient presented with severe hypercortisolemia, which was successfully controlled with continuous etomidate infusion. Complex imaging initially failed to detect thymic lesion; however, it revealed a large, inhomogeneous, metabolically active left adrenal mass infiltrating the diaphragm, suspected of primary disease origin. The patient underwent unilateral adrenalectomy, which resulted in hypercortisolemia resolve. The pathology report showed an adenoma with adrenal infarction and necrosis. The thymic tumor was eventually revealed a few weeks later on follow-up imaging studies. Due to local invasion and rapid progression, only partial resection of the thymic tumor was possible, and the patient was started on radio- and chemotherapy.

Neuroendocrine Tumors of the Thyroid and Their Mimics.

This paper will review neuroendocrine lesions of the thyroid and the differential diagnosis with the most significant such tumor of the thyroid, that is, medullary thyroid carcinoma. A brief overview of the understanding of this tumor's identification as a lesion of C cells and its familial and syndromic associations will be presented. Then, a discussion of the various mimics of medullary carcinoma will be given with an approach to the types of tests that can be done to arrive at a correct diagnostic conclusion. This review will focus on practical "tips" for the practicing pathologist.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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.

Recurrence of thymic neuroendocrine carcinoma 24 years after total excision: A case report.

A 77-year-old male presented with chest pain in March 2012. The individual had undergone surgery for an anterior mediastinal tumor 24 years earlier and the pathological diagnosis was that of a thymoma. The patient underwent a medical check-up every 6 months for the next 20 years. However, ∼3 years following the final check-up, sudden chest pain was reported and the patient was referred again. Computed axial tomography revealed a mediastinal mass adjacent to the left lung, pericardium and sternum. There was no apparent invasion to the adjacent structures. The patient underwent surgical resection following a diagnosis of recurrent thymoma. A posterolateral thoracotomy was performed under video-assisted thoracoscopy. Severe adhesions were observed around the tumor, which appeared to invade the left lung and pericardium, but not the chest wall. The tumor was extirpated in combination with partial resection of the left lung and pericardium. The pathological diagnosis of the tumor was of a well-differentiated neuroendocrine carcinoma (NEC) of the thymus. The specimen that was excised 24 years earlier was re-examined by a pathologist and was reported to exhibit the same histology. Primary NECs of the thymus are rare among anterior mediastinal tumors and the 5-year survival rate is ∼30%. The present case study reports a case of a thymic NEC and describes the pathological and clinical features.

Rapid development of thymic neuroendocrine carcinoma despite transcervical thymectomy in a patient with multiple endocrine neoplasia type 1.

Thymic neuroendocrine (NE) tumors are a rare manifestation of multiple endocrine neoplasia syndrome type 1 (MEN-1). They are malignant and aggressive tumors and form a major cause of mortality in MEN-1. Transcervical thymectomy (TCT) at the time of parathyroid surgery for primary hyperparathyroidism (PHPT) in MEN-1 usually prevents thymic NE tumors. We report a 56-year-old nonsmoker male with sporadic MEN-1 who presented with thymic NE carcinoma developing rapidly within a span of 8 months after subtotal parathyroidectomy and TCT for PHPT. We present a brief review of literature on this rare NE malignancy, focusing on its occurrence despite TCT. This case highlights the fact that thymic NE carcinoma may develop even after TCT in MEN-1. Regular surveillance for these aggressive thymic NE tumors is mandatory even after TCT in MEN-1 setting.