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Yang Lv, Ning Pu, Wei-lin Mao, Wen-qi Chen, Huan-yu Wang, Xu Han, Yuan Ji, Lei Zhang, Da-yong Jin, Wen-Hui Lou and Xue-feng Xu

clinically related to aggressive tumor behavior and devastating prognosis ( 4 ). However, study has ( 5 ) proved that NECs could also demonstrate heterogeneous oncological behavior with a relatively wide spectrum of differentiation degree. Increasing evidence

Open access

Shuang Ye, Yuanyuan Xu, Jiehao Li, Shuhui Zheng, Peng Sun and Tinghuai Wang

common therapeutic targets, TNBCs are associated with the worst prognosis and one of the highest risks of metastasis among all subtypes of breast cancer ( 2 , 3 ). Further, several population-based studies have shown that TNBC often presents at a

Open access

Andrea Mazurat, Andrea Torroni, Jane Hendrickson-Rebizant, Harbinder Benning, Richard W Nason and K Alok Pathak

Hürthle cell variants, account for over 90% of all thyroid malignancies (22, 23) . Our analysis of all consecutive WDTC seen between 1970 and 2010 confirmed the excellent prognosis of WDTC with a DSS of 95.4% (95% CI, 94.2–96.3%) at 10 years. WDTC

Open access

Catarina Tavares, Maria João Coelho, Catarina Eloy, Miguel Melo, Adriana Gaspar da Rocha, Ana Pestana, Rui Batista, Luciana Bueno Ferreira, Elisabete Rios, Samia Selmi-Ruby, Bruno Cavadas, Luísa Pereira, Manuel Sobrinho Simões and Paula Soares

behavior and prognosis. Some studies tried to understand if NIS immunohistochemical expression in thyroid primary tumors would be helpful in predicting 131 I uptake in recurrences and distant metastases. Although positive NIS immunostaining in primary

Open access

Yang Lv, Xu Han, Chunyan Zhang, Yuan Fang, Ning Pu, Yuan Ji, Dansong Wang, Xu Xuefeng and Wenhui Lou

surgical/needled specimen can give rise to the prognosis prediction and nonoperative management guidance to some extents, but this is usually based on a fixed small biopsy sample that may not reflect the heterogeneity present in advanced tumors ( 2

Open access

Simon Schimmack, Yongchao Yang, Klaus Felix, Markus Herbst, Yixiong Li, Miriam Schenk, Frank Bergmann, Thilo Hackert and Oliver Strobel

, 4 ). Since prognosis varies widely between individual pNENs ( 5 ), there is a critical need to better define the molecular features associated with prognosis in these tumors. Recently, elevated pre-operative C-reactive protein (CRP) values have

Open access

Xu Han, Xuefeng Xu, Hongyun Ma, Yuan Ji, Dansong Wang, Tiantao Kuang, Wenchuan Wu, Bin Song, Gang Li, Gang Jin and Wenhui Lou

into small cell and large cell subtype, and were associated with highly aggressive behavior and dismal prognosis ( 6 ). However, recent literature indicates that some G3 pNENs containing noticeably different genetic mutational profile have well

Open access

K G Samsom, L M van Veenendaal, G D Valk, M R Vriens, M E T Tesselaar and J G van den Berg

of unravelling the molecular events underlying NET tumorigenesis, facilitating the identification of novel therapeutic targets, rational (targeted) therapy management strategies and to improve prognosis. Recently, whole-genome sequencing of primary

Open access

Huy Gia Vuong, Nguyen Phuoc Long, Nguyen Hoang Anh, Tran Diem Nghi, Mai Van Hieu, Le Phi Hung, Tadao Nakazawa, Ryohei Katoh and Tetsuo Kondo

aggressive and associated with a poor prognosis ( 2 ). Criteria for TCVPTC was first proposed in 1976 by Hawk and Hazard ( 3 ). In the previous WHO 2004 classification, however, the morphological criterion for the diagnosis of TCVPTC was vague: ‘The TCV is

Open access

B C M Hermans, J L Derks, H J M Groen, J A Stigt, R J van Suylen, L M Hillen, E C van den Broek, E J M Speel and A-M C Dingemans


Stage IV large cell neuroendocrine carcinoma (LCNEC) of the lung generally presents as disseminated and aggressive disease with a Ki-67 proliferation index (PI) 40–80%. LCNEC can be subdivided in two main subtypes: the first harboring TP53/RB1 mutations (small-cell lung carcinoma (SCLC)-like), the second with mutations in TP53 and STK11/KEAP1 (non-small-cell lung carcinoma (NSCLC)-like). Here we evaluated 11 LCNEC patients with only a solitary brain metastasis and evaluate phenotype, genotype and follow-up.


Eleven LCNEC patients with solitary brain metastases were analyzed. Clinical characteristics and survival data were retrieved from medical records. Pathological analysis included histomorphological analysis, immunohistochemistry (pRB and Ki-67 PI) and next-generation sequencing (TP53, RB1, STK11, KEAP1 and MEN1).


All patients had N0 or N1 disease. Median overall survival (OS) was 12 months (95% confidence interval (CI) 5.5–18.5 months). Mean Ki-67 PI was 59% (range 15–100%). In 6/11 LCNEC Ki-67 PI was ≤40%. OS was longer for Ki-67 ≤40% compared to >40% (17 months (95% CI 11–23 months) vs 5 months (95% CI 0.7–9 months), P = 0.007). Two patients were still alive at follow-up after 86 and 103 months, both had Ki-67 ≤40%. 8/11 patients could be subclassified, and both SCLC-like (n = 6) and NSCLC-like (n = 2) subtypes were present. No MEN1 mutation was found.


Stage IV LCNEC with a solitary brain metastasis and N0/N1 disease show in the majority of cases Ki-67 PI ≤40% and prolonged survival, distinguishing them from general LCNEC. This unique subgroup can be both of the SCLC-like and NSCLC-like subtype.