A clinicopathologic and molecular analysis of five cases of bronchiolar adenoma with rare mutations.

Bronchiolar adenoma (BA) is a rare benign lung tumor that shows proliferation of bland bronchiolar-type epithelium containing a continuous layer of basal cells. This tumor entity has been newly added to the recent World Health Organization (WHO) classification 5th edition. This entity encompasses a spectrum of lesions: the classic ciliated muconodular papillary tumor (CMPT) and the non-classic CMPT. Although BA is reported to have driver mutations including BRAF V600E, EGFR, and KRAS, the molecular profile of BA is still incompletely understood. Five resected BAs at our institutions were analyzed. The BA lesions were subdivided into two groups: three proximal-type BAs and two distal-type BAs. NRAS codon 12/13 mutation and EML4 exon 20-ALK exon 20 fusion were found in two of the three proximal-types. BRAF V600E mutation was found in one of the two distal-types. Two cases coexisted with lung adenocarcinoma, with EGFR exon 19 deletion and KRAS mutation, respectively. No recurrence was observed at a median of 12 months (range 2-84 months) of follow-up. BA has uncommon variants of mutation seen in lung adenocarcinoma. NRAS mutation and ALK fusion partner has not been reported previously. The present cases may reinforce the distinctive biology of BA from lung adenocarcinoma.

Gastric Myeloid Sarcoma Mimicking a Scirrhous Gastric Cancer.

Myeloid sarcoma (MS) is a relatively rare manifestation of myeloid neoplasms at sites other than the bone marrow. The rarity of gastrointestinal (GI) MS is attributed to certain factors, such as misdetection due to insufficient endoscopic assessments at the initial presentation with acute myeloid leukemia (AML) as well as the difficulty of making a histologic assessment of leukemic involvement of the GI tract. We herein report a case of AML with gastric involvement and discuss the importance of screening examinations and therapies considering the location of MS and the data of cytogenetic and molecular mutation.

TTF-1 and c-MYC-defined Phenotypes of Large Cell Neuroendocrine Carcinoma and Delta-like Protein 3 Expression for Treatment Selection.

The standard treatment regimen has not yet been established for advanced pulmonary large cell neuroendocrine carcinoma (LCNEC) because of its rarity. LCNEC can be subdivided into 2 mutually exclusive molecular subgroups: STK11/KEAP1 and TP53 mutated with high neuroendocrine expression and transcriptional profile of ASCL1high/DLL3high/NOTCHlow (non-small cell lung carcinoma, NSCLC-like) or RB1 and TP53 mutated with reduced neuroendocrine markers and transcriptional pattern of ASCL1low/DLL3low/NOTCHhigh (small cell lung cancer, SCLC-like). Model-based clustering shows that SCLC has subdivided into 2 major proteomic subsets defined by either TTF-1high/c-MYClow or TTF-1low/c-MYChigh, which may correspond to 2 mutually exclusive molecular subgroups: NSCLC-like or SCLC-like, respectively. We herein investigated whether TTF-1 and c-MYC could be applied to LCNEC to identify distinct subsets immunohistochemically and assessed DLL3 expression in these subsets. The protein expression profile may be useful to select patients for potential efficacy of targeted therapies including aurora kinase inhibitors for MYC alterations or anti-DLL3 antibody-drug conjugates. TTF-1 and c-MYC expression was mutually exclusive in 25 of 27 (93%) cases; TTF-1+/c-MYC- in 10, TTF-1-/c-MYC+ in 15, and TTF-1+/c-MYC+ in 2. DLL3 expression was seen in 15 of 27 cases (56%). All 12 TTF-1+ LCNEC cases were positive for DLL3. Three of 15 (20%) TTF-1-/c-MYC+ cases showed DLL3 positivity. LCNEC could be separated into 2 subsets proteomically defined by TTF-1 and c-MYC expression, which may be suitable to guide treatment selection including aurora kinase inhibitors for c-MYC+ cases. TTF-1 positivity can serve as a surrogate marker for DLL3, but caution is necessary as 20% of TTF-1- cases showed DLL3 positivity.

Prognostic significance of spread through air spaces in pulmonary metastases from colorectal cancer.

OBJECTIVES: Surgical resection for pulmonary metastases from colorectal cancer could provide long-term survival in selected patients, and it is commonly performed in practice. However, surgical margin relapse sometimes occurs and is a problematic issue to resolve. Spread through air spaces (STAS) is one of the invasion forms in primary lung cancer and is associated with local recurrence and a poor prognosis. The aim of this study was to evaluate the prognostic significance of STAS for pulmonary metastases from colorectal cancer and to assess the predictability of STAS with preoperative clinical information. METHODS: A total of 96 pulmonary metastatic lesions from colorectal cancer in 37 patients who underwent metastasectomy at our institution from January 2008 to December 2013 were retrospectively analyzed. RESULTS: STAS was identified in 41.6 % of the 96 lesions. Surgical margin relapse was found in 8 lesions (8.3 %) from 7 patients (18.9 %). The distance of STAS was identified as an independent risk factor for surgical margin relapse on multivariable analysis (p =  0.033). The patients with STAS showed significantly worse overall survival than those without (5-year overall survival rate: 30.3 % vs. 76.9 %; p =  0.002). On multivariable analysis, patients with STAS had a significantly higher risk of death than those without (p =  0.019). An elevated pre-metastasectomy serum carcinoembryonic antigen level was independently correlated with STAS on multivariable analysis (p =  0.049). CONCLUSION: STAS was related to a poor prognosis and surgical margin relapse in pulmonary metastases from colorectal cancer.

Histology and Mechanics of In Vivo Tissue-Engineered Vascular Graft for Children.

PURPOSE: This study sought to evaluate the histologic and mechanical properties of autologous in vivo tissue-engineered vascular grafts (in vivo TEVGs) used for pediatric heart surgery. DESCRIPTION: Molds of in vivo TEVGs made of silicone drain tubes were embedded into subcutaneous spaces in 2 boys during their first operation and were used as patch materials to treat pulmonary artery stenosis during the second operation. The remaining pieces of the patches were evaluated histologically and mechanically. EVALUATION: In vivo TEVGs had very smooth luminal surfaces, and their walls mainly comprised collagen fibers and small numbers of fibroblasts. Mean wall thickness was 200 µm, mean suture retention strength was 2.26 N, and burst pressure was 3057 mm Hg. CONCLUSIONS: Human in vivo TEVGs mainly comprise collagen fibers, and their mechanical properties prove them safe for pulmonary arterioplasty. Therefore, human in vivo TEVGs may be promising alternatives to autologous pericardium for pediatric cardiovascular surgical procedures that often require multistage operations.

Omental Flap for Bronchopleural Fistula After Pneumonectomy and Aorta Replacement.

Bronchopleural fistula (BPF) is a fatal complication after lung cancer surgery. We report the case of a 56-year-old man treated with omental flap for BPF after pneumonectomy along with descending aorta replacement. He underwent left pneumonectomy with combined resection of the descending aorta, followed by replacement with prosthetic graft after the diagnosis of lung cancer, cT4 N1 M0 stage IIIA. He had BPF postoperatively and underwent an omental flap plombage after unsuccessful repair using the latissimus dorsi muscle. He did not have BPF recurrence or aortic graft infection. An omental flap is a useful option for treating BPF with an intrathoracic prosthetic graft.