Takashi Nakajima

Oncocytic lipoadenoma of the salivary gland is a rare tumor that develops mainly in the parotid gland. We report a case of oncocytic lipoadenoma of the parotid gland in a 70-year-old woman. The tumor measured 30 × 20 mm and had a well-circumscribed tan-brown surface. The tumor was histologically composed of oncocytic and lipomatous lesions without atypia. In addition to the oncocytic lipoadenoma, a small lipomatous tumor, measuring 10 × 7 mm, was found in the resected parotid gland. Macroscopically, this tumor was yellow and indistinguishable from the parotid gland. Microscopically, the tumor was rich in fats and contained an area of conglomerated duct-like proliferation and salivary gland components. Therefore, the tumor was diagnosed as a non-oncocytic lipoadenoma with a sialoadenoma component. We report the first case of double component oncocytic and non-oncocytic lipoadenomas of the salivary gland.

Although anaplastic lymphoma kinase (ALK) fusion genes are generally identified in lung adenocarcinoma patients, they are relatively rare in patients with squamous cell carcinoma (SqCC). Metastatic ALK-rearranged lung adenocarcinoma patients treated with ALK inhibitors demonstrate higher response rates, improved progression-free survival, and reduced toxicity relative to those treated with conventional chemotherapy regimens. However, the efficacy of treatment with ALK inhibitors in patients with ALK-rearranged lung SqCC remains unknown. We discuss a 52-year-old Japanese-Brazilian woman without a history of smoking who was referred to our hospital for evaluation of severe left back pain and a left hilar mass observed on a chest radiograph. The patient was eventually diagnosed on the basis of computed tomography, pathological, and immunohistochemical findings as having Stage IV lung SqCC. First-line treatment with palliative radiotherapy and systemic chemotherapy with cisplatin plus vinorelbine was administered, but was not effective. ALK testing was subsequently performed, revealing positive ALK expression and gene rearrangement. Alectinib therapy was then initiated, which resulted in a gradual, but substantial reduction in tumor size. To the best of our knowledge, this is the first case report to discuss the successful management of ALK-rearranged lung SqCC with alectinib. We propose that molecular testing for driver mutations should be considered in young patients with a light or no smoking history, even if the histological findings correspond with SqCC, and alectinib therapy represents a reasonable option in cases of ALK-rearranged lung SqCC.

The majority of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation eventually develop resistance to EGFR tyrosine kinase inhibitors (TKIs). Minimal information exists regarding genetic alterations in rebiopsy samples from Asian NSCLC patients who develop acquired resistance to EGFR-TKIs. We retrospectively reviewed the medical records of patients with NSCLC harboring EGFR mutations who had undergone rebiopsies after developing acquired resistance to EGFR-TKIs. We analyzed 27 practicable samples using a tumor genotyping panel to assess 23 hot-spot sites of genetic alterations in nine genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2), gene copy number of EGFR, MET, PIK3CA, FGFR1, and FGFR2, and ALK, ROS1, and RET fusions. Additionally, 34 samples were analyzed by commercially available EGFR mutation tests. Sixty-one patients underwent rebiopsy. Twenty-seven samples were analyzed using our tumor genotyping panel, and 34 samples were analyzed for EGFR mutations only by commercial clinical laboratories. Twenty-one patients (34%) had EGFR T790M mutation. Using our tumor genotyping panel, MET gene copy number gain was observed in two of 27 (7%) samples. Twenty patients received continuous treatment with EGFR-TKIs even after disease progression, and 11 of these patients had T790M mutation in rebiopsy samples. In contrast, only 10 of 41 patients who finished EGFR-TKI treatment at disease progression had T790M mutation. The frequency of T790M mutation in patients who received continuous treatment with EGFR-TKIs after disease progression was significantly higher than that in patients who finished EGFR-TKI treatment at disease progression (55% versus 24%, p = 0.018). The frequency of T790M mutation in this study was lower than that in previous reports examining western patients. These results suggest that continuous treatment with EGFR-TKI after disease progression may enhance the frequency of EGFR T790M mutation in rebiopsy samples.

Platinum-based chemoradiotherapy (CRT) is a standard front-line treatment for locally advanced non-small cell lung cancer (NSCLC). However, no clinical trials have compared the efficacy and toxicity of platinum combination and docetaxel as subsequent re-challenge chemotherapies after cancer recurrence following CRT. This study aimed to evaluate the efficacy and toxicity of platinum combination chemotherapy versus docetaxel monotherapy in NSCLC patients previously treated with platinum-based CRT. From September 2002 to December 2009, at three participating institutions, 24 patients with locally advanced NSCLC, who had previously received platinum-based CRT, were treated with platinum combination re-challenge therapy, whereas 61 received docetaxel monotherapy. We reviewed their medical charts to evaluate patient characteristics and data regarding treatment response, survival, and toxicity. The response rates were 16.7% and 6.6% in the platinum combination chemotherapy and docetaxel monotherapy groups, respectively (p = 0.09), whereas disease control rates were 58.3% and 57.4%, respectively (p = 0.82). Progression-free survival was similar between the two groups (median, 4.2 vs. 2.3 months; hazard ratio [HR] = 0.81; 95% confidence interval [CI] = 0.51–1.29; p = 0.38), as was overall survival (median, 16.5 vs. 13.0 months; HR = 0.82; 95% CI = 0.47–1.41; p = 0.47). The incidence and severity of toxicity was also similar between the two groups. Hematological toxicity, particularly leukopenia and neutropenia, was more frequent in the docetaxel group. Our results indicated that platinum combination re-challenge was equivalent to docetaxel for relapsed patients previously treated with platinum-based CRT.

Despite considerable recent progress in the treatment of lung adenocarcinoma, there has been little progress in the development of efficacious molecular targeted therapies for squamous cell lung cancer. In addition to the recent comprehensive genome-wide characterization of squamous cell lung cancer, it is also important to genotype this form of cancer. We therefore conducted the Shizuoka Lung Cancer Mutation Study to analyze driver mutations in patients with thoracic malignancies. Here we report the results of genotyping in patients with squamous cell lung cancer. Based on the biobanking system, in conjunction with the clinic and pathology lab, we developed a genotyping panel designed to assess 24 mutations in 10 genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, HER2 and DDR2), EGFR, MET, PIK3CA, FGFR1 and FGFR2 copy numbers, and EML4-ALK and ROS1 translocations, using pyrosequencing plus capillary electrophoresis, quantitative polymerase chain reaction (PCR) and reverse-transcription PCR, respectively. A total of 129 patients with squamous cell lung cancer and adenosquamous carcinoma were enrolled in this study between July 2011 and November 2012. We detected genetic alterations in 40% of all cases. Gene alterations included: EGFR mutations, 6%; KRAS mutations, 4%; PIK3CA mutations, 13%; NRAS mutations, 1%; KIF5b-RET fusion gene, 1%; EGFR copy number gain, 5%; PIK3CA copy number gain, 15%; and FGFR1 copy number gain, 5%. Twelve patients (9%) harbored simultaneous genetic alterations. Genetic alterations were detected more frequently in surgically-resected, snap-frozen samples than in formalin-fixed, paraffin-embedded samples (50% vs. 29%). In addition, patients aged ≤70 years old and never-smokers showed high frequencies of genetic alterations. This study represents one of the largest prospective tumor-genotyping studies to be performed in Asian patients with squamous cell lung cancer. These results suggest that incorporation of genetic profiling into lung cancer clinical practice may facilitate the administration of personalized cancer treatments in patients with squamous cell lung cancer.

Serum CYFRA 21–1 is one of the most important serum markers in the diagnosis of non-small cell lung cancer (NSCLC), especially squamous-cell carcinoma. However, it remains unknown whether pretreatment serum CYFRA 21–1 values (PCV) may also have prognostic implications in patients with advanced lung adenocarcinoma.

The early phase of salivary gland carcinomas with high-grade transformation (HGT) is extremely rare. We reported one case of adenoid cystic carcinoma (AdCC) with early HGT, herein.

Until date, there are no clear recommendations for regular perioperative measurements of serum CEA levels for lung cancer in any guidelines. The purpose in the present study is to evaluate the prognostic significance of perioperative serum carcinoembryonic antigen (CEA) levels in patients with pathological-stage I non-small cell lung cancer (NSCLC).

A 60-year-old Japanese man was found to have diffuse pneumonia-like shadow in the left S10 segment on chest computed tomographic scan. Transbronchial lung biopsy yielded a pathological diagnosis of poorly differentiated adenocarcinoma; subsequently, left lower lobectomy was performed. Histopathological analysis showed that the tumor consisted solely of discohesive cells with involvement of the hilar and mediastinal lymph nodes. The immunohistochemical expression of E-cadherin and β-catenin was low, whereas that of p53 was high in the tumor cells. Here, we describe a rare lung adenocarcinoma with discohesive cells, which are considered to indicate high tumor aggressiveness.