Spread through air spaces is an independent predictor of recurrence in stage III (N2) lung adenocarcinoma.

OBJECTIVES: Spread through air space (STAS) is recognized as a pattern of invasion in lung adenocarcinoma and has been reported to be a predictor of recurrence and survival in patients with early-stage lung adenocarcinoma. However, this parameter has not been studied well in stage III (N2) lung adenocarcinoma. In this study, we evaluated the association between STAS invasion patterns and recurrence and survival in stage III (N2) lung adenocarcinoma. METHODS: We retrospectively reviewed data from 76 patients at University of Tokyo with stage III (N2) lung adenocarcinoma who underwent surgery from August 1998 to December 2013. Statistical analysis was performed to determine the impact of STAS invasion clinicopathological features and clarify the relationship between this pattern of invasion and survival. RESULTS: Tumour STAS was observed in 46 of 76 patients (60.5%) and was significantly associated with the presence of lymphatic invasion (P < 0.001), papillary components (P < 0.001) and micropapillary components (P < 0.001). STAS was also significantly associated with recurrence (5-year recurrence-free probability: 19.0% vs 46.1%, P < 0.05). Univariate analyses showed that STAS was a significant risk factor for recurrence (hazard ratio 1.94, 95% confidence interval 1.07-3.51; P = 0.029). CONCLUSIONS: The presence of STAS invasion pattern is a significant risk factor for recurrence in stage III (N2) lung adenocarcinoma.

A comparison between 2- and 3-dimensional approaches to solid component measurement as radiological criteria for sublobar resection in lung adenocarcinoma ≤ 2 cm in size.

PURPOSE: We compared three-dimensional (3D) and two-dimensional (2D) measurements of the solid component to determine radiological criteria for sublobar resection of lung adenocarcinoma ≤ 2 cm in size. METHODS: We included 233 surgical cases. The maximum size of the solid component for 3D measurement was calculated by delineating the solid component on successive axial images and reconstructing the 3D surface model. RESULTS: The predictive performance for adenocarcinoma in situ (n = 43) and minimally invasive adenocarcinoma (n = 77) were equivalent to areas under the curve of 0.871 and 0.857 for 2D and 3D measurements (p = 0.229), respectively. A solid component of 5 mm had a prognostic impact on both measurements ( ≤ 5 mm versus > 5 mm; p = 0.003 for 2D and p = 0.002 for 3D, log-rank test). Survival rates at 5 years were 94.7-96.9% following lobectomy and sublobar resection among patients with a solid component ≤ 5 mm in size. Sublobar resection resulted in worse survival rates, with declines at 5 years of 15.8% on 2D and 11.5% on 3D measurements, than lobectomy in patients with a solid component > 5 mm in size. CONCLUSIONS: A solid component ≤ 5 mm in size is an appropriate criterion for sublobar resection for both measurements. In addition, 2D measurement is justified because of its simple implementation.

Low truncal muscle area on chest computed tomography: a poor prognostic factor for the cure of early-stage non-small-cell lung cancer†.

OBJECTIVES: Depletion in skeletal muscle is closely associated with limited physical ability and high mortality. In this study, we evaluated the prognostic significance of skeletal muscle depletion in patients with early-stage non-small-cell lung cancer. METHODS: A retrospective analysis of patients with pathological stages I-II lung cancer, who underwent curative resection between 2009 and 2013, was conducted. The truncal muscle index (TMI) (area/height2) at the first lumbar vertebral level was measured by preoperative axial computed tomography. Overall survival and recurrence-free survival were compared between the lowest gender-specific quartile of the TMI and the other quartiles. RESULTS: A total of 314 subjects were included in the study. The cumulative 5-year recurrence-free and overall survival rates were significantly shorter in patients with lower TMIs (69% vs 83.5%, P = 0.028; 64.8% vs 80.1%, P = 0.003, respectively). In multivariable models, the TMI was identified as an independent prognostic factor for overall survival (P = 0.017, hazard ratio 1.84, 95% confidence interval 1.12-3.05), after adjusting for age, gender, preoperative serum albumin, carcinoembryonic antigen, neutrophil to lymphocyte ratio and pathological stage. CONCLUSIONS: A low preoperative TMI was associated with a poor postoperative outcome in patients with early-stage non-small-cell lung cancer. This factor may be included in the preoperative assessment of patients, for whom surgical intervention is considered.

Procedure-Specific Risk Prediction for Recurrence in Patients Undergoing Lobectomy or Sublobar Resection for Small (≤2 cm) Lung Adenocarcinoma: An International Cohort Analysis.

INTRODUCTION: This work was performed to develop and validate procedure-specific risk prediction for recurrence following resection for early-stage lung adenocarcinoma (ADC) and investigate risk prediction utility in identifying patients who may benefit from adjuvant chemotherapy (ACT). METHODS: In patients who underwent resection for small (≤2 cm) lung ADC (lobectomy, 557; sublobar resection, 352), an association between clinicopathologic variables and risk of recurrence was assessed by a competing risks approach. Procedure-specific risk prediction was developed based on multivariable regression for recurrence. External validation was conducted using cohorts (N = 708) from Japan, Taiwan, and Germany. The accuracy of risk prediction was measured using a concordance index. We applied the lobectomy risk prediction approach to a propensity score-matched cohort of patients with stage II-III disease (n = 316, after matching) with or without ACT and compared lung cancer-specific survival between groups among low- or high-risk scores. RESULTS: Micropapillary pattern, solid pattern, lymphovascular invasion, and necrosis were involved in the risk prediction following lobectomy, and micropapillary pattern, spread through air spaces, lymphovascular invasion, and necrosis following sublobar resection. Both internal and external validation showed good discrimination (concordance index in lobectomy and sublobar resection: internal, 0.77 and 0.75, respectively; and external, 0.73 and 0.79, respectively). In the stage II-III propensity score-matched cohort, among high-risk patients, ACT significantly reduced the risk of lung cancer-specific death (subhazard ratio 0.43, p = 0.001), but not among low-risk patients. CONCLUSIONS: Procedure-specific risk prediction for patients with resected small lung ADC can be used to better prognosticate and stratify patients for further interventions.

High CCR4 expression in the tumor microenvironment is a poor prognostic indicator in lung adenocarcinoma.

BACKGROUND: Clinical trials of anti-CCR4 antibody for solid cancers with or without other immune-modulating agents including immune checkpoint blockade therapy are currently underway. However, little is known about the roles of CCR4+ lymphocytes and their prognostic impact in lung cancer. We hypothesized that high CCR4 expression in the tumor microenvironment would be associated with a poor prognosis and would act as a biomarker in lung adenocarcinoma. METHODS: First, the prognostic impact of CCR4 gene expression was explored using pooled data from public transcriptomic databases with online survival analysis software. Second, tissue microarrays (TMAs) were constructed from resected lung adenocarcinoma specimens from tumors up to 3 cm in size. The density of CCR4+ lymphocytes infiltrating the tumor was then assessed by immunohistochemistry and related to survival. Confounding factors were controlled for by multivariate analysis using the Cox proportional hazards model. RESULTS: Higher than median expression of the CCR4 gene was identified as an independent poor prognostic factor for overall survival (OS) by multivariate analysis of 720 lung adenocarcinoma patients in the public databases [HR =1.55 (95% CI: 1.03-2.35), P=0.037]. Consistent with this, high CCR4+ tumor-infiltrating lymphocyte (TIL) density was found to be an independent poor prognostic factor for both OS [HR =2.24 (1.01-5.34), P=0.049] and recurrence-free survival (RFS) [HR =2.20 (1.16-4.39), P=0.017] in the patients from whom TMA were obtained (n=180). Age, male gender, predominantly non-lepidic histological subtype, nodal involvement, and low CD8+ TIL density were also independent poor prognostic factors. However, FOXP3 gene expression and Foxp3+ lymphocyte infiltration did not possess any prognostic value in either study. CONCLUSIONS: High CCR4 expression in the tumor microenvironment may be a poor prognostic factor in lung adenocarcinoma. Patients with high CCR4+ lymphocyte infiltration may have a poor prognosis and thus be suitable candidates for clinical trials of anti-CCR4 antibody treatment.

Impact of the 8th Edition of the UICC-TNM Classification on Clinical Stage 0-IA Lung Adenocarcinoma: Does the New Classification Predict Postoperative Prognosis More Precisely than the Previous One?

PURPOSE: Early lung adenocarcinoma has been more frequently found recently. The 8th edition of the Union for International Cancer Control (UICC)-Tumor Node Metastasis (TNM) classification for lung cancer has been effective since January 2017. This study aims to elucidate advantages of the current classification for patients with clinical stage 0-IA lung adenocarcinoma, in comparison with the older one. METHODS: We retrospectively reviewed the data of clinical stage IA (7th edition) lung adenocarcinoma patients who underwent surgery at our institute from 2001 to 2012, and reclassified them by the 8th edition. Survival analysis was used to evaluate the impact of the two classifications. RESULTS: In all, 281 cases were eligible. Clinical T-factors (8th) were significant prognostic factors for overall survival (P = 0.001), recurrence-free survival (P <0.001), and cancer-specific survival (P = 0.001). However, those in the previous edition were not (P = 0.894, P = 0.144, and P = 0.822, respectively). CONCLUSION: The 8th edition of the UICC-TNM classification predicts postoperative prognosis more precisely than the 7th one in clinical stage 0-IA lung adenocarcinoma. It is probably because the stage distribution of the population, which included in the research project the 8th edition based on, has been changed, and the new edition develops more accurate staging criteria for ground-glass nodule (GGN).

An Unusual Invasive Ectopic Thymoma in the Thyroid and Anterior Mediastinum.

An 81-year-old woman with a 2-year history of dysphagia detected a cervical mass. Computed tomography showed a thyroid tumor extending through the superior and anterior mediastinum. Analysis of an incisional biopsy specimen revealed a thymoma. Total resection of the thyroid and mediastinal tumor was performed. The thymoma invaded the anterior tracheal wall and left brachiocephalic vein. Pathologic examination revealed thymoma type B1 concomitant with B2 and B3 (World Health Organization classification), Masaoka IVb, and T3 N2 M0-IVb, with cervical lymph node metastasis. Clinicians must be cautious during radical operations for invasive ectopic thymomas.

Prognostic significance of the preoperative neutrophil-to-lymphocyte ratio for complete resection of thymoma.

PURPOSE: The preoperative peripheral neutrophil-to-lymphocyte ratio (NLR) is associated with a poor prognosis for various cancers. We evaluated the prognostic role of the preoperative NLR in patients with thymoma. METHODS: We reviewed the medical records of 254 patients who underwent resection of thymic epithelial tumors at our institution. Patients were excluded if they had received steroid therapy, neoadjuvant therapy, or incomplete resection, or if they had thymic carcinoma or Good's syndrome, recurrence of thymoma, or missing data. The NLR was measured preoperatively, and outcomes of patients with a low (< 1.96) vs those with a high (≥ 1.96) NLR were compared statistically. RESULTS: Of 159 eligible patients, 59 (37.1%) had a high NLR and 100 (62.9%) had a low NLR. Overall survival (OS), recurrence-free survival (RFS), disease-specific survival (DSS), disease-related survival (DRS), and the cumulative incidence of recurrence (CIR) differed significantly between the groups. Multivariate analyses revealed that a high NLR was independently associated with disease-related survival and a cumulative incidence of recurrence. A high NLR was also associated with a higher risk of recurrence of Masaoka stage I or II thymoma. CONCLUSIONS: An elevated preoperative NLR was associated with poor outcomes after thymoma resection. Thus, the NLR may be a useful biomarker of the postoperative prognosis of thymoma.

Squamous cell carcinoma of the lung showing a ground glass nodule on high-resolution computed tomography associated with pneumoconiosis: a case report.

BACKGROUND: Adenocarcinoma with lepidic growth pattern presents as a ground glass nodule (GGN) on high resolution computed tomography (CT), whereas peripheral pulmonary squamous cell carcinoma (SCC) usually presents as a solid nodule. We herein report a rare case of pulmonary SCC extending along the alveolar lumen representing as a GGN on a CT scan in a patient with pneumoconiosis. CASE PRESENTATION: A 77-year-old man with pneumoconiosis was found to have a gradually enlarging GGN in the right lower lobe of the lung on CT. An adenocarcinoma of the lung was suspected. The GGN was successfully resected by thoracoscopic segmentectomy. Pathological examination of the resected specimen was pathologically diagnosed as a stage IA SCC extending along the alveolar lumen. The patient had no evidence of recurrence 19 months after surgery. CONCLUSIONS: SCC should be included in the differential diagnosis of peripherally located GGNs, especially in patients at high risk of SCC of the lung such as those with pneumoconiosis.

Bilateral segmentectomies using virtual-assisted lung mapping (VAL-MAP) for metastatic lung tumors.

BACKGROUND: Virtual-assisted lung mapping (VAL-MAP) has been used not only in wedge resection but also in segmentectomy for hardly palpable lung nodules. We herein report a case of bilateral segmentectomy using VAL-MAP with chronological change of pulmonary function test results. CASE PRESENTATION: A 50-year-old female was found to have a colorectal cancer with pulmonary nodules in both sides of the lungs considered as synchronous lung metastases. After sigmoidectomy for primary cancer and chemotherapy, treatments for small nodules in both sides of the lungs were planned. Most nodules were small and supposed to be impalpable. We performed thoracoscopic segmentectomy of right S8 with the aid of VAL-MAP and, after 2 months, combined subsegmentectomy of left S8a and 9a and wide wedge resection of left S8b with the aid of VAL-MAP. All nodules suspected of lung metastases were successfully resected with adequate margins, and the decrease in pulmonary function was minimal compared with predicted postoperative forced vital capacity (FVC) and forced expiratory volume (FEV) 1.0 calculated by the numbers of subsegments. CONCLUSIONS: Bilateral segmentectomies of small impalpable metastatic tumors were performed successfully with the aid of VAL-MAP.

Micropapillary histological subtype in lung adenocarcinoma of 2 cm or less: impact on recurrence and clinical predictors.

OBJECTIVE: This study examined the clinical and radiological characteristics of adenocarcinoma having the micropapillary histological subtype. METHODS: We included 233 patients who were operated from 2001 to 2012 for lung adenocarcinoma of 2 cm or less. The pathology was reviewed according to the 2015 WHO classification. We defined adenocarcinoma with a micropapillary component as adenocarcinoma in which the area of the micropapillary histological subtype exceeded 5% of the tumor. The difference in cumulative incidence of recurrence (CIR) in the presence of death as a competing risk between two groups was assessed using the methods of Gray. RESULTS: Twenty-one cases (9.0%) had a micropapillary component. The micropapillary component was associated with a higher frequency of lymphatic invasion (28.6 vs. 7.5% in adenocarcinoma without a micropapillary component; P = 0.008) and vascular invasion (38.1 vs. 15.1%, P = 0.014) and lymph node metastasis (31.3 vs. 5.2%, P = 0.003). The median follow-up period was 6.5 years. CIR at 5 years was 23.8% [95% confidence interval (CI), 8.3-43.7%] for adenocarcinoma with a micropapillary component, and 11.4% (95% CI, 7.4-16.2%) for adenocarcinoma without a micropapillary component (P = 0.033). Adenocarcinoma with a micropapillary component was more frequent in solid nodules (17.8%, 16/90) on high-resolution computed tomography (HRCT) than in either ground-glass nodules (1.5%, 1/67) or part-solid nodules (5.3%, 4/76) (P = 0.001). The HRCT finding was the only preoperative factor that was associated with a micropapillary component in the multivariate analysis. CONCLUSIONS: The micropapillary component in adenocarcinoma should be regarded as indicative of a high-grade malignancy and was associated with the HRCT finding.

Salvage surgery for primary lung cancer after chemotherapy in octogenarians.

An 81-year-old female patient was admitted to our institute because of abnormal X-ray results. Chest computed tomography showed a 7.7 × 5.3 cm mass located in the left lower lobe and multiple swollen lymph nodes. 18F-fluorodeoxyglucose-positron emission tomography indicated high standard uptake values in the mass and swollen lymph nodes. The patient was diagnosed with stage cT3N2M0-IIIA squamous cell carcinoma. Although the patient had multiple lymph node metastases and severe obstructive pulmonary function, four cycles of platinum doublet chemotherapy were initially performed and no side effect greater than grade 3 was experienced. As the lung cancer was downstaged to ycT2aN0M0-IB and pulmonary function had improved, a bronchodilating preparation, an uneventful left lower lobectomy, and a lymphadenectomy were performed. The patient was discharged 39 days after surgery and exhibited good health for a year at pathological stage ypT1aN0M0-IA (Ef2).

Role of post-mapping computed tomography in virtual-assisted lung mapping.

Background Virtual-assisted lung mapping is a novel bronchoscopic preoperative lung marking technique in which virtual bronchoscopy is used to predict the locations of multiple dye markings. Post-mapping computed tomography is performed to confirm the locations of the actual markings. This study aimed to examine the accuracy of marking locations predicted by virtual bronchoscopy and elucidate the role of post-mapping computed tomography. Methods Automated and manual virtual bronchoscopy was used to predict marking locations. After bronchoscopic dye marking under local anesthesia, computed tomography was performed to confirm the actual marking locations before surgery. Discrepancies between marking locations predicted by the different methods and the actual markings were examined on computed tomography images. Forty-three markings in 11 patients were analyzed. Results The average difference between the predicted and actual marking locations was 30 mm. There was no significant difference between the latest version of the automated virtual bronchoscopy system (30.7 ± 17.2 mm) and manual virtual bronchoscopy (29.8 ± 19.1 mm). The difference was significantly greater in the upper vs. lower lobes (37.1 ± 20.1 vs. 23.0 ± 6.8 mm, for automated virtual bronchoscopy; p < 0.01). Despite this discrepancy, all targeted lesions were successfully resected using 3-dimensional image guidance based on post-mapping computed tomography reflecting the actual marking locations. Conclusions Markings predicted by virtual bronchoscopy were dislocated from the actual markings by an average of 3 cm. However, surgery was accurately performed using post-mapping computed tomography guidance, demonstrating the indispensable role of post-mapping computed tomography in virtual-assisted lung mapping.

An Immunogram for the Cancer-Immunity Cycle: Towards Personalized Immunotherapy of Lung Cancer.

INTRODUCTION: The interaction of immune cells and cancer cells shapes the immunosuppressive tumor microenvironment. For successful cancer immunotherapy, comprehensive knowledge of antitumor immunity as a dynamic spatiotemporal process is required for each individual patient. To this end, we developed an immunogram for the cancer-immunity cycle by using next-generation sequencing. METHODS: Whole exome sequencing and RNA sequencing were performed in 20 patients with NSCLC (12 with adenocarcinoma, seven with squamous cell carcinoma, and one with large cell neuroendocrine carcinoma). Mutated neoantigens and cancer germline antigens expressed in the tumor were assessed for predicted binding to patients' human leukocyte antigen molecules. The expression of genes related to cancer immunity was assessed and normalized to construct a radar chart composed of eight axes reflecting seven steps in the cancer-immunity cycle. RESULTS: Three immunogram patterns were observed in patients with lung cancer: T-cell-rich, T-cell-poor, and intermediate. The T-cell-rich pattern was characterized by gene signatures of abundant T cells, regulatory T cells, myeloid-derived suppressor cells, checkpoint molecules, and immune-inhibitory molecules in the tumor, suggesting the presence of antitumor immunity dampened by an immunosuppressive microenvironment. The T-cell-poor phenotype reflected lack of antitumor immunity, inadequate dendritic cell activation, and insufficient antigen presentation in the tumor. Immunograms for both the patients with adenocarcinoma and the patients with nonadenocarcinoma tumors included both T-cell-rich and T-cell-poor phenotypes, suggesting that histologic type does not necessarily reflect the cancer immunity status of the tumor. CONCLUSIONS: The patient-specific landscape of the tumor microenvironment can be appreciated by using immunograms as integrated biomarkers, which may thus become a valuable resource for optimal personalized immunotherapy.

Mediastinal seminoma associated with multilocular thymic cyst.

An asymptomatic 26-year-old man received an annual medical check-up, and chest X-ray showed a protrusion of the aortopulmonary window. Chest computed tomography (CT) revealed an anterior mediastinal tumor and cysts with thin wall and septum enhancement. The preoperative diagnosis was cystic thymoma or malignant lymphoma. We performed total resection of the tumor through a median sternotomy. The pathological findings revealed seminoma, positive for c-kit stain, and multilocular thymic cysts. Cysts were lined by normal squamous epithelium and no seminoma cells were located on their surface. So, cysts were probably secondary changes caused by seminoma cells themselves or inflammatory stimulations. No invasion to adjacent structures was seen. After the surgery, testicular ultrasound imaging and abdominal, pelvic, and cerebral CT showed no apparent tumor or enlarged lymph nodes; however, an abnormal uptake in the right mesenteric lymph node was pointed out by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan. The patient received four courses of bleomycin, etoposide, and cisplatin (BEP) as adjuvant chemotherapy. Follow-up PET scan revealed no uptake in the right mesenteric lymph node. To date, no recurrence or metastasis has been identified for 16 months.

Prediction and prioritization of neoantigens: integration of RNA sequencing data with whole-exome sequencing.

The importance of neoantigens for cancer immunity is now well-acknowledged. However, there are diverse strategies for predicting and prioritizing candidate neoantigens, and thus reported neoantigen loads vary a great deal. To clarify this issue, we compared the numbers of neoantigen candidates predicted by four currently utilized strategies. Whole-exome sequencing and RNA sequencing (RNA-Seq) of four non-small-cell lung cancer patients was carried out. We identified 361 somatic missense mutations from which 224 candidate neoantigens were predicted using MHC class I binding affinity prediction software (strategy I). Of these, 207 exceeded the set threshold of gene expression (fragments per kilobase of transcript per million fragments mapped ≥1), resulting in 124 candidate neoantigens (strategy II). To verify mutant mRNA expression, sequencing of amplicons from tumor cDNA including each mutation was undertaken; 204 of the 207 mutations were successfully sequenced, yielding 121 mutant mRNA sequences, resulting in 75 candidate neoantigens (strategy III). Sequence information was extracted from RNA-Seq to confirm the presence of mutated mRNA. Variant allele frequencies ≥0.04 in RNA-Seq were found for 117 of the 207 mutations and regarded as expressed in the tumor, and finally, 72 candidate neoantigens were predicted (strategy IV). Without additional amplicon sequencing of cDNA, strategy IV was comparable to strategy III. We therefore propose strategy IV as a practical and appropriate strategy to predict candidate neoantigens fully utilizing currently available information. It is of note that different neoantigen loads were deduced from the same tumors depending on the strategies applied.

Flat Chest of Pleuroparenchymal Fibroelastosis Reversed by Lung Transplantation.

A patient with pleuroparenchymal fibroelastosis (PPFE) was successfully treated with living-donor lobar lung transplantation. A 27-year-old woman with a 3-month history of dyspnea received a diagnosis of PPFE. Her chest wall was extremely flattened over time, and her respiratory condition progressively deteriorated. She underwent semielective bilateral living-donor lobar lung transplantation. Her chest wall rigidity, which was secondary to PPFE, required intensive pulmonary rehabilitation postoperatively. By 6 months after transplantation, the flattening of her chest wall was reversed. Living-donor lobar lung transplantation was a life-saving procedure for this patient and improved the chest wall deformity of PPFE.

Immunohistochemical pattern analysis of squamous cell carcinoma: Lung primary and metastatic tumors of head and neck.

OBJECTIVES: This study aimed to develop an immunohistochemical (IHC) diagnostic algorithm for primary lung squamous cell carcinoma (LSCC) and pulmonary metastasis of head and neck SCC (HNSCC). MATERIALS AND METHODS: We selected three antibodies (CK19, MMP3, and PI3) from a web-based gene expression database and an IHC analysis available online. We developed an IHC diagnostic algorithm using tissue microarrays from 39 LSCCs and 48 HNSCCs as the training set. It was validated using whole tumor sections of 32 LSCCs and 23 HNSCCs. The algorithm was applied to 28 cases with a history of HNSCC and who underwent resection of pulmonary squamous cell tumors. RESULTS: The sensitivity, specificity, and accuracy of the algorithm were 90%, 62%, and 77%, respectively, in the training set and 96%, 44%, and 65%, respectively, in the validation set. Twenty-three of 28 SCCs were diagnosed as metastasis of HNSCC; the remaining five tumors were diagnosed as LSCC. Among the patients in the HNSCC group, 18 developed postoperative recurrence and 11 died of the disease, whereas only one patient in the LSCC group had recurrence. Compared with the LSCC group, the HNSCC group had poorer prognosis (P=0.07). IHC diagnosis coincided with the retrospective diagnosis in 22 (79%) of the 28 patients (sensitivity, 95%; specificity, 44%). CONCLUSION: The IHC diagnostic algorithm may be clinically useful for distinguishing between LSCC and pulmonary metastasis of HNSCC.

Microthymoma in elderly-onset myasthenia gravis detected preoperatively.

A 77-year-old woman with a 3-month history of muscle weakness was diagnosed with elderly-onset generalized myasthenia gravis (Myasthenia Gravis Foundation of America classification IIa) based on a high serum acetylcholine receptor antibody level (25.4 nmol·L-1) and neurological findings. Computed tomography detected a small nodule (diameter 15 mm) in the anterior mediastinum, which was suspected to be a thymoma. An extended thymectomy was performed. The pathological examination revealed a 6-mm-diameter thymoma, termed a microthymoma, accompanied with a unilocular thymic cyst without capsule formation (type B2 according to the World Health Organization classification). Some fat tissue was also found within the tumor.