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Background Tissue harvesting for patients with a lung nodule is sometimes unsuitable due to the size and location of the nodule. In such cases, it is unclear whether it is acceptable to proceed to definitive lobectomy without intraoperative frozen section analysis. Methods We retrospectively reviewed patients who underwent definitive lobectomy or wedge resection for frozen section analysis at our institution between 2014 and 2018. The sensitivity, specificity, and accuracies of the clinical and frozen section diagnoses were evaluated against the final pathological diagnosis. Results There were 141 patients in the definitive lobectomy group and 58 patients in the frozen section analysis group, with the latter having smaller and less deep nodules and a lower rate of malignancy on clinical and final pathological diagnoses. The sensitivity, specificity, and accuracy of the clinical diagnosis were 100%, 82%, and 95%, respectively, in the frozen section analysis group and 99%, 67%, and 97%, respectively, in the definitive lobectomy group; values of frozen section diagnosis were 98%, 82%, and 93%, respectively. On subgroup analysis, all ground‐glass nodules clinically diagnosed as malignant had a final pathological diagnosis of malignancy. Conclusions The accuracy of the clinical diagnosis was high and was not inferior to the frozen section diagnosis. These data suggest that definitive lobectomy is an acceptable treatment option for carefully selected patients with large or deep nodules and ground‐glass nodules clinically diagnosed as malignant. To avoid unnecessary lobectomy, frozen section diagnosis should be considered for nodules likely to be benign. Key points Significant findings of the study The accuracy of the clinical diagnosis was high and was not inferior to the frozen section diagnosis. What this study adds Definitive lobectomy is an acceptable treatment option for carefully selected patients with large or deep nodules and ground‐glass nodules with a clinical diagnosis of malignancy.

Programmed death‐ligand 1 (PD‐L1) is an immune modulator that promotes immunosuppression by binding to programmed death‐1 of T‐lymphocytes. Although tumor cell PD‐L1 expression has been shown to be associated with the clinical response to anti–PD‐L1 antibodies, its concise regulatory mechanisms remain elusive. In this study, we evaluated the associations of tumor PD‐L1 expression and immune cell infiltrating patterns in 146 cases of early lung adenocarcinoma (AC) to investigate the possible extrinsic regulation of tumor PD‐L1 by immune cells. Using immunohistochemistry, cell surface PD‐L1 expression in tumor cells was observed in 18.5% of stage 0‐IA lung AC patients. Tumor PD‐L1 positivity was significantly associated with stromal invasion, which was accompanied by increased tumor‐associated macrophages (TAM), CD8+ cytotoxic T cells and FoxP3+ regulatory T cells. Among these immune cells, TAM and CD8+ T cells significantly accumulated in PD‐L1‐positive carcinoma cell areas, which showed a tumor cell nest‐infiltrating pattern. Although CD8+ T cells are known to induce tumor PD‐L1 expression via interferon‐ɣ production, the increased TAM within tumors were also associated with tumor cell PD‐L1 positivity, independently of CD8+ T cell infiltration. Our in vitro experiments revealed that PD‐L1 expression in lung cancer cell lines was significantly upregulated by co–culture with M2‐differentiated macrophages; expression of PD‐L1 was reduced to baseline levels following treatment with a transforming growth factor‐β inhibitor. These results demonstrated that tumor‐infiltrating TAM are extrinsic regulators of tumor PD‐L1 expression, indicating that combination therapy targeting both tumor PD‐L1 and stromal TAM might be a possible strategy for effective treatment of lung cancer., In this study, we showed that tumor‐associated macrophage (TAM) infiltration was an additional factor related to tumor programmed death‐ligand 1 (PD‐L1) expression in early lung adenocarcinoma. Our in vitro experiments demonstrated that M2‐differentiated macrophages facilitated tumor PD‐L1 expression through transforming growth factor‐β. These results suggested that TAM were extrinsic regulators of tumor PD‐L1 expression and could serve as potential therapeutic targets.

ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells.

Background Pulmonary metastasectomies are performed for a variety of cancers, though few reports have examined their merit for head and neck cancers. This study examined the relationship between clinical and pathological characteristics and survival after resection of lung metastases of these cancers. Methods Between 1986 and 2013, 34 patients presenting with pulmonary metastases of primary head or neck cancers underwent surgical resections at our institution. We retrospectively analyzed their clinical and pathological characteristics and the patients' survival after metastasectomy in search of adverse prognostic factors. Results The primary sites of cancer were: the tongue in eight patients, the pharynx and salivary glands each in seven, the larynx in five, and miscellaneous sites in seven patients. Squamous cell carcinoma (SCC) was present in 19, adenoid cystic carcinomas in 10, and other diagnoses in five patients. The median disease-free interval (DFI) between the initial surgery and the metastasectomies was 40 months. The overall five-year survival rate was 57.9%, and median survival time was 77 months. By single variable analysis, a DFI of ≤26 months, age ≥60 years, and histology of SCC were predictors; by multiple variable analysis, a short DFI (P = 0.018) and older age (P = 0.046) remained independent predictors of poor clinical outcomes. Conclusions Young age and a long DFI are factors in favor of pulmonary metastasectomy after surgical treatment of primary head or neck cancers.

A collision tumor of the lung is relatively rare. We report a case of a 72-year-old man with a collision tumor consisting of three neoplastic components in the underlying interstitial lung disease. Computed tomography showed a parenchymal lesion with an air bronchogram. Transthoracic needle lung biopsy showed chronic inflammation, however, a malignant pulmonary tumor was clinically suspected. The patient underwent a right lower lobectomy with mediastinal lymph node dissection. The histological features of the surgical specimen showed lung cancer with three neoplastic components, which were squamous cell carcinoma, invasive mucinous adenocarcinoma, and invasive non-mucinous adenocarcinoma. To the best of our knowledge, this is the first documentation of a collision lung tumor with three components.

Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma rarely occurs. It is difficult to distinguish MALT lymphomas and pre-invasive lesions according to radiological findings. We report a case of 60-year-old woman who was found to have a rapidly growing ground glass nodule (GGN) on her left lower lobe, discovered on follow-up chest computed tomography. The radiological image was pure GGN, which was compatible with a pre-invasive lesion, such as non-mucinous adenocarcinoma in situ. Wedge resection was performed and the final diagnosis was stage I MALT lymphoma. After surgery, she was doing well with no evidence of recurrence one year later. We believe a lung biopsy for rapidly growing GGN is recommended in order to confirm the pathological diagnosis.

BACKGROUND. [18F]Fluoro-2-deoxyglucose uptake on positron emission tomography (FDG-PET) has been frequently used for diagnosis and staging of lung cancer. The prognostic significance of FDG uptake on PET was evaluated in patients with pathologic Stage I lung adenocarcinoma (tumor stages were based on the TNM classification of the International Union Against Cancer). METHODS. Disease-free survival of 98 patients with pathologic Stage I lung adenocarcinoma who were treated by curative resection was examined in relation to sex, age, histologic grade of differentiation, surgical procedure, tumor stage, and FDG uptake measured as the maximum standardized uptake value (SUV). RESULTS. Sixty-three patients were had Stage IA disease and 35 patients had Stage IB disease. Six patients each with Stage IA and Stage IB disease developed disease recurrence after a mean postsurgical follow-up period of 31 months. Ten (23%) of the 43 patients with SUV ≥ 3.3 developed a recurrence compared with 2 (4%) of the 55 patients with SUV < 3.3 (P = .020). Ten (20%) of the 51 patients with moderately or poorly differentiated adenocarcinoma developed disease recurrence, compared with 2 (4%) of the 47 patients with well-differentiated adenocarcinoma (P = .056). Multivariate analysis demonstrated that histologic grade of differentiation was not correlated with the frequency of tumor recurrence (P = .286), whereas SUV was found to be marginally correlated (P = .079). CONCLUSIONS. FDG uptake appears to be predictive of disease-free survival in patients with Stage I lung adenocarcinoma. FDG uptake could yield important information for determining the likely value of postoperative adjuvant chemotherapy in such patients. Cancer 2006. © 2006 American Cancer Society.