A case of lung carcinoma with a unique biphasic feature: Implications for histogenesis of "fake mucoepidermoid carcinoma" developing in the peripheral lung.

We present a case of lung carcinoma with a unique biphasic feature. The patient was a 67-year-old male smoker with idiopathic pulmonary fibrosis (IPF). A subpleural tumor in the left lower lobe, embedded in fibrotic tissue, was resected. Histologically, the tumor consisted of major and minor components of mucoepidermoid carcinoma (MEC) and surrounding conventional lepidic adenocarcinoma, respectively. Both components had the same TP53 somatic mutation (p.V157F) but not Mastermind-like 2 (MAML2) gene rearrangement. The two components may have developed from an identical origin. The tumor could be trans-differentiating from lepidic adenocarcinoma to MEC, possibly promoted by IPF-induced tissue damage. The final diagnosis was "adenosquamous carcinoma with mucoepidermoid-like features (that may originate from lepidic adenocarcinoma)." This case has implications for the potential histogenesis of peripheral lung MEC. Over time, the MEC would expand and outgrow the lepidic adenocarcinoma, making it impossible to distinguish between fake and true MEC. The present case suggests that peripheral MEC could differ from proximal MEC in its histogenesis and molecular genetics. Thus, careful examination is necessary to diagnose peripheral lung MEC, particularly in patients with interstitial lung diseases.

Prognostic impact of HNF4α expression in interstitial lung disease.

Pneumocyte injury is a crucial factor influencing the severity of interstitial lung disease (ILD). In this study, we investigated the potential of hepatocyte nuclear factor α (HNF4α) as an immunohistochemical marker to detect pneumocyte injury and as a prognostic marker. Surgical lung biopsy specimens were collected from 309 patients with different types of ILDs (61 idiopathic pulmonary fibrosis (IPF), 173 non-IPF, and 75 unclassifiable ILD). HNF4α expression were examined and the frequency of positive cells (per mm2 ) was calculated. HNF4α was strongly expressed in regenerating pneumocytes present on fibroblastic foci, Masson bodies/organizing alveoli. In the non-IPF and unclassifiable ILD groups, cases with high frequency expression showed significantly poorer outcome. Particularly, in the unclassifiable ILD group, the prognostic impact was more significant (death due to ILD, log-rank test, p < 0.0001), with a 10-year survival rate (hazard ratio 11.1, Wald test, p = 0.0003), as compared to the non-IPF group (log-rank test, p = 0.0269; hazard ratio 2.7, Wald test, p = 0.0334). Multivariable analysis focusing on the unclassifiable ILD group confirmed that the frequent HNF4α expression was an independent prognostic factor (hazard ratio 28.6; Wald test, p = 0.0033). Thus, HNF4α can be utilized as an immunohistochemical marker for pneumocyte injury and have prognostic impact particularly in unclassifiable ILD.

The nonsmokers' and smokers' pathways in lung adenocarcinoma: Histological progression and molecular bases.

There could be two carcinogenetic pathways for lung adenocarcinoma (LADC): the nonsmokers' pathway and the smokers' pathway. This review article describes the two pathways with special reference to potential relationships between histological subtypes, malignant grades, and driver mutations. The lung is composed of two different tissue units, the terminal respiratory unit (TRU) and the central airway compartment (CAC). In the nonsmokers' pathway, LADCs develop from the TRU, and their histological appearances change from lepidic to micropapillary during the progression process. In the smokers' pathway, LADCs develop from either the TRU or the CAC, and their histological appearances vary among cases in the middle of the progression process, but they are likely converged to acinar/solid at the end. On a molecular genetic level, the nonsmokers' pathway is mostly driven by EGFR mutations, whereas in the smokers' pathway, approximately one-quarter of LADCs have KRAS mutations, but the other three-quarters have no known driver mutations. p53 mutations are an important factor triggering the progression of both pathways, with unique molecular alterations associated with each, such as MUC21 expression and chromosome 12p13-21 amplification in the nonsmokers' pathway, and HNF4α expression and TTF1 mutations in the smokers' pathway. However, investigation into the relationship between histological progression and genetic alterations is in its infancy. Tight cooperation between traditional histopathological examinations and recent molecular genetics can provide valuable insight to better understand the nature of LADCs.

A method to obtain reproducible Ki-67 indices in lung adenocarcinoma.

AIMS: Proliferative activity, evaluated from the Ki-67 index, is a strong prognostic factor in lung adenocarcinoma (LADC). Here, we optimised a procedure to measure the Ki-67 index and establish the best cut-off value. METHODS AND RESULTS: We examined 342 stage I LADCs for the immunohistochemical expression of Ki-67 using different antibodies, MIB1 and SP6. The results revealed the superior specificity of SP6; therefore, SP6 was used in subsequent analyses. Slides were scanned with a virtual slide system. Using software, tumour cells were counted in a whole tumour. Thereafter, the tumour was evenly subdivided into 0.25-mm2 tiles. The frequency of positive cells was counted in each tile of an invasive area or the whole tumour. We calculated the number of tumour cells required to produce a 95% confidence interval (CI) <0.05. Additionally, we calculated coverage probabilities (CP) using two different methods, counting any number or 200 cells per tile. The results showed that we could meet our goal by counting 2000 cells from 10 random tiles (200 cells each) in invasive areas. CONCLUSIONS: We successfully developed an optimal procedure for determination of the Ki-67 labelling index using an SP6 antibody, which provided CP > 70% and CI of <0.05 in more than 90% of cases. Furthermore, we identified an optimal cut-off value of 0.12 with an alternative of 0.15, based on disease recurrence. This procedure and the cut-off values may be used in the routine pathological diagnosis of LADC.

A prophylaxis study of acute exacerbation of interstitial pneumonia after lung cancer surgery.

INTRODUCTION: Acute exacerbation of interstitial pneumonia (AE-IP) is a lethal complication after lung surgery. We conducted a prospective, multi-institutional phase II trial to assess the efficacy and safety of prophylactic measures. METHOD: Patients with lung cancer with dorsal subpleural fibrotic changes occupying three or more segments of both lower lobes and planned anatomical lung resection were enrolled. Prior to surgery, patients received a 125-mg bolus injection of methylprednisolone and continuous intravenous infusion of sivelestat sodium hydrate (sivelestat) for 2 days. RESULTS: Sixty-nine patients were analysed. Preoperative high-resolution computed tomography (HRCT) showed 37 (53.6%) cases presented with usual interstitial pneumonia (UIP) and possible UIP pattern. There were 60 lobectomies and 9 segmentectomies. Thirty-eight cases were in clinical stage I. No adverse events associated with prophylaxis were observed. There were four cases of AE-IP (5.8%), higher than the expected 2.0%. Three of the four cases showed inconsistencies with the UIP pattern in preoperative HRCT and were pathologically diagnosed as UIP. All patients died of respiratory failure. Overall, 89.9% were diagnosed as idiopathic interstitial pneumonias; UIP was found in 48 patients (69.6%). Severe post-operative complications occurred in 11.6% of the cases. There were 35 deaths, 17 cases of lung cancer and 11 cases related to interstitial pneumonias. The overall survival rate at 3 years was 41.8% of the total and 47.2% of cases with clinical stage I. CONCLUSIONS: Perioperative use of sivelestat and low-dose methylprednisolone in patients with anatomical lung resection was safe but did not prove to be a prophylactic effect for AE-IP.

Update on the potential significance of psammoma bodies in lung adenocarcinoma from a modern perspective.

AIMS: Psammoma bodies are concentrically lamellated microscopic structures made of calcium. They are commonly observed in papillary carcinomas of the thyroid gland and serous papillary adenocarcinomas of the ovary, but are also occasionally detected in lung adenocarcinomas. Only one study, published in 1972, has systematically described the significance of psammoma bodies in lung adenocarcinomas. The aim of this study was to update the significance of psammoma bodies in lung adenocarcinomas from a modern perspective. METHODS AND RESULTS: Psammoma bodies were detected in 7.2% (59/822) of the adenocarcinomas examined, among which the papillary (20.3%, 12/59) and acinar (44.1%, 26/59) histological subtypes, with the feature of a terminal respiratory unit (91.5%, 54/59), were dominant. Malignant potential (cell growth activity measured by Ki67 labelling, lymph node metastasis, and postoperative survival) did not significantly differ between adenocarcinomas with and without psammoma bodies. On the basis of cytogenetic features, adenocarcinomas with psammoma bodies were preferentially affected by tyrosine kinase inhibitor (TKI)-targetable driver mutations [EGFR (69.8%, 37/53), ALK (13.2%, 7/53), and ROS1 (1.9%, 1/53)]. Multivariate analyses confirmed that psammoma bodies may constitute an independent predictor for these mutations, particularly EGFR and ALK mutations. CONCLUSIONS: Psammoma bodies may predict a favourable response of lung adenocarcinomas to TKIs.

A molecular pathological study of four cases of ciliated muconodular papillary tumors of the lung.

Ciliated muconodular papillary tumors (CMPTs) are a recently categorized benign or low-grade malignant neoplasm that develops in the peripheral lung. Only about 40 cases have been reported to date, and the clinicopathological characteristics have yet to be defined in detail. Here, we present four cases of CMPTs with a focus on their immunohistochemical profiles and driver gene mutations. These tumors were a papillary proliferation of a mixture of ciliated, mucous, and basal cells located in the peripheral lung. Ciliated, mucous and basal cells were positive for TTF-1 when using the clone SPT24, but negative for HNF-4α. Basal cells were positive for p40. Mucous cells in some tumors were positive for MUC5AC and MUC6. The Ki-67 index was less than 5%, and strong expression of p53 was not detected. Three of the four tumors had a BRAF (V600E) driver mutation, an EGFR (del E746-T751/S752V) driver mutation, or driver mutations in both EGFR (E709G) and KRAS (G12V). These mutation types are rare for any histological type of lung cancer. The present results confirmed that CMPT is a neoplasm with immunohistochemical features and driver gene mutations that are distinct from those of common lung tumors.

The pathological features of idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas.

AIMS: To investigate the pathological features of idiopathic interstitial pneumonia (IIP)-associated pulmonary adenocarcinoma. METHODS AND RESULTS: Surgically resected adenocarcinomas associated with IIP (the IIP group) and adenocarcinomas without IIP (the non-IIP group) were subjected to analysis. Adenocarcinomas in the IIP group were subdivided into two groups: one group included tumours connected to bronchiolar metaplasia in honeycomb lesions (the H-IIP group), and the other included tumours unrelated to honeycomb lesions (the NH-IIP group). Histomorphological appearance and immunohistochemical expression were compared among the H-IIP group, the NH-IIP group, and the non-IIP group. Most of the tumour cells in the H-IIP group had a tall, columnar shape that showed similar features to proximal bronchial epithelium, whereas tumour cells in the NH-IIP group and the non-IIP group had a club-like shape that showed similar features to respiratory bronchiolar/alveolar epithelium. Adenocarcinomas in the H-IIP group tended to be negative for thyroid transcription factor-1 (TTF-1) and positive for hepatocyte nuclear factor-4α (HNF-4α). The frequency of EGFR mutations was significantly lower in adenocarcinomas in the H-IIP group, although the frequencies of KRAS and ALK mutations did not differ among the three groups. CONCLUSIONS: Idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas, especially those arising from honeycomb lesions, have distinct pathological features.

The potential significance of alpha-enolase (ENO1) in lung adenocarcinomas - A utility of the immunohistochemical expression in pathologic diagnosis.

We herein analyzed the relationships among the immunohistochemical expression of alpha-enolase (ENO1) and clinicopathological factors in order to define the significance of ENO1 in lung adenocarcinomas (ADCs). ENO1 expression was detected in most of the ADCs examined (95.8%), but not in bronchial and alveolar epithelia. ENO1 expression was typically observed in the cytoplasm among most ADCs (95.8%), but was also detected in the nucleus (56.3%). The levels were significantly higher in terminal respiratory unit (TRU) cytological subtype ADCs. Neither cytoplasmic nor nuclear expression was associated with any other clinicopathological factors including post-operative survival and growth activity. These results suggest that ENO1 is a crucial factor promoting neoplastic transformation exclusively in TRU subtype ADCs. We also investigated the potential utility of the immunohistochemical expression of ENO1 to differentiate TRU-type ADC cells from the reactive hyperplasia of pneumocytes and bronchiolar epithelial cells because difficulties are associated with discriminating these lesions in small biopsy specimens. The sensitivity and specificity of ENO1 (cytoplasmic/nuclear) were 87.5%/37.5% and 88.9%/100%, respectively, which are superior to those of p53 (18.8% and 100%). ENO1 has potential as a biomarker to assist in the histopathological detection of TRU subtype ADC cells.

Alterations in cathepsin L expression in lung cancers.

We herein investigated the potential role of cathepsin L in lung carcinogenesis. Lung cancer cell lines and surgically resected tumors were examined for the expression of the cathepsin L protein and copy number alterations in its gene locus. Cathepsin L was stably expressed in bronchiolar epithelial cells. Neoplastic cells expressed cathepsin L at various levels, whereas its expression was completely lost in most of the lung cancer cell lines (63.6%, 7/11) examined. Furthermore, expression levels were lower in a large fraction of lung tumors (69.5%, 139/200) than in bronchiolar epithelia. The expression of cathepsin L was lost in some tumors (16.0%, 32/200). In adenocarcinomas, expression levels were significantly lower in high-grade tumors than in low-grade tumors (one-way ANOVA, P < 0.0500). Copy number alterations were found in 18.0% (36 [32 gain + 4 loss] /200) of lung tumors. No relationship existed between cathepsin L protein expression levels and the copy number of its gene locus (Spearman's rank-order correlation, P = 0.3096). Collectively, these results suggest that the down-regulated expression of cathepsin L, which is caused by an undefined mechanism other than copy number alterations, is involved in the progression of lung adenocarcinomas.

Pericardial ectopic thymoma presenting with cardiac tamponade: report of a case.

Ectopic thymoma arising from organs other than the thymus, such as the neck, trachea, thyroid, lung and pericardium, is rare. To date, there have been only seven other cases of pericardial thymoma reported in the English literature. We herein report a case of pericardial ectopic thymoma that presented with cardiac tamponade. A 72-year-old Japanese male noticed body weight gain and leg edema. Chest computed tomography (CT) revealed pericardial effusion and an irregularly shaped mass in the pericardial space compressing the right atrium. He was considered to have cardiac tamponade due to a paracardiac tumor that developed following acute cardiac failure. The intraoperative frozen diagnosis was thymoma. Pericardectomy of the thickened pericardium, tumorectomy and thymectomy via a median sternotomy were performed. The final pathological diagnosis was pericardial ectopic thymoma associated with constrictive pericarditis. The differential diagnosis and complete resection of mediastinal tumors such as this rare case of thymoma are important to obtain a better prognosis, as patients with such tumors often present in a state of shock.

Favourable surgical outcomes for either second primary lung cancer or intrapulmonary metastasis after resection of non-small-cell lung cancer.

OBJECTIVES: Metachronous lung cancer arising after resection of non-small-cell lung cancer is either a second primary lung cancer (SPLC) or intrapulmonary metastasis (IPM) of the initial lung cancer; however, differential diagnosis is difficult. We evaluated the surgical outcomes of metachronous lung cancer in a combined population of patients with SPLC and IPM. METHODS: A retrospective study of 3534 consecutive patients with resected non-small-cell lung cancer between 1992 and 2016 was conducted at 4 institutions. RESULTS: A total of 105 patients (66 males; median age, 70 years) who underwent a second pulmonary resection for metachronous lung cancer were included. Most patients (81%) underwent sublobar resection, and there was no 30-day mortality. All metachronous lung cancers were cN0, 5 were pN1-2. The postoperative comprehensive histologic assessment revealed SPLC (n = 77) and IPM (n = 28). The 5-year overall survival rate after the second resection was 70.6% (median follow-up: 69.7 months). A multivariable analysis showed that age >70 years at the second resection (P = 0.013), male sex (P = 0.003), lymph node involvement in metachronous cancer (P < 0.001), pathological invasive size of metachronous cancer >15 mm (P < 0.001) and overlapping squamous cell carcinoma histology of the initial and metachronous cancers (P = 0.003) were significant prognostic factors for poor survival after the second resection, whereas histological IPM was not (P = 0.065). CONCLUSIONS: Surgery for cN0 metachronous lung cancer is safe and shows good outcomes. There were no statistically significant differences in the SPLC and IPM results. Caution should be exercised when operating on patients with overlapping squamous cell carcinoma.

A distinctive cytomorphological feature of interstitial pneumonia-related lung adenocarcinoma: The potential issues and solutions in practical diagnosis.

BACKGROUND: The cytological features of interstitial pneumonia (IP)-related lung adenocarcinoma (LADC) have not been clearly described. This study aimed to describe its cytomorphological features, uncover potential problems in practical cytological diagnosis, and provide possible solutions. METHODS: Bronchial brushing cytology samples from 40 IP-related LADC cases (the IP group) and 110 control cases (LADC unrelated to IP; the non-IP group) were analyzed. All patients underwent surgery after brushing cytology, and their histopathological subtypes were determined. The authors reviewed the cytological features and focused particularly on cytoplasmic mucin production. RESULTS: In the IP group, neoplastic cells with cytoplasmic mucin were detected at a significantly higher frequency (44.4% [8 of 18] vs. 6.3% [4 of 64]), and most of them were invasive mucinous adenocarcinomas (IMAs). Twenty-two of the 40 LADC cases in the IP group failed to be judged as "malignant/positive" (thus, they were judged to be "equivocal and/or negative"). The frequency of equivocal and/or negative judgments was 55.0% (22 of 40) in the IP group and 41.8% (46 of 110) in the non-IP group. The cytological diagnosis of IMA was difficult because it showed only slight nuclear atypia. Therefore, the authors examined the immunocytochemical expression of hepatocyte nuclear factor 4α (HNF4α), a diagnostic marker for IMA. As a result, four of the six cases that were judged to be equivocal in the IP group showed positive signals and could be retrospectively judged as malignant/positive. CONCLUSIONS: The cytological diagnosis of IP-related LADC may be more difficult because of the larger proportion of IMA. Immunocytochemistry for HNF4α can be used to improve diagnostic confidence in IP-related LADC.

Significant accumulation of KRAS mutations in bronchiolar metaplasia-associated honeycomb lesions of interstitial pneumonia.

Interstitial pneumonia (IP) is a major risk factor for lung adenocarcinoma (LADC). IP-related LADC predominantly develops in the bronchiolar metaplasia lining in honeycomb lesions. Kirsten rat sarcoma virus (KRAS) is the most common oncogene mutated in IP-related LADC. The present study examined the metaplastic epithelia in honeycomb lesions for KRAS mutations using digital droplet polymerase chain reaction (ddPCR), a sensitive method used to detect infrequent mutations. Significantly higher KRAS mutation variant allele frequencies (VAFs) were detected in the metaplastic lung epithelia from 13 patients with IP compared with those in 46 non-lesioned lung samples from patients without IP (G12V, P=0.0004, G12C, P=0.0181, and G12A, P=0.0234; Mann Whitney U test). Multivariate analyses revealed that higher KRAS G12V (logistic regression model; P=0.0133, odds ratio=7.11) and G12C (P=0.0191, odds ratio=5.81) VAFs in patients with IP were independent of confounding variables, such as smoking and age. In patients with IP, metaplastic epithelia exhibited significantly higher KRAS G12V and G12C VAFs compared with the non-lesioned counterparts (paired t-test; G12V, P=0.0158, G12C, P=0.0465). These results suggested that IP could increase KRAS mutations and supported the hypothesis that bronchiolar metaplasia could be a precursor for IP-related LADC.

Implications of thyroid transcription factor-1 gene methylation in carcinogenesis of interstitial pneumonia-related non-terminal respiratory unit lung adenocarcinoma.

The present study aimed to elucidate the mechanisms underlying the histogenesis of interstitial pneumonia (IP)-related lung adenocarcinoma (LADC). We focused on the methylation of thyroid transcription factor 1 (TTF-1). The TTF-1 locus was highly methylated in IP-LADCs compared to non-IP-LADCs. Among the IP-LADCs, the non-terminal respiratory unit (TRU) LADCs showed marked hypermethylation in CpG sites in a particular intragenic region. This region was also found to be highly methylated in the IP lungs. The hierarchical dendrogram based on methylation levels divided the IP lungs into three different clusters. One of them showed a methylation profile similar to that of non-TRU LADCs. The non-TRU LADCs developed from this cluster with a significantly higher frequency. Moreover, bronchiolar metaplasia lining honeycomb/cystic lesions in IP lungs, IP-related non-TRU LADCs, and bronchiolar epithelia in healthy lungs were separately collected by microdissection and examined for methylation. Bronchiolar metaplasia showed hypermethylation, but bronchiolar epithelia did not. The methylation patterns in bronchiolar metaplasia were similar to those in non-TRU LADCs. In summary, a particular region of TTF-1 was highly methylated in IP-related non-TRU LADCs and bronchiolar metaplasia, supporting the theory that IP-related non-TRU LADCs may develop from bronchiolar metaplasia lining honeycomb/cystic lesions.

Radiological unilateral pleuroparenchymal fibroelastosis as a notable late complication after lung cancer surgery: incidence and perioperative associated factors.

OBJECTIVES: Pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial pneumonia characterized by pleural-parenchymal involvement, predominantly in the upper lobes. Unilateral upper lung field pulmonary fibrosis (upper-PF) that is radiologically consistent with PPFE reportedly develops after lung cancer surgery in the operated side and presents many clinical characteristics in common with PPFE. However, the incidence and perioperative associated factors remain unclear. METHODS: All consecutive patients with lung cancer resected completely from 2008 to 2016 were investigated retrospectively. Pre-/postoperative characteristics were compared between patients with and without unilateral upper-PF. Cumulative incidence curves were estimated using competing risk analysis. RESULTS: Among the 587 included patients, 25 patients (4.3%) were diagnosed as unilateral upper-PF. The 3-, 5- and 10-year cumulative incidence of unilateral upper-PF was 2.3%, 3.3% and 5.3%, respectively. In multivariable analysis, male sex, presence of a pulmonary apical cap, lobar resection and low % vital capacity (%VC < 80%) were independent perioperative associated factors. The 10-year cumulative incidence was 6.3% in patients treated with lobar resection, 8.0% in male patients, 10.3% in patients with pulmonary apical cap and 14.5% in patients with low %VC. Postoperative pleural effusion at 6 months after surgery was much more common in the patients who later developed unilateral upper-PF (96.0% vs 24.2%). This pleural effusion persisted and was accompanied thereafter by pleural thickening and subpleural pulmonary fibrosis. During the clinical courses of 25 patients with unilateral upper-PF, 18 patients presented symptoms related to upper-PF and 6 patients died. CONCLUSIONS: Unilateral upper-PF is an occasional but under-recognized late complication after lung cancer surgery.

Frequent DYRK2 gene amplification in micropapillary element of lung adenocarcinoma - an implication in progression in EGFR-mutated lung adenocarcinoma.

The present study aimed to discern the molecular alterations involved in the progression of EGFR-mutated lung adenocarcinoma (LADC). We previously demonstrated that the micropapillary (mPAP) element is the most important histological factor for assessing malignant grades in LADCs. Therefore, mPAP and other elements were separately collected from three cases of EGFR-mutated LADC using laser capture microdissection and subjected to a comprehensive mRNA expression analysis. We focused on DYRK2 in this study because its level showed a substantial increase in EGFR-mutated LADCs with mPAP. We also immunohistochemically examined 130 tumors for the expression of DYRK2. The results confirmed a strong expression of DYRK2 in EGFR-mutated LADC with mPAP. Fluorescent in situ hybridization (FISH) analyses targeting the DYRK2 locus revealed frequent gene amplification in EGFR-mutated LADC, specifically occurring in the high-grade components, like mPAP. In summary, the results of this study suggest that DYRK2 overexpression through gene amplification is one of the molecular mechanisms responsible for promoting the progression of EGFR-mutated LADC.

Intermediate bronchial kinking after right upper lobectomy for lung cancer.

BACKGROUND: Bronchial kinking after lung lobectomy is likely, whereas that of the intermediate bronchus after right upper lobectomy is often not recognized. The aim of this study was to examine the clinical implications of this condition. METHODS: One-hundred cases of right upper lobectomy for primary lung cancer were reviewed. The cases were divided into groups with intermediate (group A) and non-intermediate (group B) bronchial kinking, and the patient characteristics and postoperative outcomes were compared. The remaining lower lobe deformation was also evaluated using the angle formed by the intrathoracic tracheal line and posterior fissure on reconstructed sagittal computed tomography. RESULTS: There were 23 cases in group A which had a higher rate of bronchial calcification, older age, and female sex, whereas and smoking and pulmonary emphysema were less frequent. Three cases in group A had respiratory symptoms such as wheezing and respiratory noise, while only one case of middle lobe atelectasis was found in group B. In multivariate analysis, upper mediastinal lymph node dissection was an independent factor for non-intermediate bronchial kinking. The lower lobe was significantly more expanded in group A than in group B. CONCLUSIONS: Intermediate bronchial kinking correlates with postoperative respiratory symptoms and was less likely after upper mediastinal lymph node dissection.

A spectrum of Thymic mucosa-associated lymphoid tissue lymphoma and Thymic amyloidosis in the patient with Auto immune disease: a case series.

BACKGROUND: The thymus is associated with an immunodeficient status, autoimmune disease (AD), and the common thymic tumor, thymoma. We encountered two rare thymic tumors, thymic mucosa-associated lymphoid tissue (MALT) lymphoma and localized thymic amyloidosis, both in the presence of Sjögren's syndrome (SjS). This suggests a possible link between rare thymic tumors and SjS. Therefore, we reviewed cases of thymic tumors to examine the spectrum of these tumors in patients with AD. METHODS: The clinical information of thymic amyloidosis and MALT lymphoma surgically treated at Kanagawa Cardiovascular and Respiratory Center, and Yokohama City University Hospital from January 2010 to December 2019 were reviewed. The correlation between resected thymic tumors at same period and ADs were also investigated. RESULTS: There were 5 cases of thymic amyloidosis and MALT lymphoma. ALL cases had coexistent ADs (4 SjS, 1 SSc). The median age was 66 (38-76) year-old, and 4 of the patients were female. Three cases had already diagnosed as ADs before detection of tumors. Only SSc case was received preceding steroid medication. Two cases diagnosed as SjS at the same time of the operation. The median maximum tumor diameter was 70 mm. On chest computed tomography (CT), tumors contained solid part and some cystic part at various rated. Calcification was recognized with appearance of amyloid deposition. All patients were surgically treated with total thymectomy and they are alive without recurrence. At the same period, there were 163 resected thymic tumors, including amyloidosis, MALT lymphoma, thymoma, thymic cancer, neuroendocrine tumor and so on. Among them, nine patients (5.5%) had ADs. There was a correlation between ADs and thymic MALT lymphoma/amyloidosis (P<0.001). CONCLUSIONS: We propose a process for tumorigenesis of thymic MALT lymphoma and amyloidosis. Underlying AD causes persistent and chronic inflammatory reactions. In this theory, ADs, especially SjS, might be important underlying conditions in formation of rare tumors. When the clinician encounters a patient with AD, routine chest CT is recommended and may provide thymic tumors. Conversely, in case of mediastinum tumor, screening test for AD is also recommended.