Pulmonary inflammatory leiomyosarcoma represents a potential diagnostic pitfall of DNA methylation-based classification of sarcomas: a case report.

BACKGROUND: Pulmonary inflammatory leiomyosarcoma (PILMS) is a rare type of myogenic tumor with prominent lymphohistiocytic infiltration. Despite their histological similarities, PILMS is immunohistochemically and genetically distinct from soft tissue inflammatory leiomyosarcoma, and its clinicopathological picture including DNA methylome data remains still unknown. CASE PRESENTATION: Here we present a case of PILMS in an 18-year-old male who underwent lobectomy. As reported previously, the current case demonstrated spindle myoid cell proliferation with smooth muscle differentiation within a prominent lymphohistiocytic infiltration and a diploid genome with a MUC3A gene alteration. DNA methylation analysis predicted this case to be an "inflammatory myofibroblastic tumor" (IMT) according to the Deutsches Krebsforschungszentrum (DKFZ) classifier. The data was analyzed by t-distributed stochastic neighbor embedding, which plotted the case tumor in the vicinity of IMT, however, there were no IMT histological features. These discordant results could be due to background non-neoplastic inflammatory cells. CONCLUSIONS: As the DNA methylation classification of PILMS might be a potential diagnostic pitfall, an integrative histological and genetic approach is required for its accurate diagnosis.

Surgical resection in patient with teratoma with somatic-type malignancy transformed into rhabdomyosarcoma resulted in long-term survival.

Introduction: Testicular germ cell tumors with somatic-type malignancy, wherein teratomas transform into sarcomas, is drug resistant and has a poor prognosis. Case presentation: A 43-year-old man presented with a left testicular tumor, multiple pulmonary metastases, and mediastinal and para-aortic lymph node metastases. The testicular tumors were diagnosed as germ cell tumors. After bleomycin, etoposide, and cisplatin chemotherapy; right upper lobectomy for the pulmonary metastasis; and paclitaxel, ifosfamide, and cisplatin chemotherapy, rapidly progressing mediastinal lymph node metastasis was observed. It was resected at another specialized center owing to the challenging surgical approach. The histopathological diagnosis of the resected tumor was a teratoma with somatic-type malignancy (rhabdomyosarcoma). Subsequently, left hilar lymph node metastasectomy and left upper lobectomy were performed for the pulmonary metastases. The patient survived for more than 8 years after initial treatment. Conclusion: Surgery, although challenging, may yield long-term survival for patients with testicular germ cell tumors with sarcomatous transformation.

A rad50 germline mutation induces tumorigenesis and ataxia-telangiectasia phenotype in a transparent medaka model.

The MRE11A-RAD50-NBS1 complex activates the ataxia-telangiectasia mutated (ATM) pathway and plays a central role in genome homeostasis. The association of RAD50 mutations with disease remains unclear; hence, we adopted a medaka rad50 mutant to demonstrate the significance of RAD50 mutation in pathogenesis using the medaka as an experimental animal. A 2-base pair deletion in the rad50 gene was introduced into transparent STIII medaka using the CRISPR/Cas9 system. The mutant was analyzed histologically for tumorigenicity and hindbrain quality, as well as for swimming behavior, to compare with existing ATM-, MRE11A-, and NBS1-mutation-related pathology. Our results revealed that the medaka rad50 mutation concurrently reproduced tumorigenesis (8 out of 10 rad50Δ2/+ medaka), had a decrease in median survival time (65.7 ± 1.1 weeks in control vs. 54.2 ± 2.6 weeks in rad50Δ2/+ medaka, p = 0.001, Welch's t-test), exhibited semi-lethality in rad50Δ2/Δ2 medaka and most of the major ataxia-telangiectasia phenotypes, including ataxia (rheotaxis ability was lower in rad50Δ2/+ medaka than in the control, Mann-Whitney U test, p < 0.05), and telangiectasia (6 out of 10 rad50Δ2/+ medaka). The fish model may aid in further understanding the tumorigenesis and phenotype of ataxia-telangiectasia-related RAD50 germline mutations and in developing novel therapeutic strategies against RAD50 molecular disorders.

Cytological characteristics of histological types of lung cancer by cytomorphometric and flow cytometric analyses using liquid-based cytology materials.

BACKGROUND: Distinguishing the histological types of lung cancer is essential for determining treatment strategies in clinical practice. In this study, cytomorphological characteristics and proliferative activities were compared among histological types of lung cancer by cytomorphometric and flow cytometric analyses using liquid-based cytology (LBC) samples. METHODS: Scraped LBC samples from 73 surgically resected specimens were collected between August 2018 and November 2019. Papanicolaou-stained and paired Ki-67-stained slides were used for cytomorphometric analyses. Another sample for each case was analyzed using a flow cytometric system (LC-1000). The cell proliferation index (CPIx) was calculated to evaluate proliferative activity. RESULTS: In total, 73 cases, including cases of adenocarcinoma (n = 53), squamous cell carcinoma (n = 14), small cell carcinoma (n = 1), large cell neuroendocrine carcinoma (NEC; n = 3), and pleomorphic carcinoma (n = 2) were evaluated. Small cell carcinoma and large cell NEC were categorized into a single group, NEC. The adenocarcinoma group tended to have a larger nuclear area and longer perimeter than other histological types. The NEC group had a considerably higher Ki-67 labeling index and significantly higher CPIx than other histological types (p = .030). A significant positive correlation was observed between the Ki-67 labeling index and CPIx for all cases (r = 0.362, p = .002). CONCLUSION: The Ki-67 labeling index and flow cytometric analyses focus on proliferative activity for the distinction of histological types of lung cancer, thereby guiding clinical decision-making.

Cytomorphometric and flow cytometric analyses using liquid-based cytology materials in subtypes of lung adenocarcinoma.

BACKGROUND: The histological classifications of invasive lung adenocarcinoma subtypes are considered to predict patient prognosis after surgical treatment. The objectives of this study were to evaluate cytomorphological characteristics and proliferative activities among the histological predominant patterns by performing cytomorphometric and flow cytometric analyses using liquid-based cytology materials. METHODS: Cytological samples fixed by liquid-based cytology preservatives from 53 surgically-resected lung adenocarcinoma specimens were obtained between August 2018 and November 2019. The Papanicolaou-stained and paired Ki-67-stained slides were analyzed for calculating nuclear morphology (nuclear area, nuclear perimeter and nuclear circularity) and Ki-67 labeling index using software. The cell proliferation index (CPIx) was calculated and cellular information including cell cycle stage of tumor cells was obtained by flow cytometry. RESULTS: The 53 cases included papillary (n = 29), acinar (n = 8), lepidic (n = 5), and solid (n = 4) subtypes, and invasive mucinous adenocarcinoma (n = 7) were also included. In the lepidic pattern, nuclear area (79.6 ± 28.8 µm2 ) and perimeter (34.1 ± 6.1 µm) were relatively larger and longer than those of the other predominant patterns. The Ki-67 labeling index of the solid pattern (27.9 ± 12.5%) was highest compared with those of other predominant patterns. There were statistically significant differences in the lepidic versus solid patterns and the papillary versus solid patterns (p = .013 and p = .039, respectively). The calculated mean CPIx of the lepidic and the acinar patterns were approximately two-fold higher than those of the other predominant patterns. CONCLUSION: By revealing the differences of cytomorphological characteristics, these methodologies might be used for diagnosing cytopathological materials using digital cytopathology.

Optimal Preservations of Cytological Materials Using Liquid-Based Cytology Fixatives for Next-Generation Sequencing Analysis.

INTRODUCTION: Molecular targeted therapies have been established for various diseases, including cancers, and there is an increasing need for molecular testing on cytology specimens. The aim of this study was to determine the optimal preservation methods of liquid-based cytology (LBC) materials for molecular testing. METHODS: Cytological samples from 35 surgical resected non-small cell lung carcinoma specimens were obtained between June 2016 and June 2021. The samples were fixed in CytoRich™ red Preservative and stored at 4°C. One week later, three tubes were prepared from each specimen sample and divided into the following groups: the SurePath™ group (continued storage at 4°C), Frozen (Fr) group (stored at -80°C after centrifugation), and LBC-Cell Block (LBC-CB) group (generation of paraffin-embedded CB and storage at 4°C). Samples from 5 patients were used for the time course analysis, and we performed evaluations on these samples at 1, 3, 6, 12, 24, and 36 months. The concentrations and purities of extracted DNA and RNA were measured. The double-stranded DNA (dsDNA) and RNA concentrations were also measured by a fluorometer. The DNA and RNA integrities were quantified by the DNA and RNA integrity number. RESULTS: Evaluation of samples was performed at baseline and the six timepoints. In the LBC-CB group, DNA and dsDNA concentrations were higher rather than those in the other groups. The RNA concentration of the LBC-CB group was relatively high compared with those of the other groups at the 36-month timepoint. The Fr group maintained higher DNA quality compared with the other groups over 3 years. The LBC-CB group maintained a higher RNA quality than the other groups until 24 months. CONCLUSION: LBC-CB preparation is an effective method to maintain DNA/RNA quality and quantity in long-duration preservation for eventual molecular testing. Therefore, LBC-CB may have applications on preanalytical stage for molecular genomic testing such as next-generation sequencing.

Pulmonary Involvement in Microscopic Polyangiitis: Computed Tomography Findings in 55 Patients With Analysis of Risk Factors for Recurrence.

Background and objective Pulmonary involvement is seen in up to 30% of microscopic polyangiitis (MPA) patients. Pulmonary radiological findings for MPA have been scarcely reported to date. This study was conducted to evaluate computed tomography (CT) and clinical findings at the time of MPA diagnosis as predictors for systemic or lung recurrence. Methods We retrospectively reviewed the medical records and radiological data of 55 MPA patients with pulmonary involvement who were admitted to our hospital between April 2008 and December 2016. Results Aside from pulmonary lesions, lesions were found in the kidneys (52.7%), skin (7.3 %), and peripheral nerves (3.6%). Biopsies were performed for 29.1% of the patients, with an overall diagnostic accuracy of 78.9%. Parenchymal opacities (74.5%, mainly ground-glass opacities and reticular shadowing) were more commonly seen than airway abnormalities were (40.0%, mainly bronchiectasis). Systemic recurrence in the first year after diagnosis was found in 10.9% of the patients, and it mainly involved the kidneys or lungs. A serum WBC count ≥ 10,900/µL was a risk factor for predicting systemic recurrence within the first year after diagnosis according to the Cox regression analysis (HR 11.1, 95%CI: 1.3-95.9, p=0.028). Lung recurrence within five years after the diagnosis was observed in 9.1% of the patients. The incidences of reticular shadowing and honeycombing in thoracic CT at diagnosis were significantly higher in recurrence-positive patients than in recurrence-negative patients, but these differences could not be used to predict lung recurrence. Conclusions Ground glass opacities, reticular shadowing, and bronchiectasis are prominent thoracic CT findings for MPA. There are no radiological patterns capable of predicting recurrence. However, a serum WBC count ≥ 10,900/µL at diagnosis might be a predictive factor for systemic recurrence within the year.

Early-stage gastric cancer with solitary brain metastasis four years after curative surgery: a case report and literature review.

Brain metastasis post-curative gastrectomy for early-stage gastric cancer is extremely rare. We present herein, a case of solitary brain metastasis that developed 4 years post-curative surgery for early-stage gastric cancer. A 60-year-old man had early-stage gastric cancer 4 years prior to presentation and underwent laparoscopy-assisted distal gastrectomy with lymph node dissection. The pathological TNM classification was T1b (submucosal) N0M0. He underwent scheduled examinations and had no recurrence. 4 years postoperatively, he presented to the emergency department with sudden onset of nausea, vomiting, and inability to speak clearly. Brain computed tomography revealed a 17-mm nodule in the right cerebral hemisphere and midline shift. The tumor could not be radically resected for anatomical reasons, and incisional biopsy was performed for histological examination. Histological examination confirmed the diagnosis of a poorly differentiated adenocarcinoma from the previous gastric cancer. Gamma knife radiosurgery and chemotherapy were scheduled. 28 months after brain metastasis, multiple liver and lung metastases appeared. The patient died 30 months after developing brain metastasis. Brain metastasis may occur during long-term follow-up even after curative resection of early-stage gastric cancer. In patients with a history of gastric cancer and neurological symptoms, brain metastasis should be considered.

Diagnostic method for malignant pleural effusion distinguishing malignant mesothelioma from lung cancer using pleural carcinoembryonic antigen and hyaluronic acid levels.

ABSTRACT: Malignant mesothelioma (MM) is difficult to diagnose because of the lack of parenchymal opacities, often revealing minimal or absent pleural thickening. Furthermore, pleural effusion has diverse differential diagnoses, including malignancies, infections, as well as collagen vascular and other benign diseases. In general practice, lung cancer (LC) is the most common malignancy causing pleural effusion; therefore, a simple method using pleural diagnostic markers to differentiate between LC and mesothelioma is crucial.We retrospectively reviewed the data of 530 adult patients diagnosed with pleural effusion between January 2010 and December 2020 in an outpatient or inpatient setting. Patients with pathologically diagnosed MM or LC with cytologically positive (class IV or V) pleural effusion were analyzed, and the characteristics of these 2 diseases were compared.During the study period, 27 patients diagnosed with MM and 100 patients diagnosed with LC were enrolled. Receiver operating characteristic curve analysis demonstrated that pleural carcinoembryonic antigen (CEA) and hyaluronic acid (HA) could discriminate MM from LC with an area under the curve of 0.925 (95% confidence interval [CI]: 0.879-0.972, P < .001) and 0.815 (95% CI: 0.686-0.943, P < .001), respectively. To diagnose MM, the accuracy of pleural HA >30,000 ng/mL revealed a sensitivity of 75.0%, specificity of 72.6%, and odds ratio of 7.94 (95% CI: 2.5-25.2, P = .001); pleural CEA <6.0 ng/mL revealed a sensitivity of 95.2%, specificity of 84.9%, smaller negative likelihood ratio of 0.06, and odds ratio of 112.5% (95% CI: 14.4-878.1, P < .001). Multiple logistic regression analysis revealed that these 2 parameters could discriminate MM from LC, with a hazard ratio of 23.6 (95% CI: 2.437-228.1, P = .006) and 252.3 (95% Cl: 16.4-3888.1, P < .001), respectively, and their combination had a high specificity of 98.3%.Pleural CEA (≥6.0 ng/mL) can rule out MM with a high degree of certainty, and the positive results for combination of pleural CEA <6.0 ng/mL and HA >30,000 ng/mL can confirm MM with high specificity, prior to cytological or pathological examinations.

Pulmonary Artery Aneurysm Diagnosed by Dynamic Digital Chest Radiography.

Pulmonary artery aneurysms (PAAs) are rare but clinically important because their rupture can cause sudden death. This report describes a case of an asymptomatic patient with an unruptured PAA that was successfully diagnosed by dynamic digital chest radiography (DDCR) and was treated surgically. DDCR is an advanced, temporally resolved radiographic technique that offers high-quality fluoroscopy-like images at a low radiation dose. Although noncontrast chest computed tomography revealed only a nonspecific nodule, DDCR delineated this lesion as a pulsatile nodule synchronized with cardiac pulsations, thereby establishing the diagnosis of PAA. This diagnosis was confirmed by computed tomographic pulmonary angiography and surgery.

Involvement of galanin and galanin receptor 2 in a mouse model of allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is caused by allergic reaction to allergens such as pollen. Galanin (GAL), a neuropeptide that regulates inflammatory processes, is widely expressed in the central and peripheral nervous systems. Although neuropeptides are implicated in arthritis and chemically induced ileitis, their roles in AR remain unclear. METHODS: We developed a murine model of AR and generated control, systemic sensitization, mild AR, and severe AR groups. We examined GAL and GAL receptor (GALR) mRNA and protein levels and localization patterns in each group using reverse transcription PCR, western blotting, and immunohistochemical analyses. Additionally, we evaluated the effects of M871, a GALR2 antagonist, on mice with severe AR. RESULTS: Gal and Galr2 are expressed in nasal mucosa and brain (control) samples from control and AR mice. GAL and GALR2 were expressed at similar levels and localized to ciliated epithelial and submucosal gland cells of the nasal mucosa in all four groups. Intranasal M871 administration significantly reduced the incidence of nose rubbing behaviors and sneezing (p < 0.001 in 30 min, respectively) in severe AR mice relative to that in controls. Mechanistically, we postulate that GALR2 is expressed in B cells, and M871 administration reduces IgE production, as well as the number of B cells in tissues. CONCLUSIONS: GAL signaling may not change progressively with increasing nasal sensitization, suggesting that this signaling process exacerbates, rather than directly trigger, AR. GAL-GALR2 signaling likely mediates AR development, suggesting that its inhibition represents a novel therapeutic strategy for AR.

An autopsy case study of lymphocytic hypophysitis induced by nivolumab treatment for esophageal malignant melanoma.

Immune checkpoint inhibitors such as anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed death-1 antibodies are effective against malignant tumors. However, they induce unique adverse events known as immune-related adverse events. Hypophysitis is one of the most frequent immune-related adverse events of anti-cytotoxic T-lymphocyte antigen-4 therapies. However, there have been few reports describing the pathological findings of hypophysitis induced by anti-programmed death-1 antibodies. The present case is the first autopsy case of hypophysitis induced by nivolumab monotherapy, an anti-programmed death-1 antibody. Pathologically, lymphocytes infiltrated the anterior lobe of the pituitary gland, and the number of pituitary cells, especially adrenocorticotropic hormone-positive cells, decreased. However, necrosis and remarkable fibrosis were not observed. Immunohistologically, some pituitary cells expressed programmed death-ligand 1. Lymphocytes were predominantly CD8-positive T cells, and CD68-positive macrophages and CD20-positive B-cells were also observed. IgG and C4d were deposited on pituitary cells, but IgG4 (a subclass of nivolumab) was not detected. These findings indicate that type IVc and type II hypersensitivity mechanisms may occur in hypophysitis induced by anti-programmed death-1 antibodies and that the inflammatory mechanisms underlying hypophysitis induced by anti-programmed death-1 and anti-cytotoxic T-lymphocyte antigen-4 antibodies are different.

STAT3 activation in thymic epithelial tumors: correlation with cyclin D1, JAK3, and clinical behavior.

OBJECTIVES: Thymic epithelial tumors are the most common adult mediastinal tumors; however, their growth mechanism remains relatively unknown. Among the JAK/STAT pathway-related proteins, which control various intracellular events, STAT3 is deeply involved in cell proliferation. Constitutive activation of STAT3 and the resulting overexpression of cyclin D1 have been confirmed in various tumors, but have not been thoroughly investigated in thymic epithelial tumors. In this study, we immunohistochemically examined STAT3 activation, cyclin D1 expression, and JAK3 activation in thymic epithelial tumors and statistically analyzed their correlation with clinicopathological features. METHODS: Formalin-fixed paraffin-embedded specimens of 94 thymic epithelial tumors surgically resected at Kyorin University Hospital between 2005 and 2018 were included in this study. pSTAT3, cyclin D1, and pJAK3 were immunohistochemically examined, and the correlation with histology, Masaoka stage, and survival time was statistically analyzed. RESULTS: Cyclin D1 was found to be significantly overexpressed in the STAT3-activated group. This phenomenon was associated with histology and Masaoka stage. JAK3 was also activated in thymic epithelial tumors; however, JAK3 and STAT3 activation were not always correlated. Using survival time analysis, the STAT3-activated group, cyclin D1-expressed group, and JAK3-activated group had significantly lower progression-free survival times than those for both the non-activated and non-expressed groups. CONCLUSIONS: STAT3 activation may promote cyclin D1 overexpression in thymic epithelial tumors, and intracellular signaling pathways other than JAK3 may be involved in STAT3 activation. STAT3 activation, cyclin D1 overexpression, and JAK3 activation are biomarker candidates that indicate clinically poor prognosis.

Successful Treatment of Mepolizumab- and Prednisolone-resistant Allergic Bronchopulmonary Aspergillosis with Dupilumab.

A 45-year-old man with allergic bronchopulmonary aspergillosis (ABPA) was treated with oral prednisolone (PSL) (30 mg/day), inhaled corticosteroids, and long-acting beta2-agonists. After confirmation of a PSL-dependent status (8 mg/day), subcutaneous injection with anti-interleukin (IL)-5 antibody (mepolizumab, 100 mg/month) was performed, and the PSL dose was tapered to 5 mg/day. However, ABPA recurred and proved refractory to oral itraconazole (200 mg/day). Alternative subcutaneous injection therapy with dupilumab (induction dose of 600 mg followed by a maintenance dose of 300 mg/2 weeks) enabled the successful withdrawal of oral PSL without clinical deterioration. This case demonstrates the potential utility of dupilumab for steroid-dependent ABPA via the synergistic suppression of IL-4 and IL-13 compared to monotherapy with anti-IL-5 antibody.

Rapidly progressive respiratory failure with multiple halo signs on computed tomography in a patient with primary cardiac angiosarcoma derived from the right atrium: a case report.

BACKGROUND: Primary cardiac neoplasms are extremely rare, with an autopsy incidence of 0.0001-0.003%. Primary cardiac sarcoma is usually derived from the right atrium and it manifests as chest pain, arrhythmia, hemoptysis, dyspnea, and fatigue. The most common target organ for metastasis of primary angiosarcoma is the lungs, but the radiological-pathological correlation has been rarely reported. CASE PRESENTATION: A 38-year-old healthy Japanese man was admitted to our hospital with persistent hemoptysis, exaggerated dyspnea, and two episodes of loss of consciousness in the past 3 months. Non-enhanced thoracic computed tomography (CT) revealed multiple scattered nodules with halo signs. Contrast-enhanced thoracic CT revealed a filling defect in the right atrium, which corresponded to the inhomogeneously enhancing tumor in the right atrium on enhanced electrocardiogram-gated cardiac CT. On day 2, acute respiratory failure occurred, and the patient was placed on mechanical ventilation. The patient was diagnosed with primary cardiac angiosarcoma based on the urgent transcatheter biopsied specimen of the right atrium mass and was treated with intravenous administration of doxorubicin. However, his respiratory status rapidly deteriorated, and he died on day 20. Postmortem biopsy showed that the multiple lung nodules with the halo signs corresponded to the intratumoral hemorrhagic necrosis and peripheral parenchymal hemorrhage in their background, suggesting the fragility of the lung tissue where the tumor had invaded, which caused hemoptysis. Furthermore, two episodes of loss of consciousness occurred probably due to a decreased cardiac output because of a massive tumor occupying the right atrium, recognized as an inhomogeneous centripetal enhancement on enhanced electrocardiogram-gated cardiac CT. CONCLUSIONS: This case clearly demonstrated that primary cardiac angiosarcoma could expand in the right atrial cavity, which led to a decreased cardiac output resulting in repeated syncope, together with the fragility of lung tissue by tumor invasion, thereby generating a halo sign on thoracic CT.

Abducens Nerve Paralysis Induced by a Primary Solitary Sphenoid Sinus Mucocele with Broad Osseous Thinning at the Cranial Base.

Primary solitary sphenoid sinus mucocele is rare, generally presenting with headaches or eye symptoms at the anatomical site. We report the case of a 39-year-old woman incidentally diagnosed with sphenoid sinus mucocele during a complete medical checkup. Imaging revealed that the cystic wall had developed from the rear sphenoid sinus and had spread expansively to diminish the clivus; however, no symptoms were reported, and the patient was managed with close observation. During the follow-up period, diplopia developed suddenly due to isolated left-sided abducens nerve paralysis. An endoscopic endonasal approach was used to open the frontal cystic wall, and fascia lata and fat were used for cranial base reinforcement to avoid future cerebrospinal fluid leakage, resulting in improvement during the early stages of follow-up. Treatment options for sphenoid sinus mucoceles include close observation or surgery. In our case, we chose surgery because of an acute symptomatic manifestation during observation.

Regulatory Single Nucleotide Polymorphism Increases TERT Promoter Activity in Thyroid Carcinoma Cells.

BACKGROUND/AIM: The telomerase reverse transcriptase (TERT) promoter has a regulatory single nucleotide polymorphism (rSNP), rs2853669, and occasionally shows point mutations C228T and C250T. Although C228T and C250T have been well examined to increase TERT promoter activity and are known as risk factors for thyroid carcinoma, the significance of rs2853669 has not been well investigated. This study aimed to clarify the influence of rs2853669 on TERT promoter activity in thyroid carcinoma cells. MATERIALS: Seven of 8 examined thyroid cell lines had rs2853669, 5 had C228T, and 1 had C250T. RESULTS: Three papillary thyroid carcinoma cell lines, harboring both rs2853669 and C228T, showed higher TERT mRNA expression on real-time PCR than the other cell lines. Anaplastic thyroid carcinoma cell lines, in contrast, showed variable TERT mRNA expression depending on the combination of rs2853669, C228T, and C250T. Luciferase assays, performed to compare the influences of rs2853669, C228T, and C250T on TERT promoter activity in thyroid carcinoma, showed that rs2853669, as well as C228T, increased the promoter activity, and the combination of rs2853669 and C228T increased the promoter activity even more strongly than C228T alone. CONCLUSION: We conclude that the presence of rs2853669 within the TERT promoter could be as significant as the C228T mutation in thyroid carcinoma.

Aggressive lung involvement in a patient with T-acute lymphoblastic leukaemia/lymphoblastic lymphoma: a tricky and rare case report.

A 39-year-old man was admitted to our university hospital because of diffuse pulmonary infiltrates on chest X-ray. He had been diagnosed with T-acute lymphoblastic leukaemia/lymphoblastic lymphoma three years before and had been treated with chemotherapy and cord blood stem cell transplantation twice. Although he had neither blast cells in the peripheral blood nor leucocytosis, urgent bronchoscopy findings demonstrated blast cells invading both the alveolar spaces/alveolar septa and the vein walls. These pathological findings corresponded to ground-glass opacities and thickening of the interlobular septa on thoracic computed tomography (CT). In acute lymphoblastic leukaemia/lymphoblastic lymphoma patients presenting with infiltrates on thoracic CT, leukaemic pulmonary involvement should be considered in the differential diagnoses, even in the absence of hyperleucocytosis or blast cells in the blood, similar to pulmonary involvement in myeloid leukaemias.

Tuberculosis-associated chylothorax revealing an enlarged lymphatic duct due to tuberculosis lymphadenitis.

A 77-year-old woman presented to our hospital with complaints of persistent cough and low-grade fever for two months. On radiological analysis, she had moderate right-sided pleural effusion with right hilar and subcarinal lymphadenopathies. Thoracentesis showed chylothorax of unknown cause. Bronchoscopy revealed a non-specific inflammatory process. However, thoracoscopic surgery demonstrated a curiously enlarged lymphatic duct with its proximal portion compressed by subcarinal lymphadenopathies, pathologically diagnosed as granulomatous lymphadenitis. Hence, tuberculous lymphadenitis was proven to be the cause of chylothorax. Interestingly, cauterization of the lymphatic duct decreased the total amount of right-sided pleural effusion along with a change in colour from milky yellow to red. These were in favour of tuberculosis (TB)-associated chylothorax with the advent of the TB pleuritis. All symptoms and pleural effusion disappeared after the initiation of anti-tuberculous drugs. The present case showed definite evidence of TB-associated chylothorax development mechanism via compression of the lymphatic duct by mediastinal lymphadenopathies.