ABSTRACT
Purpose@#NUT carcinoma (NC) is a solid tumor caused by the rearrangement of NUTM1 that usually develops in midline structures, such as the thorax. No standard treatment has been established despite high lethality. Thus, we investigated whether targeting the junction region of NUTM1 fusion breakpoints could serve as a potential treatment option for NC. @*Materials and Methods@#We designed and evaluated a series of small interfering RNAs (siRNAs) targeting the junction region of BRD4-NUTM1 fusion (B4N), the most common form of NUTM1 fusion. Droplet digital polymerase chain reaction using the blood of patients was also tested to evaluate the treatment responses by the junction sequence of the B4N fusion transcripts. @*Results@#As expected, the majority of NC fusion types were B4N (12 of 18, 67%). B4N fusion-specific siRNA treatment on NC cells showed specific inhibitory effects on the B4N fusion transcript and fusion protein without affecting the endogenous expression of the parent genes, resulting in decreased relative cell growth and attenuation of tumor size. In addition, the fusion transcript levels in platelet-rich-plasma samples of the NC patients with systemic metastasis showed a negative correlation with therapeutic effect, suggesting its potential as a measure of treatment responsiveness. @*Conclusion@#This study suggests that tumor-specific sequences could be used to treat patients with fusion genes as part of precision medicine for a rare but deadly disease.
ABSTRACT
Although the typical CT findings of Pneumocystis jiroveci pneumonia (PJP) include diffuse or multifocal areas of ground-glass opacities in both lungs, it can also rarely manifest as multiple pulmonary nodules. We report a rare case of atypical PJP in an immunocompromised patient with multiple myeloma, presenting as widespread ground-glass opacities and multiple necrotic subpleural nodules in both lungs on CT, which proved to be granulomatous PJP on percutaneous transthoracic needle biopsy.
ABSTRACT
Recurrent respiratory papillomatosis (RRP) is a chronic disease related to human papillomavirus infection. The standard treatment of RRP is surgical resection of the lesion, but due to frequent recurrence, a combination of various adjuvant therapies has been attempted. Herein, we present the first case of RRP to whom intravenous cidofovir was administered as an adjuvant therapy in Korea. A 9-year-old boy was admitted due to hoarseness, stridor and breathing difficulty. At 10 months of age, he was diagnosed with RRP in the upper airway and thereafter he had repeatedly undergone surgical removal. During this hospitalization, papilloma was found again from the superior glottis to the inferior glottis and surrounding the trachea at the age of 9 years. In addition, well-defined nodular lesions were newly found on both lung fields, and a pathologic examination revealed a squamous papilloma with highgrade dysplasia, human papilloma virus types 6, 11, and 40 (low-risk type). Because of the frequent recurrence of papilloma in the upper airway as well as lung involvement, he underwent 38 injections of intravenous cidofovir for 2 years. During treatment, the intervals required for surgical removal of the mass causing upper airway obstruction were prolonged from an average of 37.3 to 74.6 days without serious side effects. However, intravenous cidofovir treatment had no effect on the lung lesion. This case shows that an intravenous cidofovir administration can be used as an adjuvant therapy in a child with RRP to relieve the upper airway obstruction, although this treatment does not cure the disease.
ABSTRACT
Invasive fungal infection (IFI) is a serious threat to pediatric patients with cancer given high morbidity and mortality. We present an 18-year-old male with precursor T-cell lymphoblastic leukemia who developed Pancoast syndrome, presented with paresthesia and numbness in the right shoulder and arm during a neutropenic fever period. He was diagnosed with pneumonia in the right upper lung field. He was later found to have an invasive pulmonary fungal infection caused by multiple fungi species, including Rhizomucor, confirmed by histology and polymerase chain reaction (PCR) (proven infection), Penicillium decumbens diagnosed by PCR, and Aspergillus suspected from galactomannan assay (probable infection). Unfortunately, the patient's condition further worsened owing to the aggravation of leukemia, chemotherapy-induced neutropenia, and bacterial coinfection, leading to multiorgan failure and death. Here, we report a case of IFI caused by multiple fungal species that presented as Pancoast syndrome.
ABSTRACT
Following the introduction of a novel pathological concept of usual interstitial pneumonia (UIP) by Liebow and Carrington in 1969, diffuse interstitial pneumonia has evolved into UIP, nonspecific interstitial pneumonia (NSIP), and interstitial lung abnormality (ILA); the histopathological and CT findings of these conditions reflect the required multidisciplinary team approach, involving pulmonologists, radiologists, and pathologists, for their diagnosis and management. Concomitantly, traction bronchiectasis and bronchiolectasis have been recognized as the most persistent and important indices of the severity and prognosis of fibrotic lung diseases. The traction bronchiectasis index (TBI) can stratify the prognoses of patients with ILAs. In this review, the evolutionary concepts of UIP, NSIP, and ILAs are summarized in tables and figures, with a demonstration of the correlation between CT findings and pathologic evaluation. The CT-based UIP score is being proposed to facilitate a better understanding of the spectrum of pulmonary fibrosis, from ILAs to UIP, with emphasis on traction bronchiectasis/bronchiolectasis.
ABSTRACT
Vasculitis is a systemic disease, characterized by inflammation of the vascular wall. Although rare, it is sometimes life-threatening due to diffuse pulmonary hemorrhage or acute glomerulonephritis. Besides primary vasculitis, whose cause is unknown, numerous conditions such as autoimmune diseases, drugs, infections, and tumors can cause secondary vasculitis. Vasculitis displays various non-specific symptoms, signs, and laboratory findings; hence, diagnosis of the disease requires integration of various results including clinical features, imaging findings, autoantibody tests, and pathological findings. In this review, we have discussed the clinical, radiologic, and pathological features of vasculitis. Further, we elaborated the imaging findings and differential diagnosis of typical vasculitis that frequently involves the lung and introduced a new international classification of vasculitis, the Diagnostic and Classification Criteria in Vasculitis.
ABSTRACT
Invasive fungal infection (IFI) is a serious threat to pediatric patients with cancer given high morbidity and mortality. We present an 18-year-old male with precursor T-cell lymphoblastic leukemia who developed Pancoast syndrome, presented with paresthesia and numbness in the right shoulder and arm during a neutropenic fever period. He was diagnosed with pneumonia in the right upper lung field. He was later found to have an invasive pulmonary fungal infection caused by multiple fungi species, including Rhizomucor, confirmed by histology and polymerase chain reaction (PCR) (proven infection), Penicillium decumbens diagnosed by PCR, and Aspergillus suspected from galactomannan assay (probable infection). Unfortunately, the patient's condition further worsened owing to the aggravation of leukemia, chemotherapy-induced neutropenia, and bacterial coinfection, leading to multiorgan failure and death. Here, we report a case of IFI caused by multiple fungal species that presented as Pancoast syndrome.
ABSTRACT
Following the introduction of a novel pathological concept of usual interstitial pneumonia (UIP) by Liebow and Carrington in 1969, diffuse interstitial pneumonia has evolved into UIP, nonspecific interstitial pneumonia (NSIP), and interstitial lung abnormality (ILA); the histopathological and CT findings of these conditions reflect the required multidisciplinary team approach, involving pulmonologists, radiologists, and pathologists, for their diagnosis and management. Concomitantly, traction bronchiectasis and bronchiolectasis have been recognized as the most persistent and important indices of the severity and prognosis of fibrotic lung diseases. The traction bronchiectasis index (TBI) can stratify the prognoses of patients with ILAs. In this review, the evolutionary concepts of UIP, NSIP, and ILAs are summarized in tables and figures, with a demonstration of the correlation between CT findings and pathologic evaluation. The CT-based UIP score is being proposed to facilitate a better understanding of the spectrum of pulmonary fibrosis, from ILAs to UIP, with emphasis on traction bronchiectasis/bronchiolectasis.
ABSTRACT
Vasculitis is a systemic disease, characterized by inflammation of the vascular wall. Although rare, it is sometimes life-threatening due to diffuse pulmonary hemorrhage or acute glomerulonephritis. Besides primary vasculitis, whose cause is unknown, numerous conditions such as autoimmune diseases, drugs, infections, and tumors can cause secondary vasculitis. Vasculitis displays various non-specific symptoms, signs, and laboratory findings; hence, diagnosis of the disease requires integration of various results including clinical features, imaging findings, autoantibody tests, and pathological findings. In this review, we have discussed the clinical, radiologic, and pathological features of vasculitis. Further, we elaborated the imaging findings and differential diagnosis of typical vasculitis that frequently involves the lung and introduced a new international classification of vasculitis, the Diagnostic and Classification Criteria in Vasculitis.
ABSTRACT
Purpose@#The diagnosis of pulmonary fungal infections is challenging due to the difficulty of obtaining sufficient specimens. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) needle rinse fluid has become an emerging diagnostic material. This study evaluated the role of routine fungal culture from EBUS-TBNA needle rinse fluid, in addition to histopathologic examination and fungal culture of EBUS-TBNA core tissue, in the diagnosis of pulmonary fungal infections. @*Materials and Methods@#Among patients who underwent EBUS-TBNA, those with results for at least one of three tests (histopathologic examination, fungal culture of EBUS-TBNA core tissue or needle rinse fluid) were included. Patients with a positive test were divided into two groups (clinical fungal infection and suspected fungal contamination) according to their clinical assessment and therapeutic response to antifungal. @*Results@#Of 6072 patients, 41 (0.7%) had positive fungal tests and 9 (22%) were diagnosed as clinical fungal infection. Of the 5222 patients who were evaluated using a fungal culture from EBUS-TBNA needle rinse fluid, 35 (0.7%) had positive results. However, only 4 out of 35 (11.4%) were classified as clinical fungal infection. Positive results were determined in 4 of the 68 (5.9%) evaluated by a fungal culture of EBUS-TBNA core tissue, and all were diagnosed as clinical fungal infection. @*Conclusion@#Routine fungal culture of EBUS-TBNA needle rinse fluid is not useful due to the low incidence of fungal infection and high rate of contamination. However, fungal culture of EBUS-TBNA core tissue and needle rinse fluid should be considered in patients with clinically suspected fungal infection.
ABSTRACT
IgG4-related disease is a systemic inflammatory disease and is known as IgG4-related lung disease (IgG4-RLD) when it involves the respiratory system. Primary lung cancer arising from a background of IgG4-RLD is very rare. Herein, we report a case of adenosquamous carcinoma arising from the background of IgG4-RLD and presenting as an interstitial lung disease pattern. A 66-year-old man underwent lobectomy under the impression of primary lung cancer. Grossly, the mass was ill-defined and gray-tan colored, and the background lung was fibrotic. Microscopically, tumor cells showed both squamous and glandular differentiation. Dense lymphoplasmacytic infiltration with fibrosis and obliterative phlebitis were seen in the background lung. IgG4 immunohistochemical stain showed diffuse positivity in infiltrating plasma cells. Primary lung adenosquamous carcinoma has not been reported in a background of IgG4-RLD. Due to the rarity of IgG4-RLD, physicians must follow patients with IgG4-RLD over long periods of time to accurately predict the risk of lung cancer.
Subject(s)
Aged , Humans , Carcinoma, Adenosquamous , Fibrosis , Immunoglobulin G , Lung Diseases , Lung Diseases, Interstitial , Lung Neoplasms , Lung , Phlebitis , Plasma Cells , Respiratory SystemABSTRACT
PURPOSE: This study was conducted to evaluate the relationship between epidermal growth factor receptor (EGFR) mutation and clinical outcomes in patients with stage III non-squamous cell lung cancer treated with definitive concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: From January 2008 to December 2013, the medical records of 197 patients with stage III non- squamous non-small cell lung cancer treated with definitive CCRT were analyzed to determine progression-free survival (PFS) and overall survival (OS) according to EGFR mutation status. RESULTS: Among 197 eligible patients, 81 patients were EGFR wild type, 36 patients had an EGFR mutation (exon 19 Del, n=18; L858R, n=9, uncommon [G719X, L868, T790M], n=9), and 80 patients had unknown EGFR status. The median age was 59 years (range, 28 to 80 years) and 136 patients (69.0%) were male. The median follow-up duration was 66.5 months (range, 1.9 to 114.5 months). One hundred sixty-four patients (83.2%) experienced disease progression. Median PFS was 8.9 months for the EGFR mutation group, 11.8 months for EGFR wild type, and 10.5 months for the unknown EGFR group (p=0.013 and p=0.042, respectively). The most common site of metastasis in the EGFR mutant group was the brain. However, there was no significant difference in OS among the three groups (34.6 months for EGFR mutant group vs. 31.9 months for EGFR wild type vs. 22.6 months for EGFR unknown group; p=0.792 and p=0.284). A total of 29 patients (80.6%) with EGFR mutation were treated with EGFR tyrosine kinase inhibitor (gefitinib, n=24; erlotinib, n=3; afatinib, n=2) upon progression. CONCLUSION: EGFR mutation is associatedwith short PFS and the brain is the most common site of distant metastasis in patients with stage III non- squamous cell lung cancer treated with CCRT.
Subject(s)
Humans , Male , Brain , Carcinoma, Non-Small-Cell Lung , Chemoradiotherapy , Disease Progression , Disease-Free Survival , Epithelial Cells , Erlotinib Hydrochloride , Follow-Up Studies , Lung Neoplasms , Lung , Medical Records , Neoplasm Metastasis , Protein-Tyrosine Kinases , ErbB ReceptorsABSTRACT
BACKGROUND: Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) are usually effective in lung adenocarcinoma patients with anaplastic lymphoma kinase (ALK) rearrangement. However, even after a good response to ALK-TKI therapy, most patients acquire resistance to these agents. Histological transformation is one of several suggested mechanisms of acquired resistance to ALK-TKIs. The clinicopathologic features of four patients with ALK-expressing adenocarcinoma and neuroendocrine features were analyzed. METHODS: We selected combined neuroendocrine differentiation in pulmonary adenocarcinoma cases with positive ALK immunostaining. Neuroendocrine differentiation was confirmed by CD56 immunohistochemical stain. Additional ALK fluorescence in situ hybridization (FISH) study and epidermal growth factor receptor (EGFR) mutation tests were also performed. RESULTS: All four cases were positive for ALK immunohistochemistry and no EGFR mutations were detected. Interestingly, the results of ALK FISH assays showed rearrangement in only two cases. Three cases showed combined adenocarcinoma and neuroendocrine component without history of ALK-TKI administration; one of them was treated with crizotinib and experienced partial tumor regression. The remaining case had an adenocarcinoma at initial biopsy and she showed a partial response to crizotinib, and neuroendocrine changes were visible on second biopsy. Then she was treated with ceritinib and achieved a partial response. CONCLUSION: We suggest that ALK-rearranged adenocarcinoma with combined neuroendocrine component is responsive to ALK-TKIs. Moreover, even after neuroendocrine transformation as a result of resistance to ALK-TKIs, the tumor may have partial response to second generation ALK-TKIs.
ABSTRACT
Cytologic diagnosis of nuclear protein in testis (NUT) midline carcinoma (NMC) is important due to its aggressive behavior and miserable prognosis. Early diagnosis of NMC can facilitate proper management, and here we report two rare cases of thoracic NMC with cytohistologic correlation. In aspiration cytology, the tumor presented with mixed cohesive clusters and dispersed single cells, diffuse background necrosis and many neutrophils. Most of the tumor cells had scanty cytoplasm and medium-sized irregular nuclei, which had fine to granular nuclear chromatin. Interestingly, a few dyskeratotic cells or squamoid cell clusters were present in each case. Biopsy specimen histology revealed more frequent squamous differentiation, and additional immunohistochemistry tests showed nuclear expression of NUT. Because this tumor has a notorious progression and has been previously underestimated in terms of its prevalence, awareness of characteristic findings and proper ancillary tests should be considered in all suspicious cases.
Subject(s)
Biopsy , Chromatin , Cytoplasm , Diagnosis , Early Diagnosis , Immunohistochemistry , Lung , Necrosis , Neutrophils , Nuclear Proteins , Nuts , Prevalence , Prognosis , TestisABSTRACT
BACKGROUND: Pulmonary nodular lymphoid hyperplasia (PNLH) is a non-neoplastic pulmonary lymphoid disorder that can be mistaken for malignancy on radiography. Herein, we present nine cases of PNLH, emphasizing clinicoradiological findings and histological features. METHODS: We analyzed radiological and clinicopathological features from the electronic medical records of nine patients (eight females and one male) diagnosed with PNLH. IgG and IgG4 immunohistochemical staining was performed in three patients. RESULTS: Two of the nine patients had experienced tuberculosis 40 and 30 years prior, respectively. Interestingly, none were current smokers, although two were ex-smokers. Three patients complaining of persistent cough underwent computed tomography of the chest. PNLH was incidentally discovered in five patients during examination for other reasons. The remaining patient was diagnosed with the disease following treatment for pneumonia. Imaging studies revealed consolidation or a mass-like lesion in eight patients. First impressions included invasive adenocarcinoma and mucosal-associated lymphoid tissue‒type lymphoma. Aspergillosis was suspected in the remaining patient based on radiological images. Resection was performed in all patients. Microscopically, the lesions consisted of nodular proliferation of reactive germinal centers accompanied by infiltration of neutrophils and macrophages in various degrees and surrounding fibrosis. Ultimately, all nine patients were diagnosed with PNLH and showed no evidence of recurrence on follow-up. CONCLUSIONS: PNLH is an uncommon but distinct entity with a benign nature, and understanding the radiological and clinicopathological characteristics of PNLH is important.
Subject(s)
Female , Humans , Adenocarcinoma , Aspergillosis , Cough , Electronic Health Records , Fibrosis , Follow-Up Studies , Germinal Center , Hyperplasia , Immunoglobulin G , Lymphoma , Macrophages , Neutrophils , Pneumonia , Pseudolymphoma , Radiography , Recurrence , Thorax , TuberculosisABSTRACT
BACKGROUND: We reviewed a series of 188 resected pulmonary mucinous adenocarcinomas (MAs) to clarify the prognostic significance of lepidic and non-lepidic patterns. METHODS: Non-lepidic patterns were divided into bland, non-distorted acini with uncertain invasiveness (pattern 1), unequivocal invasion into stroma (pattern 2), or invasion into alveolar spaces (pattern 3). RESULTS: The mean proportion of invasive patterns (patterns 2 and 3) was lowest in small (≤ 3 cm) tumors, and gradually increased in intermediate (> 3 cm and ≤ 7 cm) and large (> 7 cm) tumors (8.4%, 34.3%, and 50.1%, respectively). Adjusted T (aT) stage, as determined by the size of invasive patterns, was positively correlated with adverse histologic and clinical features including older age, male sex, and ever smokers. aTis tumors, which were exclusively composed of lepidic pattern (n = 9), or a mixture of lepidic and pattern 1 (n = 40) without any invasive patterns, showed 100% disease- free survival (DFS). The aT1mi tumors, with minimal (≤ 5 mm) invasive patterns (n = 63), showed a 95.2% 5-year DFS, with recurrences (n = 2) limited to tumors greater than 3 cm in total size (n = 23). Both T and aT stage were significantly associated with DFS; however, survival within the separate T-stage subgroups was stratified according to the aT stage, most notably in the intermediatestage subgroups. In multivariate analysis, the size of invasive patterns (p = .020), pleural invasion (p < .001), and vascular invasion (p = .048) were independent predictors of recurrence, whereas total size failed to achieve statistical significance (p = .121). CONCLUSIONS: This study provides a rationale for histologic risk stratification in pulmonary MA based on the extent of invasive growth patterns with refined criteria for invasion.
Subject(s)
Humans , Male , Adenocarcinoma in Situ , Adenocarcinoma, Mucinous , Disease-Free Survival , Lung , Mucins , Multivariate Analysis , RecurrenceABSTRACT
PURPOSE: The discoidin domain-containing receptor tyrosine kinase 2 (DDR2) is known to contain mutations in a small subset of patients with squamous cell carcinomas (SCC) of the lung. Studying the DDR2 mutations in patients with SCC of the lung would advance our understanding and guide the development of therapeutic strategies against lung cancer. MATERIALS AND METHODS: We selected 100 samples through a preliminary genetic screen, including specimens from biopsies and surgical resection, and confirmed SCC by histologic examination. DDR2 mutations on exons 6, 15, 16, and 18 were analyzed by Sanger sequencing of formalin-fixed, paraffin-embedded tissue samples. The functional effects of novel DDR2 mutants were confirmed by in vitro assays. RESULTS: We identified novel somatic mutations of DDR2 in two of the 100 SCC samples studied. One mutation was c.1745T>A (p.V582E) and the other was c.1784T>C (p.L595P), and both were on exon 15. Both patients were smokers and EGFR/KRAS/ALK-triple negative. The expression of the mutant DDR2 induced activation of DDR2 by the collagen ligand and caused enhanced cell growth and tumor progression. Moreover, dasatinib, a DDR2 inhibitor, showed potential efficacy against DDR2 L595P mutant–bearing cells. CONCLUSION: Our results suggest that a mutation in DDR2 occurs naturally with a frequency of about 2% in Korean lung SCC patients. In addition, we showed that each of the novel DDR2 mutations were located in a kinase domain and induced an increase in cell proliferation rate.
Subject(s)
Humans , Biopsy , Carcinoma, Squamous Cell , Cell Proliferation , Collagen , Dasatinib , Epithelial Cells , Exons , In Vitro Techniques , Lung Neoplasms , Lung , Phosphotransferases , Prevalence , Protein-Tyrosine Kinases , TYK2 Kinase , TyrosineABSTRACT
No abstract available.
Subject(s)
Adenocarcinoma , Carcinoma, Squamous Cell , Epidermal Growth Factor , Epithelial Cells , Lung , ErbB ReceptorsABSTRACT
Thymic adenocarcinoma is extremely rare. Although its histologic features have been occasionally reported, a lack of description of the cytologic features has hampered the prompt and accurate diagnosis of this condition. Herein, we describe the cytologic findings and histology of four aspiration cytology specimens of thymic adenocarcinoma. The specimens were obtained from primary tumors, metastatic lymph nodes, and pericardial effusions. All four specimens showed three-dimensional glandular clusters with a loss of polarity and nuclear overlapping. One specimen had extensive extracellular mucinous material. Three specimens contained tumor cells with intracytoplasmic vacuoles. While the specimen with extracellular mucin showed relatively mild cytologic atypia, other specimens exhibited more atypical cytologic changes: irregular nuclear membranes, a coarse chromatin pattern, and prominent nucleoli. The cytologic features were correlated with the histologic features in each case of enteric type thymic adenocarcinoma. The differential diagnosis included other thymic carcinomas, yolk sac tumors, and metastatic adenocarcinoma from the lung or colorectum.
Subject(s)
Adenocarcinoma , Biopsy, Fine-Needle , Chromatin , Diagnosis , Diagnosis, Differential , Endodermal Sinus Tumor , Lung , Lymph Nodes , Mediastinum , Mucins , Nuclear Envelope , Pericardial Effusion , Thymoma , Thymus Gland , VacuolesABSTRACT
BACKGROUND: A ground-glass nodule (GGN) represents early-stage lung adenocarcinoma. However, there is still no consensus for preoperative staging of GGNs. Therefore, we evaluated the need for the routine use of positron emission tomography/computed tomography (PET)/computed tomography (CT) scans and brain magnetic resonance imaging (MRI) during staging. METHODS: A retrospective analysis was undertaken in 72 patients with 74 GGNs of less than 3 cm in diameter, which were confirmed via surgery as malignancy, at the Samsung Medical Center between May 2010 and December 2011. RESULTS: The median age of the patients was 59 years. The median GGN diameter was 18 mm. Pure and part-solid GGNs were identified in 35 (47.3%) and 39 (52.7%) cases, respectively. No mediastinal or distant metastasis was observed in these patients. In preoperative staging, all of the 74 GGNs were categorized as stage IA via chest CT scans. Additional PET/CT scans and brain MRIs classified 71 GGNs as stage IA, one as stage IIIA, and two as stage IV. However, surgery and additional diagnostic work-ups for abnormal findings from PET/CT scans classified 70 GGNs as stage IA, three as stage IB, and one as stage IIA. The chest CT scans did not differ from the combined modality of PET/CT scans and brain MRIs for the determination of the overall stage (94.6% vs. 90.5%; kappa value, 0.712). CONCLUSION: PET/CT scans in combination with brain MRIs have no additional benefit for the staging of patients with GGN lung adenocarcinoma before surgery.