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1.
Histopathology ; 84(1): 86-101, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37873676

ABSTRACT

NUT carcinoma and thoracic SMARCA4-deficient undifferentiated tumour are unique entities in the 5th edition of the World Health Organisation (WHO) Classification of Thoracic Tumours, whose definitions include molecular genetic abnormalities. These aggressive tumours require rapid work-ups on biopsies, but a broad list of differential diagnoses poses challenges for practising pathologists. This review provides an update on their key clinicopathological and molecular characteristics, as well as controversies regarding tumour classification and diagnostic strategy. Phenotypical assessment plays a substantial role in diagnosis because recurrent and predictable clinicopathological findings exist, including robust immunohistochemical phenotypes. Accurate diagnosis is crucial for appropriate management and a clearer understanding of the disease.


Subject(s)
Carcinoma , Thoracic Neoplasms , Humans , Transcription Factors/genetics , Nuclear Proteins/genetics , DNA Helicases/genetics , Biomarkers, Tumor , Carcinoma/diagnosis , Carcinoma/pathology , Thoracic Neoplasms/diagnosis , Thoracic Neoplasms/genetics , Thoracic Neoplasms/pathology
2.
Jpn J Clin Oncol ; 54(3): 265-270, 2024 Mar 09.
Article in English | MEDLINE | ID: mdl-38117955

ABSTRACT

Thoracic SMARCA4-deficient undifferentiated tumor is a newly recognized disease entity characterized as a high-grade malignant neoplasm with an undifferentiated or rhabdoid phenotype. The tumor was initially identified as a subtype of thoracic sarcoma with SMARCA4 loss, but further investigation resulted in its classification as a subtype of epithelial malignancies in the current World Health Organization classification. SMARCA4-deficient undifferentiated tumor is highly aggressive and has a poor prognosis. Because of its rarity, an optimal treatment strategy has not yet been identified. In this review, we summarize the literature on SMARCA4-deficient undifferentiated tumor in terms of its clinical characteristics, diagnosis, treatment strategy and future perspectives.


Subject(s)
Sarcoma , Soft Tissue Neoplasms , Thoracic Neoplasms , Humans , Sarcoma/diagnosis , Biomarkers, Tumor/genetics , Thoracic Neoplasms/genetics , Thoracic Neoplasms/diagnosis , Thoracic Neoplasms/pathology , DNA Helicases/genetics , Nuclear Proteins/genetics , Transcription Factors/genetics
3.
Jpn J Clin Oncol ; 54(8): 911-916, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-38717229

ABSTRACT

OBJECTIVE: Sarcomas of the bone and soft tissues are detected after the onset of pain, detectable mass and related symptoms in the absence of a standardized screening examination. However, primary chest wall sarcomas can be incidentally detected upon chest X-ray or computed tomography. Previous studies of incidental primary chest wall sarcomas lack prognosis and disease-specific clinical data. This study aimed to investigate the prognoses of patients with incidental chest wall sarcomas and compare them with those of symptomatic patients. METHODS: This study included 18 patients diagnosed with primary chest wall sarcoma between 2010 and 2023. Patient information such as age, sex, tumour diameter, tumour location, symptoms, treatment, time to treatment initiation, pathological diagnosis and outcome were retrospectively analysed. RESULTS: Among the 18 patients, the sarcomas were incidentally detected in five by chest X-ray and computed tomography in three and two patients, respectively. The pathological diagnoses of the patients were Ewing sarcoma, Chondrosarcoma grade 1, grade 2, periosteal osteosarcoma and malignant peripheral nerve sheath tumour. The patients had no symptoms at the first visit to our hospital, and no lesions in other organs were detected at the time of the initial examination. At the final follow-up, the patients remained disease-free after radical treatment. The tumour sizes of the five patients were significantly smaller than those of patients with symptoms (P = 0.003). CONCLUSIONS: The incidental detection of chest wall sarcomas and consequent early detection and treatment of tumours improves patient prognosis relative to that of symptomatically diagnosed patients.


Subject(s)
Incidental Findings , Sarcoma , Thoracic Wall , Humans , Male , Female , Thoracic Wall/pathology , Thoracic Wall/diagnostic imaging , Middle Aged , Sarcoma/pathology , Sarcoma/diagnostic imaging , Sarcoma/diagnosis , Sarcoma/therapy , Adult , Prognosis , Retrospective Studies , Aged , Young Adult , Tomography, X-Ray Computed , Adolescent , Thoracic Neoplasms/diagnostic imaging , Thoracic Neoplasms/pathology , Thoracic Neoplasms/diagnosis , Thoracic Neoplasms/therapy , Bone Neoplasms/diagnosis , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/pathology
4.
S D Med ; 77(4): 158-159, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38991159

ABSTRACT

Ewing sarcoma is a tumor primarily affecting children and young adults, and usually affects long bones. Extraosseous Ewing sarcoma (EES) is a rare primary tumor of soft tissues. We present a case of abdominal EES with metastasis to thoracic cavity, which presented as abdominal pain and vomiting in a 21-year-old previously healthy gentleman.


Subject(s)
Abdomen, Acute , Sarcoma, Ewing , Humans , Male , Sarcoma, Ewing/diagnosis , Sarcoma, Ewing/complications , Young Adult , Abdomen, Acute/etiology , Abdomen, Acute/diagnosis , Abdominal Neoplasms/diagnosis , Abdominal Neoplasms/complications , Thoracic Neoplasms/diagnosis , Thoracic Neoplasms/complications
5.
Cancer Sci ; 114(11): 4401-4412, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37732498

ABSTRACT

Comprehensive genomic profiling (CGP) is implemented to detect actionable gene aberrations and design matched therapies. Although malignant thoracic tumors are commonly detected through respiratory endoscopy, it is questionable whether the small specimens obtained thereof are sufficient for CGP. Therefore, this study aimed to investigate the suitability of respiratory endoscopy for sampling primary and metastatic thoracic tumors for CGP. Patients whose specimens were collected through respiratory endoscopy and assessed by pathologists to determine their suitability for CGP at our institution between June 2019 and May 2022 were reviewed retrospectively. The suitability of each procedure as a sampling technique for CGP and, in the cases actually analyzed, the distribution of the detected gene aberration were assessed. In total, 122 patients were eligible for analysis; the median age was 61 (range, 29-86) years, and 71 (58.2%) patients were male. Primary intrathoracic tumors were found in 91 (74.6%) cases, including 84 (68.9%) primary lung cancers; the remaining thoracic metastases of extrathoracic origin included various types. The suitability rates of specimens obtained using conventional bronchoscopy with and without cryobiopsy, endobronchial ultrasound-guided transbronchial needle aspiration, and medical thoracoscopy were 82.8% (24/29), 70.4% (19/27), 72.9% (35/48), and 100% (18/18), respectively. Of the 96 cases judged suitable, 83 were subjected to CGP, and all but one were successfully analyzed. Finally, 47 (56.6%) patients had at least one actionable gene aberration and eight (9.6%) were treated with the corresponding targeted therapies. In conclusion, specimens obtained through respiratory endoscopy are suitable for CGP; medical thoracoscopy and cryobiopsy in conventional bronchoscopy are particularly useful.


Subject(s)
Lung Neoplasms , Thoracic Neoplasms , Humans , Male , Middle Aged , Female , Retrospective Studies , Thoracic Neoplasms/genetics , Thoracic Neoplasms/diagnosis , Bronchoscopy/methods , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Genomics , Lung Neoplasms/pathology
6.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(2): 351-356, 2023 Apr 18.
Article in Zh | MEDLINE | ID: mdl-37042149

ABSTRACT

We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.


Subject(s)
Adenocarcinoma , Lung Neoplasms , Thoracic Neoplasms , Humans , Immune Checkpoint Inhibitors , Neoplasm Recurrence, Local , Lung Neoplasms/genetics , Thoracic Neoplasms/diagnosis , Thoracic Neoplasms/genetics , Thoracic Neoplasms/pathology , DNA Helicases , Nuclear Proteins , Transcription Factors
7.
Khirurgiia (Mosk) ; (10): 60-70, 2023.
Article in Russian | MEDLINE | ID: mdl-37916559

ABSTRACT

OBJECTIVE: To analyze the outcomes after different methods of post-resection chest wall defect reconstruction. MATERIAL AND METHODS: The study included 41 patients aged 22-73 years who underwent chest wall repair with local tissues and synthetic materials. Twelve (29.3±7.1%) patients had sarcoma, 9 (21.9±5.9%) - non-small cell lung cancer (NSCLC) with invasion of the chest, 9 (21.9±5.9%) - metastatic lesions, 8 (19.5±6.2%) - benign tumors, 2 (4.8±3.4%) - breast cancer with invasion of the chest wall, 1 (2.4±2.4%) - desmoid tumor. Seven patients were diagnosed with T3N0M0, 1 - T3N2M0, 1 - T2N0M1b (oss). Among patients with NSCLC with invasion into the chest wall, squamous cell cancer was verified in 4 (44.4±16.6%) patients, adenocarcinoma - in 4 (44.4±16.6%), neuroendocrine tumor - in 1 (11.2±10.5%) patient. Stages of surgeries are presented. RESULTS: We analyzed treatment outcomes in 41 patients. Five (12.2%) patients had seroma, hemothorax, thoracopleural fistula, subcutaneous emphysema and fatal asystole. There were no postoperative complications associated with paradoxical breathing. CONCLUSION: Accurate morphological verification prior to treatment is valuable to determine the stages of combined treatment of chest wall tumors. Chest wall defect closure with own tissues and synthetic materials is necessary after extensive resections. A multidisciplinary approach involving thoracic and plastic surgeons is needed.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Plastic Surgery Procedures , Thoracic Neoplasms , Thoracic Wall , Humans , Thoracic Wall/surgery , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/diagnosis , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Treatment Outcome , Thoracic Neoplasms/diagnosis , Thoracic Neoplasms/surgery
8.
Khirurgiia (Mosk) ; (8): 20-30, 2023.
Article in Russian | MEDLINE | ID: mdl-37530767

ABSTRACT

OBJECTIVE: To analyse safety and expediency of cardiac surgical technologies including cardiopulmonary bypass (CPB) in patients with locally advanced lung cancer and invasive tumors of the mediastinum. MATERIAL AND METHODS: Cardiac surgical techniques and CPB were used in 23 patients (group 1) with locally advanced thoracic tumors between 2005 and 2015. For the same period, there were 22 patients (group 2) who underwent combined surgeries and could have had similar techniques. However, these techniques were not used for various reasons. Mediastinal malignancies and non-small cell lung cancer were diagnosed in 26 (57.8%) and 19 (42.2%) patients, respectively. Invasion of superior vena cava (n=15), aorta (n=13) and pulmonary artery (n=12) was the most common. Lesion of innominate vein (n=8), left atrium (n=6) and innominate artery (n=4) was less common. A total of 21 pneumonectomies were performed (14 in the first group and 7 in the second group). Lobectomy was less common (one patient in each group). Sublobar lung resection was performed in 10 patients (2 patients in the first group and 8 ones in the second group). All resections were total in the first group (R0) that was confirmed by routine morphological examination of resection margins of different organs and vessels. The situation was worse in the second group (R1 in 19 (86.4%) patients, R2 in 3 (13.6%) patients). RESULTS: Total postoperative morbidity was 53.3%, mortality - 8.2%. These values are higher compared to patients undergoing surgical treatment for thoracic malignancies. Incidence of postoperative complications was higher in the first group (16 (69.6%) and 8 (36.4%), respectively). Four patients died in the first group. Sepsis (n=2), acute right ventricular failure (n=1) and acute myocardial infarction (n=1) caused death. There were no lethal outcomes in the second group. Various postoperative complications were diagnosed only in 8 (36.4%) patients. The long-term results were followed-up in 80% of patients. In the first group, 3- and 5-year survival rates were 30.5% and 25%, respectively (median 43.8 months). In the second group, these values were 25% and 2%, respectively (median 24.9 months). Long-term mortality in the second group was caused by progression of malignant process, including local recurrence, after palliative surgery (R1, R2 resection). CONCLUSION: Higher risk of postoperative complications and mortality in patients undergoing on-pump surgery is compensated by significantly better long-term results. Further progress is associated with higher safety of CPB, as well as solving some organizational and educational problems.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Thoracic Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/surgery , Vena Cava, Superior/surgery , Feasibility Studies , Thoracic Neoplasms/diagnosis , Thoracic Neoplasms/surgery , Thoracic Neoplasms/pathology , Postoperative Complications/epidemiology , Postoperative Complications/pathology , Retrospective Studies
9.
Monaldi Arch Chest Dis ; 92(4)2022 Feb 17.
Article in English | MEDLINE | ID: mdl-35172568

ABSTRACT

The incidence rate of tuberculosis in developed countries is low. The most common presentation of this disease is its pulmonary form but with the increasing use of immunosuppressive drugs, extra-pulmonary tuberculosis is re-emerging. Nevertheless, sternal bone involvement is uncommon. We report the case of an eighty-three-year-old man who presented a painful sternal mass which progressed towards cutaneous ulceration. The first diagnostic hypothesis was neoplasia. The pathological and microbiological diagnosis of tuberculosis was achieved after surgical biopsy. The patient received treatment against tuberculosis for nine months enabling recovery without surgery. This case illustrates the importance of having a diagnosis prior to any kind of treatment facing any voluminous parietal thoracic lesions.  This diagnosis is made possible by surgical samples and interdisciplinary teamwork. This case underlines that tuberculosis remains a differential diagnosis that must be evoked in case of unusual bone mass.


Subject(s)
Illusions , Thoracic Neoplasms , Thoracic Wall , Tuberculosis , Aged, 80 and over , Humans , Male , Sternum/microbiology , Sternum/pathology , Thoracic Neoplasms/diagnosis , Tuberculosis/diagnosis
10.
J Surg Res ; 260: 149-154, 2021 04.
Article in English | MEDLINE | ID: mdl-33340868

ABSTRACT

BACKGROUND: Primary sarcomas of the chest wall are rare aggressive tumors. Surgery is part of the multimodal treatment. We describe our institutional patient cohort and evaluate prognostic factors. METHODS: All patients who had curative intent surgery for primary chest wall sarcoma from 2004 to 2019 were retrospectively reviewed. Impact on survival-calculated from the date of surgery until last follow-up- was assessed for the following variables: age, gender, type of resection, size, grading, stage, completeness of resection, and neoadjuvant and adjuvant therapy. RESULTS: Twenty-three patients (15 males, 65%) with a median age of 54 y (4 to 82) were included. Most common histology was chondrosarcoma (n = 5, 22%). Seven patients (30%) received neoadjuvant and 13 patients (57%) received adjuvant treatment. R0 resection was achieved in 83%. Extended chest wall resection was performed in 14 patients (61%), including lung (n = 13, 57%), diaphragm (n = 2, 9%) and pericardium (n = 1, 4%). Morbidity and 90-day mortality were 23% and 0%, respectively. Three- and 5-year overall survival was 53% and 35%, respectively. R0 resection was predictor of overall survival (P = 0.029). Tumor grade and extended resections were predictors for recurrence (P = 0.034 and P = 0.018, respectively). CONCLUSIONS: Surgical resection of primary chest wall sarcoma is a safe procedure even when extended resection is required.


Subject(s)
Sarcoma/surgery , Thoracic Neoplasms/surgery , Thoracic Wall/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Sarcoma/diagnosis , Sarcoma/mortality , Survival Analysis , Thoracic Neoplasms/diagnosis , Thoracic Neoplasms/mortality , Treatment Outcome , Young Adult
11.
Cytopathology ; 32(4): 416-427, 2021 07.
Article in English | MEDLINE | ID: mdl-33606285

ABSTRACT

INTRODUCTION: The objectives were: to measure the proportion of aspirated material used to make direct slides for rapid onsite evaluation (ROSE) at endobronchial (EBUS) and endoscopic ultrasound (EUS) in suspected thoracic malignancy; and to correlate pass weights with ROSE category and needle size. METHOD: All EBUS and EUS cases for possible thoracic malignancy October 2018-May 2019 were included. All material from each pass was expelled into a Petri dish. One drop of material was placed on each of two slides; one used for ROSE, the other fixed and remaining material processed to cell block. Dish and slides were weighed before and after this procedure on a sensitive balance and weight of aspirate and slide material calculated. When ROSE identified malignancy, slide production ceased but target sampling for ancillary studies continued. RESULTS: ROSE accuracy was 96.8%. Mean percentage by target of aspirated material used to make direct slides for ROSE was 1.9% in malignant cases and 3.6% in non-malignant cases (P = .027 for difference). Mean percentage by pass was 5.9%. Mean weight of a single aspirate was 128.8 mg. Mean weight of aspirates insufficient on ROSE (175.7 mg) was significantly higher than the mean weight of benign or malignant aspirates (117.1 and 114.0 mg, respectively). Mean weight of aspirates using 22G needles (132.6 mg) was significantly higher than that for 25G needles (87.1 mg). CONCLUSION: Material made into direct slides at EBUS and EUS and used in part for ROSE uses a tiny proportion of aspirated material with over 98% processed to cell block and available for ancillary testing in malignant cases.


Subject(s)
Bronchoscopy , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Endosonography , Rapid On-site Evaluation , Thoracic Neoplasms/diagnosis , Thoracic Neoplasms/pathology , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged
12.
Ann Diagn Pathol ; 54: 151800, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34464935

ABSTRACT

BACKGROUND: Challenging emerging entities with distinctive molecular signatures may benefit from algorithms for diagnostic work-up. METHODS: Fusion sarcomas (2020-2021, during pandemic) were diagnosed by clinicoradiology, morphology, phenotype, and next-generation sequencing (NGS). RESULTS: Six fusion sarcomas in two males and four females involved the chest-wall, neck, or extremities; ages ranged 2-73, median 18 years. Sizes ranged 5.3-25.0, median 9.1 cm. These include high grade 1) TPR-NTRK1 of proximal femur with a larger rounded soft tissue mass, previously considered osteosarcoma yet without convincing tumor matrix. A pathologic fracture necessitated emergency hemipelvectomy (NED) and 2) novel KANK1-NTRK2 sarcoma of bone and soft tissue with spindled pleomorphic to epithelioid features (AWD metastases). 3) Novel ERC1-ALK unaligned fusion, a low grade infiltrative deep soft tissue hand sarcoma with prominent-vascularity, myopericytoid/lipofibromatosis-like ovoid cells, and collagenized stroma, was successfully treated with ALK-inhibitor (Crizotinib), avoiding amputation. These NTRK and ALK tumors variably express S100 and CD34 and were negative for SOX10. 4) and 5) CIC-DUX4 round cell tumors (rapid metastases/demise), one with COVID superinfection, were previously treated as Ewing sarcoma. These demonstrated mild pleomorphism and necrosis, variable myxoid change and CD99 reactivity, and a distinctive dot-like-Golgi WT1 immunostaining pattern. 6) A chest wall/thoracic round cell sarcoma, focal CD34/ keratins/CK7, revealed nuclear-STAT6, STAT6-NAB2 by NGS, confirming malignant solitary fibrous tumor, intermediate-risk-stratification (AWD metastases). CONCLUSIONS: Recent fusion sarcomas include new KANK1-NTRK2 and ERC1-ALK, the latter successfully treated by targeted-therapy. ALK/NTRK fusion partners TPR and KANK1 suggest unusual high-grade morphology/behavior. Clinicoradiologic, morphologic, and phenotypic algorithms can prompt molecular-targeted immunostains or NGS for final classification and promising inhibitor therapy.


Subject(s)
Biomarkers, Tumor/genetics , Femoral Neoplasms/genetics , Gene Fusion , Head and Neck Neoplasms/genetics , Sarcoma/genetics , Soft Tissue Neoplasms/genetics , Thoracic Neoplasms/genetics , Adolescent , Adult , Aged , Algorithms , Antineoplastic Agents/therapeutic use , Child , Child, Preschool , Extremities/pathology , Female , Femoral Neoplasms/diagnosis , Femoral Neoplasms/drug therapy , Femoral Neoplasms/pathology , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/pathology , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Neoplasm Grading , Phenotype , Prognosis , Sarcoma/diagnosis , Sarcoma/drug therapy , Sarcoma/pathology , Soft Tissue Neoplasms/diagnosis , Soft Tissue Neoplasms/drug therapy , Soft Tissue Neoplasms/pathology , Thoracic Neoplasms/diagnosis , Thoracic Neoplasms/drug therapy , Thoracic Neoplasms/pathology , Thoracic Wall/pathology , Young Adult
13.
Mod Pathol ; 33(8): 1571-1580, 2020 08.
Article in English | MEDLINE | ID: mdl-32203089

ABSTRACT

INSM1 is a diagnostic marker for neuroendocrine tumors originating in multiple anatomic sites. In the lung, INSM1 shows 76-97% sensitivity for neuroendocrine tumors overall. Our aim was to characterize INSM1 as a diagnostic marker for small cell carcinoma in the context of its epithelial, lymphoid, and mesenchymal morphologic mimics. Immunohistochemistry was performed on 231 tumors, including lung neuroendocrine tumors, nonneuroendocrine carcinomas of the thoracic cavity, diffuse large B-cell lymphomas, and small round cell sarcomas, using an anti-INSM1 mouse monoclonal antibody. Extent (0-100%) and intensity (1-3+) of nuclear INSM1 staining was multiplied in each case to calculate an H-score. Demographic and clinical information was obtained from the medical record. INSM1 had an overall sensitivity and specificity of 81.5% and 82.7% for small cell carcinoma, respectively, using a threshold established with a receiver operating characteristic curve. 40/48 (82.7%) small cell carcinomas were positive for INSM1, including 19/24 (79%) small cell carcinomas that were negative for chromogranin and synaptophysin. 5/5 carcinoids and 21/28 (75%) large cell neuroendocrine carcinomas showed INSM1 expression. Among nonneuroendocrine tumors, 7/38 (18%) lung adenocarcinomas, 2/17 (12%) lung squamous cell carcinomas, 4/10 (40%) thymic carcinomas, 4/12 (33%) adenoid cystic carcinomas, 1/19 (5%) diffuse large B-cell lymphomas, 4/11 (36%) alveolar rhabdomyosarcomas, and 4/23 (17%) Ewing sarcomas were positive for INSM1. No synovial sarcomas or desmoplastic small round cell tumors were positive. Weak, focal INSM1 expression alone is insufficient as a diagnostic marker for small cell carcinoma, but is sensitive and specific, easy to interpret in small biopsies, and makes a valuable addition to a diagnostic panel.


Subject(s)
Biomarkers, Tumor/metabolism , Lung Neoplasms/diagnosis , Repressor Proteins/biosynthesis , Small Cell Lung Carcinoma/diagnosis , Aged , Biomarkers, Tumor/analysis , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Repressor Proteins/analysis , Sensitivity and Specificity , Thoracic Neoplasms/diagnosis
14.
Int J Mol Sci ; 21(17)2020 Aug 21.
Article in English | MEDLINE | ID: mdl-32825667

ABSTRACT

Extracellular vesicles (EVs), such as exosomes, are critical mediators of intercellular communication between tumor cells and other cells located in the microenvironment but also in more distant sites. Exosomes are small EVs that can carry a variety of molecules, such as lipids, proteins, and non-coding RNA, especially microRNAs (miRNAs). In thoracic cancers, including lung cancers and malignant pleural mesothelioma, EVs contribute to the immune-suppressive tumor microenvironment and to tumor growth and metastasis. In this review, we discuss the recent understanding of how exosomes behave in thoracic cancers and how and why they are promising liquid biomarkers for diagnosis, prognosis, and therapy, with a special focus on exosomal miRNAs.


Subject(s)
Extracellular Vesicles/pathology , Thoracic Neoplasms/pathology , Tumor Microenvironment , Biomarkers, Tumor/analysis , Clinical Trials as Topic , Extracellular Vesicles/genetics , Extracellular Vesicles/metabolism , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/pathology , MicroRNAs , Prognosis , Thoracic Neoplasms/diagnosis , Thoracic Neoplasms/immunology , Thoracic Neoplasms/therapy
15.
Heart Lung Circ ; 29(10): 1566-1570, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32280015

ABSTRACT

BACKGROUND: To our knowledge, this is the first time that a three-dimensional (3D)-printed model was used as an intraoperative template to recreate the resected portion of the lateral chest wall after resection of a large chest-wall tumour. METHODS: Fabrication of 3D-printed models requires collaboration among a surgeon, radiologist, segmenter, and 3D printing centre. Three-dimensional models are created with computed tomographic and magnetic resonance data. These models can provide an accurate guide for surgical resection and can be used intraoperatively as a template to construct tailored prostheses. RESULTS: We achieved complete resection of the chest wall defect, restored skeletal function and physiologic chest excursion, and achieved the best cosmetic appearance in all cases. CONCLUSIONS: Small- to medium-sized chest wall defects can be repaired with musculocutaneous flaps with or without prosthetic materials, but more complicated defects require increasingly sophisticated reconstructive techniques and technologies. An advanced technique is the use of a 3D-printed model of the chest wall as an intraoperative template.


Subject(s)
Printing, Three-Dimensional , Prostheses and Implants , Thoracic Neoplasms/surgery , Thoracic Wall/diagnostic imaging , Thoracoplasty/methods , Humans , Prosthesis Design , Thoracic Neoplasms/diagnosis , Thoracic Wall/surgery , Tomography, X-Ray Computed
16.
Ann Pathol ; 40(2): 120-133, 2020 Apr.
Article in French | MEDLINE | ID: mdl-32035641

ABSTRACT

About 5% of gastroenteropancreatic and thoracic neuroendocrine neoplasms (NENs) arise in the context of an inherited tumour syndrome. The two most frequent syndromes are: multiple endocrine neoplasia type 1 (MEN1), associated with a large spectrum of endocrine and non endocrine tumours, including duodenopancreatic, thymic and bronchial NENs, and the von Hippel-Lindau syndrome VHL, associated with pancreatic NENs. Two inherited syndromes have a low incidence of NENs: neurofibromatosis type 1 (NF1), associated with duodenal somatostatinomas, and tuberous sclerosis (TSC), associated with pancreatic NENs. Two rare syndromes have a high incidence of NENs: multiple endocrine neoplasia type 4 (MEN4), with a tumour spectrum similar to that of MEN1, and glucagon cell hyperplasia neoplasia (GCHN), involving only the pancreas. It is likely that other syndromes remain to be characterized, especially in familial small-intestinal NENs. The diagnosis is usually raised because of the suggestive clinical setting: young age at diagnosis, multiple tumours in multiple organs, familial history. Except in VHL and NF1, tumours themselves do not show specific pathological features; they usually are well differentiated and of low histological grade; their prognosis is good, except for MEN1-associated thymic NENs. The most suggestive pathological feature is their combination with various endocrine and/or non endocrine lesions in the adjacent tissue. Pathological examination is important, for a correct diagnosis and for an accurate management of the patients and their families, who must be referred to expert centers.


Subject(s)
Neoplastic Syndromes, Hereditary , Neuroendocrine Tumors/pathology , Duodenal Neoplasms/diagnosis , Genetic Predisposition to Disease , Humans , Intestinal Neoplasms/complications , Intestinal Neoplasms/diagnosis , Intestinal Neoplasms/genetics , Intestinal Neoplasms/pathology , Intestines/pathology , Multiple Endocrine Neoplasia/complications , Multiple Endocrine Neoplasia/diagnosis , Multiple Endocrine Neoplasia/genetics , Multiple Endocrine Neoplasia/pathology , Multiple Endocrine Neoplasia Type 1/complications , Multiple Endocrine Neoplasia Type 1/diagnosis , Multiple Endocrine Neoplasia Type 1/genetics , Multiple Endocrine Neoplasia Type 1/pathology , Neoplastic Syndromes, Hereditary/complications , Neoplastic Syndromes, Hereditary/diagnosis , Neoplastic Syndromes, Hereditary/pathology , Neuroendocrine Tumors/complications , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/genetics , Pancreas/pathology , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Stomach Neoplasms/complications , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Thoracic Neoplasms/diagnosis , Thorax/pathology , Tuberous Sclerosis/etiology , Tuberous Sclerosis/pathology , von Hippel-Lindau Disease/complications , von Hippel-Lindau Disease/diagnosis , von Hippel-Lindau Disease/genetics , von Hippel-Lindau Disease/pathology
17.
Wiad Lek ; 73(3): 614-618, 2020.
Article in English | MEDLINE | ID: mdl-32285844

ABSTRACT

Tumours and tumorous lesions of head and neck account for 10% of all oncological pathologies. Branhyogenic cancer is found in 4.5% of patients with lateral cysts in the neck. The article highlights the results of research the clinical case of branhyogenic cancer, provide its clinical and morphological analysis. The aim of our work was to study the clinical case of bronchial cancer, providing clinical and pathomorphological analysis. Examination and treatment was conducted in accordance with the clinical protocol using the diagnostic criteria necessary for management of patients diagnosed with tumours and tumorous lesions in a particular clinical case. We applied ultrasound examination of the locus, angiography of head and neck vessels with tomohexol and with 3D reconstruction, histological examination of surgical specimens (macroscopy and microscopy). On the basis of clinical investigaton, ultrasound examination, angiography clinical diagnosis was formulated - lateral cyst on the left side of the neck. A radical surgical removal of the mass was conducted. Histopathological conclusion: there is a proliferation of cystic transitional cell epithelium with the locus of invasive squamous cell carcinoma in the cystic wall that suggests malignant transformation of bronchogenic cyst. Final diagnosis: branhyogenic cancer. Thorough examination and analysis of a clinical case demonstrates that the development of branhyogenic cancer, is histo-genetically associated with lateral cysts in the neck. Complexity of diagnosing and high percentage of malignancy induces to more early discovery and removal of lateral cysts in the neck.


Subject(s)
Thoracic Neoplasms/diagnosis , Cell Transformation, Neoplastic , Diagnosis, Differential , Humans , Neck , Ultrasonography
18.
Eur Radiol ; 29(5): 2553-2559, 2019 May.
Article in English | MEDLINE | ID: mdl-30547199

ABSTRACT

OBJECTIVES: Increasing awareness of potential side effects from gadolinium-based contrast agents has underlined the need for contrast-free magnetic resonance imaging (MRI). Numerous recent articles evaluated the risk of potential brain deposits, with the result that research is putting the focus more on alternative unenhanced imaging techniques. The aim of this study was to determine the need for contrast media for chest MRI in primary staging and follow-up care of lymphoma. METHODS: This monocentric, retrospective study encompassed patients under 25 years of age who had undergone histopathological examination of thoracic lymph nodes and at least one chest MRI examination with unenhanced and contrast-enhanced sequences. Seven different thoracic lymph node stations including mediastinal, hilar, periclavicular, and axillary regions were evaluated by two readers regarding lesion diameter, number, shape, necrosis, and infiltration of surrounding structures. Findings were categorized into suspicious (> 1 cm; round; necrosis; infiltration) or non-suspicious. RESULTS: Fifty-one patients (mean age, 16.0 ± 3.7 yrs) with thoracic Hodgkin (70.6%) and non-Hodgkin lymphoma (25.5%) and lymphadenopathy (3.9%) were retrospectively included. Most lymph nodes categorized as suspicious were located in the mediastinal station (86.4%). High agreement (κ = 0.81) between unenhanced and contrast-enhanced sequences was found for both suspicious and non-suspicious lymph nodes. Significant (p < 0.001), but small difference (1 mm) was observed only in sizing mediastinal lymph nodes (all other p > 0.05). No significant difference (smallest p = 0.08) was shown for the use of five different types of contrast media. CONCLUSION: MRI in young patients with thoracic lymphoma can safely be done without the use of contrast agent. KEY POINT: • Thoracic magnetic resonance imaging in young lymphoma patients can safely be done without gadolinium-based contrast agents.


Subject(s)
Lymphoma/diagnosis , Magnetic Resonance Imaging/methods , Organometallic Compounds/pharmacology , Thoracic Neoplasms/diagnosis , Adolescent , Adult , Child , Child, Preschool , Contrast Media/pharmacology , Female , Humans , Male , Retrospective Studies , Young Adult
19.
Eur Radiol ; 29(8): 4303-4314, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30350166

ABSTRACT

OBJECTIVE: To investigate the incidence of thoracic recurrence and the diagnostic value of chest CT for postoperative surveillance in curatively-resected colorectal cancer (CRC) patients. METHODS: This retrospective study consisted of 648 CRC patients (M:F, 393:255; mean age, 66.2 years) treated with curative surgery between January 2010 and December 2012. The presence of CRC recurrence over follow-ups was analysed and recurrence-free survival and risk factors of recurrence were assessed using Kaplan-Meier analysis with log-rank test and Cox-regression analysis, respectively. RESULTS: Over a median follow-up of 57 months, thoracic recurrence occurred in 8.0% (52/648) of patients with a median recurrence-free survival rate of 19.5 months. Among the 52 patients with thoracic recurrence, 18 (2.7%) had isolated thoracic recurrence, and only five (0.8%) were diagnosed through chest CT. Risk factors of overall thoracic recurrence included age, positive resection margin, presence of venous invasion, positive pathologic N-class, and presence of abdominal recurrence (odds ratio [OR] = 1.78, 19.691, 2.993, 2.502, and 31.137; p = 0.045, 0.004, 0.001, 0.005, and p < 0.001, respectively). As for isolated thoracic recurrence, serum carcinoembryonic antigen level ≥ 5 ng/mL during postoperative follow-up (OR = 9.112; p < 0.001) was demonstrated to be the only predictive factor. There were no thoracic recurrences in patients with CRC stages 0 and I. CONCLUSION: In patients with curatively-resected CRCs, routine surveillance using chest CT may be of limited value, particularly in those with CRC stages 0 or I, as recurrence only detectable through chest CT was shown to be rare. KEY POINTS: • Postoperative thoracic recurrence only detectable through chest CT was shown to be rare. • There were no thoracic recurrences in colorectal cancers stage 0 and I. • Postoperative surveillance chest CT is of limited value in patients with curatively resected colorectal cancers.


Subject(s)
Colectomy , Colorectal Neoplasms/diagnosis , Neoplasm Recurrence, Local/diagnosis , Thoracic Neoplasms/epidemiology , Tomography, X-Ray Computed/methods , Aged , Biomarkers, Tumor/blood , Carcinoembryonic Antigen/blood , Colorectal Neoplasms/secondary , Colorectal Neoplasms/surgery , Female , Humans , Incidence , Male , Postoperative Period , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors , Thoracic Neoplasms/diagnosis
20.
Future Oncol ; 15(14): 1551-1563, 2019 May.
Article in English | MEDLINE | ID: mdl-30852916

ABSTRACT

Aim: To describe I-O Optimise, a multinational program providing real-world insights into lung cancer management. Materials & methods: Real-world data source selection for I-O Optimise followed a structured approach focused on population coverage, key variable capture, continuous/consistent data availability, record duration and data latency, and database expertise. Results: As of 31 October 2018, seven real-world data sources were included in I-O Optimise, providing data on characteristics, treatment patterns and clinical outcomes from more than 45,000 patients/year with non-small-cell lung cancer, small-cell lung cancer and mesothelioma across Denmark, Norway, Portugal, Spain, Sweden and the UK. Conclusion: The ongoing I-O Optimise initiative has the potential to provide a broad, robust and dynamic research platform to continually address numerous research objectives in the lung cancer arena.


Subject(s)
Medical Informatics/methods , Research , Thoracic Neoplasms/epidemiology , Databases, Factual , Disease Management , Europe , Global Health , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Lung Neoplasms/therapy , Patient Care , Patient Outcome Assessment , Practice Patterns, Physicians' , Public Health Surveillance , Thoracic Neoplasms/diagnosis , Thoracic Neoplasms/therapy
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