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Nature Jul 2023Many cancers originate from stem or progenitor cells hijacked by somatic mutations that drive replication, exemplified by adenomatous transformation of pulmonary...
Many cancers originate from stem or progenitor cells hijacked by somatic mutations that drive replication, exemplified by adenomatous transformation of pulmonary alveolar epithelial type II (AT2) cells. Here we demonstrate a different scenario: expression of KRAS(G12D) in differentiated AT1 cells reprograms them slowly and asynchronously back into AT2 stem cells that go on to generate indolent tumours. Like human lepidic adenocarcinoma, the tumour cells slowly spread along alveolar walls in a non-destructive manner and have low ERK activity. We find that AT1 and AT2 cells act as distinct cells of origin and manifest divergent responses to concomitant WNT activation and KRAS(G12D) induction, which accelerates AT2-derived but inhibits AT1-derived adenoma proliferation. Augmentation of ERK activity in KRAS(G12D)-induced AT1 cells increases transformation efficiency, proliferation and progression from lepidic to mixed tumour histology. Overall, we have identified a new cell of origin for lung adenocarcinoma, the AT1 cell, which recapitulates features of human lepidic cancer. In so doing, we also uncover a capacity for oncogenic KRAS to reprogram a differentiated and quiescent cell back into its parent stem cell en route to adenomatous transformation. Our work further reveals that irrespective of a given cancer's current molecular profile and driver oncogene, the cell of origin exerts a pervasive and perduring influence on its subsequent behaviour.
Topics: Humans; Adenocarcinoma of Lung; Cellular Reprogramming; Lung Neoplasms; Proto-Oncogene Proteins p21(ras); Stem Cells; Extracellular Signal-Regulated MAP Kinases
PubMed: 37468622
DOI: 10.1038/s41586-023-06324-w -
Food Safety (Tokyo, Japan) Mar 2020FSCJ conducted a risk assessment of fluxametamide (CAS No. 928783-29-3), an isoxazoline insecticide, based on results from various studies. The data used in the...
FSCJ conducted a risk assessment of fluxametamide (CAS No. 928783-29-3), an isoxazoline insecticide, based on results from various studies. The data used in the assessment include the fate in animals, fate in plants, residues in crops, subacute toxicity, subacute neurotoxicity, chronic toxicity, combined chronic toxicity/carcinogenicity, carcinogenicity, two-generation reproductive toxicity, developmental toxicity, and genotoxicity. Alveolar macrophage accumulation, vacuolated epithelial cells in the small intestine, and hepatocellular vacuolation are observed in various toxicity studies. Increased incidences of thyroid follicular cell adenoma in male rats and of hepatocellular adenoma in male mice were observed in carcinogenicity studies. However, a genotoxic mechanism was unlikely to be involved in the tumor increases. FSCJ specified an acceptable daily intake (ADI) of 0.0085 mg/kg bw per day, applying a safety factor of 100 to the NOAEL, 0.85 mg/kg bw per day, that was derived from the two-year combined chronic toxicity/carcinogenicity study in rats.
PubMed: 32231959
DOI: 10.14252/foodsafetyfscj.D-20-00006 -
Medicine Dec 2023To analyze the clinical-pathological characteristics of 3 cases of bronchiolar adenoma/pulmonary ciliary mucinous nodular papillary tumors, and to improve the... (Review)
Review
OBJECTIVE
To analyze the clinical-pathological characteristics of 3 cases of bronchiolar adenoma/pulmonary ciliary mucinous nodular papillary tumors, and to improve the understanding of bronchiolar adenoma (BA)/ciliated muconodular papillary tumors (CMPT) (bronchiolar adenoma/ciliated muconodular papillary tumor).
METHODS
Retrospective analysis was done on the clinical information, diagnosis, and treatment of 3 instances of BA/CMPT at the Second People's Hospital of Weifang City. By scanning the CNKI, Wanfang, VIP database, and Pubmed database using the English key words "bronchiolar adenoma, ciliated muconodular papillary tumor," respectively patients with comprehensive clinical data were gathered, and studies from January 2002 to August 2021 that were relevant to the patients were examined.
RESULTS
A total of 35 articles and 71 instances were found, including 3 cases in our hospital, for a total of 74 cases. There were 31 males and 43 females among them, ranging in age from 18 to 84 years (average 63 years), and 15 cases had a smoking history. The majority of them were discovered by physical examination and had no clinical symptoms. The majority of the imaging revealed solid nodules with variable forms, with some ground-glass nodules displaying vacuole and bronchial inflation signs. BA/CMPT are generally gray-white, gray-brown solid nodules with obvious boundaries but no envelope with a maximum dimension of 4 to 45 mm (average 10.6 mm) on gross examination. Acinar, papillary, and lepidic formations can be seen under the microscope at high magnification; the majority of these structures are made up of tripartite epithelial components, including basal cells, mucous cells, ciliated columnar cells, and alveolar epithelial cells, demonstrating a variety of combinations. An important basis for diagnosis in immunohistochemistry is the continuous positive basal cell layer that is shown by p63, p40, and CK5/6. BRAF and epidermal growth factor receptor are the genes that are most frequently mutated. All of the patients showed no signs of metastasis or recurrence during follow-up period.
CONCLUSION
BA/CMPT is a rare benign tumor of lung epithelium. Because imaging and intraoperative cryosection diagnosis are easy to be misdiagnosed as malignant, it is necessary to further improve understanding and improve immunohistochemistry and genetic examination.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Young Adult; Adenoma; Bronchioles; Epithelial Cells; Lung Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Retrospective Studies; Case Reports as Topic
PubMed: 38115282
DOI: 10.1097/MD.0000000000036559 -
Pathologica Aug 2022Alveolar adenoma is a rare tumour of the lung. It is typically found in asymptomatic adults as a peripheral or subplerual nodule on imaging examination. Microscopically,... (Review)
Review
Alveolar adenoma is a rare tumour of the lung. It is typically found in asymptomatic adults as a peripheral or subplerual nodule on imaging examination. Microscopically, the tumour is composed of admixture of epithelial and mesenchymal component in variable sized cystic or alveolar structures. The tumour shows a benign nature. There have been no reported recurrences or metastases. Malignant transformation of alveolar adenoma and coexisting with lung carcinoma have been rarely described. In this article, we report a case of an alveolar adenoma and coexisting atypical adenomatous hyperplasia. This case, contributing to the limited numbers of cases described to date, illustrates the importance of awareness on the possibility of alveolar adenoma being associated with lung carcinoma and its precursor lesions especially when diagnosed by small biopsy specimens.
Topics: Adenoma; Adult; Carcinoma; Humans; Hyperplasia; Lung Neoplasms; Precancerous Conditions
PubMed: 36136901
DOI: 10.32074/1591-951X-755 -
Analytical Cellular Pathology... 2020Papillary adenoma of the lung is a rather rare tumor. We will present a case of papillary adenoma in the lung with malignant transformation in a 65-year-old male... (Review)
Review
Papillary adenoma of the lung is a rather rare tumor. We will present a case of papillary adenoma in the lung with malignant transformation in a 65-year-old male patient. A high dense soft tissue mass was detected in the lateral segment of the right middle lobe by CT examination. Cytologically, the tumor contained the benign cells similar to normal alveolar epithelium and the malignant cells which were significantly enlarged and irregular, crowded, or overlapping. Immunohistochemical staining showed that the epithelial cells were diffusely positive for TTF-1, napsin-A, and CK7, but were negative for p63, p40, CK5/6, CgA, Syn, CD56, and TG. The Ki67 index was about 5%. All of these evidences indicated that it was a case of papillary adenoma with malignant transformation. Thus, it should be noted that more active treatment measures should be taken to treat pulmonary papillary adenoma.
Topics: Adenoma; Aged; Bronchoscopy; Cell Aggregation; Cell Transformation, Neoplastic; Humans; Lung Neoplasms; Lymphocytes; Male; Neoplasm Proteins; Neutrophils; Plasma Cells; Tomography, X-Ray Computed
PubMed: 33282636
DOI: 10.1155/2020/8827056 -
Human Cell Jul 2020This study aimed to investigate the usefulness of the thyroid-related hormones as markers of acute systemic hypoxia/ischemia to identify deaths caused by asphyxiation...
This study aimed to investigate the usefulness of the thyroid-related hormones as markers of acute systemic hypoxia/ischemia to identify deaths caused by asphyxiation due to neck compression in human autopsy cases. The following deaths from pathophysiological conditions were examined: mechanical asphyxia and acute/subacute blunt head injury; acute/subacute non-head blunt injury; sharp instrument injury as the hemorrhagic shock condition; drowning as alveolar injury; burn; and death due to cardiac dysfunction. Blood samples were collected from the left and right cardiac chambers and iliac veins, and serum triiodothyronine (T3), thyroxine (T4), thyroglobulin (Tg), and thyroid-stimulating hormone (TSH) levels were measured using electrochemiluminescence immunoassays. Two types of thyroid cell lines were used to confirm independent thyroid function under the condition of hypoxia (3% O). The human thyroid carcinoma cell line (HOTHC) cell line derived from human anaplastic thyroid carcinoma and the UD-PTC (sample of the second resection papillary thyroid carcinoma) cell line derived from human thyroid papillary adenoma, which forms Tg retention follicles, were used to examine the secretion levels of T3, T4, and Tg hormones. The results showed a strong correlation between T3 and T4 levels in all blood sampling sites, while the TSH and Tg levels were not correlated with the other markers. Serum T3 and T4 levels were higher in cases of mechanical asphyxia and acute/subacute blunt head injury, representing hypoxic and ischemic conditions of the brain as compared to those in other causes of death. In the thyroid gland cell line, T4, T3, and Tg levels were stimulated after exposure to hypoxia for 10-30 min. These findings suggest that systemic advanced hypoxia/ischemia may cause a rapid and TSH-independent release of T3 and T4 thyroid hormones in autopsy cases. These findings demonstrate that increased thyroid-related hormone (T3 and T4) levels in the pathophysiological field may indicate systemic hypoxia/ischemia.
Topics: Adult; Aged; Aged, 80 and over; Asphyxia; Autopsy; Biomarkers; Female; Head Injuries, Closed; Humans; Hypoxia; Ischemia; Male; Middle Aged; Thyroglobulin; Thyrotropin; Thyroxine; Triiodothyronine
PubMed: 32146707
DOI: 10.1007/s13577-020-00341-x -
Diagnostic Pathology Oct 2022Pulmonary papillary adenoma is a rare benign tumor in the periphery of the lung. We report a 66-year-old female patient with a tumor in the lower lobe of the right lung... (Review)
Review
BACKGROUND
Pulmonary papillary adenoma is a rare benign tumor in the periphery of the lung. We report a 66-year-old female patient with a tumor in the lower lobe of the right lung and present the clinicopathological features and review the literature.
CASE PRESENTATION
A tumor in the lower lobe of the right lung was found incidentally on chest X-ray during the physical examination of the patient, and the patient occasionally had a dry cough that was not treated. The tumor was clearly demarcated and lobulated on CT scan. After 2 years of follow-up, the boundary of the tumor was still clear, with more lobulations and the enhanced scan showed uniform enhancement. Grossly, the tumor had a granular cut surface and was easy to fall off, which was helpful for the diagnosis of papillary adenoma during intraoperative frozen examination. Under the microscope, most areas of the tumor had the typical morphological structure of papillary adenoma. However, the tumor locally protruded into the surrounding lung tissue, accompanied by crowded cells and high cell proliferation index. It was suggested that this case of papillary adenoma had malignant potential and needed active intervention and treatment.
CONCLUSION
Pulmonary papillary adenoma is a rare epithelial tumor with malignant potential. Surgical treatment should be performed as soon as possible after diagnosis to prevent malignant transformation.
Topics: Adenoma; Aged; Female; Humans; Lung; Lung Neoplasms; Radiography; Tomography, X-Ray Computed
PubMed: 36229884
DOI: 10.1186/s13000-022-01259-8 -
Journal of Investigative Medicine High... 2023Alveolar adenoma (AA) is a rare type of pulmonary neoplasm showing proliferation of alveolar epithelium and septal mesenchyme. Clinically, AA is asymptomatic, benign,... (Review)
Review
Alveolar adenoma (AA) is a rare type of pulmonary neoplasm showing proliferation of alveolar epithelium and septal mesenchyme. Clinically, AA is asymptomatic, benign, and usually diagnosed incidentally. Surgical excision is curative. The etiology of AA is controversial and the pathogenesis is unknown, but it is thought to stem from type II pneumocytes and fibroblasts or fibroblast-like cells. The stromal cells in AA may show rare staining for CD34. Diffuse CD34 positivity of the interstitial stromal cells has rarely been described and reviewed. Here, we report a case of AA with strong and diffuse CD34 staining in the stromal cells.
Topics: Humans; Lung Neoplasms; Adenoma; Diagnosis, Differential
PubMed: 37530218
DOI: 10.1177/23247096231181959 -
The Journal of International Medical... Mar 2020Alveolar adenoma is an isolated, well-defined peripheral lung tumor that originates from type II alveolar cells. The tumor consists of a network of simple, low-cubic,...
Alveolar adenoma is an isolated, well-defined peripheral lung tumor that originates from type II alveolar cells. The tumor consists of a network of simple, low-cubic, epithelium-coated lacunae with varying amounts of fine and inconspicuous-to-thick spindle cells that sometimes contain mucus sample matrix. Few cases of alveolar adenoma have been reported. These tumors are usually detected by imaging examinations where the alveolar adenoma typically presents as a peripheral, solitary cystic nodule in the lung. The presentation may mimic that of other types of lung tumors, consequently leading to difficulties in the differential diagnosis of this condition. Thus, accurate diagnosis of alveolar adenoma is based on a combination of pathological sections and immunohistochemistry. This study describes an alveolar adenoma in a 59-year-old female patient. Chest X-ray imaging and chest computed tomography identified malignant lesions in the right upper lobe. The patient subsequently underwent a thoracoscopic right upper lobectomy. The diagnosis of alveolar adenoma was confirmed after pathological examination of the excised postoperative tissue. The disease course was stable, and there was no recurrence of pulmonary lesions during 3 years of postoperative patient follow-up. Herein, we report the case of a patient with benign alveolar adenoma with poor imaging and pathological results.
Topics: Adenoma; Female; Humans; Immunohistochemistry; Lung Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Tomography, X-Ray Computed
PubMed: 31709862
DOI: 10.1177/0300060519885269 -
International Journal of Surgery Case... Nov 2022The most common benign neoplasm of major and minor salivary glands is pleomorphic adenoma (PA). Around 80 % of all parotid neoplasms are pleomorphic adenomas, while...
INTRODUCTION AND IMPORTANCE
The most common benign neoplasm of major and minor salivary glands is pleomorphic adenoma (PA). Around 80 % of all parotid neoplasms are pleomorphic adenomas, while 44-68 % and 38-43 % tumors were pleomorphic adenomas of submandibular and minor salivary gland tumors. PA has been reported in a variety of anatomic locations including true intraosseous mandibular tumor, external ear canal, TMJ region, lacrimal gland, epiglottis, larynx and nasopharynx, breast, lung, esophagus, sinonasal and skull base and trachea. Pleomorphic adenoma has a tendency to transform into a number of malignancies; carcinoma ex-pleomorphic adenoma, carcinosarcoma or metastasizing pleomorphic adenoma. Pleomorphic adenomas most commonly transform into carcinoma ex-pleomorphic adenoma (CEPA).
CASE PRESENTATION
A 30-year-old male presented with the primary complaint of a long-standing swelling at his right mandibular region for past 18 months. On intra oral examination, there was a non-healing alveolar socket of right lower 3rd molar tooth while rest of the dentition and mucosal surfaces were normal. On extra oral examination, mouth opening was adequate with intact lower border of the mandible and no palpable lymph nodes in the neck. Initial biopsy of lesion showed pleomorphic adenoma, but later the lesion came out to be carcinoma ex-pleomorphic adenoma, for which he underwent segmental mandibulectomy and free fibular flap.
CLINICAL DISCUSSION
The prevalence of CEPA transformation from pleomorphic adenoma is 1.5 % within the first 5 years of diagnosis, going up to 10 % after 15 years. The true rate of malignant transformation in recurrent pleomorphic adenoma is reported to be 3.3 %. We report a case of an intra-osseous carcinoma ex pleomorphic adenoma (CEPA) of the mandible. It is thought that ectopic entrapment of salivary tissue or developmentally included embryonic remnants of submandibular glands within recesses or lacunae of the mandibular bone could explain the intraosseous origin of a salivary gland tumor in the mandible. Since carcinoma ex pleomorphic adenoma (CEPA) arises from primary or recurrent pleomorphic adenoma, therefore it poses a diagnostic challenge for histopathologists. The radiographic picture of primary tumor/recurrence can mimic odontogenic cyst/tumor; therefore, a sinister disease process should always be kept in mind. In the post operative period, regular follow up is required to treat any recurrence. The recurrence rate for such disease has not been documented.
CONCLUSION
Intra osseous CEPA is a very rare tumor. Intra bony tumors which rapidly increase in size have signs and symptoms of nerve involvement and cause bony destruction should have a high suspicion of index of malignancy. Therefore, biopsy must be correlated with clinical and radiological features. Regular follow up is necessary to detect any recurrence promptly.
PubMed: 36274292
DOI: 10.1016/j.ijscr.2022.107729