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PloS One 2024Mice engineered with a G12D versus Q61R mutation in Kras exhibited differences in tumorigenesis. Namely, the incidence or grade of oral or forestomach squamous...
Mice engineered with a G12D versus Q61R mutation in Kras exhibited differences in tumorigenesis. Namely, the incidence or grade of oral or forestomach squamous epithelial lesions was more prevalent in the KrasG12D background while hematolymphopoietic disease was more prevalent in the KrasQ61R background. Loss of the Trp53 gene encoding the tumor suppressor p53 enhances the ability of oncogenic Kras to initiate tumorigenesis in carcinogen and genetic models of lung cancer. Conversley, an extra copy of Trp53 (Super p53) was recently shown to suppress Kras-induced tumorigenesis in a genetic model of this disease. Given this, we evaluated whether an extra copy of Trp53 would alter tumorigenesis upon global activation of a modified Kras allele engineered with either a G12D or Q61R mutation. We report that an increase in p53 dosage significantly reduced the incidence or grade of oral and forestomach squamous tumors induced by either G12D and Q61R-mutant Kras. The incidence of myeloproliferative disease was also significantly reduced with increased p53 dosage in the KrasQ61R background. Both the percentage of mice with lung tumors and total number of adenomas per animal were unchanged. However, the incidence and grade of peripheral atypical alveolar hyperplasia was significantly decreased in both backgrounds with increased p53 dosage. Finally, the number of foci of bronchioloalveolar hyperplasia per animal significantly increased with increased p53 dosage in the KrasG12D background. These results suggest that an extra copy of p53 can impede oncogenic Kras driven tumorigenesis in some tissues.
Topics: Mice; Animals; Proto-Oncogene Proteins p21(ras); Tumor Suppressor Protein p53; Hyperplasia; Cell Transformation, Neoplastic; Carcinogenesis; Lung Neoplasms; Mutation; Carcinoma, Squamous Cell; Disease Models, Animal
PubMed: 38547169
DOI: 10.1371/journal.pone.0292189 -
Scientific Reports Mar 2024Polyhexamethylene guanidine phosphate (PHMG-p) is a major component in humidifier disinfectants, which cause life-threatening lung injuries. However, to our knowledge,...
Polyhexamethylene guanidine phosphate (PHMG-p) is a major component in humidifier disinfectants, which cause life-threatening lung injuries. However, to our knowledge, no published studies have investigated associations between PHMG-p dose and lung damage severity with long-term follow-up. Therefore, we evaluated longitudinal dose-dependent changes in lung injuries using repeated chest computed tomography (CT). Rats were exposed to low (0.2 mg/kg, n = 10), intermediate (1.0 mg/kg, n = 10), and high (5.0 mg/kg, n = 10) doses of PHMG-p. All rats underwent repeated CT scans after 10 and 40 weeks following the first exposure. All CT images were quantitatively analyzed using commercial software. Inflammation/fibrosis and tumor counts underwent histopathological evaluation. In both radiological and histopathologic results, the lung damage severity increased as the PHMG-p dose increased. Moreover, the number, size, and malignancy of the lung tumors increased as the dose increased. Bronchiolar-alveolar hyperplasia developed in all groups. During follow-up, there was intergroup variation in bronchiolar-alveolar hyperplasia progression, although bronchiolar-alveolar adenomas or carcinomas usually increase in size over time. Thirty-three carcinomas were detected in the high-dose group in two rats. Overall, lung damage from PHMG-p and the number and malignancy of lung tumors were shown to be dose-dependent in a rat model using repeated chest CT scans during a long-term follow-up.
Topics: Rats; Animals; Lung Injury; Follow-Up Studies; Carcinogens; Hyperplasia; Guanidines; Carcinogenesis; Lung Neoplasms; Carcinoma
PubMed: 38531959
DOI: 10.1038/s41598-024-57605-x -
Medicine International 2024Alveolar adenoma is a rare and benign pulmonary tumor, which originates from type II pneumocytes and is often incidentally identified on radiographic images. Alveolar...
Alveolar adenoma is a rare and benign pulmonary tumor, which originates from type II pneumocytes and is often incidentally identified on radiographic images. Alveolar adenoma presents as a peripleural, solitary and cystic nodule in the lung and may mimic other types of lung tumors, thus rendering its differential diagnosis difficult. Alveolar adenoma is diagnosed based on histopathological and immunohistochemical analyses. The present study describes the case of a 50-year-old male patient with alveolar adenoma. He visited a local doctor ~3 years prior due to left chest pain. A chest computed tomography scan revealed a cystic lesion in segment 8 of the left lung. A nodular shadow appeared in the cyst and gradually increased in size; the patient was thus referred to the authors' hospital. The nodule was well-defined, solitary and solid; thus, lung cancer or aspergilloma were suspected. Thoracoscopic wedge resection was performed as diagnostic therapy. The frozen sections were non-diagnostic, and a pathological examination revealed an alveolar adenoma with no evidence of malignancy and a negative culture. The patient had a good post-operative course, with no sign of recurrence at the follow-up evaluation 46 months later. On the whole, alveolar adenoma is a rare, benign pulmonary tumor that is difficult to diagnose pre-operatively.
PubMed: 38476983
DOI: 10.3892/mi.2024.140 -
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 -
Journal of Cardiothoracic Surgery Oct 2023Alveolar adenoma is a rare benign tumour, usually presenting as a peripherally located solid mass, sometimes mimicking malignancy.
BACKGROUND
Alveolar adenoma is a rare benign tumour, usually presenting as a peripherally located solid mass, sometimes mimicking malignancy.
CASE PRESENTATION
A 37-year-old woman presented with chronic intermittent vague chest discomfort. The chest x-ray showed a simple cyst in the left lower lung field, and serial computed tomography (CT) over the following 2-year period showed rapid growth of the cyst, from 3.5 to 9.0 cm in diameter. The CT scan suggested bronchiolar communication, which was suspected to be the cause of growth, via check-valve mechanism. Thoracoscopic surgery was performed, and we found a thin-walled cyst in the lingular segment. Wedge resection was performed and the pathology was an unexpected alveolar adenoma which had grown on the terminal bronchiole, causing the alveolus to rupture and the cyst to grow. In 48 months of follow-up, there was no evidence of recurrence and the patient's symptoms resolved.
CONCLUSIONS
Rapidly growing pulmonary cysts can lead to complications including rupture with pneumothorax and haemothorax, and surgery is always indicated. Abnormally rapid growth may indicate an underlying pathology such as alveolar adenoma. Surgical resection is the treatment of choice and there have been no reported cases of recurrence. Here we present a rare form of alveolar adenoma, which was a form of rapidly growing pulmonary cyst.
Topics: Female; Humans; Adult; Lung Neoplasms; Lung Diseases; Lung; Cysts; Rupture; Adenoma
PubMed: 37907949
DOI: 10.1186/s13019-023-02409-9 -
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 -
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 -
Folia Histochemica Et Cytobiologica 2023Incidentally discovered lung nodules can be worrisome for both the patient and their physicians. Although 95% of solitary lung nodules are benign, it is important to... (Review)
Review
INTRODUCTION
Incidentally discovered lung nodules can be worrisome for both the patient and their physicians. Although 95% of solitary lung nodules are benign, it is important to distinguish which nodules have high clinical suspicion for malignancy. Existing clinical guidelines do not apply to patients with signs and symptoms related to the lesion and with an increased baseline risk of lung cancer or metastasis. This paper highlights the vital role of pathohistological analysis and immunohistochemistry in the definitive diagnosis of such incidentally discovered lung nodules.
MATERIAL AND METHODS
The three cases presented were selected based on their similar clinical presentations. A review of the literature was performed using the online database PubMed, for articles published in the period between January of 1973 to February of 2023 using the following medical subject headlines: "primary alveolar adenoma," "alveolar adenoma," "primary pulmonary meningioma," "pulmonary meningioma," and "pulmonary benign metastasizing leiomyoma." Results (Case Series). The case series consists of three incidentally discovered lung nodule(s). Although they presented with high clinical suspicion for malignancy, detailed workup confirmed the diagnosis of three rare benign lung tumours: primary alveolar adenoma, primary pulmonary meningioma, and benign metastasizing leiomyoma.
CONCLUSIONS
Clinical suspicion for malignancy in the presented cases arose from previous and current medical history of malignancy, family history of malignancy, and/or specific radiographic findings. This paper highlights the need for a multidisciplinary approach in the management of incidentally discovered pulmonary nodules. Excisional biopsy and pathohistological analysis remain the gold standard in confirming the presence of a pathologic process and determining the nature of the disease. Common features of the diagnostic algorithm utilized among the three cases include multi-slice computerized tomography, excisional biopsy via atypical wedge resection (if the nodule is peripherally located), and lastly, pathomorphological analysis using haematoxylin and eosin staining and immunohistochemistry.
Topics: Humans; Meningioma; Lung Neoplasms; Leiomyoma; Biopsy; Meningeal Neoplasms
PubMed: 37435900
DOI: 10.5603/FHC.a2023.0011 -
Radiologia 2022
Topics: Humans; Radiography; Lung Neoplasms; Radiology; Adenoma
PubMed: 36402545
DOI: 10.1016/j.rxeng.2022.10.004 -
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