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IScience Sep 2023Adenosquamous carcinoma (ASC) is frequently misdiagnosed or overlooked in clinical practice due to its dual histological components and potential transformation from...
Adenosquamous carcinoma (ASC) is frequently misdiagnosed or overlooked in clinical practice due to its dual histological components and potential transformation from either adenocarcinoma (ADC) or squamous cell carcinoma (SCC). Our study aimed to differentiate ASC from ADC and SCC by incorporating features of enhanced CTs and clinical characteristics to build radiomics and deep learning models. The classification models were trained in Xiangya Hospital and validated in two other independent hospitals. The areas under the receiver operating characteristic curves (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were used to estimate the performance. The optimal three-class classification model achieved a maximum AUC of 0.89 and accuracy of 0.81 in external validation sets, AUC of 0.99 and accuracy of 0.99 in the internal test set. These findings highlight the efficacy of our models in differentiating ASC, providing a non-invasive, timely, and accurate diagnostic approach before and during the treatment.
PubMed: 37664612
DOI: 10.1016/j.isci.2023.107634 -
Frontiers in Oncology 2023Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare autosomal recessive genetic disorder caused by biallelic germline mutations in one of the mismatch...
Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare autosomal recessive genetic disorder caused by biallelic germline mutations in one of the mismatch repair genes. Carriers are at exceptionally high risk for developing, typically in early life, hematological and brain malignancies, as well as cancers observed in Lynch syndrome. We report a homozygous missense variant (c.1918C>A p.(Pro640Thr)) in a Tunisian patient with CMMRD syndrome and a family history of early-age colorectal cancer. The proband presented initially with colonic oligopolyposis and adenosquamous carcinoma of the caecum. He later developed several malignancies, including undifferentiated carcinoma of the parotid, grade 4 IDH-mutant astrocytoma, and ampulla of Vater adenocarcinoma. The patient was older than typical for this disease and had a remarkably prolonged survival despite developing four distinct aggressive malignancies. The current report highlights the challenges in assessing the pathogenicity of the identified variant and the remarkable phenotypic diversity in CMMRD.
PubMed: 37664053
DOI: 10.3389/fonc.2023.1195814 -
Case Reports in Women's Health Sep 2023Lung adenosquamous carcinoma (ASC) is a rare biphasic malignant tumor with squamous cell carcinoma (SCC) and adenocarcinoma (AC) components. ASC is reported to be...
Lung adenosquamous carcinoma (ASC) is a rare biphasic malignant tumor with squamous cell carcinoma (SCC) and adenocarcinoma (AC) components. ASC is reported to be aggressive; the most common metastatic sites are the regional lymph nodes and surrounding areas. A 46-year-old woman was referred to the emergency department with a persistent dry cough. She underwent fibro-bronchoscopy and was diagnosed with an adenosquamous lung carcinoma. Other than pulmonary and lymphatic findings, a total-body computed tomography (CT) examination highlighted a hypodense formation, of about 9 mm, with a cystic appearance, at the level of the vaginal region. A biopsy performed in the posterior vaginal wall highlighted a vaginal wall flap with subepithelial localization of neoplasia, compatible with the pulmonary ASC. Oncologists took charge of the case and the patient commenced medical therapy with entrectinib. Four months later, she developed dyspnea, and high-resolution CT highlighted an increase in the pathological tissue causing bronchial occlusion. The patient underwent endobronchial stent placement and thereafter restarted therapy with entrectinib, previously stopped because of the new symptoms, and was closely monitored. Apparently only one case of vaginal metastasis from pulmonary tumor has been previously reported, and this is the first report of vaginal metastasis from ASC. Although extremely rare, the presence of such metastasis should be considered in women with suspected vaginal neoformations.
PubMed: 37663888
DOI: 10.1016/j.crwh.2023.e00536 -
Breast Cancer Research and Treatment Dec 2023Low-grade adenosquamous carcinoma (LGASC) is a rare type of metaplastic carcinoma of the breast (MBC) with an indolent clinical course. A few LGASC cases with high-grade...
PURPOSE
Low-grade adenosquamous carcinoma (LGASC) is a rare type of metaplastic carcinoma of the breast (MBC) with an indolent clinical course. A few LGASC cases with high-grade transformation have been reported; however, the genetics underlying malignant progression of LGASC remain unclear.
METHODS
We performed whole-genome sequencing analysis on five MBCs from four patients, including one case with matching primary LGASC and a lymph node metastatic tumor consisting of high-grade MBC with a predominant metaplastic squamous cell carcinoma component (MSC) that progressed from LGASC and three cases of independent de novo MSC.
RESULTS
Unlike de novo MSC, LGASC and its associated MSC showed no TP53 mutation and tended to contain fewer structural variants than de novo MSC. Both LGASC and its associated MSC harbored the common GNAS c.C2530T:p.Arg844Cys mutation, which was more frequently detected in the cancer cell fraction of MSC. MSC associated with LGASC showed additional pathogenic deletions of multiple tumor-suppressor genes, such as KMT2D and BTG1. Copy number analysis revealed potential 18q loss of heterozygosity in both LGASC and associated MSC. The frequency of SMAD4::DCC fusion due to deletions increased with progression to MSC; however, chimeric proteins were not detected. SMAD4 protein expression was already decreased at the LGASC stage due to unknown mechanisms.
CONCLUSION
Not only LGASC but also its associated high-grade MBC may be genetically different from de novo high-grade MBC. Progression from LGASC to high-grade MBC may involve the concentration of driver mutations caused by clonal selection and inactivation of tumor-suppressor genes.
Topics: Humans; Female; Carcinoma, Adenosquamous; Breast Neoplasms; Breast; Carcinoma
PubMed: 37650999
DOI: 10.1007/s10549-023-07078-9 -
Frontiers in Oncology 2023Lung adenosquamous carcinoma (ASC) is a rare heterogeneous tumor containing two distinct components of adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). The...
Lung adenosquamous carcinoma (ASC) is a rare heterogeneous tumor containing two distinct components of adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). The limited biopsy sampling of the primary tumor might have overlooked either the ADC component or the SQCC component, resulting in a misdiagnosis of pure histology. Genotyping for driver mutations is now routinely performed in clinical settings to identify actionable oncogenic mutations and gene arrangements. Additionally, somatic mutations can potentially serve as a marker of clonal relationships. We report a rare case of ASC lung cancer, in which metastases were identified as ADC, while the primary was initially diagnosed as SQCC based on a fibrobronchoscope brush biopsy. The primary and metastatic tumors shared rearrangement and other mutations support they were derived from a single clone origin. Our hypothesis is that the primary tumor contained a minor component of ADC that was not present in the histologic sections of lung biopsy. After sequential -tyrosine kinase inhibitor (TKI) targeted therapy, both the patient's primary lung tumor and the site of metastatic subcutaneous nodules decreased in size, with the metastatic sites demonstrating more noticeable shrinkage. However, after 11 months of targeted therapy, the patient was found to be resistant to -TKIs. Subsequently, the patient's respiratory status deteriorated rapidly, and a cycle of immunotherapy and chemotherapy did not show efficacy. To the best of our knowledge, this is a very rare case of lung ASC, disseminated metastasizing, with distinct morphology between the primary and metastases. Different therapeutic effects of -TKIs were observed in two different morphological sites, with the metastatic cutaneous lesions shrinking more significantly than the primary lung lesions, though they both harbor the same - rearrangement. This case may provide diagnostic and therapeutic insights into lung ASC.
PubMed: 37637057
DOI: 10.3389/fonc.2023.1209799 -
NPJ Precision Oncology Aug 2023The genomic origin and development of the biphasic lung adenosquamous carcinoma (ASC) remain inconclusive. Here, we derived potential evolutionary trajectory of ASC...
The genomic origin and development of the biphasic lung adenosquamous carcinoma (ASC) remain inconclusive. Here, we derived potential evolutionary trajectory of ASC through whole-exome sequencing, Stereo-seq, and patient-derived xenografts. We showed that EGFR and MET activating mutations were the main drivers in ASCs. Phylogenetically, these drivers and passenger mutations found in both components were trunk clonal events, confirming monoclonal origination. Comparison of multiple lesions also revealed closer genomic distance between lymph node metastases and the ASC component with the same phenotype. However, as mutational signatures of EGFR-positive lung squamous carcinomas (LUSCs) were more comparable to EGFR-positive ASCs than to wild-type LUSCs, we postulated different origination of these LUSCs, with ASC being the potential intermediate state of driver-positive LUSCs. Spatial transcriptomic profiling inferred transformation from adenocarcinoma to squamous cell carcinoma, which was then histologically captured in vivo. Together, our results explained the development of ASC and provided insights into future clinical decisions.
PubMed: 37634047
DOI: 10.1038/s41698-023-00430-8 -
Diagnostics (Basel, Switzerland) Aug 2023Several solid lesions can be found within the pancreas mainly arising from the exocrine and endocrine pancreatic tissue. Among all pancreatic malignancies, the most... (Review)
Review
Several solid lesions can be found within the pancreas mainly arising from the exocrine and endocrine pancreatic tissue. Among all pancreatic malignancies, the most common subtype is pancreatic ductal adenocarcinoma (PDAC), to a point that pancreatic cancer and PDAC are used interchangeably. But, in addition to PDAC, and to the other most common and well-known solid lesions, either related to benign conditions, such as pancreatitis, or not so benign, such as pancreatic neuroendocrine neoplasms (pNENs), there are solid pancreatic lesions considered rare due to their low incidence. These lesions may originate from a cell line with a differentiation other than exocrine/endocrine, such as from the nerve sheath as for pancreatic schwannoma or from mesenchymal cells as for solitary fibrous tumour. These rare solid pancreatic lesions may show a behaviour that ranges in a benign to highly aggressive malignant spectrum. This review includes cases of an intrapancreatic accessory spleen, pancreatic tuberculosis, solid serous cystadenoma, solid pseudopapillary tumour, pancreatic schwannoma, purely intraductal neuroendocrine tumour, pancreatic fibrous solitary tumour, acinar cell carcinoma, undifferentiated carcinoma with osteoclastic-like giant cells, adenosquamous carcinoma, colloid carcinoma of the pancreas, primary leiomyosarcoma of the pancreas, primary and secondary pancreatic lymphoma and metastases within the pancreas. Therefore, it is important to determine the correct diagnosis to ensure optimal patient management. Because of their rarity, their existence is less well known and, when depicted, in most cases incidentally, the correct diagnosis remains challenging. However, there are some typical imaging features present on cross-sectional imaging modalities that, taken into account with the clinical and biological context, contribute substantially to achieve the correct diagnosis.
PubMed: 37627978
DOI: 10.3390/diagnostics13162719 -
Cancer Treatment and Research... 2023Elevated platelet lymphocyte ratio (PLR) and low body mass index (BMI) are associated with inferior survival in non-small cell lung cancer (NSCLC) patients receiving...
BACKGROUND
Elevated platelet lymphocyte ratio (PLR) and low body mass index (BMI) are associated with inferior survival in non-small cell lung cancer (NSCLC) patients receiving immunotherapy (IO). We evaluated real-world prognostic utility of PLR, BMI, and albumin level in stage IV NSCLC patients receiving first line (1L) IO.
METHODS
We identified 75 stage IV patients who received 1L IO therapy at USC Norris Comprehensive Cancer Center and Los Angeles General Medical Center from 2015 to 2022. The primary outcome was overall survival (OS) from time of IO with attention to pre-treatment BMI < 22, albumin < 3.5 g/dL, and PLR > 180.
RESULTS
Median age was 66.5 years with 49 (65.3%) males. 25 (33.3%) had BMI < 22. 45/75 (60%) had PLR > 180. Patients with BMI < 22 had inferior OS (13.1 months (m) vs. 37.4 m in BMI > 28, p-value = 0.042) along with patients with albumin<3.5 g/dL (OS: 2.8 m vs. 14.6 m, p-value = 0.0027), and patients with PLR>180 (OS: 8.7 m vs. 23.0 m, p = 0.028). Composite BMI < 22, PLR > 180 had the worst OS, p-value = 0.0331. Multivariate analysis controlling for age, smoking, gender, PD-L1 tumor proportion score (TPS), and histology (adenocarcinoma, squamous, adenosquamous, and large cell) showed that BMI (HR: 0.8726, 95% CI: 0.7892-0.954) and PLR > 180 (HR: 2.48, 95% CI: 1.076-6.055) were significant in OS mortality risk.
CONCLUSION
Patients with a composite of BMI < 22, albumin < 3.5 g/dL, and PLR > 180 had significantly worse OS. This highlights the importance of screening for poor nutritional status and high PLR to better inform stage IV NSCLC patients receiving IO therapy of their prognosis and supportive care.
MICROABSTRACT
We evaluated real-world prognostic utility of platelet lymphocyte ratio (PLR), body mass index (BMI), and albumin level in 75 Stage IV NSCLC patients receiving first line IO. Patients with a composite of BMI < 22, albumin < 3.5 g/dL, and PLR > 180 had significantly worse OS. This highlights the importance of screening for poor nutritional status and high PLR to better inform stage IV NSCLC patients of their prognosis and to emphasize supportive care needs.
Topics: Male; Humans; Aged; Female; Nutritional Status; Carcinoma, Non-Small-Cell Lung; Prognosis; Lung Neoplasms; Immunotherapy; Albumins; Lymphocytes
PubMed: 37611343
DOI: 10.1016/j.ctarc.2023.100752 -
BMC Cancer Aug 2023The optimal treatment strategy for resectable BRAF V600E mutant colorectal oligometastases (CRM) has not been established due to the rarity and rapid progression of the...
NEXUS trial: a multicenter phase II clinical study evaluating the efficacy and safety of the perioperative use of encorafenib, binimetinib, and cetuximab in patients with previously untreated surgically resectable BRAF V600E mutant colorectal oligometastases.
BACKGROUND
The optimal treatment strategy for resectable BRAF V600E mutant colorectal oligometastases (CRM) has not been established due to the rarity and rapid progression of the disease. Since the unresectable recurrence rate is high, development of novel perioperative therapies are warranted. On December 2020, the BEACON CRC triplet regimen of encorafenib, binimetinib, and cetuximab was approved for unresectable metastatic colorectal cancer in Japan.
METHODS
The NEXUS trial is a multicenter phase II clinical study evaluating the efficacy and safety of the perioperative use of encorafenib, binimetinib, and cetuximab in patients with previously untreated surgically resectable BRAF V600E mutant CRM. The key inclusion criteria are as follows: histologically diagnosed with colorectal adeno/adenosquamous carcinoma; RAS wild-type and BRAF V600E mutation by tissue or blood; and previously untreated resectable distant metastases. The triplet regimen (encorafenib: 300 mg daily; binimetinib: 45 mg twice daily; cetuximab: 400 mg/m, then 250 mg/m weekly, 28 days/cycle) is administered for 3 cycles each before and after curative resection. The primary endpoint of the study is the 1-year progression-free survival (PFS) rate and the secondary end points are the PFS, disease-free survival, overall survival, and objective response rate. The sample size is 32 patients. Endpoints in the NEXUS trial as well as integrated analysis with the nationwide registry data will be considered for seeking regulatory approval for the perioperative use of the triplet regimen.
DISCUSSION
The use of the triplet regimen in the perioperative period is expected to be safe and effective in patients with resectable BRAF V600E mutant CRM.
TRIAL REGISTRATION
jRCT2031220025, April. 16, 2022.
Topics: Humans; Cetuximab; Proto-Oncogene Proteins B-raf; Carcinoma, Adenosquamous; Colorectal Neoplasms
PubMed: 37605122
DOI: 10.1186/s12885-023-11311-5