Hepatoid Adenocarcinoma Of The Lung With Egfr Mutation And The Response To Tyrosine Kinase Inhibitors
- Hua-fei ChenAffiliationsDepartment of Thoracic Disease Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, Jiaxing, Zhejiang Province, People’s Republic of China
- Chun-wei XuCorrespondenceAddress for correspondence: Chun-wei Xu, MD, PhD, Department of Pathology, Fujian Cancer Hospital, Fujian Medical University, No. 420 Fuma Road, Fuzhou, Fujian Province, 350014 People’s Republic of China. ContactAffiliationsDepartment of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian Province, People’s Republic of China
- Kai-qi DuAffiliationsDepartment of Thoracic Disease Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, Jiaxing, Zhejiang Province, People’s Republic of China
- You-cai ZhuAffiliationsDepartment of Thoracic Disease Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, Jiaxing, Zhejiang Province, People’s Republic of China
Pathol Oncol Res.
Data Sources And Search Strategy
This review conforms to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement.14 Several electronic databases, including PubMed, MEDLINE, and Web of Science, were searched systematically using predetermined terms Hepatoid adenocarcinoma, HAC, HAL, lung, and pulmonary between January 1, 1990 and December 31, 2020 . In this study, 1990 was selected as the starting year for search because the conception of HAC was first introduced in this year.15 In addition, the electronic search strategy was supplemented by hand-searching reference lists of key articles.
Hepatoid Adenocarcinoma Of The Lung: A Systematic Review Of The Literature From 1981 To 2020
- 1Department of Oncology, The Affiliated Fifth Peoples Hospital of Chengdu University of TCM, Chengdu Fifth Peoples Hospital, Chengdu, China
- 2Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
- 3Department of Clinical Laboratory, The Affiliated Fifth Peoples Hospital of Chengdu University of TCM, Chengdu Fifth Peoples Hospital, Chengdu, China
- 4Department of Pathology, The Affiliated Fifth Peoples Hospital of Chengdu University of TCM, Chengdu Fifth Peoples Hospital, Chengdu, China
Objectives: We report the first case of hepatoid adenocarcinoma of the lung with PIK3CA mutation. In addition, we analyzed data from HAL cases over the past 40 years to study its main treatment methods, prognosis, and the relationship between prognosis and the serum alpha-fetoprotein level before treatment.
HAL patients have a poor prognosis, and the survival benefits for patients receiving chemoradiotherapy or chemotherapy alone appear to be limited. We demonstrate statistically for the first time that pretreatment serum AFP values are not related to the prognosis of HAL patients and RS can significantly improve patient prognosis.
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Measurements And Main Results
The purpose of this report is to present a new case of HAC, with typical clinical and histologic features of this malignancy, and to summarize findings of previously reported cases. A systematic literature search of the electronic database PUBMED was conducted to identify all cases of hepatoid adenocarcinoma reported in the English literature, between January 1980 and June 2015. HAC and HCC can be distinguished by immunohistochemical staining. HAC usually presents as a large bulky solitary mass in the upper lobe there is an exceedingly high prevalence in males and most patients with this tumor are smokers. Serum alpha-fetoprotein in very high levels has been a distinguishing feature of this tumor. Nodal and distant metastases are common at initial presentation and, as a result, the prognosis is very poor. Resection and long-term survival, however, have been reported.
Histological And Immunohistochemical Analysis
Tissue sections, 5m thick, were cut from formalin-fixed, paraffin-embedded archival surgical specimens for hematoxylin and eosin, mucicarmine and immunohistochemical stains. Immunohistochemical stains for CK8, CK14 and CK18 were carried out via an avidinbiotin conjugate method with an automated stainer and a commercial peroxidase-conjugated streptavidinbiotin detection system . Immunohistochemical stains for CK5/6, CK7, CK19, CK20, AFP, HepPar1, TTF-1, napsin A, HEA125, MOC31, CEA , -isoform of estrogen receptor , ALK 1 and Ki-67 were performed on an automated stainer and a commercial Bond polymer detection system . All immunohistochemical stains were carried out with appropriate positive and negative controls.
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Cox Proportional Hazards Regression Analysis
The Cox proportional hazards regression analysis was composed of 30 patients who had tumor size, location of tumor, serum AFP level before treatment, specific treatment methods, and survival data . RS was shown to significantly improve the prognosis of HAL patients . Compared with the right upper lobe group, there were no significant differences in the prognosis of the non-right upper lobe group . The tumor size and serum AFP value before treatment also had no significant effect on the prognosis .
Table 3 Cox proportional hazard regression model.
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Immunohistochemical Scores For Estrogen Receptors
The Allred immunohistochemical score for estrogen receptor expression was calculated in a semiquantitative manner. The proportion score was dependent on the proportion of tumor cells with positive staining: 0, none 1, < 1/100 2, 1/100 to 1/10 3, 1/10 to 1/3 4, 1/3 to 2/3 and 5, > 2/3. The intensity score was assigned according to staining intensity: 0, none 1, weak 2, intermediate and 3, strong. Intensity score and proportion score were added together for a combined immunohistochemical score: negative , weak and strong .
Survival Analysis In Patients With Hal
The median OS of the 65 patients with HAL was 5 months the 3- and 5-year survival rates were 7.7 and 6.2%, respectively. A total of 50 patients died during the follow-up period, of which 48 were cancer-specific and 2 were due to other causes . Multivariant analysis of prognostic factors for OS prediction in patients with HAL included age , chemotherapy , and surgery , all of which were associated with cancer-specific survival. The American Joint Committee on Cancer staging was the only prognostic factor for OS in patients with HAL stage IV HAL was significantly different from other stages . No conventional antitumor therapies, including surgery, chemotherapy, and radiotherapy, were shown to have a significant survival benefit in patients with HAL .
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Exploration Of Potential Mechanism
Primary HAL is an extremely rare tumor whose molecular mechanisms and genetic characteristics remain unclear. Although HAL has been reported for more than 50 years and concepted for 31 years, mainly single cases are reported, and research on the molecular mechanism and genomic profiling of HAL is scarce. Ishikura et al15 argued that the aberrant differentiation process may lead to the differentiation of certain adenocarcinomas tissues in the lung into hepatocytes because the respiratory system below the throat is similar to the liver and gastrointestinal tract and develops in the anterior intestine of the embryonic primitive digestive tract. Over time, a small amount of HACs was also found in organs that did not develop from the original digestive tract, such as endometrium60 and adrenal glands.61,62
Table 2 The Cox Proportional Hazards Regression Analysis for Various Clinicopathological Parameters
Table 3 The Information of Hepatoid Adenocarcinoma of the Lung -Related Oncogene from Previous Articles
Table 4 Key Regulated Factor of Hepatoid Adenocarcinoma of the Lung -Related Genes
Figure 8 Potential biological functions of genes related to hepatoid adenocarcinoma of the lung. Protein-protein interaction network for HLA-related genes using STRING. Protein-function interaction network for HLA-related genes using GeneMANIA. Gene Ontology functional enrichment for HLA-related genes. Kyoto Encyclopedia of Genes and Genomes pathway for HLA-related genes.
Hepatoid Adenocarcinoma Of The Lung Responsive To Frontline Combination Chemotherapy With Immunotherapy: Case Report
- Catherine A. ShuCorrespondenceCorresponding author: Address for correspondence: Catherine A. Shu, MD, Thoracic Medical Oncology, Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Ave., New York, NY 10032.
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Hepatoid Adenocarcinoma Of The Lung: Review Of A Rare Form Of Lung Cancer
- 1 Current address: 1601 E, Broadway Suite 240, Columbia, MO, 65203, USA.Kate Grossman1 Current address: 1601 E, Broadway Suite 240, Columbia, MO, 65203, USA.AffiliationsDivision of Pulmonary, Critical Care and Sleep Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029-6574, USA
- Sidney S. BramanCorrespondenceCorresponding author. Icahn School of Medicine at Mount Sinai, 1 Gustav L. Levy Place, Box 1232, New York, NY 10029, USA. ContactAffiliationsDivision of Pulmonary, Critical Care and Sleep Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029-6574, USA
- 1 Current address: 1601 E, Broadway Suite 240, Columbia, MO, 65203, USA.
- Hepatoid adenocarcinoma is a rare malignant lung tumor.
- HAC histologically resembles typical hepatocellular carcinoma .
- HAC is usually a large upper lobe mass of males who smoked. The prognosis is poor.
- A high level of serum alpha-fetoprotein is a distinguishing feature of HAC.
- HAC shows hepatoid morphology immunohistochemical staining differs from HCC.
Correlation Analysis Of Clinical Features In Patients With Hal
Male patients with HAL were more likely to receive radiotherapy compared with female patients with HAL . Patients with HAL treated by chemotherapy were more likely to be younger . Of the 51 patients with HAL, 30 had primary tumors located in the upper lobes of the lungs, with a median tumor diameter of 173.2 ± 306.2mm. Ten of 51 HALs with the largest median tumor diameter were located in the lungs with no specific anatomic location. Of 51 HALs, 9 were in the lower lobes of the lungs, with a median tumor diameter of 151.8 ± 318.7mm. One patient had a tumor in the main bronchus and a patient had a tumor in the middle lobe . HAL size was associated with the location of the primary lesion .
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This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License . Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor. The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
A Rare Case Of Hepatoid Adenocarcinoma In The Lung And Literature Review: Case Report
Fudong Wang1, Yuan Weng1, Jiqun Geng1, Jun Zhu1, Baoming Mi2, Xinyi Zhou3, Jing Qian3, Qingjun You1
1 The Affiliated Hospital of Jiangnan University , The Affiliated Hospital of Jiangnan University , The Affiliated Hospital of Jiangnan University , , China
Abstract: Hepatoid adenocarcinoma is a rare type of adenocarcinoma with adenoid and hepatocyte-like differentiation that occurs outside the liver. It is highly malignant and has poor prognosis. The tumor can occur in different organs, most often being in the stomach. Primary hepatoid adenocarcinoma of the lung are extremely rare with few reports. Here, we report a case of a 67-year-old male with HAL. Serum alpha-fetoprotein level at diagnosis was > 2,000 ng/mL. He underwent right lower lobectomy with lymph nodes dissection under video-assisted thoracoscopic surgery followed by adjuvant chemotherapy . Two months after surgery, the level of serum AFP declined to normal level. The patient received regular outpatient follow-up and no local recurrence or distant metastasis was found after 18 months and the serum AFP level remained within the normal range. Review of the literature showed that HAL is a rare highly malignant disease with no standard treatment scheme. We need more cases and further studies to explore for treatment of this rare disease.
Keywords: Lung neoplasm hepatoid adenocarcinoma immunohistochemistry
Received: 26 November 2019 Accepted: 10 February 2020 Published: 25 August 2020.
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