A rare case of hepatoid adenocarcinoma of the lung

Abstract Hepatoid adenocarcinoma of the lung is a special type of primary origin in the lung with obvious pathological features and short survival time. However, standard treatment guidelines have not yet been established. Herein, we report a case of hepatoid adenocarcinoma with the primary lesion located in the left upper lung. The tumour size was reduced after four cycles of combined therapy. Subsequent postoperative pathology confirmed complete remission.


| INTRODUCTION
Hepatoid adenocarcinoma of the lung (HAL) is a rare type of primary origin in the lung with obvious pathological features of hepatocellular carcinoma. 1In 1990, HAL was first reported by Ishikura et al 2 in five patients with α-fetoprotein expression and was considered similar to hepatocellular carcinoma and produce AFP.Nagai et al 3 believed that gastric hepatoid adenocarcinoma can be diagnosed by the histomorphology of hepatoid adenocarcinoma, because it does not depend on the production of AFP.Although most cases of hepatoid adenocarcinoma are associated with AFP levels, an elevated AFP is only suggestive. 4,5he clinical symptoms of HAL are non-specific, and the treatment options are unclear.The current treatment methods depend on the primary site. 6Herein, we report the case of a patient with pulmonary hepatoid adenocarcinoma who achieved complete remission after receiving neoadjuvant chemotherapy, immunotherapy and targeted treatment.Thus, the present study aimed to enrich the available treatment information on HAL.

| CASE REPORT
A 46-year-old man presented to our hospital with complaints of intermittent chest pain on the left side for 3 months, accompanied by a non-irritating cough and sticky white phlegm.Specifically, it was a stabbing pain behind the sternum, occurring two to three times a day, lasting for several seconds each time and worsened after deep breathing but resolved on their own.The patient had a smoking history of 45 pack-years of and 20 years of alcohol consumption but without any remarkable relevant family medical history.Non-contrast computed tomography (CT) images revealed a lobulated mass in the inferior lingual segment of the left upper lobe of the lung; the longest cross-sectional area measured 47 Â 39 mm (Figure 1A,B).However, the patient declined puncture examination.Three months later, his symptoms exacerbated.Contrast-enhanced CT images revealed an inhomogeneous enhancement of the mass, with bronchial truncation and identification of vascular structures within.The mass was larger, and the maximum crosssectional area became 91 Â 61 mm (Figure 1C-E).No metastasis was found in the brain MR or bone nuclide scan.Abdominal CT scans revealed intrahepatic calcification, renal cyst and kidney stones.

| DISCUSSION
Hepatoid adenocarcinoma (HAC) is a rare primary extrahepatic organ or tissue with adenoid and the characteristics of hepatocellular differentiated adenocarcinoma, and its morphological and immunohistochemistry are similar to hepatocellular carcinoma (HCC).The most common site of HAC is the stomach, accounting for 63% of all cases, while HAL has an extremely low incidence, accounting for 5% of HAC cases. 7AL is indicated mainly by imaging that shows inhomogeneous masses in the upper lung fields; enhanced CT scans reveal homogeneous or heterogeneous density. 5,8,9hus, HAL is difficult to distinguish from other malignant tumours in the lung by imaging alone.Imaging studies can also detect lymph nodes or distant metastases, which aid in the evaluation of the clinical stage of the disease.Moreover, HAL is mainly diagnosed by histopathology and immunohistochemistry, which must rule out primary HCC or other HAC metastasis to the lungs. 9,10ue to non-specific clinical manifestations, HAL is often diagnosed at its advanced stage (stage III or IV), thereby resulting in shorter survival time. 7HAL patients who undergo surgery have an average life expectancy between 7 months and 7 years and a 1-year survival rate of 55%. 11arly implementation of anatomic pneumonectomy is crucial for enhancing the survival rate of patients.Therefore, surgeons should actively participate in the assessment and functional evaluation of the patient's clinical stage and resectability, as well as determine surgical indications and techniques based on tumour progression and the patient's functional status. 12For patients with late-stage HAL or unresectable tumour, chemoradiotherapy can be combined with other adjuvant therapy. 13Valle et al 14 reported a case of stage IV HAL, with an overall survival of 55 months after four chemotherapy regimens, including cisplatin and pemetrexed with radiotherapy for metastatic lesions, highlighting the benefit of the combination of chemotherapy and radiotherapy.Basse et al 15 reported a case of a partial response to immunotherapy despite a PD-L1-negative status, which subsequently resulted in death due to infectious complications.In the present case, neoadjuvant chemotherapy, immunotherapy and targeted therapy were started before surgery.After 3 months of treatment, imaging studies demonstrated efficacy.Subsequent postoperative pathology results confirmed complete remission.
To date, there is no preferred treatment prescription due to the challenges of organising large-scale trials.More case reports are needed to provide guidance for the future treatment.

AUTHOR CONTRIBUTIONS
Xuejian Sun was involved in drafting the manuscript.Jialin Liu and Ting Hu was involved in acquisition of data.Yefan Wu has gathered medical records.Hao Zhang designed and revised the manuscript.All authors have read and approved the final manuscript.

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I G U R E 1 (A,B) Non-contrast chest computed tomography (CT) scan revealed a soft tissue in the left upper lobe, measuring 47 Â 39 mm in size.(C-E) Three months later, contrast-enhanced CT showing the mass appeared inhomogeneous enhancement, which was larger than before, measuring 91 Â 61 mm in size.