Hepatoid Adenocarcinoma of the Lung: Beyond a Shadow of Doubt and Risk of High Mortality [Letter]

Dear editor

We have read the paper by Chen¹ with great interest. We further like to share our outlook on the matter.

The authors presented the case of a 67 years old male Chinese patient of hepatoid adenocarcinoma of lung (HAL). The context of selecting this particular case to help study the centralized clinicopathology and potential biological pathways in HAL is not included.

In the inclusion criteria, no discussion or cut-off for clinicopathology of HAL, which is the prime construct of the study, is mentioned. Setting criteria for the inclusion of valid clinicopathological information related to HAL would establish a standard for its quality synthesis.

In the inclusion criteria, there is no specification of study types or design, and similarly, methods to control for heterogeneity or the confirmation of the homogeneity of the data is not provided.

In this paper which presents a case report and a review of literature, the authors confirm that the clinicopathological diagnosis of their patient relates with Hepatoid adenocarcinoma of the lung but do not mention the clinical events in their patient after the patient’s first presentation to their hospital.

In the case presented by the authors, their patient had a 30-year smoking history with 60 cigarettes in a day. This much smoking can prove to be a significant contributor to the specific presentation and prognosis of their patient. Accurate analysis with respect to the smoking history and then comparison with other cases of HAL can reveal interesting insights into the pathogenesis, clinicopathological features, prognosis, and even HAL-related oncogenes.²

The authors have not given the means of quality assessment of their included studies and also have not commented on the quality and biases of the included studies.

The review reported regarding prognosis of HAL patients to have a median overall survival (OS) time of 16 months ranging from 0.4 to 108 months. A 54-year-old white, smoker (35 pack years) woman with metastatic HAL and a 5 cm² by 4 cm² mass at the left fifth costosternal junction, clinical stage IV, and multiple relapses was treated with endobronchial tumour debridement and chemoradiation. The patient continued to live for more than 9 years.³ Hence, a thorough and deep study of HAL epidemiology and pathogenesis in multiple population groups is still needed for deriving valuable insights for the most suitable treatment options which may also potentially change the OS time for patients.

The authors reported the involvement of TP53 in HAL. Recently published reports⁴ show that TP53 mutation is the most frequent mutation in the pathogenesis of HAL and due to increased susceptibility, drugs acting upon PD-1 are thought to be a suitable treatment option. It is hypothesized that pembrolizumab, a PD-1 acting drug, would lead to a better and tumour progression-free survival in HAL patients.

The authors rightly reported that HAL is a rare disease of the lung. Hence, large-scale studies across different populations and a thorough consideration of confounders are required to understand the disease and to derive valuable insights for better treatment.