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. 2021 Aug 6:11:702216.
doi: 10.3389/fonc.2021.702216. eCollection 2021.

Hepatoid Adenocarcinoma of the Lung: A Systematic Review of the Literature From 1981 to 2020

Zan Hou  1   2 , Jiaqing Xie  3 , Li Zhang  4 , Gangyi Dai  1 , Yuanhang Chen  1 , Lang He  1
Affiliations

Hepatoid Adenocarcinoma of the Lung: A Systematic Review of the Literature From 1981 to 2020

Zan Hou et al. Front Oncol. .

Abstract

Objectives: We report the first case of hepatoid adenocarcinoma of the lung (HAL) 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 (AFP) level before treatment.

Methods: We report a 66-year-old male case who was diagnosed with locally advanced HAL with PIK3CA mutation and carried out a systematic literature search for HAL cases documented between 1981 and 2020. General patient information including case characteristics was extracted and summarized. The median OS (mOS) of HAL patients was determined using the KM survival curve. The Cox proportional hazards regression model was used to evaluate the effect of tumor size, location, and serum AFP value before treatment and radical surgery (RS) on the prognosis of patients.

Results: A total of 46 studies including 51 HAL patients was included in our review. Our study revealed that 52.9% of tumors were located in the upper lobe of the right lung. The proportion of serum AFP-positive patients before treatment, early-stage patients (TNM stage I and II), and patients who had received surgery were 69.2%, 34.1%, and 40%, respectively. The mOS of HAL patients was 16.0 months. The 2-year and 5-year survival rates of the patients were 35.3% and 8.0%, respectively. In the subgroup analysis, the 2-year survival rate for patients who received RS was 62.5%, while for patients who were unable to undergo RS, it was only 12.5% (p = 0.009). The Cox proportional hazards regression model indicated that RS can significantly improve the prognosis of HAL patients (p = 0.011), although the location and size of tumor as well as the serum AFP value before treatment had no significant effect on their prognosis (p = 0.82, p = 0.96, p = 0.25).

Conclusions: 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.

Keywords: case report; clinical features; hepatoid adenocarcinoma of the lung; prognosis; systematic review; treatment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Paper selection flowchart.
Figure 2
Figure 2
CT images of lung tumor and mediastinal lymph nodes of patient. (A, B) Baseline inspection on April 18, 2019, showed right upper lobe tumor and subcarinal lymph node metastasis, respectively. (C, D) Images on April 6, 2020, suggested multiple pulmonary metastases and multiple mediastinal lymph node metastases, respectively.
Figure 3
Figure 3
Hematoxylin and eosin staining and immunohistochemistry. (A) Neoplastic cells arranged in an alveolar pattern and the glandular lumen can be seen in the lesion area (magnification, ×200). (B) Neoplastic cells with prominent and hyperchromatic nucleoli, nuclear pleomorphism, and abundant eosinophilic cytoplasm, consistent with an adenocarcinoma with hepatoid differentiation (magnification, ×400). (C) The tumor cells were positive for GPC-3 (magnification, ×200). (D) The tumor cells were negative for hepatocyte (magnification, ×200). (E) The tumor cells were positive for CK7 (magnification, ×200). (F) The tumor cells were negative for TTF-1 (magnification, ×200).
Figure 4
Figure 4
Survival curve of HAL patients.
See this image and copyright information in PMC

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