Hepatoid Adenocarcinoma of the Lung: A Review of the Most Updated Literature and a Presentation of Three Cases

Abstract

In a Surgical Thoracic Center, two females and a man were unexpectedly diagnosed with hepatoid adenocarcinoma of the lung (HAL) in a single year. HAL is a rare lung cancer with pathological features of hepatocellular carcinoma with no evidence of liver tumor or other primitive sites of neoplasms. As of today, a comprehensive treatment is still not written. We reviewed the most updated literature on HAL, aiming to highlight the proposed treatments available, and comparing them in terms of survival. General hallmarks of HAL are confirmed: it typically affects middle-aged, heavy-smoker males with a median of 5 cm bulky right upper lobe mass. Overall survival remains poor (13 months), with a longer but non-significant survival in females. Treatments are still unsatisfactory today: surgery guarantees a small benefit compared to non-operated HALs, and only N0 patients demonstrated improved survival (p = 0.04) compared to N1, N2, and N3. Even though the histology is fearsome, these are probably the patients who will benefit from upfront surgery. Chemotherapy seemed to behave as surgery, and there is no statistical difference between chemotherapy only, surgery, or adjuvant treatments, even though adjuvant treatments tend to be more successful. New chemotherapies have been reported with notable results in recent years, such as Tyrosine Kinase Inhibitors and monoclonal antibodies. In this complicated picture, new cases are needed to further build shared evidence in terms of diagnosis, treatments, and survival opportunities.

Metastatic mediastinal hepatoid adenocarcinoma

“…It was previously believed that most extrahepatic HACs express aFP, a fetal protein which is expressed during liver regeneration and in certain tumours such as HCC and yolk sac tumour, however, elevated aFP does not necessarily confirm a diagnosis of HAC 8. More recently, literature reviews by Chen et al 5 and Bonis et al 9 state that elevated aFP may contribute to clinical diagnosis but are not necessary for the diagnosis of HAL. In fact, aFP may be used to identify the degree of tumour differentiation 10…”

“…There is no specific staging method for this rare type of mediastinal hepatic adenocarcinoma 9. Since HAC is an extremely heterogeneous type of tumour, the treatment for HAC is not standardised.…”

“…Targeted therapy is usually reserved for patients who have EGFR (Epidermal growth factor receptor) or KRAS (Kirsten rat sarcoma virus) mutations, or ALK rearrangement mutations 7. Bonis et al 9 discussed the possibility of using tyrosine kinase inhibitors such as anlotinib, osimertinib and sorafenib as part of the treatment regimen especially in HAL with HepPar1 positivity 12. Since this condition is quite rare, scientific literature regarding chemotherapy is quite limited and further research should be carried out in order to ascertain which treatment regimens are most effective in patients with this rare disease.…”

A rare case of hepatoid adenocarcinoma of the lung

“…HAL is indicated mainly by imaging that shows inhomogeneous masses in the upper lung fields; enhanced CT scans reveal homogeneous or heterogeneous density 5,8,9 . Thus, HAL is difficult to distinguish from other malignant tumours in the lung by imaging alone.…”

Long survival after neoadjuvant and adjuvant camrelizumab plus chemotherapy and surgery in a patient with hepatoid adenocarcinoma of the lung: A case report

“…Hepatoid adenocarcinoma of the lung (HAL) is an uncommon variant of lung cancer characterized by morphological and immunohistochemical features resembling hepatocellular carcinoma, 1 and it is generally associated with poor survival. 2 , 3 The survival for patients with resectable HAL spans from 3 to 108 months, with less than 50% beyond 24 months.…”