EML4-ALK rearrangement of lung large cell neuroendocrine carcinoma: a case report

Abstract

Background: Lung large cell neuroendocrine carcinoma (L-LCNEC) is a subtype of lung cancer with a low incidence and a high degree of malignancy. For early stage patients, surgical treatment is limited, and the risk of postoperative recurrence is high. For patients with unresectable or advanced disease, platinum-based chemotherapy is currently the mainstay of treatment, but its efficacy is unsatisfactory. L-LCNEC with the anaplastic lymphoma kinase (ALK) gene mutation is very rare and currently has no standard therapy. In this article, we report the case of a locally advanced L-LCNEC patient with ALK mutations who underwent first-line treatment with alectinib.

Case description: A previously healthy, 46-year-old, non-smoking woman was clinically diagnosed with unresectable locally advanced L-LCNEC. Next generation sequencing (NGS) of the patient's plasma and tumor specimen showed echinoderm microtubule-associated protein-like 4 (EML-4) (exon 13)-ALK (exon 20) fusion with a mutation frequency of 14.48% and 15.37%. The patient refused chemotherapy, and received first-line treatment with alectinib 600 mg, bis in die (bid), per day. After taking alectinib for 1 month, the patient's chest enhanced computed tomography (CT) scan showed a partial response (PR). After 12 months of treatment with alectinib, a radiological evaluation showed that the patient had maintained the PR. A grade 2-3 rash was observed at the beginning of the treatment. After symptomatic treatment, the rash disappeared, and the side effects were fully tolerated. At present, the patient can work normally, has a performance status of 0 and has not experience any major adverse events.

Conclusions: Our case suggests that the first-line use of targeted therapy is also a good choice for L-LCNEC patients of stage III with gene mutations. The side effects are light, the patient can tolerate well, and the quality of life of can be improved.

Keywords: Alectinib; Lung large cell neuroendocrine carcinoma (L-LCNEC); anaplastic lymphoma kinase (ALK); case report; neuroendocrine tumors (NET).

Figure 1

Comparison of chest CT between 2021-06-17, 2021-08-19 and 2022-08-29. (A) The primary lesion of the lung. (B) Metastatic lymph node of 4R region. (C) Metastatic lymph node of 11R region.

Figure 2

Ultrasonic bronchoscope. (A) is metastatic lymph node of 4R region (the largest short lymph nodes is 20.4×30.6 mm). (B) is metastatic lymph node of 11R region (the largest short lymph nodes is 12.9×21.6 mm); blood flow signal can be seen in it.

Figure 3

Pathological results of the mediastinal lymph node puncture. (A) Histology 10× HE. (B) Histology 40× HE. (C) tumor expression Syn 20× HE. (D) Tumor expression CgA 20× HE. HE, hematoxylin and eosin.

Figure 4

The tumor marker CEA gradually decreased. CEA, carcinoembryonic antigen.

Figure 5

Treatment-related adverse skin rashes. (A) Skin rashes appeared on the palm. (B,C) After symptomatic treatment, the skin gradually peeled off and then returned to normal. (D) Skin rashes appeared on the back of the hand. (E) After symptomatic treatment, the rash subsided and there was no pigmentation. (F) Skin rashes on the upper limb. (G) During the course of medication, the rash subsided, but pigmentation remained after the symptomatic treatment.

Figure 6

Timeline of the case. CT, computed tomography; NGS, next generation sequencing; L-LCNEC, lung large cell neuroendocrine carcinoma; NGS, next generation sequencing; EML4, echinoderm microtubule-associated protein-like 4; ALK, anaplastic lymphoma kinase.