Differential response in patients with large cell neuroendocrine carcinoma of the lung to initial therapy: A case series

Abstract

Background: Large cell neuroendocrine tumors of the lung (LCNEC) are rare. Chemotherapy with the small cell lung carcinoma (SCLC) regimen is the most appropriate treatment for LCNEC. However, there is evidence that the non-small cell lung cancer regimen is also effective in some reported cases. Due to the differences in response to LCNEC treatment, a standard of care for LCNEC has not been established.

Cases: The clinical records of nine patients with LCNEC who were treated with anticancer drugs based on an SCLC regimen from March 2016 to March 2022 were retrospectively reviewed. The patients who responded to treatment after one cycle of systemic chemotherapy were compared to those who did not respond. All patients in the responder group had a performance status (PS) of 0 or 1. However, 5 of the 6 patients in the non-responder group had a PS of 2 or 3, indicating that many patients were in poor general condition. Although patients with multiple metastases to more than one organ prior to treatment were not identified in the responder group, five of these patients were in the non-responder group. In the non-responder group, all patients discontinued treatment due to deterioration of general condition during first-line treatment. Thus, none of them were able to start the second-line treatment.

Conclusion: The results of this study may suggest that early diagnosis and initiation of treatment before multiple organ metastasis development and PS decline may have clinical implications that could lead to improved treatment response in patients with LCNEC.

Keywords: chemotherapy; large cell neuroendocrine carcinoma; non-small cell lung cancer; small cell lung carcinoma; treatment.

FIGURE 1

Computed tomography (CT) image of the chest (soft‐tissue windows). Chest CT image of a 69‐year‐old man (case 4 in Table 2). (A) Pre‐treatment chest CT shows a mass protruding from the right pleura (white arrow). (B) Chest CT after 1 cycle of treatment with CBDCA + VP‐16 therapy shows disappearance of the right pleural mass (white arrow)

FIGURE 2

Histological and immunohistochemical findings. Histopathology of the lung tumor (hematoxylin and eosin [H&E] staining) shows large tumor cells with numerous mitotic figures and a rosette‐like arrangement. Immunostaining shows positivity for CD56 and synaptophysin and partial positivity for chromogranin A. (A) H&E staining, bar: 50 μm. (B) Synaptophysin staining, bar: 50 μm. (C) CD56 staining, bar: 50 μm. (D) Chromogranin A staining, bar: 50 μm. (A–D) Magnification, ×20

FIGURE 3

CT image of the chest (soft‐tissue windows). Chest CT image of a 67‐year‐old woman (case 5 in Table 2). (A) Pretreatment chest CT shows a 23 mm × 10 mm mass in the right lower lobe (white arrow). (B) Chest CT after one cycle of CBDCA + VP‐16 therapy shows no change in the size of the right lower lobe tumor (white arrow)

FIGURE 4

Histological and immunohistochemical findings. Histopathology of the lymph node (hematoxylin and eosin [H&E] staining) shows a palisade of tumor cells with a high nuclear/cytoplasmic (N/C) ratio and nuclear fission. Immunostaining reveals positivity for CD56, synaptophysin, and chromogranin A. (A) H&E staining, bar: 20 μm. (B) Synaptophysin staining, bar: 20 μm. (C) CD56 staining, bar: 20 μm. (D) Chromogranin A staining, bar: 20 μm. (A–D) Magnification, ×40