PD-L1 Expression in Small Cell and Large Cell Neuroendocrine Carcinomas of Lung: an Immunohistochemical Study with Revie
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ORIGINAL ARTICLE
PD-L1 Expression in Small Cell and Large Cell Neuroendocrine Carcinomas of Lung: an Immunohistochemical Study with Review of Literature Prerna Guleria 1
&
Sunil Kumar 2 & Prabhat Singh Malik 3 & Deepali Jain 4
Received: 5 February 2020 / Revised: 10 April 2020 / Accepted: 26 May 2020 # Arányi Lajos Foundation 2020
Abstract High-grade neuroendocrine tumors (HGNET) have distinctive tumor biology/behaviour. Newer modalities of treatment (immunotherapy) for them have been included in recent NCCN guidelines. Detection of programmed death receptor-ligand 1 (PD-L1) expression by immunohistochemistry have made easy identification of patients eligible for immunotherapy. We aimed to ascertain expression of PD-L1 on small cell and large cell neuroendocrine carcinomas of lung and review existing literature. Eighty-five cases of HGNET lung (primary/metastatic), were retrieved and reviewed. Immunostaining for PD-L1 using clone SP263 was done. Any amount/intensity of membranous staining of > = 1% tumor cells was cut-off for positivity. Previously published studies using Google and/Pubmed search engines were reviewed. Of 85 cases, 70 were small-cell lung cancer (SCLC), 11 large-cell neuroendocrine carcinoma (LCNEC) and 4 combined SCLC. Median age was 46.5 years with male preponderance. No PD-L1 expression was seen in 91.6% cases. The 7 positive cases were 4 LCNEC, 2 SCLC and 1 combined SCLC. The percentage positivity varied from 1–100%; lower percentage positivity was seen in SCLC. PD-L1 expression on immune cells was seen in 31.3% cases. Sixteen studies evaluating 1992 NET were found; E1L3N PD-L1 clone was commonly used clone. PDL1 positivity was associated with better prognosis in most studies. There are only a few studies available in literature related to PDL1 expression in high grade neuroendocrine carcinomas of lung. In general, PD-L1 positivity is highly variable and seen in lower percentage of these tumors. With the recent approval of immunotherapy, biomarkers other than PD-L1 should also be investigated in these tumors. Keywords Pulmonary high grade neuroendocrine tumors . PD-L1 . SP263 . Immunotherapy . Small cell lung carcinoma
Introduction The 2015 World Health Organization (WHO) classification of the tumors of lung, pleura and thymus has classified the neuroendocrine tumors (NET) of the lung into preinvasive
* Deepali Jain [email protected] Prerna Guleria [email protected]
lesions, the carcinoids (typical and atypical), large cell neuroendocrine carcinoma (LCNEC) and the small cell lung carcinoma (SCLC) including the combined LCNEC and SCLC respectively [1]. Even though they are grouped together, the carcinoids differ significantly from the high grade LCNEC
1
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
2
Department of Surgical Oncology, Dr BRA Institute-Rotary Cancer Hospital All India Institute of Medical Sciences, New Delhi 110029, India
3
Department of Medical Oncology, Dr BRA Institute-Rotary Cancer Hospital All India Institute of
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