Neuroendocrine tumours—challenges in the diagnosis and classification of pulmonary neuroendocrine tumours

Abstract

Pulmonary neuroendocrine (NE) proliferations are a diverse group of disorders which share distinct cytological, architectural and biosynthetic features. Tumours composed of NE cells are dispersed among different tumour categories in the WHO classification of tumours and as such do not conform to a singular group with regards to treatment and prognosis. This is reflected by the highly variable behaviour of NE proliferations, ranging from asymptomatic, for instance in diffuse idiopathic pulmonary NE cell hyperplasia and tumourlets, to highly malignant cancers such as small cell lung cancer and large cell NE carcinoma. In this review NE proliferations are described as distinct entities ranging from low grade lesions to high grade cancers. The differential diagnoses are considered with each of the entries. Finally, mention is made of tumours which may show some NE features.

What clinicians are asking pathologists when dealing with lung neuroendocrine neoplasms?

“…Accordingly, TC is deemed to be a low-grade malignant tumor with longer life expectation and time to recurrence, AC an intermediate-grade malignant tumor with more aggressive clinical course, somewhat unpredictable clinical behavior and shorter time to recurrence, and LCNEC and SCC high-grade malignant tumors with dismal prognosis, challenging therapy options and, often, difficulties in reliably distinguishing from each others, either pathologically, genetically or clinically 1,4,8,[14][15][16][17][18][19] .…”

“…There are a number of issues accounting for inconsistency between morphology and clinical behavior 6,12,63 . Difficulties in recognizing mitoses and necrosis in the group of TC and AC 55 and variability in assessing cell size and cytological features in the group of LCNEC and SCLC 6,15,16,23,57 may explain inconsistencies in the diagnostic reproducibility of lung NET.…”

“…Cytological criteria are then used to split SCC from LCNEC, although there is a considerable morphologic overlap between them making this separation quite subjective and difficult to carry out, with disappointingly low inter-observer diagnostic reproducibility 12,15,16,[22][23][24][25] .…”

Comprehensive analysis of pulmonary Large Cell Neuroendocrine Carcinoma (LCNEC)

“…Dit klinkt erg overzichtelijk maar in de huidige klinische praktijk worden zowel pathologen als (long)oncologen met verschillende problemen met betrekking tot de diagnose en behandeling van LCNEC geconfronteerd 7,8 .…”

“…The clinical characteristics of LCNEC are further described in chapter 1 and 2. In current clinical practice, pathologists and clinicians come across several problems regarding the diagnosis and treatment of LCNEC 7,8 ; with the two biggest difficulties being: I. Pathologist may find it difficult to diagnose LCNEC because of overlapping diagnostic classification criteria with SCLC [9][10][11][12][13] and the lack of diagnostic criteria for LCNEC on a biopsy specimen [14][15][16][17][18] . II.…”