Diagnostics and treatment in bronchial carcinoid tumors
Authors:   , Reuling Ellen Marie Brigitte Paulien 
Published: October 2023

At the start of this thesis there were several unanswered questions with regard to
optimal patient selection for different treatments of bronchial carcinoid. Also, there
were unanswered questions with regard to classification of bronchial carcinoid on
small histological samples and with regard to prognostic value of several new tissue
biomarkers. The aim of this thesis was to further optimize patient selection for
parenchyma sparing techniques, and to explore the potential value of biomarkers in
the treatment of bronchial carcinoid.

Part one (chapter 2-5) of this thesis describes the classification of bronchial carcinoid
on small histological samples and the use of diagnostic and prognostic biomarkers.

In Chapter 2 we analyze patient selection for endobronchial treatment and
underscore the importance of radiological assessment of bronchial carcinoids.

Differentiation between typical and atypical carcinoid according to the current WHO
classification is accomplished by obtaining the mitotic count and the presence of
necrosis. As outlined above, TC is defined as a neuroendocrine tumour with less than
2 mitoses per 2 mm2 and absence of necrosis, while AC is defined by 2-10 mitoses
per 2 mm2 and/or the presence of (dot-like) necrosis. However, it is known that small biopsies have limited diagnostic value for the distinction between TC and AC. In Chapter 3 and Chapter 4 we analyzed biopsy-resection paired specimens of
patients referred for treatment for bronchial carcinoid to measure accuracy of
pretreatment biopsies and analyze the value of tumor biopsy size. Furthermore, we
describe the reliability of different immunohistochemical markers on different
biopsies and resection specimens, and assessed the impact of specimen size on the
accuracy of the diagnosis.

Because the current classification of TC and AC only partially reflects their metastatic
potential, there is a need for more accurate prognostic biomarkers for bronchial
carcinoids. In Chapter 5 we investigated a combination of morphological and novel
immunohistochemical markers for predicting dissemination.

Part two (chapter 6-8) focuses on therapeutic strategies and patient selection for EBT.
In Chapter 6 we present the results of a systematic review of the available literature
on the feasibility and outcome of endobronchial treatment compared to surgical
resection. We studied several endpoints such as overall survival, disease free survival,
recurrence rate, complications, quality of life, and healthcare costs.

Where EBT can be curative for patients with small intraluminal carcinoid tumors,
tumor debulking prior to surgery may potentially result in less lung parenchyma that
has to be removed during surgery to achieve complete resection of the tumor. In
addition, EBT may reduce the need for sleeve resection to achieve radical margins
when bulky tumors are removed. It is in Chapter 7 that we investigated whether
endobronchial therapy for bronchial carcinoid, if not curative, can reduce the extent
of the surgical resection and whether EBT prior to surgery is associated with
increased surgical morbidity.

Several letters, in reply to comments from experts in the field of treatment for
bronchial carcinoid tumors, regarding published studies by our group, are bundled
in Chapter 8.