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J.L. Derks
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-024 - Large Cell Neuroendocrine Carcinoma: How Accurate Are the WHO 2004 Classification Criteria Applied? (ID 2127)
09:30 - 17:00 | Author(s): J.L. Derks
- Abstract
Background:
According to the WHO 2004 (and 2015) classification, the diagnosis large cell neuroendocrine carcinoma (LCNEC) is established on presence of neuroendocrine morphology (i.e. organoid nesting/trabecular pattern, palisading cells and/or rosette formation) and neuroendocrine staining by immunohistochemical (IHC) markers. Furthermore, large cells should be present. However, diagnosis of LCNEC is restrained by the need of a resection or large biopsy specimen. Nonetheless, lung cancer is often diagnosed on small biopsies and therefore application of these WHO criteria in daily practice can be difficult. In this nationwide study we investigate on what tissue the diagnosis of LCNEC was established and to what extend the WHO 2004 criteria are reported in pathology reports established in the daily pathology practice in the Netherlands.
Methods:
Written conclusions (diagnoses) of pathology reports (2003-2012) were retrieved from the Dutch Pathology Registry (PALGA). Conclusions describing LCNEC were selected by queries on anatomic location, diagnosis and keywords (e.g. large cell + endocrine) and screened in accordance with a pathologist (JLD & RJS). Histologically diagnosed LCNEC cases were then selected and pathology centers were requested to send the report. After screening (JLD), consultation reports were excluded and the following data were extracted and compared: 1) mitotic index, 2) necrosis, 3) growth pattern (reported ≥1 feature(s) according to WHO or mentioning neuroendocrine morphology) and 4) neuroendocrine IHC marker staining. Additionally, the sampling method was recorded and retrieved diagnoses were clustered.
Results:
N=892 (72%) of 1235 requested reports were received (43 centers, mean 20 (range 1-67) reports). In N=869 pathology reports the conclusion was LCNEC including 759 original and 110 consultation reports. Most diagnoses were established on resection specimens (N=404, 53%) followed by needle (N=195, 26%) and small biopsies (N=160, 20%). Retrieved diagnoses could be clustered into LCNEC (N=658, 87%), combined LCNEC (N=41, 5%) and carcinoma favor LCNEC (N=60, 8%) respectively. Presence of mitoses was reported in N=541 (71%) yet only N=121 (16%) mentioned the mitotic index (≥10 mitoses 2mm[2] N=107). Necrosis was described in N=466 (61%) reports, most had central/abundant necrosis N=317 (68%) but in N=84 (11%) necrosis was undefined. Neuroendocrine morphology or a feature of neuroendocrine morphology was described in N=452 (60%) reports and in all except N=13 reports a neuroendocrine IHC marker was positive. When combining the WHO criteria, only N=66 (9%) of reports described all criteria, this increased to N=253 (33%) when mitosis without description of an index was included and N=403 (53%) if the report described either mitosis or necrosis. Lowest reported rates were observed in reports of needle biopsy (8-27%) and biopsy (4-15%) specimens.
Conclusion:
In 91% of retrieved pathology reports the WHO criteria for the diagnosis LCNEC could not be retrieved. Although 53% of reports included descriptions of neuroendocrine growth pattern and mitosis or necrosis, these regularly were incomplete or not quantifiable. Most commonly this was observed in reports from (needle) biopsy specimens. Whether the WHO criteria could not be established or if it is due to preference of the pathologist remains unclear and requires further investigation. Nevertheless, implementation of structured pathology reporting protocols for LCNEC should be considered.
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P2.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 225)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.08-023 - Aberrant Neuroendocrine Lung Tumor Nomenclature in Daily Practice, How Common Is It? (ID 2120)
09:30 - 17:00 | Author(s): J.L. Derks
- Abstract
Background:
The WHO 2015 classification for pulmonary carcinoids (PC) and high-grade neuroendocrine carcinomas (NEC) has in essence, not been changed compared to the previous one, despite known limitations in the diagnostic process such as 1) the need for resection material or large biopsies 2) reported inter-observer variability and 3) sporadic exposure in daily practice. Furthermore, nomenclature used in previous or different classification systems for neuroendocrine tumors may result in an aberrantly applied description of the WHO 2004 diagnoses. Here we evaluate if nomenclature established in daily pathology practice in the Netherlands is according to that advised by the WHO 2004 for PC, NEC and non-small cell lung cancer (NSCLC) with neuroendocrine differentiation established by immunohistochemistry (IHC).
Methods:
Written conclusions (diagnoses) of pathology reports (2003-2012) were retrieved from the Dutch Pathology Registry. Conclusions describing PC, NEC and carcinomas with neuroendocrine features/differentiation were selected by multiple queries on anatomic location, diagnosis and keywords (e.g. carcinoma + endocrine). All conclusions were screened in concordance with an experienced pathologist (JLD & RJS) and data on sampling method, diagnoses and origin of primary tumor were collected. Conclusions were excluded if established on autopsy cases or if it reported differential diagnoses, diagnoses of non-pulmonary/unknown primary, non-neuroendocrine or small cell lung cancer. We compared the retrieved diagnoses with the advised WHO 2004 nomenclature after which all diagnoses were clustered (e.g. typical/well differentiated/grade I carcinoid into “PC”). For statistical analysis the X[2] test was used.
Results:
4612 conclusions were eligible for analysis of which N=698 (15%) described a diagnoses that did not match the WHO nomenclature. Foremost non-WHO diagnoses were: (poorly differentiated) neuroendocrine carcinoma; high-grade neuroendocrine carcinoma/tumor; NSCLC neuroendocrine carcinoma; neuroendocrine tumor and low grade (well differentiated) neuroendocrine carcinoma/tumor (carcinoids). After discussion, we clustered N=2005 (43%) diagnoses into PC, N=1788 (39%) in high-grade NEC, N=763 (17%) in carcinoma with neuroendocrine features/differentiation and N=56 (1%) in neuroendocrine tumor n.o.s., respectively. Deviations from the WHO nomenclature occurred in 8% (N=157) of PC and 21% (N=377) of high-grade NEC and this occurred mainly on biopsy/cytology specimens (75% (N=399)). In (NSCLC) carcinomas with neuroendocrine features/differentiation diagnoses deviated from the WHO in 14% (N=108). Additionally, both the terms neuroendocrine “features” and “differentiation” were used to address positive neuroendocrine IHC staining (16% vs 25%) though differentiation was used slightly more often (p=0.001). Finally, 52% (N=1045) of PC diagnoses were established on biopsy/cytology specimens and a strong increase in diagnoses of large cell neuroendocrine carcinoma (LCNEC) on biopsy/cytology specimens was observed (<2008 N=174 vs. ≥2008 N=464, p<0.001).
Conclusion:
In daily practice 8% of PC, 21% of high-grade NEC and 14% of (NSCLC) carcinomas with neuroendocrine features/differentiation diagnoses deviated from the WHO 2004 nomenclature. This occurred mainly on biopsy/cytology specimens. Also, the diagnosis (NSCLC) carcinoma with neuroendocrine ‘differentiation/features’ was unclear and should be specified (i.e. IHC or morphologically based (or both)). Finally, often the diagnosis LCNEC was established on biopsy/cytology specimens whereas this is not advised by the WHO. Whether these findings are due to personal preferences or difficulties applying current classification to limited samples, require further investigation.
