Elsevier

Seminars in Oncology

Volume 40, Issue 1, February 2013, Pages 23-36
Seminars in Oncology

The evolving landscape of neuroendocrine tumors
Pathology Reporting of Neuroendocrine Tumors: Essential Elements for Accurate Diagnosis, Classification, and Staging

https://doi.org/10.1053/j.seminoncol.2012.11.001Get rights and content

Much recent debate has focused on the optimal classification of epithelial neuroendocrine tumors (NETs). Multiple different systems of terminology, grading, and staging have been proposed, and some systems combine elements of grade and stage into a single prognostic classification. Recently, national and international consensus groups have attempted to standardize the classification of NETs, especially for those arising in the gastrointestinal tract and pancreas. Furthermore, the recognition that common classification criteria (such as proliferative rate) span multiple different systems allows the basic data necessary to predict outcome and tailor therapy to be included in pathology reports, even though a single uniform system of terminology may remain elusive. Formal tumor-node-metastasis (TNM)-based staging systems also have been developed recently, and advances in the treatment of some NETs (pancreatic in particular) are pointing towards the need to assess therapeutic biomarkers in routine practice. This review will present the most widely used systems for classifying, grading, and staging NETs and will summarize the recommendations for the data to be included in standard pathology reports of these uncommon tumors.

Section snippets

Nomenclature

There has been considerable debate about the terminology for NETs, with the nomenclature changing through the years and also varying among different primary sites. The term “carcinoid tumor” was originally proposed to mean “carcinoma-like,” a reflection of the relatively less aggressive clinical course of well differentiated NETs, compared to exocrine carcinomas of the same organs. However, carcinoid tumor has been criticized as a diagnostic term36, 37 because of the mistaken assumption of

Grading

Historically, much debate centered on the prediction of malignancy in NETs. However, over the past decade there has been a gradual move from a dichotomous, “benign” versus “malignant” approach to a risk stratification approach, identifying factors that correlate with an increased risk for more aggressive behavior, rather than attempting to sharply separate benign and malignant NETs. Now, in most organ systems, all clinically relevant NETs are regarded to have some malignant potential, and none

Staging

The prognostic importance of tumor stage is one of the more universal aspects of cancer biology, yet curiously, there were no specific tumor-node-metastasis (TNM) staging systems for NETs until very recently.14, 15, 19, 69 A relatively crude staging system has been used for years in the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute, which categorizes the extent of disease as “localized,” “regional” or “distant.”70 But no TNM system was developed for

Other Pathology Information

In addition to the information needed for proper classification, grading, and staging of NETs, there is other pathology information that may be of importance for prognosis, primary site determination, and therapy. For surgical resection specimens, the status of the resection margins should be reported, both for primary tumors and for resected metastases. For resected tumors with close margins (ie, within <0.5 cm), it has been recommended that the distance to the margin be indicated.13

Specimen-Specific Considerations

It is clear that some of the useful pathologic information can only be ascertained on the basis of resection specimens. Since a significant proportion of NET patients present with stage IV disease, it is common that the only specimen obtained for pathologic interpretation is a biopsy or a cytology specimen (such as a fine-needle aspiration). The information that may be gleaned from these small specimens is much more limited, although valuable data to direct therapy can still be obtained in most

Information for Pathology Reports

This review has addressed much of the important pathology data that should appear in routine reports. Much more optional information may be useful in specific clinical scenarios, and with growing knowledge about treatment-related biomarkers, it is likely that additional studies using immunohistochemistry or molecular techniques may become more widely indicated. Several recent publications have reviewed the basic pathology data that should currently be reported.13, 20, 22, 23, 24, 25 Although

Conclusions

Despite the persistence of a number of different classification systems that employ different terminology and grading and staging parameters, the approach to the pathologic analysis and reporting of neuroendocrine neoplasms has become much more standardized in the recent past. The important role of the proliferative rate in predicting outcome is clear, and major international consensus groups have recently revised the criteria for classification. Staging systems are now in place as well. It

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  • Conflicts of interest: none.

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