Pathology

Essential to diagnosis and clinical decision-making

Dr David Klimstra talks about key pathology data that physicians can use in diagnosing and managing neuroendocrine disease.

Pathology is important for an accurate diagnostic classification of a NET. Pathology reports should also include grade and stage of the NET, as well as information relevant to prognosis, adequacy of surgical excision, and disease management.1,2

It is not always easy to discern this information. NETs may have similar pathologic features, but they can exhibit vastly different clinical biology. Pathologists are challenged to definitively identify different types of NETs and develop a standardized mechanism for evaluating and reporting their findings. 1-3

An additional complication is that several different classification and naming systems are used for NETs, notably those proffered by the World Health Organization (WHO), European Neuroendocrine Tumor Society (ENETS), American Joint Committee on Cancer (AJCC), and North American Neuroendocrine Tumor Society (NANETS). The 2010 WHO guidelines for classification of GI NETs achieve some consensus among these systems, but comparisons among outcome and clinical studies still can be hard to make.1,4 It is important that all of your colleagues involved with patient care are in agreement as to which naming and classification system will be used.

7 key components

Because the optimal management of patients with NETs involves multiple specialists, pathology reports for NETs should contain certain information that facilitates accurate decision-making by all members of the management team.2,4

This core data set includes 7 key components.2

  1. Site and diagnosis: When the NET has been excised, the size of the tumor also should be stated.1,2
  2. Stage: For resected primary NETs, the report should provide TNM staging information, as recommended in the WHO 2010 classification guidelines.5 For the primary stage ("T stage"), this information generally includes size of the tumor and extent of invasion into the organ of origin. Involvement of regional lymph nodes and distant metastatic sites also should be documented.1,2
  3. Differentiation: For all surgical pathology reports, the diagnosis must indicate whether the NET is well- or poorly differentiated.1 Without reference to differentiation or grade, the pathology report is inadequate for prognosis or patient management.2
  4. Grade and proliferative index: Although these 2 assessments are linked, proliferative index may vary within a primary NET and between the primary tumor and metastatic sites.1,2 Proliferative index can be assessed as the number of mitoses per unit area or as the number of neoplastic cells immunolabeling for Ki-67.2 Mitotic rate is reliable when there is a large volume of tumor to evaluate (eg, surgical resection); Ki-67 staining usually is necessary when the sample size is limited (eg, biopsy).1
  5. Other prognostic features: The report should include findings of other pathologic prognostic features, such as necrosis or vascular invasion.2
  6. Non-NET-related features: The presence of non-neuroendocrine components within the tumor should be documented.2
  7. Status of margins: For resected NETs, the adequacy of surgical resection (status of the margins) should be reported.1

If pathology reports are unclear or incomplete, it is important to seek clarification directly with the primary pathologist.

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1. Klimstra DS, Modlin IR, Adsay NV, et al. Pathology reporting of neuroendocrine tumors: application of the Delphic consensus process to the development of a minimum pathology data set. Am J Surg Pathol. 2010;34(3):300-313.
2. Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas. 2010;39(6):707-712.
3. Modlin IM, Öberg K, Chung DC, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9(1):61-72.
4. Modlin IM, Moss SF, Chung DC, Jensen RT, Snyderwine E. Priorities for improving the management of gastroenteropancreatic neuroendocrine tumors. J Natl Cancer Inst 2008;100(18):1282-1289.
5. Rindi G, Arnold R, Bosman FT, et al. Nomenclature and classification of neuroendocrine neoplasms of the digestive system. In: Bosman FT, Carniero F, Hruban RH, Theise ND, eds. WHO Classification of Tumours of the Digestive System. 4th ed. Lyon, France: International Agency for Research on Cancer (IARC) Press; 2010:13-14.
1. Klimstra DS, Modlin IR, Adsay NV, et al. Pathology reporting of neuroendocrine tumors: application of the Delphic consensus process to the development of a minimum pathology data set. Am J Surg Pathol. 2010;34(3):300-313.
2. Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas. 2010;39(6):707-712.
3. Modlin IM, Öberg K, Chung DC, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9(1):61-72.