The history of the neuroendocrine neoplasia or what is commonly called neuroendocrine tumors (NETs) is fascinating and parallels the overall history of the modern medicine. It included multiple stages, starting from early descriptive findings of tumors scattered throughout different parts of the body while having similar appearance on general and specific staining. It was followed by understanding of macroscopic behavior that was somewhat different and less aggressive that usual malignancies, thus the name of carcinoid (cancer-like), masterfully created by Siegfried Obendorfer in 1907. The next and probably most important step was understanding of the functional capacity of these tumors and their ability to synthesize a massive variety of biologically active substances. This phenomenon is absolutely unique, extremely complex and based on cellular expression of specific transporters that define the synthetic profile, advanced enzymatic machinery, capable of producing a wide variety of intermediate products, intracellular processing capacity and finally potent secretory capability. It culminated in the “age of great unification” and a new definition of these tumors as APUDomas (amine precursor uptake and decarboxylation), which included a wide variety seemingly unrelated neoplasms – benign or less so, which showed a common functionality and included pituitary, adrenal, thymic neoplasia, as well as carcinoids and some small cell carcinomas. As the time passed, we learned that different types of these tumors may vary in their embryonic origins – pheochromocytomas, carcinoids, medullary thyroid cancers, as well as organ-specific behavior even while having similar histologic structure – thymic, pulmonary and GI carcinoids, which are currently called – neuroendocrine tumors (NETs). Even within the same organ, tumors with different degree of differentiation can behave strikingly different.
Over recent decades, the field of NETs had dissipated to narrow organ- and subspecialty-specific micro-cosmoses, which mainly communicate within themselves, “coming out to light” for field-specific meetings. These meetings, on the other hand, and especially the European Neuroendocrine Tumor Society (ENETS) had provided us with updated knowledge and numerous guidelines and spearheaded development of the Neuroendocrine Tumor Centers of Excellence, that introduces an innovate comprehensive multispecialty approach, that involves representatives from multiple subspecialties that combine their effort into advanced management protocols. While these centers rapidly proliferate in Europe and around the rest of the world, US still remains somewhat resistant to this approach for several reasons, one of which is historically rigid intra-specialty approach with relatively narrow inter-specialty collaborative management. This is in striking difference to overall patients’ management in current oncology, which is widely accepted advanced multispecialty management for quite extended time. More discussion about the future of the field, collaborative intersociety relationships and application of already available positive experience is needed for providers that care for patients with NETs.
In this proposal, I suggest reviewing several issues related to current State of the Art in the NET field:
1. History of neuroendocrine neoplasia-related medical field
2. Advanced embryology, anatomy and physiology of NETs
3. Similarities in enzymatic machinery of different NETs
4. New advances in NET genetics and mutation-related
5. Advances in current diagnostic and therapeutic approaches
These can be divided by:
1. System-specific NETs – GI, pulmonary, GU etc.
2. Tumors of different biological profiles – pituitary, adrenal, systemic, etc
3. Gene-driven syndromes – MEN1, MEN2, SDHX, etc.
The history of the neuroendocrine neoplasia or what is commonly called neuroendocrine tumors (NETs) is fascinating and parallels the overall history of the modern medicine. It included multiple stages, starting from early descriptive findings of tumors scattered throughout different parts of the body while having similar appearance on general and specific staining. It was followed by understanding of macroscopic behavior that was somewhat different and less aggressive that usual malignancies, thus the name of carcinoid (cancer-like), masterfully created by Siegfried Obendorfer in 1907. The next and probably most important step was understanding of the functional capacity of these tumors and their ability to synthesize a massive variety of biologically active substances. This phenomenon is absolutely unique, extremely complex and based on cellular expression of specific transporters that define the synthetic profile, advanced enzymatic machinery, capable of producing a wide variety of intermediate products, intracellular processing capacity and finally potent secretory capability. It culminated in the “age of great unification” and a new definition of these tumors as APUDomas (amine precursor uptake and decarboxylation), which included a wide variety seemingly unrelated neoplasms – benign or less so, which showed a common functionality and included pituitary, adrenal, thymic neoplasia, as well as carcinoids and some small cell carcinomas. As the time passed, we learned that different types of these tumors may vary in their embryonic origins – pheochromocytomas, carcinoids, medullary thyroid cancers, as well as organ-specific behavior even while having similar histologic structure – thymic, pulmonary and GI carcinoids, which are currently called – neuroendocrine tumors (NETs). Even within the same organ, tumors with different degree of differentiation can behave strikingly different.
Over recent decades, the field of NETs had dissipated to narrow organ- and subspecialty-specific micro-cosmoses, which mainly communicate within themselves, “coming out to light” for field-specific meetings. These meetings, on the other hand, and especially the European Neuroendocrine Tumor Society (ENETS) had provided us with updated knowledge and numerous guidelines and spearheaded development of the Neuroendocrine Tumor Centers of Excellence, that introduces an innovate comprehensive multispecialty approach, that involves representatives from multiple subspecialties that combine their effort into advanced management protocols. While these centers rapidly proliferate in Europe and around the rest of the world, US still remains somewhat resistant to this approach for several reasons, one of which is historically rigid intra-specialty approach with relatively narrow inter-specialty collaborative management. This is in striking difference to overall patients’ management in current oncology, which is widely accepted advanced multispecialty management for quite extended time. More discussion about the future of the field, collaborative intersociety relationships and application of already available positive experience is needed for providers that care for patients with NETs.
In this proposal, I suggest reviewing several issues related to current State of the Art in the NET field:
1. History of neuroendocrine neoplasia-related medical field
2. Advanced embryology, anatomy and physiology of NETs
3. Similarities in enzymatic machinery of different NETs
4. New advances in NET genetics and mutation-related
5. Advances in current diagnostic and therapeutic approaches
These can be divided by:
1. System-specific NETs – GI, pulmonary, GU etc.
2. Tumors of different biological profiles – pituitary, adrenal, systemic, etc
3. Gene-driven syndromes – MEN1, MEN2, SDHX, etc.