Neuroendocrine Tumor Heterogeneity Adds Uncertainty to the World Health Organization 2010 Classification: Real-World Data from the Spanish Tumor Registry (R-GETNE).

BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a complex family of tumors of widely variable clinical behavior. The World Health Organization (WHO) 2010 classification provided a valuable tool to stratify neuroendocrine neoplasms (NENs) in three prognostic subgroups based on the proliferation index. However, substantial heterogeneity remains within these subgroups, and simplicity sometimes entails an ambiguous and imprecise prognostic stratification. The purpose of our study was to evaluate the prognostic impact of histological differentiation within the WHO 2010 grade (G) 1/G2/G3 categories, and explore additional Ki-67 cutoff values in GEP-NENs. SUBJECTS, MATERIALS, AND METHODS: A total of 2,813 patients from the Spanish National Tumor Registry (RGETNE) were analyzed. Cases were classified by histological differentiation as NETs (neuroendocrine tumors [well differentiated]) or NECs (neuroendocrine carcinomas [poorly differentiated]), and by Ki-67 index as G1 (Ki-67 <2%), G2 (Ki-67 3%-20%), or G3 (Ki-67 >20%). Patients were stratified into five cohorts: NET-G1, NET-G2, NET-G3, NEC-G2, and NEC-G3. RESULTS: Five-year survival was 72%. Age, gender, tumor site, grade, differentiation, and stage were all independent prognostic factors for survival. Further subdivision of the WHO 2010 grading improved prognostic stratification, both within G2 (5-year survival: 81% [Ki-67 3%-5%], 72% [Ki-67 6%-10%], 52% [Ki-67 11%-20%]) and G3 NENs (5-year survival: 35% [Ki-67 21%-50%], 22% [Ki-67 51%-100%]). Five-year survival was significantly greater for NET-G2 versus NEC-G2 (75.5% vs. 58.2%) and NET-G3 versus NEC-G3 (43.7% vs. 25.4%). CONCLUSION: Substantial clinical heterogeneity is observed within G2 and G3 GEP-NENs. The WHO 2010 classification can be improved by including the additive effect of histological differentiation and the proliferation index. IMPLICATIONS FOR PRACTICE: Gastroenteropancreatic neuroendocrine neoplasms are tumors of widely variable clinical behavior, roughly stratified by the World Health Organization (WHO) 2010 classification into three subgroups based on proliferation index. Real-world data from 2,813 patients of the Spanish Registry RGETNE demonstrated substantial clinical heterogeneity within grade (G) 2 and G3 neuroendocrine neoplasms. Tumor morphology and further subdivision of grading substantially improves prognostic stratification of these patients and may help individualize therapy. This combined, additive effect shall be considered in future classifications of neuroendocrine tumors and incorporated for stratification purposes in clinical trials.

Evaluation of a Method for Long-Term Cryopreservation of Fungal Strains.

The conservation of microorganisms is essential for their in-depth study. However, today's most widely used conservation methods, based on the use of distilled water, soil, oils, or silica, do not guarantee the stability of fungal cells, especially dermatophytes. This problem led us to evaluate the conservation capacity of a cryogenic vials system containing glass beads covered in a cryopreservant hypertonic solution as an alternative method of storage of fungal cells at -80°C. Up to 570 strains of fungi belonging to 27 different species, isolated from clinical samples, were inoculated into cryotubes containing 25 glass beads covered in a cryopreserving hypertonic solution. Suspensions were mixed vigorously and the cryopreserving solution was discarded. The tubes were frozen at -80°C for a period of 42 months and periodically, a glass bead was removed from each cryotube and inoculated onto Sabouraud dextrose agar, and incubated at 30°C for 7-14 days to evaluate the number of colonies recovered, their purity, and phenotypic characteristics. All yeast isolates were recovered, unlike 2 isolates (4.4%) of the mold group and 21 (10.7%) of the dermatophytes. Survival rates were close to 100% for yeasts and molds, with expiration times being estimated for almost indefinite stocks, and 62% for dermatophytes, with an average expiration date of 25.5 years. The phenotypic characteristics remained comparable to those of the strains before storage. Conservation at -80°C using cryogenic vials is a reliable and efficient system for the conservation of fungal collections, and although the behavior differs by groups, stratified survival data are obtained to avoid extinction.

Gastrointestinal stromal tumors: diagnosis and treatment.

BACKGROUND: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the digestive tract. They originate from the interstitial cells of Cajal and are characterized by the overexpression of KIT protein (tyrosine kinase). Their prognosis has improved significantly with the discovery of imatinib mesylate for advanced GIST treatment. METHODS: We carried out a retrospective, descriptive study of GISTs diagnosed in our center during the past 5 years. We excluded patients with incidental diagnoses in the context of other pathologies because GIST did not affect outcome or prognosis. The variables studied were clinical characteristics, location, size, imaging techniques, resectability, neoadjuvant imatinib, surgical technique, histology, immunohistochemistry, prognostic classification of Fletcher, morbidity, monitoring, and disease-free and overall survival. RESULTS: Nineteen patients were diagnosed (14 males/5 females) with a mean age of 63 years (range: 30-84 years). Diagnosis was incidental in eight patients (42%). Tumor location of the remaining 11 patients (58%) was six tumors of the small intestine (55%), four gastric (36%) and one rectal (9%). Predominant gastrointestinal bleeding and anemia were diagnosed mainly by abdominal computed tomography (CT). At diagnosis, nine patients were considered resectable with radical intent (82%) and the other two patients (18%) received neoadjuvant treatment with a favorable response after 6 months. Three patients were treated with imatinib after surgery (33%). Median survival was 34 months (range: 5-58 months). CONCLUSIONS: Diagnosis of GIST is often incidental. The predominant clinical symptom is usually gastrointestinal bleeding and anemia and the most widely used imaging test is CT. Treatment is surgical unless advanced GIST is diagnosed, which will be treated with imatinib mesylate neoadjuvant therapy. A multidisciplinary approach to this pathology is essential, a fact that affects prognosis and patient survival.