Have we reached a molecular era in myelodysplastic syndromes?

Myelodysplastic syndromes (MDS) are characterized by heterogeneous biological and clinical characteristics, leading to variable outcomes. The availability of sophisticated platforms of genome sequencing allowed the discovery of recurrently mutated genes, which have led to a new era in MDS. This is reflected by the 2016 update of the World Health Organization classification, in which the criteria to define MDS with ringed sideroblasts include the presence of SF3B1 mutations. Further, the detection of somatic mutations in myeloid genes at high variant allele frequency guides the diagnostic algorithm in cases with cytopenias, unclear dysplastic changes, and normal karyotypes, supporting MDS over alternative diagnoses. SF3B1 mutations have been shown to play a positive prognostic role, while mutations in ASXL1, EZH2, RUNX1, and TP53 have been associated with a dismal prognosis. This is particularly relevant in lower- and intermediate-risk disease, in which a higher number of mutations and/or the presence of “unfavorable” somatic mutations may support the use of disease-modifying treatments. In the near future, the incorporation of mutation profiles in currently used prognostication systems, also taking into consideration the classical patient clinical variables (including age and comorbidities), will support a more precise disease stratification, eg, the assignment to targeted treatment approaches or to allogeneic stem cell transplantation in younger patients.

5-azacytidine for the treatment of massive hepatosplenomegaly in a case of myelodysplastic/myeloproliferative neoplasm-unclassifiable

Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) represent a distinct category of myeloid diseases in the World Health Organization classification, defined at diagnosis by clinical, morphologic and laboratory features which overlap both those of MDS and MPN. Within the “Overlap” MDS/MPN syndromes, MDS/MPN-Unclassifiable (MDS/MPN-U) is the least well characterized. MDS/MPN-U is a rare diagnosis, making up less than 5% of all myeloid disorders with no standard prognostic or treatment algorithms. 5-azacytidine is a standard treatment for MDS, but controversial results are available about its role for MDS/MPN-U and its effectiveness on extramedullary disease and hepatosplenomegaly. We reported the clinical management of a MDS/MPN-U patient characterized by massive hepatosplenomegaly with optimal response to 5-azacytidine.

Goblet cell adenocarcinoma of the appendix: An incidental finding of a rare tumor which was recently renamed in 2019 World Health Organization classification update

Introduction/Objective Goblet cell adenocarcinoma (formerly goblet cell carcinoid) is a rare tumor almost exclusively involving the appendix. It is an amphicrine tumor consisting of both epithelial and neuroendocrine elements containing goblet cells. In the 2019 WHO classification update, GCC was reclassified as goblet cell adenocarcinoma of the appendix as it is recognized to have predominantly mucin secreting cells and a minor neuroendocrine component. Methods/Case Report A 72 year old,morbidly obese male presented with a 2 week history of abdominal pain and bilious vomiting. Imaging revealed a peri-appendiceal abscess. Due to the chronicity of his symptoms, he was treated conservatively with drainage of the abscess and intravenous antibiotics. He responded well and underwent elective laparoscopic appendectomy; at which time, the appendix appeared grossly unremarkable, measuring 5.1 x 0.9 x 0.3 cm with a wall thickness of 0.5 cm. Microscopically small nests and clusters of goblet cells circumferentially invaded dense collagenous stroma in the appendiceal wall. The neoplastic cells had large mucin vacuoles and small basally located nuclei. The cells were positive for CK20, CDX2, CD56, synaptophysin and focally positive for chromogranin. Ki-67 was 10%. CK7 was negative. These tumors are now graded and staged similar to colonic adenocarcinomas according to the 5 th edition of the World Health Organization Classification of Tumors - Digestive System Tumors. Results (if a Case Study enter NA) NA Conclusion This case demonstrates that this rare tumor may be an incidental finding in an elderly patient presenting with appendicitis; accurate diagnosis of this rare tumor may require submission of the entire appendix for microscopic evaluation.