Objectives
SF3B1 mutations are the most common mutations in myelodysplastic syndromes (MDS). The International Working Group for the Prognosis of MDS (IWG-PM) recently proposed SF3B1-mutant MDS (SF3B1-mut-MDS) as a distinct disease subtype. We evaluated the spectrum and molecular landscape of SF3B1-mutated myeloid disorders and assessed the prognostication in MDS harboring SF3B1 mutations (MDS-SF3B1).
Methods
Cases were selected by retrospective review. Clinical course and laboratory and clinical findings were collected by chart review. SF3B1-mut-MDS was classified following IWG-PM criteria.
Results
SF3B1 mutations were identified in 75 of 955 patients, encompassing a full spectrum of myeloid disorders. In MDS-SF3B1, Revised International Prognostic Scoring System (IPSS-R) score greater than 3 and transcription factor (TF) comutations were adverse prognostic markers by both univariate and multivariate analyses. We confirmed the favorable outcome of IWG-PM-defined SF3B1-mut-MDS. Interestingly, it did not show sharp prognostic differentiation within MDS-SF3B1.
Conclusions
SF3B1 mutations occur in the full spectrum of myeloid disorders. We independently validated the favorable prognostication of IWG-PM-defined SF3B1-mut-MDS. However it may not provide sharp prognostication within MDS-SF3B1 where IPSS-R and TF comutations were prognostic-informative. Larger cohort studies are warranted to verify these findings and refine MDS-SF3B1 prognostication.
Myeloid/lymphoid neoplasms with FLT3 gene fusions have recently been included among myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) in the World Health Organization classification and International Consensus Classification. As this entity remains remarkably rare, its scope and phenotypic features are evolving. In this report, we describe a 33-year-old male with MLN-TK. Conventional chromosome analysis revealed a t(13;14)(q12;q32). Further analysis with mate-pair sequencing (MPseq) confirmed a TRIP11::FLT3 gene fusion. A diagnosis of MLN-TK was rendered. To the best of our knowledge, we report the third case of MLN-TK with a TRIP11::FLT3 gene fusion. In contrast to previously described cases, our case exhibited distinctly mild clinical features and disease behavior, emphasizing the diverse spectrum of MLN-TK at primary presentation and variability in disease course. MLN-TK with FLT3 gene fusions are a genetically defined entity which may be targetable with tyrosine kinase inhibitors with anti-FLT3 activity. Accordingly, from diagnostic and therapeutic viewpoints, genetic testing for FLT3 rearrangements using FISH or sequencing-based assays should be pursued for patients with chronic eosinophilia.
Background
Pathologists frequently encounter neuroendocrine tumors (NETs) presenting as multiple liver masses in routine practice. Most often, these are well-differentiated tumors with characteristic histologic features. In contrast, pituitary carcinoma is very rare, and there is limited data on its natural history and pathologic characterization.
Methods
The aim of this study was to describe clinical characteristics, histomorphology, immunophenotype and follow-up of pituitary carcinoma involving the liver and mimicking well-differentiated NETs of visceral origin. We selected a group of well-differentiated NETs of the pancreas to use as immunophenotypic controls. We identified 4 patients (age range, 51 to 73) with pituitary corticotroph carcinoma with liver metastases. Three patients presented with Cushing syndrome.
Results
All cases histologically resembled well-differentiated NETs of visceral origin with Ki-67 proliferation indices of 5–42% and expression of T-PIT; metastatic tumors were not immunoreactive with CDX2, Islet 1 or TTF-1.
Conclusions
Frequently, these cases display adrenocorticotropic hormone (ACTH) secretion and pituitary-specific transcription factor immunohistochemistry may be used as a reliable marker to distinguish metastatic pituitary carcinoma from NETs of visceral origin in addition to delineating a corticotroph carcinoma from somatotroph, lactotroph, thyrotroph, and gonadotroph lineage. Although rare, the differential diagnosis of pituitary carcinoma should be considered in metastatic well-differentiated NETs in which the site of origin is uncertain. In summary, pituitary corticotroph carcinoma can metastasize to the liver and mimic well-differentiated NET.
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