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The classification of myeloid neoplasms and acute leukemias was last updated in 2016 within a collaboration between the World Health Organization (WHO), the Society for Hematopathology, and the European Association for Haematopathology. This collaboration was primarily based on input from a clinical advisory committees (CAC) composed of pathologists, hematologists, oncologists, geneticists, and bioinformaticians from around the world. The recent advances in our understanding of the biology of hematologic malignancies, the experience with the use of the 2016 WHO classification in clinical practice, and the results of clinical trials have indicated the need for further revising and updating the classification. As a continuation of this CAC-based process, the authors, a group with expertise in the clinical, pathologic and genetic aspects of these disorders, developed the International Consensus Classification (ICC) of myeloid neoplasms and acute leukemias. Using a multiparameter approach, the main objective of the consensus process was the definition of real disease entities, including the introduction of new entities and refined criteria for existing diagnostic categories, based on accumulated data. The ICC is aimed at facilitating diagnosis and prognostication of these neoplasms, improving treatment of affected patients, and allowing the design of innovative clinical trials.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with recognized variability in clinical outcome, genetic features, and cells of origin. To date, transcriptional profiling has been used to highlight similarities between DLBCL tumor cells and normal B-cell subtypes and associate genes and pathways with unfavorable outcome. To identify robust and highly reproducible DL-BCL subtypes with comprehensive transcriptional signatures, we used a large series of newly diagnosed DLBCLs, whole genome arrays, and multiple clustering methods. Tumors were also analyzed for known common genetic abnormalities in DLBCL. There were 3 discrete subsets of DLBCL-"oxidative phosphorylation," "Bcell receptor/proliferation," and "host response" (HR)-identified characterized using gene set enrichment analysis and confirmed in an independent series. HR tumors had increased expression of T/natural killer cell receptor and activation pathway components, complement cascade members, macrophage/dendritic cell markers, and inflammatory mediators. HR DLBCLs also contained significantly higher numbers of morphologically distinct CD2 ؉ /CD3 ؉ tumor-infiltrating lymphocytes and interdigitating S100 ؉ /gamma interferon-induced ly-

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SUMMARYInflammatory myofibroblastic tumor (IMT) is a distinctive mesenchymal neoplasm characterized by a spindle-cell proliferation with an inflammatory infiltrate. Approximately half of IMTs carry rearrangements of the anaplastic lymphoma kinase (ALK) locus on chromosome 2p23, causing aberrant ALK expression. We report a sustained partial response to the ALK inhibitor crizotinib (PF-02341066, Pfizer) in a patient with ALK-translocated IMT, as compared with no observed activity in another patient without the ALK translocation. These results support the dependence of ALK-rearranged tumors on ALK-mediated signaling and suggest a therapeutic strategy for genomically identified patients with the aggressive form of this soft-tissue tumor.Inflammatory myofibroblastic tumors (IMTS) occur primarily during the first two decades of life and typically arise in the lung, retroperitoneum, or abdominopelvic region. 1,2 Abdominal tumors may be multifocal. Lesional cells are predominantly myofibroblasts in a myxoid to collagenous stroma admixed with inflammatory cells. 2,3 Local recurrence may occur after initial surgery, with a low risk of distant metastases, 1,2 so that IMTs are considered to be soft-tissue tumors of intermediate biologic potential, with a small fraction behaving aggressively. 4 Rearrangements involving the ALK locus on chromosome 2p23 have been documented in approximately 50% of IMTs. 5,6 ALK aneuploidy has also been described, with a gain in copy number without rearrangement. 5 Among cancers with rearrangements, several fusion partners have been identified that serve to constitutively activate ALK. 7-10 ALK expression reliably correlates with ALK rearrangement. 11 Distant metastases occur primarily in ALKnegative IMTs, but local recurrence occurs regardless of ALK expression. 5 Several ALK fusion proteins, including TPM3-ALK found in IMT, induce transformation in cell lines and animal models, 13 a finding that suggests that ALK rearrangement may define a subgroup of IMTs that is sensitive to targeted kinase inhibition. We therefore enrolled two patients with IMT in a dose-escalation phase 1 trial of crizotinib, an orally bioavailable ATP-competitive inhibitor of the ALK and MET tyrosine kinases. 14,15 CASE REPORTSPatient 1 was a 44-year-old man who had been well until May 2007, when he reported having early satiety and abdominal pain. Computed tomography (CT) of the abdomen and pelvis revealed ascites, a mass in the right upper quadrant, and omental caking. The results of esophagogastroduodenoscopy and colonoscopy were unremarkable. The patient then underwent paracentesis. Combined 18 F-fluorodeoxyglucose positron-emission tomography and CT (FDG-PET-CT) revealed hypermetabolic masses in the abdomen and pelvis. In June 2007, he underwent exploratory laparotomy, which showed massive omental caking with discrete, round, gelatinous, grape-size tumor nodules and extensive peritoneal disease. Maximal tumor debulking was performed along with catheter placement to facilitate administration of a hyperthermic periton...