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Patients with core-binding factor (CBF) acute myeloid leukemia (AML), caused by either t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22), have higher complete remission rates and longer survival than patients with other subtypes of AML. However, ∼40% of patients relapse, and the literature suggests that patients with inv(16) fare differently from those with t(8;21). We retrospectively analyzed 537 patients with CBF-AML, focusing on additional cytogenetic aberrations to examine their impact on clinical outcomes. Trisomies of chromosomes 8, 21, or 22 were significantly more common in patients with inv(16)/t(16;16): 16% vs 7%, 6% vs 0%, and 17% vs 0%, respectively. In contrast, del(9q) and loss of a sex chromosome were more frequent in patients with t(8;21): 15% vs 0.4% for del(9q), 37% vs 0% for loss of X in females, and 44% vs 5% for loss of Y in males. Hyperdiploidy was more frequent in patients with inv(16) (25% vs 9%, whereas hypodiploidy was more frequent in patients with t(8;21) (37% vs 3%. In multivariable analyses (adjusted for age, white blood counts at diagnosis, and KIT mutation status), trisomy 8 was associated with improved overall survival (OS) in inv(16), whereas the presence of other chromosomal abnormalities (not trisomy 8) was associated with decreased OS. In patients with t(8;21), hypodiploidy was associated with improved disease-free survival; hyperdiploidy and del(9q) were associated with improved OS. KIT mutation (either positive or not tested, compared with negative) conferred poor prognoses in univariate analysis only in patients with t(8;21).

Background: The presence of measurable residual disease after therapy is a significant risk factor of relapse in patients with acute myeloid leukemia (AML). By detecting cells with leukemia-associated immunophenotype (LAIP), multiparameter flow cytometry (MFC) can detect residual leukemia at a level significantly lower than that detected by morphology. However, changes in LAIPs during or after therapy may pose a challenge to MRD testing. AML with mutated NPM1 represents the largest subtype of AML sharing a common leukemogenic mechanism and similar LAIPs. Here, we identified a common pattern of LAIPs in myeloid blasts with mutated NPM1, and studied its stability and limit of detection after therapy.Methods: We summarized aberrancies of leukemic blasts with mutated NPM1 at diagnosis in 61 patients and paired relapse in 25 patients. In addition, we examined the detection of leukemic blasts in 590 specimens collected from 152 patients in complete remission after induction for AML/MDS-EB with mutated NPM1.Results: Our findings demonstrate myeloid blasts with mutated NPM1 have a characteristic pattern of LAIPs that is present in nearly all cases of AML/MDS-EB with mutated NPM1 at initial diagnosis and relapse, regardless of morphologic variations, FLT3 ITD status, or karyotype abnormality. The myeloid blasts with mutated NPM1 can be detected at an approximate level of 0.1% of total leukocytes in morphologic remission with high specificity validated by clinical outcome.Conclusion: The characteristic pattern of LAIPs of myeloid blasts with mutated NPM1 is common and stable, and allows sensitive and specific detection of AML or MDS with mutated NPM1 after therapy.

Indolent T lymphoblastic proliferations have been reported rarely in extramedullary and extrathymic tissues. Recent work has identified these indolent T lymphoblast populations to be mostly CD4+/CD8+ (characterized by immunohistochemistry), with only limited immunophenotypic evaluation of these populations by flow cytometry (FC). We retrospectively reviewed our institutional FC archives and identified 12 samples from 10 patients with incidental T lymphoblastic populations. Samples

Immature B cells, occasionally including a small subset with an abnormal phenotype can be observed in chronic phase CML at diagnosis. We believe an approach incorporating clinical data, cytogenetic/molecular findings, and morphologic evaluation may be helpful when determining the best management of CML patients at diagnosis if small ABLB populations are identified by FC. © 2016 Clinical Cytometry Society.

BackgroundAlthough the prognosis of core‐binding factor (CBF) acute myeloid leukemia (AML) is better than other subtypes of AML, 30% of patients still relapse and may require allogeneic hematopoietic cell transplantation (alloHCT). However, there is no validated widely accepted scoring system to predict patient subsets with higher risk of relapse.MethodsEleven centers in the US and Europe evaluated 247 patients with t(8;21)(q22;q22).ResultsComplete remission (CR) rate was high (92.7%), yet relapse occurred in 27.1% of patients. A total of 24.7% of patients received alloHCT. The median disease‐free (DFS) and overall (OS) survival were 20.8 and 31.2 months, respectively. Age, KIT D816V mutated (11.3%) or nontested (36.4%) compared with KIT D816V wild type (52.5%), high white blood cell counts (WBC), and pseudodiploidy compared with hyper‐ or hypodiploidy were included in a scoring system (named I‐CBFit). DFS rate at 2 years was 76% for patients with a low‐risk I‐CBFit score compared with 36% for those with a high‐risk I‐CBFit score (P < 0.0001). Low‐ vs high‐risk OS at 2 years was 89% vs 51% (P < 0.0001).ConclusionsI‐CBFit composed of readily available risk factors can be useful to tailor the therapy of patients, especially for whom alloHCT is not need in CR1 (ie, patients with a low‐risk I‐CBFit score).

The diagnosis of both local recurrences and distant metastases of mesothelioma can be accomplished by fine-needle aspiration (FNA) biopsy. Although the previous history of mesothelioma provides strong support for recurrent/metastatic mesothelioma, other diagnostic possibilities (particularly adenocarcinoma) may require exclusion via special stains in some cases. In this study, we report on the morphologic findings in 13 cases of mesothelioma which underwent FNA (7 metastatic lesions, 6 local recurrences). In addition, immunohistochemical staining results for 7 cases with available material using antibodies directed against cytokeratin AE 1/3 and two antibodies reported to show consistently positive results in mesothelioma (calretinin and cytokeratin 5/6) are reported and compared to results seen for 10 cases of adenocarcinoma. All cases of mesothelioma and adenocarcinoma showed strong staining with cytokeratin AE 1/3. Three of 7 cases of mesothelioma showed strong staining with calretinin, while only focal staining was detected in 3 additional cases; only one case showed positive staining with cytokeratin 5/6. One of 10 cases of adenocarcinoma showed calretinin positivity; however, at least focal staining with cytokeratin 5/6 was seen in 4 cases. These results suggest that cytokeratin 5/6 is neither a sensitive nor specific stain for the diagnosis of mesothelioma in cytology material. Calretinin appears to be more specific for mesothelioma but showed disappointing sensitivity for this tumor, potentially limiting its diagnostic utility in FNA material.