Comparison of therapy-related and de novo core binding factor acute myeloid leukemia: A bone marrow pathology group study.

This multi-institutional study retrospectively evaluated clinicopathologic and genetic characteristics in 351 patients with core-binding-factor acute myeloid leukemia (CBF-AML), comprising 69 therapy-related (t-CBF-AML) and 282 de novo cases. The T-CBF-AML patients were older, had lower WBC counts, and slightly higher hemoglobin than patients with de novo disease. Secondary cytogenetic abnormalities were more frequent in patients with de novo disease than t-CBF-AML (57.1% vs 41.1%, P = .026). Patients with secondary cytogenetic abnormalities had longer overall survival (OS) than those without abnormalities (median 190 vs 87 months, P = .021); trisomy 8, trisomy 22, and loss of the X or Y chromosome were associated with longer OS. In the 165 cases performed of targeted gene sequencing, pathogenic mutations were detected in 75.7% of cases, and were more frequent in de novo than in therapy-related disease (P = .013). Mutations were found in N/KRAS (37.0%), FLT3 (27.8%), KIT (17.2%), TET2 (4.9%), and ASXL1 (3.9%). The TET2 mutations were associated with shorter OS (P = .012) while N/KRAS mutation was associated with longer OS in t(8;21) AML patients (P = .001). The KIT mutation did not show prognostic significance in this cohort. Although they received similar therapy, t-CBF-AML patients had shorter OS than de novo patients (median 69 vs 190 months, P = .038). In multivariate analysis of all patients, older age and absence of any secondary cytogenetic abnormalities were significant predictors of shorter OS. Among the t-CBF-AML subset, age and hemoglobin were significant on multivariate analysis. This study demonstrated that although de novo and t-CBF-AML patients share many features, t-CBF-AML patients have worse clinical outcome than de novo patients.

Cytological diagnosis of papillary thyroid carcinoma with tall cells on ThinPrep liquid-based cytology.

BACKGROUND: The tall cell variant of papillary thyroid carcinoma (PTC-TC) has been associated with aggressive features including extrathyroidal extension, higher rate of lymph node and distant metastases, and higher recurrence rate. We aimed to evaluate the cytomorphologic features of PTC-TC on ThinPrep (TP) along with its diagnostic efficacy to detect PTC-TC. METHODS: Preoperative cytology samples from 30 cases of histologically-proven PTC-TC and 30 classical PTC controls were selected for this study. TP preparations were evaluated for varying architectural and cytomorphologic features. RESULTS: Tall cells were present in the majority of PTC-TC cases and were located at the periphery of cell clusters and as single cells. Cytoplasmic cuff along the periphery of cell clusters and soap-bubble pseudoinclusions were very specific features of PTC-TC, when present. PTC-TC cases were more likely to show abundant oncocytic cytoplasm and distinct cell borders. Cytoplasmic tails were more likely to be present and more numerous in PTC-TC. The presence of nuclear grooves, papillary architecture, and giant cells were not reliable distinguishing features of PTC-TC vs controls. CONCLUSION: Our results indicate that tall cell cytomorphologic and architectural features in PTC are identifiable on TP.

The role of BRCA1-associated protein 1 in the diagnosis of malignant mesothelioma in effusion and fine-needle aspiration cytology.

BACKGROUND: Malignant mesothelioma (MM) is a diagnostically challenging entity in cytology specimens due to the lack of architectural context and a cytomorphologic overlap between malignant and reactive mesothelial cells (RMCs). A diagnostic marker with excellent specificity is not currently available in clinical practice. The newly appreciated BRCA1-associated protein 1 (BAP1) antibody may help distinguish MM from RMC based on its immunohistochemical (IHC) staining pattern but its role in cytopathology is controversial. METHODS: Immunohistochemistry with BAP1 antibody was performed on cell blocks from 39 cytology specimens including 13 cases of RMC and 26 cases of effusion and fine-needle aspiration specimens (FNAC) with tissue-specimen-proven MM. Cases were dichotomised into positive and negative cohorts. Positivity was defined as >50% loss of nuclear BAP1 IHC staining. RESULTS: Of the 26 MM cases, a slight majority (14/26, 54%) showed loss of BAP1 nuclear IHC staining, while all 13 RMC controls showed strong nuclear BAP1 IHC staining. MM was more likely to show loss of BAP1 than RMC (P < .001); and peritoneal MM was more likely to demonstrate loss of BAP1 than pleural MM (P = .04). There was perfect specificity at 1.0 and positive predictive value of 1.0 for loss of nuclear BAP1 IHC staining. However, only modest sensitivity at 0.52 and negative predictive value of 0.50 was seen. CONCLUSION: These data confirm that absence of BAP1 nuclear staining identifies malignant mesothelial cells. On the other hand, positive BAP1 nuclear staining can occur in both benign and malignant pleural effusions.

Hematopoietic neoplasms with 9p24/JAK2 rearrangement: a multicenter study.

The purpose of this study is to examine hematopoietic neoplasms with 9p24/JAK2 rearrangement including neoplasms associated with t(8;9)(p22;p24)/PCM1-JAK2 fusion neoplasm as well as cases with translocations involving 9p24/JAK2 and other partner genes. From seven large medical centers, we identified ten patients with t(8;9)(p22;p24) /PCM1-JAK2 and 3 with t(9p24;v)/JAK2 at diagnosis. Majority of the cases showed myeloproliferative neoplasm (MPN) associated features (n = 7) characterized by variable degrees of eosinophilia, myelofibrosis, frequent proliferations of early erythroblasts in bone marrow and extramedullary sites, and infrequent/absent somatic mutations. Other less common presentations included myelodysplastic syndromes (MDS) or MDS/MPN (one each). Four patients presented with B-lymphoblastic leukemia (B-ALL), and of them, two patients with t(8;9)(p22;p24.1) were proven to be B-lymphoblastic crisis of MPN; and the other two cases with t(9p24;v) both were de novo B-ALL, BCR-ABL1-like (Ph-like). We show that the hematopoietic neoplasms with 9p24/JAK2 rearrangement are extremely rare, and most of them are associated with t(8;9)(p22;p24)/PCM1-JAK2, a recent provisional World Health Organization entity under "myeloid/lymphoid neoplasm with a specific gene rearrangement". Cases of t(8;9)(p22;p24)/PCM1-JAK2, though heterogeneous, do exhibit some common clinicopathological characteristic features. Cases with t(9p24;v)/JAK2 are extremely rare; while such cases with a MPN presentation may resemble t(8;9)(p22;p24.1)/PCM1-JAK2, B-ALL cases presenting de novo B-ALL might belong to Ph-like B-ALL.

Cytomorphologic features distinguishing Bethesda category IV thyroid lesions from parathyroid.

BACKGROUND: Thyroid follicular cells share similar cytomorphological features with parathyroid. Without a clinical suspicion, the distinction between a thyroid neoplasm and an intrathyroidal parathyroid can be challenging. The aim of this study was to assess the distinguishing cytomorphological features of parathyroid (including intrathyroidal) and Bethesda category IV (Beth-IV) thyroid follicular lesions, which carry a 15%-30% risk of malignancy and are often followed up with surgical resection. METHODS: A search was performed to identify "parathyroid" diagnoses in parathyroid/thyroid-designated fine-needle aspirations (FNAs) and Beth-IV thyroid FNAs (follicular and Hurthle cell), all with diagnostic confirmation through surgical pathology, immunocytochemical stains, Afirma® analysis, and/or clinical correlation. Unique cytomorphologic features were scored (0-3) or noted as present versus absent. Statistical analysis was performed using R 3.3.1 software. RESULTS: We identified five FNA cases with clinical suspicion of parathyroid neoplasm, hyperthyroidism, or thyroid lesion that had an eventual final diagnosis of the parathyroid lesion (all female; age 20-69 years) and 12 Beth-IV diagnoses (11 female, 1 male; age 13-64 years). The following cytomorphologic features are useful distinguishing features (P value): overall pattern (0.001), single cells (0.001), cell size compared to red blood cell (0.01), nuclear irregularity (0.001), presence of nucleoli (0.001), nuclear-to-cytoplasmic ratio (0.007), and nuclear chromatin quality (0.028). CONCLUSIONS: There are cytomorphologic features that distinguish Beth-IV thyroid lesions and (intrathyroidal) parathyroid. These features can aid in rendering correct diagnoses and appropriate management.