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Panel based next generation sequencing was performed on a discovery cohort of AML with RUNX1-RUNX1T1. Supervised machine learning identified NRAS mutation and absence of mutations in ASXL2, RAD21, ...

Anaplastic large cell lymphoma (ALCL) is a rare form of non-Hodgkin lymphoma (NHL) in children. Most treatment regimens include high-dose methotrexate (HDMTX), which is logistically difficult to administer in resource-limited settings. We evaluated the outcomes of pediatric ALCL patients treated on a uniform protocol (Modified Multicentric Protocol, MCP-842 regimen) at our hospital between January 2005 and December 2016. Of the 68 patients who received treatment on the Modified MCP842 protocol, 46 patients are alive in remission, 11(16%) had disease progression, 9(13%) relapsed after achieving remission, and 5(7%) had treatment-related mortality (TRM). Seventeen of 20 relapsed/progressed patients subsequently expired. With a median follow-up of 55 months (range 2-165 months), the 4-year event-free survival (EFS) and overall survival (OS) are 63% (95% CI of 50-73%) and 70%(95% CI of 57-79%), respectively. An indigenous protocol using vinblastine (without HDMTX and steroids) is feasible in a resource-limited setting and achieves outcomes comparable to regimens incorporating HDMTX, with lower toxicity.

Plasmablastic lymphoma (PBL) can rarely be seen as a transformation from plasma cell myeloma (PCM), especially in late stages of the disease where it portends a poorer prognosis and a different line of management for the patient. When unrelated to PCM, PBL is considered to be a separate aggressive variant of B-cell lymphoma typically seen in the oral cavity of immunocompromised adults. We describe a case of plasmablastic transformation having a pan T-cell phenotype with CD3 and CD4 positivity, in an immunocompetent elderly lady diagnosed with PCM. This 60-year-old lady presented with worsening backache and a 2-cm skin nodule in the left cervical region, while she was on treatment with vincristine, cyclophosphamide, dexamethasone (VCD), and bortezomib. On biopsy, the skin nodule showed an infiltrating lymphoid tumor composed of immunoblastic cells with brisk mitosis and apoptosis. On Immunohistochemistry (IHC), lymphoid cells revealed plasma cell markers CD38, CD138, CD56, and MUM1. Pan-T-cell markers CD3 and CD4 were also diffusely expressed in tumor cells. B-cell markers CD20 and PAX5 were not expressed; c-Myc IHC and EBER by in situ hybridization (ISH) were negative in the tumor. Mitotic index by Ki67 was >95%. Thus, a diagnosis of plasmablastic transformation in a known PCM case was made. This is the first case, to the best of our knowledge, with a heterotropic T-cell phenotype in a plasmablastic transformation from PCM. It is critical to correctly diagnose such cases as they may occasionally be misinterpreted as T-cell neoplasms. Clinically, a more aggressive treatment is indicated for such patients. Further studies in these cases may enhance our understanding of complex underpinnings of lymphoma biology.

We document the characteristics of BCR-ABL kinase domain mutations (KDM) in the largest study from India comprising of 385 patients and demonstrate that more than half (51.9%) of these patients have detectable abnormalities in the KD both in adult and in pediatric chronic myelogenous leukemia (CML). These comprise singly occurring missense mutations (25.5%), polyclonal/compound point mutations (4.9%), and insertions/deletions (29.6%). Missense mutations were most commonly seen in the imatinib-binding region followed by the P-loop. The commonest mutation in our dataset was T315I. Other common missense mutations were Y253H, M244V, and F317L. A high prevalence of BCR-ABL exon7 deletion (p.R362fs*) was also seen (25.5% of the entire cohort), whereas the 35bpintron-derived insertion/truncation mutation detected in 12 patients. In the pediatric age group, 58.8% of patients harbored missense mutations, polyclonal/compound mutations as well as insertions and deletions. We detected 11 novel mutations (seven missense mutations and four insertions/deletions).

This single institutional study evaluated the prognostic factors and treatment outcome of 113 Indian patients with primary nasopharyngeal non-Hodgkin's lymphoma. At presentation, 28% had stage I and 62% had stage II disease. Treatment comprised of a combination of chemotherapy (CTh) and radiotherapy (RT) in the majority of the patients (76%). After a median follow-up of 56 months, the 5-year disease-free survival (DFS) and overall survival (OS) for the whole group were 55.8% and 57.9%, respectively. Multivariate analysis showed that; age30 years [hazard ratio (HR) = 6.59, 95% confidence interval (CI) = 2.59 - 16.7, P0.0001], WHO performance scoreor = 2 (HR = 2.34, 95% CI = 1.01 - 5.46, P = 0.050), T-cell lymphomas (HR = 2.81, 95% CI = 1.14 - 6.96, P0.001) and the presence of B symptoms (HR = 3.65, 95% CI = 1.77 - 7.53, P = 0.025), had a negative influence on survival. Patients treated with a combination of CTh and RT had a significantly better outcome than those treated with CTh alone (OS: 69%vs. 31%, P0.00001). HR for death in the CTh alone group was 3.73 (95% CI = 1.95 - 7.13). The CR (P = 0.01), DFS (P = 0.01) and OS (P = 0.03) rates were significantly better for patients receiving a RT dose ofor =4500 cGy. HR in the subgroup that received a RT dose of4500 cGy was 2.51 (95% CI = 1.04 - 6.06). These results suggest that combined modality treatment, comprising of CTh and RT (with an RT dose ofor =4500 cGy), results in satisfactory outcome in patients with this rare neoplasm.

Histopathologists face various types of artifacts in day-to-day practice, which often hinders the actual diagnosis. A case is presented in which a staff member left a lymph node biopsy in the freezer compartment overnight. Histopathology of this biopsy revealed large vacuolated cells. A long list of differential diagnoses was entertained, ranging from metastatic deposits of a carcinoma to an inflammatory lesion. However, it was determined that the vacuolation was caused by freezing artifacts. A rebiopsy was performed, which confirmed a diagnosis of Hodgkin's disease. Artifacts can cause difficulty in diagnosis and a pathologist should be aware of them. The supporting staff should be trained on preserving specimens that are received after working hours. (The J Histotechnol 31:29, 2008)Submitted March 19, 2007; accepted with revisions February 8, 2008