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Dermatopathic lymphadenopathy is a distinctive form of paracortical lymph node hyperplasia that usually occurs in the setting of chronic dermatologic disorders. The aim of this study is to update our understanding of the clinicopathologic and immunophenotypic features of dermatopathic lymphadenopathy. The study cohort was 50 lymph node samples from 42 patients diagnosed with dermatopathic lymphadenopathy. The patients included 29 women and 13 men with a median age of 49 years (range, 12–79). Twenty-two (52%) patients had a dermatologic disorder, including mycosis fungoides ( n  = 6), chronic inflammatory dermatoses ( n  = 13), melanoma ( n  = 1), squamous cell carcinoma ( n  = 1), and Kaposi sarcoma in the context of human immunodeficiency virus infection ( n  = 1). Twenty (48%) patients did not have dermatologic manifestations. Lymph node biopsy specimens were axillary ( n  = 22), inguinal ( n  = 21), cervical ( n  = 4), and intramammary ( n  = 3). All lymph nodes showed paracortical areas expanded by lymphocytes; dendritic cells, including interdigitating dendritic cells and Langerhans cells; and macrophages. Melanophages were detected in 48 (98%) lymph nodes. Immunohistochemical analysis provided results that are somewhat different from those previously reported in the literature. In the paracortical areas of lymph node, S100 protein was expressed in virtually all dendritic cells, and CD1a was expressed in a significantly greater percentage of cells than langerin (80 vs. 35%, p  < 0.0001). These results suggest that the paracortical regions of dermatopathic lymphadenopathy harbor at least three immunophenotypic subsets of dendritic cells: Langerhans cells (S100 + , CD1a +(high) , langerin + ), interdigitating dendritic cells (S100 + , CD1a +(low) , langerin − ), and a third (S100 + , CD1a − , langerin − ) minor population of dendritic cells. Furthermore, in more than 60% of dermatopathic lymph nodes, langerin highlighted trabecular and medullary sinuses and cords, showing a linear and reticular staining pattern, which could be a pitfall in the differential diagnosis with Langerhans cell histiocytosis involving lymph nodes.

Sporadic reports of t(3;12)(q26.2;p13) indicate that this abnormality is associated with myeloid neoplasms, myelodysplasia, and a poor prognosis. To better characterize neoplasms with this abnormality, we assessed 20 patients utilizing clinicopathological data, cytogenetic, and targeted next-generation sequencing analysis. We also performed literature review of 58 prior reported cases. Patients included ten men and ten women with median age 55.8 years (range, 27.8–78.8). Diagnoses included 11 acute myeloid leukemia (AML, 5 de novo and 6 secondary), 5 myelodysplastic syndromes (MDS, 3 de novo excess blasts-2 and 2 therapy-related), 2 chronic myeloid leukemia BCR-ABL1-positive blast phase (1 de novo and 1 secondary), 1 primary myelofibrosis (secondary), and 1 mixed-phenotype acute leukemia T/myeloid (MPAL, secondary). Morphologic dysplasia was identified in all AML cases (5/5), MDS cases (4/4), therapy-related cases (3/3), half of myeloproliferative neoplasm cases (1/2), and one MPAL case assessed. The t(3;12) was detected de novo and in subsequent workups in 9 and 11 patients, respectively. Seven patients had t(3;12) only and eight patients had additional chromosome 7 abnormalities. Fluorescence in-situ hybridization detected MECOM (n = 11) and ETV6 (n = 7) rearrangements in all cases assessed. FLT3 internal tandem duplication was identified in five (25%) patients. We identified 13 genetic abnormalities in the de novo group (n = 9), and 25 in the secondary disease group (n = 11). All patients received chemotherapy, with seven allogeneic and two autologous stem cell transplantations. At last follow-up, 14 (70%) patients died with median survival of 6.3 months (range, 0.1–17.3) after detection of t(3;12). In summary, t(3;12)(q26.2;p13) is a rare cytogenetic abnormality in myeloid neoplasms. Myelodysplasia, chromosome 7 abnormalities, and high blast counts are common, and the prognosis is poor. Given the close relationship between the presence of this cytogenetic abnormality and the MDS-related changes, we recommend adding t(3;12)(q26.2;p13) to the list of AML with myelodysplasia-related changes defining abnormalities of the World Health Organization 2017 classification of myeloid neoplasms.

Monomorphic post-transplant lymphoproliferative disorder commonly resembles diffuse large B-cell lymphoma or Burkitt lymphoma, and most are Epstein–Barr virus (EBV) positive. We retrospectively identified 32 cases of monomorphic post-transplant lymphoproliferative disorder from two institutions and evaluated EBV in situ hybridization; TP53 mutation status; p53, CD30, myc, and BCL2 expression by immunohistochemistry; proliferation index by Ki67; and germinal center vs non-germinal center immunophenotype by Hans criteria. Post-transplant lymphoproliferative disorder arose after hematopoietic stem cell transplant in five and solid organ transplant in 27 patients, a median of 4 and 96 months after transplant, respectively (overall median latency 71 months, range 2–295). The most common morphology was diffuse large B-cell lymphoma (28 cases), with three cases of Burkitt lymphoma, and one case of plasmablastic lymphoma. Ten cases (31%) were EBV negative. Of those with the morphology of diffuse large B-cell lymphoma, the EBV-negative cases were more frequently TP53-mutated (P<0.001), p53 positive by immunohistochemistry (P<0.001), CD30 negative (P<0.01), and of germinal center immunophenotype (P=0.01) compared with EBV-positive cases. No statistically significant difference in overall survival was identified based on EBV, TP53 mutation status, germinal center vs non-germinal center immunophenotype, or other immunohistochemical parameters evaluated. Patients who died of post-transplant lymphoproliferative disorder were older with a longer latency from time of transplant to diagnosis (P<0.05). Our study demonstrates that diffuse large B-cell lymphoma-related immunohistochemical prognostic markers have limited relevance in the post-transplant setting and underscores differences between EBV-positive and EBV-negative post-transplant lymphoproliferative disorder in terms of immunophenotype and TP53 mutation frequency, supporting an alternative pathogenesis for EBV-negative post-transplant lymphoproliferative disorder.

Chromosomal insertion-derived BCR–ABL1 fusion is rare and mostly cryptic in chronic myeloid leukemia (CML). Most of these cases present a normal karyotype, and their risk and/or prognostic category are uncertain. We searched our database and identified 41 CML patients (20 M/21 F, median age: 47 years, range 12–78 years) with insertion-derived BCR–ABL1 confirmed by various FISH techniques: 31 in chronic phase, 1 in accelerated phase, and 9 in blast phase at time of diagnosis. Conventional cytogenetics analysis showed a normal karyotype ( n  = 19); abnormal karyotype with morphologically normal chromosomes 9 and 22 ( n  = 5); apparent ins(9;22) ( n  = 2) and abnormal karyotype with apparent abnormal chromosomes 9, der(9) and/or 22, der(22) ( n  = 15). The locations of insertion-derived BCR–ABL1 were identified on chromosome 22 (68.3%), 9 (29.3%), and 19 (2.4%). Complex chromosomal abnormalities were often overlooked by conventional cytogenetics but identified by FISH tests in many cases. After a median follow-up of 58 months (range 1–242 months), 11 patients died, and 3 lost contact, while the others achieved different cytogenetic/molecular responses. The locations of BCR–ABL1 (der(22) vs. non-der(22)) and the karyotype results (complex karyotype vs. noncomplex karyotype) by conventional cytogenetics were not associated with overall survival in this cohort. However, redefining the complexity of chromosomal abnormality by correlating karyotype and FISH findings, CML cases with simple chromosomal abnormalities had a more favorable overall survival than that with complex chromosomal abnormalities. We conclude that insertion-derived BCR–ABL1 fusions often involve complex chromosomal abnormalities which are overlooked by conventional cytogenetics, but can be identified by one or more FISH tests. We also suggest that the traditional cytogenetic response criteria may not apply in these patients, and the complexity of chromosomal abnormalities redefined by correlating karyotype and FISH findings can plays a role in stratifying patients into more suitable risk groups for predicting prognosis. (Word count: 292)

Immune checkpoint inhibitors (PD-1 inhibitors) have shown clinical activity in Richter transformation-diffuse large B-cell lymphoma variant (RT-DLBCL), thus providing for a novel therapeutic approach. The study group consists of 64 patients with RT-DLBCL. Expression of PD-1, PD-L1, CD30, and microsatellite instability (MSI) status (hMLH1, hMSH2, hMSH6, PMS1) was assessed using immunohistochemistry. EBV-encoded RNA (EBER) was evaluated using colorimetric in situ hybridization. PD-1 and PD-L1 expression levels were categorized on the basis of tumor cell expression as follows: negative (< 5%), positive to low-positive (5–50%), or high-positive (> 50%). An “immune evasion phenotype” (IEP) was defined as RT-DLBCL cases having high-positive expression of PD-1 and/or PD-L1 on tumor cells. The level of PD1-positive tumor-infiltrating lymphocytes (TILs) was estimated as a fraction of total lymphocytes and categorized as negative/low vs. brisk (> 20%). 28/64 (43.7%) patients were characterized as IEP+ RT-DLBCL. A brisk level of PD1+ TILs was significantly more common in IEP1+ compared with IEP- tumors (17/28, 60.7% vs. 5/34, 14.7%; p = 0.001). In addition, CD30 expression was significantly more common in IEP+ compared with IEP- RT-DLBCL (6/20, 30% vs. 1/27, 3.7%; p = 0.0320). Two (2/36; 5.5%) cases were positive for EBER, both IEP+. There was no significant difference between the two groups in terms of age, sex, or time to transformation. Assessment of mismatch repair proteins demonstrated absence of microsatellite instability (MSI) in all cases (18/18; 100%). Notably, patients with brisk PD1+ TILs had a significantly better OS compared to those with a negative/low infiltrate (p = 0.0285).

The three major criteria are 1) An elevated hemoglobin (≥16.5 g/dL in men and ≥16.0 g/dL in women) or elevated hematocrit (≥49% in men and ≥48% in women); 2) Bone marrow biopsy specimen with age-adjusted hypercellularity with panmyelosis and pleomorphic megakaryocytic proliferation, and 3) Presence of JAK2 p.V617F or JAK2 exon 12 mutation; the minor criterion is a subnormal EPO level [1, 2]. Low serum EPO level and appropriate bone marrow morphology with JAK2 mutation are useful clues for an accurate diagnosis and management in masked PV patients with iron deficiency due to gastric bypass surgery. CONFLICT OF INTEREST STATEMENT The authors declare no conflict of interest.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background Expression of B‐cell antigens is rare in T‐lymphoblastic leukemia/lymphoma (T‐LBLL), and the significance is uncertain. Objective and Methods We present a pediatric case of acute leukemia characterized by the expression of T‐cell markers and CD19, as determined by multicolor flow cytometry (MFC). Next‐generation sequencing (NGS) revealed a SET::NUP214 gene fusion. The patient was treated with conventional intensive acute lymphoblastic leukemia (ALL) therapy. The end‐of‐induction evaluations showed significant residual disease. Results While the patient failed high‐risk T‐LBLL induction therapy, blinatumomab followed by decitabine and venetoclax induced a morphologic remission. He then underwent a bone marrow stem cell transplant (BMSCT) and achieved a complete molecular remission. Conclusions This case illustrated the importance of integrating MFC analysis with NGS data to provide individualized patient treatment. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.

MYD88 mutations in chronic lymphocytic leukemia (CLL) are not well characterized. Earlier reports yielded conflicting results in terms of clinicopathologic presentation and prognostic impact of MYD88 mutations in CLL patients. In addition, the morphological and immunophenotypic features of CLL cases carrying MYD88 mutations have not been explored. Finally, the clinical or biologic implications of the canonical L265P MYD88 mutation vs. mutations in other sites of MYD88 within the context of CLL are also unknown. In this study, a cohort of 1779 CLL patients underwent mutational analysis, and 56 (3.1%) cases were found to have MYD88 mutations, including 38 with L265P mutations (designated here as group A) and 18 with non-L265P mutations (group B). Cases with wild type MYD88 were included as controls. There was no morphological difference in cases with and without MYD88 mutations. Immunophenotypically, cases with mutated MYD88 (both groups A and B) more frequently had an atypical immunophenotype when compared to wild type cases. Group A patients were younger and were associated with variable favorable prognostic factors, including less elevated β2-microglobulin level, negative CD38 and ZAP70, higher frequency of mutated IGHV and isolated del(13q14.3), and lower frequency of del(11q22.3) and mutations of NOTCH1 and SF3B1. In contrast, group B patients were more similar to CLL patients with wild type MYD88. There was no difference in time to first treatment when comparing MYD88-mutated vs. wild type CLL patients before and after stratification according to IGHV mutation status. In summary, MYD88 mutations are uncommon in CLL and cases with L265P mutation have distinctive clinical, immunophenotypic, cytogenetic, and molecular features. There is no significant impact of MYD88 mutations on time to first treatment in CLL.