Natural Killer Cell Homing and Persistence in the Bone Marrow After Adoptive Immunotherapy Correlates With Better Leukemia Control.

Cellular immunotherapy using allogeneic natural killer (NK) cells may overcome chemotherapy-refractory acute myeloid leukemia. Our goal was to document NK cell homing/persistence in the bone marrow following adoptive immunotherapy. Our cohort included 109 patients who received NK cell therapy for refractory acute myeloid leukemia following lymphodepleting conditioning +/- denileukin diftitox, +/- low-dose total body irradiation. We evaluated the NK cell density in bone marrow core biopsies performed an average of 14 days after NK cell transfer using a CD56 immunohistochemical stain. The NK cell density in core biopsies showed only moderate correlation with NK cell percentage in bone marrow aspirates evaluated by flow cytometry (rs=0.48) suggesting that distribution of CD56 cells in the bone marrow niche offers unique insight into NK cell homing. Better leukemia control was associated with increased NK cell density, such that patients with <5% blasts had a higher NK cell density (P=0.01). As well, NK cell density above the median of reference group was significantly associated with morphologic remission of leukemia (P=0.01). Moreover, the NK cell density varied significantly between conditioning protocols. Our findings suggest that the use of low-dose irradiation or CD25-targeting immunocytokine (denileukin diftitox, IL2DT) as part of conditioning results in increased NK cell homing/persistence in the bone marrow. These novel results will help guide future immunotherapy with NK cells.

Clonal Lymphoproliferations in a Patient With Common Variable Immunodeficiency.

Common variable immunodeficiency (CVID) comprises a heterogeneous group of disorders of humoral immunity, characterized by marked deficiencies in serum immunoglobulins. Immune dysregulation causes susceptibility to recurrent bacterial infections, as well as autoimmune and lymphoproliferative disorders. Although the lymphoid cells comprising the atypical proliferations are often clonally related, their malignant potential and clinical significance differ from similar lesions in individuals with immunocompetence. Herein, we describe a Caucasian woman with CVID who over 7 years developed multiple clonal lymphoproliferative lesions, comprising a spectrum of morphologic characteristics. Many of the lesions harbored distinct clonal populations. Though a majority responded to conservative intervention, 1 lesion persisted, met the diagnostic criteria for diffuse large B-cell lymphoma, and responded well to conventional chemotherapeutic treatment. The patient subsequently developed additional lymphoproliferations, but the lesions were clonally distinct and responded to conservative therapy. The clinical course of this patient emphasizes the variable nature of lymphoproliferative lesions arising in patients with CVID and underscores an individualized approach to pathologic interpretation and diagnostic intervention.

Disseminated peritoneal leiomyomatosis postmorcellated resection of uterine leiomyomatous tissue.

In a retrospective review, we identified six cases of disseminated peritoneal leiomyomatosis (DPL) that occurred after resection for uterine leiomyoma(ta) using a morcellation procedure between 2010 and 2016. DPL occurred in less than 1% of all patients who underwent a prior hysterectomy with morcellation, and DPL never occurred without having underwent such a resection. The median age of women at the time of their original resection of uterine tissue was 38.6 years; the median time interval until resection of DPL after the primary morcellation procedure was 73 months and the median age was 48 years. At the time of DPL resection, a median of 6.5 individual lesions was present per patient, with each lesion having a median size of 1.2 cm in the greatest dimension. The most common peritoneal sites of involvement included the sigmoid colon serosa, right pelvis/pelvic side wall, and anterior abdominal parietal peritoneum. The same parameters are described for previously reported cases of DPL in the literature developing after a morcellated resection of uterine leiomyoma(ta). The use of morcellating hysterectomy specimens with leiomyomata may lead to the development of DPL by seeding, may involve numerous peritoneal sites, and often presents 2 years after the original resection.

Double- and triple-hit lymphomas can present with features suggestive of immaturity, including TdT expression, and create diagnostic challenges.

Double- and triple-hit lymphomas (DHL/THL) are aggressive B-cell neoplasms characterized by translocation of MYC with concurrent BCL2 and/or BCL6 translocation. In this retrospective study from one institution, we report clinicopathologic features of 13 cases (9 DHL/4 THL). The median age was 59 years (range 30-74) and patients included eight females and five males. Presentation included enlarging lymphadenopathy/masses (11 patients) and abnormal peripheral blood findings (2 patients). Features which raised the differential of an immature neoplasm included terminal deoxynucleotidyl transferase positivity (four cases, two THL/two DHL); dim CD45 expression (seven cases), lack of CD20 (two cases), or lack of surface immunoglobulin light chain (three cases) by flow cytometry; and blastoid morphology (two cases). We conclude that expression of TdT in a B-cell lymphoma with mature features or expression of surface light chain in a case otherwise suggestive of B-lymphoblastic leukemia/lymphoma should prompt an expedited evaluation for DHL/THL.

Detection of Prostate Cancer: Quantitative Multiparametric MR Imaging Models Developed Using Registered Correlative Histopathology.

Purpose To develop multiparametric magnetic resonance (MR) imaging models to generate a quantitative, user-independent, voxel-wise composite biomarker score (CBS) for detection of prostate cancer by using coregistered correlative histopathologic results, and to compare performance of CBS-based detection with that of single quantitative MR imaging parameters. Materials and Methods Institutional review board approval and informed consent were obtained. Patients with a diagnosis of prostate cancer underwent multiparametric MR imaging before surgery for treatment. All MR imaging voxels in the prostate were classified as cancer or noncancer on the basis of coregistered histopathologic data. Predictive models were developed by using more than one quantitative MR imaging parameter to generate CBS maps. Model development and evaluation of quantitative MR imaging parameters and CBS were performed separately for the peripheral zone and the whole gland. Model accuracy was evaluated by using the area under the receiver operating characteristic curve (AUC), and confidence intervals were calculated with the bootstrap procedure. The improvement in classification accuracy was evaluated by comparing the AUC for the multiparametric model and the single best-performing quantitative MR imaging parameter at the individual level and in aggregate. Results Quantitative T2, apparent diffusion coefficient (ADC), volume transfer constant (K(trans)), reflux rate constant (kep), and area under the gadolinium concentration curve at 90 seconds (AUGC90) were significantly different between cancer and noncancer voxels (P < .001), with ADC showing the best accuracy (peripheral zone AUC, 0.82; whole gland AUC, 0.74). Four-parameter models demonstrated the best performance in both the peripheral zone (AUC, 0.85; P = .010 vs ADC alone) and whole gland (AUC, 0.77; P = .043 vs ADC alone). Individual-level analysis showed statistically significant improvement in AUC in 82% (23 of 28) and 71% (24 of 34) of patients with peripheral-zone and whole-gland models, respectively, compared with ADC alone. Model-based CBS maps for cancer detection showed improved visualization of cancer location and extent. Conclusion Quantitative multiparametric MR imaging models developed by using coregistered correlative histopathologic data yielded a voxel-wise CBS that outperformed single quantitative MR imaging parameters for detection of prostate cancer, especially when the models were assessed at the individual level. (©) RSNA, 2016 Online supplemental material is available for this article.