Purpose To develop multiparametric magnetic resonance imaging (mpMRI) models for generating a quantitative, user-independent, voxel-wise composite biomarker score (CBS) for prostate cancer (PCa) detection utilizing co-registered correlative histopathology and comparing CBS-based detection performance against single quantitative MRI (qMR) parameters. Materials and Methods After providing informed consent to participate in an IRB approved protocol, patients with an initial diagnosis of PCa electing surgery as definitive therapy were imaged preoperatively with an mpMRI protocol from which quantitative MR parameters (qMR) were calculated. Per patient, all voxels in the prostate from an MRI imaging slice were classified as cancer or non-cancer based on deformably mapped histologically determined regions of disease to assess individual qMR parameters. Predictive models were developed using more than one qMR to generate CBS maps for cancer detection. Model development and evaluations of individual qMR and CBS were performed separately for the peripheral zone (PZ) alone and the whole gland (WG). Model accuracy was evaluated using the area under the receiver operating characteristic curve (AUC) and confidence intervals were calculated using the bootstrap procedure. The improvement in classification accuracy was evaluated by comparing the AUC for our multiparametric model and the single best performing qMR both at the individual level and in aggregate. Results T2TSE, ADC, Ktrans, kep and AUGC90 were significantly different between cancer and non-cancer voxels (p < 0.001 in all cases), with ADC exhibiting the best classification accuracy (AUC 0.82 for PZ and 0.74 for WG). A 4 parameter PZ-Model (AUC =0.85; p = 0.010 vs. ADC alone) and a 4 parameter WG-Model (AUC = 0.77; p = 0.043 vs. ADC alone) had the best performance of the multiparametric models considered. Based on individual-level analysis, we observed a statistically significant improvement in the AUC in 82% (23/28) and 71% (24/34) of patients when using the PZ and WG models, respectively, compared to ADC alone. Model-based CBS maps for cancer detection demonstrate improved visualization of cancer location and extent. Conclusions Co-registered correlative histopathology data was used as the ground truth for development of quantitative mpMRI models yielding voxel-wise CBS which outperform single qMR parameters for PCa detection especially when assessed at the individual level.

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 to 74) and patients included 8 females and 5 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 TdT positivity (4 cases, 2 THL/2 DHL); dim CD45 expression (7 cases), lack of CD20 (2 cases), or lack of surface immunoglobulin light chain (3 cases) by flow cytometry; and blastoid morphology (2 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.

Cellular immunotherapy using allogeneic natural killer (NK) cells may overcome chemotherapyrefractory acute myeloid leukemia (rAML). 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 rAML 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 (r s = 0.48) suggesting that distribution of CD56 positive 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.

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.

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.