Cutaneous B‐cell lymphomas: 2021 update on diagnosis, risk‐stratification, and management

Disease OverviewApproximately one‐fourth of primary cutaneous lymphomas are B‐cell derived and are generally classified into three distinct subgroups: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), and primary cutaneous diffuse large B‐cell lymphoma, leg type (PCDLBCL, LT).DiagnosisDiagnosis and disease classification is based on histopathologic review and immunohistochemical staining of an appropriate skin biopsy. Pathologic review and an appropriate staging evaluation are necessary to distinguish primary cutaneous B‐cell lymphomas from systemic B‐cell lymphomas with secondary skin involvement.Risk‐StratificationDisease histopathology remains the most important prognostic determinant in primary cutaneous B‐cell lymphomas. Both PCFCL and PCMZL are indolent lymphomas that infrequently disseminate to extracutaneous sites and are associated with 5‐year survival rates that exceed 95%. In contrast, PCDLBCL, LT is an aggressive lymphoma with an inferior prognosis.Risk‐Adapted TherapyBoth PCFCL and PCMZL patients with solitary or relatively few skin lesions may be effectively managed with local radiation therapy. While single‐agent rituximab may be employed for patients with more widespread skin involvement, multi‐agent chemotherapy is rarely appropriate. In contrast, management of patients with PCDLBCL, LT is comparable to the management of patients with systemic DLBCL.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162801/2/ajh25970.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162801/1/ajh25970_am.pd

A diagnosis of mycosis fungoides in a pediatric patient with recurrent Langerhans cell histiocytosis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141250/1/pbc26835.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141250/2/pbc26835_am.pd

Kappa and lambda immunohistochemistry and in situ hybridization in the evaluation of atypical cutaneous lymphoid infiltrates

BackgroundAtypical cutaneous lymphoid infiltrates are challenging lesions in dermatopathology. We present a summary of the literature regarding kappa and lambda immunohistochemistry (IHC) and in situ hybridization (ISH) in the evaluation of atypical cutaneous or mucosal lymphoid infiltrates.MethodsRelevant articles from 1967 to 2018 in the English language were identified and summarized. In the absence of larger studies, case series of n ≥ 3 were included.ResultsSixty‐three articles assessing kappa and lambda IHC and/or ISH were identified. Most focused on marginal zone lymphomas. Other lymphomas included follicle center lymphoma, diffuse large B‐cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, lymphoplasmacytic lymphoma, plasmablastic lymphoma, multiple myeloma, monoclonal gammopathy of undetermined significance, and polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS). Non‐neoplastic lesions included reactive lymphoid hyperplasia, cutaneous plasmacytosis, connective tissue disease, IgG4‐related disease, acrodermatitis chronic atrophicans, Zoon balanitis, dermatitides, and infiltrates around epithelial dysplasias/neoplasias.ConclusionKappa and lambda IHC and ISH are useful tools in the evaluation of cutaneous B‐cell lymphomas and plasma cell neoplasms. The literature supports that the detection of light‐chain restriction by IHC and ISH is one of the most useful findings in the differential diagnosis of reactive lymphoid hyperplasia vs B‐cell lymphoma with plasmacytic differentiation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163451/2/cup13858.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163451/1/cup13858_am.pd

Utility of CD123 immunohistochemistry in differentiating lupus erythematosus from cutaneous T cell lymphoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149293/1/his13817_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149293/2/his13817.pd

A retrospective comparative outcome analysis following systemic therapy in Mycosis fungoides and Sezary syndrome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134845/1/ajh24564_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134845/2/ajh24564.pd

A single center phase II study of ixazomib in patients with relapsed or refractory cutaneous or peripheral T‐cell lymphomas

The transcription factor GATA‐3, highly expressed in many cutaneous T‐cell lymphoma (CTCL) and peripheral T‐cell lymphomas (PTCL), confers resistance to chemotherapy in a cell‐autonomous manner. As GATA‐3 is transcriptionally regulated by NF‐κB, we sought to determine the extent to which proteasomal inhibition impairs NF‐κB activation and GATA‐3 expression and cell viability in malignant T cells. Proteasome inhibition, NF‐κB activity, GATA‐3 expression, and cell viability were examined in patient‐derived cell lines and primary T‐cell lymphoma specimens ex vivo treated with the oral proteasome inhibitor ixazomib. Significant reductions in cell viability, NF‐κB activation, and GATA‐3 expression were observed preclinically in ixazomib‐treated cells. Therefore, an investigator‐initiated, single‐center, phase II study with this agent in patients with relapsed/refractory CTCL/PTCL was conducted. Concordant with our preclinical observations, a significant reduction in NF‐κB activation and GATA‐3 expression was observed in an exceptional responder following one month of treatment with ixazomib. While ixazomib had limited activity in this small and heterogeneous cohort of patients, inhibition of the NF‐κB/GATA‐3 axis in a single exceptional responder suggests that ixazomib may have utility in appropriately selected patients or in combination with other agents.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139920/1/ajh24895.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139920/2/ajh24895_am.pd

A cryogenic rotation stage with a large clear aperture for the half-wave plates in the Spider instrument

We describe the cryogenic half-wave plate rotation mechanisms built for and used in Spider, a polarization-sensitive balloon-borne telescope array that observed the Cosmic Microwave Background at 95 GHz and 150 GHz during a stratospheric balloon flight from Antarctica in January 2015. The mechanisms operate at liquid helium temperature in flight. A three-point contact design keeps the mechanical bearings relatively small but allows for a large (305 mm) diameter clear aperture. A worm gear driven by a cryogenic stepper motor allows for precise positioning and prevents undesired rotation when the motors are depowered. A custom-built optical encoder system monitors the bearing angle to an absolute accuracy of +/- 0.1 degrees. The system performed well in Spider during its successful 16 day flight.Comment: 11 pages, 7 figures, Published in Review of Scientific Instruments. v2 includes reviewer changes and longer literature revie

Modeling and characterization of the SPIDER half-wave plate

Spider is a balloon-borne array of six telescopes that will observe the Cosmic Microwave Background. The 2624 antenna-coupled bolometers in the instrument will make a polarization map of the CMB with approximately one-half degree resolution at 145 GHz. Polarization modulation is achieved via a cryogenic sapphire half-wave plate (HWP) skyward of the primary optic. We have measured millimeter-wave transmission spectra of the sapphire at room and cryogenic temperatures. The spectra are consistent with our physical optics model, and the data gives excellent measurements of the indices of A-cut sapphire. We have also taken preliminary spectra of the integrated HWP, optical system, and detectors in the prototype Spider receiver. We calculate the variation in response of the HWP between observing the CMB and foreground spectra, and estimate that it should not limit the Spider constraints on inflation

Pointing control for the SPIDER balloon-borne telescope

We present the technology and control methods developed for the pointing system of the SPIDER experiment. SPIDER is a balloon-borne polarimeter designed to detect the imprint of primordial gravitational waves in the polarization of the Cosmic Microwave Background radiation. We describe the two main components of the telescope's azimuth drive: the reaction wheel and the motorized pivot. A 13 kHz PI control loop runs on a digital signal processor, with feedback from fibre optic rate gyroscopes. This system can control azimuthal speed with < 0.02 deg/s RMS error. To control elevation, SPIDER uses stepper-motor-driven linear actuators to rotate the cryostat, which houses the optical instruments, relative to the outer frame. With the velocity in each axis controlled in this way, higher-level control loops on the onboard flight computers can implement the pointing and scanning observation modes required for the experiment. We have accomplished the non-trivial task of scanning a 5000 lb payload sinusoidally in azimuth at a peak acceleration of 0.8 deg/s$^2$, and a peak speed of 6 deg/s. We can do so while reliably achieving sub-arcminute pointing control accuracy.Comment: 20 pages, 12 figures, Presented at SPIE Ground-based and Airborne Telescopes V, June 23, 2014. To be published in Proceedings of SPIE Volume 914

GRB 221009A, The BOAT

GRB 221009A has been referred to as the Brightest Of All Time (the BOAT). We investigate the veracity of this statement by comparing it with a half century of prompt gamma-ray burst observations. This burst is the brightest ever detected by the measures of peak flux and fluence. Unexpectedly, GRB 221009A has the highest isotropic-equivalent total energy ever identified, while the peak luminosity is at the $\sim99$th percentile of the known distribution. We explore how such a burst can be powered and discuss potential implications for ultra-long and high-redshift gamma-ray bursts. By geometric extrapolation of the total fluence and peak flux distributions GRB 221009A appears to be a once in 10,000 year event. Thus, while it almost certainly not the BOAT over all of cosmic history, it may be the brightest gamma-ray burst since human civilization began.Comment: Resubmitted to ApJ