Cost-Effective Flow Cytometry Testing Strategies.

Cost-effective flow cytometry (FC) requires development of FC panels focused to common diagnoses and strategies to identify cases where limited FC testing is sufficient. Focused panels include sufficient antibodies and to identify common diseases and appropriate analysis strategies to identify rare diseases that need additional FC testing. Strategies to limit FC testing include the use of algorithms to predict disease probability, with limited FC performed if disease is unlikely.

Transmission of Babesia microti Parasites by Solid Organ Transplantation.

Babesia microti, an intraerythrocytic parasite, is tickborne in nature. In contrast to transmission by blood transfusion, which has been well documented, transmission associated with solid organ transplantation has not been reported. We describe parasitologically confirmed cases of babesiosis diagnosed ≈8 weeks posttransplantation in 2 recipients of renal allografts from an organ donor who was multiply transfused on the day he died from traumatic injuries.

A unique CD4+ large granular lymphocytosis occurring in patients treated with tumor necrosis factor α inhibitors: report of 2 cases.

We report 2 cases of CD4(+) large granular lymphocyte (LGL) lymphocytosis occurring in patients being treated with a monoclonal antibody against tumor necrosis factor α for underlying autoimmune disorders. CD4(+) LGL lymphocytosis is a rare subset of LGL disease that has previously only been described in patients without underlying autoimmune disorders, and most demonstrate uniform coexpression of CD56 on the atypical T cells. The clinical features, with both cases occurring in patients with autoimmune disease, and immunophenotypic features, with both cases showing dim CD8 coexpression without CD56 in the CD4(+) LGLs, suggest that the reported cases are distinct from those previously described and may represent a novel T-cell LGL lymphocytosis emerging from iatrogenic immune modulation of patients with underlying autoimmune disorders.

Efficient assessment of peripheral blood lymphocytosis in adults: developing new thresholds for blood smear review by pathologists.

Background: Peripheral smear review is a critical, but labor intensive adjunct for evaluation of lymphocytosis. Standard practice based on consensus guidelines is to review cases with absolute lymphocyte count (ALC) >5×109/L. We hypothesize that identifying cases for review by applying appropriately adjusted ALC and age discriminators will decrease laboratory workload without compromising patient care.

Kaposi sarcoma herpesvirus/human herpesvirus-8-negative effusion-based lymphoma: report of 3 cases and review of the literature.

Background: Primary effusion lymphoma (PEL) is a rare subtype of large B-cell lymphoma that arises in body cavities without detectable tumor masses. PEL is universally associated with Kaposi sarcoma herpesvirus (KSHV)/human herpesvirus-8 (HHV8). Despite overlapping features, KSHV/HHV8-negative effusion-based lymphoma is a distinct entity from PEL.

Use of tissue microarray and automated quantitative analysis for screening and validation of potential biomarkers in mantle cell lymphoma.

Background: Cancer biomarker studies using the combination of tissue microarray and automated quantitative assessment of immunofluorescence (TMA-AQUA) have been successfully performed for various types of human carcinoma, but its performance characteristics have yet to be evaluated in human lymphoma.

Methods: A pilot TMA was constructed containing duplicate 1.5 mm cores from 15 cases of mantle cell lymphoma (MCL), 3 cases of low-grade B-cell lymphoma, and 3 cases of benign lymphoid tissue.

Bone marrow stromal cells from multiple myeloma patients uniquely induce bortezomib resistant NF-kappaB activity in myeloma cells.

Background: Components of the microenvironment such as bone marrow stromal cells (BMSCs) are well known to support multiple myeloma (MM) disease progression and resistance to chemotherapy including the proteasome inhibitor bortezomib. However, functional distinctions between BMSCs in MM patients and those in disease-free marrow are not completely understood. We and other investigators have recently reported that NF-kappaB activity in primary MM cells is largely resistant to the proteasome inhibitor bortezomib, and that further enhancement of NF-kappaB by BMSCs is similarly resistant to bortezomib and may mediate resistance to this therapy.

Bortezomib-resistant nuclear factor-kappaB activity in multiple myeloma cells.

Bortezomib (Velcade/PS341), a proteasome inhibitor used in the treatment of multiple myeloma (MM), can inhibit activation of nuclear factor-kappaB (NF-kappaB), a family of transcription factors often deregulated and constitutively activated in primary MM cells. NF-kappaB can be activated via several distinct mechanisms, including the proteasome inhibitor-resistant (PIR) pathway. It remains unknown what fraction of primary MM cells harbor constitutive NF-kappaB activity maintained by proteasome-dependent mechanisms.

Overexpression of protein kinase C-{epsilon} in the mouse epidermis leads to a spontaneous myeloproliferative-like disease.

Protein kinase C (PKC)-epsilon, a Ca(2+)-independent, phospholipid-dependent serine/threonine kinase, is among the PKC isoforms expressed in mouse epidermis. We reported that FVB/N transgenic mouse lines that overexpress (8- or 18-fold) PKC-epsilon protein in basal epidermal cells and cells of the hair follicle develop papilloma-independent squamous cell carcinoma (SCC) elicited by 7,12-dimethylbenz(a)anthracene initiation and 12-O-tetradecanoylphorbol-13-acetate-promotion or by repeated ultraviolet radiation exposures. The susceptibility to the development of SCC was proportional to the level of expression of the PKC-epsilon transgene.