Utility of CD279/PD-1 immunohistochemistry in the evaluation of benign and neoplastic T-cell-rich bone marrow infiltrates.

OBJECTIVES: CD279 expression is used to help identify angioimmunoblastic T-cell lymphoma (AITL) or other T-cell lymphomas of T-follicular helper (TFH) cell origin; however, its utility in assessing lymphoid infiltrates in the bone marrow (BM) is not well established. METHODS: Immunohistochemistry for CD279 was performed on normal staging BM and in BM with benign lymphoid aggregates (LAs), AITLs, and other T-cell lymphomas. RESULTS: Seven of 10 staging BMs demonstrated scattered, usually weakly CD279+ cells. Thirty-four of 38 BMs had scattered weakly/variably intense CD279+ cells within LAs, but only four contained 11% to 25% CD279+ cells. Three of four AITLs were strongly CD279+, but one contained only around 10% CD279+ cells. Eleven of the other 38 T-cell lymphomas were CD279+, including five possible AITLs; four peripheral T-cell lymphomas, not otherwise specified; and two T-cell large granular lymphocytic leukemias. CONCLUSIONS: Although useful in assessing selected BM lymphoid infiltrates, CD279 expression may be limited in AITLs, is not specific for TFH lymphomas, and can be seen in benign lymphoid infiltrates, although without extensive strong positivity.

Nasal septal angiofibroma, a subclass of extranasopharyngeal angiofibroma.

OBJECTIVE: Extranasopharyngeal angiofibromas (ENA) arising from the nasal septum or nasal septal angiofibromas are extremely rare; only 13 such cases have been reported in the international literature. Our objective is to describe the presentation, workup, and surgical management of these lesions. STUDY DESIGN: Case reports were done. SETTING: The setting was a tertiary care referral center and the Veterans Affairs Medical Center. PATIENTS, INTERVENTIONS, AND RESULTS: We present 2 cases of extranasopharyngeal angiofibroma occurring on the nasal septum. CONCLUSIONS: In this report, we discuss the occurrence, the histopathologic findings, and the treatment of nasal septal angiofibroma.

Evaluation of a microarray-based genotyping assay for the rapid detection of cytochrome P450 2C19 *2 and *3 polymorphisms from whole blood using nanoparticle probes.

Numerous drugs such as clopidogrel have been developed to reduce coagulation or inhibit platelet function. The hepatic cytochrome P450 (CYP) pathway is involved in the conversion of clopidogrel to its active metabolite. A recent black-box warning was included in the clopidogrel package insert indicating a significant clinical link between specific CYP2C19 genetic variants and poor metabolism of clopidogrel. Of these variants, *2 and *3 are the most common and are associated with complete loss of enzyme activity. In patients who are carriers of a CYP2C19 *2 or *3 allele, the conversion of clopidogrel to its active metabolite may be reduced, which can lead to ischemic events and negative consequence for the patient. We examined the ability of the Verigene CLO assay (Nanosphere, Northbrook, IL) to identify CYP2C19 *2 and *3 polymorphisms in 1,286 unique whole blood samples. The Verigene CLO assay accurately identified homozygous and heterozygous *2 and *3 phenotypes with a specificity of 100% and a final call rate of 99.7%. The assay is fully automated and can produce a result in approximately 3.5 hours.

Mycobacterium avium intracellulare infection coexistent with nodular lymphocyte predominant Hodgkin lymphoma involving the lung.

A 5.5-year-old asymptomatic Hispanic/African American male presented with matted lymph nodes in the neck and reticulonodular opacities in the right upper lung. An extensive diagnostic work up was performed to rule out infectious etiologies. Biopsies of the lymph node and lung tissue were diagnostic of nodular lymphocyte predominant Hodgkin lymphoma. Two weeks into the chemotherapy, gastric aspirates grew Mycobacterium avium intracellulare. This is the first case of nodular lymphocyte predominant Hodgkin lymphoma involving the lung with coexistent Mycobacterium avium intracellulare.

Gastrointestinal pathology of autologous graft-versus-host disease following hematopoietic stem cell transplantation: a clinicopathological study of 17 cases.

Graft-versus-host disease is the major complication after allogeneic hematopoietic stem cell transplantation and is attributable to donor T-cell recognition of recipient alloantigens. In patients undergoing autologous hematopoietic stem cell transplantation in which there is no genetic disparity to induce an alloresponse, a syndrome similar to allogeneic graft-versus-host disease has been described. Designated as autologous graft-versus-host disease, it typically involves the skin and has reportedly caused little morbidity in this patient population. Recent data, however, suggest that autologous graft-versus-host disease can cause significant disease in the gastrointestinal tract, but its pathological spectrum of abnormalities and disease incidence are not well established. We report the development of autologous graft-versus-host disease following hematopoietic stem cell transplantation in 17 patients (15 with multiple myeloma) based on 388 autologous stem cell transplants carried out at our institution over a 6-year period. This represents a total incidence rate of 4% and among those transplanted for multiple myeloma, 6%. In all, 16 of the 17 patients had colonic biopsies performed for the diagnostic evaluation of persistent diarrhea. Biopsies in all 16 patients showed pathological evidence for graft-versus-host disease and were graded using standard grading criteria established for allogeneic graft-versus-host disease. Grades ranged from mild (grade 1/4) to severe (grade 4/4). Changes secondary to medication or infection were excluded. Responses to steroid and immunosuppressive therapy were variable but improved with continuing institutional experience. Outcomes ranged from a prompt, complete resolution of symptoms to death. Patients treated with autologous hematopoietic stem cell transplantation, particularly those with multiple myeloma, may develop a potentially life-threatening syndrome pathologically identical to allogeneic graft-versus-host disease. This diagnosis must be considered when interpreting biopsies from patients with gastrointestinal symptoms following autologous hematopoietic stem cell transplantation.

Efficacy of thalidomide for the treatment of amyotrophic lateral sclerosis: a phase II open label clinical trial.

Neuroinflammation through the cytokine, tumor necrosis factor-alpha (TNF-alpha) is thought to play an important role in the pathogenesis of amyotrophic lateral sclerosis (ALS). We conducted a preliminary phase II trial of thalidomide, which reduces levels of TNF-alpha pre-transcriptionally and post-transcriptionally in vivo and has been shown to prolong disease duration and extend the lifespan of transgenic animal models of ALS. Patients who met diagnostic criteria for ALS received thalidomide at escalating doses to a target dose of 400 mg/day. The primary endpoints in the trial were the ALS Functional Rating Scale (ALSFRS) and pulmonary function testing (PFT) curves after nine months of thalidomide treatment that were compared to historical controls. Secondary endpoints were: survival stratified for newly diagnosed and progressive disease, toxicity, quality of life, and serum cytokine measurements. Twenty-three patients were enrolled, but only 18 were evaluable for the primary outcome. There was no improvement in the ALSFRS or PFT compared to historical controls. Thalidomide had several side-effects in our ALS patients. There was no significant shift in cytokine profile after treatment compared to baseline. In conclusion, treatment of ALS with the TNF-alpha inhibitor, thalidomide, does not appear to effectively modulate disease progression and can cause adverse effects.