Interleukin-8 blockade prevents activated endothelial cell mediated proliferation and chemoresistance of acute myeloid leukemia.

One of the greatest challenges in treating acute myeloid leukemia (AML) is chemotherapy refractory disease. Previously, we demonstrated a novel mechanism whereby AML-induced endothelial cell (EC) activation leads to subsequent leukemia cell adherence, quiescence and chemoresistance, identifying activated ECs as potential mediators of relapse. We now show mechanistically that EC activation induces the secretion of interleukin-8 (IL-8) leading to significant expansion of non-adherent AML cells and resistance to cytarabine (Ara-C). Through crystallography and computational modeling, we identified a pocket within IL-8 responsible for receptor binding, screened for small molecules that fit within this pocket, and blocked IL-8 induced proliferation and chemo-protection of AML cells with a hit compound. Results from this study show a new therapeutic strategy for targeting the sanctuary of an activated leukemia microenvironment.

Unusual Presentation of a Small-Cell Variant of Anaplastic Large-Cell Lymphoma Case: When a Septic Picture Is Not Sepsis.

We report a case of a small-cell variant of anaplastic large-cell lymphoma, with an unusual clinical presentation mimicking sepsis and a fulminant clinic course, in a 48-year-old Caucasian female. In this report, we discuss the diagnostic challenge, histopathologic features, and unique cytogenetic features of this case, in order to raise awareness of this rare presentation and emphasize the importance of meticulous peripheral smear examination and early bone marrow evaluation.

Early, Isolated Duodenal Mucosa-Associated Lymphoid Tissue Lymphoma Presenting without Symptoms or Grossly Apparent Endoscopic Lesions and Diagnosed by Random Duodenal Biopsies.

Clinical data regarding mucosa-associated lymphoid tissue lymphoma (MALToma) solely involving the duodenum are sparse because of the relative rarity of the disease. A comprehensive literature review revealed only 17 cases reported until 2004, and only a moderate number of cases have been reported since. MALToma can be asymptomatic in its very early stages but frequently produces localized or nonspecific symptoms, including early satiety, abdominal pain, vomiting, and involuntary weight loss in later stages. While gastric MALToma is strongly associated with gastric Helicobactor pylori infection, duodenal MALToma is often unassociated with H. pylori infection. A 74-year-old female presented with only dysphagia (without symptoms referable to a duodenal lesion), without systemic 'B' symptoms, and with no evident duodenal lesions at esophagogastroduodenoscopy; however, she was diagnosed with duodenal MALToma by pathologic examination of random duodenal biopsies performed to exclude celiac disease. An important clinical feature of this case is that duodenal MALToma was diagnosed by pathologic analysis of duodenal biopsies despite (1) no endoscopically apparent duodenal lesions; (2) duodenal involvement without gastric involvement; (3) lack of symptoms attributable to duodenal MALToma, and (4) absence of evident H. pylori infection. This work shows that early duodenal MALToma can be difficult to diagnose because of absent symptoms, absence of gastric involvement, absence of endoscopic abnormalities, and absence of H. pylori infection; it may require random duodenal biopsies for diagnosis.

Anaplastic large cell lymphoma associated with breast implants: a report of 13 cases.

We report 13 cases of anaplastic large cell lymphoma (ALCL) associated with breast implants. Patient age ranged from 39 to 68 years, and the interval from implant to ALCL was 4 to 29 years. All tumors were composed of large, pleomorphic cells that were CD30 and ALK1, and all 7 cases assessed had monoclonal T-cell receptor γ-chain rearrangements. Two patient subgroups were identified. Ten patients presented with effusion surrounded by fibrous capsule without a grossly identifiable tumor mass. Nine patients had stage I and 1 had stage II disease. Eight patients underwent implant removal and capsulectomy. Four patients received chemotherapy and 4 radiation therapy. All patients were alive without disease at last follow-up. A second subgroup of 3 patients had effusion and a distinct mass adjacent to the implant. One patient had stage I and 2 stage II disease. One patient had a 3-year history of lymphomatoid papulosis, and 1 patient had a 1-year history of CD30 T-cell lymphoma adjacent to the breast before the diagnosis of ALCL associated with breast implant. Two patients received chemotherapy and 1 radiation therapy. Two patients died 2 and 12 years after diagnosis, respectively. We conclude that the clinical behavior of ALCL associated with breast implants is heterogeneous. Patients who present with effusion without a distinct mass have an indolent disease course, similar to CD30 lymphoproliferative disorder of skin. In contrast, patients who present with a distinct mass may have advanced stage or possibly systemic disease and have a poorer prognosis.

Composite biclonal marginal zone lymphoma of lung and chronic lymphocytic leukemia: pathologic, phenotypic, cytogenetic, and molecular study.

The simultaneous diagnosis of marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare. This study reports a patient with composite synchronous biclonal occurrence of MALT lymphoma of the lung and CLL/SLL. The morphology of the lung and peripheral blood showed features of MALT lymphoma and CLL, respectively. The cytogenetic evaluation of the lung specimen revealed a t(1;14) (p22;q32), a frequent genetic abnormality in MALT lymphoma. Flow cytometry analysis of the lung tissue showed features of MALT lymphoma and CLL/SLL with different light chain restriction, whereas the blood showed phenotypic evidence of CLL/SLL. Fluorescence in situ hybridization study of the blood showed a deletion of 13q14 and 17p13. Immunoglobulin heavy chain (IgH) gene rearrangement study of the lung tissue and blood showed a monoclonal IgH gene rearrangement with distinct light chain restriction, suggesting that the immunophenotypically different cell populations originated from separate clones.

A peer comparison program for the quality assurance of human papillomavirus DNA detection using the Digene Hybrid Capture II/SurePath method shows excellent analytic interlaboratory correlation.

BACKGROUND: Interlaboratory peer comparison programs are quality-assurance activities mandated by the Clinical Laboratory Improvement Amendments of 1988. No commercial program is available currently that was designed for cytology laboratories performing only human papillomavirus (HPV) DNA testing. In this report, the authors provide the results from a self-developed program between 2 cytology laboratories. METHODS: Between 4 and 11 SurePath liquid-based cervical cytology samples were selected at each of the 2 participating laboratories each quarter and exchanged without accompanying patient information. Samples were selected to test both positive and negative high-risk HPV DNA results in roughly equivalent numbers. Samples were run with the Hybrid Capture II method using each laboratory's standard procedure. The result obtained was compared with the originating laboratory's result. Correlation was compared on an ongoing basis as a method to assess analytic performance. RESULTS: Over a 3-year period, 12 exchanges took place, constituting 113 total specimens. Overall, there were 9 exchanges of 76 specimens that had 100% correlation, and 3 exchanges in which 4 of 37 specimens had discordant results. Overall, this represented a 97% correlation (109 of 113 specimens) of results between laboratories. All 4 discordant cases were reported as negative by the original laboratory and positive by the exchange laboratory (2 in each direction). CONCLUSIONS: The interlaboratory peer comparison result of 97% concordance demonstrated excellent analytic agreement between the HPV DNA-detection procedures of each laboratory. All discordant cases were "negative to positive" and were distributed equally by originating laboratory. The procedure was easily set up and provided assurance to each laboratory of ongoing performance for the detection of the HPV DNA analyte.