Tiffany Tang

Objective: The primary objective of this study is to prospectively evaluate the role of procalcitonin (PCT) in distinguishing infectious fever from noninfectious fever (NIF) among febrile lymphoma patients. The secondary objective is to evaluate the usefulness of PCT in distinguishing among bloodstream infections (BSI), local infections and unidentified infections (LIUI), and NIF.Methods: Patients with lymphoma and fever were prospectively recruited between August 2014 and November 2015. PCT was measured within 24 hours of fever onset (PCT1) and 24–72 hours thereafter (PCT2). The higher PCT value between PCT1 and PCT2 was also documented (PCT_max). PCT levels (PCT1, PCT2, and PCT_max) were compared for BSI, LIUI, and NIF. In addition, the difference between PCT1 and PCT2 was evaluated in patients with complete data on both PCT1 and PCT2.Results: Of 108 eligible patients, 12 were diagnosed with BSI, 83 with LIUI, and 13 with NIF. PCT_max was statistically different between the infectious fever (BSI and LIUI combined) and NIF groups (median PCT_max: 0.44 ng/ml vs 0.19 ng/ml; p=0.026). PCT1 was not statistically different for patients with BSI, LIUI, and NIF (p=0.217). However, PCT2 and PCT_max were significantly higher in patients with BSI compared to those with NIF (p=0.026 and 0.002, respectively). Meanwhile, patients with BSI have significantly higher PCT_max values than those with LIUI (p=0.034). Among 90 cases with complete data on both PCT1 and PCT2, PCT2 was significantly higher than PCT1 in patients with BSI (median PCT: 0.98 ng/ml vs 0.47 ng/ml; p=0.045) and patients with LIUI (median PCT: 0.43 ng/ml vs 0.24 ng/ml; p=0.004), while not significant in patients with NIF (p=0.374).Conclusion: Two separate PCT measurements can differentiate between infectious fever and NIF and predict for BSI in lymphoma patients with fever.

Von Hippel–Lindau (VHL) syndrome is a dominantly inherited multisystem cancer syndrome caused by a heterozygous mutation in the VHL tumor suppressor gene. Previous studies suggested that similar populations of Caucasian and Japanese patients have similar genotype or phenotype characteristics. In this comprehensive study of East Asian patients, we investigated the genetic and clinical characteristics of patients with VHL syndrome. To create a registry of clinical characteristics and mutations reported in East Asian patients with VHL syndrome, we conducted a comprehensive review of English language and non-English language articles identified through a literature search. Publications in Japanese or Chinese language were read by native speakers of the language, who then performed the data extraction. Of 237 East Asian patients with VHL syndrome, 154 unique kindreds were identified for analysis. Analyzed by kindred, missense mutations were the most common (40.9%, 63/154), followed by large/complete deletions (32.5%, 50/154) and nonsense mutations (11.7%, 18/154). Compared with a previously reported study of both East Asian and non-East Asian patients, we found several key differences. First, missense and frameshift mutations in the VHL gene occurred less commonly in our population of East Asian patients (40.9% vs. 52.0%; P = 0.012 and 8.4% vs. 13.0%; P < 0.001, respectively). Second, large/complete deletions were more common in our population of East Asian patients (32.5% vs. 10.5%; P < 0.001). Third, phenotypically, we observed that, in our population of East Asian patients with VHL syndrome, the incidence of retinal capillary hemangioblastoma was lower, whereas the incidence of renal cell carcinoma was higher. Evidence suggests that the genotypic and phenotypic characteristics of East Asian patients with VHL syndrome differ from other populations. This should be considered when making screening recommendations for VHL syndrome in Asia.

To the Editor,Programmed death-1 (PD-1) checkpoint inhibitors have shown promising results for the treatment of various tumor types, including relapsed and refractory Hodgkin’s lymphoma (HL) [1,2]....

Vasculitis is an inflammation that can present as acute or chronic in nature, which causes changes in the walls of blood vessels, including thickening, weakening, narrowing and scarring. Gemcitabine, an antimetabolite chemotherapeutic agent, is generally well tolerated with a favorable side effect profile. However, there is increasing evidence that it is associated with vasculitis, which can affect small and large vessels. In this case report, we report a patient who has experienced fever with severe tenderness over right carotid artery, which occurred on the fifth day after the administration of gemcitabine. The exact mechanism of gemcitabine-induced vasculitis is unknown but cessation of gemcitabine and initiation of anti-inflammatory treatment appears to aid in the resolution of the clinical syndrome.

The entity 'B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL)' refers to B cell neoplasms that share overlapping characteristics of BL and DLBCL. A subset of these 'grey-zone lymphomas' possesses C-MYC and IGH translocations but, in addition, contains additional rearrangements of BCL2 and/or BCL6 genes. The aim of this study was to investigate if the proliferation fraction by Ki67 immunostaining can be used to identify such double-/triple-hit lymphomas. We studied 492 cases of mature aggressive B cell neoplasms by histology, immunohistochemistry and interphase fluorescence in-situ hybridization (FISH) using break-apart probes against C-MYC, BCL2, BCL6, IGH, MALT1, PAX5 and CCND1. Forty Burkitt lymphomas and 28 cases of MYC(+) double-/triple-hit lymphomas were identified. Of the latter, 77% and 54% displayed proliferation fractions exceeding 75% and 90%, respectively. With a cut-off of >75% by Ki67 immunostaining, the sensitivity and specificity for detection of MYC(+) double/triple translocations was 0.77 and 0.36. Raising the proliferation fraction criterion to >90% improved the specificity to 0.62 at the expense of a low sensitivity of 0.54. Immunostaining for Ki67 is not a useful approach to prescreen B cell lymphomas for MYC(+) double/triple translocations.