TAFRO syndrome: A case report and review of the literature.

TAFRO syndrome is a rare clinicopathologic variant of idiopathic multicentric Castleman disease characterized by Thrombocytopenia, Ascites (anasarca), myeloFibrosis, Renal dysfunction, and Organomegaly. Here, we report a case of TAFRO syndrome in an HIV-negative young Caucasian male who presented with fever, normocytic anemia, thrombocytopenia, and acute renal insufficiency. The serum interleukin-6 (IL-6) level was elevated. Chest and abdominal CT revealed bilateral pleural effusion, ascites, splenomegaly, and multiple mildly enlarged lymph nodes. An excisional biopsy of inguinal lymph node showed a few atrophic follicles and expansion of interfollicular areas by marked vascular proliferation and polytypic plasmacytosis. HHV-8 was negative. Subsequent bone marrow biopsy was normocellular with moderately increased megakaryocytes and occasional megakaryocytic emperipolesis. His signs and symptoms improved after treatment with methylprednisolone and tocilizumab (anti-IL-6 receptor antibody). Our study confirms the distinctive nature of this syndrome, which should allow for better recognition and appropriate therapy.

Maximizing derivable information from cytologic specimens for pathologic and molecular diagnostics.

INTRODUCTION: The advent of precision medicine will increase the demand for molecular testing on patient tumor specimens. Cytology specimens have been shown to be ideal substrates for molecular testing, but their often paucicellular nature can lead to conflicts in prioritizing sample management. A microfluidic platform was investigated to determine whether cytologic and molecular data could be procured from the same cells, obviating the need for partitioning a sample by multiplexing it instead. MATERIALS AND METHODS: Cytology samples were created from a tissue source, stained with a supravital dye, and enriched using immunomagnetic beads. These cells and the attached immunomagnetic beads were then run through a microfluidic channel, temporarily immobilized for cytologic examination, and then recovered. The cytologic characteristics of these cells was compared with cells from the same source prepared by conventional cytologic preparatory means. DNA was extracted from the cells recovered from the microfluidic channel and the nature of their integrity was assessed. RESULTS: Cytologic features between cells run in a microfluidic channel and prepared by conventional means were similar. The DNA recovered from the cells run through the microfluidic channel was of high molecular weight. CONCLUSIONS: Microfluidics enables multiplex testing of cytologic specimens, allowing for cytology-based diagnostic examination and recovery of high-quality DNA. This approach will be of particular benefit for cytology specimens that are paucicellular and will need molecular testing.

Phospho-p70S6K/p85S6K and cdc2/cdk1 are novel targets for diffuse large B-cell lymphoma combination therapy.

PURPOSE: This study aimed to identify and evaluate molecular targets for the development of a novel combination chemotherapy to treat refractory and recurrent diffuse large B-cell lymphoma (DLBCL). EXPERIMENTAL DESIGN: Lymphoma samples from 38 cases of primary and recurrent DLBCL were analyzed using real-time quantitative PCR of the RPS6KB1 and CDC2 genes, and immunohistochemistry for their gene products p70S6K/p85S6K and cdc2/cdk1. The Farage, Karpas422, Pfeiffer, and Toledo DLBCL cell lines were subsequently treated with rapamycin and UCN-01 alone or in combination. Cell proliferation, apoptosis, and cell cycle progression were analyzed after the drug treatment. In addition, the levels of several key protein kinases involved in the phosphoinositide 3'-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, apoptosis, and cell cycle progression were analyzed in the presence and absence of the drugs. RESULTS: Amplification of the RPS6KB1 and CDC2 genes was found in both primary and recurrent DLBCL. Moreover, the vast majority of these lymphomas (approximately 94%) were strongly positive for phospho-p70S6K and cdc2/cdk1 proteins. The combination of rapamycin and UCN-01 synergistically inhibited the DLBCL cell proliferation by inducing G1 arrest as well as apoptosis by suppressing the phosphorylation of p70S6K/p85S6K and CDC2 expression. CONCLUSION: RPS6KB1 and CDC2 overexpression is common in DLBCL. Simultaneously targeting the RPS6KB1 and CDC2 products phospho-p70S6K/p85S6K and cdc2/cdk1 is very effective in inhibiting DLBCL proliferation and overcoming drug resistance. This work suggests that multilevel inhibition of the PI3K/Akt/mTOR pathway and double-block of cell cycle progression are effective strategies for DLBCL therapy.

Recurrence of nodal diffuse large B-cell lymphoma as intravascular large B-cell lymphoma: is an intravascular component at initial diagnosis predictive?

We report a case of a 59-year-old man who first presented with a nodal diffuse large B-cell lymphoma that later relapsed as an intravascular large B-cell lymphoma. In the initial biopsy specimen, a few intranodal small vessels that contained large lymphoma cells were noted. After 8 months of multiagent chemotherapy, clinical remission was attained. Two years after the initial diagnosis of nodal diffuse large B-cell lymphoma, the patient presented with a rapid onset of multiorgan failure, which at autopsy was shown to be due to intravascular large B-cell lymphoma. Molecular genetic studies showed that these 2 lymphomas had immunoglobulin heavy-chain gene rearrangements that were of identical size, suggesting that they were derived from the same clone. To our knowledge, this is the first report of a nodal large B-cell lymphoma that relapsed as an intravascular large B-cell lymphoma. Although this report is of only a single case, the presence of a relatively inconspicuous intravascular component in an otherwise typical nodal large B-cell lymphoma may be predictive and could affect clinical decisions regarding diagnosis, monitoring, and prognosis of such lymphomas.