IgG4 Expression in Primary Cutaneous Marginal Zone Lymphoma: A Multicenter Study.

BACKGROUND: Primary cutaneous marginal zone lymphoma (PCMZL) is the second most common B-cell lymphoma of the skin. A recent study has demonstrated a strikingly high prevalence of immunoglobulin (Ig)G4 expression in PCMZL with plasmacytic differentiation. OBJECTIVE: The objective was to investigate the incidence of IgG4 expression in PCMZL, and its correlation with clinical and immunophenotypic features. MATERIALS AND METHODS: Multicenter study that utilized immunohistochemistry and in-situ hybridization to evaluate the expression of IgG4, Ig light (κ and λ), and heavy chains (IgM, IgG), and the ratio of T (CD3+) and B (CD20+) cells in biopsy specimens from 30 patients with PCMZL and to correlate these findings with the clinical features. RESULTS: IgG4 expression was observed in 4 out of 30 patients (13%) with PCMZL. Patients with IgG4-positive lymphomas were 57 to 77 years of age (mean, 69) at biopsy. The lesions were solitary in 2 patients with IgG4-positive lymphomas, and were most commonly located on the trunk. Patients with IgG4-negative lymphomas experienced earlier disease onset at an average age of 53 years. The majority of the IgG4-negative cases presented with localized disease, on the trunk and upper extremities. There was no significant difference in the IgG4-positive versus negative cases for the following parameters: Ig κ or λ restriction, B-cell or T-cell predominance, and site of the lesions. CONCLUSIONS: IgG4 expression was observed in a minority of PCMZL patients. We did not identify significant clinical or immunophenotypic differences between IgG4 positive and negative cases.

Characterization of the tumor microenvironment in primary cutaneous CD30-positive lymphoproliferative disorders: a predominance of CD163-positive M2 macrophages.

BACKGROUND: The tumor microenvironment is essential for tumor survival, growth and progression. There are only a few studies on the tumor microenvironment in cutaneous CD30-positive lymphoproliferative disorders. METHODS: We assessed the composition of the tumor microenvironment using immunohistochemistry studies in skin biopsies from cases diagnosed with lymphomatoid papulosis (LyP: 18 specimens), primary cutaneous anaplastic large-cell lymphoma (PC-ALCL: 8 specimens), and reactive diseases harboring CD30-positive cells (18 specimens). RESULTS: The predominant cells present in LyP and PC-ALCL were CD163+ M2 macrophages (44.7%, 35%), followed by CD8+ tumor infiltrating lymphocytes (11%, 15%), FOXP3+ T-regulatory cells (9%, 4.5%) and programmed cell death 1(PD-1) + lymphocytes (2.2%, 6.8%). In contrast, CD30-positive reactive inflammatory and infectious disorders were characterized by higher numbers of CD123+ plasmacytoid dendritic cells (6.3%) when compared to LyP (1%), and PC-ALCL (1.1%). CONCLUSIONS: Key differences exist between the microenvironment of CD30-positive lymphoproliferative disorders and reactive conditions harboring CD30-positive lymphocytes. The high number of tumor associated macrophages, and the close vicinity of these immune cells to the CD30-positive tumor cells might suggest that tumor associated macrophages have direct influence on tumorigenesis in LyP and ALCL. Therefore, modulation of M2 macrophages may represent a new therapeutic strategy in cutaneous CD30-positive lymphoproliferative disorders.

The Impact of Menstrual Cycle Phase on Economic Choice and Rationality.

It is well known that hormones affect both brain and behavior, but less is known about the extent to which hormones affect economic decision-making. Numerous studies demonstrate gender differences in attitudes to risk and loss in financial decision-making, often finding that women are more loss and risk averse than men. It is unclear what drives these effects and whether cyclically varying hormonal differences between men and women contribute to differences in economic preferences. We focus here on how economic rationality and preferences change as a function of menstrual cycle phase in women. We tested adherence to the Generalized Axiom of Revealed Preference (GARP), the standard test of economic rationality. If choices satisfy GARP then there exists a well-behaved utility function that the subject's decisions maximize. We also examined whether risk attitudes and loss aversion change as a function of cycle phase. We found that, despite large fluctuations in hormone levels, women are as technically rational in their choice behavior as their male counterparts at all phases of the menstrual cycle. However, women are more likely to choose risky options that can lead to potential losses while ovulating; during ovulation women are less loss averse than men and therefore more economically rational than men in this regard. These findings may have market-level implications: ovulating women more effectively maximize expected value than do other groups.

Loss of expression of 5-hydroxymethylcytosine in CD30-positive cutaneous lymphoproliferative disorders.

BACKGROUND: The methylation of DNA at position 5 of cytosine, and the subsequent reduction in intracellular 5-hydroxymethylcytosine (5-hmC) levels, is a key epigenetic event in several cancers, including systemic lymphomas. However, no studies have analyzed this epigenetic marker in cutaneous lymphomas. Therefore, we aimed to analyze the expression of 5-hmC in cutaneous CD30-positive lymphoproliferative disorders and compare it with a control group composed of reactive infectious and inflammatory disorders with CD30-positive cells. METHODS: Retrospective case series study with immunohistochemical analysis using anti-CD30 and anti-5-hmC antibodies in control (n = 19), lymphomatoid papulosis (LyP) (n = 27) and primary cutaneous anaplastic large cell lymphoma (ALCL) (n = 14) specimens. RESULTS: Complete loss of 5-hmC nuclear staining by CD30+ cells was observed in 63% of LyP cases, 57% of ALCL cases and 0% of control cases. CONCLUSIONS: The presence of 5-hmC+ and CD30+ lymphocytes was highly suggestive of a benign process. In contrast, loss of 5-hmC nuclear staining was highly suggestive of a lymphoproliferative disorder (ALCL or LyP). Under these circumstances, the use of 5-hmC staining can be a useful adjunctive tool for discriminating between neoplastic CD30+ lymphoproliferations and inflammatory/infectious simulators harboring reactive CD30+ cells.

An expected utility maximizer walks into a bar

We conducted field experiments at a bar to test whether blood alcohol concentration (BAC) correlates with violations of the generalized axiom of revealed preference (GARP) and the independence axiom. We found that individuals with BACs well above the legal limit for driving adhere to GARP and independence at rates similar to those who are sober. This finding led to the fielding of a third experiment to explore how risk preferences might vary as a function of BAC. We found gender-specific effects: Men did not exhibit variations in risk preferences across BACs. In contrast, women were more risk averse than men at low BACs but exhibited increasing tolerance towards risks as BAC increased. Based on our estimates, men and women's risk preferences are predicted to be identical at BACs nearly twice the legal limit for driving. We discuss the implications for policy-makers.

Neural responses to taxation and voluntary giving reveal motives for charitable donations.

Civil societies function because people pay taxes and make charitable contributions to provide public goods. One possible motive for charitable contributions, called "pure altruism," is satisfied by increases in the public good no matter the source or intent. Another possible motive, "warm glow," is only fulfilled by an individual's own voluntary donations. Consistent with pure altruism, we find that even mandatory, tax-like transfers to a charity elicit neural activity in areas linked to reward processing. Moreover, neural responses to the charity's financial gains predict voluntary giving. However, consistent with warm glow, neural activity further increases when people make transfers voluntarily. Both pure altruism and warm-glow motives appear to determine the hedonic consequences of financial transfers to the public good.