Vocal similarity predicts the relative attraction of musical chords.

Musical chords are combinations of two or more tones played together. While many different chords are used in music, some are heard as more attractive (consonant) than others. We have previously suggested that, for reasons of biological advantage, human tonal preferences can be understood in terms of the spectral similarity of tone combinations to harmonic human vocalizations. Using the chromatic scale, we tested this theory further by assessing the perceived consonance of all possible dyads, triads, and tetrads within a single octave. Our results show that the consonance of chords is predicted by their relative similarity to voiced speech sounds. These observations support the hypothesis that the relative attraction of musical tone combinations is due, at least in part, to the biological advantages that accrue from recognizing and responding to conspecific vocal stimuli.

Practical diagnostic approaches to composite plasma cell neoplasm and low grade B-cell lymphoma/clonal infiltrates in the bone marrow.

Composite plasma cell neoplasm (PCN) and low grade B-cell lymphoma (B-NHL) in the bone marrow are uncommon and raise the differential diagnosis of B-NHL with plasmacytic differentiation and PCN with lymphoplasmacytic morphology. This can be a challenging differential diagnosis, and the distinctions are important because of differences in management. We report five cases of composite PCN with B-NHL or clonal B-cell infiltrates involving the bone marrow. By using multiple different diagnostic modalities, including immunophenotyping by flow cytometry and immunohistochemistry, cytogenetic analysis and IGH gene rearrangement studies by polymerase chain reaction, we were able to distinguish two distinct clonally unrelated neoplasms in all cases. We describe the utility and pitfalls of these different diagnostic modalities. Flow cytometric analysis with a panel of antibodies that includes CD19, CD56, CD138, CD45 and other aberrant markers commonly expressed by PCN will allow identification of clonally unrelated PCN and B-NHL in a composite neoplasm, and distinguish them from B-NHL with plasmacytic differentiation and PCN with lymphoplasmacytic morphology. Cytogenetic and molecular analyses can give false-negative or false-positive results. In summary, a multimodal approach utilizing these different tools, including clinical data, should be used to arrive at the correct diagnosis.

MYC protein expression in primary diffuse large B-cell lymphoma of the central nervous system.

Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a rare, aggressive subtype of DLBCL, the biology of which is poorly understood. Recent studies have suggested a prognostic role of MYC protein expression in systemic DLBCL, but little is known about the frequency and significance of MYC protein expression in CNS DLBCL. Hence, we investigated MYC protein expression profiles of CNS DLBCL and assessed the relationship between MYC expression and a variety of histopathologic, immunophenotypic, genetic, and clinical features. Fifty-nine CNS DLBCL diagnosed at our institution over the past 13 years were evaluated. The majority of cases (80%) showed centroblastic morphology, and 12 (20%) displayed a perivascular pattern of infiltration. According to the Hans criteria, 41 (69%) cases had a non-germinal center B-cell and 18 (31%) had a germinal center B-cell cell-of-origin (COO) phenotype. Mean MYC protein expression was 50% (median: 50%, range: 10-80%). Forty-three cases (73%) showed MYC overexpression (≥ 40%), and 35 (60%) showed MYC/BCL2 coexpression. MYC overexpression was seen in the single case harboring MYC translocation and in the cases showing increased copies of MYC (27%); however, no significant difference in mean MYC expression was seen between groups harboring or lacking MYC aberrations. In our series, age was associated with a significantly increased risk of death, and the perivascular pattern of infiltration was associated with a significantly increased risk of disease progression. Neither MYC expression (with or without BCL2 coexpression) nor other variables, including COO subtype were predictive of clinical outcome. Our findings indicate that the proportion of CNS DLBCL overexpressing MYC is higher compared to systemic DLBCL, and MYC overexpression appears to be independent of genetic MYC abnormalities. Thus, MYC expression and other immunophenotypic markers used for prognostication of systemic DLBCL might not apply to CNS DLBCL due to differences in disease biology.

C-myc protein expression in B-cell acute lymphoblastic leukemia, prognostic significance?

C-myc protein expression has been studied in mature B-cell lymphomas and overexpression has been associated with poor prognosis. We sought to determine the prognostic significance of c-myc protein expression in B-ALL. We found ≥ 20% c-myc expression to predict risk of persistent disease in all age groups (odds ratio 7.487, p=0.013). There was no statistically significant association between c-myc expression and risk of relapse or death in our study. Routine c-myc immunostaining may help identify higher risk patients and guide management of B-ALL. Additional studies are needed to further determine the molecular mechanisms and role of c-myc expression in B-ALL.

CD30-positive lymphoproliferative disorders arising after regional therapy for recurrent melanoma: a report of two cases and analysis of CD30 expression.

BACKGROUND AND OBJECTIVES: Primary cutaneous CD30-positive T-cell lymphoproliferative disorders (CD30(+) LPD), including primary cutaneous anaplastic large cell lymphoma (CALCL) and lymphomatoid papulosis (LyP), comprise the second most common group of cutaneous T-cell lymphomas (CTCL). The etiology of these disorders is not known. Isolated limb perfusion (ILP) and isolated limb infusion (ILI) are forms of regional chemotherapy used to treat recurrent tumors of the extremity, most commonly, melanoma. Secondary malignancy following regional therapy is rarely reported. METHODS/RESULTS: We identified two cases of CD30(+) LPD arising in the affected limbs of patients treated with ILP/ILI. We subsequently performed CD30 immunohistochemical stains on 11 pre- and post-treatment skin specimens from melanoma patients treated with ILP/ILI and found that 5 of the 11 cases showed an increase in CD30(+) lymphocytes following ILP/ILI. CONCLUSIONS: We hypothesize that ILP/ILI causes upregulation of CD30 expression in the extremities of treated patients, and suggest that this may be a marker of treatment response. However, a rare but long-term effect may be an increased risk of T-cell cutaneous lymphoproliferative disease in the affected limb.

A tumor suppressor function for the lipid phosphatase INPP4B in melanocytic neoplasms.

The phosphoinositide-3 kinase (PI3K) pathway is deregulated in a significant proportion of melanomas, and PI3K pathway activation in combination with constitutively active mitogen-activated protein kinase signaling shows synergistic effects in the process of melanoma tumorigenesis. Recently, a tumor suppressor function for the lipid phosphatase inositol polyphosphate 4-phosphatase type II (INPP4B) has been described in breast and prostate cancers, with impact on PI3K signaling output. Given the importance of PI3K pathway activity for melanoma formation and growth, we aimed to assess the role of INPP4B in melanocytic tumors. Our studies in native tumors suggest that decreased INPP4B expression is an event correlating with tumor progression in melanocytic neoplasms. We further demonstrate that INPP4B regulates PI3K/Akt signaling and exerts a tumor suppressor effect, impacting the proliferative, invasive, and tumorigenic capacity of melanoma cells. INPP4B expression in melanocytic neoplasms may therefore have potential as a biomarker for disease progression and as a modulator for the prediction of treatment outcome.

Expression of immune inhibitory receptor ILT3 in acute myeloid leukemia with monocytic differentiation.

BACKGROUND: The diagnosis of AML with monocytic differentiation is limited by the lack of highly sensitive and specific monocytic markers. Immunoglobulin-like transcript 3 (ILT3) is an immune inhibitory receptor expressed by myelomonocytic cells and at high levels by tolerogenic dendritic cells. METHODS: Using flow cytometry, we analyzed the expression of ILT3 in 37 patients with AML and 20 patients with no detectable disease. RESULTS: We showed that ILT3 was expressed in all cases of AML displaying monocytic differentiation (FAB M4/M5; N = 18), but not in AML M1/M2 and M3 (N = 19; P < 0.0001). Co-expression of ILT3 and immature cell markers, such as CD34 and CD117, was observed in monoblastic leukemia. ILT3 expression was preserved after treatment in M4/M5 patients with refractory or relapsed disease. ILT3 expression was associated with the presence of cytogenetic abnormalities linked to an intermediate prognosis (P = 0.001). Rare CD45dimCD34+CD117+ILT3+ cells were identified in noninvolved bone marrow, suggesting that ILT3 expression is acquired at an early stage by normal myelomonocytic precursors. CONCLUSIONS: ILT3 is a highly sensitive and specific marker which distinguishes AML with monocytic differentiation from other types of AML. Testing of ILT3 expression should be incorporated into the initial diagnostic work-up and monitoring of patients with AML.