Atypical development of configural face recognition in children with autism, Down syndrome and Williams syndrome.

BACKGROUND: Configural processing in face recognition is a sensitivity to the spacing between facial features. It has been argued both that its presence represents a high level of expertise in face recognition, and also that it is a developmentally vulnerable process. METHOD: We report a cross-syndrome investigation of the development of configural face recognition in school-aged children with autism, Down syndrome and Williams syndrome compared with a typically developing comparison group. Cross-sectional trajectory analyses were used to compare configural and featural face recognition utilising the 'Jane faces' task. Trajectories were constructed linking featural and configural performance either to chronological age or to different measures of mental age (receptive vocabulary, visuospatial construction), as well as the Benton face recognition task. RESULTS: An emergent inversion effect across age for detecting configural but not featural changes in faces was established as the marker of typical development. Children from clinical groups displayed atypical profiles that differed across all groups. CONCLUSION: We discuss the implications for the nature of face processing within the respective developmental disorders, and how the cross-sectional syndrome comparison informs the constraints that shape the typical development of face recognition.

One Patient, Two Uncommon B-Cell Neoplasms: Solitary Plasmacytoma following Complete Remission from Intravascular Large B-Cell Lymphoma Involving Central Nervous System.

Second lymphoid neoplasms are an uncommon but recognized feature of non-Hodgkin's lymphomas, putatively arising secondary to common genetic or environmental risk factors. Previous limited evaluations of clonal relatedness between successive mature B-cell malignancies have yielded mixed results. We describe the case of a man with intravascular large B-cell lymphoma involving the central nervous system who went into clinical remission following immunochemotherapy and brain radiation, only to relapse 2 years later with a plasmacytoma of bone causing cauda equina syndrome. The plasmacytoma stained strongly for the cell cycle regulator cyclin D1 on immunohistochemistry, while the original intravascular large cell lymphoma was negative, a disparity providing no support for clonal identity between the 2 neoplasms. Continued efforts atcataloging and evaluating unique associations of B-cell malignancies are critical to improving understanding of overarching disease biology in B-cell malignancies.

Does the proliferation fraction help identify mature B cell lymphomas with double- and triple-hit translocations?

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: Immunostaining for Ki67 is not a useful approach to prescreen B cell lymphomas for MYC(+) double/triple translocations.

Angioimmunoblastic T-cell lymphoma with hyperplastic germinal centres (pattern 1) shows superior survival to patterns 2 and 3: a meta-analysis of 56 cases.

AIMS: Angioimmunoblastic T-cell lymphoma (AITL) may present in patterns 1, 2 or 3, representing those with hyperplastic, regressed or effaced germinal centres (GCs), respectively, but the prognostic utility of this subclassification has not been previously validated. METHODS AND RESULTS: Twenty-five cases of AITL were reviewed immunohistologically and with in-situ hybridization for Epstein-Barr virus-encoded RNA and polymerase chain reaction for T-cell receptor gamma and immunoglobulin heavy chain clonality and followed for up to 120 months. Four cases had conventional hyperplastic GCs, two had floral GCs, and one had progressively transformed GCs, consistent with pattern 1 and one additional case had hyalinized GCs, consistent with pattern 2. The remaining 17 (pattern 3) cases lacked morphologically discernible GCs. The Kaplan-Meier survival distribution of pattern 1 cases (5-year survival 83%) was superior to that of pattern 2 and 3 cases [5-year-survival 36% (P = 0.0417)] only when combined with the 31 cases, seven of which were pattern 1, that Attygalle et al. had followed for up to 247 months and previously published. Furthermore, the development of B-lineage (classical Hodgkin or diffuse large-cell) lymphoma was associated exclusively with pattern 3 (P = 0.0057). CONCLUSIONS: Pattern 1 represents an indolent phase/grade of AITL, unassociated with the development of secondary B-lineage lymphoma and uninfluenced by treatment regimen.

MicroRNA-mediated down-regulation of PRDM1/Blimp-1 in Hodgkin/Reed-Sternberg cells: a potential pathogenetic lesion in Hodgkin lymphomas.

PRDM1/Blimp-1, a master regulator in terminal B-cell differentiation, has been recently identified as a tumor suppressor target for mutational inactivation in diffuse large B-cell lymphomas of the activated B-cell type. Our studies here demonstrate that PRDM1/blimp-1 is also a target for microRNA (miRNA)-mediated down-regulation by miR-9 and let-7a in Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL). MiRNA expression profiling by direct miRNA cloning demonstrated that both of these miRNAs are among the most highly expressed in cultured HRS cells. These miRNAs functionally targeted specific binding sites in the 3' untranslated region of PRDM1/blimp-1 mRNA and repressed luciferase reporter activities through repression of translation. In addition, high levels of miR-9 and let-7a in HL cell lines correlated with low levels of PRDM1/Blimp-1. Similar to their in vitro counterparts, the majority of HRS cells in primary HL cases showed weak or no PRDM1/Blimp-1 expression. Over-expression of miR-9 or let-7a reduced PRDM1/Blimp-1 levels in U266 cells by 30% to 50%, whereas simultaneous inhibition of their activities in L428 cells resulted in an approximately 2.6-fold induction in PRDM1/Blimp-1. MiRNA-mediated down-regulation of PRDM1/Blimp-1 may contribute to the phenotype maintenance and pathogenesis of HRS cells by interfering with normal B-cell terminal differentiation, thus representing a novel molecular lesion, as well as a potential therapeutic target in HL.

Expression of Bcl-x in normal skin and benign cutaneous adnexal tumors.

BACKGROUND: Bcl-x appears to have an antiapoptotic role in the epidermis. Little is known about the expression of Bcl-x in cutaneous adnexal structures and benign cutaneous adnexal tumors. METHODS: Tissues from 31 cases of benign cutaneous adnexal tumors (five trichofolliculomas, five trichoepitheliomas, two sebaceous adenomas, five apocrine hidradenomas, five eccrine poromas, five eccrine spiradenomas, and four syringomas) were immunostained for Bcl-x. RESULTS: Strong staining for Bcl-x was seen in cells of the epidermal granular layer and inner root sheath of hair follicles. Sebaceous gland cells showed strong staining. Apocrine gland cells showed weak to moderate staining. No staining was seen in eccrine gland cells. The basaloid cells of trichofolliculomas and trichoepitheliomas showed no staining. In sebaceous adenomas, the sebaceous cells showed strong staining while the basaloid cells were negative. The cells of apocrine hidradenomas showed patchy weak staining. No staining was seen in eccrine poromas, eccrine spiradenomas, and syringomas. CONCLUSIONS: The degree of Bcl-x expression in cutaneous adnexal glandular structures appears to be related to their mode of secretion, being strongest in cells with apoptotic degradation of the entire cell (sebocytes). This pattern is recapitulated in the corresponding benign cutaneous adnexal tumors. Bcl-x may be useful in identifying cells with sebaceous differentiation in poorly differentiated adnexal tumors.

Unravelling the mystery in a case of persistent ACTH-independent Cushing's syndrome.

INTRODUCTION: We present a rare variety of adrenocorticotrophic hormone (ACTH)-independent Cushing's syndrome known as primary pigmented nodular adrenocortical disease (PPNAD). CLINICAL PICTURE: The patient initially underwent unilateral adrenalectomy for what was thought to be a left adrenal adenoma. OUTCOME: Partial resolution of symptoms and demonstrable persistent hypercortisolism after surgery prompted further evaluation with findings leading to the diagnosis of Carney complex. A review of the adrenal histology was consistent with PPNAD. CONCLUSION: This entity of PPNAD, which has rarely been reported in Asians, forms part of the Carney complex. The diagnosis may not be simple and straightforward, as illustrated in this patient.

Unravelling the mystery in a case of persistent ACTH-independent Cushing's syndrome

<p><b>INTRODUCTION</b>We present a rare variety of adrenocorticotrophic hormone (ACTH)-independent Cushing's syndrome known as primary pigmented nodular adrenocortical disease (PPNAD).</p><p><b>CLINICAL PICTURE</b>The patient initially underwent unilateral adrenalectomy for what was thought to be a left adrenal adenoma.</p><p><b>OUTCOME</b>Partial resolution of symptoms and demonstrable persistent hypercortisolism after surgery prompted further evaluation with findings leading to the diagnosis of Carney complex. A review of the adrenal histology was consistent with PPNAD.</p><p><b>CONCLUSION</b>This entity of PPNAD, which has rarely been reported in Asians, forms part of the Carney complex. The diagnosis may not be simple and straightforward, as illustrated in this patient.</p>

Long-term follow-up of pediatric cardiac transplant recipients on a steroid-free regime: the role of endomyocardial biopsy.

BACKGROUND: Endomyocardial biopsy is used in long-term follow-up of cardiac transplant recipients to detect sub-clinical rejection. The value of this for adults and children on triple-drug immunosuppression has been disputed. We investigated its value in children maintained on a steroid-free regime. METHODS: We used a retrospective review of annual surveillance biopsy results from children younger than 13 years at the time of cardiac transplant. RESULTS: In a series of 40 children older than 10 years, we found no evidence of rejection in 88/130 (67.7%) biopsies; 41/130 (31.5%) showed grade 1A rejection, and 1/130 (0.8%) showed grade 1B rejection. No grade 2, 3, or 4 biopsies were found. Nine patients with 1A rejection had subsequent grade 0 biopsies, without any adjustment in treatment. Seven children had treatment changes and repeat biopsies because of grade 1A biopsies. CONCLUSION: Significant late rejection is rare even in children on steroid-free maintenance. It is unlikely to be detected unexpectedly, and the practice of indefinite routine biopsy in children who are well is not justified. Future use should focus on individuals at higher risk of rejection.