RESUMEN
ABSTRACT: Atypical fibroxanthoma (AFX) is a neoplasm that most commonly occurs on sun-damaged skin of the head and neck in elderly patients and that usually exhibits indolent clinical behavior with complete excision. The granular cell variant of AFX demonstrates overlapping histopathologic features with dermal non-neural granular cell tumor (NNGCT), which typically arises on the extremities of young to middle aged adults with rare reports of regional metastasis. A subset of NNGCT harbors ALK rearrangements and expresses ALK by immunohistochemistry. Here, we present 2 cases of granular cell AFX occurring on the scalp of males aged 73 and 87 with ALK expression by immunohistochemistry and no evidence of an ALK rearrangement on fluorescence in situ hybridization, representing a diagnostic pitfall for NNGCT.
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Quinasa de Linfoma Anaplásico/metabolismo , Tumor de Células Granulares/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Cuero Cabelludo , Neoplasias Cutáneas/metabolismo , Xantomatosis/metabolismo , Anciano , Anciano de 80 o más Años , Quinasa de Linfoma Anaplásico/genética , Reordenamiento Génico , Tumor de Células Granulares/genética , Tumor de Células Granulares/patología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunohistoquímica , Masculino , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Xantomatosis/patologíaRESUMEN
Children with chronic myeloid leukemia (CML) tend to present with higher white blood counts and larger spleens than adults with CML, suggesting that the biology of pediatric and adult CML may differ. To investigate whether pediatric and adult CML have unique molecular characteristics, we studied the transcriptomic signature of pediatric and adult CML CD34+ cells and healthy pediatric and adult CD34+ control cells. Using high-throughput RNA sequencing, we found 567 genes (207 up- and 360 downregulated) differentially expressed in pediatric CML CD34+ cells compared to pediatric healthy CD34+ cells. Directly comparing pediatric and adult CML CD34+ cells, 398 genes (258 up- and 140 downregulated), including many in the Rho pathway, were differentially expressed in pediatric CML CD34+ cells. Using RT-qPCR to verify differentially expressed genes, VAV2 and ARHGAP27 were significantly upregulated in adult CML CD34+ cells compared to pediatric CML CD34+ cells. NCF1, CYBB, and S100A8 were upregulated in adult CML CD34+ cells but not in pediatric CML CD34+ cells, compared to healthy controls. In contrast, DLC1 was significantly upregulated in pediatric CML CD34+ cells but not in adult CML CD34+ cells, compared to healthy controls. These results demonstrate unique molecular characteristics of pediatric CML, such as dysregulation of the Rho pathway, which may contribute to clinical differences between pediatric and adult patients.
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D-cyclin proteins play a central role in cell-cycle regulation and are involved in the pathogenesis of lymphomas. In mantle-cell lymphoma, the t(11;14) translocation leads to overexpression of cyclin-D1, in addition to which cyclin-D1-negative mantle-cell lymphoma that overexpress cyclin-D2 or D3 have also been described. Although cyclin-D2 and D3 have been implicated in the prognosis of specific lymphoma subtypes, a thorough characterization of D-cyclin protein expression in human hematolymphoid neoplasia has not been reported. To evaluate the tissue expression patterns of D-cyclins, particularly D2 and D3, in normal and neoplastic hematolymphoid tissues, we optimized the commercially available antibodies for D-cyclins for use on paraffin-embedded tissue and stained tissue microarrays of over 700 patient samples. Our results show that cyclin-D2 and D3 proteins are expressed in many more lymphoma subtypes than cyclin-D1. Cyclin-D1, D2 and D3 were expressed in 100, 22 and 6% of mantle-cell lymphomas and 2, 49 and 20% of diffuse large B-cell lymphomas. Fluorescence in situ hybridization studies confirmed the presence of the CCND1/IGH translocation in the majority of mantle-cell lymphoma, but not in diffuse large B-cell lymphoma that expressed cyclin-D1 protein. In addition, a subset of follicular, marginal zone, lymphoplasmacytic, lymphoblastic, classical Hodgkin, mature T-cell and natural killer cell lymphomas and acute myeloid leukemias also expressed cyclin-D2 and D3. These data support the hypothesis that dysregulation of cell-cycle control by D-cyclins contribute to the pathogenesis of hematolymphoid neoplasia, and suggest a potential role for these proteins in the prognostic and therapeutic aspects of these diseases. For diagnostic purposes, however, the expression of D-cyclin proteins should be interpreted with caution in the subclassification of lymphoma types.
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Ciclina D2/metabolismo , Ciclina D3/metabolismo , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células del Manto/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Ciclina D1/genética , Ciclina D2/genética , Ciclina D3/genética , Femenino , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Inmunohistoquímica , Hibridación Fluorescente in Situ , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células del Manto/patología , Masculino , Análisis de Matrices Tisulares , Translocación GenéticaRESUMEN
Accurate assessment of Her-2/neu (erb-b2) status in breast carcinoma is essential for therapy planning. Clinical assays are targeted at protein overexpression (immunohistochemical analysis) or gene amplification (fluorescence in situ hybridization [FISH]). Cases with aberrant FISH signal patterns are problematic and may lead to underreporting of Her-2/neu amplification. We performed FISH with additional chromosome 17 probes, SMS (Smith-Magenis syndrome critical region) and RARA (retinoic acid receptor), on 7 cases with unusual Her-2/CEP17 (chromosome 17 centromere control probe) results to assess whether different measurements of chromosome 17 copy number might clarify the Her-2/neu amplicon status. Although the Her-2/CEP17 ratio scores were within normal range (<2.0), the Her-2/SMS or Her-2/RARA ratio revealed amplification of Her-2/neu in 5 of 7 cases. Immunohistochemical analysis demonstrated Her-2/neu protein overexpression in the same 5 cases only. We describe novel application of SMS/RARA FISH probes for assessing cases with complex Her-2/CEP17 FISH patterns. Such additional data, correlated with immunohistochemical analysis, may help guide therapy in patients with breast carcinoma.
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Neoplasias de la Mama/patología , Cromosomas Humanos Par 17/genética , Neoplasias Ováricas/patología , Receptor ErbB-2/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Centrómero/genética , Aberraciones Cromosómicas , Femenino , Amplificación de Genes , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Receptor ErbB-2/análisis , Receptores de Ácido Retinoico/genética , Receptor alfa de Ácido RetinoicoRESUMEN
We present an unusual case of gliosarcoma containing numerous islands of well-differentiated melanocytes in a 65 year-old man. Melanocytic differentiation of medulloblastomas is well described, and it has also rarely been reported in low-grade glial neoplasms. Histologic features and immunophenotyping are helpful in differentiating divergent differentiation in a gliosarcoma from melanoma. To our knowledge, this is the first description of a gliosarcoma with melanocytic differentiation. Awareness of the phenomenon of melanocytic differentiation within primary neuroepithelial and glial neoplasms is important to prevent the misdiagnosis of these tumors such as metastatic melanoma or primary melanocytic neoplasms of the CNS.