RESUMO
Many malignant hematologic neoplasms can directly and indirectly involve the skin with lesions that are disfiguring, painful, and compromise integumentary function. The majority of lymphomas that directly infiltrate the skin are of T-cell origin but B-cell lymphomas, and other hematologic neoplasms, including acute myeloid and lymphoblastic leukemias, can also have cutaneous involvement, whereas some have an indolent course, eg, mycosis fungoides and marginal zone lymphoma, and easily respond to localized therapy with overall survival (OS) measured in years to decades. Others have a more clinically aggressive course, eg, natural killer (NK)/T-cell lymphoma and diffuse large B-cell lymphoma, leg type, that require high-dose multimodality therapy, and have an OS measured in months to a few years. Lymphoma can also lead to secondary cutaneous alterations, including a variety of paraneoplastic phenomena. We present an overview of direct and indirect skin involvement by malignant lymphocytes and other hematologic neoplasms. We also describe molecular and immunophenotypic aspects of these diseases and how they are treated.
Assuntos
Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/classificação , Neoplasias Hematológicas/imunologia , Humanos , Linfoma de Células B/etiologia , Linfoma de Células B/patologia , Linfoma de Células T/patologia , Micose Fungoide/patologia , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/secundárioRESUMO
The oncogenic phosphatidylinositol 3-kinase-AKT-mammlian target of rapamycin pathway (PI3K-AKT-mTOR) pathway is known to be activated in uterine smooth muscle tumors, and Stathmin 1 (STMN1) expression has been identified as a marker of PI3K-AKT-mTOR pathway activation. We hypothesized that STMN1 may have some diagnostic utility and explored how well STMN1 expression correlated with histologic classifications of uterine smooth muscle tumors into benign and malignant groupings. 84 smooth muscle tumors were assessed for STMN1 expression by immunohistochemistry. These included spindle cell leiomyosarcoma (n=32), conventional spindle cell leiomyomas (n=30), atypical (symplastic) leiomyoma (n=5), cellular leiomyoma (n=7), smooth muscle tumor of uncertain malignant potential (n=4), mitotically active leiomyomas (n=2), benign metastasizing leiomyoma (n=3), and cotyledonoid dissecting leiomyoma (n=1). All spindle cell leiomyosarcomas were positive (32/32 positive; 100%) as compared with conventional leiomyomata (11/30; 37%) (P<0.0001). The average immunohistochemical score (0-12+, reflective of intensity and extent) for leiomyosarcomas was 8.7 (±1.43) whereas the conventional leiomyomata average score was 1.6 (±1.07) (P<0.0001). This difference in scores was reflected in the patterns of expression: leiomyosarcomas were predominantly strongly and diffusely positive whereas leiomyomata were predominantly weakly, albeit diffusely positive when expression was present. The sensitivity of STMN1 expression for leiomyosarcomas was 100%. However, the specificity was found to be only 55% (CI=43-68%). The negative and positive predictive values for leiomyosarcomas were 100% and 52% respectively. The odds ratio (OR) for any STMN1 expression in predicting a spindle cell leiomyosarcoma diagnosis from this dataset was highly significant (OR=144, P=0.0006). Thirteen non-smooth muscle tumors that involved the uterus all showed at least focal STMN1 immunoreactivity. In summary, STMN1 is a highly sensitive marker for leiomyosarcoma but is suboptimally specific for diagnostic purposes. The 100% negative predictive value for leiomyosarcoma may offer some diagnostic utility in a small sample, since the absence of STMN1 immunoreactivity in a putative leiomyosarcoma is a strong argument against this diagnostic possibility.
Assuntos
Biomarcadores Tumorais/análise , Imuno-Histoquímica , Leiomioma/química , Leiomiossarcoma/química , Estatmina/análise , Neoplasias Uterinas/química , Diagnóstico Diferencial , Feminino , Humanos , Leiomioma/classificação , Leiomioma/patologia , Leiomiossarcoma/classificação , Leiomiossarcoma/patologia , Valor Preditivo dos Testes , Prognóstico , Neoplasias Uterinas/classificação , Neoplasias Uterinas/patologiaRESUMO
AIM: Previous studies showed that CD200 expression is a prognostic factor for plasma cell myeloma (PCM), but the prognostic effect is conflicting between studies. We studied CD200 protein expression and the stability of expression in PCM to clarify its potential utility in diagnosis, prognosis and monitoring of disease. METHOD: CD200 expression was studied in 77 cases of PCM by immunohistochemistry on paraffin sections from decalcified bone marrow biopsies. RESULT: There were 16 newly diagnosed cases and 61 post-treatment cases from 54 patients: 37 men and 17 women, with a median age of 62â years (range, 4188â years). CD200 demonstrated moderate to strong membrane expression in positive cases. Fifty-six of 77 cases (73%) showed CD200 expression. Twenty of the 22 (91%) patients with serial specimens demonstrated stable CD200 expression (n=15) or lack of CD200 expression (n=5). One patient lost CD200 expression, while another one gained CD200 expression during treatment. The clinical, pathologic and cytogenetic features between the CD200+ group and the CD200− group were similar in most instances. However, CD200 expression was associated with lower serum ß2-microglobulin (p=0.03). There was no significant difference in overall survival and progression-free survival between the CD200+ and CD200− patients (p>0.05). CONCLUSIONS: CD200 is expressed in a majority of PCM cases, and the expression is stable during the treatment process. Therefore, immunohistochemical expression of CD200 is a useful marker for the diagnosis and follow-up of PCM.
Assuntos
Antígenos CD/análise , Mieloma Múltiplo/imunologia , Plasmócitos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biópsia , Exame de Medula Óssea , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Plasmócitos/patologia , Valor Preditivo dos Testes , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Lower serum vitamin D (25(OH)D) among individuals with African ancestry is attributed primarily to skin pigmentation. However, the influence of genetic polymorphisms controlling for skin melanin content has not been investigated. Therefore, we investigated differences in non-summer serum vitamin D metabolites according to self-reported race, genetic ancestry, skin reflectance and key pigmentation genes (SLC45A2 and SLC24A5). MATERIALS AND METHODS: Healthy individuals reporting at least half African American or half European American heritage were frequency matched to one another on age (+/- 2 years) and sex. 176 autosomal ancestry informative markers were used to estimate genetic ancestry. Melanin index was measured by reflectance spectrometry. Serum vitamin D metabolites (25(OH)D3, 25(OH)D 2 and 24,25(OH)2D3) were determined by high performance liquid chromatography (HPLC) tandem mass spectrometry. Percent 24,25(OH)2D3 was calculated as a percent of the parent metabolite (25(OH)D3). Stepwise and backward selection regression models were used to identify leading covariates. RESULTS: Fifty African Americans and 50 European Americans participated in the study. Compared with SLC24A5 111Thr homozygotes, individuals with the SLC24A5 111Thr/Ala and 111Ala/Ala genotypes had respectively lower levels of 25(OH)D3 (23.0 and 23.8 nmol/L lower, p-dominant=0.007), and percent 24,25(OH)2D3 (4.1 and 5.2 percent lower, p-dominant=0.003), controlling for tanning bed use, vitamin D/fish oil supplement intake, race/ethnicity, and genetic ancestry. Results were similar with melanin index adjustment, and were not confounded by glucocorticoid, oral contraceptive, or statin use. CONCLUSIONS: The SLC24A5 111Ala allele was associated with lower serum vitamin 25(OH)D3 and lower percent 24,25(OH)2D3, independently from melanin index and West African genetic ancestry.