RESUMO
Pleomorphic fibroma is a rare benign cutaneous neoplasm characterized by spindle-shaped cells and multinucleated giant cells scattered throughout collagenous stroma. These morphologic features can lead to diagnostic confusion, including atypical lipomatous tumor as one consideration. In contrast to atypical lipomatous tumor, previous studies have found pleomorphic fibroma to be negative for MDM2 immunohistochemical staining and MDM2 gene amplification. Here, we present a case of pleomorphic fibroma of skin with nuclear MDM2 immunoreactivity in the absence of MDM2 gene amplification, underscoring the superiority of fluorescence in situ hybridization as a diagnostic test in this differential diagnosis. The RB1 locus is also explored for differential diagnosis with pleomorphic/spindle cell lipoma and related entities.
Assuntos
Biomarcadores Tumorais/análise , Histiocitoma Fibroso Benigno/diagnóstico , Proteínas Proto-Oncogênicas c-mdm2/biossíntese , Neoplasias Cutâneas/diagnóstico , Feminino , Histiocitoma Fibroso Benigno/patologia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Lipoma/diagnóstico , Proteínas Proto-Oncogênicas c-mdm2/análise , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
The legitimacy and etiology of Dissociative Identity Disorder (DID) remains a controversial topic within Psychiatry. The two schools of thought are the Post-Traumatic Model (PTM) and the Socio-Cognitive Model (SCM). This case highlights the validity of PTM in an individual who suffered severe and prolonged physical, psychological, and sexual abuse from 2 years old through adulthood. The reported abuse was corroborated and proven on two separate occasions via medical professionals/rape kit and the police. This resulted in the incarceration of one of her abusers. The only way for the patient to cope with the trauma she suffered was to dissociate, which resulted in the development of four full identity alters. In addition to being diagnosed with DID, the patient has been diagnosed with Major Depressive Disorder (MDD), Post-Traumatic Stress Disorder (PTSD), and chronic suicidality. Unable to manage the suicidal ideations and MDD after nearly 10 years of therapy and psychiatric medications, the patient was referred for Electroconvulsive Therapy (ECT). Upon receiving ECT weekly for 2 years, the patient reported having "lost the others." As ECT progressed she went from having four alters to no alters and at the time of this report only being able to vaguely hear alter #4. With the integration of these alters she had access to the memories and pain that the alters had protected her from. Prior to losing the alters, her long-term memory was impaired by dissociative processes. Her long-term memory was also impaired because when one of the alters was in control of consciousness only that alter remembered what had happened during that time, unless that alter shared what had happened with one or more of the others. It is unclear if frequent ECT was the catalyst that lead to the integration of her alters however, integration finally began following prolonged ECT. This case highlights the importance of the PTM as an etiological description for DID and the importance of mental health providers further studying and researching the effects of ECT on patients with chronic MDD, PTSD, and suicidal intent, especially if these are comorbid with DID.
RESUMO
Nordihydroguaiaretic acid (NDGA) is a plant lignan produced by Larrea tridentata, the creosote bush of the American southwest. In this report we examine the mechanism underlying the ability of NDGA to inhibit TNF-induced apoptosis. Our results show that NDGA blocks many key indicators of apoptosis. Caspase cleavage, mitochondrial inactivation, externalization of phosphatidyl serine, and (51)Cr-release were all blocked by low micromolar concentrations of NDGA. NDGA also inhibited the cPLA(2)-dependent release of (3)H-arachidonic acid. We investigated this activity and found that NDGA prevented the rise in intracellular calcium necessary for the apoptotic activation of cPLA(2). On the other hand, NDGA did not interfere with the TNF-induced phosphorylation of cPLA(2), indicating that NDGA does not block all TNF-dependent signaling. Finally, we asked whether the anti-apoptotic effect of NDGA could be attributed to its anti-oxidant activity. Comparison with the effects of butylated hydroxyanisole (BHA) did not completely support this hypothesis. While BHA strongly inhibited caspase activation and partially blocked the release of (51)Cr, it was unable to significantly block the calcium response or the release of (3)H-arachidonic acid associated with TNF-induced apoptosis. The anti-oxidant activity of NDGA may, therefore, explain some but not all of its anti-apoptotic activity.
Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Masoprocol/farmacologia , Fosfolipases A/antagonistas & inibidores , Fator de Necrose Tumoral alfa/farmacologia , Animais , Ácido Araquidônico/metabolismo , Western Blotting , Hidroxianisol Butilado/farmacologia , Caspases/metabolismo , Linhagem Celular , Radioisótopos de Cromo , Ativação Enzimática/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Imunoprecipitação , Masculino , Camundongos , Microscopia de Contraste de Fase , Fosfatos/metabolismoRESUMO
Clear cell papillary renal cell carcinoma is increasingly recognized as a distinct tumor with unique morphology, immunohistochemistry, and cytogenetics. Histopathology often mimics clear cell renal cell carcinoma; however, metastasis has not been reported, emphasizing the clinical value of recognizing these likely nonaggressive tumors. We studied tumors with borderline morphology of clear cell papillary renal cell carcinoma, utilizing immunohistochemistry and fluorescence in situ hybridization or karyotyping. Tumors from 22 patients (ages 33 to 82 y) were analyzed. Clear cell papillary renal cell carcinoma-like morphology varied from 10% to 90% of the tumor (median 25%). Sources of resemblance included: branched glands (95%), nuclear alignment (68%), small papillary tufts (32%), focal branching papillae (27%), and prominent papillary structures (9%). Carbonic anhydrase IX uniformly revealed diffuse positivity. Staining for cytokeratin 7 (CK7) was focal (64%) or negative (18%) in most tumors (82%); however, >50% labeling was present in 4 (18%). Reactivity for both CD10 and α-methyl-acyl-CoA-racemase (AMACR) was usually present (median 80% and 60% of cells). Seven tumors showed reactivity for high-molecular weight keratin (32%). Chromosome 3p loss was confirmed in 15 tumors (68%), including 4/7 with labeling for high-molecular weight keratin or >50% reactivity for CK7. A discordant immunohistochemical pattern typically correlates with loss of material from chromosome 3p in tumors with incomplete morphology of clear cell papillary renal cell carcinoma, supporting classification as clear cell renal cell carcinoma. Diffuse labeling for CK7 can uncommonly be observed in clear cell renal cell carcinomas confirmed to have chromosome 3p loss, although these do not exhibit the expected staining pattern of clear cell papillary renal cell carcinoma, including positivity for CD10 and AMACR.
Assuntos
Biomarcadores Tumorais , Carcinoma Papilar/diagnóstico , Carcinoma de Células Renais/diagnóstico , Análise Citogenética , Imuno-Histoquímica , Neoplasias Renais/diagnóstico , Neoplasias Complexas Mistas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Carcinoma Papilar/química , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Carcinoma de Células Renais/química , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Diagnóstico Diferencial , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Indiana , Cariotipagem , Neoplasias Renais/química , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Michigan , Pessoa de Meia-Idade , Neoplasias Complexas Mistas/química , Neoplasias Complexas Mistas/genética , Neoplasias Complexas Mistas/patologia , Valor Preditivo dos TestesRESUMO
Donor cell neoplasms are rare complications of treatment regimens that involve stem cell transplantation for hematological malignancies, myelodysplastic processes, or certain genetic or metabolic disorders. We report a case of donor cell leukemia in a pediatric patient with a history of acute myeloid leukemia that manifested as recurrent AML FAB type M5 fourteen months after umbilical cord blood transplantation. Although there was some immunophenotypic drift from the patient's original AML and their posttransplant presentation, the initial pathological impression was of recurrent disease. Bone marrow engraftment analysis by multiplex PCR of short tandem repeat markers performed on the patient's diagnostic specimen showed complete engraftment by donor cells, with a loss of heterozygosity in the donor alleles on chromosome 7. This led to the reinterpretation of this patient's disease as donor-derived leukemia. This interpretation was supported by a routine karyotype and fluorescence in situ hybridization analysis showing loss of chromosome 7 and a male (donor) chromosome complement in this female patient. Also noted was a loss of the patient's presenting chromosomal abnormality, t(11;19)(q23;p13). This case highlights the need for close coordination between all aspects of clinical testing for the transplant patient, including molecular engraftment studies, when distinguishing the very common complication of recurrent disease from the exceedingly rare complication of donor cell leukemia.