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Dermatitis , Granuloma , Humanos , Dermatitis/patología , Dermatitis/diagnóstico , Granuloma/patología , Granuloma/diagnóstico , Masculino , Femenino , AdultoRESUMEN
Lymphoepithelioma carcinoma (LELC) is an extremely rare type of mammary cancer. Based on the histology, it can be misdiagnosed with inflammatory lesions like mastitis and medullary carcinoma or other hematopoietic neoplasms like lymphoma in the breast. Since LELC has a good response to chemotherapy with a good prognosis, t is prognostically important to recognize LELC. We report a rare case of LELC in a 51-year-old pre-menopausal female with a left breast mass, diagnosed with invasive ductal carcinoma (IDC), LELC type, treated with mastectomy, followed by adjuvant chemotherapy and radiotherapy, with a disease-free interval of 10 months. Herein, we present the case with its clinical presentation, radiologic imaging, histopathological features, and immunohistochemistry (IHC) findings. The rarity of this type of breast tumor warrants studying the behavior of these uncommon tumors to avoid misdiagnosis and establish well-defined criteria for diagnosis.
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Sister Mary Joseph nodule (SMJN) is a rare metastasis to umbilical skin originating from internal tumors including the stomach, ovary and large intestine and less commonly from pancreatic cancers. We report an uncommon case of metastatic pancreatic adenocarcinoma to umbilical skin. An 85-year-old female presented with a 1.8 cm protrusion of the right lateral umbilicus. The CT scan showed a 3.5 cm pancreatic lesion, peritoneal carcinomatosis and abdominal lymphadenopathy. Histology examination revealed atypical infiltrative glandular structures. Immunohistochemistry showed positive CK7, negative CDX2 and P53 with mutated patterns. These were consistent with metastatic adenocarcinoma most consistent with pancreatobiliary or upper GI origin. CK7 expresses in the ductal cells in pancreatic ductal adenocarcinoma. While CDX2 is positive in intestinal-type adenocarcinoma, it is negative in pancreatic ductal adenocarcinoma. The diagnosis of adenocarcinoma is rendered based on the presence of a pancreatic lesion in CT scan, positive CK7 and negative CDX2 in umbilical nodule tumor cells in the current patient.
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ABSTRACT: A 58-year-old man presented with a lesion on the nose suspicious for basal cell carcinoma. An initial biopsy specimen reviewed at an outside institution showed a cytologically atypical spindle cell proliferation that lacked expression of cytokeratins or melanocytic markers. The resulting differential diagnosis included atypical fibroxanthoma and pleomorphic dermal sarcoma. Histopathologic examination of the excision specimen at our institution revealed an intradermal pleomorphic and spindle cell tumor which extended into underlying skeletal muscle. The tumor was associated with a fibromyxoid stroma, scattered adipocytes, and hyperplastic folliculosebaceous epithelium at the periphery. The pleomorphic tumor cells showed hyperchromatic nuclei with smudgy chromatin, and no mitotic activity was detected. Overall, the cellularity was less than would be expected for atypical fibroxanthoma/pleomorphic dermal sarcoma. Furthermore, the tumor cells were strongly positive for CD34 and showed diffuse loss of retinoblastoma protein by immunohistochemistry. Consequently, a diagnosis of benign CD34-positive pleomorphic spindle cell tumor was rendered, with features overlapping between spindle cell/pleomorphic lipoma and trichodiscoma. Subsequent single-nucleotide pleomorphism array testing revealed heterozygous loss of chromosome 13q in a region that spanned the RB1 locus and copy number loss at 16q, favoring that the proliferation in fact represents a spindle cell/pleomorphic lipoma with trichodiscoma-like epithelial induction. This case highlights an important diagnostic pitfall that may be avoided by recognizing characteristic architectural and cytologic features of this spectrum of lesions.
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Neoplasias Óseas , Histiocitoma Fibroso Maligno , Lipoma , Neoplasias Cutáneas , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Cromatina , Diagnóstico Diferencial , Humanos , Hiperplasia , Lipoma/patología , Masculino , Persona de Mediana Edad , Nucleótidos , Proteína de Retinoblastoma/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismoRESUMEN
Originally described in a rare subset of poorly differentiated squamous cell carcinomas termed NUT carcinomas, NUTM1 rearrangements are now known to characterize a wide spectrum of neoplasms including sarcomas, poromas/porocarcinomas, unclassified adnexal carcinomas and pediatric acute lymphoblastic leukemia. The advent of next-generation sequencing (NGS) has led to the identification of a multitude of novel fusion partners in addition to BRD4, which was initially reported in the majority of NUT carcinomas. NUTM1-rearranged sarcomas usually harbor fusions with the MAD gene family (MXD1, MXD4, MGA) and present as spindle cell proliferations in diverse locations in patients of all ages. Herein, we present a very rare case of spindle cell sarcoma of the lung, which harbored a NUTM1::MGA fusion and offer a comprehensive update of the recent data.
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Carcinoma , Sarcoma , Neoplasias de los Tejidos Blandos , Niño , Humanos , Factores de Transcripción/genética , Proteínas Nucleares/genética , Proteínas de Neoplasias/genética , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/patología , Neoplasias de los Tejidos Blandos/patología , Carcinoma/genética , Pulmón/patología , Proteínas de Fusión Oncogénica/genética , Proteínas Represoras/genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Proteínas de Ciclo CelularRESUMEN
BACKGROUND: Hailey-Hailey disease (HHD) is an uncommon hereditary and benign skin condition characterized by blisters and erosions on intertriginous areas. It is related to a mutation of the ATP2C1 gene, which encodes a Ca2+ pump. It is characterized by multiple foci of skin acantholysis in the epidermis, with dyskeratosis and suprabasilar clefting. Galectin-3 is a beta-galactoside-binding protein that has an essential role in cell-to-cell and cell-to-matrix adhesion. We assessed galectin-3 immunohistochemical expression in HHD to explore its impact on the pathogenesis of this hereditary blistering disorder. METHOD: In a retrospective study, seven specimens from seven patients diagnosed with HHD were stained with antibodies to galectin-3. We evaluated the nuclear and cytoplasmic expression of galectin-3, as well as the staining intensity around blisters and distant normal skin. RESULTS: We observed a significant decrease in cytoplasmic and nuclear expression of galectin-3 as well as stain intensity around blisters compared with distant normal skin. CONCLUSIONS: While the acantholysis process in HHD is related to abnormality in cadherin expression caused by altered Ca2+ pump concentration, lower expression of galectin-3 may cause the extension of blisters by initiating cell-to-cell disassembly in the epidermis.
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Galectina 3/biosíntesis , Regulación de la Expresión Génica , Pénfigo Familiar Benigno/metabolismo , Piel/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pénfigo Familiar Benigno/patología , Estudios Retrospectivos , Piel/patologíaRESUMEN
Fibromatoses encompass a broad group of histopathologically similar fibroblastic/myofibroblastic proliferations with divergent clinical manifestations and behavior. Deep (desmoid-type) fibromatoses are typically large, rapidly growing, and locally aggressive tumors that occur in the abdominal wall, mesentery, and extra-abdominal soft tissue, principally the musculature of the trunk and extremities. Most sporadic cases of desmoid fibromatosis harbor inactivating mutations in CTNNB1, the gene encoding beta-catenin. Tumors occurring in the context of familial adenomatous polyposis and Gardner syndrome bear inactivating mutations in APC. By contrast, mutations in CTNNB1 or APC have not been identified in cases of superficial fibromatosis. Cutaneous involvement by desmoid fibromatosis is exceedingly rare. Here we present a 78-year-old male with desmoid-type fibromatosis arising in the dermis of the right medial calf with a pathogenic mutation in CTNNB1 and a variant of unknown significance in APC.
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Poliposis Adenomatosa del Colon/patología , Dermis/patología , Fibromatosis Agresiva/diagnóstico , Síndrome de Gardner/patología , Poliposis Adenomatosa del Colon/genética , Proteína de la Poliposis Adenomatosa del Colon , Anciano , Diagnóstico Diferencial , Fibromatosis Agresiva/genética , Fibromatosis Agresiva/cirugía , Síndrome de Gardner/genética , Humanos , Masculino , Mutación , Resultado del Tratamiento , beta Catenina/metabolismoRESUMEN
ABSTRACT: Pemphigus vulgaris (PV) is an autoimmune bullous disorder related to immunoglobulin-G autoantibodies against desmoglein-3. Galectin-3 is one of the main elements of the immunoglobulin-E group which is essential in the cell-cell or cell-matrix adhesion. Although the presence of immunoglobulin-E autoantibodies in PV has been observed, no studies have been performed to describe the role of galectin-3 in PV. We evaluated galectin-3 expression in PV as a first step in assessing its impact in the pathogenesis of this autoimmune blistering process. In a retrospective study, 56 specimens from 45 patients diagnosed with PV were stained with antibodies to galectin-3. The percentages of nuclear and cytoplasmic galectin-3 expression as well as staining intensity were evaluated around blisters and adjacent unaffected skin. We observed a significant decrease in galectin-3 cytoplasmic and nuclear expression as well as stain intensity around blisters compared with adjacent unaffected skin. Although autoantibodies against desmogleins trigger the blister formation in PV patients, loss of galectin-3 may play a role in the extension of blister formation by initiating cell-cell disassembly at the level of the intercellular keratinocyte desmosome. We demonstrated a lower expression of galectin-3 around the blisters in PV. The pathogenesis of the blister formation may be related to lower expression of galectin-3. Additional studies are necessary to clarify the result of this outcome and determine the accurate pathogenesis of blister formation in PV.
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Proteínas Sanguíneas/metabolismo , Galectinas/metabolismo , Pénfigo/patología , Biomarcadores/metabolismo , Humanos , Inmunohistoquímica , Estudios RetrospectivosRESUMEN
BACKGROUND: Bullous pemphigoid (BP) is a subepidermal blistering disorder caused by autoantibodies directed against hemidesmosomal proteins. Many patients with BP demonstrate circulating IgE autoantibodies. Although the role of IgE in the pathogenesis of BP is unknown, a correlation between IgE antibodies and eosinophilia has been observed. Soluble CD23 and galectin-3 are the main elements of the IgE group. The roles for CD23 in BP as a potential biomarker and IgE production regulator have been characterized, but no studies have evaluated any roles for galectin-3 in this disease. OBJECTIVE: In this study, we evaluated galectin-3 expression in BP as a first step in assessing its role in the pathogenesis of this autoimmune blistering process. PATIENTS AND METHODS: Sixty specimens diagnosed as BP were stained with antibodies to galectin-3. The percentages of nuclear and cytoplasmic galectin-3 expression and staining intensity were evaluated. RESULTS: There was a significant difference in galectin-3 cytoplasmic and nuclear expression within keratinocytes immediately surrounding and above the blisters: (1) cytoplasmic (mean = 17.2% ± 2.4%) vs adjacent unaffected skin (mean = 66.7% ± 2.0%, P < 0.0001) and (2) nuclear (mean = 1.9% ± 0.4%) vs adjacent unaffected skin (mean = 13.2% ± 1.2%, P < 0.0001). CONCLUSIONS: Lower expression of galectin-3 around blisters in BP may suggest a role as an adhesion molecule. Loss of galectin-3 may add to the extension of blister formation by initiating cell-extracellular matrix disassembly and may be involved with the associated dermal inflammation and the eosinophil chemotaxis. Further studies will be necessary to elucidate the result of this observed loss on disease pathogenesis.
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Recent evidence of gadolinium deposition in the brain has raised safety concerns. Iron oxide nanoparticles are re-emerging as promising alternative MR contrast agents, because the iron core can be metabolized. However, long-term follow up studies of the brain after intravenous iron oxide administration have not been reported thus far. In this study, we investigated, if intravenously administered ferumoxytol nanoparticles are deposited in porcine brains. Methods: In an animal care and use committee-approved prospective case-control study, ten Göttingen minipigs received either intravenous ferumoxytol injections at a dose of 5 mg Fe/kg (n=4) or remained untreated (n=6). Nine to twelve months later, pigs were sacrificed and the brains of all pigs underwent ex vivo MRI at 7T with T2 and T2*-weighted sequences. MRI scans were evaluated by measuring R2* values (R2*=1000/T2*) of the bilateral caudate nucleus, lentiform nucleus, thalamus, dentate nucleus, and choroid plexus. Pig brains were sectioned and stained with Prussian blue and evaluated for iron deposition using a semiquantitative scoring system. Data of ferumoxytol exposed and unexposed groups were compared with an unpaired t-test and a Mann-Whitney U test. Results: T2 and T2* signal of the different brain regions was not visually different between ferumoxytol exposed and unexposed controls. There were no significant differences in R2* values of the different brain regions in the ferumoxytol exposed group compared to controls (p>0.05). Prussian blue stains of the same brain regions, scored according to a semiquantitative score, were not significantly different either between the ferumoxytol exposed group and unexposed controls (p>0.05). Conclusions: Our study shows that intravenous ferumoxytol doses of 5-10 mg Fe/kg do not lead to iron deposition in the brain of pigs. We suggest iron oxide nanoparticles as a promising alternative for gadolinium-enhanced MRI.
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Encéfalo , Medios de Contraste/farmacocinética , Óxido Ferrosoférrico/farmacocinética , Imagen por Resonancia Magnética , Nanopartículas de Magnetita , Administración Intravenosa , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encéfalo/patología , Química Encefálica , Estudios de Casos y Controles , Medios de Contraste/administración & dosificación , Medios de Contraste/química , Óxido Ferrosoférrico/administración & dosificación , Óxido Ferrosoférrico/química , Estudios Prospectivos , Porcinos , Porcinos Enanos , Distribución TisularRESUMEN
Lichen spinulosus (LS) is an uncommon skin condition mostly in children and adolescents but uncommon in adults. It presents as a group of hypopigmented or skin-colored follicular papules and keratotic spines with a sandpaper-like appearance. There is a lymphohistiocytic infiltrate in the dermis centered around hair follicles. We present a rare case of LS in a 52-year-old woman with a rough, bumpy, itchy rash affecting the trunk and extremities. Her rash consisted of clusters of hyperkeratotic follicular-based spiny papules. Histologic sections demonstrated several dilated hair follicles filled with keratotic plugs surrounded by a dense perifollicular lymphohistiocytic infiltrate, particularly at the level of the infundibula, that extended into the follicular epithelium.
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Struma ovarii is a variant of a germ cell tumor composed predominantly of thyroid tissue. It is most often unilateral. The incidence of malignancy arising in patients with struma ovarii is rare. Here, we present a case of struma ovarii in a female presented with abdominal distension. The patient was treated with a total hysterectomy and bilateral salpingo-oophorectomy, which revealed an enlarged cystically dilated ovary. Histopathologic examination showed mature thyroid follicles with abundant colloid consistent with struma ovarii and focal area with nuclear features of papillary thyroid carcinoma. No other teratomatous elements were identified. Thyroid hormone levels were within their respective reference ranges. A diagnosis of struma ovarii should be considered in the differential diagnosis of pelvic masses in peri- and postmenopausal patients.
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Despite considerable progress with our understanding of glioblastoma multiforme (GBM) and the precise delivery of radiotherapy, the prognosis for GBM patients is still unfavorable with tumor recurrence due to radioresistance being a major concern. We recently developed a cross-linked iron oxide nanoparticle conjugated to azademethylcolchicine (CLIO-ICT) to target and eradicate a subpopulation of quiescent cells, glioblastoma initiating cells (GICs), which could be a reason for radioresistance and tumor relapse. The purpose of our study was to investigate if CLIO-ICT has an additive therapeutic effect to enhance the response of GBMs to ionizing radiation. Methods: NSG™ mice bearing human GBMs and C57BL/6J mice bearing murine GBMs received CLIO-ICT, radiation, or combination treatment. The mice underwent pre- and post-treatment magnetic resonance imaging (MRI) scans, bioluminescence imaging (BLI), and histological analysis. Tumor nanoparticle enhancement, tumor flux, microvessel density, GIC, and apoptosis markers were compared between different groups using a one-way ANOVA and two-tailed Mann-Whitney test. Additional NSG™ mice underwent survival analyses with Kaplan-Meier curves and a log rank (Mantel-Cox) test. Results: At 2 weeks post-treatment, BLI and MRI scans revealed significant reduction in tumor size for CLIO-ICT plus radiation treated tumors compared to monotherapy or vehicle-treated tumors. Combining CLIO-ICT with radiation therapy significantly decreased microvessel density, decreased GICs, increased caspase-3 expression, and prolonged the survival of GBM-bearing mice. CLIO-ICT delivery to GBM could be monitored with MRI. and was not significantly different before and after radiation. There was no significant caspase-3 expression in normal brain at therapeutic doses of CLIO-ICT administered. Conclusion: Our data shows additive anti-tumor effects of CLIO-ICT nanoparticles in combination with radiotherapy. The combination therapy proposed here could potentially be a clinically translatable strategy for treating GBMs.
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Neoplasias Encefálicas/tratamiento farmacológico , Desoxiadenosinas/uso terapéutico , Glioblastoma/tratamiento farmacológico , Nanomedicina Teranóstica , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/radioterapia , Caspasa 3/metabolismo , Línea Celular Tumoral , Terapia Combinada , Desoxiadenosinas/química , Desoxiadenosinas/farmacología , Portadores de Fármacos/química , Femenino , Compuestos Férricos/química , Glioblastoma/mortalidad , Glioblastoma/radioterapia , Humanos , Estimación de Kaplan-Meier , Imagen por Resonancia Magnética , Nanopartículas del Metal/química , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microvasos/fisiologíaRESUMEN
Malignant ascites in prostatic acinar adenocarcinoma is very rare. We present an 84-year-old man with a rare malignant ascites due to prostatic adenocarcinoma demonstrating hepatoid differentiation by immunohistochemistry. The patient was diagnosed with the malignant ascites due to metastatic prostatic adenocarcinoma. We identified the unique cytological feature of envelopment of tumour cell clusters by benign mesothelial monolayers.
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Adenocarcinoma/secundario , Ascitis/etiología , Ascitis/patología , Neoplasias Peritoneales/secundario , Neoplasias de la Próstata/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Benzamidas , Docetaxel/uso terapéutico , Humanos , Masculino , Nitrilos , Neoplasias Peritoneales/tratamiento farmacológico , Feniltiohidantoína/análogos & derivados , Feniltiohidantoína/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Resultado del TratamientoRESUMEN
The long-term survival of osteosarcoma patients with metastatic or recurrent disease remains dismal, and new therapeutic options are urgently needed. The purpose of our study was to compare the efficacy of CD47 mAb plus doxorubicin combination therapy in mouse models of osteosarcoma with CD47 mAb and doxorubicin monotherapy. Forty-eight NOD scid gamma (NSG) mice with intratibial MNNG/HOS tumors received CD47 mAb, doxorubicin, combination therapy, or control IgG treatment. Twenty-four mice (n = 6 per group) underwent pre- and post-treatment magnetic resonance imaging (MRI) scans with the macrophage marker ferumoxytol, bioluminescence imaging, and histological analysis. Tumor ferumoxytol enhancement, tumor flux, and tumor-associated macrophages (TAM) density were compared between different groups using a one-way ANOVA. Twenty-four additional NSG mice underwent survival analyses with Kaplan-Meier curves and a log-rank (Mantel-Cox) test. Intratibial osteosarcomas demonstrated significantly stronger ferumoxytol enhancement and significantly increased TAM quantities after CD47 mAb plus doxorubicin combination therapy compared to CD47 mAb (P = 0.02) and doxorubicin monotherapy (P = 0.001). Tumor-bearing mice treated with CD47 mAb plus doxorubicin combination therapy demonstrated significantly reduced tumor size and prolonged survival compared to control groups that received CD47 mAb (P = 0.03), doxorubicin monotherapy (P = 0.01), and control IgG (P = 0.001). In conclusion, CD47 mAb plus doxorubicin therapy demonstrates an additive therapeutic effect in mouse models of osteosarcomas, which can be monitored with an immediately clinically applicable MRI technique.
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Antígeno CD47/inmunología , Doxorrubicina/uso terapéutico , Osteosarcoma/tratamiento farmacológico , Animales , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/inmunología , Línea Celular Tumoral , Óxido Ferrosoférrico/análisis , Humanos , Luminiscencia , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Imagen por Resonancia Magnética , Ratones Endogámicos NOD , Imagen Óptica , Osteosarcoma/diagnóstico por imagen , Osteosarcoma/inmunología , Fagocitosis/efectos de los fármacosRESUMEN
Purpose: Tumor-associated macrophages (TAMs) in malignant tumors have been linked to tumor aggressiveness and represent a new target for cancer immunotherapy. As new TAM-targeted immunotherapies are entering clinical trials, it is important to detect and quantify TAM with noninvasive imaging techniques. The purpose of this study was to determine if ferumoxytol-enhanced MRI can detect TAM in lymphomas and bone sarcomas of pediatric patients and young adults.Experimental Design: In a first-in-patient, Institutional Review Board-approved prospective clinical trial, 25 pediatric and young adult patients with lymphoma or bone sarcoma underwent ferumoxytol-enhanced MRI. To confirm ferumoxytol enhancement, five pilot patients (two lymphoma and three bone sarcoma) underwent pre- and postcontrast MRI. Subsequently, 20 patients (10 lymphoma and 10 bone sarcoma) underwent ferumoxytol-enhanced MRI 24 to 48 hours after i.v. injection, followed by tumor biopsy/resection and macrophage staining. To determine if ferumoxytol-MRI can differentiate tumors with different TAM content, we compared T2* relaxation times of lymphomas and bone sarcomas. Tumor T2* values of 20 patients were correlated with CD68+ and CD163+ TAM quantities on histopathology.Results: Significant ferumoxytol tumor enhancement was noted on postcontrast scans compared with precontrast scans (P = 0.036). Bone sarcomas and lymphomas demonstrated significantly different MRI enhancement and TAM density (P < 0.05). Within each tumor group, T2* signal enhancement on MR images correlated significantly with the density of CD68+ and CD163+ TAM (P < 0.05).Conclusions: Ferumoxytol-enhanced MRI is immediately clinically applicable and could be used to stratify patients with TAM-rich tumors to immune-targeted therapies and to monitor tumor response to these therapies. Clin Cancer Res; 24(17); 4110-8. ©2018 AACR.
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Neoplasias Óseas/diagnóstico por imagen , Linfoma/diagnóstico por imagen , Macrófagos/ultraestructura , Sarcoma/diagnóstico por imagen , Adolescente , Adulto , Neoplasias Óseas/patología , Niño , Medios de Contraste/administración & dosificación , Femenino , Óxido Ferrosoférrico/administración & dosificación , Humanos , Linfoma/patología , Macrófagos/efectos de los fármacos , Macrófagos/patología , Imagen por Resonancia Magnética , Masculino , Sarcoma/patología , Adulto JovenRESUMEN
PURPOSE: To evaluate whether ultrasmall superparamagnetic iron oxide nanoparticle (USPIO)-enhanced magnetic resonance imaging (MRI) can detect allograft rejection in pediatric kidney transplant patients. PROCEDURES: The USPIO ferumoxytol has a long blood half-life and is phagocytosed by macrophages. In an IRB-approved single-center prospective clinical trial, 26 pediatric patients and adolescents (age 10-26 years) with acute allograft rejection (n = 5), non-rejecting allografts (n = 13), and normal native kidneys (n = 8) underwent multi-echo T2* fast spoiled gradient-echo (FSPGR) MRI after intravenous injection (p.i.) of 5 mg Fe/kg ferumoxytol. T2* relaxation times at 4 h p.i. (perfusion phase) and more than 20 h p.i. (macrophage phase) were compared with biopsy results. The presence of rejection was assessed using the Banff criteria, and the prevalence of macrophages on CD163 immunostains was determined based on a semi-quantitative scoring system. MRI and histology data were compared among patient groups using t tests, analysis of variance, and regression analyses with a significance threshold of p < 0.05. RESULTS: At 4 h p.i., mean T2* values were 6.6 ± 1.5 ms for native kidneys and 3.9 ms for one allograft undergoing acute immune rejection. Surprisingly, at 20-24 h p.i., one rejecting allograft showed significantly prolonged T2* relaxation times (37.0 ms) compared to native kidneys (6.3 ± 1.7 ms) and non-rejecting allografts (7.6 ± 0.1 ms). Likewise, three additional rejecting allografts showed significantly prolonged T2* relaxation times compared to non-rejecting allografts at later post-contrast time points, 25-97 h p.i. (p = 0.008). Histological analysis revealed edema and compressed microvessels in biopsies of rejecting allografts. Allografts with and without rejection showed insignificant differences in macrophage content on histopathology (p = 0.44). CONCLUSION: After ferumoxytol administration, renal allografts undergoing acute rejection show prolonged T2* values compared to non-rejecting allografts. Since histology revealed no significant differences in macrophage content, the increasing T2* value is likely due to the combined effect of reduced perfusion and increased edema in rejecting allografts.
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Aloinjertos/inmunología , Óxido Ferrosoférrico/metabolismo , Rechazo de Injerto/inmunología , Trasplante de Riñón , Adolescente , Aloinjertos/patología , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Niño , Rechazo de Injerto/diagnóstico , Humanos , Cinética , Imagen por Resonancia Magnética , Receptores de Superficie Celular/metabolismo , Adulto JovenRESUMEN
PURPOSE: To provide clinically useful gadolinium-free whole-body cancer staging of children and young adults with integrated positron emission tomography/magnetic resonance (PET/MR) imaging in less than 1 h. PROCEDURES: In this prospective clinical trial, 20 children and young adults (11-30 years old, 6 male, 14 female) with solid tumors underwent 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET/MR on a 3T PET/MR scanner after intravenous injection of ferumoxytol (5 mg Fe/kg) and [18F]FDG (2-3 MBq/kg). Time needed for patient preparation, PET/MR image acquisition, and data processing was compared before (n = 5) and after (n = 15) time-saving interventions, using a Wilcoxon test. The ferumoxytol-enhanced PET/MR images were compared with clinical standard staging tests regarding radiation exposure and tumor staging results, using Fisher's exact tests. RESULTS: Tailored workflows significantly reduced scan times from 36 to 24 min for head to mid thigh scans (p < 0.001). These streamlined PET/MR scans were obtained with significantly reduced radiation exposure (mean 3.4 mSv) compared to PET/CT with diagnostic CT (mean 13.1 mSv; p = 0.003). Using the iron supplement ferumoxytol "off label" as an MR contrast agent avoided gadolinium chelate administration. The ferumoxytol-enhanced PET/MR scans provided equal or superior tumor staging results compared to clinical standard tests in 17 out of 20 patients. Compared to PET/CT, PET/MR had comparable detection rates for pulmonary nodules with diameters of equal or greater than 5 mm (94 vs. 100 %), yet detected significantly fewer nodules with diameters of less than 5 mm (20 vs 100 %) (p = 0.03). [18F]FDG-avid nodules were detected with slightly higher sensitivity on the PET of the PET/MR compared to the PET of the PET/CT (59 vs 49 %). CONCLUSION: Our streamlined ferumoxytol-enhanced PET/MR protocol provided cancer staging of children and young adults in less than 1 h with equivalent or superior clinical information compared to clinical standard staging tests. The detection of small pulmonary nodules with PET/MR needs to be improved.