RESUMO
Gadolinium-based contrast agents are linked to nephrogenic systemic fibrosis in patients with renal insufficiency. The pathology of nephrogenic systemic fibrosis is characterized by abnormal tissue repair: fibrosis and ectopic ossification. The mechanisms by which gadolinium could induce fibrosis and ossification are not known. We examined in vitro the effect of a gadolinium-based contrast agent on human peripheral blood mononuclear cells for phenotype and function relevant to the pathology of nephrogenic systemic fibrosis using immunofluorescence, flow cytometry, real-time PCR, and osteogenic assays. We also examined tissues from patients with nephrogenic systemic fibrosis, using IHC to identify the presence of cells with phenotype induced by gadolinium. Gadolinium contrast induced differentiation of human peripheral blood mononuclear cells into a unique cellular phenotype--CD163(+) cells expressing proteins involved in fibrosis and bone formation. These cells express fibroblast growth factor (FGF)23, osteoblast transcription factors Runt-related transcription factor 2, and osterix, and show an osteogenic phenotype in in vitro assays. We show in vivo the presence of CD163(+)/procollagen-1(+)/osteocalcin(+) cells in the fibrotic and calcified tissues of nephrogenic systemic fibrosis patients. Gadolinium contrast-induced CD163(+)/ferroportin(+)/FGF23(+) cells with osteogenic potential may play a role in systemic fibrosis and ectopic ossification in nephrogenic systemic fibrosis.
Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Meios de Contraste/efeitos adversos , Gadolínio/efeitos adversos , Dermopatia Fibrosante Nefrogênica/induzido quimicamente , Dermopatia Fibrosante Nefrogênica/patologia , Osteogênese , Receptores de Superfície Celular/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Colágeno/metabolismo , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/metabolismo , Gadolínio DTPA/efeitos adversos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Dermopatia Fibrosante Nefrogênica/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteocalcina/metabolismo , Fenótipo , Pele/metabolismo , Pele/patologia , Fatores de Transcrição/metabolismoRESUMO
Cutaneous ciliated cysts (CCC) are rare benign cysts known to occur in the lower extremities of females of reproductive age. Currently, there are 2 theories that attempt to explain the histogenesis of this rare entity. The theory of Mullerian heterotopia provides a plausible histogenetic explanation for the vast majority of CCC. A proposed alternative theory is the ciliated metaplasia of eccrine glands. We believe that previously reported cases of CCC include 2 distinct entities. We report, herein, the first case reported in the literature of a cutaneous ciliated eccrine cyst occurring on the scalp.
Assuntos
Cistos/patologia , Glândulas Écrinas/patologia , Couro Cabeludo/patologia , Biomarcadores/análise , Biópsia , Cistos/química , Cistos/cirurgia , Glândulas Écrinas/química , Glândulas Écrinas/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Metaplasia , Pessoa de Meia-Idade , Couro Cabeludo/química , Couro Cabeludo/cirurgiaRESUMO
Influenza A (H1N1), like many other viral infections, has been associated with cutaneous eruptions. Differential diagnoses in a viral exanthem generally include spongiotic dermatitis, urticaria and drug reaction. The aim of this series was to retrospectively review three cases (five biopsies) involving patients with a clinical history of H1N1 and an accompanying rash, and to evaluate whether unique histopathologic and immunohistochemical features exist among these patients' cutaneous eruptions. Findings among all cases included a sparse superficial perivascular infiltrate, and interestingly, scattered interstitial and prominent intravascular neutrophils. Two cases demonstrated mild spongiosis and mild interface change. Immunohistochemistry in all cases revealed a CD4-predominant lymphocytic infiltrate of the dermis with a sparse intraepidermal population of admixed CD4 and CD8 positive lymphocytes. Many changes found in the cutaneous eruption associated with H1N1 are similar to those of other viral eruptions, including a mild perivascular lymphocytic infiltrate, mild spongiosis and mild interface change; however, sparse dermal and intravascular neutrophils and intraepidermal lymphocytes appear to be the features unique to these cases of H1N1-associated cutaneous eruptions. Such a distinction may prove diagnostically important in the clinical setting and useful in the surveillance of this historically pandemic virus.
Assuntos
Exantema/patologia , Exantema/virologia , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/patologia , Influenza Humana/virologia , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Mycosis fungoides (MF) exhibits a variety of underlying molecular defects including aberrations involving the PTEN tumor suppressor gene. Specifically, loss of heterozygosity of PTEN has been previously demonstrated. We hypothesize that abnormalities of PTEN may result in altered immunohistochemical expression of its protein product. METHODS: Thirty-six MF specimens were stained with monoclonal antibody against PTEN protein. The percentage of nuclei retaining PTEN expression and the staining intensity was recorded. RESULTS: Average percentage of lymphoma cells retaining expression of the PTEN protein was 92% within patch-stage lesions, 81.4% in plaque-stage lesions, and 81.1% in tumor-stage lesions. Average intensity of staining for patch-stage lesions was 2.90, 2.50 for plaque lesions and 2.44 for tumor lesions. Cases lacking loss of heterozygozity at PTEN (n = 6) had an average expression of 81% and an average intensity of staining of 2.42. Whereas, cases with loss of heterozygozity at PTEN (n = 6) had an average expression of 75% of cells with an average staining intensity of 2.33. CONCLUSIONS: The percentage of cells retaining PTEN and staining intensity decrease from patch- to plaque-stage lesions, whereas both parameters show mild diminution in tumor lesions compared with plaque lesions. PTEN expression in a small sample seems to correlate with previous demonstration of loss of heterozygosity at the molecular level. Although a trend for loss of PTEN expression exists with histologic progression of MF, the effect is modest and may not represent the pivotal defect in MF pathogenesis.
Assuntos
Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Perda de Heterozigosidade , Micose Fungoide/enzimologia , Micose Fungoide/genética , PTEN Fosfo-Hidrolase/análise , PTEN Fosfo-Hidrolase/genética , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Biópsia , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Micose Fungoide/patologia , Estadiamento de Neoplasias , Fenótipo , Neoplasias Cutâneas/patologiaRESUMO
DNA double-strand breaks are increased in human melanoma tissue as detected by histone H2AX phosphorylation.(1-3) We investigated two of the downstream effectors of DNA double-strand breaks, Rad50 and 53BP1 (tumor suppressor p53 binding protein 1), to determine if they are altered in human primary melanoma cells. Melanoma cases showed high Rad50 staining (81.8%; 9/11) significantly more frequently than conventional or atypical melanocytic nevi (0%; 0/18). In contrast, the staining pattern for 53BP1 appears similar between melanoma and nevi. This is the first study that shows activation and misregulation of the DNA repair pathway in human melanoma cells. The staining features of Rad50, a component of an essential DNA double-strand break repair complex, are clearly increased in melanoma cells with regards to both staining intensity and the number of positive melanoma cells. Interestingly, among the melanoma cases with increased Rad50 staining, most demonstrated cytoplasmic rather than nuclear staining (88.9%, 8/9). Further studies are needed to determine the cause of this mislocalization and its affects, if any, on DNA double-strand break repair in melanoma.
Assuntos
Enzimas Reparadoras do DNA/biossíntese , Proteínas de Ligação a DNA/biossíntese , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Melanoma , Proteínas de Neoplasias/metabolismo , Hidrolases Anidrido Ácido , Quebras de DNA de Cadeia Dupla , Reparo do DNA , DNA de Neoplasias/metabolismo , Feminino , Histonas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Melanoma/enzimologia , Melanoma/patologia , Pessoa de Meia-Idade , Nevo Pigmentado/metabolismo , Nevo Pigmentado/patologia , Fosforilação , Células Tumorais Cultivadas , Proteína 1 de Ligação à Proteína Supressora de Tumor p53RESUMO
A heterogeneous group of benign fibrohistiocytic lesions has been assembled under the umbrella term, dermatofibroma. These lesions share a morphology of bland spindled cells encompassed by and intercalating through thick dermal collagen; unique variants have been described based on secondary histologic features, some of which include aneurysmal, myxoid, lipidized, signet ring, angiomatous, and keloidal. Here, we present a distinct dermatofibroma variant henceforth known as collapsing angiokeloidal dermatofibroma identified in 2 patients with slowly growing nodules of the buttock and the arm. Microscopically, the lesions have a characteristic dermatofibroma appearance but are accompanied by unusual diffuse small caliber vessels whose walls are collapsed by a thick, eosinophilic, keloid-like substance. The eosinophilic material resembles the adjacent dermal collagen; however, it does not stain for type-4 collagen or type-1 procollagen, amyloid, or glycogen. Although the exact composition of the keloidal material remains ambiguous, the architectural novelty of collapsing angiokeloidal dermatofibroma serves to further expand the morphologic spectrum of benign fibrous histiocytomas, although highlighting the difficulty in distinguishing between it and similar lesions.
Assuntos
Vasos Sanguíneos/patologia , Histiocitoma Fibroso Benigno/patologia , Queloide/patologia , Neoplasias Cutâneas/patologia , Adulto , Biomarcadores Tumorais/análise , Biópsia , Vasos Sanguíneos/química , Nádegas , Feminino , Histiocitoma Fibroso Benigno/irrigação sanguínea , Histiocitoma Fibroso Benigno/química , Histiocitoma Fibroso Benigno/classificação , Humanos , Imuno-Histoquímica , Masculino , Neoplasias Cutâneas/irrigação sanguínea , Neoplasias Cutâneas/química , Neoplasias Cutâneas/classificação , Extremidade SuperiorRESUMO
Nephrogenic systemic fibrosis (NSF) is a fibrosing disorder that occurs in some patients with renal insufficiency. Exposure to gadolinium-based contrast agents (GdCA) has been associated with the development of NSF. No uniformly effective treatment options exist. We present immunohistochemical evidence to show that the proliferating fibrocytes of NSF express phospho-70-s6 kinase (PI-3-K), a protein downstream of PI-3-K, and the target of the drug rapamycin. In our patient, use of rapamycin resulted in rapid clinical improvement marked by reduced edema, reduced skin induration, and decreased pain. This suggests a possible role for PI-3-K and rapamycin (mTOR) pathways in the pathogenesis of NSF. Drugs that inhibit these pathways may be a target for future therapy. While our patient did attribute disease onset to GdCA exposure, used on a single occasion for abdominal imaging, he was also exposed to iron, calcium, and darbepoetin alpha at the time of imaging.
Assuntos
Dermopatia Fibrosante Nefrogênica/tratamento farmacológico , Proteínas Quinases S6 Ribossômicas 70-kDa/fisiologia , Sirolimo/uso terapêutico , Meios de Contraste/efeitos adversos , Gadolínio DTPA/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Dermopatia Fibrosante Nefrogênica/metabolismo , Dermopatia Fibrosante Nefrogênica/patologiaAssuntos
Eritema/etiologia , Neoplasias Faciais/patologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Linfoma de Células B/diagnóstico , Prurido/etiologia , Couro Cabeludo , Neoplasias Cutâneas/diagnóstico , Adulto , Alopecia/complicações , Eritema/patologia , Dermatoses Faciais/diagnóstico , Dermatoses Faciais/etiologia , Neoplasias Faciais/complicações , Neoplasias Faciais/terapia , Testa , Humanos , Masculino , Prurido/patologiaRESUMO
BACKGROUND: Calcific uremic arteriolopathy (CUA) is an often fatal disease that affects patients with end-stage renal disease. Although animal studies support a role for metals in the pathogenesis of CUA, metal accumulation in human tissue has not been previously evaluated. OBJECTIVE: We sought to evaluate metal deposition in CUA. METHODS: Twelve histologically proven cases of CUA were identified from our dermatopathology database. Five skin biopsy specimens from patients with chronic kidney disease exposed to gadolinium contrast but without CUA were used as controls. Quantification of metals including iron, aluminum, and gadolinium in the lesional skin was performed using inductively coupled mass spectrometry. RESULTS: Seven patients had documented exposure to gadolinium-based contrast in the 2 years before CUA. Three of them had concurrent nephrogenic systemic fibrosis. Highly significant quantities of iron (P = .03) and aluminum (P = .0002) were detected in CUA specimens compared with controls. Significant amounts of gadolinium were present in several CUA biopsy specimens. LIMITATIONS: Observational, retrospective study design and small sample size are limitations. CONCLUSION: Tissue iron and aluminum content is increased in CUA. A significant amount of gadolinium is also present in some CUA specimens. Based on animal studies that strongly implicate metals in the pathogenesis of CUA, our data suggest that metal deposition should be considered in the pathogenesis of human CUA.
Assuntos
Alumínio/metabolismo , Arteriopatias Oclusivas/induzido quimicamente , Arteriopatias Oclusivas/metabolismo , Calciofilaxia/induzido quimicamente , Calciofilaxia/metabolismo , Gadolínio/metabolismo , Ferro/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Arteríolas/patologia , Meios de Contraste/efeitos adversos , Feminino , Gadolínio/efeitos adversos , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Dermopatia Fibrosante Nefrogênica/complicações , Dermopatia Fibrosante Nefrogênica/metabolismo , Estudos Retrospectivos , Pele/metabolismo , Dermatopatias/induzido quimicamenteRESUMO
Atypical fibroxanthoma (AFX), spindle cell squamous cell carcinoma (SCSCC) and spindle cell melanoma are the primary entities in the differential diagnosis of a cytologically atypical spindle cell tumor arising on sun-damaged skin. AFX is generally regarded as a diagnosis of exclusion in this context: in the absence of S100 or keratin reactivity, a diagnosis of AFX is favored. However, keratin reactivity may be focal or even absent in SCSCC, and although numerous positive markers of AFX have been proposed, none has shown sufficient sensitivity and specificity for routine diagnostic use. We evaluated 20 AFX and 10 SCSCC with a panel of cytokeratins and p63 to assess the utility of the latter antibody in this differential diagnosis. All 10 SCSCC showed strong expression of p63, whereas all 20 AFX were p63 negative. Two additional cases (excluded from the study) were negative for keratins and S100 on initial shave biopsies, resulting in a favored diagnosis of AFX, but p63 stains performed retrospectively were positive. However, review of the excision specimens in both cases revealed deep subcutaneous extension, excluding AFX. p63 reactivity argues against the diagnosis of AFX and is therefore a useful addition to the standard immunohistochemical panel for cutaneous spindle cell neoplasms.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/diagnóstico , Histiocitoma Fibroso Benigno/diagnóstico , Proteínas de Membrana/metabolismo , Neoplasias Cutâneas/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , Diagnóstico Diferencial , Feminino , Histiocitoma Fibroso Benigno/metabolismo , Humanos , Imuno-Histoquímica , Queratinas/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas S100/biossíntese , Neoplasias Cutâneas/metabolismoRESUMO
A 21-year-old pregnant woman presented with a rapidly growing >2 cm nodule on her right leg, involving dermis and subcutaneous tissue. Histologically, the tumor was composed of sheets and nests of neoplastic cells with variable cytomorphology, including typical round to ovoid glomus cells with clear cytoplasm and well-defined cell borders, small cells and spindle cells. Numerous medium to large vessels were present throughout the tumor. Moderate- to high cellularity, nuclear atypia and frequent mitotic figures (42 MF/50 High power field (HPF)) were noted. Immunohistochemistry showed cytoplasmic and membranous expression of actin (HHF-35) and membranous expression of type IV collagen. The histologic features and immunoprofile were consistent with the diagnosis of malignant glomus tumor, a rare soft tissue neoplasm that typically arises on the extremities. Histologic features that infer malignancy in glomus tumors include the combination of large size (>2 cm) and deep location, or atypical mitotic figures, or moderate to severe cytologic atypia with high mitotic activity (>5 mitoses /50 HPF). Although our case was superficially located, the nuclear atypia and mitotic rate, as well as the large size, fulfilled the criteria for a malignant glomus tumor.
Assuntos
Tumor Glômico/patologia , Perna (Membro)/patologia , Complicações Neoplásicas na Gravidez/patologia , Neoplasias Cutâneas/patologia , Actinas/metabolismo , Adulto , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Colágeno Tipo IV/metabolismo , Citoplasma/metabolismo , Citoplasma/patologia , Feminino , Tumor Glômico/metabolismo , Humanos , Mitose , Proteínas de Neoplasias/metabolismo , Gravidez , Complicações Neoplásicas na Gravidez/metabolismo , Neoplasias Cutâneas/metabolismoRESUMO
Mycosis fungoides (MF) exhibits a variety of underlying molecular defects. Loss of heterozygosity (LOH) is a technique used to detect chromosomal imbalances in neoplastic disorders using archival tissue. We analyzed skin biopsies of MF in different stages for the presence of LOH at specific loci to evaluate underlying genetic aberrations involved in MF and its progression. Twenty-five skin biopsies (15 plaque stage and 10 tumor stage) from 19 patients were evaluated. LOH was examined at 1p22 (D1S2766), 9p21 [IFNA, p15 (D9S1748), p16 (D9S171)], 10q23 [PTEN (D10S185, D10S541, D10S2491)], and 17p13 [p53 (TP53)]. Abnormal lymphocytes were microdissected from formalin-fixed, paraffin-embedded tissue sections. Sixteen of the 25 (64%) specimens evaluated had at least one abnormal LOH locus and LOH was identified in 7 of 15 (47%) plaque and in 9 of 10 (90%) tumor stage lesions, respectively. All 3 patients with sequential biopsies (plaque followed by tumor lesions) had additional LOH abnormalities in tumor specimens compared with plaque stage lesions. LOH most frequently involved chromosome 10, including 7 of 10 (70%) tumor stage lesions. Loss of multiple alleles was only identified in tumor stage cases, with 3 tumors undergoing allelic losses at 3 separate loci. Our results suggest that LOH studies are a robust method for evaluating genetic abnormalities in MF. Tumor stage lesions manifest increasing allelic losses compared with plaque stage. Further, in this series, several loci associated with the tumor suppressor gene PTEN on chromosome 10 appear to be associated with progression from plaque to tumor stage.
Assuntos
Aberrações Cromossômicas , Perda de Heterozigosidade , Micose Fungoide/genética , Neoplasias Cutâneas/genética , Biópsia , Progressão da Doença , Humanos , Linfócitos/patologia , Microdissecção , Micose Fungoide/metabolismo , Micose Fungoide/patologia , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
Heparanase (HPSE-1) is an endo-beta-D-glucuronidase that cleaves heparan sulfate proteoglycans (HSPG), and its expression has been associated with increased growth, metastasis, and angiogenesis of tumors. Since metastatic melanoma cells express high levels of HSPG and because melanoma tumors grow highly vascularized, we analyzed melanoma tissue specimens for HPSE-1 expression from experimental animals as well as from patients. Laser capture microdissection microscopy was used to extract melanoma cell populations and to isolate them from adjacent tissue. In experimental animals, a 29-fold upregulation of HPSE-1 expression was detected by real-time PCR in metastatic melanoma compared to normal lung tissue. Additionally, immunohistochemistry (IHC) revealed selective HPSE-1 staining in human metastatic melanoma when compared to primary melanoma tumors from the same patient. IHC also showed a marked staining for the enzyme around blood vessels and in vascularized regions. Our results provide evidence demonstrating that HPSE-1 likely plays important roles in regulating the in vivo growth and progression of melanoma. These results further emphasize the importance that therapies designed to block HPSE-1 activity may aid in controlling this type of cancer.
Assuntos
Regulação Neoplásica da Expressão Gênica , Glucuronidase/biossíntese , Melanoma/enzimologia , Animais , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/secundário , Linhagem Celular Tumoral , Proliferação de Células , Primers do DNA/química , DNA Complementar/metabolismo , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Lasers , Pulmão/patologia , Melanoma/patologia , Camundongos , Camundongos Endogâmicos C57BL , Metástase Neoplásica , Transplante de Neoplasias , Neoplasias/metabolismo , Neovascularização Patológica , Reação em Cadeia da Polimerase , RNA/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Regulação para CimaRESUMO
BACKGROUND: Hepatitis C virus (HCV) infection is globally epidemic. Several mucocutaneous diseases are well established in association with HCV infection. Few case reports describe the recently recognized HCV-related skin disorder termed necrolytic acral erythema (NAE). METHODS: Thirty patients with NAE were identified in a university-based dermatology clinic in Cairo, Egypt. These patients were observed over time to document the clinical and histologic findings of this disorder. RESULTS: All patients were infected with HCV. Erythematous papules arose most commonly on the dorsal aspect of the feet, particularly the dorsal surface of the great toe. Progression resulted in confluence into erythematous dusky plaques with adherent scale and central erosion. The eruption extended to involve the lower leg and other regions in some patients but never affected palms or soles, the nail bed, nail plate, or mucous membranes. Skin biopsy specimens from fully evolved lesions displayed psoriasiform changes in association with more characteristic findings of keratinocyte necrosis and papillomatosis. LIMITATIONS: We did not perform a prospective review of patients known to be infected with HCV. Patients were identified from a general clinic population and then assayed for HCV serology. CONCLUSIONS: NAE is a distinctive skin disorder associated with HCV infection in all cases reported to date. Recognition of this disease should alert practitioners to the need for viral testing and appropriate counseling of patients.
Assuntos
Eritema/etiologia , Dermatoses do Pé/etiologia , Dermatoses da Mão/etiologia , Hepatite C/complicações , Dermatoses da Perna/etiologia , Adolescente , Adulto , Eritema/patologia , Feminino , Dermatoses do Pé/patologia , Dermatoses da Mão/patologia , Humanos , Dermatoses da Perna/patologia , Masculino , Pessoa de Meia-Idade , NecroseRESUMO
Nephrogenic systemic fibrosis is associated with gadolinium contrast exposure in patients with reduced kidney function and carries high morbidity and mortality. We have previously demonstrated that gadolinium contrast agents induce in vivo systemic iron mobilization and in vitro differentiation of peripheral blood mononuclear cells into ferroportin (iron exporter)-expressing fibrocytic cells. In the present study we examined the role of iron in a mouse model of nephrogenic systemic fibrosis. Chronic kidney disease was induced in 8-week-old male Balb/C mice with a two-step 5/6 nephrectomy surgery. Five groups of mice were studied: control (n = 5), sham surgery control (n = 5), chronic kidney disease control (n = 4), chronic kidney disease injected with 0.5 mmol/kg body weight of Omniscan 3 days per week, for a total of 10 injections (n = 8), and chronic kidney disease with Omniscan plus deferiprone, 125 mg/kg, in drinking water (n = 9). Deferiprone was continued for 16 weeks until the end of the experiment. Mice with chronic kidney disease injected with Omniscan developed skin changes characteristic of nephrogenic systemic fibrosis including hair loss, reddening, ulceration, and skin tightening by 10 to 16 weeks. Histopathological sections demonstrated dermal fibrosis with increased skin thickness (0.25±0.06 mm, sham; 0.34±+0.3 mm, Omniscan-injected). Additionally, we observed an increase in tissue infiltration of ferroportin-expressing, fibrocyte-like cells accompanied by tissue iron accumulation in the skin of the Omniscan-treated mice. The deferiprone-treated group had significantly decreased skin thickness (p<0.05) and significantly decreased dermal fibrosis compared to the Omniscan-only group. In addition, iron chelation prevented tissue infiltration of ferroportin-expressing, fibrocyte-like cells. Our in vitro experiments demonstrated that exposure to Omniscan resulted in the release of catalytic iron and this was prevented by the iron chelator deferiprone. Deferiprone inhibited the differentiation of human peripheral blood mononuclear cells into ferroportin-expressing cells by immunohistochemical staining and western blot analysis. Our studies support an important role of iron in the pathophysiology of gadolinium chelate toxicity and nephrogenic systemic fibrosis.
Assuntos
Ferro/metabolismo , Dermopatia Fibrosante Nefrogênica/tratamento farmacológico , Dermopatia Fibrosante Nefrogênica/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Animais , Meios de Contraste/efeitos adversos , Deferiprona , Modelos Animais de Doenças , Gadolínio/efeitos adversos , Gadolínio DTPA/administração & dosagem , Humanos , Masculino , Camundongos , Dermopatia Fibrosante Nefrogênica/induzido quimicamente , Dermopatia Fibrosante Nefrogênica/patologia , Piridonas/administração & dosagem , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/patologiaRESUMO
Mortality from melanoma, the deadliest of skin cancers, continues to increase in all age groups. A small number of melanomas spontaneously regress. In vitro studies suggest a role for the natural killer cell in effecting regression. In this study, the goal was to determine if natural killer cells are preferentially involved in the cytotoxic response in regressing lesions. Forty-two cases were selected: nevi with regression, nonregressing melanoma with brisk inflammation, and regressing melanoma. Sections were stained with hematoxylin and eosin and immunostained for CD8, CD56, and T-cell intracytoplasmic antigen 1. Numbers of total lymphocytes, CD8-positive lymphocytes, and T-cell intracytoplasmic antigen 1-positive lymphocytes did not differ among the 3 populations or based on location. CD56 positivity was significantly different among the 3 populations. Regressing melanomas showed the greatest CD56 activity, followed by regressing nevi, whereas inflamed, nonregressing melanomas showed the least. CD56(+) lymphocytes were mostly counted in areas of early regression. The natural killer cell could plausibly play a role in the occurrence of regression as a cytotoxic effector cell or as a mediator of the cytotoxic mechanism.
Assuntos
Células Matadoras Naturais/imunologia , Melanoma/imunologia , Regressão Neoplásica Espontânea/imunologia , Nevo/imunologia , Neoplasias Cutâneas/imunologia , Antígeno CD56/imunologia , Linfócitos T CD8-Positivos/imunologia , Humanos , Imuno-Histoquímica , Melanoma/patologia , Regressão Neoplásica Espontânea/patologia , Inclusão em Parafina , Neoplasias Cutâneas/patologiaRESUMO
INTRODUCTION: Pancoast syndrome is characterized by Horner syndrome, shoulder pain radiating down the arm, compression of the brachial blood vessels, and, in long-standing cases, atrophy of the arm and hand muscles. It is most commonly associated with lung carcinoma but rarely is seen with certain infections. CASE PRESENTATION: We present the case of a 51-year-old Caucasian man who had acute myeloid leukemia and who developed a rapidly fulminating pneumonia along with signs and symptoms of acute brachial plexopathy and left Horner syndrome. Also, a purpuric plaque developed over his left chest wall and progressed to skin necrosis. The skin biopsy and bronchoalveolar lavage showed a Rhizopus species, leading to a diagnosis of mucormycosis. This is a rare case of pneumonia due to mucormycosis associated with acute Pancoast syndrome. CONCLUSIONS: According to our review of the literature, only a few infectious agents have been reported to be associated with Pancoast syndrome. We found only three case reports of mucormycosis associated with acute Pancoast syndrome. Clinicians should consider mucormycosis in their differential diagnosis in a patient with pulmonary lesions and chest wall invasion with or without neurological symptoms, especially in the setting of neutropenia or other immunosuppressed conditions. It is important to recognize this condition early in order to target therapy and interventions.
RESUMO
Classic Kaposi sarcoma is rare and occurs predominantly in Mediterranean and Middle Eastern men. Since the emergence of acquired immune deficiency syndrome (AIDS)-related Kaposi sarcoma, the incidence, clinicopathologic features, and molecular human herpesvirus 8 (HHV-8) association of American Classic Kaposi Sarcoma has not been fully explored. This study compares Classic Kaposi Sarcoma to AIDS-related Kaposi Sarcoma over the same two decade time period. There were 438 histologically and clinically confirmed Classic Kaposi Sarcoma patients. The ethnic/racial distribution included Caucasian/American (56%), Mediterranean (22%), South American Hispanic (18%), Black (10%), western European (4%), Middle East (4%), Scandinavian (2%), and other (2%). Classic Kaposi Sarcoma was more common in men, 7:1, with a mean age of 74 years. The lesions presented in the lower extremity (69%), in the nodular stage (83%), and HHV-8 was detected by PCR in 40/41 randomly selected cases. A second, non-Classic Kaposi Sarcoma, malignancy was present in 42% (n=45) of the 108 Classic Kaposi Sarcoma patients with complete clinical information, 73% (33 patients) with a higher incidence over the general population. Follow-up of <1-19 years (mean=4.8 years) revealed that 24% of patients died of second malignancy, 22% died of other medical conditions, 2% died of treatment-related complications, and 2% patients died of widespread disease. Thirty-five percent are alive with no evidence of disease and 15% with persistent disease. Human immunodeficiency virus-related Kaposi Sarcoma was observed in 354 cases. There was a male predominance and more aggressive behavior, with higher rates of visceral and disseminated disease. While Classic Kaposi Sarcoma in the United States is an indolent disease and rarely accounts for patient demise, predominantly affecting Caucasian/American males on the lower extremity in the nodular phase, it more importantly may denote an underlying other malignancy. Current PCR probes detect HHV-8 in 98% of Classic Kaposi Sarcoma cases. In comparison, AIDS-related Kaposi Sarcoma is predominately multicentric, visceral, and disseminated, with more aggressive behavior.