RESUMO
BACKGROUND/OBJECTIVE: Focal papillary thyroid carcinoma (PTC) arising within a follicular adenoma (PTCFA) represents a clinically significant, but rare, histopathologic subset of papillary carcinomas whose cytologic features have not been well described. This uncommon presentation of PTC may contribute to a subset of thyroid aspirates interpreted as 'atypia of undetermined significance/follicular lesion of undetermined significance' (AUS/FLUS). STUDY DESIGN: Seventeen fine-needle aspiration biopsy (FNAB) cases diagnosed as 'PTCFA' on corresponding surgical excision were identified from the archival records of 2 large academic medical centers. A control group of 40 FNAB comprised of 20 follicular adenomas (FA) and 20 PTC was identified (based on the corresponding surgical pathology diagnosis) for comparison. All 57 FNAB were reviewed in a masked fashion and scored for a series of 31 cytomorphologic features. The intraclass correlation between diagnostic categories and overall agreement between cytopathologists was statistically evaluated. RESULTS: Aspirates of PTCFA were originally diagnosed as 'negative' (n = 3), 'AUS/FLUS' (n = 7), 'suspicious for a follicular neoplasm' (n = 3), 'suspicious for malignancy' (n = 3), and 'malignant' (n = 1). On masked review, the most common cytomorphologic features of PTCFA were a nonmacrofollicular cytoarchitectural pattern (71%), medium-large cell size (74%), and micronucleoli (79%). Intranuclear pseudoinclusions and a papillary architecture were absent in 85 and 88% of the cases, respectively. Relative to the 2 control groups, the PTCFA cases demonstrated overlapping features between FA and PTC for the majority of the 31 examined cytomorphologic features. CONCLUSION: PTCFA represent a rare subset of PTC that is difficult to recognize as PTC by FNAB. Most cases exhibit overlapping features between a benign thyroid nodule and conventional PTC, and they are often interpreted as 'AUS/FLUS'.
Assuntos
Adenoma/patologia , Carcinoma/patologia , Neoplasias Complexas Mistas/patologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Adenoma/classificação , Adenoma/diagnóstico , Adulto , Biópsia por Agulha Fina , Carcinoma/classificação , Carcinoma/diagnóstico , Carcinoma Papilar , Reações Falso-Negativas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Complexas Mistas/classificação , Neoplasias Complexas Mistas/diagnóstico , Guias de Prática Clínica como Assunto , Prognóstico , Estudos Retrospectivos , Risco , Terminologia como Assunto , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/classificação , Neoplasias da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/classificação , Nódulo da Glândula Tireoide/diagnósticoRESUMO
Insulin-like growth factor I (IGF-I)/somatomedin C is an important mediator of keratinocyte growth in vitro, and the expression of IGF-I receptors in the basal layer of normal epidermis suggests that this growth pathway may function in the regulation of keratinocyte growth in vivo as well. The pattern of IGF-I receptor expression in normal skin is distinct from that of the epidermal growth factor (EGF) receptor, suggesting that these receptors might be differentially regulated. The purpose of this study was to obtain a better understanding of IGF-I receptor function in the skin by examining IGF-I receptor expression in psoriatic epidermis and in cultured human keratinocytes. Our findings indicate that IGF-I receptor expression is increased in psoriasis as measured by protein tyrosine kinase assays of biopsy extracts and by immunohistochemical staining with an IGF-I receptor-specific monoclonal antibody. Unlike EGF receptor expression, which is also increased in psoriatic epidermis, the pattern of IGF-I receptor expression corresponds closely with the increased size of the keratinocyte proliferative compartment in psoriasis. Biochemical agents that diminish EGF receptor ligand binding (phorbol ester or calcium ionophore treatment) produce opposite effects on the IGF-I receptor. These results suggest that cellular expression and differential regulation of both growth factor receptor systems may control critical aspects of epidermal proliferation or function.
Assuntos
Receptores ErbB/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Psoríase/metabolismo , Receptores de Superfície Celular/metabolismo , Anticorpos Monoclonais , Calcimicina/farmacologia , Fator de Crescimento Epidérmico/farmacologia , Epiderme/metabolismo , Humanos , Queratinócitos/metabolismo , Testes de Precipitina , Proteínas Quinases/metabolismo , Receptores de Superfície Celular/imunologia , Receptores de Somatomedina , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
Notch locus EGF-like element mutations spl, altering eye development, and AxE2, affecting wing and sensilla development, are modified by mutations at Delta. It is shown that two allele-specific suppressors of spl involve single amino acid substitutions in the 4th (Dlsup5) and 9th (Dlsup4) EGF-like elements of the Delta protein. Cultured cells producing spl or AxE2 aggregate with cells producing wild-type Delta or Dlsup5 protein, and Dlsup5-producing cells adhere to cells producing wild-type Notch protein. However, spl,AxE2, and Dlsup5 are each defective in promoting these cell affinities, as none of the mutant proteins can compete with the corresponding wild-type proteins for formation of cell aggregates. Thus, widely separated EGF-like elements of Notch and Delta appear to participate in functional molecular interactions between the proteins. Dlsup5 does not improve adhesiveness of spl in vitro, so suppression in vivo may involve altered developmental signaling by spl-Dlsup5 complexes, rather than modified cell adhesion.
Assuntos
Drosophila melanogaster/genética , Fator de Crescimento Epidérmico/química , Hormônios de Inseto/química , Proteínas de Membrana/química , Mutagênese , Sequência de Aminoácidos , Animais , Sequência de Bases , Western Blotting , Adesão Celular , Agregação Celular , Linhagem Celular Transformada , Proteínas de Drosophila , Drosophila melanogaster/crescimento & desenvolvimento , Fator de Crescimento Epidérmico/genética , Hormônios de Inseto/genética , Hormônios de Inseto/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Dados de Sequência Molecular , Receptores Notch , TransfecçãoRESUMO
PDGF has been implicated as one of the principal mitogens involved in cutaneous wound healing. While it has been previously reported that both platelets and monocytes are a source of PDGF in human dermal wound repair, the production of PDGF by human keratinocytes has not yet been described. In this manuscript, we report the production of PDGF by cultured human keratinocytes. Both PDGF A and B chain mRNA can be detected in cultured cells. While only PDGF-AA polypeptide is found in significant levels in keratinocyte-conditioned culture media, all three PDGF isoforms (AA, AB, and BB) are present in detergent-solubilized cell extracts. No evidence of PDGF receptor expression was observed in cultured keratinocytes when analyzed for either mRNA levels or polypeptide expression, suggesting that PDGF does not play an autocrine role in keratinocyte growth. Analysis of cryosections of human cutaneous wounds by immunostaining for PDGF showed that both PDGF A and B chain is constitutively expressed in normal epidermis, as well as in newly reconstituted wound epidermis. No evidence for PDGF receptor polypeptide expression in the epidermis was detected by immunostaining of cryosections.
Assuntos
Queratinócitos/metabolismo , Fator de Crescimento Derivado de Plaquetas/biossíntese , Pele/metabolismo , Ferimentos e Lesões/fisiopatologia , Anticorpos Monoclonais , Biópsia , Células Cultivadas , Meios de Cultivo Condicionados , Ensaio de Imunoadsorção Enzimática , Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Imuno-Histoquímica , Recém-Nascido , Cinética , Substâncias Macromoleculares , Masculino , Fator de Crescimento Derivado de Plaquetas/análise , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Receptores do Fator de Crescimento Derivado de Plaquetas/análise , Receptores do Fator de Crescimento Derivado de Plaquetas/biossíntese , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Ferimentos e Lesões/patologiaRESUMO
Thymidine kinase from herpes simplex virus type 1 (ATP:thymidine 5'-phosphotransferase; EC 2.7.1.21) has been purified from an overexpression system and crystallized against ammonium sulfate by using the hanging-drop technique. The tetragonal crystals are of space group P4122 or P4322, and have unit cell dimensions a = b = 84 A, c = 180 A.
Assuntos
Simplexvirus/enzimologia , Timidina Quinase , Cristalização , Timidina Quinase/isolamento & purificação , Difração de Raios XRESUMO
Psoriasis is characterized by epidermal hyperplasia, altered epidermal maturation, and local accumulation of acute and chronic inflammatory cells. Keratinocyte hyperplasia in psoriasis may be explained in part by overproduction of growth factors or cytokines which stimulate epidermal proliferation and by altered metabolism of growth-factor receptors in affected skin. Psoriatic epidermis displays overproduction of TGF-alpha and interleukin-6 (IL-6), factors produced by keratinocytes and other cell types in psoriatic skin. TGF-alpha and IL-6 are mitogens for normal human keratinocytes and act via specific receptors. The TGF-alpha receptor (EGF receptor) is overexpressed in psoriatic epithelium and its altered expression could be caused in part by gamma interferon which prevents normal receptor down-regulation in response to EGF binding. Several phenotypic features of the psoriatic keratinocyte, including growth activation and expression of HLA-DR, gamma-IP-10, ICAM-1, and other molecules, are best explained as resulting from the combined effects of TGF-alpha, IL-6, and gamma interferon (and possibly other cytokines) on epidermal keratinocytes. The multiple histologic features of psoriasis, including epidermal hyperplasia and accumulation of acute and chronic inflammatory cells, may be mediated by defined growth factors and cytokines that are produced in psoriatic skin and affect the function of diverse cell types.
Assuntos
Fatores Biológicos/fisiologia , Substâncias de Crescimento/fisiologia , Psoríase/etiologia , Receptores de Superfície Celular/fisiologia , Animais , Citocinas , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Psoríase/genéticaRESUMO
Anthralin is an effective topical treatment for active psoriasis; however, its mechanism of action is unknown. Both TGF-alpha and its receptor, the EGF receptor, are overexpressed in active psoriatic plaques and might, therefore, play a role in psoriatic epidermal hyperplasia. In order to assess whether anthralin might act via alteration of this growth factor pathway, we examined the in vitro effects of pharmacologic concentrations of anthralin on cultured normal human keratinocytes. Keratinocyte proliferation was inhibited by 98% at an anthralin concentration of 10 ng/ml. In contrast, lymphocyte proliferation was inhibited by only 50% at an anthralin concentration of 10 micrograms/ml. Anthralin treatment did not induce cell-cycle-specific growth arrest as assessed by flow-cytometric analysis of acridine-orange-stained keratinocytes. Northern analysis of anthralin-treated keratinocytes demonstrated a marked decrease in TGF-alpha mRNA expression. Anthralin-treated keratinocytes showed decreased binding of 125I-EGF and 125I-IGF-I to their respective receptors, but EGF receptor binding was inhibited to a greater extent. Anthralin decreased ligand-binding affinity and cell-surface numbers of EGF receptors as assessed by Scatchard analysis of 125I-EGF binding to anthralin-treated keratinocytes. These results indicate that anthralin alters components of the EGF receptor pathway in cultured keratinocytes and that these effects might contribute to the clinical efficacy of anthralin in the treatment of active psoriasis.
Assuntos
Antralina/farmacologia , Receptores ErbB/metabolismo , Queratinócitos/química , Queratinócitos/ultraestrutura , Psoríase/metabolismo , Fator de Crescimento Transformador alfa/análise , Divisão Celular/efeitos dos fármacos , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Queratinócitos/citologia , Receptores de Superfície Celular/efeitos dos fármacos , Receptores de Somatomedina , Fator de Crescimento Transformador alfa/antagonistas & inibidoresRESUMO
The epidermal growth factor (EGF) receptor pathway is an important mediator of keratinocyte growth in vitro and both receptor and ligand components of this pathway are abnormally expressed in hyperproliferative epidermis. The purpose of this study was to examine interactions between the EGF receptor pathway and the insulin-like growth factor I/somatomedin C (IGF-I) receptor pathway in modulating the growth of cultured normal human keratinocytes. Short-term growth of keratinocytes in a chemically defined medium demonstrated that neither EGF nor IGF-I alone could support significant keratinocyte spreading or proliferation, but that a combination of EGF with IGF-I or high-dose insulin could. IGF-I or high-dose insulin transmodulates keratinocyte EGF receptor expression via the IGF-I receptor in a dose- and time-dependent manner, increasing EGF receptor binding an average of 1.8 times up to a maximum of fourfold without altering EGF binding affinity. Staining of normal human epidermis with an IGF-I receptor specific monoclonal antibody demonstrates that IGF-I receptors localize to the basal proliferative cell compartment, suggesting that IGF-I receptor and EGF receptor pathway interactions may play a role in the regulation of epidermal growth and in the pathogenesis of hyperproliferative skin diseases.
Assuntos
Fator de Crescimento Epidérmico/farmacologia , Receptores ErbB/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Queratinócitos/citologia , Divisão Celular/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Queratinócitos/ultraestrutura , Masculino , Receptores de Superfície Celular/fisiologia , Receptores de Somatomedina , Regulação para CimaRESUMO
Platelet-derived growth factor (PDGF) is a potent mitogenic and chemotactic factor for fibroblasts and other cell types. PDGF effects are mediated by binding of PDGF to dimeric PDGF receptors possessing intrinsic tyrosine kinase activity. We examined the expression pattern of PDGF receptors in cryostat sections of normal and growth-activated human skin using a monoclonal antibody, PR7212, specific for the beta subunit of the PDGF receptor. PDGF receptors were expressed at low levels in normal skin, with only occasional staining of dermal connective tissue cells. In contrast, PDGF receptor expression was greatly elevated in the dermis of growth-activated skin from 15 chronic wounds and 10 psoriatic lesions. PDGF receptors were increased in dermal fibroblasts and in dermal blood vessels in both conditions. Immunoblot analysis confirmed the increased expression of beta-subtype PDGF receptors in psoriatic lesional tissue. PDGF receptors were not detected in normal or growth-activated epidermis. Differential expression of PDGF receptors could regulate increased proliferation of vascular and connective tissue cells observed in psoriasis and chronic wounds.
Assuntos
Fator de Crescimento Derivado de Plaquetas , Psoríase/metabolismo , Receptores de Superfície Celular/metabolismo , Pele/metabolismo , Ferimentos e Lesões/metabolismo , Anticorpos Monoclonais , Western Blotting , Humanos , Imuno-Histoquímica , Receptores do Fator de Crescimento Derivado de Plaquetas , Pele/lesõesRESUMO
We tested the hypothesis that extensively keratinized squamous intraepithelial lesions (SILs) are difficult to grade precisely by identifying 100 Papanicolaou smears with a keratinizing SIL that had been originally judged difficult to grade. Of these, 65 were confirmed as low-grade SIL (LSIL) or high-grade SIL (HSIL) on subsequent biopsy. The 65 smears were reviewed independently by 3 cytopathologists who graded each case as LSIL or HSIL (by Bethesda System criteria). The accuracy of the grade was determined by the subsequent biopsy results; accuracy was compared with that of a historic control group of SILs with biopsy follow-up. In the study group, biopsies showed LSIL in 41 cases and HSIL in 24. The mean accuracy for a smear diagnosis of LSIL was 60% for the study group and 92% for the control group. For a smear diagnosis of HSIL, the accuracy was 60% for the study group and 95% for the control group. The overall kappa value for the study group confirmed poor interobserver agreement. Some keratinizing SILs are difficult if not impossible to grade precisely using standard criteria. For such lesions, the diagnosis "SIL, grade cannot be determined due to extensive keratinization" is justified.
Assuntos
Colo do Útero/metabolismo , Colo do Útero/patologia , Queratinas/metabolismo , Doenças do Colo do Útero/metabolismo , Doenças do Colo do Útero/patologia , Adolescente , Adulto , Idoso , Epitélio/metabolismo , Epitélio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou , Esfregaço VaginalRESUMO
Recent studies have proposed subclassifying ASCUS into "favor reactive" (ASFR), "not otherwise specified" (ASNOS), and "favor squamous intraepithelial lesion (SIL)" (ASFS). This study explored the reproducibility of these diagnoses with Thin-Prep cytology and their association with high-risk human papillomavirus DNA (HRHPV). Three pathologists and 1 cytotechnologist with 2 to 25 years of experience reviewed 144 Thin-Prep (Cytyc, Boxborough, MA) specimens previously diagnosed as normal, ASFR, ASNOS, ASFS, and SIL. Interobserver reproducibility was computed with the kappa statistic. The original laboratory diagnosis was compared with the presence of HRHPV types. Interobserver reproducibility for a normal or SIL diagnosis was very good (kappa = .68 and .63). Reproducibility for ASFR, ASNOS, and ASFS ranged from poor to fair (kappa = .21, .19, and .32). In a weighted analysis, kappa values for ASFR/ASNOS and ASFS/SIL were .36 and .62, respectively. HRHPV-positivity for preparations originally diagnosed as N, ASFR, ASNOS, ASFS, and SIL were 5.7%, 8.8%, 17.4%, 47.8%, and 54.5%, respectively. The difference in index of HRHPV for either N or ASFR and ASFS or SIL was significant (P < .001). Reproducibility for ASCUS is generally poor, but better reproducibility is obtained by combining ASFS with SIL and, to a lesser degree, ASNOS with ASFR. ASFS and SIL confer a similar index of HRHPV and merit similar management. ASFR may be managed with cytologic follow-up; but this may depend upon the individual laboratory. HPV testing, in conjunction with cytologic and biopsy follow-up, appears useful for estimating the significance of ASCUS subgroups in laboratory practice.
Assuntos
Papillomaviridae/isolamento & purificação , Lesões Pré-Cancerosas/patologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal , DNA Viral/isolamento & purificação , Feminino , Humanos , Variações Dependentes do Observador , Lesões Pré-Cancerosas/classificação , Lesões Pré-Cancerosas/virologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Neoplasias do Colo do Útero/classificação , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/classificação , Displasia do Colo do Útero/virologiaRESUMO
Cyclosporine, an immunosuppressive drug, is effective in the treatment of recalcitrant psoriasis. Previous work suggested that keratinocyte hyperproliferation and inflammation are linked in psoriasis and that immune mechanisms participate in the pathogenesis of psoriasis. Transforming growth factor (TGF) alpha may be an important regulatory factor of epidermal growth as overproduction of TGF-alpha is associated with epidermal hyperplasia in psoriatic plaques and epidermal growth factor receptors are overexpressed in psoriatic epithelium. In this study, the effects of cyclosporine on cultured human keratinocytes were examined. Cyclosporine specifically inhibited keratinocyte cell-cycle progression in the G1 phase without causing keratinocytes to terminally differentiate. Cyclosporine did not decrease the expression of TGF-alpha or epidermal growth factor receptors. These results suggest that the effects of cyclosporine on psoriatic skin are unrelated to direct effects on autocrine growth regulation of keratinocytes via TGF-alpha production or of epidermal growth factor receptor modulation.
Assuntos
Quimiocinas CXC , Ciclosporinas/farmacologia , Receptores ErbB/biossíntese , Fase G1/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Fator de Crescimento Transformador alfa/biossíntese , Quimiocina CXCL10 , Ciclosporinas/uso terapêutico , Citocinas/biossíntese , Citocinas/genética , Receptores ErbB/efeitos dos fármacos , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Psoríase/tratamento farmacológico , Transcrição Gênica/efeitos dos fármacos , Fator de Crescimento Transformador alfa/efeitos dos fármacos , Transglutaminases/metabolismoRESUMO
OBJECTIVE: To define the role of microbiologic stains and culture in lung fine needle aspiration (FNA) specimens. STUDY DESIGN: All lung FNA specimens over a nine-year period, with results of both culture and microbiologic stains (Gram's, methenamine silver and acid fast) were reviewed and correlated with clinical information. RESULTS: Sixty-five cases were identified; 13 cases represented clinically significant infections (20%). Gram's stain identified 3 infections and had 1 false positive result, while culture identified 7 infections and had 9 false positive results. However, all false positive cultures represented easily identifiable contaminants, and eight of nine cases had no associated acute inflammation or necrosis. Aspergillus species were detected in four cases by Papanicolaou and silver stain, while culture was positive in only one case. Coccidioides immitis was detected by both Papanicolaou stain and culture in one case. A single case of Mycobacterium tuberculosis was identified by both culture and acid-fast stain. While culture appeared more cost-effective than Gram's stain for identifying bacteria, both Papanicolaou and methenamine silver stain were more cost-effective for identifying fungi. CONCLUSION: In lung FNA specimens, culture and special stains should be restricted to specimens with acute inflammation or necrosis. Gram's stain and fungal culture are insensitive and not cost-effective, and fungi are often identifiable with routine stains.
Assuntos
Pneumopatias/microbiologia , Pneumopatias/patologia , Pulmão/microbiologia , Pulmão/patologia , Coloração e Rotulagem/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Biópsia por Agulha/economia , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/microbiologia , Micoses/patologia , Coloração e Rotulagem/métodosAssuntos
Angiomiolipoma/complicações , Angiomiolipoma/terapia , Infarto/etiologia , Neoplasias Renais/complicações , Neoplasias Renais/terapia , Doenças Testiculares/etiologia , Angiografia , Angiomiolipoma/diagnóstico por imagem , Diagnóstico Diferencial , Fluoroscopia , Humanos , Infarto/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Leucocitose/etiologia , Masculino , Microesferas , Pessoa de Meia-Idade , Necrose/etiologia , Orquiectomia , Radiografia Abdominal , Artéria Renal/patologia , Seminoma/diagnóstico , Doenças Testiculares/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Calretinin (CR) is a valuable marker in the immunohistochemical distinction between malignant mesothelioma (MM) and adenocarcinoma (ACA) in tissue sections. However, there is limited and conflicting data regarding the utility of CR in this differential diagnosis on cytologic material, especially cell block preparations. Also, the possible role of CR in the distinction of papillary serous borderline tumor (SBT) cells from reactive mesothelial cells in peritoneal washings has not been examined. METHODS: Formalin-fixed paraffin-embedded cell block specimens of cytologic fluids, washings, and aspirates with a suspicious or positive cytologic diagnosis and a confirmed diagnosis of MM (29 cases), ACA (39 cases), and SBT (10 cases) were used for CR immunohistochemistry (IHC). RESULTS: Moderate to strong staining in > 50% of tumor cells was noted in 26 of 29 (90%) MMs but in only 3 of 39 (8%) ACAs and 1 of 10 (10%) SBTs. Admixed reactive mesothelial cells (when present) were strongly positive in all fluid specimens, but the staining pattern of benign non-reactive mesothelial cells in washing specimens was less reliable. CONCLUSIONS: CR is both a sensitive and specific marker of reactive and neoplastic mesothelial cells in cytologic cell block preparations and is thus useful in the differential diagnosis of MM and metastatic ACA in malignant effusions. However, CR IHC does not appear to allow definitive identification of SBT in peritoneal washings.
Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/análise , Mesotelioma/diagnóstico , Proteína G de Ligação ao Cálcio S100/análise , Adenocarcinoma/química , Adenocarcinoma/secundário , Calbindina 2 , Diagnóstico Diferencial , Células Epiteliais/química , Feminino , Técnicas de Preparação Histocitológica , Humanos , Imuno-Histoquímica , Mesotelioma/química , Neoplasias Ovarianas/química , Neoplasias Ovarianas/diagnóstico , Sensibilidade e EspecificidadeRESUMO
Focal myxoid change is a well-recognized feature of synovial sarcoma, but the presence of a predominantly myxoid stroma is rare. We describe seven cases of myxoid synovial sarcoma in which marked myxoid change initially obscured the diagnosis, leading to confusion (principally with malignant peripheral nerve sheath tumor). The median age (20 yr) and tumor location (four lower extremity, two upper extremity, and one head and neck region) were similar to those found in typical synovial sarcoma. Histologically, five cases were monophasic spindle cell lesions with a lacy appearance in areas with a prominent Alcian blue-positive myxoid stroma. Each case had foci with more typical features of synovial sarcoma, including a fascicular growth pattern with a variably collagenized stroma, stromal mast cells, a hemangiopericytoma-like vascular pattern, and calcification. Two cases showed small foci of glandular (biphasic) differentiation. Immunohistochemically, all of the seven cases were positive for epithelial membrane antigen, four of six were positive for pan-keratin, three of six were positive for S-100, two of four were positive for CD99, and six of six were negative for desmin. Clinical follow-up in six cases ranged from 8 to 48 months (median, 21 mo). Local recurrence developed in three patients at 9, 20, and 24 months, respectively. In one of these three patients, lung metastases developed at 13 months, and the patient died of disseminated disease at 23 months. In another of the three patients, lung metastases developed at 27 months. Three patients had no evidence of disease at 8, 15, and 15 months. Our data are too limited to indicate any clinical differences between myxoid synovial sarcoma and conventional synovial sarcoma Recognition of this rare histologic variant of synovial sarcoma is important because it can easily be mistaken for other myxoid spindle cell neoplasms, potentially resulting in suboptimal therapy.
Assuntos
Mixossarcoma/patologia , Sarcoma Sinovial/patologia , Adolescente , Adulto , Biomarcadores Tumorais/metabolismo , Criança , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Mixossarcoma/metabolismo , Mixossarcoma/mortalidade , Sarcoma Sinovial/metabolismo , Sarcoma Sinovial/mortalidade , Taxa de SobrevidaRESUMO
The src genes of four Rous sarcoma virus (RSV) mutants temperature-sensitive (ts) for cell transformation were analyzed. The mutant src genes were cloned into a replication-competent RSV expression vector, and the contribution of individual mutations to the ts phenotype was assessed by in vitro recombination with wild-type src sequences. Three of the mutants, which were derived from the Schmidt-Ruppin strain of RSV, each encoded two mutations within the conserved kinase domain. In all three cases, one of the two mutations was an identical valine to methionine change at amino acid position 461. Virus encoding recombinant src genes containing each of these mutations alone were not ts for transformation, demonstrating that two mutations are required for temperature sensitivity. The sequence of the src gene of the Bryan high-titer strain of RSV was determined and compared with that of the fourth ts mutant which was derived from it, again revealing two lesions in the kinase domain of the mutant.
Assuntos
Vírus do Sarcoma Aviário/genética , Oncogenes , Proteínas dos Retroviridae/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Ciclo Celular , Transformação Celular Viral , Células Cultivadas , Galinhas , Clonagem Molecular , Mutação , Proteína Oncogênica pp60(v-src) , Fenótipo , Conformação Proteica , Relação Estrutura-Atividade , TemperaturaRESUMO
BACKGROUND: Papanicolaou smear sensitivity for cervical adenocarcinoma (CVCA) is not well established. Also uncertain are the relative contributions to falsely negative diagnoses of sampling, screening, and interpretive errors. METHODS: Papanicolaou smears were identified from all patients at our institutions with biopsy-proven cervical adenocarcinoma from 1988-1998. All available negative and unsatisfactory smears were reviewed. RESULTS: Of 49 patients with CVCA, 66 smears initially diagnosed as negative and 4 smears initially diagnosed as unsatisfactory from 30 patients were identified. Thirty-two negative smears and 4 unsatisfactory smears from 19 patients were available for review. The retrospective diagnoses in the cases initially called negative were: unsatisfactory in 2, negative in 15, and atypical glandular cells consistent with either adenocarcinoma in situ (AIS) or CVCA in 15. Three of four smears initially called unsatisfactory had neoplastic glandular cells identified retrospectively. The 18 falsely negative or falsely unsatisfactory smears were from 13 patients obtained up to 5 years before biopsy diagnosis. These smears contained neoplastic cells likely to have been mistaken for lower segment endometrial cells (LUS) or endocervical cells with tubal metaplasia (TM) in 11, reactive endocervical cells in 6, and both in 1. In 16 of the 18 smears, the abnormal cells were abundant, although preservation was suboptimal in 6. CONCLUSIONS: Sensitivity of a single Papanicolaou smear for CVCA was between 45% and 76% depending on the classification of negative slides that were not available for review, comparable to previously reported sensitivity for AIS. The diagnostic false-negative or false-unsatisfactory rate in reviewed smears was 50% (18 of 36). Diminished sensitivity is due to the under recognition of glandular neoplasia resembling LUS, TM, or reactive endocervical cells. Cancer (Cancer Cytopathol)
Assuntos
Adenocarcinoma/patologia , Teste de Papanicolaou , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal , Biópsia , Reações Falso-Negativas , Feminino , Humanos , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Granular cell tumors (GCTs) are uncommon tumors of putative schwannian derivation that are rarely malignant. Although recent studies have addressed a histologic correlation with malignant behavior, similar studies have not been done on cytologic material. METHODS: The authors evaluated 3 malignant GCTs and 17 benign GCTs (comprising 17 fine-needle aspiration biopsy samples and 3 samples from direct scrapes) for the following cytologic features: hyperchromasia; coarse chromatin; nuclear-to-cytoplasmic (N/C) ratio; nuclear pleomorphism; and vesicular nuclei with enlarged nucleoli, mitoses, necrosis, and spindle cell morphology. RESULTS: Hyperchromasia, coarse chromatin, increased N/C ratio, nuclear pleomorphism, and vesicular nuclei with enlarged nucleoli and spindle cell morphology were associated the most closely with malignancy when they were present throughout the cytologic sample. All were diffusely present in three of three malignant tumors, except vesicular nuclei and spindle cell morphology, which were present diffusely in two tumors and focally in one tumor. By contrast, although one to five of these features were present focally in 8 of 17 benign GCTs, none was present diffusely in any benign GCTs, with one exception, which had a combination of focal nuclear pleomorphism and hyperchromasia together with diffuse vesicular nuclei, large nucleoli, and coarse chromatin. The N/C ratio in this tumor was not increased, and there were no spindle cells or mitoses. Mitoses were present in 2 of 3 malignant GCTs and absent from all 17 benign GCTs. Necrosis was not seen in any tumors. CONCLUSIONS: Malignant GCTs have characteristic cytologic features that differ from those of benign GCTs. However, morphologic heterogeneity precludes definitive classification of some tumors by cytologic features alone.
Assuntos
Cromatina , Tumor de Células Granulares/patologia , Adolescente , Adulto , Biópsia por Agulha , Núcleo Celular/patologia , Citoplasma , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitose , Necrose , Valor Preditivo dos Testes , Prognóstico , Estudos RetrospectivosRESUMO
Sodium-N-butyrate (NaB) induces terminal differentiation and cornified envelope formation in cultured human keratinocytes. In the present study we explored the question of whether NaB-induced maturation could be mediated through changes in TGF-alpha and TGF-beta expression in normal keratinocytes. NaB induced a four-fold increase in TGF-beta mRNA transcript levels. This increase in TGF-beta mRNA abundance occurred only within the nonbasal keratinocyte subpopulation which maximally responds to NaB treatment by progression to cornified envelopes. Basal keratinocytes, which are relatively refractive to cornified envelope formation, did not show any increase in TGF-beta mRNA abundance after NaB treatment. By comparison, TGF-alpha mRNA transcript and extracellular TGF-alpha protein levels were unaffected by NaB treatment. A 50% decrease in EGF receptor binding was observed in NaB-treated keratinocyte cultures, rendering the cells less responsive to proliferation induction.