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1.
Acad Pathol ; 5: 2374289518777463, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29978019

RESUMO

Faculty value equitable and transparent policies for determining salaries and expect their compensation to compare favorably to the marketplace. Academic institutions use compensation to recruit and retain talented faculty as well as to reward accomplishment. Institutions are therefore working to decrease salary disparities that appear arbitrary or reflect long-standing biases and to identify metrics for merit-based remuneration. Ours is a large academic pathology department with 97 tenure-track faculty. Faculty salaries are comprised of 3 parts (A + B + C). Part A is determined by the type of appointment and years at rank; part B recognizes defined administrative, educational, or clinical roles; and part C is a bonus to reward and incentivize activities that forward the missions of the department and medical school. A policy for part C allocations was first codified and approved by department faculty in 1993. It rewarded performance using a semiquantitative scale, based on subjective evaluations of the department director (chair) in consultation with deputy directors (vice chairs) and division directors. Faculty could not directly calculate their part C, and distributions data were not widely disclosed. Over the last 2 years (2015-2017), we have implemented a more objective formula for quantifying an earned part C, which is primarily designed to recognize scholarship in the form of research productivity, educational excellence, and clinical quality improvement. Here, we share our experience with this approach, reviewing part C calculations as made for individual faculty members, providing a global view of the resulting allocations, and considering how the process and outcomes reflect our values.

2.
Mod Pathol ; 26(12): 1586-93, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23640129

RESUMO

Hepatocellular carcinomas exhibit heterogeneous morphologies by routine light microscopy. Although some morphologies represent insignificant variations in growth patterns, others may represent unrecognized subtypes of hepatocellular carcinoma. Identification of these subtypes could lead to separation of hepatocellular carcinomas into discrete groups with unique underlying genetic changes, prognosis, or therapeutic responses. In order to identify potential subtypes, two pathologists independently screened a cohort of 219 unselected hepatocellular carcinoma resection specimens and divided cases into potential subtypes. One of these promising candidate subtypes was further evaluated using histological and molecular techniques. This subtype was characterized by a unique and consistent set of histological features: smooth chromophobic cytoplasm, abrupt focal nuclear anaplasia (small clusters of tumor cells with marked nuclear anaplasia in a background of tumor cells with bland nuclear cytology), and scattered microscopic pseudocysts--we designate this variant as 'chromophobe hepatocellular carcinoma with abrupt anaplasia'. Thirteen cases were identified (6% of all hepatocellular carcinomas), including 6 men and 7 women with an average age of 61 years. Six cases occurred in cirrhotic livers. Serum AFP was elevated in 6 out of 10 cases. There were a variety of underlying liver diseases, but cases were enrichment for chronic hepatitis B, P=0.006. Interestingly, at the molecular level, this variant was strongly associated with the alternative lengthening of telomere (ALT) phenotype by telomere FISH. ALT is a telomerase-independent mechanism of telomere maintenance and is found in approximately 8% of unselected hepatocellular carcinomas. In contrast, 11/12 (92%) of the cases of chromophobe hepatocellular carcinoma with abrupt anaplasia were ALT-positive. In summary, we propose that chromophobe hepatocellular carcinoma with abrupt anaplasia represents a new subtype of hepatocellular carcinoma with unique morphological and molecular features.


Assuntos
Carcinoma Hepatocelular/classificação , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/classificação , Neoplasias Hepáticas/patologia , Anaplasia/patologia , Carcinoma Hepatocelular/genética , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Telômero
4.
Am J Clin Pathol ; 138(2): 223-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22904133

RESUMO

The use of human papillomavirus DNA testing plus Papanicolaou (Pap) testing (cotesting) for cervical cancer screening in women 30 years and older has been recommended since 2006. However, few studies have detailed the adoption of such cotesting in clinical practice. We examined the trends in monthly percentage of Pap tests ordered as cotests in our laboratory over a 2.5-year period and used joinpoint regression to identify periods in which there was a change in the average monthly proportion of cotests. Cotesting of patients 30 years and older increased from 15.9% in January 2008 to 39.4% in June 2010. In patients aged 18 to 29 years, cotesting initially increased, but showed a downward trend in the last 14 months of the study, ending at 7.7% in June 2010. Our study highlights increased adoption of age-appropriate cotesting as well as the persistence of age-inappropriate cotesting.


Assuntos
Detecção Precoce de Câncer/estatística & dados numéricos , Programas de Rastreamento/métodos , Teste de Papanicolaou , Padrões de Prática Médica/estatística & dados numéricos , Infecções Tumorais por Vírus/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Esfregaço Vaginal/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colo do Útero/virologia , Feminino , Humanos , Maryland , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Papillomaviridae , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/virologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Adulto Jovem
5.
JIMD Rep ; 5: 95-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23430923

RESUMO

Gaucher disease type 2 [OMIM #230800] is a rare lysosomal storage disorder with usual onset between 3 and 6 months of age leading to progressive neurodegeneration and death within the first 2 years of life. Rarely it may lack the characteristic symptom-free period and initially manifest prenatally or in the neonatal period. The early course of neonatal onset classic type 2 variants is not well known, and reports of early histological changes in the liver of type 2 Gaucher disease patients are scarce. We describe a patient who presented in the immediate postnatal period with cholestasis without hepatomegaly associated with hepatocellular giant-cell transformation on liver biopsy, thrombocytopenia, and failure to thrive. This was initially thought to represent neonatal giant-cell hepatitis and the correct diagnosis was not made until the age of 6 months. Hepatocellular giant transformation has not been described in the classic acute neuronopathic form of GD. However, it has been reported in congenital GD with nonimmune hydrops and neonatal hepatitis, an example of perinatal lethal Gaucher disease (PLGD), which sometimes is regarded as an entity separate from GD type 2. Our case illustrates that neonatal cholestasis may be part of a spectrum of manifestations which spans a continuum between the PLGD and classic type 2 GD. Giant cells are a nonspecific finding but may reflect the presence of a systemic inflammatory process that recently has been implicated in the brain stem degeneration associated with acute neuronopathic GD.

6.
Obstet Gynecol ; 118(2 Pt 1): 289-295, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21775844

RESUMO

OBJECTIVE: To estimate time trends of actual provider use of human papillomavirus (HPV) testing in cervical cancer screening by using laboratory and administrative data from the Johns Hopkins Hospital Division of Cytopathology in Baltimore, Maryland. METHODS: In this ecologic trend study, we analyzed 178,510 Pap specimen records and 12,221 HPV tests among 85,048 patients from 2001 to 2007. Monthly frequencies and proportions of HPV reflex testing and HPV cotesting with Pap (stratified by patient ages 30 and older and 18-29 years) were calculated. Time trends of monthly HPV testing proportions were analyzed using joinpoint regression methods. RESULTS: From April 2002, when the American Society for Colposcopy and Cervical Pathology added HPV reflex testing to its guidelines, to December 2007, the monthly the proportion of reflex testing was 95.8%. From February 2004, when the society added HPV cotesting with Pap among women aged 30 years or older to its guidelines, to December 2007, the overall proportion HPV cotesting with Pap among patients aged 30 years or older was 7.8% (compared with 4.9% among patients 18-29 years [P<.01]). The highest proportion of HPV cotesting among women aged 30 years or older, 15%, was observed in September 2006, and the trend later plateaued around 13%. The monthly proportions of HPV reflex testing and cotesting with Pap changed significantly over time. CONCLUSION: These data reveal that a small percentage of women aged 30 years or older received HPV cotesting with Pap, thus identifying a significant opportunity for providers to improve patient care in cervical cancer prevention. LEVEL OF EVIDENCE: III.


Assuntos
Papillomaviridae , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal , Centros Médicos Acadêmicos , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/estatística & dados numéricos , Adulto Jovem
7.
Clin Gastroenterol Hepatol ; 9(4): 357-362.e2, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21238606

RESUMO

BACKGROUND & AIMS: Pathologists participating in the National Institutes of Health-sponsored Biliary Atresia Research Consortium (BARC) developed and then evaluated a standardized system for histologic reporting of liver biopsies from infants with cholestasis. METHODS: A set of 97 anonymous liver biopsy samples was sent to 10 pathologists at BARC centers. A semiquantitative scoring system that had 16 histologic features was developed and then used by the pathologists, who had no knowledge of clinical history, imaging results, or laboratory data. Interobserver agreement was evaluated statistically. Agreement on scoring of each feature and on the pathologists' diagnosis, compared with the final clinical diagnosis, was evaluated by using weighted kappa statistics. RESULTS: There was moderate to substantial interobserver agreement in identification of bile plugs in ducts, giant-cell transformation, extramedullary hematopoiesis, and bile duct proliferation. The pathologists' diagnosis of obstruction in clinically proven cases of biliary atresia (BA) ranged from 79%-98%, with a positive predictive value of 90.7%. Histologic features that best predicted BA, on the basis of logistic regression, included bile duct proliferation, portal fibrosis, and absence of sinusoidal fibrosis (each P<.0001). CONCLUSIONS: The BARC histologic assessment system identified features of liver biopsies from cholestatic infants, with good interobserver agreement, that might be used in diagnosis and determination of prognosis. The system diagnosed BA with a high level of sensitivity and identified infants with biliary obstruction with reasonable interobserver agreement. However, distinguishing between BA and disorders such as total parenteral nutrition-associated liver disease and alpha(1)-antitrypsin deficiency is not possible without adequate clinical information.


Assuntos
Atresia Biliar/diagnóstico , Atresia Biliar/patologia , Colestase/diagnóstico , Colestase/patologia , Histocitoquímica/métodos , Biópsia , Histocitoquímica/normas , Humanos , Lactente , Recém-Nascido , Fígado/patologia , Sensibilidade e Especificidade
8.
Dig Liver Dis ; 42(9): 657-60, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20227931

RESUMO

Autoimmune hepatitis (AIH) is thought to be a primary liver disease, occurring in the absence of any known etiology. We present three unusual cases of new-onset AIH in young female patients with longstanding preexisting liver disease (Alagille's syndrome, cystic fibrosis liver disease and sickle cell hepatopathy). All patients developed an insidious onset of abdominal pain, fatigue, jaundice and hepatitis after many years of their primary diagnosis and had negative serology for hepatitis A, B, C, cytomegalovirus and Epstein-Barr virus. The occurrence of AIH in these patients may be due to a complex interaction between the underlying liver disease, chronic medication use and genetic predisposition resulting in altered immunoregulatory mechanisms.


Assuntos
Síndrome de Alagille/complicações , Anemia Falciforme/complicações , Fibrose Cística/complicações , Hepatite Autoimune/complicações , Hepatite Autoimune/diagnóstico , Adolescente , Feminino , Hepatite Autoimune/patologia , Humanos , Adulto Jovem
9.
Dig Dis Sci ; 55(11): 3052-8, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20108035

RESUMO

BACKGROUND: Alagille syndrome is a multi-system developmental disorder associated with paucity of interlobular bile ducts and cholestasis, rarely associated with hepatocellular carcinoma. Associated syndromic co-morbidities may complicate surgical management. As such, we herein review the modern management of a large hepatocellular carcinoma in an adult patient with Alagille syndrome and review the literature of adult Alagille patients with hepatocellular carcinoma. CASE PRESENTATION: A 29-year-old woman with a history of Alagille syndrome was referred with biopsy-proven 12 × 8 cm hepatocellular carcinoma replacing her right liver. Biopsy of the contralateral liver demonstrated findings consistent with Alagille syndrome, but no underlying cirrhosis. CT volumetrics demonstrated a future liver remnant of 40%. Extensive hematologic and cardiac work-up was performed pre-operatively, given the syndrome's associated bleeding dyscrasias and cardiac abnormalities. The patient underwent a margin-negative right hepatectomy using the "hanging" technique through a thoracoabdominal approach. The patient developed a transient hyperbilirubinemia but no hepatic insufficiency and did well post-operatively. CONCLUSION: Since Alagille syndrome affects multiple organ systems, preoperative evaluation of cardiac, hematologic, and hepatic function should be considered. This case illustrates the peri-operative management of an Alagille patient, and highlights several key technical points that contributed to a successful resection.


Assuntos
Síndrome de Alagille/epidemiologia , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/cirurgia , Adulto , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Comorbidade , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X
10.
Am J Clin Pathol ; 131(2): 243-9, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19141384

RESUMO

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by inflammatory destruction of the intrahepatic bile ducts. The differential diagnosis for PBC often includes autoimmune hepatitis (AIH). Both diseases can show prominent plasma cells and other overlapping histologic features. It is interesting that both diseases can involve elevated levels of serum immunoglobulins, with IgM elevations typical of PBC and IgG elevations typical of AIH. We investigated whether this difference could be useful histologically by immunostaining plasma cells in liver biopsy specimens for IgG and IgM. We examined 56 cases: 18 of PBC and 38 of AIH. In PBC, plasma cells in the portal tracts were predominantly IgM+, whereas in AIH, plasma cells were predominately IgG+ (P < .0001). Immunostaining for IgM and IgG can be helpful in differentiating PBC from AIH.


Assuntos
Cirrose Hepática Biliar/patologia , Fígado/patologia , Plasmócitos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Biomarcadores/metabolismo , Diagnóstico Diferencial , Feminino , Hepatite Autoimune/diagnóstico , Humanos , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Imuno-Histoquímica , Fígado/metabolismo , Cirrose Hepática Biliar/metabolismo , Masculino , Pessoa de Meia-Idade , Plasmócitos/metabolismo , Sistema Porta/metabolismo , Sistema Porta/patologia , Adulto Jovem
11.
Hum Pathol ; 40(4): 484-8, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19084266

RESUMO

Common variable immunodeficiency is an important form of primary immunodeficiency disease. The most recognized histologic manifestation of common variable immunodeficiency is a paucity of plasma cells in gut biopsies. However, chronic inflammation can affect other organs including the liver. This study was designed to characterize the histologic findings in liver biopsies of individuals with common variable immunodeficiency. Thirteen liver biopsies from 10 patients were identified. The most common indication for biopsy was elevated liver enzymes, hepatomegaly, and/or splenomegaly. The biopsies typically showed mild portal and mild-to-moderate lobular chronic inflammation with minimal or absent interface activity. Plasma cells were absent in all cases. The biopsy specimens showed no fibrosis (n = 5) or mild portal fibrosis (n = 5). In 2 patients with follow-up biopsies, no fibrosis progression was identified. Four individuals showed small numbers of scattered portal and/or lobular granulomas, 3 of whom had diagnoses of coexistent sarcoidosis. Overall, the inflammatory changes in the biopsies were reminiscent of those seen in individuals with chronic inflammation of the gut, which can lead to translocation of intestinal luminal antigens to the liver and a mild hepatitis. Subsequent review of concurrent intestinal biopsies available in 7 individuals showed intestinal inflammation in 5 of 7 cases. In conclusion, liver biopsies in individuals with common variable immunodeficiency show mild portal and lobular inflammation with no or mild portal fibrosis. The etiology of the common variable immunodeficiency hepatitis remains unclear but, in some cases, may be secondary to mucosal inflammation in the gastrointestinal tract.


Assuntos
Imunodeficiência de Variável Comum/complicações , Hepatite/complicações , Hepatite/imunologia , Hepatite/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/patologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade
12.
J Pediatr Gastroenterol Nutr ; 46(4): 423-8, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18367956

RESUMO

OBJECTIVE: To develop a protocol for safe performance of percutaneous liver biopsies in children with deficiency of factor VIII (n = 12) or IX (n = 2) and chronic hepatitis C virus infection. PATIENTS AND METHODS: Liver biopsies were performed after administration of factor VIII or IX, before and 24 weeks after cessation of antiviral therapy. To define the optimal means of providing replacement therapy, 10 children were enrolled in a randomized crossover design study of bolus versus continuous factor VIII for performance of the liver biopsy. For the crossover study, all of the patients were given a loading dose of 50 +/- 5 IU recombinant factor (rF)VIII/kg; a minimum of factor VIII activity of > or = 80% 30 to 60 minutes following factor VIII infusion was required for liver biopsy. For the bolus protocol, rFVIII 25 to 50 IU/kg was given 6, 14, 24, 36, 48, and 60 hours after completion of the loading dose. For the continuous protocol, rFVIII was given 3 to 4 IU/kg per hour for 48 hours, followed by a bolus of 25 IU/kg at 60 hours. In patients with factor IX deficiency, a loading dose of 100 IU/kg was followed by a bolus of 50 IU/kg at 3, 15, 27, and 48 hours after the loading dose. RESULTS: Twenty liver biopsies were performed in children with factor VIII deficiency without major complications. One of the 3 biopsies in the patients with factor IX deficiency was complicated by a hemoperitoneum. Midazolam and fentanyl were used in the first 8 patients. However, postbiopsy pain, presumably secondary to hematoma in 2 patients and hemoperitoneum in 1, prompted us to use ultrasound to locate a suitable biopsy site and to change to propofol; this allowed us to better immobilize the liver, to minimize postbiopsy bleeding. The subsequent 15 biopsies were well tolerated without postbiopsy pain or other complication. CONCLUSIONS: Percutaneous liver biopsy in children with factor VIII deficiency can be safely performed using either bolus or continuous infusion of recombinant factor VIII. A brief general anesthetic and ultrasound guidance are recommended.


Assuntos
Biópsia/métodos , Hemofilia A/complicações , Hepatite C Crônica/complicações , Fígado/patologia , Biópsia/efeitos adversos , Criança , Estudos Cross-Over , Fator IX/administração & dosagem , Fator VIII/administração & dosagem , Hematoma/etiologia , Hemoperitônio/etiologia , Hemofilia A/virologia , Humanos , Masculino , Complicações Pós-Operatórias , Segurança , Resultado do Tratamento
13.
Mod Pathol ; 21(4): 491-7, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18246041

RESUMO

Hepatic adenomas are benign neoplasms of the liver that occur in several well-defined clinical settings, but principally that of excess hormone exposure. They have a small but poorly characterized risk of malignant degeneration. The clinical presentation and pathological findings were reviewed for all hepatic adenomas resected between January 1, 2003 and July 1, 2006. Immunohistochemistry for p53, beta-catenin and alpha-fetoprotein (AFP) were performed on those cases with malignant transformation and exon 3 of beta-catenin was amplified and sequenced. A total of 17 hepatic adenomas were resected and 3 showed malignant transformation. All three cases were in women with an age range of 23-33 years. The clinical presentations were vague abdominal pain. Histologically, the malignant transformation occurred within otherwise typical hepatic adenomas. Two of three cases showed patchy atypia throughout the hepatic adenoma. The hepatocellular carcinoma arose as distinct nodules directly within the adenomas, effectively ruling out synchronous lesions. The hepatocellular carcinomas were unifocal in two cases and multifocal in one case with the greatest dimensions of the hepatocellular carcinoma being 2.5, 2.2, and 1 cm. Immunostains for AFP and beta-catenin were negative in both the hepatic adenomas and areas of hepatocellular carcinoma. p53 immunostaining was positive within the areas of malignant transformation in one case. No mutations or deletions were seen in exon 3 of the beta-catenin gene for either the adenomas or the carcinoma. In conclusion, two of the cases that developed hepatocellular carcinomas showed cytological atypia in the background adenoma. The hepatocellular carcinomas arose as distinct nodules within the adenomas. No common molecular pathway of hepatocellular carcinogenesis was observed by examining AFP, beta-catenin, and p53 immunostains and no beta-catenin mutations or deletions were found.


Assuntos
Adenoma de Células Hepáticas/patologia , Carcinoma Hepatocelular/patologia , Transformação Celular Neoplásica/patologia , Neoplasias Hepáticas/patologia , Adenoma de Células Hepáticas/genética , Adenoma de Células Hepáticas/metabolismo , Adulto , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Anticoncepcionais Orais Hormonais/efeitos adversos , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteína Supressora de Tumor p53/biossíntese , alfa-Fetoproteínas/biossíntese , beta Catenina/genética
14.
Am J Surg Pathol ; 31(11): 1754-8, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18059233

RESUMO

Acute hepatitis C in immunocompetent individuals is rarely symptomatic and rarely biopsied. Thus, the histologic descriptions of acute hepatitis C remain limited. The histology of 5 cases of acute hepatitis C in adults were studied by selecting cases from the consult and surgical pathology files of a single institution. The 5 individuals, 3 males and 2 females, had an average age at biopsy of 50+/-17 years. They presented with jaundice and other nonspecific abdominal symptoms. The time interval from clinical presentation to biopsy ranged from 2 to 18 weeks. The average alanine aminotransferase/aspartate aminotransferase/alkaline phosphatase at the time of biopsy was 308/73/85 U/L. The average total bilirubin was 5.2 mg/dL. Each individual had a single liver biopsy. The histologic findings of the 2 cases biopsied in close temporal proximity to the initial clinical presentation showed similar histologic findings of mixed portal infiltrates with lymphocytes and neutrophils along with bile ductular proliferation that raised the possibility of down stream biliary tract disease. The lobules showed canalicular cholestasis and mild to moderate inflammation. In the third and fourth case, obtained 8 weeks after presentation, the biopsies showed mild to moderate portal and lobular lymphocytic inflammation, findings that were also present in the last case, obtained 18 weeks after presentation. In conclusion, early after acute hepatitis C viral infection, biopsies can have a cholestatic pattern whereas later biopsies tend to show mild nonspecific portal and lobular lymphocytic inflammation. Proper histologic diagnosis can be aided by an awareness of the various histologic findings, which vary depending on the time interval from clinical symptoms to biopsy.


Assuntos
Colestase/patologia , Hepatite C/patologia , Imunocompetência , Fígado/patologia , Adulto , Idoso , Antivirais/uso terapêutico , Ductos Biliares Intra-Hepáticos/patologia , Biópsia , Proliferação de Células , Colestase/imunologia , Diagnóstico Diferencial , Feminino , Hepatite C/tratamento farmacológico , Hepatite C/imunologia , Humanos , Interferons/uso terapêutico , Fígado/imunologia , Fígado/virologia , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Necrose , Infiltração de Neutrófilos , Neutrófilos/patologia , Polietilenoglicóis/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
15.
Am J Surg Pathol ; 30(9): 1085-90, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16931952

RESUMO

Ground glass cytoplasmic change in hepatocytes is typically associated with chronic hepatitis B infection. We report 12 cases of glycogen pseudoground glass change that closely mimics hepatitis B inclusions. Nine individuals were immunosuppressed secondary to liver or kidney transplant (N=3), bone marrow transplant (N=2), HIV infection (N=2), kidney dialysis (N=1), or chronic inflammatory bowel disease (N=1). Medication history was available in 10 individuals and all were on multiple medications (range 2 to 33). Histologically, the pseudoground glass change was identical to the ground glass change seen in chronic hepatitis B infection, with distinct, circumscribed, gray-glassy inclusions surrounded by a rim of cytoplasm. The background livers showed mild or no inflammation and mild or no fibrosis. All cases were negative for chronic hepatitis B infection. The pseudoground glass change was PAS positive and diastase sensitive. Electron microscopy of the inclusions showed glycogen in 3/3 cases. No evidence for viral particles or significant endoplasmic reticulum proliferation was seen. Three cases had follow-up biopsies (1, 1, and 36 mo), and the pseudoground glass was persistent in 2 cases and showed partial resolution in 1 case (1 mo biopsy interval). We conclude that glycogen pseudoground glass change is typically seen in immunosuppressed individuals on numerous medications. The changes are generally seen in the background of mild chronic hepatitis with mild or no fibrosis. Glycogen pseudoground glass change can resolve, but may also persist for years.


Assuntos
Glicogênio/análise , Hepatócitos/ultraestrutura , Adulto , Criança , Pré-Escolar , Citoplasma/ultraestrutura , Feminino , Hepatite B Crônica/patologia , Hepatócitos/química , Humanos , Terapia de Imunossupressão , Corpos de Inclusão/ultraestrutura , Masculino , Pessoa de Meia-Idade
16.
Am J Clin Pathol ; 124(4): 512-8, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16146811

RESUMO

Primary liver carcinomas in children and young adults are uncommon and poorly described. We examined primary liver carcinomas in people younger than 30 years and performed immunostains for markers of biliary (cytokeratin [CK] 7, CK19, CD56) and hepatocellular (HepPar) differentiation. We found 23 primary liver carcinomas were found: 13 hepatocellular carcinomas (HCCs), 9 fibrolamellar carcinomas (FLCs), and 1 cholangiocarcinoma. Most HCCs showed compact (n = 7) or trabecular (n = 4) growth patterns. The Edmondson grades were as follows: 1, 3 tumors; 2, 8 tumors; and 3, 2 tumors). All HCCs and FLCs were HepPar(+). All FLCs and 7 of 9 HCCs were CK7(+). In contrast, a control group of 65 adult HCCs showed less CK7 positivity (24 [37%]; P = .03). CK19 was positive in 2 HCCs and CD56 in 1 HCC. No chronic background liver disease was seen, although 3 cases showed foci of altered hepatocytes. HCCs are the most common primary liver carcinoma in children and young adults followed by FLCs. They are morphologically similar to adult HCC, but more likely to be CK7(+).


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias dos Ductos Biliares/química , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/química , Ductos Biliares Intra-Hepáticos/patologia , Biomarcadores Tumorais/análise , Antígeno CD56/análise , Carcinoma Hepatocelular/química , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica/métodos , Queratina-7 , Queratinas/análise , Neoplasias Hepáticas/química , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
17.
J Urol ; 172(5 Pt 1): 1835-9, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15540733

RESUMO

PURPOSE: Radical retropubic prostatectomy (RRP) as definitive management for clinically localized prostate cancer is commonly performed within months of diagnosis. Despite patient anxiety there is little evidence to suggest that a delay of several months from diagnosis to RRP is associated with a worse cancer control rate. However, a recent study cast doubt on the safety of such a delay with respect to cancer control. Therefore, in a contemporary series we determined long-term cancer control in men who underwent RRP for clinically localized prostate cancer with some treated early and others treated after a longer delay. MATERIALS AND METHODS: We analyzed data on 926 men who underwent RRP between January 1989 and December 1994. Age, preoperative serum prostate specific antigen (PSA), biopsy Gleason score, clinical and pathological stage, and biochemical recurrence were compared between 162 men who underwent RRP 60 days or less from biopsy and 764 who underwent RRP after a greater delay. Disease-free (PSA less than 0.2 ng/ml) survival rates were compared using Kaplan-Meier analysis. Pathological staging was compared using logistic regression. RESULTS: The different groups were well matched for age, serum PSA, pathological stage and followup. However, significantly more men who underwent RRP between 121 and 150 days, and 151 days or greater had T1c disease (48% and 57% vs 35%, p<0.04 and <0.0001, respectively). In addition, significantly more men operated on at 151 days or greater had biopsy Gleason scores 2 to 6 (86% vs 65%, p<0.0001) and significantly fewer had Gleason score 7 disease (13% vs 30%, p<0.002). Men who underwent RRP after 60 or less days had 5 and 10-year biochemical disease-free survival rates comparable to those in men who underwent RRP after 61 to 90, 91 to 120 and 121 to 150 days after diagnosis (82% and 78%, 86% and 78%, 86% and 75%, and 86% and 82%, respectively). Those operated on at 151 days or greater had significantly greater 5 and 10-year biochemical disease-free survival rates (89% and 87%, p<0.04). However, when patients were stratified into different subgroups based on clinical stage, serum PSA and biopsy Gleason score a delay of 150 days or greater no longer impacted differently on long-term cancer control rates. CONCLUSIONS: Delays of up to several months from prostate cancer diagnosis to RRP do not appear to impact long-term biochemical cancer control rates. Therefore, patients can be reassured that there is no immediate urgency to perform RRP after prostate cancer diagnosis, especially in those with T1c disease and biopsy Gleason scores less than 7.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias da Próstata/cirurgia , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
18.
J Hepatol ; 39(5): 738-41, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14568255

RESUMO

BACKGROUND/AIMS: Fibrosis in chronic hepatitis C infection begins in portal tracts, and can progress to 'bridging fibrosis' and eventually lead to cirrhosis. All current fibrosis staging systems are based on these three conceptual fibrosis stages (portal fibrosis, bridging fibrosis, cirrhosis) and vary only in how these stages are further subdivided. Despite the importance of bridging fibrosis, little is known about its three-dimensional characteristics. METHODS: Foci of bridging fibrosis were digitally reconstructed in three dimensions on two separate liver specimens with chronic hepatitis C viral infection. The amount of portal fibrosis was then correlated with bile duct diameter on trichrome-stained sections. RESULTS: After three-dimensional reconstruction, the bridges were seen to represent webs or membranes of fibrosis located at branch points of the portal tracts that extended between two portal branches, much like the webbing between the thumb and forefinger in a baseball-mitt. Direct measurements indicated that early portal fibrosis was associated with portal tracts containing bile ducts of approximately 18-19 mum diameter. CONCLUSIONS: Fibrosis bridges are located at branch points of portal tracts and are composed of three-dimensional webs or membranes that extend between portal tracts; when viewed as two dimensions on a glass slide, a 'bridge' of fibrosis is seen.


Assuntos
Hepatite C Crônica/complicações , Processamento de Imagem Assistida por Computador , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Idoso , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Sistema Porta/patologia
19.
Am J Surg Pathol ; 27(11): 1454-7, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14576479

RESUMO

The diagnosis of extrahepatic biliary atresia can be challenging as the histologic features can overlap with other pediatric cholestatic liver diseases. Several previous studies have noted that biliary epithelium is positive for CD56 in the setting of extrahepatic biliary tract disease. Thus, we explored the use of CD56 in evaluating liver biopsy specimens for extrahepatic biliary atresia. A total of 22 cases were selected and immunostained for CD56, including 14 cases of confirmed extrahepatic biliary atresia and 8 cases of other cholestatic liver diseases in which the differential diagnosis included extrahepatic biliary atresia. Bile ducts and proliferating ductules were positive for CD56 in 13 of 14 cases of extrahepatic biliary atresia. The staining intensity was generally strong with most cases showing positivity in more than two thirds of portal tracts. The one negative case was a very small biopsy (<0.3 cm), and sampling may have played a role. In contrast, 4 of 8 cases in the control group were completely negative for CD56, with the remaining cases showing weak and focal positivity. In conclusion, bile ducts and ductules are CD56 positive in most cases of extrahepatic biliary atresia, and CD56 immunostaining can be a useful supplemental stain for diagnosing extrahepatic biliary atresia in its early, ductular proliferative phase when used in conjunction with traditional hematoxylin and eosin morphology and clinical information.


Assuntos
Ductos Biliares Extra-Hepáticos/patologia , Atresia Biliar/patologia , Antígeno CD56/metabolismo , Ductos Biliares Extra-Hepáticos/metabolismo , Atresia Biliar/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Masculino
20.
Am J Surg Pathol ; 27(10): 1313-20, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14508392

RESUMO

Previous studies of gallbladder pathology in primary sclerosing cholangitis (PSC) have suggested that a distinctive histologic triad ("diffuse lymphoplasmacytic acalculous cholecystitis," composed of diffuse, mucosal-based, dense lymphoplasmacytic infiltrates) is commonly present in gallbladders of patients with PSC and is relatively specific for that disease. However, prior control populations have included only patients with cholecystitis/cholelithiasis and hepatitis, and have not evaluated patients with non-PSC-associated extrahepatic biliary tract disease. We recently observed cases of diffuse lymphoplasmacytic chronic cholecystitis in a subset of patients with biliary tract disease associated with lymphoplasmacytic sclerosing pancreatitis and among patients undergoing Whipple resection for pancreatic head malignancy, suggesting that diffuse lymphoplasmacytic chronic cholecystitis is not specific for PSC. We studied 20 gallbladders from patients with obstructive jaundice due to malignancies of the pancreatic head, duodenum, or ampulla and 5 gallbladders from patients with choledocholithiasis, and compared them with 20 gallbladders from patients with PSC and 20 gallbladders with cholelithiasis. The following histologic features were evaluated: degree of mucosal and deep inflammation, lymphoid nodules, epithelial metaplasia, muscular hypertrophy, Rokitansky-Aschoff sinuses, fibrosis, and cholesterolosis. Gallbladders in malignancy-associated obstructive jaundice were nearly identical to gallbladders in PSC with respect to scores for mucosal inflammation, lymphoid nodules, and frequency of diffuse lymphoplasmacytic chronic cholecystitis (60% vs. 50%, respectively). PSC gallbladders, however, were significantly more likely to contain focal or extensive epithelial metaplasia (P = 0.01). The cholelithiasis control group was characterized by lack of significant mucosal inflammation in the majority of cases (95%) and frequent Rokitansky-Aschoff sinuses, fibrosis, and muscular hypertrophy. Gallbladders in the choledocholithiasis group showed overlapping histologic features with PSC/malignancy-associated obstructive jaundice and cholelithiasis. These results suggest that a pattern of diffuse lymphoplasmacytic chronic cholecystitis is highly specific for extrahepatic biliary tract disease but does not distinguish between primary and secondary cholangiopathies.


Assuntos
Quimiotaxia de Leucócito , Colangite Esclerosante/patologia , Colangite Esclerosante/fisiopatologia , Colecistite/patologia , Colecistite/fisiopatologia , Linfócitos/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colangite Esclerosante/complicações , Colecistite/complicações , Colelitíase/complicações , Colelitíase/patologia , Colelitíase/fisiopatologia , Colestase/complicações , Colestase/patologia , Colestase/fisiopatologia , Doença Crônica , Doenças do Sistema Digestório/complicações , Doenças do Sistema Digestório/patologia , Doenças do Sistema Digestório/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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