RESUMEN
BACKGROUND AND AIMS: Autoimmune pancreatitis seems to be a disease with a heterogeneous appearance. Our intention was to establish key diagnostic criteria, define grades of severity and activity, identify features of potential subtypes and evaluate the diagnostic relevance of biopsy specimens. METHODS: Histopathological criteria and clinical features were recorded in pancreatic resection specimens from 53 patients who were found to have chronic pancreatitis lacking pseudocysts, calculi, irregular duct dilatations, pancreas divisum and/or duodenal wall inflammation. The severity of the chronic inflammation was graded, and the activity of the acute inflammatory component and the granulocytic epithelial lesion (GEL) were determined. Additionally, pancreatic biopsy specimens from 9 patients with suspected AIP were assessed. RESULTS: Periductal lymphoplasmacytic infiltration was identified in all cases, followed in order of frequency by periductal fibrosis and venulitis. These changes were absent in 147 pancreatic specimens that showed chronic pancreatitis associated with pseudocysts, calculi, pancreas divisum and/or duodenal wall inflammation. In 90% of the cases, these chronic changes were graded as 3 or 4. In 81%, the inflammatory process resided in the head of the pancreas and involved the common bile duct. GELs were present in 42% of the patients, who had a mean age of 40.5 years, an almost equal male-female ratio and a high coincidence of ulcerative colitis or Crohn's disease. Patients without GELs were older (mean age 64 years), showed a male preponderance, commonly had Sjogren's syndrome and often developed recurrent bile-duct stenosis. Diagnostically relevant lesions were present in two of five wedge biopsy specimens and three of four fine-needle specimens. CONCLUSIONS: Periductal lymphoplasmacytic infiltration and fibrosis, preferential occurrence in the pancreatic head and venulitis characterize autoimmune pancreatitis. GELs predominantly occur in a subset of patients who are younger, more commonly have ulcerative colitis and Crohn's disease and seem to have fewer recurrences than patients without GELs. Pancreatic biopsy material proved to be a very helpful adjunct for establishing the diagnosis.
Asunto(s)
Enfermedades Autoinmunes/patología , Páncreas/patología , Pancreatitis/patología , Adolescente , Adulto , Anciano , Biopsia , Enfermedad Crónica , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pancreatitis/metabolismoRESUMEN
BACKGROUND: Tenascin-C (TN-C), a large extracellular matrix (ECM) glycoprotein with a molecular weight of 180-250 kilodaltons, is present in several normal adult tissues. TN-C is up-regulated during embryogenesis, in wound healing, and in tumor tissues. Glioblastoma multiforme (GBM) is the most frequent and malignant astrocytic tumor comprised of poorly differentiated, neoplastic astrocytes. Recently, TN-C-based radioimmunotherapy was administered to patients with GBM. METHODS: In the current study, the authors used immunohistochemistry to conduct a systematic investigation of TN-C distribution patterns in normal human brain tissue and in a large variety of brain tumors (n = 485 tumors). Immunoreactivity for TN-C was assessed with regard to its localization within tumor cells, blood vessels, and ECM using three different monoclonal antibodies (clones BC2, BC4, and TN2). RESULTS: In control human brains, a significant difference was noted in the expression of TN-C when comparing gray with white matter using either Western blot analysis or immunohistochemistry. TN-C was found in the white matter of the frontal, temporal, parietal, and occipital lobes and in the hippocampus, where the immunoreaction was especially strong in the hippocampal formation. In 181 astrocytomas of different grades (World Health Organization [WHO] Grade 2-4), TN-C immunopositivity was seen to varying degrees in the cellular and stromal components of the tumor and in tumor-associated vessels. Glioblastomas (n = 113 tumors) showed strong immunopositivity in the vessels and moderate immunopositivity of the ECM. A statistically significant reduction of TN-C immunopositivity in tumor-associated vessels or ECM was observed in anaplastic astrocytomas (WHO Grade 3) compared with GBM (WHO Grade 4). A Kaplan-Meier analysis showed that patients who had GBM lesions that lacked TN-C immunopositivity in the ECM had a significantly longer survival (median, 28 months; standard error, 7.8 months) (n = 12 patients) compared with patients who had GBM lesions with TN-C immunopositivity (median, 12 months; standard error, 1.6 months) (n = 87 patients). In meningiomas (n = 24 tumors), the neoplastic cells, the ECM of the tumor, and the vessels were TN-C negative. In schwannomas (n = 31 tumors), the tumor cells were TN-C negative; whereas, in > 50% of tumors, the vessels and the ECM of regressively altered tumor areas were positive. In metastatic carcinomas (n = 53 tumors), the tumor cells were negative; seldom were vessels stained positive for TN-C. Focal areas of the ECM, often accompanied with fibrotic changes, were immunopositive for TN-C. CONCLUSIONS: The most constant TN-C immunopositivity was noted in the ECM of the fibrotic stroma in highly malignant brain tumors and along the tumor border, especially in high-grade astrocytomas. The current results suggest that TN-C expression may be correlated with the grade of malignancy in astrocytic tumors and that the presence or absence of TN-C expression in the stroma of astrocytic tumors may play a not yet clearly understood role in shortening or prolonging, respectively, the survival of patients.