Immunohistopathological Features Research Articles

Expression of decay-accelerating factor is reduced on hyperplastic synovial lining cells in rheumatoid synovitis

Decay-accelerating factor (DAF), a membrane inhibitor of homologous complement activation, is present in synovial cells lining joint space and detected in synovial fluid. DAF is considered to protect synovial membrane from complement-mediated injury associated with articular inflammation. We studied the immunohistopathological features of DAF molecules in synovial membrane of rheumatoid synovitis using a DAF-specific monoclonal antibody, 1C6. Reacting molecules with the 1C6 antibodies in synovial tissue extracts formed a 70-kD band in Western blot analysis. DAF was strongly detected on the flat synovial lining cells, but weakly on the hyperplastic and multi-layered lining cells in rheumatoid synovitis. The latter cells reacted with anti-Leu-M3 antibodies specific for a cell surface marker of activated macrophages, sometimes accompanied by C3 and IgM deposition on the superficial synovial membrane. These results suggest that active rheumatoid synovitis characteristically with hyperplastic synovial lining cells is out of control by DAF, thereby permitting further complement-mediated injury.

Assoziation zwischen dem histopathologischen Synovialitis-Typ II und einem erhöhten Pyridinolin-Gehalt im Synovialgewebe bei rheumatoider Arthritis

To investigate the association between immunohistopathological and morphological features of synovitis in rheumatoid arthritis and the amounts of collagen degradation products pyridinoline and deoxypyridinoline in the synovial tissue and in body fluids in order to discover potential markers of erosive disease. Histopathological analysis of synovial tissue samples from 22 patients with RA was performed according to the histopathologic scoring system of RA synovitis by P. Stiehl. Accordingly, the samples were (a) classified into type I synovitis, type II synovitis, or undifferentiated synovitis and were (b) characterized for local features of disease activity, including basic activity and actual activity. The contents of pyridinoline and deoxypyridinoline were measured in the synovial tissue, the synovial fluid, serum and urine by HPLC analysis. The amounts of pyridinoline in synovial tissue samples characterized by type II synovitis were 1.7-fold and 2.7-fold higher compared with those with type I synovitis and undifferentiated synovitis, respectively. In contrast, the content of deoxypyridinoline was not different between the histopathologic types of synovitis. At the same time, increased amounts of pyridinoline, but not deoxypyridinoline, were detected in synovial tissue samples with basic activity or actual activity grade II compared with synovial tissue samples with basic activity or actual activity grade I. The concentrations of both collagen degradation products in the synovial fluid, serum and urine did not differ between patients when they were analyzed either for histopathologic types of synovitis or local disease activity. The amount of cartilage collagen degradation product pyridinoline in synovial tissue is positively correlated with the histopathological grading of local disease activity. Furthermore, the increased amounts of pyridinoline in synovial tissue samples with type II synovitis suggest a more erosive course of RA in patients with this type of synovitis.

Clinical and pathological prognostic markers for survival in adult patients with post-transplant lymphoproliferative disorders: BCL2 as a prognostic marker

8073 Background: PTLD is the most serious hematological complications of solid-organ transplantation. We determined clinical and immunohistopathological prognostic factors for overall survival (OS) in patients with PTLD. Methods: Eighty-four patients with PTLD between 1980 and 2004 at University of Pittsburgh were identified. Immunohistochemistry staining was performed on tumor at diagnosis for BCL2, BCL6, cMYC, p53, PS6k, HSP90 and NFkB. Univariate associations between individual clinical and immunohistopathological features and OS were compared using Cox proportional hazard models. Survival curves were generated via the method of Kaplan-Meier. Results: The median age at the time of diagnosis of PTLD was 53 years. Thirty four percent of patients presented with early PTLD. Sixty-four percent of patients were EBV positive by in situ hybridization. Lung transplant was significantly related to grafted organ involvement (p=0.035). Lung and multiorgan transplants were associated with a higher risk for early PTLD (p=0.0033 and p=0.054), while renal transplant was associated with risk for late PTLD (p=0.0011). The median survival for all patients was 20.8 months, 95% CI: (7.4–77.6). On univariate analysis for OS, poor prognostic factors were identified: age of transplant >60 yr (p=0.02), multiorgan transplant (p=0.02), ECOG>2 (p<0.0001), grafted organ involvement and extranodal disease at the time of diagnosis (p<0.011), early PTLD (p<0.0001), and elevated white blood cell count (WBC) 1 month prior to diagnosis (p=0.01). Good prognostic factors included late PTLD, monomorphic disease, CD20 positive and rituximab use. Only BCL2 strongly correlated with prognosis (p=0.002). A final clinico-pathological model for survival was constructed using three factors: ECOG >2, elevated WBC one month prior diagnosis and BCL2 overexpression. Patients with these three risk factors had median survival of 10 days (95% CI: 0–41), in comparison with patients with none of these risk factors had median survival of 1,414 days. Conclusions: Patients who had 3 factors ECOG >2, elevated WBC one month prior diagnosis, and BCL2 overexpression in tumor tissue had worse median survival than the patients with none of these three factors. No significant financial relationships to disclose.

Clinical and Pathological Prognostic Markers for Survival in Adult Patients with Post-Transplant Lymphoproliferative Disorders (PTLD), BCL2 Is a Poor Prognostic Marker in PTLD.

Background. PTLD represent one of the most serious hematological complications of solid-organ transplantation. Our objective was to determine clinical and immunohistopathological prognostic factors for overall survival (OS) in adult patients with PTLD.Methods. Eighty-four patients diagnosed with PTLD between1980 and 2004 at University of Pittsburgh Medical Center were identified for this study. Immunohistochemistry staining was performed on tumor tissue at the time of diagnosis for the following proteins: BCL2, BCL6, cMYC, p53, phosphorylated ribosomal S6kinase, HSP90 and NFk-B. Univariate associations between individual clinical and immunohistopathological features and OS were compared using Cox proportional hazard models. Survival curves were generated via the method of Kaplan-Meier.Results. The median age at the time of diagnosis of PTLD was 53 years (range 18–77). The median time from transplant to PTLD was 32 months (range 0.87–288). Twenty-nine (34%) patients presented with early PTLD (within 1 year of transplant). The tumors were EBV positive by in situ hybridization in 64% of the patients, and CD20 positive in 60%. The majority of the patients presented with extranodal disease (73%). Twenty-two (27%) patients had involvement of the grafted organ. Reduction of immunosuppression was performed in 77% of the cases, and rituximab was given in 27% of the patients. Lung transplant was significantly related to grafted organ involvement (p=0.035). Lung and multiorgan transplants were associated with a higher risk for early PTLD (p=0.0033 and p=0.054 respectively), while renal transplant was associated with risk for late PTLD (p=0.0011). The median survival for all patients was 20.8 months, 95% CI: (7.4–77.6). On univariate analysis for OS, the following poor prognostic factors were identified: age of transplant >60 yr (p=0.02), multiorgan transplant (p=0.02), ECOG>2 (p<0.0001), grafted organ involvement and extranodal disease at the time of diagnosis (p<0.011), early PTLD (p<0.0001), and elevated white blood cell count (WBC) 1 month prior to diagnosis (p=0.01). Good prognostic factors included ECOG of 1 (p=0.0004), late PTLD (p=0.002), early stage at diagnosis (stage I and II, p=0.005), monomorphic disease (p=0.0034), CD20 positive (p=0.033), initial immunosuppression reduction (p=0.05) and rituximab use (p=0.047). We analyzed whether the presence of BCL2, BCL6, cMYC, p53, pS6, HSP90 and NFk-B correlated with prognosis, and demonstrated that only BCL2 strongly correlated with prognosis (p=0.0020). PTLD-related survival strongly correlated with the intensity of BCL2 staining. A final clinico-pathological multivariable model for survival in PTLD was constructed using three factors: ECOG >2, elevated WBC one month prior diagnosis and BCL2 overexpression at the time of diagnosis. Patients with these three risk factors had median survival of 10 days (95% CI: 0–41), in comparison with patients with none of these risk factors had median survival of 1,414 days.Conclusion: We developed a prognostic model based on clinical and pathological markers. Patients who had all 3 factors ECOG >2, elevated WBC one month prior diagnosis, and BCL2 overexpression in tumor tissue had worse median survival than the patients with none of these three factors.

The expression of collagenase 3 (MMP-13) mRNA in the synovial tissue is associated with histopathologic type II synovitis in rheumatoid arthritis

The histopathologic analysis of the synovial tissue is important to distinguish rheumatoid arthritis (RA) from other forms of synovitis and to provide information about prognosis and therapeutic strategies at early stages of the disease. In this context, the present study was performed to investigate the correlation between immunohistopathological and morphological features of synovitis and the expression of collagenase 3 (MMP-13) known to contribute significantly to cartilage degradation in RA. In the histopathologic scoring system used in this study, type I synovitis is characterized by B lymphocyte infiltration and an intact lining, and is only mild destructive to cartilage and bone. Type II shows marked diffuse infiltrations of macrophages and T lymphocytes, an ulcerated lining, fibrin exudation, and invasive growth into cartilage and bone tissue. Investigating 36 patients with RA, 21 patients (58%) were positive for the expression of collagenase 3 mRNA in the synovial tissue. Among these patients, 19 showed a histopathologic type II synovitis and only 2 patients had undifferentiated synovitis. In contrast, synovial tissue samples from patients without collagenase 3 mRNA expression were characterized in 6 cases by type I, in 5 cases by type II and in 4 cases by undifferentiated synovitis. The analysis of the clinical data revealed that RA patients with a histopathologic type II synovitis and synovial tissue collagenase 3 mRNA expression had elevated levels of systemic markers of inflammation and received stronger therapies. The data suggest, that collagenase 3 expression and the histopathologic type II synovitis are associated with a severe and destructive course of RA.

Immunohistopathological study of the oral lichenoid lesions of chronic GVHD

Chronic graft-vs.-host disease (cGVHD) is a common and serious complication after bone marrow transplantation (BMT). However, the detailed process of oral lichenoid lesions of cGVHD is still unknown. Therefore, we investigated the immunohistopathological features of cGVHD compared with oral lichen planus (OLP) and healthy controls. Nineteen allogenic BMT recipients with a histopathological diagnosis of cGVHD were investigated. We investigated the immunohistopathological features of cGVHD compared with OLP and healthy controls. Immunohistopathological features showed that the infiltrations of CD4-positive T cells of cGVHD and OLP were significantly larger than those of the normal oral mucosa (P < 0.005). A larger number of CD8-positive T cells was infiltrated in cGVHD and OLP compared with the normal oral mucosa (P < 0.001). The difference in the number of CD4- and CD8-positive T cells between cGVHD and OLP was not significant. The infiltrations of Langerhans cells (CD1a) in cGVHD and OLP were significantly larger than those in the normal oral mucosa (P < 0.005). The difference in the number of Langerhans cells between cGVHD and OLP was not significant. CD68-positive macrophages were more frequently seen in cGVHD and OLP than in the normal oral mucosa (P < 0.0001). The difference in the number of CD68-positive macrophages between cGVHD and OLP was not significant. It is suggested that Langerhans cells and CD8-positive T cell may play a major role in the pathogenesis of the oral lichenoid lesions of cGVHD, and the immune response was inducted in OLP as well as the oral lichenoid lesion of cGVHD in this study.

Immunohistopathological and molecular genetic features of a case in which gastrointestinal stromal tumor recurred five times

Gastrointestinal stromal tumor (GIST) is a distinct group of mesenchymal neoplasms recently shown to exhibit differentiation toward interstitial cells of Cajal. Although previous studies have shown that the clinical outcome of patients with GIST is associated with mitotic activity, the proliferation index determined by the Ki-67 labeling index, immunophenotype (CD34 and/or p53) and mutation in exon 11 of the c-kit, a definitive discrimination between benign and malignant GIST has not yet been established. We report a patient in whom malignant GIST in the abdomen recurred five times. In this case, the primary GIST and the five recurrent GIST were associated with c-kit immunoreactivity, but the mitotic index of the GIST tended to be increasingly higher with subsequent recurrences. Mutational analysis of the c-kit revealed that the primary and recurrent GIST were mutant-negative. These data indicated that 'morphologically appearing benign' tumors with lower proliferative parameters may also have the capacity of metastasis and recurrence.

Strong expression of CD40, CD54 and HLA-DR antigen and lack of evidence for direct cellular cytotoxicity are unique immunohistopathological features in alopecia areata.

The pathological role played by T cells infiltrating hair follicles in lesions of alopecia areata (AA) is unknown. We examined the expression in cryostat sections of scalp skin obtained from a total of 28 patients with AA and from five normal control subjects of (1) molecules related to the induction of cell death including Fas, Fas ligand (FasL), perforin, granzyme B (GB), and TIA-1, (2) molecules related to antigen presentation including CD1a, CD40, CD54, CD80, and CD86, and (3) molecules induced by interferon gamma (IFN-gamma) including CD40, CD54, Fas, and HLA-DR. CD3(+) T cells infiltrated perifollicularly, perivascularly and in the hair structure and there was a predominance of CD4(+) over CD8(+) cells. Antigen-presenting cells expressing CD1a, CD40, CD54, or HLA-DR were also seen. Expression of CD40, CD54, HLA-DR and CD95 was also seen in the hair structure including the dermal papilla. Consistent with these observations, IFN-gamma-producing cells were also detected in the perifollicular infiltrate. In contrast, few Fas-L(+), perforin(+), GB(+) or TIA-1(+) cells were found adjacent to the follicles. Apoptotic cells were recognized only in the outer root sheath of catagen hairs. These findings suggest that infiltrating T cells interact with perifollicular or follicular antigen-presenting cells to produce IFN-gamma, which deprives dermal papilla cells of their ability to maintain anagen hair growth.

The immunohistopathological features of prurigo Hebra

Until now the pathologic mechanisms of prurigo Hebra (PH) is still understood. Earlier study the genetic inheritance of PH showed the multifactorial pattern. Considering the genetic inheritance and the existence of allergic reaction to insects bite in all patients, might be the mechanisms followed hypersensitivity reactions. The purpose of this study is to evaluate the general and specific local inflammatory features of early and late lesions of prurigo Hebra (PH). Fifty biopsy specimens of early and late lesions of prurigo Hebra patients were processed with haematoxylin-eosin (HE) and immunoperoryde (lP) staining using monoclonal antibodies against specific inflammatory cells namely B cells, T cells, helper T (CD4+) cells, supressor T (CD8+) cells, Langerhans cells, and antigen presenting cells (APC) that expressed HLA-DR antigen. HE-stained specimens: In early lesions, PMN cells were few, while eosinophils were present in great quantity and independent of mast cells and plasma cells; this feature was similar to that of insect bite reaction. IP-stained specimens: In late lesions, the amounts of lympho-histiocytic infiltration consisting of T cells, CD8+ cells, HLA-DR-expressing APCs were greater than those of early lesions, although it was not statistically significant. An exception was for the CD4+ cells, whose number in early lesions was significantly higher. The ratio of CD4+ to CD8+ in early lesions was higher than in late lesions (3/1: 2/1). This suggested that CD4+ cells were predominant. B cells, which were normally absent, appeared in small quantity in both early and late Lesions. The presence of B cells was not statistically correlated with T cells or eosinophils. The number of Langerhans cells in late lesions was higher than in early lesions. There was a strong correlation (r=0.39) between T cells and HLA-DR-expressing antigen-presenting cells (APCs/HLA-DR). Those cells found in great qunntity suggested that PH patients usually expose to extrinsic factors. In some cases with severe condition, the presence of eosinophils was more profound and was statistically significant. It is conclude that immunohistopathological mechanisms of PH follow the mixed types (one and IV) hypersensitivity reaction. (Med J Indones 2001;10:1-15) Keywords: Prurigo Hebra, eosinophils, CD4+cells, mixed (I and IV) types of hypersensitivity.

Immunohistopathological Study of Autoimmune Pemphigus

Paraneoplastic pemphigus (PNP) is a form of pemphigus considered to bear characteristic immunohistopathological features (vacuolar-interface dermatitis, keratinocyte dyskeratosis and reactivity of patients' sera with transitional epithelia). The present study was undertaken in order to investigate whether these criteria are specific enough so as to allow the diagnosis of PNP in the absence of clinical data. A retrospective study of 66 biopsies of pemphigus revealed that one third of them comprised histological signs of PNP; one of the corresponding sera reacted with mouse bladder epithelium. However, no evidence of a neoplastic disease was present in any of the patients, and Western blotting further excluded the diagnosis of PNP. These results suggest that some of the features considered characteristic of PNP are not strictly specific for this variety of pemphigus; hence this diagnosis cannot be reliably established by histology or immunofluorescence but requires biochemical studies.

Histoanalytical study of the cellular infiltrate in the tuberculin reaction

In contrast to the generally held view, in previous studies it has been found that the histopathological changes in delayed-type hypersensitivity reactions to intradermal purified protein derivative of tuberculin (PPD) in humans were not uniform. These were classified into three types based on their resemblance to features seen in other dermatoses, i.e.: (i) perivascular dermatitis type; (ii) basal spongiotic dermatitis type; and (iii) erythema multiforme type. These histopathological patterns correlated well with the clinical response seen in tuberculin hypersensitivity of tested subjects. In the present study, the immunohistopathological features in 44 skin biopsy specimens were assessed quantitatively by using multivariate analysis. The numbers of infiltrating cells in the epidermis and in the dermis which were immunohistologically positive to monoclonal antibodies against various mononuclear cells were counted separately to determine if there was any statistical correlation between the histopathological patterns and the phenotypes of infiltrating cells. As a result, a significant correlation was found between the histopathological patterns and the phenotypes of cells infiltrating the epidermis, such as CD8+ cells, CD4+ cells, CD11c+ cells and interleukin 2 receptor positive cells. All these cells showed a high correlation coefficient to the expression of HLA-DR antigen by keratinocytes. Next, factors that might regulate the inflammation and interaction among the infiltrating cells were assessed.(ABSTRACT TRUNCATED AT 250 WORDS)

Lymphocyte populations in the synovial membranes of dogs with rheumatoid arthritis

Lymphocyte populations in the synovial membranes of dogs with canine rheumatoid arthritis (CRA) were investigated by immunohistochemical staining techniques. T-lymphocytes were the predominant cell type distributed throughout the supporting layer of the synovial membranes. B-lymphocytes expressing IgG were seen far more commonly than those expressing either IgA or IgM. Synovial membrane biopsies from normal and osteoarthritic joints did not have the marked cellular infiltrates seen in joints with CRA. The synovial immunohistopathological features in dogs with CRA are similar to those seen in human rheumatoid arthritis.

Malignant melanotic schwannoma of the oral cavity

Intraoral malignant melanotic schwannoma is an extremely rare tumor. Two cases are presented, one occurring in the mandible of a 62-year-old man, the other in the maxilla of a 79-year-old man. The clinical presentation, light microscopic findings and immunohisto-pathological features are described. The difficulty of diagnosing this special tumor at initial presentation correctly, is discussed.