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PubMed1992

Roles of Langerhans' cells and T-lymphocytes infiltrating cancer tissues in patients treated by radiation therapy for cervical cancer.

Correlations between infiltration of immunologic cells in tumor tissues and prognosis of radiation therapy were investigated for 275 patients with cervical cancer who were treated with radiation therapy alone, including 216 patients with Stage III squamous cell carcinomas and 59 with adenocarcinomas of all stages. Langerhans' cell (LC) and T-cell were stained immunohistochemically on the specimens excised from the cervical cancer. In squamous cell carcinoma, 5-year survival rates for patients with LC infiltration were significantly better than those without LC (78% versus 60%; P < 0.01). The 5-year survival rate of patients with T-cell infiltration also was significantly better than that of patients without such infiltration (83% versus 61%; P < 0.05). Similar trends were observed in patients with adenocarcinoma; 5-year survival rates for patients with LC infiltration and those without LC infiltration were 49% and 25%, respectively (P < 0.025). The survival rates for patients with T-cell infiltration and those without were 50% and 33%, respectively (P < 0.1). An analysis of patterns of failure of radiation therapy demonstrated that the favorable prognosis in LC infiltration was attributable mainly to improvement of local control rates, but that in T-cell infiltration was not. T-cells infiltrated into tumor specifically in the patients with LC infiltration in both cell types. The authors suggest that the host anti-cancer immune response of individual patients may be remarkably different at the first step of antigen recognition by LC. The LC may induce T-cell-mediated antitumor response and improve local response in radiation therapy.

Adenocarcinoma↗

PubMed1989

Influence of infiltrating lobular histology on local tumor control in breast cancer patients treated with conservative surgery and radiotherapy.

To determine the influence of infiltrating lobular histology on local tumor control, the authors studied 49 patients with Stages I and II infiltrating lobular breast carcinoma treated by limited excision of the tumor and radiotherapy between 1968 and 1981 (median follow-up, 75 months). Results were compared with those in 561 cases of infiltrating ductal carcinoma similarly treated during the same period. The 5-year actuarial risk of local recurrence was similar for patients with infiltrating lobular or ductal carcinoma when the latter was evaluated as a single group (12% versus 11%). However, the 12% 5-year actuarial local recurrence risk for patients with infiltrating lobular carcinoma was intermediate between that for patients with infiltrating ductal carcinomas with an extensive intraductal component (23%) and those without an extensive intraductal component (5%). The pattern of recurrence in the breast was similar in the infiltrating lobular and ductal groups. All recurrences in patients with infiltrating lobular carcinoma and 80% of recurrences in the infiltrating ductal group occurred in the vicinity of the primary tumor (P = not significant). None of the clinical or morphologic features examined significantly influenced the risk of local recurrence in patients with infiltrating lobular carcinoma. The authors conclude that combined conservative surgery and radiotherapy appear to be a reasonable treatment option for patients with infiltrating lobular carcinoma, but further follow-up will be required to confirm these results.

Adult↗

PubMed2006

Induction of prolonged infiltration of T lymphocytes and transient T lymphocyte-dependent collagen deposition in mouse lungs following adenoviral gene transfer of CCL18.

OBJECTIVE: Levels of CCL18 are elevated in patients with scleroderma lung disease and other fibrotic pulmonary diseases associated with T lymphocyte involvement. We sought to determine whether CCL18 alone can induce pulmonary T lymphocytic infiltration and fibrosis in mouse lungs. METHODS: An adenovirus vector was constructed and used for CCL18 delivery to mouse lungs in vivo. Immunohistochemical, flow cytometric, and enzyme-linked immunosorbent assay analyses were used to assess the resulting changes. RESULTS: Overexpression of CCL18 led to massive perivascular and peribronchial infiltration of T lymphocytes. Although the expression of CCL18 peaked on day 7, the infiltration persisted up to day 64 after infection. The infiltrates were negative for proliferating cell nuclear antigen and TUNEL, suggesting the role of cell trafficking, rather than proliferation and apoptosis, in the infiltration dynamics. Patchy destruction of the alveolar architecture and collagen accumulation in association with the infiltrates were also noticed. These changes were infiltration-dependent, rather than CCL18-dependent, since treatment with antilymphocyte serum completely abrogated the CCL18-induced changes. The infiltrates consisted almost exclusively of T lymphocytes that were minimally activated, with a minimal increase in the expression of CD69 and no changes in the expression of CD25, Fas, FasL, or CD40L. There was no increase in total pulmonary levels of profibrotic cytokines transforming growth factor beta1 (TGFbeta1) or interleukin-13, although active TGFbeta1 was present locally in association with the infiltrates and areas of distorted alveolar architecture. Prestimulation of primary T lymphocytes with CCL18 in vitro caused an up-regulation of TGFbeta1 and collagen production in T lymphocyte/fibroblast cocultures. CONCLUSION: CCL18 promotes selective, long-term pulmonary infiltration of T lymphocytes and infiltration-dependent accumulation of collagen through a TGFbeta1-dependent mechanism.

Adenoviridae↗

PubMed2006

Mononuclear cell infiltration in clear-cell renal cell carcinoma independently predicts patient survival.

BACKGROUND: The impact of mononuclear cell infiltration on renal cell carcinoma (RCC) biology has been controversial, previously reported to be associated with either a favorable or unfavorable prognosis. The objective of the current study was to evaluate associations between mononuclear cell infiltration in routinely prepared paraffin-embedded specimens with survival in patients with clear-cell RCC. METHODS: A total of 306 patients were identified treated with nephrectomy for clear-cell RCC between 1990 and 1994. A single urologic pathologist, blinded to patient outcome, reviewed the specimens and quantified the extent of mononuclear cell infiltration as absent, focal, moderate, or marked. Cancer-specific survival was estimated using the Kaplan-Meier method. Associations of mononuclear cell infiltration with death from RCC were assessed using Cox proportional hazards regression models. RESULTS: At last follow-up, 173 of the 306 patients studied had died, including 96 patients who died from RCC. Mononuclear cell infiltration was absent in 165 (54%), focal in 70 (23%), moderate in 53 (17%), and marked in 18 (6%). Univariately, patients with specimens that had mononuclear cell infiltration were over 2 times more likely to die from RCC compared with patients whose specimens exhibited no mononuclear cell infiltration (risk ratio, 2.63; P < .001). After adjusting for the Mayo Clinic SSIGN (stage, size, grade, and necrosis) score, patients with specimens that had mononuclear cell infiltration exhibited a significantly increased likelihood of dying from RCC compared with patients whose specimens had no mononuclear cell infiltration (risk ratio, 1.61; P = .028). CONCLUSIONS: Mononuclear cell infiltration is associated with death from RCC even after multivariate adjustment. Routine documentation of mononuclear cell infiltration is recommended during the pathologic assessment of RCC.

Carcinoma, Renal Cell↗

PubMedDate not supplied

Immunohistologic study of mononuclear cell infiltrates in oral squamous cell carcinomas.

Intensity of mononuclear cell infiltrates in 50 oral cancer tissues was evaluated by immunohistochemical stainings. The intensity of the infiltrates was graded into four degrees from marked ( ) to absent (-); and the degree of each infiltrated lymphocyte subpopulation including Leu-3a3b/Leu-2a ratio was matched against clinical and histopathologic features. The vast majority of the infiltrated lymphocytes had antigens which were reactive with anti-T cell antibodies. In T cell subsets, Leu-3a3b+ cells infiltrated clearly (grade ++ or ) in 44 cases, and infiltration greater than grade ++ of Leu-2a+ cells was found in nearly half of the cases (26 of 50). In contrast, B cells (Leu-14+ cells) were obviously detectable in only a few cases, and moderate or marked infiltration of the natural killer (NK) population (Leu-11b+ cells) was not observed. Regarding correlation of T cell infiltrates with clinicopathologic features of the tumors, the degrees of Leu-4+ cell and Leu-2a+ cell infiltration became weak with advancing T stage. Leu-2a+ cells also infiltrated weakly into diffusely invading tumors. Out of 28 cases with no metastasis, 22 cases (78.6%) showed grade ++ approximately of Leu-2a+ cells, and only 4 (18.2%) of 22 cases with lymph node metastasis were clearly positive for Leu-2a+ cells (p less than 0.001). However, Leu-3a3b+ cell infiltration was only slightly related to T stage, metastasis, and to mode of invasion. Therefore, the Leu-3a3b/Leu-2a ratio increased significantly in advanced (T3 + T4) tumors, metastasized cases, or diffuse invasion type.

Antibodies, Monoclonal↗

PubMed1996

Differential expression of ICAM-1 and LFA-1 versus L-selectin and VCAM-1 in autoimmune insulitis of NOD mice and association with both Th1- and Th2-type infiltrates.

The infiltration of pancreatic islets by mononuclear cells is the hallmark of the development of insulin dependent diabetes mellitus (IDDM) in the NOD mouse, an animal model for human IDDM. The aim, of this study was to correlate adhesion molecule expression with the degree of islet infiltration and to compare Th1- and Th2-driven islet inflammation. Cryostat sections of NOD mouse pancreata before and after diabetes development were analysed by semiquantitative immunohistochemistry. NOD mouse islets did not show the expression of ICAM-1, LFA-1, L-selectin and VCAM-1 prior to infiltration by mononuclear cells. Furthermore, islets with early stage insulitis (grade 1, periinsular location of small infiltrates) still were devoid of adhesion molecule expression. ICAM-1 and LFA-1 were first demonstrable in islets with strong periinsular infiltrates (insulitis grade 2) while L-selectin and VCAM-1 were only seen in islets with mild or strong intraislet infiltration (grade 3-4). Adhesion molecules were demonstrable in areas of macrophage and T-lymphocyte infiltrates but not in adjacent endocrine islet tissue. Islets of all infiltration stages contained Th2 lymphocytes (positive for IL-4). Substantial numbers of Th1 cells (positive for IFN-gamma, TNF-alpha, IL-2 and/or IL-2 receptor) were observed only after acceleration of diabetes development by a single injection of cyclophosphamide (250 mg/kg i.p.). Interestingly, the adhesion molecule expression pattern in islets with "Th1' versus "Th2 insulitis' was not different. In conclusion, the expression of adhesion molecules in islets during the development of autoimmune diabetes does not precede mononuclear infiltration but probably occurs in response to the activation of initial small infiltrates. ICAM-1 and LFA-1 expression is seen prior to L-selectin and VCAM-1. However, adhesion molecule expression during Th1 versus Th2 cell infiltration is very similar, suggesting similar adhesion molecule requirements of the two Th subsets.

Animals↗

PubMed1992

Induction of neutrophil infiltration by rat chemotactic cytokine (CINC) and its inhibition by dexamethasone in rats.

In vivo effects of cytokine-induced neutrophil chemotactic factor (CINC) derived from rats on neutrophil infiltration were investigated using an air-pouch-type inflammation model in rats, and effects of dexamethasone on neutrophil infiltration induced by CINC was also examined in order to gain further insight into the mechanism of antiinflammatory activity of glucocorticoids. Injection of CINC into the air pouch made on the dorsum of rats induced a marked infiltration of neutrophils into the pouch fluid but not mononuclear cells and eosinophils during a 30-min interval after the injection. Maximum effect was induced at a dose of 1.4 micrograms/pouch. Treatment with dexamethasone 3 h before the injection of CINC suppressed the neutrophil infiltration in a dose-dependent manner, but no complete inhibition was observed. CINC injection into the air pouch of rats that had been sacrificed by bleeding in order to minimize neutrophil infiltration from blood stream also stimulated neutrophil infiltration into the pouch fluid when the carcass was incubated at 37 degrees C for 30 min, but the number of infiltrated neutrophils was about 35% of CINC-induced neutrophil infiltration in intact rats. CINC-induced neutrophil infiltration in the carcass, which is supposed to be a reflection of neutrophil migration from extravascular space in subcutaneous tissues to pouch fluid, was not inhibited by dexamethasone treatment. Therefore, the inhibition of neutrophil infiltration by dexamethasone might be due to inhibition of the extravasation of peripheral neutrophils but not due to inhibition of neutrophil chemotaxis from subcutaneous extravascular space to pouch fluid. These findings suggest that clinical effects of steroidal antiinflammatory drugs on neutrophil infiltration in inflammatory disease is partly due to inhibition of neutrophil extravasation induced by preformed neutrophil chemotactic factors in the inflammatory site.

Animals↗

PubMed2005

Pre-incisional infiltration for pediatric tonsillectomy: a randomized double-blind clinical trial.

OBJECTIVE: Tonsillectomy is frequently associated with post-operative pain of considerable duration. The aim of the current study is to corroborate our previous observational data by conducting a prospective double-blind placebo-controlled randomized clinical trial to determine the potential effect of pre-incision infiltration of local anesthesia on post-operative pain after tonsillectomy. DESIGN: Randomized double-blind controlled clinical trial. SETTING: Tertiary care facility in Beirut, Lebanon. PATIENTS: Ninety patients who underwent tonsillectomy allocated evenly in three groups. INTERVENTIONS: Pre-incision infiltration of 1.5 local anesthetic mixture in each tonsil was performed in conjunction with general anesthesia (infiltration, n=30). Pre-incision infiltration of 1.5 ml of 0.9% of normal saline was applied with general anesthesia (placebo, n=30). GA received only general anesthesia. OUTCOME MEASURES: Post-operative pain at rest, eating soft diet, jaw opening at 0, 6, 12, and once daily for the 10-day follow-up period, hemodynamic stability, hospital stay, parent and surgeon satisfaction, ear pain and analgesics consumption were assessed. RESULTS: Hemodynamic stability was maintained during pre, per and post-operation. 93.1% of infiltration group left the hospital the same day compared to 60% in placebo groups and 41.4% in general anesthesia group (p=0.001). Surgeon's satisfaction was significantly higher in infiltration group compared to placebo and general anesthesia groups (p=0.001). Parent's satisfaction was significantly higher in infiltration group (89.65%) compared to general anesthesia group (13.8%) and placebo group (36.7%) (p=0.001). The average pain scores at rest, on jaw opening and when eating soft diet were significantly lower in infiltration group compared to placebo group and general anesthesia group (p<0.05). Analgesic consumption in placebo and general anesthesia groups were significantly higher compared to infiltration group (p<0.05). CONCLUSION: This modified pre-incision infiltration of anesthetic mixture combined with general anesthesia reduces significantly post-tonsillectomy pain in children and provides a more rapid return to normal activity compared to general anesthesia alone or in combination with a placebo infiltration.

Anesthetics, Local↗

PubMedDate not supplied

On the physics of unstable infiltration, seepage, and gravity drainage in partially saturated tuffs.

To improve understanding of the physics of dynamic instabilities in unsaturated flow processes within the Paintbrush nonwelded unit (PTn) and the middle nonlithophysal portion of the Topopah Spring welded tuff unit (TSw) of Yucca Mountain, we analyzed data from a series of infiltration tests carried out at two sites (Alcove 4 and Alcove 6) in the Exploratory Studies Facility (ESF), using analytical and empirical functions. The analysis of infiltration rates measured at both sites showed three temporal scales of infiltration rate: (1) a macro-scale trend of overall decreasing flow, (2) a meso-scale trend of fast and slow motion exhibiting three-stage variations of the flow rate (decreasing, increasing, and [again] decreasing flow rate, as observed in soils in the presence of entrapped air), and (3) micro-scale (high frequency) fluctuations. Infiltration tests in the nonwelded unit at Alcove 4 indicate that this unit may effectively dampen episodic fast infiltration events; however, well-known Kostyakov, Horton, and Philip equations do not satisfactorily describe the observed trends of the infiltration rate. Instead, a Weibull distribution model can most accurately describe experimentally determined time trends of the infiltration rate. Infiltration tests in highly permeable, fractured, welded tuff at Alcove 6 indicate that the infiltration rate exhibits pulsation, which may have been caused by multiple threshold effects and water-air redistribution between fractures and matrix. The empirical relationships between the extrinsic seepage from fractures, matrix imbibition, and gravity drainage versus the infiltration rate, as well as scaling and self-similarity for the leading edge of the water front are the hallmark of the nonlinear dynamic processes in water flow under episodic infiltration through fractured tuff. Based on the analysis of experimental data, we propose a conceptual model of a dynamic fracture flow and fracture-matrix interaction in fractured tuff, incorporating the time-dependent processes of water redistribution in the fracture-matrix system.

Filtration↗

PubMed2000

Clinical impact of intratumoral natural killer cell and dendritic cell infiltration in gastric cancer.

Intratumoral natural killer cells (NKC) and dendritic cells (DC) may affect the clinical features of various gastrointestinal cancers. However, the relationship between intratumoral NKC and DC remains unclear. We examined 169 patients with gastric cancer who underwent gastrectomy at Kagoshima University Hospital. Immunohistochemical staining of CD57 and S-100-protein was performed to evaluate NKC and DC infiltration, respectively. A total of 25 areas containing pericancerous tissue were selected for determining the number of NKC and DC under high power microscopy (x400). Patients were classified into two groups according to NKC and DC population. Intratumoral lymphocytic infiltration was also calculated in 15 areas with a high power (x400) objective. The degree of NKC and DC infiltration was gradually decreased according to the progression of nodal involvement. Patients with many NKC infiltration had a lower positivity of lymph node metastasis and lymphatic invasion than patients with little NKC infiltration. DC infiltration was also negatively correlated with depth of invasion, lymph node metastasis and curativity. DC infiltration was positively correlated with lymphocytic infiltration (P=0.01. r=0.6). The 5-year survival rates of patients with many NKC infiltration and patients with DC many infiltration were 75 and 78%, respectively, both of which were significantly better than that of patients with little NKC and DC infiltration (P<0.05). NKC may be activated without DC or intratumoral lymphocytes. Intratumoral NKC may act as an independent immunologic effector against tumor cells, unlike DC.

CD57 Antigens↗

PubMed1999

Infiltrative subcutaneous malignant fibrous histiocytoma: a comparative study with deep malignant fibrous histiocytoma and an observation of biologic behavior.

Malignant fibrous histiocytoma (MFH) is one of the most common soft tissue sarcomas of adulthood. Although it is usually intramuscular and pseudocapsulated, we have recently observed MFHs with extremely infiltrative growth margins, which are predominantly located in the subcutis. These lesions are often associated with incomplete primary surgical excision, the subsequent need for additional surgery or adjuvant therapy, and an increased risk for local recurrence. To further analyze the growth pattern and clinical implication of the subcutaneous infiltrative MFHs, we reviewed a series of 24 subcutis and 21 intramuscular MFHs of the extremities. Morphologically, we defined "infiltrative" as tumor extension along normal tissue planes for a minimum measurable distance of 2 mm from the edge of the main mass. Radiographic findings were correlated with pathologic findings. Of the 24 subcutis MFHs, 83% showed an infiltrative growth pattern, involving 5% to 90% (mean, 51%) of the evaluable margin. Fifty percent of patients with subcutaneous MFH had both an infiltrative growth pattern and positive surgical resection margin on initial resection. Only 25% noninfiltrative subcutaneous MFHs had a positive initial surgical resection margin. Of the 21 intramuscular MFHs, only 5 (24%) had an infiltrative growth pattern that involved 5% to 90% (mean, 40%) of the evaluable margin. One of the five tumors had 90% margin infiltration with multiple positive surgical resection margins. Of 16 noninfiltrative intramuscular MFHs, 3 (19%) had positive resection margins. Magnetic resonance imaging (MRI) and/or computed tomography (CT) scan correctly identified the growth pattern in 87% of subcutaneous and 88% of intramuscular MFHs. Patient follow-up evaluation showed that four (17%) patients with subcutaneous MFHs had resection-proven recurrences, 6 to 57 months after diagnosis. All four of these tumors had infiltrative growth patterns and positive margins on the original surgical resection. There were no local recurrences of the intramuscular MFHs. Two patients of 20 in the infiltrative subcutaneous MFH group and two patients of four in the well-circumscribed subcutaneous MFH group had biopsy-proven metastases, which developed within 5 years after diagnosis. Six patients had metastases in the intramuscular MFH group. A group of MFHs, predominantly subcutaneous, have an extremely infiltrative growth pattern. This growth pattern, documented by radiographic methods and/or light microscopic examination of biopsy specimens, should indicate that a wider margin on initial resection is necessary to entirely excise the lesion. The presence or absence of an infiltrative growth pattern is not predictive of the tumor's metastatic potential.

Adult↗

PubMed1999

Diffusely infiltrative endometrial adenocarcinoma: an adenoma malignum pattern of myoinvasion.

The prognostic significance of a diffusely infiltrative intramyometrial growth pattern was evaluated in 110 cases of low-stage (stages I and II) endometrial adenocarcinoma. Fifty cases were associated with diffuse infiltration (DI group), and 50 cases had more conventional granulation tissue type intramyometrial infiltration (GTT group). Ten cases with carcinomatous involvement of deeply situated adenomyosis (ADMY group) were also studied. The diffusely infiltrative "adenoma malignum" growth pattern featured typically round, regular individual glands, clearly within myometrium but with minimal or absent stromal or inflammatory cell response. Myoinvasion of the conventional sort was characterized by irregular, sharply angulated abnormal glands within myometrium without interposed normal glands or endometrial stroma. The abnormal glands were surrounded, at least focally, by edematous stroma with granulation tissue type reaction and/or an inflammatory cell infiltrate. Mean follow-up was 77.8 months (range 3-219 months) for the patients with diffusely infiltrative myoinvasion and deep adenomyosis and 86.9 months (range 1-206 months) for the patients with conventional myoinvasion. Recurrence-free survival for patients with stage I disease and conventional myoinvasion (94%) was similar to that of patients with diffuse adenoma malignum infiltration (98%; p = 0.13). Survival rates for both groups were also similar. Two (4%) of the 50 patients with diffusely infiltrative adenoma malignum pattern of myoinvasion died of endometrial carcinoma 36 and 72 months after hysterectomy, and 2 (4%) of the 50 patients with conventional myoinvasion died 34 and 67 months after hysterectomy (p = 0.41). Survival in these patients correlated with depth of myometrial invasion and stage. There were no recurrences in the patients with deep adenomyosis. These results suggest that although endometrial carcinomas with diffuse myometrial infiltration are fully capable of aggressive clinical behavior, they do not appear to behave any more aggressively than those with conventional myometrial invasion. Prognostic indicators of clinically aggressive disease are similar to those that have been previously identified for endometrial carcinomas with the more conventional pattern of myometrial infiltration. They include cervical involvement, deep myometrial invasion, higher histologic grade, and lymph-vascular space invasion. Endometrial carcinomas with extensive involvement of adenomyosis and adjacent foci of minimal myometrial infiltration appear to have very low malignant potential, but the number of cases with this finding and adequate clinical follow-up is limited. This finding needs to be confirmed in a much larger series of cases.

Adenocarcinoma, Mucinous↗

PubMed1984

Relationships among the histologic pattern, intensity, and phenotypes of T cells infiltrating renal allografts.

The evaluation of renal allograft rejection by routine histologic evaluation of transplant biopsy is often a diagnostic problem. Advances in monoclonal antibody and immunohistochemical technology have led to their application in characterizing the phenotype of peripheral blood lymphocytes in transplant recipients, as well as the infiltrating lymphocytes in renal biopsy specimens (both tissue and aspiration cytology samples). Recent reports suggest that the relative number of infiltrating T cells and the T cell phenotypic subset ratio may have some association with graft survival. However, most allograft biopsy studies have not examined the relationship of the intensity and phenotype of T cells to the histologic pattern of infiltration, while fine-needle aspiration cytology (FNAC) and peripheral blood analysis do not allow for this assessment. To examine the association of histologic pattern with the intensity and phenotype of T cell infiltrates, immunoperoxidase labeling of cells using monoclonal antibodies was evaluated in 66 renal allograft biopsies performed because of clinical suspicion of rejection. Our findings indicate that the ratio of T helper-inducer (Leu 3) cells to T suppressor-cytotoxic (Leu 2) cells is significantly lower in the pattern of diffuse renal cortex infiltration (cortical diffuse [CD] pattern) when compared with other histologic patterns (cortical aggregate or perivascular), regardless of the overall intensity of the T cell infiltrate. A significant difference in T cell phenotypes was also found among different histologic patterns as expressed by Leu 3/Leu 2 ratios and by the number of Leu 2 cells. An increase in the overall intensity of T cell infiltrate was not associated with significant changes in T cell phenotype seen in any pattern, but an increase in the intensity of the cortical diffuse T cell infiltrate was associated with a significant decrease in the Leu 3/Leu 2 ratio (P less than 0.04), which was due to an increase in the population of Leu 2 cells (P less than 0.002). Interestingly, increases in the intensity of either cortical aggregate or perivascular T cell infiltrates were associated with significant increases in both Leu 3 and Leu 2 cells, as well as a tendency towards higher Leu 3/Leu 2 ratios. These findings indicate that evaluation of T cell infiltrates by phenotype in renal allografts is dependent upon the pattern as well as the intensity of infiltrate.

Adolescent↗

PubMed1996

Prognostic evaluation of specific cutaneous infiltrates in B-chronic lymphocytic leukemia.

The relationship between numerous histologic variables and survival was investigated in 54 consecutive lesions of specific skin infiltrates of B-cell chronic lymphocytic leukemia (B-CLL) from 27 patients (16 males and 11 females, mean age 65 years, range 42-83 years). All patients were followed for up to 204 months or until death. Histopathologically, the infiltrates showed a patchy perivascular (35%), diffuse (31.5%), nodular (31.5%) or bandlike (1.9%) pattern. In 28% of the cases, an admixture of reactive cells within the infiltrate including eosinophils, histiocytes, neutrophils and plasma cells was observed. Cytomorphologically, small B-lymphocytes with condensed chromatin predominated in most infiltrates. However, some biopsies showed a small but significant number of medium- or large-sized neoplastic cells of the B-lymphocyte lineage with variable cytomorphological features. In a multivariate analysis, several histologic parameters within the infiltrates were found to show a significant association with long survival, namely, an infiltrate of moderate density, a nodular pattern, involvement of the lower dermis only, and presence of predominantly small B-lymphocytes (more than 95%) with condensed chromatin. Histologic variables that independently correlated with relatively short survival included an infiltrate of severe intensity, a diffuse pattern, epidermal changes (especially acanthosis and ulceration), medium-sized and large B-lymphocyte (more than 5%), and reactive cells within the infiltrate (neutrophils, eosinophils, and plasma cells). Overall analysis of our results showed two histologic patterns with a significant prognostic impact (p < 0.01; z = 5.4). Pattern I (33 biopsies) correlated with relatively long survival (2-year survival rate; 97%) and consisted of infiltrates showing predominantly small B-lymphocytes (more than 95%) without reactive cells or epidermal changes. Pattern II (21 biopsies) indicated short survival (2-year survival rate; 49%) and included all the rest of the biopsies i.e., infiltrates with medium- and large-sized B-lymphocytes (more than 5%), admixture of reactive cells, and epidermal changes. Results from our study suggest that histologic features in specific skin infiltrates of B-chronic lymphocytic leukemia may be helpful in identifying prognostically different subgroups of patients and planning therapeutic schedules.

Adult↗

PubMed1998

T cells with similar T-cell receptor beta-chain complementarity-determining region 3 motifs infiltrate inflammatory lesions of synthetic peptides inducing rat autoimmune myocarditis.

Experimental autoimmune myocarditis (EAM) resembles the giant cell myocarditis seen in humans, and recurrent forms lead to dilated cardiomyopathy. EAM has been shown to be a T cell-mediated autoimmune myocarditis. We have previously shown that cDNA encoding Vbeta complementarity-determining region (CDR) 3 from heart- and pericardial space-infiltrating T cells in EAM induced by rod cardiac myosin contains more restricted sequences than that from normal spleen T cells. Recently, it has become apparent that several epitopes of EAM exist in rod cardiac myosin; therefore, T cells infiltrating into lesions may recognize certain epitopes in EAM induced by rod cardiac myosin. In this study, we examined heart- and pericardial space-infiltrating T-cell clonotypes in EAM induced by synthetic peptides of cardiac myosin. EAM was produced by immunization with synthetic peptides corresponding to N-terminally acetylated amino acids 1539 to 1555 of rat cardiac myosin alpha heavy chain. Five of 12 rats receiving synthetic peptides developed macroscopic signs of myocarditis. To examine T-cell receptor (TCR) Vbeta expression and CDR3 of the TCR beta chain of lesion-infiltrating T cells in EAM, total RNA was isolated from heart, pericardial effusion, spleen, lymph node, and peripheral blood. TCR Vbeta expression of the T cells infiltrating the lesions revealed a predominance of Vbeta4. On the basis of single-strand conformation polymorphism analysis for CDR3 of the TCR Vbeta4 chain, heart- and pericardial space-infiltrating T cells were considered to be oligoclonal, whereas spleen, lymph node, and peripheral blood in a rat with EAM and spleen in a native rat were considered to be polyclonal. In the same rat, clonotypes of heart-infiltrating T cells were almost the same as those of pericardial space-infiltrating T cells. Furthermore, on sequence analysis for CDR3 of the TCR Vbeta4 chain, the amino acid motifs were similar among T cells infiltrating into lesions of different EAM rats. In the present study, TCR beta chains of heart- and pericardial space-infiltrating T cells in EAM induced by synthesized peptide consisting of 17 amino acids were examined. Vbeta4+ T cells with similar Vbeta CDR3 motifs that infiltrate the heart and pericardial space may recognize the same epitope.

Amino Acid Sequence↗

PubMed2001

Focal fatty infiltration of the liver: analysis of prevalence and CT findings in children and young adults.

OBJECTIVE: Focal fatty infiltration of the liver, a benign entity that can be confused with a malignant lesion, is well characterized in adults but not in children. The goal of this study was to determine by CT the prevalence and characteristics of focal fatty infiltration in children and young adults. MATERIALS AND METHODS: We retrospectively analyzed 305 consecutive contrast-enhanced abdominal CT examinations of 218 children and young adults with no known liver disease, performed during 2 years at our institution, to identify focal fatty infiltration of the liver. The imaging criterion for focal fatty infiltration of the liver on helical CT was a geometric or ovoid low-attenuation area adjacent to the falciform ligament, gallbladder fossa, or porta hepatis. If a patient's findings met the CT criterion for focal fatty infiltration of the liver, all previous abdominal CT and MR imaging examinations performed for that patient were reviewed to assess the evolution of focal fatty infiltration of the liver. RESULTS: Of 218 children and young adults, 20 (9.2%) met the CT criterion for focal fatty infiltration of the liver. In our population, focal fatty infiltration of the liver was identified only adjacent to the falciform ligament. The prevalence of focal fatty infiltration of the liver increased significantly with advancing age: 0% for ages 1 month-4 years; 7.3% for 5-9 years; 10.2% for 10-14 years, and 25.6% for 15-19 years (p < 0.0001). CONCLUSION: Focal fatty infiltration of the liver was identified in 9.2% of patients in our population, and occurrence of this lesion in children increases significantly with advancing age. However, focal fatty infiltration of the liver is uncommon in infants and young children and should be a diagnosis of exclusion.

Adolescent↗

PubMed2005

Stromal responses to carcinomas of the pancreas: juxtatumoral gene expression conforms to the infiltrating pattern and not the biologic subtype.

If there is a "science" of tumor-stromal interactions, there must be a set of biologic rules that are organ-site dependent. One way to explore this hypothesis would be to compare the patterns of gene expression of two biologically distinct neoplasms that arise within the same organ site. Using nonradioactive in situ hybridization, we evaluated the gene expression patterns of three genes previously shown to be robust markers of the juxtatumoral stroma within eight infiltrating ductal adenocarcinoma of the pancreas (ApoC1, ApoD and MMP11), and compared these patterns to those associated with seven infiltrating colloid and tubular carcinomas arising in association with intraductal papillary mucinous neoplasms (IPMNs), a histologically distinct form of primary carcinoma of the pancreas, two surgically resected samples of chronic pancreatitis and two surgically resected pancreatic cancer liver metastases. Robust juxtatumoral stromal expression was noted for all three markers within all eight conventional infiltrating ductal adenocarcinoma tissues, but not in samples of chronic pancreatitis. Among the carcinomas arising within an IPMN, expression for all three markers was also noted for five of seven infiltrating carcinomas analyzed. However, when labeling for these three markers was analyzed with respect to infiltrative growth pattern, positive labeling was only seen in areas of tubular (ductal-type) growth and not in areas of colloid carcinoma. This observation was further supported by two infiltrating carcinomas arising in an IPMN that showed both tubular and colloid growth patterns within the same neoplasm indicating the host stromal response observed may relate to infiltrative growth pattern rather than the biology of the primary tumor type. Moreover, these robust patterns within conventional infiltrating ductal adenocarcinomas were not retained within matched metastases to the liver, indicating the importance of the tumor microenvironment in the host stromal response. Juxtatumoral stroma was found to be composed of a least two cell types, tumor-infiltrating macrophages and fibroblasts, highlighting the complexity of tumor-stromal interactions within an infiltrating carcinoma. Since the juxtatumoral gene expression response is the strongest indication of direct communication between stroma and cancer cells, we provide evidence of a stereotypical response to infiltrative growth that might predominate in tumor-stromal interactions independent of cancer type, a finding with clinical implications for therapeutic modalities that target this response in human tumors.

Adenocarcinoma, Mucinous↗

PubMed2001

The distribution and significance of renal infiltrating cells in patients with diffuse crescentic glomerulonephritis.

OBJECTIVE: To study the significance and distribution of renal infiltrating cells, including monocytes (CD68+ cells), proliferative cell nuclear antigen positive cells (PCNA+ cells), CD4+ and CD8+ cells in diffuse crescent glomerulonephritis (DCGN). METHODS: Fifty-six patients with DCGN were studied, including 10 cases of anti-glomerular basement membrane (GBM)--type I DCGN, 26 immune complex--type II DCGN, and 20 cases of pauci-immune--type III DCGN. Glomerular and interstitial infiltrates of CD68+ and PCNA+ cells, and interstitial infiltrates of CD4+ and CD8+ cells were detected by using four-layer PAP methods. RESULTS: There was a significant increase of renal infiltrating CD68+, PCNA+, CD4+ and CD8+ cells in patients with DCGN compared with that in normal controls. In patients with type I DCGN, there was a higher number of renal infiltrating CD68+ and PCNA+ cells than that in patients with type II and III DCGN. A glomerular infiltrates of CD68+ and PCNA+ cells correlated with the interstitial infiltrates of CD4+ cells in type I or III DCGN patients. In lupus DCGN patients, the numbers of renal infiltrating CD68+ and PCNA+ cells were similar to vasculitis or type III DCGN patients. CONCLUSION: These findings demonstrate that the renal infiltrates of CD68+ and PCNA+ cells play an important role in patients with DCGN, that the infiltrates of CD4+ cells correlate with the infiltrates of CD68+ and PCNA+ cells may be an active marker of DCGN, and that cell-mediated immunity may contribute to crescent formation in lupus DCGN patients.

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