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PubMed2007

Immunohistochemical study of the reticular and vascular network of mouse lymph node using vibratome sections.

The function of lymph nodes is greatly influenced by their unique microanatomy, in which distinct subpopulations of cells are compartmentalized by a meshwork of reticular cells and fibres, specialized blood and lymphatic vessels and nerves. Using antibodies against extracellular matrix (ECM) proteins (fibronectin, collagen IV and laminin), proteoglycan (perlecan), and a fibroblastic marker (ERTR-7), the distribution and molecular organization of the system of reticular fibres was investigated by three-dimensional (3D) reconstruction methods. Fibronectin, collagen IV and laminin are restricted to reticular fibres and have a similar distribution pattern, whereas perlecan is limited to the vascular system of the lymph node. Various compartments of the lymph node, such as the B-cell follicle, paracortex (including the high endothelial venules and paracortical cord), and medulla have been reconstructed to visualize their vasculature with respect to B and T cells. Since the morphology of lymph nodes may change significantly in pathological conditions, different compartments of reactive lymph node (after low-dose Listeria monocytogenes infection), especially germinal centres, were also investigated. The data presented here should facilitate our understanding of the 3D organization of non-immune cell components of lymph nodes, which is crucial for cell adhesion, migration, activation, and differentiation in normal and pathological conditions.

Animals↗
PubMedDate not supplied

Surgical treatment of advanced gastric cancer with metastasis in para-aortic lymph node.

We have studied the incidence and prognosis of N4 node (para-aortic lymph node) metastases in gastric cancer in 434 patients who had been referred to our department for surgical treatment during the period between 1978 and 1988. N4 nodal involvement was found in 76 (17.5%) of 434 patients who had received a laparotomy with resection, and in 42 (10.5%) of 400 patients who had "curative" resection. When the surgeon assessed that the patients had metastasis in para-aortic lymph nodes, the para-aortic lymph nodes lying above and below the left renal vein were completely removed (R4 gastrectomy). During this period, 42 patients with N4 nodal involvement underwent "curative" resection by R4 gastrectomy. Their treatment results were compared with those of 32 patients who underwent subtotal or total gastrectomy (R2 or R3 gastrectomy) without resection of metastases of para-aortic lymph nodes ("palliative" resection). The operating time and the operative mortality rate were similar in both groups (R4 vs R2 or R3 gastrectomy). The patients who had undergone "curative" resection (R4 gastrectomy) had a significantly higher five-year survival rate than those who had received "palliative" resection. The R4 gastrectomy is a rational and useful surgical procedure for treating patients with N4 nodal involvement.

Carcinoma↗
PubMedDate not supplied

The role of sentinel lymph-node biopsy (SLNB) in the treatment of breast cancer.

Sentinel lymph-node biopsy is an innovative method for axillary staging in breast cancer patients, based on the concept that information about the status of the entire lymphatic drainage from a tumour site could be obtained by identification and sampling of a "sentinel node". The aim of the study was to evaluate the impact of sentinel lymph-node biopsy in the management of patients with early invasive breast carcinoma. Three hundred and forty-one patients with primary invasive breast carcinoma measuring less than 2 cm (less than 3 cm from January 2001) and clinically negative axillary nodes were recruited into the study. Sentinel lymph-nodes were positive for metastases in 108/341 cases (31.7%). Micrometastases were found in 22 patients and isolated tumour cells in 1 case. The mean number of sentinel lymph-nodes removed was 1.8 per patient. The sentinel lymph-node was the only positive node in 57 of 108 patients (52.8%). The percentage of axillary recurrence in sentinel lymph-node-negative patients was 0%. The accuracy of sentinel lymph-node biopsy for axillary staging has been confirmed in many studies. Axillary recurrences after sentinel lymph-node biopsy range from 0 to 1.6% in many series, while axillary recurrence after axillary lymph-node dissection is about 0-3%. In our experience we observed no axillary recurrences in 233 patients with sentinel lymph-node biopsy alone, with a median follow-up of 33 months, confirming the accuracy of the procedure, and sentinel lymph-node-negative patients with sentinel lymph-node biopsy alone are no more at risk for axillary recurrences than those undergoing axillary lymph-node dissection.

Adult↗
PubMed2002

Is a limited lymph node dissection an adequate staging procedure for prostate cancer?

PURPOSE: Generally lymph node dissection is only considered a staging procedure for prostate cancer. Therefore, the need for meticulous lymph node dissection is often questioned and only sampling is suggested. We performed a prospective study to identify the pattern of lymph node metastasis in prostate cancer and determine how extensive lymph node dissection must be not to under stage cases. MATERIALS AND METHODS: All patients with clinically organ confined prostate cancer, no prior hormonal treatment, negative preoperative staging computerized tomography and bone scan, who underwent radical prostatectomy between 1989 and 1999, were evaluated prospectively as to the number and location of lymph node metastasis. A meticulous lymph node dissection was performed along the external iliac vein, obturator nerve and internal iliac (hypogastric) vessels. Nodes from each location and side were submitted separately for histological evaluation. RESULTS: In 365 patients with a median serum prostate specific antigen of 11.9 ng./ml. (range 0.4 to 172) the median number of nodes removed was 21 (range 6 to 50). Lymph nodes were positive in 88 (24%) patients and the median number of positive nodes was 2 (range 1 to 19). Internal iliac lymph nodes were positive in 51 (58%) of the 88 patients, including 34 with additional positive lymph nodes along the external iliac vein and/or obturator nerve. Internal iliac lymph nodes alone were positive in 17 (19%) of 88 patients. CONCLUSIONS: There were significant numbers of lymph node metastases at all 3 different areas of lymphadenectomy. Positive lymph nodes were found along the internal iliac artery in more than half (58%) of the patients and exclusively in 19%. Therefore, we consider lymph node dissection along the internal iliac (hypogastric) vessels essential for representative staging. Without this dissection a fifth of node positive cases would have been under staged and diseased nodes would have remained in more than half of the cases.

Adult↗
PubMed1983

Gastric carcinoma with lymphoid stroma: correlation to reactive hyperplasia in regional lymph nodes and prognosis.

The pathological changes of regional lymph nodes in cases of gastric carcinomas with lymphoid stroma (LS group) and the prognostic significance of the findings were studied in comparison with those in cases of ordinary stroma (OS group). The purpose of this study was to elucidate the immune responses of regional lymph nodes, histologically, in patients with gastric carcinoma and lymphoid stroma. In the LS group, the incidence of paracortical hyperplasia (PH) was high, irrespective of lymph node metastasis, while that of germinal center hyperplasia (GH) was high in the absence of lymph node metastasis but tended to be low in the presence of metastasis. In the OS group, the incidences of PH and GH were low, particularly in the presence of lymph node metastasis. The five year survival rate in those with no lymph node metastasis was as favorable as that of patients with lymph node metastasis in the LS group, the latter being significantly higher than the rate in the OS group. These results indicate that gastric carcinomas with lymphoid stroma are closely related to reactive hyperplasias of the regional lymph nodes, particularly paracortical hyperplasia, and in such cases, there is a favorable prognosis, regardless of the lymph node metastasis.

Adenocarcinoma↗
PubMed2004

Sentinel lymph node biopsy in breast cancer: results of intradermal periareolar tracer injection and follow-up of sentinel lymph node-negative patients.

Several methods are in use for identification of the sentinel lymph node (SLN) in breast cancer. We set up the hypothesis that intradermal (i.d.) infra-areolar injection of technetium-99m in combination with i.d. injection of patent blue dye lateral to the areola can identify the same lymph node as peritumoral injection, regardless of the location of the tumour. Each of 50 patients with breast cancer (group I) received an i.d. injection of technetium-99m 1cm caudal to the areola. After induction, blue dye was injected intradermally 1cm lateral to the areola. These patients underwent axillary dissection regardless of their lymph node status. The SLN was identified in 96% of these patients. One of them had axillary lymph node metastases even though the SLN was negative (6%). Further 82 patients (group II) underwent SLN identification and removal without further axillary dissection. The duration of mean follow-up for these patients was 28 months (16-39 months). One patient developed axillary recurrence (1%) 24 months after the initial operation. Intradermal periareolar tracer injection is an accurate method of locating the sentinel node. Long-term follow-up of patients who had negative sentinel nodes and did not undergo axillary dissection revealed a low axillary recurrence rate.

Adult↗
PubMed1987

Distribution of p24 HTLV3 major core protein in lymph nodes of LAS patients.

Lymph nodes of patients with lymphadenopathy syndrome (LAS) are characterized by two main histological patterns: hyperplastic reactive (H) and regressive (R). In both conditions, the paracortex (PC) is markedly activated with presence of selectively Ia-1+ high endothelial venules. Using a monoclonal antibody for p24, the major core protein of HTLV3, we have immunohistochemically determined the distribution of p24+ cells in lymph nodes from 23 LAS patients' HTLV3-ab serologically positive. p24+ cells were demonstrated in 11 cases. Control nodes were negative. p24+ cells included high endothelial cells of PC postcapillary venules, large perivenular cells, large mono- or binucleated cells in PC and in GC, and few lymphocytelike cells. Our preliminary observations indicate that the majority of p24+ cells are high endothelial and accessory cells that may act either as virus reservoir or as antigen-presenting cells to T4 lymphocytes and to GC B cells. In addition, the positivity of high endothelial cells for p24 might help to explain their selective Ia-1+.

AIDS-Related Complex↗
PubMedDate not supplied

Increased production of interferon-gamma, but not IL-4 mRNA, by streptozotocin in the popliteal lymph node assay.

The popliteal lymph node (PLN) assay has been proposed as a tool to predict systemic autoimmune reactions induced by medicinal products and chemicals, the mechanisms of which are poorly understood. To determine whether PLN responses involved Th1 or Th2 cell control, or both, the effects of streptozotocin (STZ), a prototypic immunotoxic compound, were analysed on the production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) mRNA by lymph node cells after injection into the hind footpad of C57 BL/6 mice. Streptozotocin induced a dramatic increase in IFN-gamma mRNA production, which correlated with PLN responses as evidenced by augmented weight and cellularity indices. No effect on IL-4 mRNA synthesis was noted. These results suggest that a Th1 response is involved in the PLN response to STZ.

Animals↗
PubMed2005

Metastatic lymph node impostor in pancreatic cystadenocarcinoma.

CONTEXT: Lymph node involvement in pancreatic cancer is a predictor of poor patient long-term survival. The detection of multiple metastatic peri-pancreatic nodes by EUS-FNA may dissuade the surgeon from undertaking a curative pancreatic resection. CASE REPORT: We report an interesting case of a man with chronic lymphocytic leukemia, who presented with the diagnostic problem of a pancreatic solid-cystic lesion and multiple malignant-looking peri-pancreatic lymphadenopathy on EUS. EUS-FNA yielded chronic lymphocytic leukaemia involvement in the peri-pancreatic lymph nodes and a markedly elevated CEA in the cystic fluid. The absence of adenocarcinoma involvement of the lymph nodes prompted surgery on the pancreatic lesion with a curative intent. Pancreatic mucinous cystadenocarcinoma was diagnosed and a sub-total pancreatectomy was performed with clear resection margins. All 30 resected peri-pancreatic lymph nodes showed chronic lymphocytic leukemia involvement only. CONCLUSIONS: This case illustrates that abnormal lymphadenopathy adjacent to a primary pancreatic lesion may not necessarily be due to the latter. Systemic lymphoproliferative disease, as in this case, can masquerade as metastatic adenocarcinoma lymph nodes on EUS. EUS-FNA is useful in diagnosing lymphoproliferative disease.

Aged↗
PubMed2001

Sulfation of L-selectin ligands by an HEV-restricted sulfotransferase regulates lymphocyte homing to lymph nodes.

Lymphocytes home to lymph nodes, using L-selectin to bind specific ligands on high endothelial venules (HEV). In vitro studies implicate GlcNAc-6-sulfate as an essential posttranslational modification for ligand activity. Here, we show that genetic deletion of HEC-GlcNAc6ST, a sulfotransferase that is highly restricted to HEV, results in the loss of the binding of recombinant L-selectin to the luminal aspect of HEV, elimination of lymphocyte binding in vitro, and markedly reduced in vivo homing. Reactivity with MECA 79, an adhesion-blocking mAb that stains HEV in lymph nodes and vessels in chronic inflammatory sites, is also lost from the luminal aspects of HEV. These results establish a critical role for HEC-GlcNAc6ST in lymphocyte trafficking and suggest it as an important therapeutic target.

Animals↗
PubMed2003

Fluid and cellular pathways of rat lymph nodes in relation to lymphatic labyrinths and Aquaporin-1 expression.

The aim of the present study was to examine the organization of lymph fluid and cellular pathways and distribution of the membrane water channel Aquaporin-1 (AQP-1) in rat lymph nodes. Lymph fluid and cellular pathways within lymph nodes were examined by fluorescent protein tracer/confocal microscopy and by scanning electron microscopy (SEM), While the distribution of AQP-1 was studied immunohistochemically. Tracer studies showed the subcapsular sinuses continued directly at the hilum or via the intermediate sinuses to the medullary sinuses, and lymphatic labyrinths originating with blind-ends in the deep cortex drained into medullary sinuses. Afferent lymph tracers were also observed in node cortex interstitium. By SEM, lymphatic labyrinths appeared densely filled with lymphocytes and had few intraluminal sinus reticular cells, while medullary sinuses possessed well-developed networks of sinus reticular cells. The presence of many lymphocytes wedged in the walls of the lymphatic labyrinth suggested that lymphocytes migrate between the node parenchyma and lymphatic labyrinths. AQP-1 was distributed on the membrane of lymphatic endothelium and reticular cells as well as on both luminal and abluminal cell membranes of high endothelial venules (HEVs). Our SEM findings support the concept that lymphocytes migrate from the node parenchyma into lymphatic labyrinths in the deep cortex. The nodal distribution of AQP-1 plus the presence of a polarized distribution of ion pumps and/or ion channels in the HEV endothelium hypothesized in our discussion could explain the mechanism of the reported lymph-to-plasma fluid flux in lymph nodes and also facilitate the entry of afferent lymph antigens into the node cortex interstitium.

Animals↗
PubMed2000

Efficacy of immunoscintigraphy for detection of lymph node metastases.

The size of a lymph node is not in principle a limitation for the detection of cancer by Nuclear Medicine techniques. A radioactive pinhead is detectable if it has enough radioactivity on it. The approach of Nuclear Medicine to the demonstration of impalpable lymph nodes or to those lymph nodes detected by radiological techniques that are under 1 cm as to whether or not they contain cancer, is to increase the activity attached to cancer cells in such a lymph node as much as possible and to use sophisticated image analysis techniques to distinguish such uptake from its environment. This may be undertaken using a non specific technique such as F-18 Deoxyglucose and Positron Emission Tomography which is highly sensitive and which has been successful. The alternative approach is to use a highly specific and sensitive agent, such as a radio-labelled peptide or a radio-labelled monoclonal antibody together with image analysis. This paper describes these approaches and in particular the use of Tc-99m SM3 monoclonal antibody in the detection of impalpable axillary nodes in patients with breast cancer before surgery, using a change detection analysis providing a probability map of the significance of uptake of this radiopharmaceutical. It is a robust approach, providing the patient and the surgeon with information as to the likely need for extensive axillary surgery well prior to operation. A negative study should be followed by a sentinel node evaluation at surgery.

Axilla↗
PubMed1997

Prospective evaluation of computed tomography and mediastinoscopy in mediastinal lymph node staging.

Precise mediastinal lymph node (LN) staging is imperative in otherwise operable non-small cell lung cancer (NSCLC), as it determines subsequent treatment and possible inclusion in a neoadjuvant trial. The roles of mediastinoscopy and computed tomography (CT) remain controversial. To determine the accuracy of current CT scanners, a prospective study was performed. From April 1993 until September 1995, 100 consecutive patients with NSCLC without distant metastases underwent staging by CT and cervical mediastinoscopy. Naruke's map was used for classification, and LNs larger than 1 cm were considered CT positive. There were 91 males and 9 females, with a mean age of 64 (range 45-82) yrs. Fifty nine tumours were central and 41 peripheral, 64 right-sided and 36 left-sided. Thoracotomy with mediastinal LN sampling was performed in 74 patients, nonoperated patients having multilevel stage IIIA or stage IIIB disease. Twenty five (25%) mediastinoscopies were positive and three were false-negative (3%). There were 29 false-positive CT scans and 12 false-negative. Overall sensitivity and specificity of CT were 63 and 57%, respectively, and of mediastinoscopy 89 and 100%, respectively. Positive and negative predictive values of CT were 41 and 77%, respectively, and of mediastinoscopy 100 and 96%, respectively. Accuracy of CT was 59% and of mediastinoscopy 97%. Accuracy of CT was lowest for left-sided and centrally located tumours, and for LN station 7. Even with current computed tomography scanners, sensitivity and specificity remain low. Although overall cost may increase, routine cervical mediastinoscopy is necessary for precise staging of non-small cell lung cancer, and subcarinal lymph nodes should be routinely sampled.

Carcinoma, Non-Small-Cell Lung↗
PubMed1985

Lectin I of Ulex europaeus as a marker for a subset of histiocytic tumours of the lymph node.

We describe four lymph node based tumours in which numerous neoplastic cells and some mitotic figures were characterized by staining affinity for Lectin I of Ulex europaeus (UEA-I). The patients had no vascular or epithelial tumours and presented symptoms suggestive of a systemic lymphoproliferative disease. Histologically, the tumours were composed of large, cohesive, cells which were mainly located in the paracortex. UEA-I reactivity was more evident in the Golgi area and was present in large mononucleated cells often arranged to delimit vascular-like spaces. The neoplastic cells were weakly muramidase-positive in one case, and were ANAE+/AP+ in two other cases. Large dots of UEA-I reactivity were detected in S-100+/muramidase-negative Langerhans-like cells present in one case of Letterer-Siwe disease. UEA-I staining was consistently negative in 20 cases of B cell- or T cell lymphoma and in 9 other cases of histiocytic lymphoma. It is suggested that UEA-I+ tumours of the lymph nodes are part of a distinct subset of histiocytic malignancies whose neoplastic cells present some morphological and phenotypic properties normally associated with endothelial cells.

Adolescent↗
PubMed2004

Cytokine release does not improve the sensitivity and specificity of the direct popliteal lymph node assay.

The popliteal lymph node assay (PLNA) is being considered as a tool to predict the potential of drugs for inducing systemic autoimmune and hypersensitivity reactions. Despite the use of different technical approaches and the evaluation of over 130 compounds, the sensitivity and specificity of the PLNA are still debatable due to many false positive and negative responses. In this study, cytokine production was assessed as a possible endpoint to improve the direct (primary) PLNA. Diclofenac, imipramine, hydralazine, glafenin and minocycline were tested using the classical procedure. TH1 cytokines (IL-2 and IFN-gamma), TH2 cytokines (IL-4 and IL-5) and pro-inflammatory cytokines (IL-6, TNF-alpha, monocyte chemoattractant protein-1 (MCP-1), IL-12p70 and IL-10) were measured in the serum and in suspensions of popliteal lymph node cells of female Balb/c mice by flow cytometry 7 days after drug administration. Only diclofenac and imipramine induced a cellularity index above 5 (considered as a positive response). Of the five tested drugs, only diclofenac induced a slight increase in TH1 cytokines, but there were no effects on TH2 cytokine production whatever the drug tested. Diclofenac increased the production of pro-inflammatory cytokines, whereas the production of MCP-1 was increased by minocycline and decreased by imipramine. No changes in serum cytokine levels were evident. These results suggest that measuring cytokine release is unlikely to improve the sensitivity and specificity of the direct PLNA.

Animals↗
PubMed1998

Ultrasonographic appearance of normal superficial cervical and subiliac lymph nodes in cattle.

The superficial cervical and the subiliac lymph nodes of 18 healthy, non-pregnant Simmental cows with a mean (sd) age of 5-6 (1.6) years were examined ultrasonographically in transverse and longitudinal planes with a real-time B-mode unit equipped with a 7.5 MHz linear-transducer. The position, demarcation and echogenicity of the lymph nodes were examined, and the craniocaudal and lateromedial diameters of each lymph node were measured three times within a period of six weeks. The pole to pole length of the lymph nodes was determined with a tape measure on the surface of the skin because the whole length could not be imaged in a single scan field. The gross anatomical and histological results showed that the lymph nodes were normal. Ultrasonographically, they were well demarcated from the adjoining muscular and subcutaneous tissue. Their internal structure was characterised by an anechoic to hypoechoic cortical zone corresponding to the lymphoid tissue, and an echogenic medullary zone, where the lymphatic sinuses converge towards the hilus and produce numerous acoustic interfaces. In all the lymph nodes, the hilar area had an echoic to hyperechoic appearance. The mean (sd) pole to pole length of the superficial cervical lymph nodes was 15.5 (3.2) cm and of the subiliac lymph nodes 13.5 (2.4) cm. The mean craniocaudal and lateromedial diameters of the superficial cervical lymph nodes were 2.8 (0.3) cm and 1.6 (0.3) cm, and those of the subiliac lymph nodes were 2.4 (0.4) cm and 1.1 (0.3) cm. The ultrasonographic morphology of these normal lymph nodes was consistent and provides basic reference data for the investigation of lymphadenopathies in cattle.

Animals↗
PubMed1999

Detection of melanoma micrometastases in the sentinel lymph node and in nonsentinel nodes by tyrosinase polymerase chain reaction.

The aim of our study was to investigate the metastatic pathways of melanoma cells in sentinel and other regional lymph nodes. The term "sentinel lymph node" means that the first lymph node of the draining site of a primary tumor is never bypassed in malignant melanoma. In this case lymph node dissection would be necessary only when melanoma cells are detected in the sentinel node. Tyrosinase reverse transcriptase-polymerase chain reaction was applied to search for metastatic melanoma in the sentinel lymph node and in further lymph nodes of a complete lymph node basin in patients who underwent lymph node dissection. In 24 patients with malignant melanoma the draining site of the tumor was marked by lymphoscintigraphy and by intraoperative injection of patent blue V in the area around the primary tumor. The lymph nodes of the affected basin were excised and prepared for histopathologic, immunohistochemical, and molecular biologic examinations. Regarding the sentinel lymph node, 10 of 24 patients showed morphologic evidence for metastases, three additional patients showed only tyrosinase transcripts. In 11 of these 13 cases we found one or more nonsentinel lymph nodes with morphologically detectable melanoma cells and/or tyrosinase mRNA. Interestingly, in seven of 24 patients a positive tyrosinase reverse transcriptase-polymerase chain reaction was received in nonsentinel lymph nodes, whereas the sentinel lymph node was negative, not only for all histologic examinations but also by tyrosinase reverse transcriptase-polymerase chain reaction. In five of seven patients of the latter group, gp100 reverse transcriptase-polymerase chain reaction was carried out, showing also gp100 mRNA in nonsentinel lymph nodes only. Our data indicate that the concept of the sentinel lymph node may miss micrometastases. Whether such micrometastases cause a recurrence or a metastasis of malignant melanoma, or can be destroyed by the immune system, remains to be clarified.

Adult↗