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Lymph node macrophage heterogeneity: the phenotypic and functional characterization of two distinct populations of macrophages from rat lymph node.

The isolation and characterization of lymph node macrophages (M phi) has shown a hitherto unknown heterogeneity. Two types of M phi were distinguished by morphology, monoclonal antibody staining and functional assays. The type I M phi failed to express surface Ia even when activated, a characteristic which has only previously been reported for splenic marginal zone M phi; despite studies suggesting an antigen presentation role for the M phi, the failure to express surface Ia would seem to eliminate an interaction with T helper cells for the type I M phi in the lymph node. In contrast, the type I M phi, other characteristics of clustering with activated B cells in vitro, the colocalization of the type I M phi and activated B cells in situ, the specific uptake of thymus-independent type 2 antigens and the failure to undergo respiratory burst activity all suggest a M phi-B cell interaction, possibly of a trophic nature. The defective microbicidal activity of the type I M phi may have been compensated for by the type II M phi, which expresses both strong respiratory burst activity and surface Ia expression when freshly isolated. However, unlike the inflammatory M phi the activated phenotype of the type II M phi did not appear to be interferon-gamma dependent because type II M phi could also be isolated from nude rat lymph nodes.

Animals↗

[Correlation of lymph node size and metastatic involvement of lymph nodes in bronchial cancer].

For preoperative staging in lung cancer mediastinoscopy is in competition with X-ray, tomography, and computer-tomography (CT). Many authors certify a high sensitivity and specificity to CT in staging lung cancer preoperatively by measuring the diameter of the hilar and mediastinal lymph nodes. In this study we measured the diameter of 162 lymph nodes from 83 patients postoperatively. In view of staging we found no sufficient correlation between the diameter of the lymph nodes and their infiltration by cancer cells. Even 35.7% of the nodes with a diameter of more than 2 cm were not infiltrated. The data support the opinion that CT alone is not sufficient for preoperative staging in lung cancer.

Adenocarcinoma↗

Lymph node accessory cells in the immune response. The primary response to paratyphoid vaccine in rat parathymic lymph nodes.

The immune response in the rat parathymic lymph node was studied after administration of antigen into the peritoneal cavity. Special attention was paid to the accessory cells, which might induce the response. During the induction phase of the response a heterogeneous population of non-lymphoid mononuclear cells was present in the subcapsular sinus and the cortex of the node. These cells resemble "veiled cells" described in skin draining lymph and interdigitating cells in the paracortex of skin draining lymph nodes, but they do not contain Birbeck granules. It is concluded that the appearance of these granules depends on the site of the exudate provocation and that the presence of the organelles in these accessory cells is not obligatory for lymphocyte stimulation.

Animals↗

[Erythrocytes in cervical lymph nodes of the human as a sequela of stasis and/or lymph drainage. Questionable diagnostic significance in strangulation and mechanical injuries of the head].

Information on the diagnostic significance of follicular hemorrhage and/or presence of red blood cells in the lymph node sinus was obtained by microscopic investigation of the superficial and deep human cervical lymph nodes. Fifty cases were selected on the basis of the following criteria: (1) cases without strangulation or mechanical head trauma; (2) cases in which death occurred by strangulation without additional mechanical head trauma; (3) cases without strangulation but with mechanical head trauma; (4) cases with strangulation and mechanical head trauma. The usual degree of stasis and hemorrhages and the dilation of the veins and/or capillaries are not sufficient to discriminate between cases with and cases without strangulation. Moreover, erythrocytes, erythrophages, and siderophages were encountered in the lymph node sinus of both cases with and cases without mechanical head trauma. Neither follicular hemorrhage nor the presence of red blood cells in the sinus is therefore diagnostically significant in forensic pathology.

Asphyxia↗

Predictors of positive axillary lymph nodes in breast cancer patients with metastatic sentinel lymph node.

INTRODUCTION: Breast cancer with metastatic sentinel lymph nodes (SLN) may have clinico-pathologic factors associated with the presence of positive non-sentinel axillary nodes (NSLN). The aim of the present study was to determine factors that predict involvement of NSLN in breast cancer patients with positive SLN. MATERIAL AND METHODS: A prospective database search identified 80 patients who underwent SLN biopsy for invasive breast cancer between January 1999 and August 2002. Clinico-pathologic data was analyzed to determine factors that predicted additional positive axillary nodes. RESULTS: A total of 23 patients had positive SLN and underwent conventional axillary lymph node dissection. Statistical analysis revealed that lympho-vascular invasion (p~0.00000), SLN metastasis >2 mm (p=0.002), and the presence of extra-nodal involvement (p=0.002), were positive predictors of the metastatic involvement of NSLN. CONCLUSIONS: The likelihood of positive NSLN correlates with pathologic parameters such as the presence of lympho-vascular invasion, size of the SLN metastasis, and extra-nodal involvement. These data may be helpful with the regard to the decision to undertake axillary dissection in breast cancer patients with metastatic sentinel lymph nodes.

Adult↗

Preoperative ultrasonographic examination for lymph node metastasis: usefulness when designing lymph node dissection for papillary microcarcinoma of the thyroid.

Papillary microcarcinoma has an excellent prognosis after surgical treatment, but how to dissect the lymph nodes remains an open question. In this study, we investigated whether modified radical neck dissection (MND) affected the lymph node recurrence-free survival (LN-RFS) rate for 590 patients with papillary microcarcinoma and recurrence in the lateral compartment who underwent surgery in our hospital between 1993 and 2001. MND was performed in 316 patients, and metastasis in lateral compartment was preoperatively detected on ultrasonography in 67. These 67 patients showed significantly worse LN-RFS (p = 0.0038) than the remaining 249 patients without preoperatively detectable lateral node metastasis. Of the 523 patients (590 minus the 67 patients) whose lateral node metastasis was not detected preoperatively, 249 underwent MND; the remaining 274 patients did not. There was no significant difference in LN-RFS between these two groups. Our preliminary data suggest that with papillary microcarcinoma: (1) MND is not necessary in patients without lateral node metastasis detected on ultrasonography preoperatively, and (2) patients with preoperatively detected lateral node metastasis are more likely to develop recurrence in the lymph nodes so careful MND should be performed.

Adolescent↗

Immunohistochemical study of bovine lymph nodes with antibodies against S100 protein subunits: comparison between lymph nodes of healthy and Mycobacterium paratuberculosis-infected cattle.

Using immunohistochemistry, the differential distribution of the alpha subunit (S100 alpha) and beta subunit (S100 beta) of S100 protein was studied in mesenteric lymph nodes from normal or Mycobacterium paratuberculosis-infected cattle. In epithelioid cell granulomas, S100 alpha-positive epithelioid cells and some giant cells were scattered among S100 alpha-negative cells, which were predominant. The S100 beta-positive and -negative cells contained acid-fast bacilli. The presence of S100 beta-positive cells was not demonstrated in the granulomas. In normal component cells in the lymph nodes, follicular dendritic cells in the germinal centres and endothelium of lymphatic sinus and lymph vessels were positive for S100 alpha. S100 beta was positive only in the endothelial cells of blood vessels. Results shown in the present paper are discussed in light of results obtained in other work on human tissues using the same sources of antibodies.

Animals↗

Intramammary lymph nodes and breast cancer: a marker for disease severity, or just another lymph node?

BACKGROUND: Axillary lymph node status is still considered the most significant prognostic factor for breast cancer outcome, and treatment decisions are based on the presence or absence of nodal disease. Intramammary lymph nodes (IMLNs) can be a site of regional spread. Is this a marker for more aggressive disease? METHODS: We reviewed the cancer center pathology database from 1991 to 2005 for all cases of breast cancer with IMLNs. RESULTS: IMLNs were identified in 64 breast cancer patients, with metastatic spread in 20 patients, and benign IMLNs described in 44 patients. Positive IMLNs were associated with more aggressive disease, including higher rates of invasive versus noninvasive cancers (5% ductal carcinoma-in-situ [DCIS] with positive IMLNs vs. 23% with negative IMLNs), lymphovascular invasion (55% vs. 11%), and a higher rate of axillary lymph node involvement (72% vs. 18%). Patients with positive IMLNs were also more likely to undergo mastectomy (75% vs. 54%). CONCLUSIONS: IMLN metastases are a marker for disease severity; recognition of this may influence choice of adjuvant therapy. The presence of metastatic disease in an IMLN is associated with a high rate of axillary nodal involvement, and should mandate axillary dissection. Preoperative lymphoscintigraphy may help identify these extra-axillary metastases.

Adult↗

Cytokine mRNA expression in leukocytes of efferent lymph from stimulated lymph nodes in pigs.

To test the hypothesis that characteristic cytokine responses occur in stimulated porcine lymph nodes (LNs), lymph node efferent ducts were surgically cannulated. Efferent lymph (EL) leukocytes were collected before and after stimulation of LNs with mitogens [bacterial lipopolysaccharide (LPS) or phytohemagglutinin-P(PHA-P)] and antigens [hen egg white lysozyme (HEWL) or purified protein derivative of tuberculin (PPD)]. Cytokine mRNA expression was evaluated by quantitative reverse transcription polymerase chain reaction (Q-RT-PCR). Interleukin (IL)-1alpha was predominantly produced after all stimuli except for HEWL after which tumour necrosis factor (TNF)-alpha message was dominant. None of the stimuli induced message for IL-2, IL-4 or IL-8. Other cytokine mRNAs were produced in variable amounts and percentage of overall production of each cytokine message was in the following descending rank: LPS: IL-1alpha, TNF-alpha, interferon (IFN)-gamma, IL-10, IL-12-p35, IL-6, IL-12-p40 and TNF-beta; PHA-P: IL-1alpha, TNF-alpha, IL-10, IFN-gamma, IL-12-p40 and TNF-beta; HEWL: TNF-alpha, IL-1alpha, IFN-gamma, IL-10, IL-6, IL-12-p40, TNF-beta and IL-12-p35 and PPD: IL-1alpha, IFN-gamma, TNF-alpha and IL-10. Time course response of cytokines revealed early (IL-1alpha, 10, TNF-alpha) and intermediate (IL-12-p40, TNF-beta, IFN-gamma) responses for PHA-P and early (IL-1alpha, 6, 10, IL-12-p35, IL-12-p40, TNF-alpha), intermediate (TNF-beta, IFN-gamma) and late (IL-1alpha, 6) for LPS. Cytokine mRNA response induced by HEWL was early (IL-alpha, IFN-gamma), intermediate (IL-10, IL-12-p40, TNF-beta), late (IL-1alpha, IL-12-p35) and very late (IL-1alpha, 6, 10, IL-12-p40, TNF-alpha). In Bacillus Calmette-Guérin (BCG) sensitized pigs, stimulation of LNs with PPD induced message for IL-1alpha, 10, TNF-alpha and IFN-gamma which peaked at 24h. Cytokine mRNAs varied by stimulus and differed for antibody and cell-mediated immune response.

Animals↗

Increased activity of lymph node cells in experimental thermal injury: changes in accessory cells in injured area-draining lymph nodes.

Accessory cell content and some of their functional characteristics were determined in regional lymph nodes which drain burn injury (DLN) in rats. Increase in percentages of non-specific esterase-positive cells and NBT+ macrophages and in numbers of dendritic cells were noted in cytospin preparations of draining lymph node cells (DLC) 24 and 72 h following thermal injury. An accumulation of B cells was also noted in the DLN paracortex region at these time points. Enrichment of ED1+ (rat macrophage marker) cells was noted in the adherent DLC population. Increased activity of interleukin-1 (IL-1) in conditioned medium from adherent DLC population and the increased stimulatory capacity of whole DLC or dendritic cell enriched-DLC fraction were noted in functional assays. Enrichment in accessory cells and an increase in their functional activity could contribute to the endogenous activity of regional lymph nodes which drain burned areas.

Animals↗

Evaluation of lymph node status in male breast cancer patients: a role for sentinel lymph node biopsy.

Sentinel lymph node (SLN) biopsy is rapidly emerging as an alternative to axillary lymph node dissection (ALND) for many female breast cancer patients. In contrast, ALND remains the standard of care for male breast cancer patients with similar tumors. We evaluated the results of SLN biopsy in male breast cancer patients with clinically negative axillae. This study included all male breast cancer patients who underwent SLN biopsy at our institution between October 1999 and 2000. All patients had negative axillae on clinical examination and sonography. All patients underwent preoperative lymphoscintigraphy followed by SLN biopsy performed using a combination of isosulfan blue dye and technetium Tc 99m sulfur colloid. Tc 99m sulfur colloid was injected at a dose of 2.5 mCi 24 h before surgery (four patients) or 0.5 mCi 2-4 h before surgery (three patients). Intraoperatively, 5 ml of 1% isosulfan blue was injected adjacent to the breast tumor or biopsy cavity prior to SLN biopsy. A gamma probe was used intraoperatively in order to localize SLNs. Any node that was blue or associated with ex vivo radioactivity counts at least 10 times higher than the axillary background counts was defined as a SLN. SLNs were assessed intraoperatively using touch preparation cytologic examination. Completion ALND was performed if nodal metastases were identified. Seven patients, 44-76 years of age, were included in the study. Preoperative lymphoscintigraphy identified SLNs in five patients. Intraoperatively, SLNs were identified in all seven patients. SLNs were identified in six patients using the gamma probe and in all seven patients using blue dye. The mean number of SLNs encountered was 2.9. Findings on touch preparation cytology correlated with findings on the final pathological analysis examination in all patients. One patient had a positive SLN, this patient had three additional positive nodes identified in his completion ALND specimen. Three patients with negative SLNs had been elected preoperatively to undergo ALND regardless of findings on SLN biopsy, no positive lymph nodes were identified in the ALND specimens from these patients. These findings compare favorably with findings reported in the literature regarding SLN biopsy in female breast cancer patients. Blue dye injection and radioisotope injection were complementary. SLN biopsy should be considered for axillary staging in male breast cancer patients with clinically negative axillae.

Adult↗

[Contrast retention in retroperitoneal lymph nodes after lymphography; the effect of lymph node abnormalities, radiotherapy and contrast quantity].

The rate of contrast loss from retroperitoneal lymph nodes after lymphography was studied radiologically over a prolonged period in 302 patients. It varied remarkably, even in normal persons who were not receiving any treatment. Lymph nodes empty more quickly if only a small quantity of contrast has been used. Irradiation accelerates contrast transport, not only in the irradiated, but also in the neighbouring, group of nodes. This effect is dose dependent. There is evidence that pathological lymph nodes empty more quickly than normal ones.

Adult↗

Extraperitoneal endoscopic pelvic lymph node dissection vs. laparoscopic lymph node dissection in the staging of prostatic and bladder carcinoma.

Eighteen patients undergoing laparoscopic pelvic lymphadenectomy were compared with eighteen patients undergoing lymph node dissection performed via a totally extraperitoneal approach called extraperitoneal endoscopic pelvic lymph node dissection. Operative time, nodal yield, and hospital stays were essentially the same in both groups. However, the laparoscopic approach had a greater incidence of morbidity, leading the authors to adopt a totally extra-peritoneal endoscopic approach to pelvic lymph node dissection. Advantages of using an extraperitoneal approach are presented.

Aged↗

Retroperitoneal lymph node dissection in patients with interaortocaval lymph node metastases of transitional cell carcinoma of the urinary tract.

Three patients suffered from renal pelvic, ureteral and bladder cancers that were treated with both standard surgical treatments and two adjuvant cycles of cisplatin-based combination chemotherapy. Metastases of interaortocaval lymph nodes were detected in all patients between 9 and 33 months from the surgery for primary lesions. All patients received three cycles of cisplatin-based combination chemotherapy and retroperitoneal lymph node dissection (RPLND). The chemotherapy achieved partial response (62-98%). Two patients with viable cancer cells died with hepatic metastases; the first 15 months and the second 25 months from the date of diagnosis of distant lymph node metastasis. The third patient, who had no viable cancer cells, remains alive and disease-free 36 months later. Therefore, RPLND after chemotherapy provides prognostic information that helps to define patients who might benefit from additional systemic chemotherapy.

Aged↗

Implications of popliteal lymph node detected by sentinel lymph node biopsy.

BACKGROUND: Although there is lymphatic flow into the popliteal fossa from a skin tumor located in the lower leg, popliteal metastasis is extremely rare. Recently, sentinel lymph nodes outside traditional nodal basins have been identified. This study investigated the incidence of sentinel nodes in the popliteal region and the indication for biopsy. METHODS: Fourteen patients with various skin cancers involving the lower extremities (nine melanomas, four squamous cell carcinomas, and one sweat gland carcinoma) underwent lymphoscintigraphy and excision with sentinel lymph node biopsy. RESULTS: In all 14 patients, hot spots showed accumulation in the groin region. Five of 14 patients (36%) demonstrated popliteal sentinel nodes in addition to the inguinal nodes. Three of five popliteal sentinel nodes were histologically studied. A patient with acral melanoma demonstrated micrometastasis of melanoma cells in a popliteal node but not in the groin node. CONCLUSION: This study demonstrates that sentinel lymph nodes located in the popliteal fossa are frequently detected by lymphoscintigraphy and that biopsy should be performed if popliteal nodes are identified.

Aged↗

Type of lymph node involvement influences survival rates in T1N1M0 non-small cell lung carcinoma. Lymph node involvement by direct extension compared with lobar and hilar node metastases.

Stage II non-small cell lung cancer represents a group of patients with varying 5-year survival rates. Of 2,009 patients, we reviewed 58 patients with pT1N1M0 disease operated on from 1977 through 1994. The N1 status was refined into lymph node involvement by direct extension and/or involvement by metastases (lobar or hilar). The cumulative 5-year survival of all hospital survivors (n = 57) was 45.7%. The 5-year survival of patients with N1 direct extension was superior to survival of patients with N1 metastases (68.6% vs 31.2%; p = 0.0038). Survival of patients with N1 direct extension was better then survival of patients with N1 hilar metastases (p = 0.0006), but did not differ from survival of patients with lobar metastases. Survival was not related to histologic features, sex, and type of resection. Recurrence of malignancy occurred less in patients with N1 direct extension. In patients with N1 hilar nodes, the most common pattern was distant metastases. Survival differs according to the type of lymph node involvement: "direct extension" seems to be an early stage of the disease, while lymph node metastases represent a more advanced form.

Adult↗

Formation of lymph follicles in draining lymph nodes after local injection of various antigenic substances in mice.

Formation of lymph follicles in draining popliteal lymph nodes was examined in 8-week-old, male C57Bl/6 mice which had been injected in the rear footpad with any one of eleven test substances including thymus-dependent and thymus-independent antigens, and killed after 6-14 days. HGG (10-100 micrograms), MGG, tetanus and diphtheria toxoids (2-10 Lf) and influenza HA vaccine (35 CCA) induced germinal centers in association with existing follicles, but failed to produce new follicles in draining nodes. KLH (10-100 micrograms), SRBC (1 X 10(8)) and formalin-killed pertussis organisms (5 X 10(8)) induced germinal centers in existing follicles and also produced new follicles which soon developed germinal centers. Levan and PVP (10-100 micrograms) induced neither germinal centers nor new follicles. Ferritin (100 micrograms) virtually failed to induce germinal centers but produced a significant number of new primary follicles. In further experiments, artificially aggregated substances were examined with regards to their ability of inducing lymph follicle formation in draining nodes. Precipitated proteins such as alum-precipitated PHA, HGG, tetanus and diphtheria toxoids, "Sepharose"-PHA and "Sepharose"-HGG induced a significant number of new follicles. These observations suggest that efficient follicle formation is associated with particulate and high-molecular-weight antigens which are liable to be phagocytized, whereas soluble, poorly phagocytized antigens tend to be inefficient. Soluble proteins may be effective if given in precipitated form. Thymic dependency appears to be irrelevant. The present results point to a possible participation of macrophages in the mechanism of follicle formation.

Animals↗

Sentinel lymph node concept in gastric cancer with solitary lymph node metastasis.

AIM: To study the localization of the solitary metastases in relation to the primary gastric cancers and the feasibility of sentinel lymph node (SLN) concept in gastric cancer. METHODS: Eighty-six patients with gastric cancer, who had only one lymph node involved, were regarded retrospectively as patients with a possible sentinel node metastasis, and the distribution of these nodes were assessed. Thirteen cases with jumping metastases were further studied and followed up. RESULTS: The single nodal metastasis was found in the nearest perigastric nodal area in 65.1% (56/86) of the cases and in 19.8% (17/86) of the cases in a fairly remote perigastric area. Out of 19 middle-third gastric cancers, 3 tumors at the lesser or greater curvatures had transverse metastases. There were also 15.1% (13/86) of patients with a jumping metastasis to N2-N3 nodes without N1 involved. Among them, the depth of invasion was mucosal (M) in 1 patient, submucosal (SM) in 2, proper-muscular (MP) in 4, subserosal (SS) in 5, and serosa-exposed (SE) in 1. Five of these patients died of gastric cancer recurrence at the time of this report within 3 years after surgery. CONCLUSION: These results suggest that nodal metastases occur in a random and multidirectional process in gastric cancer and that not every first metastatic node is located in the perigastric region near the primary tumor. The rate of "jumping metastasis" in gastric cancer is much higher than expected, which suggests that the blind examination of the nodal area close to the primary tumor can not be a reliable method to detect the SLN and that a extended lymph node dissection (ELND) should be performed if the preoperative examination indicates submucosal invasion.

Gastrectomy↗