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[Computed tomography of the soft tissues of the neck. Lymph node metastases and their differential diagnosis. I. Methods and the principal CT criteria for lymph node metastases].

Standardisation of the examination method is imperative to guarantee reproducible and valid assessability of the cervical lymph node status. To this end, update high-resolution CT equipment of the third generation will be suitable, provided it meets certain minimum requirements, such as: 120 kV, 280 mAs, 480 projections over 360 degrees, 4-5 mm slice thickness, continuous tomography. If a primary tumour is known to exist, no plain examination is needed. The decisive examination is effected after intravenous administration of contrast medium in a dosage of 2.0-2.5 ml contrast medium/kg body weight (assuming a body weight of 70 kg, this would amount to 150 ml = 45 g iodine), one-third of the total dosage to be given as bolus and two-thirds as a rapid infusion. This procedure ensures sharp definition of lymph nodes against vessels and musculature over the entire period of examination. If tumour anamnesis has been established the size of the lymph node is significant for assessing the lymph node status. Even lymph node metastases less than 15 mm can be properly identified if the structure of the lymph nodes is known and employed as a criterion (central hypodensity with rim enhancement, inhomogeneity).

Carcinoma, Squamous Cell↗

The human peripheral lymph node vascular addressin is a ligand for LECAM-1, the peripheral lymph node homing receptor.

The trafficking of lymphocytes from the blood and into lymphoid organs is controlled by tissue-selective lymphocyte interactions with specialized endothelial cells lining post capillary venules, in particular the high endothelial venules (HEV) found in lymphoid tissues and sites of chronic inflammation. Lymphocyte interactions with HEV are mediated in part by lymphocyte homing receptors and tissue-specific HEV determinants, the vascular addressins. A peripheral lymph node addressin (PNAd) has been detected immunohistologically in mouse and man by monoclonal antibody MECA-79, which inhibits lymphocyte homing to lymph nodes and lymphocyte binding to lymph node and tonsillar HEV. The human MECA-79 antigen, PNAd, is molecularly distinct from the 65-kD mucosal vascular addressin. The most abundant iodinated species by SDS-PAGE is 105 kD. When affinity isolated and immobilized on glass slides, MECA-79 immunoisolated material binds human and mouse lymphocytes avidly in a calcium dependent manner. Binding is blocked by mAb MECA-79, by antibodies against mouse or human LECAM-1 (the peripheral lymph node homing receptor, the MEL-14 antigen, LAM-1), and by treatment of PNAd with neuraminidase. Expression of LECAM-1 cDNA confers PNAd binding ability on a transfected B cell line. We conclude that LECAM-1 mediates lymphocyte binding to PNAd, an interaction that involves the lectin activity of LECAM-1 and carbohydrate determinants on the addressin.

Antigens, Surface↗

Lymph node metastases of prostatic adenocarcinoma in the mesorectum in patients with adenocarcinoma or villous tumor of the rectum with collision phenomenon in a single lymph node: report of five cases.

PURPOSE: Lymph node involvement is the most important prognostic factor when staging patients with rectal cancer. Cancer originating from sites other than rectum rarely may metastasize to the mesorectum. We report five patients with metastatic prostatic carcinoma to mesorectal lymph nodes, with the "collision phenomenon" in one lymph node. The diagnosis of prostate cancer was clinically unsuspected in two cases. METHODS: We examined three cases of primary adenocarcinoma and two villous tumors with high-grade dysplasia (patient age range, 52-74 (mean, 63) years) of the middle or lower third of the rectum. All patients underwent low anterior rectal resection with total mesorectal excision and colorectal or coloanal anastomosis. We used a manual technique for lymph node detection after overnight fixation in 10 percent formalin. All lymph nodes identified (range, 15-32; mean, 21 nodes per patient) were examined histologically. RESULTS: Of 106 lymph nodes examined, 20 contained metastases: 9 from rectal adenocarcinoma, 10 from prostatic adenocarcinoma, and 1 with metastatic foci from both tumors. The diagnosis of prostatic carcinoma was readily confirmed by immunostaining for prostatic-specific antigen, and prostatic acid phosphatase. CONCLUSIONS: Mesorectal lymph node dissection provides prognostic information in rectal cancer, but careful examination may reveal other unsuspected pathology. Immunohistochemical staining is an essential tool in distinguishing the origin of a lymph node metastasis, especially when the histology does not look typical for rectal carcinoma. Moreover, these observations highlight the connection that can exist between mesorectal lymph node drainage, and extra mesorectal lymph nodes drainage.

Adenocarcinoma↗

Sentinel lymph node biopsy or detection of micrometastasis in bone marrow: which might be an alternative to axillary lymph node dissection in breast cancer patients?

Axillary lymph node status has limited prognostic significance in breast cancer patients and much improvement can be made. Sentinel lymph node biopsy is emerging as an alternative to axillary lymph node dissection for staging, but its prognostic relevance is still uncertain. Detection of micrometastases in sentinel nodes and bone marrow may provide more information, but the clinical significance still needs to be confirmed by ongoing large trials. In this review, we focus on the possibility of sentinel lymph node biopsy or detection of bone marrow micrometastasis replacing traditional axillary lymph node dissection.

Axilla↗

Pathologic review of negative sentinel lymph nodes in melanoma patients with regional recurrence: a clinicopathologic study of 1152 patients undergoing sentinel lymph node biopsy.

A sentinel lymph node (SLN) that is melanoma negative by pathologic examination implies absence of melanoma metastasis to that regional lymph node field. However, a small proportion of patients develop regional node field recurrence after a negative SLN biopsy. In this study, we reviewed the histopathology of negative SLNs from such patients to determine whether occult melanoma cells were present in the SLNs, to characterize the pathologic features of false-negative SLNs, and to provide recommendations for the histopathologic examination of these specimens. Between March 1992 and June 2001, of 1152 patients who had undergone SLN biopsy for primary melanomas at the Sydney Melanoma Unit, 976 were diagnosed with negative SLNs by initial pathologic examination (using 2 hematoxylin and eosin stained sections, and 2 immunostained sections for S-100 protein and HMB45), and follow-up was available in 957. Of these, 26 (2.7%) developed regional lymph node recurrence during a median follow-up period of 35.7 months. For 22 of them, the original slides and tissue blocks were available for reexamination. The original slides of each block were reviewed. Multiple further sections were cut from each block and stained with hematoxylin and eosin, for S-100, HMB45, and Melan A. Deposits of occult melanoma cells were detected in 7 of the 22 cases (31.8%). In 5 of the 7 cases, deposits of melanoma cells were present only in the recut sections. There were no significant differences in clinical and pathologic variables for those patients in whom occult melanoma cells were found by pathologic reexamination of their SLNs, compared with those in whom no melanoma cells were detected. The detection of melanoma cell deposits in only 7 of 22 false-negative SLNs suggests that mechanisms other than failure of histopathologic examination may contribute to the failure of the SLN biopsy technique in some patients. The failure rate for melanoma detection in SLNs by our routine pathologic examination, using the current protocol at our institution, was <1% (7 of 957 patients). Routinely performing more intensive histopathologic examination of SLNs is difficult to justify from a cost benefit perspective; we therefore recommend examining two hematoxylin and eosin stained sections and two immunostained sections (for S-100 and HMB45) routinely on SLNs from melanoma patients.

Adult↗

Topographic distribution of inguinal lymph nodes metastasis: significance in determination of treatment margin for elective inguinal lymph nodes irradiation of low pelvic tumors.

PURPOSE: To study the distribution of gross inguinal lymph node metastasis and, in particular, its correlation with major pelvic bony structures on a simulation film. METHODS AND MATERIALS: Thirty-seven cases of low pelvic tumors having gross inguinal lymph node metastasis that were treated with radiation therapy between November 1987 and December 1992 were segregated for study. The patient's nodes were palpated and marked with lead wire before the simulation film was assumed to be the origin of the previously uninfested node. A total of 84 such labeled nodes was taken. The geometric center of the usually round or elliptical node on the film was obtained from these 37 cases. These centers were transferred to and mapped collectively on a new simulation film showing major pelvic bony structures of left hemipelvis and upper femur. RESULTS: Distribution of gross inguinal lymph nodes was found confined to the following area, as related to major pelvic bony structure: laterally, just abutting the tangential line that passes through lateral border of the femoral head; medially: 3 cm away from the body's midline axis; superiorly: 1 cm below the line that joins both upper borders of the femoral head; inferiorly: 2.5 cm below the low borders of ischial tuberosity. According to this rectangular boundary, three nodes were out of the field, nine nodes near the border less than 1 cm margin. This area adequately covered 86% (72 of 84) of the studied nodes. CONCLUSION: Distribution study is important in determining the treatment margin. In general, an additional 1-2 cm beyond the area described above is the recommended treatment margin for elective inguinal lymph nodes irradiation with high confidence level of coverage.

Adult↗

Determination of the sensitising activity of the rubber contact sensitisers TMTD, ZDMC, MBT and DEA in a modified local lymph node assay and the effect of sodium dodecyl sulfate pretreatment on local lymph node responses.

A modified local lymph node assay (LLNA) was used to determine the sensitising activity of four chemicals used for the production of natural rubber latex products. Tetramethylthiuramdisulfide (TMTD), 2-mercaptobenzothiazole (MBT) and zincdimethyldithiocarbamate (ZDMC), three moderate human sensitisers, and diethylamine (DEA) a known human sensitiser, were epicutaneously administered on the ear and the proliferating activity in the draining (auricular) lymph node (LN) was determined by ex vivo (3)H-thymidine incorporation. Consistent results were obtained for TMTD and ZDMC with stimulation indices (SI) above 3, identifying these compounds as sensitiser, while for DEA and MBT inconsistent results were obtained. For all parameters determined such as LN weight, LN cell number, cell proliferation per 2 x 10(6) cells, and cell proliferation per LN statistical significant increases were observed. The SI, expressed as cellular proliferation per LN or per animal (left and right LN combined), was the most sensitive parameter with an optimum at day 5 after start of treatment.Furthermore, we investigated whether the use of sodium dodecyl sulfate (SDS) was able to enhance weak responses in the LLNA. SDS treatment with dosages of 10% and higher resulted in a SI above 3, while a dosage of 1% SDS showed no activity. Pretreatment with 1% SDS 1 h before application of the rubber chemicals enhanced the responses to these chemicals consistently, identifying also DEA and MBT as sensitisers. Our results indicate that SDS had synergistic activity on the LN responses of the administered rubber chemicals in the LLNA. For the moderately responding sensitisers TMTD and ZDMC both IFN-gamma and IL-4 production was observed. For the weakly responding sensitisers DEA and MBT both IFN-gamma and IL-4 cytokine production was only observed after pretreatment of the animals with 10% SDS. For 10% and 20% SDS, inducing approximately a SI of 20 in the LLNA, no induction of cytokines was observed.

Allergens↗

The impact of lymph node metastases on the survival of breast cancer patients with ten or more positive lymph nodes.

To investigate the impact of the number of involved lymph nodes on survival, we retrospectively reviewed the data for 37 patients with breast cancer and metastases of ten or more lymph nodes who underwent treatment between 1987 and 1995. Based on the number of positive lymph nodes, the patients were allocated to one of three groups. The 5-year disease-free and overall survival rates for all patients were both 53.0%. The 7 patients with 26 or more positive nodes had significantly poorer survival than either the 19 patients with 10-15 nodes, or the 11 with 16-25 nodes, although there were no differences in survival related to the extent of node involvement as defined using the Japanese staging system. Patients with 50%-75% frequency of metastasis, defined as the positive nodes/total resected nodes, had significantly better survival than those with < 50% or > 75% frequency. These results indicate that the number of involved lymph nodes is related to survival and that 25 positive nodes is a cutoff point in breast cancer patients with ten or more positive lymph nodes.

Adult↗

Active macromolecule uptake by lymph node antigen-presenting cells: a novel mechanism in determining sentinel lymph node status.

BACKGROUND: Although sentinel lymph node (SLN) biopsy is a powerful staging tool for patients with melanoma and breast cancer, controversy remains regarding specific aspects of technique. We examined particle uptake by antigen-presenting cells (APCs) to determine if this mechanism is responsible for the differential retention of radioactivity in SLNs relative to nonsentinel lymph nodes (NSLNs). METHODS: Mapping was conducted in pigs injected with vital blue dye, fluoroscein isothiocyanate-labeled human serum albumin (FITC-HSA), and one of two 99mtechnetium-labeled tracers, i.e., human serum albumin, a small macromolecule, or unfiltered sulfur colloid, a mixture of small and large particles. Macromolecule uptake by APCs was studied in vitro by using FITC-HSA and measured by fluorescence-activated cell sorting (FACS). SLNs and NSLNs were analyzed by fluorescence microscopy or FACS, with counterstaining for leukocyte cell surface markers. RESULTS: Both radiotracers were effective. Cultured APCs rapidly took up FITC-HSA. Microscopy showed FITC-HSA in the subcapsular sinus of SLNs shortly after injection and subsequent distribution to interfollicular areas. FACS revealed increasing amounts of FITC-HSA in SLNs over time. Cells responsible for uptake were APCs, expressing major histocompatibility (locus) class II. CONCLUSIONS: This report establishes active macromolecule uptake as a mechanism that determines SLN status. This mechanism has important implications for performing SLN biopsy.

Animals↗

[Morphologic correlations of anti-tumor immunity. III. Reactions of regional lymph nodes].

Regional lymph nodes were examined in 4 groups of oncologic patients (with cancer of oral cavity, breast, stomach and lung). Histological types of the lymph node reaction were correlated to patients' survival. Favourable prognosis in all four groups was related to lymphocytic predominance, especially when combined with sinus histiocytosis. The predominance of germinal centres (combined with sinus histiocytosis) was a favourable sign but in stomach cancer. A marker of unfavourable prognosis was lymphocytic depletion, especially when sinus histiocytosis was absent.

Carcinoma↗

Minimal number of lymph nodes that need to be examined for adequate staging of colorectal cancer--factors influencing lymph node harvest.

BACKGROUND/AIMS: Accurate assessment of lymphatic node status is an essential component in staging of colorectal cancer and determining the need for adjuvant treatment. The risk of understaging nodal status decreases by increasing the number of examined lymph nodes. Several recommendations have been published for the minimum number of lymphatic nodes that need to be harvested for accurate nodal staging with minimal chance of error, ranging from 6 to 17 lymph nodes. However, the number of harvested lymph nodes is very variable, and this variability is poorly understood. The aim of this study was to determine factors associated with the number of retrieved lymph nodes in patients with colorectal cancer. METHODOLOGY: Clinical and histological characteristics of 177 patients operated for colorectal cancer were analyzed. RESULTS: In multiple regression analysis, male gender, better tumor differentiation and greater tumor size, as well as the presence of acute inflammation were determined as significant independent predictors of the increased number of resected and examined lymph nodes. CONCLUSIONS: The determination of the minimum number of lymph nodes required for accurate nodal staging of patients with colorectal cancer needs to be individualized.

Aged↗

Sonographic appearance of normal lymph nodes.

Normal lymph nodes appear sonographically as somewhat flattened hypoechogenic structures. Chronic inflammation, obesity, and degenerative changes leading to benign fatty replacement of lymphoid tissue are responsible for the variations seen with high-resolution ultrasonography. These fatty deposits, beginning in the center of the lymph node and progressing toward the periphery, are easily recognized as highly reflective defects in the hypoechogenic lymphoid tissue.

Humans↗

The risk of axillary relapse after sentinel lymph node biopsy for breast cancer is comparable with that of axillary lymph node dissection: a follow-up study of 4008 procedures.

OBJECTIVE: We sought to identify the rate of axillary recurrence after sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: SLN biopsy is a new standard of care for axillary lymph node staging in breast cancer. Nevertheless, most validated series of SLN biopsy confirm that the SLN is falsely negative in 5-10% of node-positive cases, and few studies report the rate of axillary local recurrence (LR) for that subset of patients staged by SLN biopsy alone. METHODS: Through December of 2002, 4008 consecutive SLN biopsy procedures were performed at Memorial Sloan-Kettering Cancer Center for unilateral invasive breast cancer. Patients were categorized in 4 groups: SLN-negative with axillary lymph node dissection (ALND; n = 326), SLN-negative without ALND (n = 2340), SLN-positive with ALND (n = 1132), and SLN-positive without ALND (n = 210). Clinical and pathologic characteristics and follow-up data for each of the 4 cohorts were evaluated with emphasis on patterns of axillary LR. RESULTS: With a median follow-up of 31 months (range, 1-75), axillary LR occurred in 10/4008 (0.25%) patients overall. In 3 cases (0.07%) the axillary LR was the first site of treatment failure, in 4 (0.1%) it was coincident with breast LR, and in 3 (0.07%) it was coincident with distant metastases. Axillary LR was more frequent among the unconventionally treated SLN-positive/no ALND patients than in the other 3 conventionally treated cohorts (1.4% versus 0.18%, P = 0.013). CONCLUSIONS: Axillary LR after SLN biopsy, with or without ALND, is a rare event, and this low relapse rate supports wider use of SLN biopsy for breast cancer staging. There is a low-risk subset of SLN-positive patients in whom completion ALND may not be required.

Axilla↗

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↗