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The influence of the lymph node on the protein concentration of efferent lymph leaving the node.

1. Experiments have been performed in sheep to determine the contribution of lymph formed within a lymph node to the total protein output in lymph leaving the node. 2. The lymphatic duct leaving the popliteal lymph node was cannulated and the protein and lymphocyte output in efferent lymph determined. The afferent lymph flow to the popliteal node was then diverted and lymph formed only within the lymph node collected from the efferent cannula. It appeared from the results that the popliteal lymph node forms lymph at the rate of approximately 1 ml. per hour and may contribute 30-50% of the protein output observed in efferent lymph. 3. The importance of lymph formation within the lymph node varied between nodes found in different regions of the body. This was due in part to the different protein concentrations in the afferent lymph to the different nodes. 4. A positive correlation was found between the protein and lymphocyte concentrations in efferent lymph from the popliteal lymph node in seven out of eleven sheep and in lymph formed within the popliteal lymph node in two out of three sheep. It is suggested that this relationship may be due to an increased transfer of plasma proteins through the post-capillary venules in the lymph node accompanying the continual traffic of lymphocytes across the wall of these vessels. The results indicated that the protein transfer across the post-capillary venules was not an indiscriminate transfer of plasma per se but a selective transport from the blood plasma compartment based on molecular size.

Animals↗

Dermatopathic lymphadenopathy and lymph node involvement in mycosis fungoides.

Lymph node involvement in mycosis fungoides (MF) is associated with a poor prognosis, Histologically, in most cases of clinical lymphadenopathy the excised lymph node shows dermatopathic lymphadenopathy (DL). The diagnosis of MF involvement can readily be made when the lymph node tissue has partly or wholly been replaced by atypical lymphoreticular tissue. Early involvement of a dermatopathic lymph node by MF may be difficult to diagnose. A histologic study was performed on 30 lymph nodes from 24 patients with MF. Most of these lymph nodes had been excised as part of the staging procedure. The maximal follow-up period was five years. A classification of lymph node involvement into four categories is suggested and correlations with clinical courses and results of DNA cytophotometry of lymph node imprints are shown. Lymph nodes showing the histologic picture of DL can be divided into two groups: a group with MF involvement (category I) and a group with MF involvement (category II). The latter group is considered to represent early involvement of lymph nodes by MF. Partial or complete replacement of lymph node tissue by atypical lymphoreticular tissue corresponds with cagegories III and IV, respectively.

Adult↗

Outpatient pelvic lymph node dissection.

PURPOSE: Staging pelvic lymph node dissection is an important part of the evaluation of most patients with prostatic carcinoma. While laparoscopic pelvic lymph node dissection provides an alternative to standard pelvic lymph node dissection, it has been associated with a significant learning curve, high major complication rate, frequent hospitalization and greater expense. We sought to modify the technique of pelvic lymph node dissection to allow its performance as an outpatient procedure. MATERIALS AND METHODS: Pelvic lymph node dissection was performed through bilateral 3 cm. incisions overlying the obturator fossa in 11 patients. RESULTS: Nodes sampled ranged from 5 to 26 per patient that differed insignificantly from those undergoing standard pelvic lymph node dissection. Four patients had lymph node metastases. Nine procedures were performed entirely on an outpatient basis. One complication (external vein injury) was repaired with a single suture after extending the incision to 6 cm. CONCLUSIONS: Outpatient pelvic lymph node dissection through small incisions provides an attractive alternative to standard or laparoscopic lymph node dissection. With further experience it may become the procedure of choice for staging prostatic carcinoma in patients with a high risk of pelvic lymph node metastases.

Aged↗

A new model for lymphatic metastasis: development of a variant of the MDA-MB-468 human breast cancer cell line that aggressively metastasizes to lymph nodes.

Breast cancer often spreads from the primary tumor to regional lymph nodes. Lymph node status provides clinically important information for making treatment decisions. Spread via lymphatics is also important for the biology of breast cancer, as tumor cells in lymph nodes may provide a reservoir of cells leading to distant, lethal metastases. Improved understanding of the biology of lymphatic spread thus is important for improved breast cancer survival. Advances towards understanding the interactions between tumors cells and lymphatic vessels have in part been limited by the lack of suitable cell lines and experimental models. We have addressed this need by developing a new model of lymphatic metastasis. Here we describe the establishment of 468LN cells, a variant of the MDA-MB-468 human breast adenocarcinoma cell line, which produces extensive lymph node metastasis following orthotopic injection of nude mice. 468LN cells are also more aggressive in vitro, produce more osteopontin and express different surface integrins compared to the parent line. The dramatic in vitro and in vivo phenotypic and molecular differences of 468LN and parental 468GFP cells make this pair of cell lines a unique model for the specific study of lymph node metastasis of breast cancer.

Adenocarcinoma↗

Doppler ultrasound examination of pathologically enlarged lymph nodes.

Pathologically enlarged lymph nodes have been examined with a commercially available 10 MHz continuous-wave Doppler flowmeter. Many enlarged lymph nodes gave rise to significant Doppler-shift signals indicating increased blood flow. The signals have been spectrum analysed and the large diastolic flow components suggest that there is considerable arterio-venous shunting within lymph glands involved in leukemia, lymphoma and carcinoma. It also seems that the signals tend to diminish in response to treatment. The Doppler signals have been used in an imaging system to produce a vascular map of the region of the enlarged gland. It is suggested that these findings might be applicable to the detection of neoplastic tissues in less accessible sites.

Doppler Effect↗

Stimulation of cells from a non-invaded and an invaded lymph node with a HER-2+ tumor with peptides corresponding to T-cell epitopes E75 and G89 induced expansion of central memory cells (TCM) from the metastasis-negative lymph nodes.

Breast cancer metastasizes from the primary site to the axillary lymph nodes (LN). It is unknown whether tumor metastasis abolishes or enhances the ability of LN cells to develop a specific response to the Ag expressed by the tumor, and whether an immune response to the same Ag is present in the tumor-free LN. We stimulated lymphocytes from a metastasis negative (Met-) and a metastasis positive (Met+) LN, invaded by a HER-2+ tumor, from the same patient, with HER-2 peptides E75 (369-377) and G89 (776-778). E75 define a CTL epitope presented by HLA-A2, while G89 define a CD4+ cell recognized epitope. Met- LN responded to E75+G89 with higher expansion of E75 TCR+ CD45RO+ CCR7- (CCR7-) and E75-TCR+ CD45RO+ CCR7+ (CCR7+) cells than Met+ LN. Stimulation with E75+G89 induced a significant increase in CCR7+ cells in Met- LN compared with Met+ LN. The levels of IFN-alpha and IL-15 were higher in Met- LN cultures stimulated with E75+G89 than in Met+ LN cultures. This increase did not correlate with the levels of induction of IFN-gamma, IL-4, and IL-10. The finding of higher expansion of Ag specific CCR7+ cells and of differentiation to CCR7- cells, which define the TCM and TEM subsets respectively, in Met- LN, by G89 is novel for tumor systems. This may have implications for preventative vaccination strategies for breast and ovarian cancer.

Breast Neoplasms↗

The effect of antigenic stimulation on incorporation of phosphate and methionine into proteins of isolated lymph node cells.

Isolated lymph node cells incorporate inorganic orthophosphate into a protein fraction. The phosphorylated product is a phosphoprotein. The rate of phosphate incorporation into phosphoprotein was determined in cells isolated from regional lymph nodes at varying times after antigen injection. The rate was unaltered on the 3rd day, but was enhanced on the 4th day after injection. Parallel results were obtained with L-methionine incorporation into the same gross protein fraction. Possible relationships between antibody formation and the observed enhancement in phosphate incorporation into phosphoprotein are discussed.

Antibody Formation↗

Incidence, location, and significance of periprostatic and periseminal vesicle lymph nodes in prostate cancer.

Pelvic lymph node metastases in prostate cancer (PCa) carry an ominous prognosis. Periprostatic/periseminal vesicle (PP/PSV) lymph nodes are present in some individuals, but their incidence and involvement by metastases are unknown. A total of 832 of 1233 (67.5%) patients who underwent radical retropubic prostatectomy for clinically localized PCa at the Methodist Hospital from 1983 to 1998 by one surgeon (P.T.S.) had whole-mount slides available for review. Of these, 92 (11.1%) had received preoperative therapy (radiation in 48 [5.8%], hormonal in 44 [5.3%]). Slides were examined with the naked eye by placing them on a white illuminated background, and any area suggestive of a lymph node in PP/PSV fat was confirmed microscopically and assessed for the presence of metastases. Thirty-seven of 832 patients (4.4%) had 39 PP/PSV lymph nodes-one bilateral, one with two ipsilateral lymph nodes, and the rest solitary. Sizes ranged from 0.7 to 4.5 mm (mean 1.8 mm). Distribution was 2 of 39 (5.1%) apical, 3 of 39 (7.7%) mid, 17 of 39 (43.6%) base, and 17 of 39 (43.6%) seminal vesicle. Five patients (0.6%) had metastatic PCa to the PP/PSV lymph nodes. All five patients were of advanced pathologic T stage [one pT3a (extraprostatic extension) and four pT3b (seminal vesicle invasion)]. Only two of those five (40%) had metastases (all ipsilateral) to pelvic lymph nodes. In three of five (60%) the metastases were isolated to the PP/PSV lymph nodes. Metastases were to the lymph nodes in the periseminal vesicle fat in four of five (80%) of the cases and in the fat surrounding the base of the prostate in one of five (20%). Four of five (80%) patients recurred. Histologic grade (Gleason score), tumor volume, and failure (recurrence) rates were significantly different between the five patients with metastases and the 32 patients without metastases to the PP/PSV lymph nodes (p <0.0001, p <0.0001, and p = 0.005, respectively). However, there was no evidence that an individual patient's probability of having a PP/PSV lymph node increased with resection of the neurovascular bundle (p = 0.7698). PP/PSV lymph nodes are uncommon, but based upon these limited data, it appears that patients with metastases limited to PP/PSV lymph nodes have a poor prognosis (similar to pelvic lymph node metastases) and should be included in the American Joint Committee on Cancer (AJCC) Staging Manual to indicate "N1" if positive for metastases.

Adenocarcinoma↗

Inflammatory pseudotumor of pelvic lymph nodes.

Inflammatory pseudotumor of lymph nodes (IPT) is a rare, recently described benign cause of lymphadenopathy. The IPT is composed of a proliferation of spindle cells, small vessels and inflammatory cells without atypia and formed by high and poor cellular areas. This study reports a case of IPT. It was a 50-years-old man in whom the abdominal mass was an incidental finding during exploratory laparatomy. The mass was a lymphadenopathy measuring 12 x 10 x 5 cm in diameters. Histologic examination revealed IPT of the lymph nodes. The patient has remained asymptomatic for more than 10 months following surgery without any treatment. In conclusion, IPT of the lymph nodes is being recognized increasingly and should be considered in the differential diagnosis of lymphadenopathies. Inflammatory pseudotumor (IPT) of the lymph nodes resembling the IPT of other organs was recently described as a possible cause of lymphadenopathy. Histologically, the process showed a proliferation of spindle cells associated with a mixture of polymorphic inflammatory cells and small blood vessels involving the connective tissue framework (hilum, trabecula, capsule) of the lymph node. In this report, the case of a patient with IPT of pelvic lymph nodes is presented with the clinical and pathological features.

Cell Division↗

The results of node resection for clinically enlarged lymph nodes in malignant melanoma.

Patients with malignant melanoma who require a block dissection for clinically enlarged lymph nodes have a relatively good prognosis if only one node is involved histologically and the primary is on the lower limb. Sixty per cent of these patients with single nodes show a 10 year disease-free survival rate, compared with 9% for those with multiple node involvement. The local recurrence rate at the resection site of hyperplastic nodes was 26% but fell to 10% when only a single node was involved. The disease-free interval and the survival time are a useful measure of the effectiveness of node resection.

Axilla↗

[Is surgery useful in kidney cancer with lymph node invasion?].

SUMMARY: lymph node involvement in renal cell carcinoma is factor of very poor prognosis. In a series of 55 node-positive patients, 33 (60%) had simultaneous renal vein or vena cava invasion and 32 (58.2%) had metastases. Gross lymph node involvement was found in 39 patients (70.9%). Patients without venous invasion or metastasis may have a prolonged survival. In this group, those with microscopic nodal involvement can be cured, as the 10 and 15-year the actuarial survival rate is 54.5% Formal lymphadenectomy might have played a role in these results. Surgery can be performed when vein invasion is present without metastasis, but the prognosis is generally poor. Survival does not seem to be influenced by surgery when metastasis is present, regardless of the vein status.

Actuarial Analysis↗

In vitro B-mode ultrasonographic criteria for diagnosing axillary lymph node metastasis of breast cancer.

Axillary lymph node status is an important factor for staging and treatment planning in breast cancer. Our study was performed in vitro on a node-by-node basis to evaluate the ability of B-mode ultrasonographic images to distinguish metastatic from nonmetastatic nodes. Immediately prior to histologic examination, individual dissected axillary nodes were scanned in a water bath using a 10 MHz B-mode ultrasonographic transducer. Four B-mode features (size, circularity, border demarcation, and internal echo) were evaluated for their ability to distinguish metastatic from nonmetastatic lymph nodes. Lymph node metastasis was indicated by (1) a large size (i.e., a length of the longest axis of 10 mm or greater); (2) a circular shape (i.e., the ratio of the shortest axis to the longest axis between 0.5 and 1.0); (3) a sharply demarcated border compared with surrounding fatty tissue; and (4) a hypoechoic internal echo, with obliteration of the fatty hilum. The sensitivity and specificity were compared for all combinations of features. We examined 84 histologically characterized axillary nodes from 27 breast cancer patients, including 64 nonmetastatic and 20 metastatic nodes. Of the criteria cited, circular shape was the best single feature for distinguishing metastatic from nonmetastatic nodes (sensitivity, 65%; specificity, 73%). The best combination of sensitivity (85%) and specificity (73%) was obtained using the criterion that a lymph node contained cancer when at least three positive features were present. The present in vitro study demonstrated that the sensitivity and specificity of B-mode ultrasonography for diagnosing lymph node metastasis were lower than 90%. Therefore, B-mode ultrasonography may not be an optimal noninvasive screening method for diagnosing axillary lymph node metastasis in breast cancer patients, particularly under in vivo clinical conditions.

Adult↗