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Functional anatomy of lymph nodes. II. Peripheral lymph-borne mononuclear cells.

In the rabbit a number of large mononuclear cells with ruffled surface membranes travel from the skin and superficial tissues of the leg, via the lymphatics, to the popliteal lymph node: they constitute 40-50% of the total cell population in the afferent lymph. About 10% of these cells are actively phagocytic when tested in vitro and about 3% are found to contain Langerhans granules. After isotopic labelling the majority of lymph-borne mononuclear cells can be detected within the regional node for at least 24 hours; most being located in the paracortex and a few in the interfollicular cortex. It is proposed that these cells, including those containing Langerhans granules, belong to the "mononuclear phagocyte system." Possible functions of these lymph-borne cells are discussed with particular reference to antigen transport.

Adenosine

Breast cancer and regional lymph node dissections.

Regional lymph node metastases were evaluated in 289 patients with operable breast cancer. The metastases of the axillary and internal mammary lymph node were shown to be closely related to the survival of patients, but the status of these nodes was shown to be impossible to estimate before the operation. Thus, axillary and internal mammary node dissections seem to be very important in order to attain an acceptable amount of information for staging of certain breast cancer patients. Due to the radicality of operations including internal mammary node dissection, the use of modified extended mastectomy is proposed as the staging operation. In this manner, the anterior chest deformity created by an extended radical mastectomy can be avoided and the pectoralis major muscle spared in patients without internal mammary lymph node involvement. Also found in this study, was some evidence of the beneficial use of en bloc extended radical mastectomy for the survival of a selected group of patients.

Adult

Superficial lymph node infarction.

Superficial lymph node necrosis is an unusual pathologic diagnosis encountered in clinical practice. When seen it is usually indicative of involvement of the affected lymph nodes with either metastatic cancer or lymphoma. Occasionally it has been associated with hypersensitivity phenomena with arteriolar involvement. The underlying etiology in all of these instances is extensive occlusion of the rich vascular supply to the node. Rarely cases are seen where no clear-cut etiology can be found. Ten such cases have been reported in the medical literature including the case published in this report. Its occurrence, however, may be more common than previously recognized. Preoperatively it is usually not possible to distinguish this entity from the other diagnoses for which it is generally mistaken. These other diagnoses most commonly include femoral hernia and mass in the axillary tail of the breast. The patient reported here is unusual in regard to the size of the lesion encountered. In other published reports very few lymph nodes were involved. In this case extensive involvement of a large mass of nodes was noted. Once the diagnosis is made limited work-up as well as further close observation is important since it may herald the occurrence of a lymphoproliferative disorder.

Diagnosis, Differential

The in vitro differentiation of mast cells. Cultures of cells from immunized mouse lymph nodes and thoracic duct lymph on fibroblast monolayers.

When cells from lymph nodes or thoracic duct of mice hyperimmunized with protein antigens are cultivated on embryo monolayers in the presence of the antigen, numerous clones of mast cells appear. The histochemical and ultrastructural characteristics of the cells permit their identification as mast cells and distinguish them from the phagocytic histiocytes that usually arise in abundance in similar cultures from unimmunized mouse cells or from immunized mouse cells cultured in the absence of the antigen. Only a few colonies of mast cells appeared in the latter cultures. The basis for the induction of mast cell differentiation is not known.

Animals

Eosinophil chemotaxis of supernatants from cultured Hodgkin's lymph node cells.

Cultured lymph node cell supernatants from five out of six cases of Hodgkin's disease were relatively more chemotactic for peripheral blood eosinophils than neutrophils. In contrast, supernatants from two cases of lymphocytic lymphoma and four nodes showing reactive hyperplasia were chemotactic for neutrophils but had little eosinophil chemotactic activity. In most instances the dgree of eosinophil infiltration observed histologically in the Hodgkin's lymph node correlated with elaboration of eosinophil chemotactic activity from the cultured cells. Following gel-filtration of three of the Hodgkin's lymphnode supernatants, four peaks of eosinophil chemotactic activity were demonstrated in each case. One of these corresponded in molecular size to th previously described eosinophil chemotactic factor of anaphylaxis (ECF-A). It is suggested that the eosinophil chemotactic activity of cultured lymph node cell supernatants may be on value in the diagnosis and classification of Hodgkin's disease.

Anaphylaxis

Dramatic hyperplasia of mtv-2+ lymph node grafts in mtv-2- recipients and selective stimulation of V beta 14+ T cells in recipients' lymph nodes in the DDD mouse.

DDD/1 (DDD) mice contrast strikingly with DDD-mtv-2/mtv-2 (DDD-mtv-2) congenics in their marked lymph node (LN) T cell paucity. To clarify the possible difference in LN function between them, reciprocal LN grafting experiments were conducted. DDD-mtv-2 LN grafts in DDD recipients underwent hyperplasia as dramatic as 10-to 20-fold increase in weight between 3 and 4 wk after implantation. Lymphoid cells in hyperplastic LN grafts were of recipient origin. Similar hyperplasia of mtv-2-heterozygous LN grafts also occurred on various hybrid backgrounds involving DDD mice. Moreover, LN grafts from BALB/c mice infected with mtv-2-derived exogenous mouse mammary tumor virus (MMTV) swelled in MMTV-free BALB/c recipients. Genetic analysis of DDD x (DDD x DDD-mtv-2)F1 backcross progeny demonstrated that LN hyperplasia was closely linked to mtv-2. The frequencies of V beta 5+ and V beta 8+ T cells unresponsive to mtv-2-encoded superantigen (SAg) changed with practically the same kinetics in both LN grafts and recipients' LN. Thus, the cells responsible for LN hyperplasia were polyclonal. V beta 14+ CD4+ cells responsive to mtv-2 SAg were specifically stimulated in recipients' LN but selectively deleted in hyperplastic LN grafts. DDD mice carrying hyperplastic mtv-2+ LN grafts or pretreated with mtv-2+ spleen cells developed an unresponsive state in terms of influx of mtv-2- lymphoid cells into mtv-2+ LN grafts. These results indicate that mtv-2 gene products including SAg may stimulate mtv-2- lymphoid cells of recipients and cause them to migrate into mtv-2+ LN grafts in a nonspecific manner with resulting LN hyperplasia.

Animals

Lymph node biopsy.

The lymph node biopsy may well be the most important surgical operation that the patient ever has. Recent advances in the immunological characterization of human lymphocyte sub-populations, and the use of selected cytochemistry techniques have enabled increased understanding of the pathogenesis of malignant lymphomas, as well as providing more precise categorization of the cell of origin of many of these tumours. The fact is, however, that the vast majority of diagnoses of lymph node biopsies are made on morphological features observed at light microscopy level. The diagnosis and differential diagnosis of lymphomas, and particularly their distinction from benign conditions, are among the most frequent and most difficult problems in diagnostic histopathology. Whilst many of the principles enumerated in the text apply to all areas of surgical pathology, meticulous attention to detail is essential at all phases in the preparation of a satisfactory lymph node biopsy.

Biopsy

Development of IgE-forming cells in vitro from rat mesenteric lymph node cells.

Mesenteric lymph node cells from normal rats and rats infected with Nippostrongylus brasiliensis (Nb) were cultured with pokeweed mitogen (PWM) or Nb antigen, and the development of IgM-, IgG2a-, or IgE-containing cells was assessed by immunofluorescence. Normal lymph node cells stimulated with PWM developed into both IgM- and IgE-containing cells, whereas similar stimulation of cells from Nb-infected rats resulted in the development of IgM-, IgG2a-, and IgE-containing cells. The in vitro plasma cell response to PWM was dependent on the presence of T lymphocytes. Lymph node cells from Nb-infected rats responsed to Nb antigen and developed into plasma cells of IgM, IgG, and IgE classes. The response was antigen specific and required antigen-primed T cells. Depletion of IgE-bearing cells or IgM-bearing cells before stimulation with either PWM or Nb antigen diminished the level of IgE forming cell development, suggesting that IgE-IgM double bearing cells are precursors of IgE-forming cells. The distribution of the three isotypes among the If-forming cells that developed in response to PWM was influenced by the source of both B and T cells. When B cells from Nb-infected rats were employed as a source of precursors, T cells from infected animals were more effective than normal T cells for the development of IgE-forming cells, whereas the latter cells were more effective for the development of IgG2a-forming cells than T cells from infected animals.

Animals

Lymph pathways of the medial retropharyngeal lymph node in dogs.

In dogs, lymph drains from tissues throughout the head, including the tonsils, along lymphatic vessels to the facial, parotid, lateral retropharyngeal and mandibular lymph nodes. From the mandibular lymph nodes, lymph may flow to the ipsilateral medial retropharyngeal lymph nodes, or along anastomotic connections to the contralateral node. Afferent lymphatics convey lymph from these nodes to defined areas in the medial retropharyngeal nodes. They divide over the surface of the node, and within trabeculae. Terminal afferent lymphatics are connected to the subcapsular and trabecular sinuses either through circular or oval holes in the vessel wall, or terminate at the sinus where the vessel contains a valve adjacent to the point of entry. The subcapsular sinus surrounds the entire node, and is continuous with an interconnecting network of trabecular and cortical sinuses which convey lymph through the cortex. Connective tissue septa extend through the sinuses and lymph flows freely between adjacent sinuses through holes in the septal walls. Initial efferent lymphatic vessels, which arise from the medullary sinuses between medullary cords, converge towards and unite within the network of medullary trabeculae. Other vessels, which contain valve-like flaps, drain lymph from the subcapsular sinus. Efferent vessels emerge along the hilus and coalesce to form the tracheal trunk. The tracheal trunk has several layers of smooth muscle cells, well developed elastic laminae and connective tissue, surrounding the lymphatic endothelium.

Animals

Study of AIDS-related lymphadenopathy in the intraparotid and perisubmaxillary gland lymph nodes.

Salivary gland lymph node involvement is rare in patients at risk for AIDS. Intraparotid and perisubmaxillary gland lymph node biopsies from 2 intravenous drug abusers serologically positive for human immunodeficiency virus (HIV) affected by persistent generalized lymphadenopathy (PGL) were also analyzed immunohistologically. We found hypervascular reactive lymphoid hyperplasia with prevalence of suppressor T-cells within follicular centers often lacking surface IgD-positive mantle zone cells and showing disruption of the network of dendritic reticulum cells revealed with DRC-1 and anti-S-100 protein antibodies. Within the nodes there were numerous cysts lined by metaplastic squamous epithelium/positive for epithelial membrane antigen and containing numerous lymphocytes positive for leukocyte common antigen, macrophages positive for alpha 1 -antichymotrypsin, and Langerhans cells positive for OKT6. Salivary gland lymph nodes are immunohistologically similar to those of other sites in PGL and their increased epithelial metaplastic component containing cells involved in the immune response might represent an exuberant reaction to HIV infection.

AIDS-Related Complex

Endoscopic exploration and lymph node sampling of the axilla. Preliminary findings of a randomized pilot study comparing clinical and anatomo-pathologic results of endoscopic axillary lymph node sampling with traditional surgical treatment.

OBJECTIVE: To describe the technique of endoscopic exploration of the axilla. To compare this technique to open surgical treatment by comparing the following variables: operative time, peri-operative complications, duration of hospital stay, node's histology and morphologic aspects and esthetic results. MATERIALS: Standard instruments for traditional operative laparoscopy plus a lipo-aspirator (0.8 Bar). PATIENTS: Forty patients, 20 (group A) undergoing open surgery and 20 (group B) undergoing axilloscopy. All patients with early invasive breast cancer are eligible for conservative operative treatment. METHOD: Randomized study. The technique is described and preliminary results are presented. RESULTS: The operative time for axilloscopy is approximately double that for open surgery. A comparable number of lymph nodes is collected by axilloscopy and open surgery. The nodes collected by axilloscopy are more likely to be fractured. What is the clinical consequence? Two loco-regional relapses are observed in the endoscopic group. DISCUSSION: Axillary sampling by endoscopic procedure gives the same pathologic information than surgical axillary sampling. Anatomo-pathologic aspects of nodes and possibilities of relapses were two drawbacks of this procedure. CONCLUSION: Operative time is increased for axilloscopy compared with open surgery. The techniques yield comparable anatomo-pathologic results. It is still unknown whether this endoscopic technique is as effective as traditional surgery or if the frequency or severity of lymphedema is decreased by the endoscopic approach.

Adult

Atrophy of lymph node compartments lacking lymph-carried lymphocytes in athymic rats.

This paper reports on a form of atrophy of lymph node compartments occurring in mesenteric nodes of athymic nude rats whose perinodal tissue had become unusually rich in mast cells and fibrotic. The subcapsular sinus of an affected compartment was depleted of lymphocytes, while the medullary sinuses were loaded with macrophages. A progressive expansion of medullary sinuses into the medullary cords, the extrafollicular zone, the deep cortex unit and, finally, the folliculo-nodules of the compartment was accompanied by a gradual atrophy of the usual lymphoid cell populations of these nodal components. The occurrence of such a mode of atrophy of a compartment, associated with a lack of lymphocytes in the afferent lymph, agrees with our previous proposal that lymphocytes of the afferent lymph provide the stimuli for the development and maintenance of the structures of the node. The involvement of mast cells and fibrosis in the emergence of the present form of nodal atrophy, which further weakens the immune system of an immunodeficient animal, is considered.

Animals

Gamma-probe guided localization of lymph nodes.

The initial draining lymph node (Sentinel node) of a tumour may reflect the status of the tumours spread to the remaining lymphatic bed. The sentinel node, which has been reported to predict metastatic melanoma, has recently been localized by a new invasive technique [1]. The goal of our pre-clinical trial was to test a non-invasive technique to localize the sentinel node. Gamma-probe guided localization was used to identify and then surgically remove the first draining lymph node(s) in 16 inguinal lymphatic basins of eight cats. This method was found to be comparable to an invasive method using a blue dye. Gamma-probe localization has several potential advantages in that it can: (a) precisely locate on the surface of the skin the position of an underlying lymph node, (b) intraoperatively guide the surgeon to the lymph node during dissection, (c) verify that the correct node has been biopsied, (d) determine the possible presence of residual lymph nodes, (e) allow lymph nodes to be harvested through a small incision as opposed to raising a skin flap, and (f) be rapidly and easily performed.

Animals