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A human monoclonal antibody to cytokeratin intermediate filament antigens derived from a tumor draining lymph node.

Human lymphocytes derived from a lymph node draining a primary breast adenocarcinoma were fused with the mouse myeloma P3X63Ag8.653 to generate human-mouse hybridomas secreting human monoclonal antibodies (MAbs) to tumor associated antigens (TAAs). One of the resulting human MAbs, YBB 190 (IgM) is described. Enzyme-linked immunosorbent assays (ELISA) employing membrane and cytosol fractions of human tissues demonstrated YBB 190 reactivity against cytosol but not membrane components of malignant and normal epithelial tissues. When tested by an indirect immunoperoxidase staining method against fresh frozen human tissue sections, YBB 190 reacted with malignant cells in 26 of 28 epithelial cancers and with normal epithelia in 11 different benign tissues. Preliminary western blot antigen characterization indicated that YBB 190 recognizes cytokeratin intermediate filaments, or a protein that is closely associated with cytokeratins. These data indicate that B cells with specificity for intermediate filaments are present in tumor draining lymph nodes. Our findings provide insights into the nature of potential autoimmune responses in cancer patients and suggest that improved tumor directed sensitization procedures may be required to more effectively utilize lymphocytes from tumor draining lymph nodes to generate therapeutically useful human MAbs to TAAs.

Adenocarcinoma↗

[Contrast media for magnetic resonance tomographic lymph node diagnosis (MR lymphography)].

In MR-imaging, similar to computed tomography, diagnosis of metastatic lymph-node disease is based on lymph-node sizes, and thereby it is non-specific. Super-paramagnetic iron oxide as a potential contrast medium for MR-lymphography accumulate in normal lymph node tissue after endolymphatic, interstitial and, in case of very small particles, after intravenous injection. No accumulation occures in lymph node metastases. Lymph-node metastases can be detected by all three injection techniques. It has been shown experimentally, that in particular small metastases can be detected in normal sized lymph nodes. However, MR-lymphography also has inherent methodologic problems, as there may occure an uneven distribution of the contrast medium between different lymph-node groups. The experimental results with endolymphatic, interstitial, and intravenous MR-lymphography as well as first clinical results with intravenous contrast medium injection are presented and discussed.

Contrast Media↗

[Extent of lymph node dissection in rectal carcinoma].

Basing on 170 specimens of advanced rectal cancers radically resected, metastatic rule and extent of lymph node dissection were studied in order to guide future surgical treatment. In 170 cases, 77 had lymph node metastases. The lymph node metastatic rate was 45.3% and metastatic degree was 8.9% (527/5 912). Metastasis of the rectal cancer, according to the lymphatic anatomy, can be divided into upward, lateral and downward drain. Because the rectal cancer at any site can lead to the upward metastasis, the upward lymph node dissection, up to the base of inferior mesenteric artery (the third line of lymph nodes), must be done in all rectal cases, otherwise, 10% of patients would have residual cancer. In view of the lateral metastasis occurring only in rectal cancers under the peritoneal reflection, for which lateral lymph node dissection is necessary or one eighth of patients would have residual lesion. Generally, no lateral lymph node dissection is needed in cancers above the peritoneal reflection. Pathologic factor influencing the lymphatic metastasis is the form of tumor growth, such as poorly differentiated and mucoid adenocarcinomas aggressively growing deeply and extensively resulting in a higher lymph node metastatic rate, for which lymph node dissection must be performed.

Adenocarcinoma↗

Pilot study comparing the accuracy of lymphoscintigraphy sentinel lymph node localisation with axillary node dissection in women with operable breast cancer.

AIM: To evaluate the use of lymphoscintigraphy sentinel lymph node mapping with scintillation gamma probe detection and blue dye assisted sentinel lymph node biopsy in patients with invasive breast cancer. To compare the lymph nodes detected lymphosintigraphically and at surgery for invasive breast cancer and the accuracy of sentinel node prediction of axillary status. METHODS: A prospective pilot study was performed on 36 women diagnosed with invasive breast cancer requiring axillary node dissection. Lymphoscintigraphy involving peritumoral injection of 99mTechnetium antimony sulphide or rhenium sulphur colloid was performed prior to surgery. Sentinel lymph node biopsy was then performed using gamma probe and blue dye localisation. RESULTS: Sentinel lymph nodes were identified on lymphoscintigrams in 100% of cases, and sentinel nodes located surgically in 34/36 (94.4%) of patients. All women with positive axillary lymph nodes on axillary dissection were correctly identified on sentinel node biopsy. Eight patients demonstrated internal mammary (IM) node radiocolloid uptake, one returning positive IM histology in the presence of positive axillary sentinel node metastasis. CONCLUSION: A high proportion of sentinel nodes were demonstrated by lymphoscintigraphy and were subsequently removed surgically. When internal mammary nodes are identified surgical removal should be considered. In this small series sentinel lymph node status correctly predicted axillary node status in 100% of patients for whom sentinel nodes were retrieved supporting the concept of sentinel node biopsy only for women with normal sentinel lymph nodes. Evidence from randomised trials that sentinel node based management does not compromise regional control of breast cancer or survival, is awaited.

Adult↗

[Diagnostic significance of multinuclear giant cells in lymph node fine needle aspiration].

Enlarged lymph nodes, commonly seen in inflammatory or tumorous conditions, is often suspected as Hodgkin's disease in cytologic diagnosis. Twenty cases originally diagnosed as Hodgkin's disease by fine needle aspiration of lymph nodes are reported. Eighteen of these 20 cases were checked by histopathology. It was found that only 3 had reached the correct diagnosis. The authors believe that by thorough understanding of the origin and characteristics of various types of multinuclear giant cells, differentiation from Hodgkin's disease is possible.

Biopsy, Needle↗

[Gonadal load in 60Co irradiation of peripheral, mediastinal and retroperitoneal lymph nodes].

A telecobalt therapy of lymph node groups was simulated on the Alderson phantom and the gonad dose caused by each irradiation field was measured with LiF dosimeters. When the supradiaphragmatic and the para-aortal lymph nodes were irradiated, the ovary dose showed rates up to 20% of the dose maximum. The irradiation of the same zones brought about a testicle dose of less than 50% of the dose maximum, and only 1/20 of this rate was achieved when a lead plate of about four cm was used in order to protect the testicles. The results are discussed under the point of view of the genetic risk.

Cobalt Radioisotopes↗

Lymph-node dissection in breast cancer.

BACKGROUND: Along with the ongoing modifications in treatment of primary breast cancer, the purpose and extent of lymph-node dissection has changed. The following is an overview of the current knowledge and practice of lymph-node dissection in breast cancer, with special regard to expected developments in the near future. Axillary dissection is described as a ten-step procedure, including dissection of level-I and -II and Rotter's nodes, without level-III nodes, providing at least ten lymph nodes for accurate staging information. DISCUSSION: Axillary dissection still offers the most efficient local control in node-positive patients, whereas, in primarily node-negative patients, irradiation seems to be equally effective. In general, lymph-node dissection does not alter overall survival but there is no doubt that surgical therapy still contributes to cure in early-breast-cancer patients and seems to be curative for certain patients with stage-I carcinoma. The lymph node status of the axilla is crucial for the indication of adjuvant therapy in early invasive breast cancer, but an increasing number of clinical node-negative patients could be managed with information based on features of the primary tumor, regardless of the nodal status. The most promising new concept for the selection of node-positive patients, while avoiding unnecessary morbidity of axillary dissection in early-breast-cancer patients, is the sentinel-node concept. The principle is based on the identification of the first "sentinel" lymph node reached by lymphatic flow. Thus, only proven node-positive patients undergo axillary dissection. Local failure of internal mammary lymph nodes is rarely recognized; however, internal mammary lymph nodes seem to have an underestimated prognostic significance in about 10-20% of axillary node-negative patients. This may lead to the withholding of systemic therapy for patients with early breast cancer. Nevertheless, there is no indication for a routine parasternal dissection today. The sentinel-node concept may also support the selection of diagnostic internal lymph-node biopsy and subsequent adjuvant therapy in cases with no axillary lymph-node metastases but with internal lymph-node metastases.

Breast Neoplasms↗

Long-term postoperative survival of a gastric cancer patient with numerous para-aortic lymph node metastases.

A56-year-old man with advanced gastric cancer was referred to our hospital. Preoperative abdominal computed tomography revealed numerous enlarged lymph nodes, including the lymph nodes of the paraaortic region. The patient underwent total gastralectomy, splenectomy, left-adrenalectomy and resection of the body and tail of the pancreas by Appleby's method, along with paraaortic lymph node dissection. Microscopic examination revealed that the tumor was a solid type, poorly differentiated adenocarcinoma, which displayed invasion of the serosal surface. There were apparently many lymph node metastases. We identified 31 cancer-positive paraaortic nodes, while the total number of lymph node metastases was 81. It was not possible to administer sufficient postoperative adjuvant chemotherapy, as the patient experienced postoperative complications, including pancreatic fistula and watery diarrhea. Despite the lack of sufficient chemotherapy, the patient has subsequently remained disease-free for 9 years and 3 months, and continues to visit our hospital as an outpatient. In conclusion, we wish to emphasize the need for a critical application of paraaortic lymph node dissection as one modality of multidisciplinary treatment in patients with advanced gastric cancer in whom paraaortic lymph node metastasis is strongly suspected preoperatively.

Journal Article↗

Tuberculous lymph node calcification detected on routine panoramic radiography: a case report.

Cervical lymph node calcification is usually asymptomatic and may be found on a routine panoramic survey. Such calcifications in tuberculosis occur most often after caseation of the node or after treatment. Our patient had lymph node tuberculosis about 50 years ago. On the panoramic radiograph, several massive, irregular, radiopaque masses were detected. These masses were regarded as submandibular cervical lymph node calcifications. We suggest that lymph node tuberculosis may have been due to ingesting milk infected with Mycobacterium bovis, and that both the delay in the diagnosis and the successful treatment was the cause of lymph node calcification.

Calcinosis↗

Lymphocyte recognition of lymph node high endothelium. III. Enhancement by a component of thoracic duct lymph.

The first step in the entry of blood lymphocytes into lymph node is the binding of these cells to venules lined by high endothelium (HEV). This recognition event has been studied using a model system in which rat thoracic duct lymphocytes (TDL) adhere selectively to HEV when overlaid onto lymph node sections. We now report that this binding is increased by a lymph fraction designated adherence enhancing factor (AEF). Lymph depleted of cells and chylomicra was fractionated with (NH4)2SO4. Material that precipitated between 60 and 80% saturation was dissolved in buffer and extracted with chloroform/methanol; the aqueous phase was used as the source of AEF. The factor was nondialyzable, trypsin sensitive, and heat stable (70 degrees C, 30 min). Lymph node sections pretreated with AEF showed a 2- to 3-fold increase in the number of TDL bound to HEV and a 5 to 10-fold increase in the number of HEV with more than 5 adherent lymphocytes. The effect of AEF was specific: 1) No increase in lymphocyte binding to non-HEV areas of the tissue section occurred. 2) The binding of both TDL and spleen lymphoid cells to HEV was enhanced, but thymocyte attachment was not promoted. We conclude that AEF has biologic properties that might enable it to play a physiologic role in lymphocyte recirculation.

Animals↗

Immunohistochemical detection of lymph node metastases in node-negative breast cancer patients.

BACKGROUND: Axillary lymph node metastases in breast cancer patients are one of the most important prognostic factors. Many previous studies have shown that in the detection of occult micrometastases immunohistochemical methods are superior when compared to routine hematoxylin-eosin staining. The aim of the study was to document the rate of missed occult micrometastases on routine hematoxylin-eosin staining in our department, in a retrospective study. PATIENTS AND METHODS: One hundred and one tumors of patients with breast cancer were included in this study. Immunohistochemical staining was performed using Pan-Cytokeratin AE1/AE3 antibody. The number of nodes examined was 1301 (mean per patient: 12.9; range: one to 26). RESULTS: Of the 101 tumors studied, eleven had occult lymph node metastases detected by immunohistochemical methods. After repeated review by two independent pathologists, in two out of eleven patients lymph node metastases were confirmed even on hematoxylin-eosin staining. In nine out of eleven patients hematoxylin-eosin staining was not sufficient to detect occult micrometastases. CONCLUSION: Immunohistochemical methods enhance the detection rate of occult micrometastases in axillary lymph nodes of breast cancer patients and are recommended for routine diagnostic use in patients who have been diagnosed node-negative on routine hematoxylin-eosin staining.

Adult↗

Identification and evaluation of axillary sentinel lymph nodes in patients with breast carcinoma treated with neoadjuvant chemotherapy.

Sentinel lymph node (SLN) biopsy has been shown to predict axillary metastases accurately in early stage breast cancer. Some patients with locally advanced breast cancer receive preoperative (neoadjuvant) chemotherapy, which may alter lymphatic drainage and lymph node structure. In this study, we examined the feasibility and accuracy of SLN mapping in these patients and whether serial sectioning and keratin immunohistochemical (IHC) staining would improve the identification of metastases in lymph nodes with chemotherapy-induced changes. Thirty-eight patients with stage II or III breast cancer treated with neoadjuvant chemotherapy were included. In all patients, SLN biopsy was attempted, and immediately afterward, axillary lymph node dissection was performed. If the result of the SLN biopsy was negative on initial hematoxylin and eosin-stained sections, all axillary nodes were examined with three additional hematoxylin and eosin sections and one keratin IHC stain. SLNs were identified in 31 (82%) of 38 patients. The SLN accurately predicted axillary status in 28 (90%) of 31 patients (three false negatives). On examination of the original hematoxylin and eosin-stained sections, 20 patients were found to have tumor-free SLNs. With the additional sections, 4 (20%) of these 20 patients were found to have occult lymph node metastases. These metastatic foci were seen on the hematoxylin and eosin staining and keratin IHC staining. Our findings indicate that lymph node mapping in patients with breast cancer treated with neoadjuvant chemotherapy can identify the SLN, and SLN biopsy in this group accurately predicts axillary nodal status in most patients. Furthermore, serial sectioning and IHC staining aid in the identification of occult micrometastases in lymph nodes with chemotherapy-induced changes.

Adenocarcinoma, Mucinous↗

Mediastinal lymph node detection with endosonography.

Eighty-two persons with chronic abdominal pain, submucosal or extrinsic masses, or achalasia and 20 volunteers without symptoms were prospectively examined with endosonography to assess the incidence and features of mediastinal lymphadenopathy. In 99 persons without malignant disease, 86% were found to have paraesophageal lymph nodes by endosonography. Overall, 352 lymph nodes were found, with a mean of 3.6 +/- 2.8 SD lymph nodes per person (range, 0 to 14 lymph nodes). Increasing age and chronic pancreatitis were found to correlate with a greater number of lymph nodes. Otherwise, clinical features including quantity of tobacco use, height, weight, sex, and race did not correlate with a greater number of lymph nodes as assessed by regression analysis. The mean width and length among the lymph nodes was 4.9 +/- 2.4 mm (range, 1 to 15 mm) and 9.9 +/- 5.2 mm (range, 1 to 30 mm), respectively, with the largest lymph nodes occurring in the peritracheal and peribronchial regions. Of all subjects, 95% had a maximum lymph node width of 10 mm or less, but only 40% had a maximum lymph node length of 10 mm or less. The most common ultrasound features of these lymph nodes included a triangular or crescent-shaped and homogeneous or centrally echogenic pattern. These ultrasound characteristics were distinct from those previously described in malignant lymph nodes. In summary, a high background prevalence of mediastinal lymph nodes exists as detected by endosonography and must be considered when performing esophageal or lung carcinoma staging examinations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Characteristics of submucosal gastric carcinoma with lymph node metastatic disease.

AIM: To study the correlation between lymph node metastatic disease and various pathological parameters. Lymph node metastasis is the most important factor in determining the prognosis of patients with early gastric cancer and is significantly associated with the submucosal invasion of neoplastic cells. However, the depth of submucosal layer as well as the depth of submucosal tumour invasion varies among different cases. METHODS AND RESULTS: We studied various pathological parameters including the macroscopic appearance, location, size, area, differentiation, invasion depth, vascularity and fibrosis of submucosal gastric carcinomas (SMGC), using 248 age- and sex-matched tissue samples. The presence of lymphatic emboli, a larger area, greater size, a non-flat gross type and an increased vascularity of the tumour were significantly associated with node-positive SMGC. Among the three depth-related parameters, the ocular scale measurement, the sm3 method and the sm2 method, only the ocular scale measurement showed a significant correlation with node-positive SMGC. Using multivariate analysis, the incidence of lymph node metastasis increased in the lymphatic tumour emboli and in the tumours that invaded more than half of the submucosal layer. CONCLUSIONS: These histological indicators seem to be a feasible and easy way to predict lymph node metastatic disease from limited surgery specimens. Pathologists should carefully investigate the lymphatic invasion of tumour cells and measure the invasion depth of the tumour.

Adult↗

Determination of aetiology of superficial enlarged lymph nodes using fine needle aspiration cytology.

OBJECTIVE: To asses the causes and patterns of enlarged superficial lymph nodes. DESIGN: Cross sectional survey. SETTING: Jimma Teaching Hospital, Pathology Department, Jimma University, Southwest Ethiopia for a study conducted between September 1999 and August 2001. PARTICIPANTS: Eight hundred and eight patients presenting with enlarged superficial lymph nodes in cervical, axillary, inguinal etc. regions were included (456 males and 352 females) whereas non lymph node samples and deep-seated lymphoid lesions were excluded from the study. MAIN OUTCOME MEASURES: Fine needle aspiration cytology (FNAC) technique and Wright's staining procedure were utilized to diagnose the causes of enlarged lymph nodes. RESULTS: Of the 1693 patients attended to at the cytologic diagnostic service, 808(47.7%) had lymph node disorders with benign and malignant causes of lymph node enlargements comprising of 93.2% and 6.8% respectively. The most frequent cause of benign enlargement was tuberculous lymph adenities (66.3%), followed by reactive lymph node hyperplasia (19.2%). Among malignant ones, non-Hodgkin's lymphomas (2.7%) and metastatic carcinomas (2.2%) were most frequently diagnosed. The cervical region was the most frequent site for enlarged lymph node disorders accounting for more than three quarters of all cases. CONCLUSION: This study revealed a huge burden of benign lymph node enlargements in general, and tuberculous lymph adenities in particular. The latter was responsible for about two-third of lymph node enlargements in South Western parts of this country. It is recommended that health providers undertake intensive public health education and screening activities in order to help salvage our community from these potentially preventable and treatable causes of enlarged lymph node disorders.

Adolescent↗

Histopathological detection of lymph node metastases from colorectal carcinoma.

AIM: To evaluate whether the assessment of multiple sections from retrieved nodes yields an increased number of metastases compared with the number that would be detected by the commonly applied method of microscopy of a single section of lymph node only. METHODS: A prospective study of 72 colorectal carcinoma resection specimens. Lymph node sampling was based on the current guidelines for the detection of breast cancer metastases in axillary nodes. Lymph nodes up to approximately 5 mm in maximum extent were processed in entirety, without prior sectioning, and assessed histologically at three levels; larger lymph nodes were processed in entirety as multiple sections and histologically assessed at one level. RESULTS: From a total of 72 carcinomas, eight were Dukes's A, 26 were Dukes's B, and 38 were Dukes's C. The mean and median numbers of nodes identified were 13 and 12, respectively (range, three to 44). Of the Dukes's C cases, four contained lymph node metastases identified by our method that might have gone undetected by the current, generally applied method. In one case, this led to the detection of the only nodal metastasis present and therefore "upstaged" the tumour from Dukes's B to C. On average, six extra tissue blocks were processed for each case in applying this method. CONCLUSION: The assessment of multiple sections of lymph nodes from colorectal specimens leads to the detection of only a small number of additional nodal metastases. The method involves increased workload for pathologists and laboratory staff.

Colorectal Neoplasms↗

High-sensitivity power Doppler imaging of normal superficial lymph nodes.

PURPOSE: This study was conducted to describe the various patterns of vascularity of the normal superficial lymph nodes detected using high-sensitivity power Doppler imaging according to the dimension and anatomic location of the nodes. SUBJECTS AND METHODS: A total of 712 lymph nodes (416 in the neck, 205 in the groin, and 91 in the axilla) were studied in 118 patients with high-sensitivity Power doppler. Three categories of vascularity were defined: absence of vascularity (type 1), hilar and perihilar vascularity (type 2), and vascularity in the entire node (type 3). The 3 types of vascularity were correlated with the anatomic location and the dimension (maximum transverse diameter) of the nodes. RESULTS: Type 3 vascularity was found in all lymph nodes with a maximum transverse diameter > 6 mm, in the 67.9% (133/196) of lymph nodes between 4 and 6 mm in diameter, and in 45.7% (42/92) of lymph nodes between 2 and 4 mm in diameter. In lymph nodes with transverse diameters of 2-6 mm, type 3 vascularity was detected in 80.7% (46/57) of the axillary nodes, in 69.0% (87/126) of the inguinal nodes, and in 40.0% (42/105) of the cervical nodes. Type 2 vascularity was seen in 14.2% (101/712) of all examined lymph nodes. The absence of vascularity (type 1) was noted in only 1.9% (8/416) of cervical and 2.0% (4/205) of inguinal nodes. CONCLUSIONS: State-of-the-art power Doppler equipment can demonstrate type 3 vascularity in a high percentage of normal superficial lymph nodes. This pattern of intense, extensive-but harmonious-vascularity must be considered as an indicator of benignity.

Adolescent↗

Immunocytochemical increased evidence of inducible nitric oxide synthase, tumor necrosis factor-alpha, and adrenocorticotropic hormone in human peritumoral lymph nodes.

In the current study, mesenteric and peritumoral lymph nodes surgically removed from patients with colon-rectum cancer were studied. Morphologic and immunocytochemical investigations demonstrated that mesenteric (control) and peritumoral lymph nodes of a same patient showed the same morphologic structure, but a different immunocytochemical pattern. Indeed, an increased immunoreactivity to anti-inducible nitric oxide synthase, anti-tumor necrosis factor-alpha, and anti-adrenocorticotropic hormone antibodies in the lymphatic tissue of peritumoral lymph nodes compared with mesenteric lymph nodes was observed. These findings suggest that in colon-rectum cancer, the pathologic event induces an increased expression of the molecules involved in the processes of inflammation and carcinogenesis that occurs earlier than the appearance of morphologic modifications.

Adrenocorticotropic Hormone↗