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The role of sentinel lymph nodes in malignant melanoma.

Selective sentinel lymph node dissection should be considered a standard approach in the treatment of primary malignant melanoma. With the combination of blue dye and radioisotope mapping, the sentinel lymph nodes (SLNs) can be harvested with pinpoint accuracy. This article compares blue dye and radioisotope mapping techniques. Based on the clinical outcome data of selective sentinel lymph node dissection, micrometastasis to the SLNs carries a poor prognosis for patients with primary invasive melanoma.

Coloring Agents↗

Axillary recurrence in women with a negative sentinel lymph node and no axillary dissection in breast cancer.

OBJECTIVES: Sentinel lymph node biopsy (SLNB) is widely used for staging breast cancer. SLNB accurately determines axillary lymph node status with a low false negative rate. There remains concern that omitting axillary dissection may lead to recurrence in the axilla, and impact long term survival. The purpose of this study was to determine the frequency of axillary lymph node recurrence in patients who had a negative sentinel lymph node and did not undergo axillary node dissection. METHODS: Data was collected on all patients who had negative SLNB at Roswell Park Cancer Institute between July 1997 and June 2002. Demographics, type of operation, postoperative systemic, and radiation therapy, co-morbidity score, hormone receptor status, and the pathologic features of the tumor were abstracted for each patient. For each woman with recurrence, the dates of recurrence, the site(s) of recurrence, and the treatment for recurrence were recorded. RESULTS: With a median follow-up of 33 months, 15 of 335 (4.5%) women who had negative SLNBs and who did not undergo completion axillary dissection developed a cancer recurrence. Only two patients (0.6%) had an axillary recurrence. CONCLUSIONS: The rate of axillary recurrence following a negative sentinel node biopsy is the same or less than axillary lymph node dissection (ALND) alone. Concerns that omitting completion axillary dissection following a negative SLNB will increase the rate of axillary recurrence appear unfounded.

Adult↗

[Detecting micrometastases in sentinel lymph nodes].

Many investigators have reported micrometastases in sentinel lymph nodes, which have been detected by various methods. The most common method of detecting micrometastases is pathological examination using a combination of hematoxylin-eosin and immunohistochemical staining of multisectioned specimens. However, no standard method has been established concerning how to slice the specimen and how many slides should be examined. On the other hand, a more sensitive method utilizing the reverse-transcriptase polymerase chain reaction (RT-PCR) has also been applied for the detection of micrometastases. However, this method is so sensitive that it may detect isolated tumor cells (ITC), which are not defined as metastases according to the 6th edition of the American Joint Committee on Cancer and Union Internationale contre le Cancer cancer staging manuals for breast cancer. Therefore it is an urgent task to establish a standard method for detecting micrometastases in sentinel lymph nodes. For this purpose, further examination of many patients is needed to determine the most efficient and convenient way for detection of micrometastases in sentinel lymph nodes, whether the micrometastases influences the prognosis of patients, and whether regional lymph node clearance is needed in the case of micrometastases in sentinel lymph nodes.

Breast Neoplasms↗

The parotid, mandibular and lateral retropharyngeal lymph nodes of the camel (Camelus dromedarius).

The parotid, mandibular and lateral retropharyngeal lymph nodes of the dromedary camel were examined using both light and electron microscopy. All three lymph nodes were lobulated. They did not show the characteristic medulla, cortex and paracortex of typical lymph nodes. Instead, they contained lymphatic nodules, dense anodular lymphoid tissue and diffuse lymphoid tissue dispersed throughout the lymph node. Networks of sinuses were present in the diffuse lymphoid tissue. The diffuse lymphoid tissue in the periphery of all lymph nodes examined was characterized by numerous erythrocytes within and around its network of sinuses. The nodal sinuses were contiguous with the septal vessels, which are considered the possible source of erythrocytes seen in this study. The lymph nodes that were seen in this study resembled the haemolymph nodes of other mammals with regard to their content of erythrocytes but were unique in being located in sites that were typical of ordinary lymph nodes. Morphometric analysis has shown that the percentage volume densities of the stroma and the various parenchymal components were similar in the three lymph nodes.

Animals↗

Detection of normal mediastinal lymph nodes by ultrasonography.

PURPOSE: The detection by US (in contrast to CT) of lymph nodes of any size in the mediastinum is usually considered to be a pathological finding. The aim of this study was to find out whether it was possible to detect normal lymph nodes by high-resolution mediastinal US. MATERIAL AND METHODS: Six different mediastinal regions in 80 healthy asymptomatic volunteers and in 20 human cadavers were examined by means of US (with colour Doppler imaging) to assess US access to the respective regions and to demonstrate the number and size of detectable lymph nodes. All the cadaveric lymph nodes that were detected were examined histologically to exclude inflammatory or malignant infiltration. RESULTS: In almost all subjects, we obtained US access to the supra-aortic (100%), paratracheal (95%), prevascular (99%), and pericardial (98%) regions, and to the aorticopulmonary window (98%). US access to the subcarinal region was more difficult (75%). In the healthy subjects, lymph nodes were detected in the paratracheal region (in 35% of these subjects, mean lymph-node diameter 12 x 7 mm), in the aorticopulmonary window (45%, 14 x 8 mm), and in the subcarinal region (13%, 13 x 7 mm). In the cadavers, histologically normal lymph nodes were detected frequently in the paratracheal region (85%, mean size 11 x 6 mm) and in the aorticopulmonary window (90%, 11 x 5 mm). CONCLUSION: These results indicate that normal lymph nodes (and not only pathological lymph nodes) can be demonstrated by high-resolution mediastinal US.

Adult↗

Mesothelial pelvic lymph node inclusions mimicking metastatic thyroid carcinoma.

Benign lymph node inclusions are commonly encountered during surgery for gynecologic neoplasms and are potential mimics of metastatic disease. A 52-year-old woman presented with ascites, a complex adnexal mass, and a CA-125 of 1891 units/mL. A staging laparotomy was performed, diagnosing struma ovarii. Pathologic evaluation of pelvic lymph nodes demonstrated mesothelial inclusions in nodal sinuses suspicious for metastatic disease. Immunocytochemical evaluation revealed benign mesothelial inclusions rather than metastatic thyroid carcinoma. Benign mesothelial lymph node inclusions in nodal sinuses are potential mimics of metastatic carcinoma. Their presence in pelvic lymph nodes has not previously been reported. Given the potential difficulty in determining the origin of these inclusions, immunocytochemical evaluation is useful in reaching the correct diagnosis.

Diagnosis, Differential↗

Micrometastasis to axillary lymph nodes and bone marrow in breast cancer patients.

The axillary lymph nodes of 100 lymph node-negative breast cancer patients with known bone marrow status have been re-examined to explore the presence of micrometastasis in lymph nodes and the covariance of micrometastasis to bone marrow and lymph nodes. Nodes were serially sectioned at three intervals of 100 microm, followed by immunohistological (two sections) and haematoxylin-eosin staining (one section). Tumours were mainly T1 and T2, and the patients had on average 13 (4-22) lymph nodes removed. In two patients, micrometastasis was detected in one node. Another 25 patients possessed single positive immunostained cells mimicking tumour cells. These cells have been shown to be false positive cells by Perl and melanin staining. One patient had metastasis to several nodes missed by the original examination. Immunocytochemical detection of micrometastasis in bone marrow revealed 11 marrow-positive patients. This study has identified a low frequency of micrometastasis to lymph nodes, and no covariance with micrometastasis in the bone marrow was seen. Bone marrow micrometastasis may be an independent prognostic variable, separate from axillary node status.

Journal Article↗

Small pelvic lymph node metastases: evaluation with MR imaging.

The purpose of this study was to determine if lymph node asymmetry in small (< 1.0 cm) pelvic lymph nodes was a significant prognostic feature in determining metastatic disease. Two hundred and sixteen patients who presented with pelvic carcinoma underwent magnetic resonance imaging (MRI). They were correlated with pathological findings obtained at surgery. We considered the maximum diameter (MAD) of both round- or oval-shaped suspicious masses seen in the axial plane. Two different cut-off values were determined: lymph node diameter greater than 1.0 cm (criterion 1) and lymph node diameter greater than 0.5 cm with asymmetry relative to the opposite side for lymph nodes ranging from 0.5 cm to 1.0 cm (criterion 2). With criterion 1, MRI had an accuracy of 88%, a sensitivity of 65%, a specificity of 96%, a positive predictive value (PPV) of 88% and a negative predictive value (NPV) of 88% in the detection of pelvic lymph node metastasis. By considering criterion 2, MRI had an accuracy of 85%, a sensitivity of 75%, a specificity of 91%, a PPV of 71% and a NPV of 91%. Normal small asymmetric lymph nodes were present in 5.6% of cases. Normal asymmetry of pelvic lymph nodes is not uncommon. It cannot be relied on to diagnose metastatic involvement in cases of small suspicious lymph nodes.

Adult↗

Distribution of estrogen and progesterone receptors in primary tumor and lymph nodes in individual patients with breast cancer.

Primary breast cancer tissue and lymph nodes were obtained from 48 patients. Estrogen receptors (ER) and progesterone receptors (PgR) were determined by a dextran-coated charcoal assay. ER were present in 72.9% of the primary tumors and in 62.4% of the malignant lymph nodes, whereas PgR were present in 73.0% and 50.0% of the cases, respectively. The primary tumor and the corresponding malignant lymph nodes showed an identical ER and PgR status, i.e., both tumor sites were receptor positive or both receptor negative in 89.6% and 77.1%, respectively. However, 10.4% of the patients had ER-positive tumors but ER-negative lymph nodes and 22.9% had PgR-positive primaries with PgR-negative lymph nodes. No receptor-positive lymph nodes showed a combination with receptor-negative primary tumor. This preliminary data shows that receptor-positive malignant lymph nodes mostly display the same receptor status as the corresponding primary tumor, whereas receptor-negative lymph nodes may have a receptor-positive primary tumor.

Axilla↗

[Anatomy and topography of the cardial lymph nodes of the adult human stomach].

Cardial lymph nodes in the human stomach occur in 97% of cases. Their number varies from 1 to 11 (in 54% of cases--1-4). They are situated in front (in 75% of cases--from 1 to 10 nodes), to the left (in 73% of cases--from 1 to 7) and at the back (in 37% of cases--from 1 to 3) of the cardia. The most often studied lymph nodes localize simultaneously in front and to the left from the cardial opening of the stomach (in 32% of cases), or in front, to the left and to the back of it (in 20%). Size of the human cardia lymph nodes varies within the limits of 0.5 X 0.5 up to 20.4 X 11.9 mm. With age their size decreases somewhat. In 15% of cases the cardial lymph nodes together with lymphatic vessels connecting them form a closed chain in front, to the left and at the back of the cardia.

Adult↗

Significance and management of thyroid lesions in lymph nodes as an incidental finding during neck dissection.

BACKGROUND: The incidental discovery of thyroid lesions in lymph nodes during a lymph node dissection performed for a separate primary head and neck tumor is an unusual clinical entity. Its discovery has led to controversy regarding its significance and management. METHODS: We identified five patients over the years 1991-1999 with this finding. All five patients were subsequently treated with a total thyroidectomy and a level VI lymph node dissection. RESULTS: Pathological examination revealed three papillary carcinomas and level VI lymph node metastases in the two patients who had carcinoma in their thyroid glands. All five patients are presently free of their primary and thyroid disease on follow-up examinations. CONCLUSIONS: These patients should be addressed with additional work-up and surgery if metastatic thyroid cancer is documented in the lymph node. We offer a diagnostic algorithm that may aid in further work-up and treatment in these unusual cases.

Adult↗

Keratin 20 is a specific marker of submicroscopic lymph node metastases in colorectal cancer: validation by K-RAS mutations.

Lymph node status has major prognostic importance in colorectal cancer and greater precision in the diagnosis of lymph node metastases should provide better prognostic and therapeutic guidance. Keratin 20 (K20) gene expression has been used as a marker of lymph node metastases, but the evidence for this remains circumstantial. This study has therefore sought to determine K20 specificity and to correlate K20 expression with mutant K-RAS expression, in order to provide direct evidence that K20 expression in lymph nodes of colorectal cancer patients genuinely reflects metastatic disease. Specificity of K20 expression was established against a range of tissue types and 289 lymph nodes from 41 non-cancer control patients. K20 expression was restricted to gastrointestinal epithelia and was only present in one of the 289 control lymph nodes, giving a calculated specificity of 97.6% (95% confidence limits: 87.1-99.9%). Forty-two tumour samples were analysed for the presence of K-RAS codon 12 gene mutations using a RT-PCR mutant allele-specific amplification (MASA) technique. Thirteen tumours (31%) had codon 12 mutations detected by MASA and these were further analysed to determine the exact nature of the mutation. MASA was then used to screen the lymph nodes from these patients for the presence of the tumour-specific K-RAS transcript and the results were compared with K20 RT-PCR and histopathology from the same samples. Whilst K-RAS MASA was not as sensitive as K20 RT-PCR, there was substantial agreement between the assays. There were no K20-negative lymph nodes which were found to be K-RAS MASA-positive, whereas seven nodes in four patients were K20-positive and K-RAS-negative, in keeping with the differences in assay sensitivity. These results further validate K20 as a marker by providing greater certainty that what is being detected represents occult metastatic disease.

Biomarkers, Tumor↗

Prediction of axillary lymph node involvement of women with invasive breast carcinoma: a multivariate analysis.

BACKGROUND: The increasing use of systemic therapy for women with lymph node negative breast carcinoma and earlier stage of disease at mammographic detection raises questions regarding the need for routine axillary lymph node dissection. Predictive modeling for lymph node involvement may be one way to reduce the need for axillary lymph node dissection and its morbidity. METHODS: A multivariate analysis of 12 factors predictive of axillary lymph node involvement was conducted in a population-based cohort of 4312 women with invasive breast carcinoma diagnosed between January 1, 1993 and December 31, 1996. RESULTS: Clinical palpability, lymphatic or vascular invasion, lesion size, margin status, histology, and patient age were independent predictors of axillary lymph node involvement. The model correctly identified lymph node status in 76.6% of cases. Model accuracy and fit were equally high when applied to randomly selected halves of the study subjects. Approximately 32.0% of the patients in the study sample (1363/4312) were identified as having an extremely high (91%; n = 1102) or low (10%; n = 261) risk of lymph node involvement. In a second analysis, a clinically useable, three-variable model identified a very low risk group of patients (n = 147) with a 4.8% risk of lymph node metastasis and a high risk group of patients (n = 1008) with a 74.2% risk of lymph node metastasis. Greater than 90% of subjects in the high risk group received adjuvant systemic therapy even if they were lymph node negative pathologically. CONCLUSIONS: A clinically useable, three-variable model employing tumor and lymph node palpability, size, and lymphatic or vascular invasion can identify women with invasive breast carcinoma in whom axillary lymph node dissection is very unlikely to alter recommendations regarding adjuvant systemic therapy.

Adult↗

Axillary lymph node dissection in breast cancer: an evolving question?

Axillary lymph node dissection (ALND) is performed for staging purposes. Sentinel lymph node biopsy may decrease the cost and morbidity of ALND. Are there patients that the procedure is not indicated avoiding cost and morbidity? We retrospectively studied the incidence of lymph node metastasis in 423 patients with T1 breast cancer. Thirty-one T1a, 146 T1b, and 246 T1c tumors were seen. The mean age was 61 years. Ten per cent were premenopausal, and 84 per cent were postmenopausal. Tumor size averaged 1.29 cm. Eighty-one per cent of the tumors were node negative and 19 per cent were node positive. One T1a patient (3 per cent) had an axillary metastasis, 19 T1b patients (13%), and 61 T1c patients (25%) were node positive, respectively. Seventy-three per cent were ER positive. Thirty-three patients (8%) died from cancer. Eighty-seven per cent received surgery with axillary lymph node dissection (ALND), and three per cent had surgery without ALND. Younger age, increased tumor size, premenopausal status, and ER negativity affected node positivity rates (P < 0.05). Death from breast cancer was more common among node-positive patients (P < 0.05). No difference was found regarding the performance of ALND and survival (P > 0.05). We feel that ALND can be safely omitted in T1a to reduce the morbidity and the expense of breast cancer treatment. In T1b and T1c tumors, the use of ALND is necessary, but morbidity and cost can be reduced by the use of sentinel lymph node biopsy.

Adult↗

[Detection and significance of lymph node micrometastases in patients with histologically node-negative gastric carcinoma].

OBJECTIVE: To study micrometastasis in lymph nodes from patients with node-negative gastric carcinoma according to routine histologic examination and its relevance to prognosis. METHODS: A total of 1,245 perigastric lymph nodes histologically free of metastasis from 105 patients were immunohistochemically stained with monoclonal antibody AE1 against low molecular weight cytokeratin for micrometastases. RESULTS: Micrometastases were observed in 81 lymph nodes(6.5%) of 31 patients (29.5%). The incidence of lymph node micrometastases was significantly higher in the diffuse type(22 of 53 cases, 41.5%) than in the intestinal type of gastric carcinoma (9 of 51 cases, 17.6%, P < 0.01). The presence of micrometastases was closely correlated with the size and invasion depth of primary tumor, but was not correlated with age, sex and location of the primary tumor. The 5-year survival rate after surgery was 61.3% and 82.4%, respectively in patients with and without micrometastases (P = 0.0116). When the number of lymph node with micrometastases was > or = 3, the 5-year survival rate significantly decreased. CONCLUSION: The detection of lymph node micrometastases is necessary to more accurately determine the clinical staging and prognosis of patients with node-negative gastric carcinoma by routine histologic examination.

Adult↗

Salivary gland lymph nodes. The site of lymphadenopathies and lymphomas associated with human immunodeficiency virus infection.

Normally, lymph nodes are intimately associated with the salivary glands, particularly the parotid gland. Several lymph nodes are embedded in the parotid gland, other lymph nodes are adjacent to the submaxillary gland, and ectopic salivary gland acini and ducts are commonly present in cervical lymph nodes. These salivary gland lymph nodes may become the primary site of the benign lymphadenopathy and the malignant lymphomas characteristically associated with human immunodeficiency virus (HIV) infection. This report of a series of HIV-associated lymphatic lesions originating in salivary gland lymph nodes comprises nine cases of salivary gland masses that were surgically excised, it includes six cases of lymphadenitides and three cases of lymphoma--all originating in salivary gland lymph nodes and showing the histologic lesions known to occur in association with the acquired immunodeficiency syndrome. The HIV-related infections and neoplasias located in the salivary gland lymph nodes raise interesting questions about the possible etiologic role of an oral portal of entry and of the virus-infected saliva. The recognition of their clinical and pathologic features is indispensable to enable correct diagnosis and treatment.

Acquired Immunodeficiency Syndrome↗

Surgical management of aberrant sentinel lymph node drainage in cutaneous melanoma.

BACKGROUND: Sentinel lymph node (SLN) mapping by lymphoscintigraphy has changed the surgical management of regional lymph node metastases for melanoma. SLNs lying outside of traditional nodal basins are now being identified. Our hypothesis is that when preoperative lymphoscintigraphy identifies aberrant SLNs, these nodes should be excised and, if histologically positive, lymphadenectomy of the aberrant nodal basin should be performed. METHODS: Patients with melanomas 1 mm or larger Breslow thickness and clinical stage N0M0 underwent lymphoscintigraphy and excision with SLN biopsy. Preoperative lymphoscintigraphy, intraoperative gamma probe, and intraoperative injection of isosulfan blue were performed to identify the SLN. Aberrant SLNs were defined as epitrochlear, supraclavicular, or popliteal nodes for extremity lesions and intramuscular nodes for truncal and head and neck lesions. RESULTS: Thirty-two patients were entered into the protocol. Seven (22%) were found to have aberrant nodes. Five of 19 patients with extremity melanoma had an aberrant SLN; 2 of 13 patients with truncal and head and neck melanoma had an aberrant SLN. CONCLUSIONS: This study demonstrates that (1) aberrant SLNs are encountered with similar frequency for extremity and truncal lesions, (2) biopsy should be performed on aberrant SLNs with intraoperative lymph node mapping with the gamma probe and blue dye, and (3) lymphadenectomy of the aberrant region should be considered if the aberrant SLN is positive.

Adolescent↗

Experimental frontiers for clinical applications: novel approaches to understanding mechanisms of lymph node metastases in melanoma.

Sentinel lymph nodes are the first nodes to receive lymph from primary tumors and are the preferential site of initial metastases. Sentinel nodes show morphology changes that suggests immune modulation with reduced antigen-presenting dendritic cells, activated T lymphocytes, high endothelial venules and transvenular migration of T lymphocytes. Tumor cells generate down-regulatory molecules. We postulate that tumor-induced immune dysfunction facilitates establishment of nodal metastases. Nodal immune modulation can be reversed by granulocyte macrophage colony-stimulating factor (GMCSF), a finding with implications for future therapy to prevent or reverse these nodal metastases.

Animals↗