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PubMedDate not supplied

Pathologic examination of the sentinel lymph node: what is the best method?

Sentinel lymph node biopsy (SLNB) has become an acceptable alternative to complete axillary dissection to determine whether breast cancer has spread to axillary lymph nodes. Yet the best method for pathologic examination of the sentinel lymph node (SLN) remains controversial. For years there has been speculation that micrometastases in axillary lymph nodes were clinically insignificant and thus lymph nodes did not require sectioning at close intervals. Yet essentially all studies, including a recent large prospective study, have found a significantly poorer prognosis associated even with metastases less than 2 mm in size-the most common definition of micrometastasis-suggesting that such small metastases cannot be safely overlooked. The use of immunohistochemistry (IHC) to detect keratin proteins will reveal metastatic breast carcinoma in about 18% of axillary lymph nodes that appear negative on routine stains. The preponderance of evidence to date suggests a significantly poorer prognosis in patients with such occult metastases, although data from large prospective studies are lacking. Molecular techniques such as polymerase chain reaction (PCR) offer even more sensitive methods for detecting occult metastasis in SLNs, although false positives are a particular problem in techniques that do not permit morphologic correlation, and for now they remain a research tool. Intraoperative examination of the SLN permits a completion axillary dissection to be performed during the same procedure if metastatic tumor is found; however, intraoperative techniques such as cytologic examination and frozen section lack sensitivity, and can result in loss of up to 50% of the SLN tissue. A proposal for optimal pathologic examination of the SLN is offered based on the above data.

Biomarkers, Tumor↗

PubMed2003

How 'hot' is the pathologically positive sentinel lymph node in breast cancer patients?

When many lymph nodes are found by using lymphoscintigraphic techniques performed to detect the sentinel lymph nodes (SLNs) in breast cancer, it is usual to find that the 'hottest' SLN is not always the node that is pathologically positive (pN+). Various criteria have been proposed to define which radioactive lymph nodes should be removed. In order to determine the frequency with which the hottest SLN 'fails' to be pN+, and to determine which criteria best define the radioactive lymph node to be removed, we reviewed and analysed our cases in which more than one SLN was detected and where there was also at least one pN+ node. From a series of 181 patients, 40 were selected. In 11 of these 40 cases (27.5%), the hottest SLN was not pN+. Radioactivity levels in the pN+SLN of these 11 patients ranged from 2% to 94% of the activity of the hottest SLN. Twenty-one patients (52.5%) showed only micrometastatic (pN1a) disease in one or more SLNs. In four of these patients (19%) the pN1a SLN was not the hottest node. Two of the patients had radioactivity levels in the pN+SLN which were more than 50% of that of the hottest SLN. In another two of these patients (9.5%), radioactivity levels were lower than 50% of that of the hottest node (respectively, 38% and 2%). However, in these two last cases, the first and hottest SLN removed surgically was found, by the pathologist, to consist of six nodes. Macrometastases (dimensions greater than 2 mm) were found in 19 patients. In 12 of these patients, the hottest SLN was macrometastatic although macrometastases and/or micrometastases were found in other 'cooler' SLNs in four of them. In another seven of these patients (36.8%), macrometastases were found in SLNs with radioactive levels lower than 51% of that of the hottest node. One patient (with three SLNs) out of the 40 (2.5%) had one SLN pN+ with less than 10% of that of the hottest. In fact, it contained only one micrometastasis and its activity was equal to 2%. Upon pathological examination, however, the hottest lymph 'node' was found to consist of six nodes. It is concluded that, with four intra-mammary and peritumoural injections of 99mTc labelled nanosized colloids of Human Serum Albumin (Nanocoll R: Sorin: 74 MBq and 0.05 mg per injection) performed 18-24 h before using a gamma probe to detect the SLNs, the hottest SLN was not the pathologically positive node in 27.5% of patients in our series. By using the activity in the hottest SLN as the reference point, and 10% of this activity as the lower threshold for removing active SLNs, the sensitivity of the technique is 97.5%.

Adult↗

PubMed2003

Rapid immunohistochemistry of sentinel lymph nodes for metastatic melanoma.

Sentinel lymph node (SLN) biopsy is performed on patients with malignant melanoma (MM) to assess the need for selective complete lymphadenectomy. Melanoma metastasis to regional lymph nodes is an important prognostic indicator in patients with MM. This study assesses the sensitivity and specificity of rapid immunohistochemistry (RIHC) in intraoperative delineation of melanoma metastasis to SLN. RIHC for S-100 protein, HMB45, and a melanoma marker cocktail (melan A, HMB45, and tyrosinase) was performed on 71 SLNs obtained from 28 patients with MM. Frozen sections (6 micro thick) on plus slides were fixed for 2 to 3 minutes in cold acetone and then stored at -70 degrees C. The EnVision kit (Dako, Carpinteria, CA) for rapid immunohistochemistry (RIHC) on frozen tissue sections was used, and the staining technique took 19 minutes. Together with preparation of the frozen sections and fixation in acetone, immunostained slides were available in approximately 25 minutes. Of the 71 SNLs examined, 7 showed melanoma metastasis in permanent sections. RIHC of frozen sections detected metastatic melanoma in 6 SLNs, with a sensitivity of 86% for HMB45 and 71% for S-100 protein and the melanoma cocktail and a specificity of 97% for HMB45 and 100% for S-100 and the melanoma cocktail. We conclude that RIHC for HMB45, S-100 protein, and the melanoma cocktail may help detect melanoma metastasis in SLN intraoperatively, leading to total lymph node dissection and obviating the need for 2 surgical procedures. Section folds and background stain can make interpretation difficult. Intraoperative time constraints require a more rapid technique. A recent consensus group has discouraged frozen-section examination of SLN.

Adolescent↗

PubMed2001

[Management of axillary and internal mammary lymph nodes in primary breast cancer].

Axillary lymph node dissection (ALND) is an effective staging procedure and is essential for local control of breast cancer. The regimen of the adjuvant systemic therapy is largely based on the number of nodes involved. There is as yet no evidence of survival benefit from axillary treatment by either surgery or radiotherapy, but this issue remains controversial. In general, the standard treatment of the axilla is surgical clearance of nodes from level I and II (partial ALND). If these nodes are involved, the clearance of level III nodes (complete ALND) is indispensable from the viewpoint of local control. Because a high rate of adverse events is observed, the extent of ALND should be determined by considering the balance between side effects and therapeutic benefit on a case-by-case basis. For the management of internal mammary nodes, most reports on randomized trials indicate that neither surgical treatment nor radiotherapy influences survival. However, the prognostic significance of internal mammary node status is high and a selected biopsy of lymph nodes with adenopathy should be considered for staging purposes. The significance of local control in this region is still controversial at present. About 30% to 40% of all invasive breast cancers are node positive. Thus, in most cases, the potential morbidity of ALND could be avoided if the status of the axillary nodes was ascertained with a less invasive procedure. The technique of sentinel lymph node biopsy may eventually prove to decrease the need for standard ALND. The randomized trial NSABP-B32 is ongoing and the results should indicate the clinical need for ALND.

Axilla↗

PubMed2000

Histopathologic analysis of sentinel lymph nodes in breast carcinoma.

BACKGROUND: Intraoperative lymphatic mapping and identification of the first draining lymph node (the sentinel lymph node) may allow some patients with breast cancer to avoid the morbidity of formal axillary clearance. The aim of this study was to determine the accuracy of sentinel lymph node (SLN) biopsy in predicting axillary nodal involvement. METHODS: From August, 1998 until July, 1999, 41 patients with clinically node-negative breast cancer underwent SLN biopsy that was immediately followed by axillary lymph node dissection. If the SLN section was found free of metastasis by routine hematoxylin and eosin staining (H&E), then an additional four sections of the SLN were cut and examined for the presence of tumor cells by H&E staining (three sections) and by cytokeratin immunohistochemical staining (IHC) (one section). If the SLN had metastatic cells and the other remaining nonsentinel axillary lymph nodes were free of metastases by routine H&E staining, then an additional three sections of the nonsentinel axillary lymph nodes were cut and examined for the presence of tumor cells by H&E staining. RESULTS: The 41 patients had a mean of 2.2 sentinel (range, 1-7) and 14.6 nonsentinel (range, 5-32) lymph nodes excised per patient. Routine H&E staining identified 13 patients (31.7%) with SLN metastases and 28 patients (68.3%) with tumor-free SLNs. Applying IHC and the additional three sections stained with H&E to these tumor-free SLNs showed one additional patient with sentinel node metastasis. The conversion rate from being a sentinel node-negative patient to a sentinel node-positive patient was 3.6% (1/28). Overall, SLN metastases were detected in 14 (34.1%) of the 41 patients. The SLNs were negative in 27 patients (65.9%), two of whom had at least one positive nonsentinel lymph node each (7.4% "skip" metastasis). Biopsy of SLNs was 92.6% accurate in predicting the absence of nonsentinel nodal metastasis (p=0.001). CONCLUSIONS: Our results suggest that formal axillary lymph node dissection may need only be performed in SLN-positive patients. Nonetheless, further experience and refinement are needed to perfect this technique.

Adult↗

PubMed2005

Equivalent cross-relaxation rate imaging for sentinel lymph node biopsy in breast carcinoma.

Sentinel lymph node biopsy (SLNB) is an important technique for detecting axillary lymph node metastasis in breast carcinoma patients. However, false-negative results are a problem. Equivalent cross-relaxation rate (ECR) imaging (ECRI) is a measurement method that can be used to quantitatively evaluate a change in the structural organization of lymph nodes by magnetic resonance imaging (MRI). We performed axillary ECRI in an attempt to decrease the false-negative results of SLNB. Regions without metastases showed a higher ECR value. On the other hand, regions with metastases showed a lower ECR value. The ECR images were compared with macroscopic histology images in which the presence or absence of axillary lymph node metastasis could be evaluated. ECRI is a potentially useful method for evaluating the efficacy of SLNB.

Adult↗

PubMed2002

Radioguided sentinel lymph node biopsy in malignant cutaneous melanoma.

The procedure of sentinel lymph node biopsy in patients with malignant cutaneous melanoma has evolved from the notion that the tumor drains in a logical way through the lymphatic system, from the first to subsequent levels. As a consequence, the first lymph node encountered (the sentinel node) will most likely be the first affected by metastasis; therefore, a negative sentinel node makes it highly unlikely that other nodes in the same lymphatic basin are affected. Although the long-term therapeutic benefit of the sentinel lymph node biopsy per se has not yet been ascertained, this procedure distinguishes patients without nodal metastases, who can avoid nodal basin dissection with its associated risk of lymphedema, from those with metastatic involvement, who may benefit from additional therapy. Sentinel lymph node biopsy would represent a significant advantage as a minimally invasive procedure, considering that an average of only 20% of melanoma patients with a Breslow thickness between 1.5 and 4 mm harbor metastasis in their sentinel node and are therefore candidates for elective lymph node dissection. Furthermore, histologic sampling errors (amounting to approximately 12% of lymph nodes in the conventional routine) can be reduced if one assesses a single (sentinel) node extensively rather than assessing the standard few histologic sections in a high number of lymph nodes per patient. The cells from which cutaneous melanomas originate are located between the dermis and the epidermis, a zone that drains to the inner lymphatic network in the reticular dermis and, in turn, to larger collecting lymphatics in the subcutis. Therefore, the optimal route for interstitial administration of radiocolloids for lymphoscintigraphy and subsequent radioguided sentinel lymph node biopsy is intradermal or subdermal injection. (99m)Tc-Labeled colloids in various size ranges are equally adequate for radioguided sentinel lymph node biopsy in patients with cutaneous melanoma, depending on local experience and availability. For melanomas along the midline of the head, neck, and trunk, particular consideration should be given to ambiguous lymphatic drainage, which frequently requires interstitial administration virtually all around the tumor or surgical scar from prior excision of the melanoma. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy because images are used to direct the surgeon to the sites of the nodes. The sentinel lymph node should have a significantly higher count than that of the background (at least 10:1 intraoperatively). After removal of the sentinel node, the surgical bed must be reexamined to ensure that all radioactive sites are identified and removed for analysis. Virtually the entire sentinel lymph node should be processed for histopathology, including both conventional hematoxylin-eosin staining and immune staining with antibodies to the S-100 and HMB-45 antigens. The success rate of radioguidance in localizing the sentinel lymph node in melanoma patients is approximately 98% in institutions that perform a high number of procedures and approaches 99% when combined with the vital blue-dye technique. Growing evidence of the high correlation between a sentinel lymph node biopsy negative for cancer and a negative status for the lymphatic basin-evidence, therefore, of the high prognostic value of sentinel node biopsy-has led to the procedure's being included in the most recent version of the TNM staging system and starting to become the standard of care for patients with cutaneous melanoma.

Colloids↗

PubMed1983

Production of antibodies by inoculation into lymph nodes.

The intra-lymph node technique used to inoculate rabbits with small quantities of antigen has been described. A variety of antigens in the 20,000-22,000 molecular weight range, as well as a 15-amino acid peptide coupled to BSA, have been inoculated successfully by this procedure. We have made no attempt to compare the success rate of the intra-lymph node inoculation route with other techniques utilizing small (microgram) quantities of antigen.

Animals↗

PubMed2005

The occurrence of nymphal stage of Linguatula serrata in water buffaloes (Bubalus bubalis): nymphal morphometry and lymph node pathology.

The mesenteric lymph nodes (MLN) of buffaloes (n = 100) were examined for the presence of parasitic infection. The nymphal stage of Linguatula serrata was observed in two buffaloes. A single white-coloured nymph with transversely striated spines on a segmented body, two pairs of oral suckers and hooks was observed in the MLN. The morphometrics of the nymphs were studied. The affected lymph nodes were grossly enlarged with cyst and showed pathological lesions of fibroblastic reaction with a mild underlying inflammatory zone.

Animals↗

PubMed1987

Crystals and calcification patterns in two lymph node calcifications.

Two calcified lymph nodes from the submandibular and neck regions, were studied by micro-radiography, X-ray micro-diffraction and X-ray micro-analysis. The submandibular specimen showed a conglomerate texture of small blocks which seemed to reflect the lobular structure of the lymph node. The degree of calcification of these blocks varied from one location to another. The neck specimen was composed of several islets surrounded by soft tissues. The main islet showed a central X-ray translucent region and outer calcified layers which could be subdivided into 2 types; those with spherulitic calcification and those with smooth calcification. In the submandibular specimen, well crystallized apatite was found, sometimes together with a minor amount of whitlockite. In the neck specimen, isolated and well-crystallized whitlockite was found most frequently in the regions of spherulitic calcification. The occurrence of whitlockite in both specimens was attributed to the sporadic distribution of magnesium, as revealed by X-ray micro-analysis.

Calcinosis↗

PubMed1995

Beta 1 integrin expression in malignant melanoma predicts occult lymph node metastases.

BACKGROUND: Elective lymph node dissection for malignant melanoma is still controversial. Experimental studies suggest that differential expression, activation, or both of beta1 integrins facilitate melanoma metastases. However, the clinical significance of beta1 integrin expression in human melanoma is unclear. METHODS: We examined primary cutaneous melanomas from 76 patients undergoing elective lymph mode dissection. We quantified the percentage of tumor area stained by beta1 integrin antibody with an image analyzer. RESULTS: beta1 integrin was expressed in all 23 primary tumors from patients with pathologically positive lymph nodes (LNs) but in only 14 (26%) of 53 cases with pathologically negative nodes (p < 0.001). No patients with beta1 integrin-negative tumors had LN involvement, whereas 23 (62%) of 37 patients with beta1 integrin-positive tumors had LN metastases (p < 0.001). Furthermore, 21 (91%) of 23 cases with LN metastases but only 4 (8%) of 53 cases without had beta1 integrin staining of 10% or more of tumor area (p < 0.001). CONCLUSIONS: Our study is the first to show a correlation between expression of a molecular marker in the primary cutaneous melanoma and likelihood of regional LN metastases. beta1 immunostaining of 10% or more of tumor area reliably predicts patients most likely to harbor occult LN metastases and likely to benefit from ELND.

Adult↗

PubMed1979

Membranous nephropathy. Its association with multicentric angiofollicular lymph node hyperplasia.

Multicentric angiofollicular lymph node hyperplasia of the plasma cell type with systemic manifestations developed in a 51-year-old man. One year later, the nephrotic syndrome due to typical immune complex mediated membranous nephropathy developed. Elevated titers to Epstein-Barr viral antigens suggesting reactivation of a latent infection were present. The patient has required conservative medical management only. The association of membranous nephropathy with angiofollicular lymph node hyperplasia lends further evidence to the postulate that the disorder is a manifestation of chronic immune stimulation by a foreign antigen.

Antigens, Viral↗

PubMed1987

Transnodal cancer chemotherapy for metastatic lymph nodes in rats.

The antitumor effects of transnodal cancer chemotherapy were studied using rat models. After inoculation of AH-66 tumor cells into the iliac lymph nodes (target lymph node), emulsionized bleomycin (BLM emulsion) or BLM water solution was injected into an intact popliteal lymph node and chronological changes in BLM levels in the target lymph node were measured. In the target lymph node of the iliac lymph node, the level of BLM emulsion continuously was greater than 2 micrograms/g for 9 hours after the injection, while the level of BLM water solution decreased rapidly. The antitumor effects were quantitatively estimated in the tumor of the target lymph node. The ratio of necrotic area in the BLM-emulsion-treated group was significantly greater than that in the emulsion- or saline-treated groups. Survival rate in rats treated with BLM emulsion was significantly higher than that in control groups and was slightly higher than that in the group given BLM water solution iv. The concentration of BLM in the serum and lung in case of transnodal administration of BLM was much lower than that in rats given an iv administration of BLM water solution. These findings suggest that transnodal administration of BLM emulsion is an effective and safe treatment for metastatic lymph nodes, at least in rats.

Animals↗

PubMed1994

Development of the high endothelial venule in rat lymph node autografts.

Vascular reconstruction during rat lymph node regeneration was investigated in autotransplanted mesenteric lymph node fragments, which had been implanted in the renal parenchyma. In addition to light microscopy, vascular casting and transmission electron microscopy were used. From day 3 onwards capillaries grew into the autografts together with lymphatic vessels. The capillaries showed obvious signs of proliferation by day 5. The surviving interstitial cells at the outer border of the transplant produced extracellular substance. High endothelial venules (HEV) differentiated from capillaries from about day 7. A first sign of their development was a vessel with a narrow, branching luminal space and with endothelial cells containing rich cytoplasm and small Golgi complexes. As the Golgi complexes grew and the cisternae and vesicles increased, the lumen dilated, the cell coat on the luminal surface became prominent, and, finally, lymphocytes emigrated through these venules from around day 10. The typical lymph node structure was complete by day 28. These results suggest that the interaction among the remaining interstitial cells, invading capillaries, and lymphatic penetration results in differentiation and maturation of HEV in lymph node regeneration. The development of Golgi complexes is strongly associated with lymphocyte emigration from the blood.

Animals↗

PubMed1999

Intrapulmonary lymph nodes: CT and pathological features.

Intrapulmonary lymph nodes are not uncommon and may be seen frequently in high quality computed tomography (CT) images and chest radiographs. We report four patients, older than 55 years, who had a long history of heavy smoking. Four intrapulmonary lymph nodes were located in the subpleural region (within 3 mm of the visceral pleural surface) of the right or left lower lobes. The lymph nodes were ovoid or round, homogeneous, well-defined and ranged from 9 to 10 mm in diameter. In one case, coexistent small nodules in the same or in other lobes on initial CT studies increased slightly in size over the following 3 years. All nodules contained lymphoid follicles and anthrocotic pigment, and in one case adjacent small aggregates of lymphocytes along interlobular septa were seen. Intrapulmonary lymph nodes have non-specific CT and clinical features. Follow-up CT may be useful in patients with suspected intrapulmonary lymph nodes.

Aged↗

PubMed1985

Incidence of malignancy in peripheral lymph node biopsy.

A review was made of 62 lymph node biopsy procedures during a 12-month period, from January 1, 1982, to December 31, 1982. The overall diagnostic yield was 56.5 per cent. Malignant lymph nodes were found in 53.2 per cent of cases. Seventy-two and two-tenths per cent (72.2%) of all malignant lymph nodes were metastatic carcinoma, including 6.1 per cent of metastatic lymph nodes with unknown primary. Twenty-seven and three-tenths per cent (27.3%) of all malignant lymph nodes belonged to the lymphoma-leukemia group. Among all the superficial lymph node regions, enlarged supraclavicular lymph nodes are associated with the highest incidence (75%) of malignancy. Clinical features associated with high incidence malignancy were: age greater than 55 years (75.8%), duration of less than 1 month (66.6%)--particularly, with a history of previous malignancy (91.7%). The anatomic knowledge of regional lymphatic drainage is essential in localizing the primary lesion of a metastatic lymph node.

Adolescent↗

PubMed2001

Follow-up of sentinel node negative breast cancer patients without axillary lymph node dissection.

BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the feasibility of sentinel lymph node biopsy in breast cancer patients at our institution and to report the follow-up status of node-negative patients with removal of only the sentinel node. METHODS: A total of 247 breast cancer patients underwent sentinel node (SN) mapping between June of 1996 and September of 2000. The SN was identified by using a combination of vital blue dye and a radiolabeled colloid. RESULTS: A SN was identified in 227 of 247 patients (91.9%). One hundred forty-five were SN negative, 82 were SN positive. All SN-positive patients underwent axillary dissection of level I and II, whereas 83 patients with a negative SN had SN biopsy only. Median follow-up of these patients at 22 months revealed no axillary recurrence; the morbidity resulting from SN biopsy was negligible. CONCLUSIONS: Although the follow-up is very short, SN biopsy only in node-negative breast cancer patients had no negative impact on the axillary failure rate and resulted in negligible morbidity.

Adult↗

PubMed2000

Frozen section analysis of sentinel lymph nodes in melanoma patients.

BACKGROUND: The sentinel lymph node biopsy (SLNB) is a diagnostic or staging option in the treatment of patients with cutaneous malignant melanoma (CMM) and is investigated intensively. A positive SLNB has appeared to identify patients who might have benefited from a lymph node dissection (LND). Intraoperative frozen section analysis (FSA) of the sentinel lymph node (SLN) during surgery would allow SLNB and LND to be performed in the same procedure. In the current study, we tested the reliability of FSA on the sentinel lymph node in patients with CMM. METHODS: Before definitive treatment of their melanomas began, FSA was performed on the SLNBs of 58 patients, whose median age was 56 (22-81) years, and who were 55% male and 45% female. Serial sections (500 micrometer interval), stained with routine hematoxylin and eosin and immunohistochemistry (S-100 and HMB-45), obtained definitive histology of the sentinel lymph node. RESULTS: Detection of the sentinel lymph node was possible in 56 patients (97%). Sixty-one SLNBs were performed in these patients. FSA detected metastases in 5 of 108 SLN (5%) in 5 patients. This was upgraded after definitive histology to 13 SLN (12%) in 11 patients (20%). Sensitivity of the FSA was 38%. After a median follow-up of 35 (range: 24-54) months, the false-negative rate of the SLN was 4% (2 patients). CONCLUSION: The combination of the low sensitivity of FSA and a finding that only 12% of the SLNBs contained metastases does not justify routine use of FSA on the SLN of patients with CMM.

Adult↗