Pathological Examination Of Lymph Nodes Research Articles

Sentinel Lymph Node Mapping in Lung Cancer: A Pilot Study for the Detection of Micrometastases in Stage I Non-Small Cell Lung Cancer.

Lymphadenectomy represents a fundamental step in the staging and treatment of non-small cell lung cancer (NSCLC). To date, the extension of lymphadenectomy in early-stage NSCLC is a debated topic due to its possible complications. The detection of sentinel lymph nodes (SLNs) is a strategy that can improve the selection of patients in which a more extended lymphadenectomy is necessary. This pilot study aimed to refine lymph nodal staging in early-stage NSCLC patients who underwent robotic lung resection through the application of innovative intraoperative sentinel lymph node (SLN) identification and the pathological evaluation using one-step nucleic acid amplification (OSNA). Clinical N0 NSCLC patients planning to undergo robotic lung resection were selected. The day before surgery, all patients underwent radionuclide computed tomography (CT)-guided marking of the primary lung lesion and subsequently Single Photon Emission Computed Tomography (SPECT) to identify tracer migration and, consequently, the area with higher radioactivity. On the day of surgery, the lymph nodal radioactivity was detected intraoperatively using a gamma camera. SLN was defined as the lymph node with the highest numerical value of radioactivity. The OSNA amplification, detecting the mRNA of CK19, was used for the detection of nodal metastases in the lymph nodes, including SLN. From March to July 2021, a total of 8 patients (3 female; 5 male), with a mean age of 66 years (range 48-77), were enrolled in the study. No complications relating to the CT-guided marking or preoperative SPECT were found. An average of 5.3 lymph nodal stations were examined (range 2-8). N2 positivity was found in 3 out of 8 patients (37.5%). Consequently, pathological examination of lymph nodes with OSNA resulted in three upstages from the clinical IB stage to pathological IIIA stage. Moreover, in 1 patient (18%) with nodal upstaging, a positive node was intraoperatively identified as SLN. Comparing this protocol to the usual practice, no difference was found in terms of the operating time, conversion rate, and complication rate. Our preliminary experience suggests that sentinel lymph node detection, in association with the accurate pathological staging of cN0 patients achieved using OSNA, is safe and effective in the identification of metastasis, which is usually undetected by standard diagnostic methods.

A 41-Year-Old Man With an Abdominal Mass and Hepatomegaly

A 41-Year-Old Man With an Abdominal Mass and Hepatomegaly

Commemorating the Silver Anniversary of the International Association for the Study of Lung Cancer International Workshop on Intrathoracic Staging

Commemorating the Silver Anniversary of the International Association for the Study of Lung Cancer International Workshop on Intrathoracic Staging

Clinical application of three-dimensional computed tomography bronchography and angiography in thoracoscopic segmentectomy

Objective To explore the clinical value of three-dimensional computed tomography bronchography and angiography (3D-CTBA) in thoracoscopic dissection or combined segmentectomy. Methods The clinical data of 30 patients with isolated or multiple pulmonary nodules from September 2017 to August 2019 were retrospectively analyzed. All cases were treated with 3D-CTBA to locate the nodules accurately before operations, in order to explicit the courses of bronchi and vessels, and to observe the variations. The target bronchi, arteries and veins were resected accurately during the operations, and the intersegmental plane was determined by expansion-collapse method. Results 13 patients underwent segmentectomy and 17 patients underwent combined segmentectomy. The diameter of the nodule was (11.56±3.79)mm; the depth of the nodule (the shortest distance from the visceral pleura) was (13.88±3.96)mm; the operation time was (134.94±18.68)min, and the intraoperative bleeding volume was (94.38±37.94)ml. No cancer metastasis was found by rapid pathological examination of lymph nodes during operations. No conversion to thoracotomy. The indwelling time of thoracic tube was (3.69±1.30)days, and the hospitalization days after operations was (4.81±1.47)days. No serious complications or death during the perioperative period. Conclusions Preoperative 3D-CTBA has advantages in pulmonary segmentectomy, which is a safe and effective method for accurate segmentectomy. Key words: Imaging, three-dimensional; Bronchography; Thoracoscopy; Pneumonectomy

Local-Regional Metastases and Mortality After Sentinel Biopsy and Complete Dissection of Axillary Lymph Nodes in Patients with Early Invasive Breast Cancer.

Introduction:Current, standard procedure for evaluation of axillary lymph node pathological (PH) status has been sentinel lymph node biopsy (SLNB). To demonstrate the long-term validity of sentinel lymph node biopsy (SLNB) using the radioactive isotope only Technetium 99m albumin-colloid (Tc99m) we compared the loco-regional recurrence and mortality of breast cancer patients with negative SLNB without axillary lymph node dissection (ALND) (SLNB group) to that of lymph node-positive patients undergoing ALND (ALND group).Aim:The aim of our study is to evaluate the results of long-term monitoring of patients with early invasive breast cancer in which the radio-actively guided axillary SLN biopsy and complete ALND were studied, with special emphasis on local-regional recurrence and mortality.Patients and methods: We studied a total of 63 patients with T1-2early invasive breast cancer diagnosed at Clinic for general and abdominal surgery, Clinical Center University of Sarajevo (CCUS) between 2004 and 2007, with follow-up till 2013, retrospectively, who met the criteria for inclusion. Preoperative peritumorous injection of radioactive isotope (Tc99m albumin-colloid) is done on the Clinic for Endocrine and Nuclear Medicine-CCUS. Intra and postoperative pathohistological (PH)examination of SLN node (or nodes) and PH examination of lymph nodes after complete ALND was done at the Clinic for Clinical Pathology and Cytology-CCUS. Statistical evaluation was done by statistical program MedCalc Statistical Software, version 18.10. Depending on the given variables were used: mean, standard deviation, median values, 95% CI for median value, Chi-square test, D’Agostino-Pearson test, Kaplan-Maier curve of survival. Defined level of significance was p<0,05.Results:The SLNB group consisted of 33 SLN-negative women and ALND group consisted of 30 axillary lymph node-positive women. The sentinel node identification rate was 100%. In the SLNB group no patients has developed axillary recurrence during the follow-up. The mortality rate in the SLNB group was equivalent to that in the ALND group.Conclusions:The SLN biopsy conducted with only a radioactive isotope TC 99m have the same results as loco-regional recurrence and mortality as well as the complete ALND method and may be the method of choice for the treatment of axillary in breast cancer patients and the clinically negative axillary lymph node (or nodules) with the notion that patients should be micro metastases given special attention during long-term monitoring.

Impact of Positive Nodal Metastases in Patients with Thymic Carcinoma and Thymic Neuroendocrine Tumors

Thymic carcinomas and thymic neuroendocrine tumors are rare diseases often treated with surgical resection. Currently, there are no guidelines regarding nodal dissection at the time of tumor resection. Moreover, the prognostic significance of nodal metastases is unclear. The goal of this study was to define the incidence and prognostic relevance of nodal metastases in patients with thymic carcinoma and thymic neuroendocrine tumors. The Surveillance, Epidemiology and End Results database was queried for patients who underwent surgical resection of thymic carcinoma or a thymic neuroendocrine tumor with documented pathological examination of lymph nodes. The incidence of nodal metastases and the impact on survival were examined. We identified 176 patients with thymic carcinoma and 53 with thymic neuroendocrine tumors. A median of three lymph nodes was sampled per patient. Positive metastasis to at least one lymph node was identified in 92 patients (40.2%). Nodal metastasis was more common in patients with thymic neuroendocrine tumors than in patients with thymic carcinoma (62.3% versus 33.5%). In multivariate analysis, nodal metastasis was more likely in patients with thymic neuroendocrine tumors and with more advanced tumors. The presence of nodal metastases had significant, independent, adverse impact on survival (hazard ratio, 2.933, 95% confidence interval, 1.903-4.521, p = 0.001). Median survival was 47 months in patients with nodal metastasis and 124 months in patients without nodal metastases (p < 0.001). Nodal status seems to be an important prognostic factor in patients with thymic carcinoma and thymic neuroendocrine tumors. Nodal sampling should be performed during resection of these thymic malignancies.

Are small rectal neuroendocrine tumors safe?

Neuroendocrine tumors (NETs) are slow-growing tumors with different biological and clinical characteristics. The incidence of NETs varies depending on the organ; however, the rectum is the most prevalent tumor site in the gastrointestinal system, accounting for 60-89% of all gastrointestinal NETs.1 These tumors are often found incidentally during colonoscopy without any symptoms. They are usually detected on endoscopy as small, protruding subepithelial lesions located between 4-20 cm above the dentate line on the anterior or lateral rectal wall. According to the European Neuroendocrine Tumor Society (ENETS) 2012 Consensus Guidelines,2 well-differentiated rectal NETs <10 mm without muscle invasion or lymph node involvement could be treated by performing local resection. For local resection, various treatment modalities have evolved, including endoscopic polypectomy, endoscopic mucosal resection (EMR), endoscopic submucosal dissection, transanal excision, and transanal endoscopic microsurgery.3 To evaluate the risk of metastasis, pathological examination of lymph nodes should be implemented. However, small rectal NETs are known to have little risk of metastasis, making local resection desirable. Radical surgery is reserved for selected cases with risk factors associated with lymph node metastasis. In rectal NETs 20 per 10 HPF and/or Ki-67 >20%. In the current case,7 it may be reasonable to omit surgical resection for the perirectal lymph nodes after EMR, as histological analysis of the tumor revealed no lymphovascular invasion, no mitosis per 50 HPF, and a Ki-67 labeling index of 0.8%. In the current case, the authors followed the patient using annual endoscopy and abdominopelvic CT for 7 years after resection. Fortunately, the perirectal lymph node metastasis was completely removed via laparoscopic surgical resection and lymph node dissection, vigorous surveillance in this case. A population-based study4 in Japan also reported a prevalence of 3.7% for lymph node metastasis in rectal NETs 20 mm within the first year, and every 4-6 months in the first year and at least annually thereafter for G3 tumors. In the current case, the authors followed the patient using annual endoscopy and abdominopelvic CT. Although ENETS guidelines3 do not recommend routine follow-up with CT or MRI for rectal NETs <10 mm, follow-up modalities may include endoscopy, EUS or MRI. Considering the possibility of lymph node metastasis in the first presentation of the current case, additional investigation with rectal MRI or EUS that can more accurately assess perirectal lymph nodes than conventional CT may be helpful in assessing the nature of perirectal lymph node enlargement.11 Furthermore, EUS-guided fine needle aspiration or laparoscopic lymph node sampling may be considered if MRI or EUS suggests the possibility of lymph node metastasis. As the natural course of rectal NETs is not fully understood and the risk of lymph node metastasis has varied in previous studies, the metastatic potential of rectal NETs, even in tumors <10 mm, should not be ignored. The current case report is very informative for clinicians, because the natural course of untreated perirectal lymph node metastasis of G1 rectal NETs <10 mm has never been described previously. Generally, the risk of lymph node metastasis for rectal NETs <10 mm is low; however, NETs are classified as a malignant disease in the recently revised American Joint Committee on Cancer (AJCC) cancer staging guidelines. Therefore, clinicians should remember that the clinical behavior of rectal NETs might sometimes resemble that of malignant tumors, even when tumors are small.

Resection of thymoma should include nodal sampling

Thymoma is best treated by surgical resection; however, no clear guidelines have been created regarding lymph node sampling at the time of resection. Additionally, the prognostic implications of nodal metastases are unclear. The aim of this study was to analyze the prognostic implications of nodal metastases in thymoma. The Surveillance, Epidemiology, and End Results database was queried for patients who underwent surgical resection of thymoma with documented pathologic examination of lymph nodes. The impact of nodal status on survival and thymoma staging was examined. We identified 442 patients who underwent thymoma resection with pathologic evaluation of 1 or more lymph nodes. A median of 2 nodes were sampled per patient. Fifty-nine patients (59 of 442, 13.3%) had ≥ 1 positive node. Patients with positive nodes were younger and had smaller tumors than node-negative patients. Median survival in the node-positive patients was 98 months, compared with 144 months in node-negative patients (P = .013). In multivariable analysis, the presence of positive nodes had a significant, independent, adverse impact on survival (hazard ratio 1.945, 95% confidence interval 1.296-2.919, P = .001). The presence of nodal metastases resulted in a change in classification to a higher stage in 80% of patients, the majority from Masaoka-Koga stage III to stage IV. Nodal status seems to be an important prognostic factor in patients with thymoma. Until the prognostic significance of nodal metastases is better understood, surgical therapy for thymoma should include sampling of regional lymph nodes.

Inguinal sentinel node dissection versus standard inguinal node dissection in patients with vulvar cancer: A comparison of the size of metastasis detected in inguinal lymph nodes

Objective.The emergence of sentinel lymph node (SLN) technology has provided the ability for an in depth pathologic evaluation for the detection of metastasis to lymph nodes through the use of ultra-staging. The SLN has been shown to be predictive of the metastatic status of its nodal basin. More recently, SLN dissections have been employed in the evaluation of the inguinal lymphatic basins in patients with vulvar malignancies. We hypothesize that the average size of metastasis detected in non-palpable inguinal lymph nodes is smaller when detected through the use of SLN dissection and ultra-staging versus complete inguinal node dissection (CND). Methods.This was an IRB approved retrospective study. The tumor registry database was searched to identify all patients diagnosed with a vulvar malignancy from 1990 to 2004. The records were reviewed to identify patients with inguinal lymph node metastasis. Only patients with non-palpable inguinal lymph nodes (metastasis 1 cm or less) were included in the analysis. All pathology slides were reviewed. The smallest metastatic foci of cells were measured from lymph nodes obtained through the traditional complete inguinal lymph node dissection (CND) and compared with the largest metastatic foci of cells detected in sentinel lymph node dissections. The mean size and standard deviation for each group was calculated and analyzed with a Mann–Whitney test. Results.There were 336 inguinal node dissections performed in patients identified with a vulvar malignancy. SLN dissections were performed in 52 groins and CND in 284 groins. Fifty-eight patients were found to have metastatic disease to the inguinal lymph nodes. Thirty of these patients had no evidence of lymph node metastasis on clinical exam or at the time of their EUA. There were 7 groins with metastasis detected through an SLN and 23 groins through a CND. The mean size of the metastatic foci detected in the SLN group was 2.52 mm (SD 1.55) and in the CND group was 4.35 mm (SD 2.63). This was not statistically significant (P = 0.109). However, when comparing the detection of micrometastasis in each set, there was a significant difference (P = 0.02) in the detection of the size of metastasis detected with smaller cluster of cells detected in the SLN group. Conclusion.SLN dissection with ultra-staging allows for a more extensive pathologic examination of lymph nodes and may allow for the detection of smaller tumor foci than the traditional pathological examination of lymph nodes obtained from a CND. The clinical implication of the detection of these micrometastasis and smaller metastasis remains to be determined.

Utility of lymphangiography in the prediction of lymph node metastases in patients with cervical cancer

Our objective was to assess the value of lymphangiography in selecting patients for surgical staging of locally advanced cervical cancer. We reviewed our computerized database to identify patients with cervical cancer who had abnormal findings on lymphangiography and underwent retroperitoneal lymph node dissection between September 1991 and January 1996. The records of these patients were retrospectively reviewed, and the following data were retrieved: clinical tumor stage and findings on lymphangiography at surgery, and on pathologic examination of resected lymph nodes. The lymphangiograms were reviewed and reinterpreted in blinded fashion by two of the authors. The positive and negative predictive values of lymphangiography for the presence of lymph node metastases were calculated, with findings on pathologic examination of lymph nodes used as the gold standard. The positive and negative predictive values of surgeons' clinical assessments at surgery were also calculated. Fifty patients met the selection criteria and constituted the study population. Fourteen patients (28%) had histologically negative nodes, and 36 patients (72%) had lymph node metastases. Thirty-three patients had metastases to pelvic nodes, 1515 patients had metastases to common iliac nodes, and 1616 patients had metastases to para-aortic nodes. The positive predictive value of lymphangiography for lymph node metastases was 74% for pelvic nodes, 73% for common iliac nodes, and 88% for para-aortic nodes. The negative predictive value of lymphangiography for lymph node metastasis was 76% for common iliac nodes and 77% for para-aortic nodes. Overall, 46% of the patients selected for surgical exploration had histologic findings of either common iliac or para-aortic lymph node metastases; these findings led clinicians to extend radiation fields to cover the para-aortic lymph nodes. Lymphangiography is helpful in selecting patients with cervical cancer who have a high risk of common iliac or para-aortic lymph node metastasis. However, more accurate and more readily available noninvasive methods of evaluating cervical patients for the presence of regional disease continue to be needed.

Ultrastaging of early colon cancer using lymphatic mapping and molecular analysis

Approximately one-third of node-negative colon cancers will recur, possibly due to understaging and inadequate pathological examination of lymph nodes (LNs). We evaluated the sensitivity, accuracy and feasibility of staging based on lymphatic mapping, focused examination, and molecular analysis of the sentinel node (SN) in patients with primary colorectal carcinoma. Between 1996 and 2000, 100 patients with colon carcinoma (CRC) underwent lymphatic mapping immediately after peritumoral injection of 1.0 cc of isosulphan blue dye. All LNs in the CRC specimen were examined by routine haematoxylin and eosin (H&E) staining. Sentinel nodes were examined by step serial sectioning, cytokeratin immunohistochemistry (CK-IHC) and/or reverse transcriptase-polymerase chain reaction (RT-PCR) analysis in an attempt to identify occult micrometastatic disease. Lymphatic mapping was successful in 97% of the cases. There were 5 false-negative cases, predominately associated with T3/T4 tumours. Aberrant lymphatic drainage was identified in 8 patients (8%) altering the operative approach. 26 patients had H&E-positive LNs. In 74 patients who were node-negative by routine H&E, 18 (24%) had occult nodal micrometastases missed on routine H&E examination, but detected by focused analysis of the SN. RT-PCR analysis of the SN was performed in 40 patients, 26 of which were negative by H&E and CK-IHC. In 12/26 (46%) of these patients, there was additional evidence of micrometastatic disease. In this study, focused examination of the SN in conjunction with RT-PCR analysis identified micrometastatic disease in a significant number of node-negative patients. This may have important implications when selecting patients for adjuvant treatment protocols.

Molecular staging of malignant melanoma: correlation with clinical outcome.

For most solid tumors, the metastatic status of regional lymph nodes is the strongest predictor of relapse and survival. However, routine pathological examination of lymph nodes may underestimate the number of patients with melanoma who have nodal metastases. To determine the clinical significance of a highly sensitive molecular assay for occult nodal metastases for the staging of patients with melanoma. A prospective cohort study of consecutive patients in which lymphatic mapping and sentinel lymph node (SLN) biopsy were performed on 114 melanoma patients with clinical stage I and stage II disease. The SLNs were bivalved, and half of each specimen was submitted for routine pathological examination. The other half was submitted for molecular detection of submicroscopic metastases using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay for tyrosinase messenger RNA as a marker for the presence of melanoma cells. Patient follow-up averaged 28 months. A major university-based melanoma referral center at a National Cancer Institute-designated cancer center. A total of 114 patients with newly diagnosed cutaneous malignant melanoma who were at risk for regional nodal metastases. Melanoma recurrence and overall survival. Twenty-three patients (20%) had pathologically positive SLNs, and all of these patients were also RT-PCR positive. Of the 91 pathologically negative patients, 44 were RT-PCR negative and 47 were RT-PCR positive. There was a recurrence rate among 14 (61%) of the 23 patients who were both pathologically and RT-PCR positive and a recurrence rate among 1 (2%) of 44 patients who were both pathologically and RT-PCR negative. For patients who were upstaged by the molecular assay (pathologically negative, RT-PCR positive), there was a recurrence rate among 6 (13%) of 47 patients. The differences in recurrence rates and overall survival between the pathologically negative, RT-PCR-negative and pathologically negative, RT-PCR-positive patient groups were statistically significant (P= .02 for disease-free survival and for overall survival). In both univariate and multivariate regression analyses, the histological and RT-PCR status of the SLNs were the best predictors of disease-free survival. The use of an RT-PCR assay for detection of submicroscopic melanoma metastases in SLNs improved the prediction of melanoma recurrence and overall survival over routine pathological examination.

Surgery, radiotherapy, and chemotherapy for esophageal cancer

During the past year, several excellent reviews have been published on various aspects of esophageal cancer treatment. Pathologic examination of lymph nodes after extensive resections has reconfirmed the early lymphatic spread at a relatively large distance of the primary tumor. Approximately 50% of the patients with intrathoracic tumors invading the submucosa have positive lymph nodes, half of which are located outside the chest. It has been demonstrated that patients with a limited number of positive nodes can be cured by extensive surgery at the cost of increased morbidity and mortality, even in experienced hands. Although the effectiveness of surveillance programs for patients with Barrett's mucosa is still unclear, both tumor classification and survival appear to be more favorable in patients who were referred from surveillance programs as compared with patients who had not been in such programs. The role of video-assisted thoracic surgery seems to be limited to diagnostic procedures. Prolonged collapse of the lung during video-assisted thoracic surgery-esophagectomy induces severe pulmonary complications. The role of primary radiotherapy is limited, but favorable results have been described in the treatment of early tumors. Primary chemoradiation can achieve a high frequency of local tumor resolution, albeit at the expense of high toxicity. Both after limited and en-bloc resection, locoregional recurrence is most frequently accompanied by distant metastases, underlining the need for (neo)adjuvant systemic therapy. Preoperative chemotherapy has resulted in a 45% (partial) response rate. Several phase II trials have tested the efficacy of preoperative chemoradiotherapy. The disappointing results of two studies indicate that the treatment should be aggressive to reach a substantial improvement of survival.

Two Programmes for Examination of Regional Lymph Nodes in Colorectal Carcinoma with Regard to the New pN Classification

The new pN classification for colorectal carcinoma requires not only a statement on absence or presence of regional lymph node metastases but also, if present, a knowledge of the site and number of involved nodes. Subdivision of the fatty tissue with nodes adhering to the tumor resection specimen into two compartments is therefore the first step in pathological examination of lymph nodes. The methods for this as well as the different techniques used in searching for nodes and further histological processing of nodes are presented. We outline a minimal programme for pN classification in which step-wise sequence of examination reduces work load. An extended programme designed to answer special questions regarding lymphatic spread and surgical method is recommended only within the framework of special clinico-pathological studies.

Lymphatic toxoplasmosis

SummaryNo specific symptomatology can be ascribed to the lymphadenopathic form of the acquired toxoplasmosis, which may run a subclinical course or evoke severe diseases, such as infectious mononucleosis or Hodgkin's disease.The physician and even the pathologist, when confronted with a case of adenopathies of obscure aetiology, may miss the true diagnosis if they do not look for a toxoplasmic infection. Pathological examination of lymph nodes is not always conclusive. Serologic tests and inoculation of lymph node material into mice afford a definitive diagnosis.The two clinical cases reported above suggest that toxoplasmosis should be more frequently thought of as a cause of adenopathy in the adult.