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I have to thank the contributors who helped me realize this atlas by providing ideas and enabling me to complete this project in a timely fashion. A special note of appreciation to my family for tolerating my time away to complete this book.

Digumarthy, M. Harisinghani, M. Hedgire, M. Nadkarni, M. Pargaonkar, M. Sutphin, M. Careful analysis of nodes in the neck and knowledge of the various compartments is critical in the assess- ment and staging of primary head and neck malignancies. The risk of cervical metastasis depends on the site of origin of the primary tumor [2]. Classification The classification of cervical lymph nodes is complicated by the use of several dif- ferent systems and the rather loose intermixing of specific names for a particular node from one system to another [3].

Of the approximately lymph nodes in the body, about are located in the neck. Thus, between one fifth and one sixth of all the nodes in the body are located in either side of the neck, making development of a classification system very complex [4].

The direc- tion of nodal classification changed from that of a pure anatomic study to a nodal mapping guide for selecting the most appropriate surgical procedure among the various types of neck dissections [5].

In , Shah et al. Since then, a number of classifications have been proposed that use such level, region, or zone termi- nology. In the past few decades, the simple level-wise classification see Tables 1. This system M. Harisinghani ed. However, it did not recommend adding additional levels and stated that the nodes involving regions outside the VI levels should be referred to by the name of their specific nodal group e.

Table 1. At the time of this writing, the criteria to define cervical lymphadenopathy are 1 a discrete mass great than 1. A nodal mass with central low density is specifically indicative of tumor necrosis [7, 9—11]. Level I: Submental IA and Submandibular IB Metastatic Involvement These nodes contain metastatic disease when the primary site is lip, buccal mucosa, anterior nasal cavity, and soft tissue of cheek see Table 1.

Of course it is important to distinguish between level IA and IB as IA is likely to con- tain metastatic disease associated with floor of mouth, lower lip, ventral tongue, and anterior nasal cavity tumors [12], whereas lesions from oral cavity subsite are likely to spread to level IB, II, and III.

In the study by Candela et al. The corresponding figure for oropharyngeal cancer was These nodes can be further divided into IIA and IIB by spinal accessory nerve The red colors represent branches of external carotid artery Unusual Site of Metastasis They do not form part of the primary drainage pathway of nasopharyngeal carcino- mas but may be the sole site of tumour recurrence after radiotherapy. This is thought to be due to fibrosis of the lymphatic vessels in the irradiated regions resulting in diversion of lymph drainage to the submental nodes [14].

Level II Internal jugular chain lymph nodes see Fig. As the nerve cannot be identified on the CT scan, the Brussels guidelines used a criteria from radiological point of view proposed by Som et al. Level II 9 Fig. Note central hypodensity in these nodes which represent necrosis. They drain lymph from oral cavity, nasal cavity, nasopharynx, oropharynx, hypopharynx, lar- ynx, and parotid gland see Figs. The first draining lymph node station of supraglottic carcinomas is located in level IIA.

Involvement in papillary thyroid carcinoma is not uncommon especially of level IIB nodes. Unusual Site of Metastasis Intraparotid lymph nodes may be involved by lymphoma or metastatic spread from tumors of the scalp and face region [17]. Metastatic Involvement 13 a b Fig. Sagittal image shows necrotic level IIA node. Skip metastasis from carcinoma tongue is not unusual in this group [18].

Part of the inferior body of hyoid bone is seen medial to these nodes. The classical Virchow node hails from this group. Involvement of level V nodes precedes their involvement in thyroid malignancies see Figs. These nodes accompany level III nodes in skip metastasis from carcinoma tongue [18]. Involvement of Virchow node in carcinoma stomach is attributed to the predominant drainage by thoracic duct and partial filtration by Virchow node.

Level IV can be an unusual site of testicular metastasis [21]. Level VA see Fig. Metastatic involvement of this group alone is seen in a small subset of patients but occurs commonly if group I to IV harbor the tumor spread.

Level VB see Fig. Involvement of level VB is an ominous sign in aerodigestive tract malignancies. Level VB nodes should be carefully identified and differentiated from Virchow nodes [2]. Involvement of these nodes is considered as a bad prognostic sign in aerodigestive tract malignancies.

These nodes are not included in the level system The facial, mastoid occipital, and retropharyngeal nodes see Fig.

Facial nodal group is a blanket term applied for nodes at mandibular, buccinators, infraorbital, retrozygomatic, and malar nodes. These nodes are rarely identified and their metastatic involvement is seen in nasopha- ryngeal and epidermal malignancies [17]. Medial and lateral retropharyngeal nodes may be involved in pharyngeal and sinonasal, thyroid and cervical, esophageal primaries and are considered abnormal if larger than 5 mm [22, 23].

Occipital, facial, and mastoid groups of nodes are not included in the level sys- tem Fig. References 29 References 1. Bethesda: National Cancer Institute. Accessed 17 May Arch Otolaryngol Head Neck Surg. Paff GH. Anatomy of the head and neck. Philadelphia: Saunders; Schuller DE. Management of cervical metastasis in head and neck cancer.

Washington, D. Robbins KT. Classification of neck dissection: current concepts and future considerations. Otolaryngol Clin North Am. Surgical grand rounds. Neck dissection: current status and future possibilities. Clin Bull. Som PM. Detection of metastasis in cervical lymph nodes: CT and MR criteria and differential diagnosis. Cervical lymph node metastasis: assessment of radiologic criteria. Rouviere H. Lymphatic system of the head and neck. Ann Arbor: Edwards Brothers; Spiral CT in evaluation of head and neck lesions: work in progress.

Detection of lymph node metastases in the neck: radiologic criteria. Imaging of lymph nodes in the neck. Semin Roentgenol. Buckley JG, Feber T. Surgical treatment of cervical node metastases from squamous carci- noma of the upper aerodigestive tract: evaluation of the evidence for modifications of neck dissection.

Head Neck. Submental metastases from nasopharyngeal carcinoma. Clin Radiol. An imaging-based classification for the cervical nodes designed as an adjunct to recent clinically based nodal classifications. Level IIb lymph node metastasis in neck dissection for papil- lary thyroid carcinoma. Unusual sites of lymph node metastases and pitfalls in their detection.

Seethala RR. Current state of neck dissection in the United States. Head Neck Pathol. Stomach cancer: prevalence and significance of neck nodal metastases on sonography. Eur Radiol. Cervical lymph node dissection for meta- static testicular cancer. Ann Surg Oncol. Retropharyngeal space and lymph nodes: an anatomical guide for surgical dissection. Acta Otolaryngol.

Computed tomography of cervical and retropharyngeal lymph nodes: normal anatomy, variants of normal, and applications in staging head and neck cancer. Part II: pathology. Supraclavicular Nodes 1 1R and 1L. Low cervical, supraclavicular, and sternal notch nodes see Figs. Upper border: Lower margin of cricoid cartilage.

Lower border: Clavicles bilaterally and, in the midline, the upper border of the manubrium; 1R designates right-sided nodes; 1L designates left-sided nodes in this region. For lymph node station 1, the midline of the trachea serves as the border between 1R and 1L.

Upper paratracheal. Includes nodes extending to the left lateral border of the trachea. Upper border: Apex of the right lung and pleural space and in the midline, the upper border of the manubrium. Lower border: Intersection of caudal margin of innominate vein with the trachea.

Upper border: Apex of the left lung and pleural space and in the midline, the upper border of the manubrium. Lower border: Superior border of the aortic arch see Figs. Prevascular see Figs. On the right: Upper border: Apex of chest. Lower border: Level of carina. Anterior border: Posterior aspect of sternum.

Posterior border: Anterior border of superior vena cava. On the left: Upper border: Apex of chest. Posterior border: Left carotid artery. Retrotracheal see Fig.

Upper border: Apex of chest. Lower border: Carina. Lower paratracheal. Includes right paratracheal nodes, and pretracheal nodes extending to the left lateral border of trachea see Figs. Upper border: Intersection of caudal margin of innominate veins with the trachea. Lower border: Lower border of azygos vein. Includes nodes to the left of the left lateral border of the trachea, medial to the ligamentum arteriosum.

Upper border: Upper margins of the aortic arch. Lower border: Upper rim of the left main pulmonary artery. Lymph nodes lateral to the ligamentum arteriosum see Fig. Upper border: The lower border of the aortic arch. Lymph nodes anterior and lateral to the ascending aorta and aortic arch see Figs.

Upper border: A line tangential to the upper border of the aortic arch. Lower border: The lower border of the aortic arch. Inferior Mediastinal Nodes 7—9 7. Subcarinal see Fig. Upper border: The carina of the trachea. Lower border: The upper border of the lower lobe bronchus on the left; the lower border of the bronchus intermedius on the right. Lymph nodes adjacent to the wall of the esophagus and to the right or left of the midline, excluding subcarinal nodes see Figs.

Upper border: The upper border of the lower lobe bronchus on the left; the lower border of the bronchus intermedius on the right. Lower border: The diaphragm. Pulmonary ligament. Lymph nodes lying within the pulmonary ligament see Fig. Upper border: The inferior pulmonary vein. Mediastinal Lymph Nodes 39 Fig. These are seen interspersed between the paraesopha- geal group of lymph nodes violet.

Includes lymph nodes immediately adjacent to the mainstem bronchus and hilar vessels, including the proximal portions of the pulmonary veins and the main pulmonary artery see Fig. Upper border: The lower rim of the azygos vein on the right; upper rim of the pulmonary artery on the left. Lower border: Interlobar region bilaterally. Between the origin of the lobar bronchi see Fig.

Adjacent to the lobar bronchi see Fig. Adjacent to the segmental bronchi. Adjacent to the subsegmental bronchi. The four param- eters evaluated were 1 node location, 2 homogenicity, 3 border delineation, and 4 delineation by fat. Of 54 carcinoma patients, nodes were pathologically malignant in The most common cause of malignant lymph node enlargement in the mediasti- num is lung cancer. In patients with esophageal cancer, location of mediastinal lymph nodes depend on the location of the primary tumor.

Thoracic mediastinal lymph nodes were involved in Another cause of thoracic lymphadenopthy is lymphoma, in which mediastinal lymph node involvement is more frequent than hilar, which is usually asymmetrical and accompanied by mediastinal involvement [9] see Figs. They were detected on chest radiograph in 25 of 1, patients 2. The primary malignancies included eight tumors of the head and neck, 12 genitourinary malignancies, three carcinomas of the breast, and two malignant lymphomas. Mabon and Libshitz [12] analyzed 50 mediastinal metastases of infradiaphrag- matic malignancies on computed tomodensitography, a technique allowing a better visualization of all nodal groups in the mediastinum.

Besides a majority of genitourinary malignancies kidney, 25; testis, 7; prostate, 4; ovary, 3; bladder, 2 , they also observed metastases from carcinoma of the colon or rectum in 6 and stomach in 3.

In a recent study on the role of surgery in intrathoracic lymph node metastases from extrathoracic carcinoma [14], 26 of patients with mediastinal lymph node enlargement had a history of extrathoracic carcinoma breast, 7; kidney, 5; testis, 3; prostate, 2; bladder, 1; head and neck, 3; thyroid gland, 2; rectum, 1; intestine, 1; melanoma, 1.

Axillary Lymph Nodes Axillary lymph nodes are divided into five groups according to their afferent vessels and respective relationships with the vascular structures of the axilla [15] see Figs. Axillary Lymph Nodes 49 a b Fig. Afferent vessels: Drain the lymph from the superficial and deep compartments of upper lymph, except for the superficial vessels of the arm that run along the cephalic vein. Efferent vessels: Most terminate in the central or apical groups, whereas others pass into the supraclavicular nodes.

Anterior or Pectoral Group Nodes located behind the pectoralis major muscle and along the lower border of the pectoralis minor, forming a chain along and behind the lateral thoracic vessels.

Afferent vessels: From the skin and muscles of the anterior and lateral walls of the trunk above the umbilicus, and the lateral parts of the breast. Efferent vessels: Extend to the central and apical groups of axillary nodes. Posterior or Subscapular Group Nodes arranged in a chain that follows the subscapular vessels in the groove that separates the teres minor and subscapularis muscles.

Afferent vessels: Collect the lymph nodes arising from the muscles and skin of the back and from the scapular area down to the iliac crest. Efferent vessels: Drain into the central and apical lymph nodes Central Group Located in the central part of the adipose tissue of the axilla between the preceding chains that progressively converge toward them. Efferent vessels: Extend into the apical group.

Apical Group Nodes that occupy the apex of the axilla, behind the upper portion of the pectoralis minor and partly above this muscle. The majority of these nodes rest on the infero- medial side of the proximal part of the axillary vein, in close contact with the upper digitations of serratus anterior.

Afferent vessels: From all other axillary nodes; they also drain some superficial vessels running along the cephalic vein. Efferent vessels: The efferent vessels of this group unite to form the subclavian trunk, which finally opens into the right lymphatic duct on the right side or into the thoracic duct on the left side. Chest Wall Nodes 51 The inferior border of the pectoralis major and the inferolateral and superomedial edges of the pectoralis minor can be used as anatomical landmarks to separate the inferior I , middle II , and superior III levels of the axillary space.

Narrowing progressively, these levels contain the anterior pectoral , lateral brachial , posterior subscapular , and central groups of nodes level I , and then the central and apical groups levels II and III. Malignant Causes of Enlargement The most common cause of malignant axillary lymph node enlargement is breast cancer. The relationship between the tumor diameter and the probability of nodal involvement in all tumor sizes appears linear.

For patients with cancer 5 cm or greater, Other common causes include lymphoma and malignant melanoma. Rare causes would include basal cell carcinoma [17] and ovarian cancer [18]. Chest Wall Nodes Internal Mammary Internal Thoracic or Parasternal Nodes These nodes lie at the anterior ends of the intercostal spaces, along the internal mammary internal thoracic vessels see Figs.

Afferent vessels: These nodes receive lymphatic drainage from the anterior dia- phragmatic nodes, anterosuperior portions of the liver, medial part of the breasts, and deeper structures of the anterior chest and upper anterior abdominal wall. Efferent vessels: May empty into the right lymphatic duct, the thoracic duct, or the inferior deep cervical nodes [19]. Malignant Causes of Enlargement One of the commonest causes of internal mammary lymph node enlargement is breast cancer.

In a study on patients undergoing free flap breast reconstruction, 43 patients had internal mammary lymph node sampling and six patients had positive lymph nodes [20]. Posterior Intercostal Nodes These nodes are located near the heads and necks of the posterior ribs. Afferent vessels: They receive lymphatic drainage from the posterolateral inter- costal spaces, posterolateral breasts, parietal pleura, vertebrae, and spinal muscles. Efferent vessels: From the upper intercostal spaces end in the thoracic duct on the left, and in one of the lymphatic ducts on the right.

Those from the lower four to seven intercostal spaces unite to form a common trunk, which empties into the tho- racic duct or cisterna chyli [19]. They communicate with posterior mediastinal lymph nodes and the posterior intercostal nodes, and similarly drain to the right lymphatic duct or thoracic duct [19].

Diaphragmatic Nodes They are located on or just above the thoracic surface of the diaphragm and are divided into three groups [21]. Chest Wall Nodes 53 Anterior Pre-pericardial or Cardiophrenic Group These are located anterior to the pericardium, posterior to the xiphoid process, and in the right and left cardiophrenic fat see Figs.

Afferent vessels: From the anterior part of the diaphragm and its pleura, and the anterosuperior portion of the liver. Efferent vessels: They drain to the internal mammary nodes alongside the xiphoid and can provide a route for retrograde spread of breast cancer to the liver via lymphatics of the rectus abdominis muscle when the upper internal thoracic trunks are blocked. Middle Juxtaphrenic or Lateral Group This group receives lymph from the central diaphragm and from the convex surface of the liver on the right.

Posterior Retrocrural Group These nodes lie behind diaphragmatic crura and anterior to the spine. Afferent vessels: Lymph from the posterior part of the diaphragm. Efferent vessels: They communicate with the posterior mediastinal and para- aortic nodes in the upper abdomen. Figure 2. The color coding is also depicted on Fig.

Lymph node mapping and curability at various levels of metastasis in resected lung cancer. J Thorac Cardiovasc Surg. Regional lymph node classification for lung cancer staging. The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer.

J Thorac Oncol. Improving specificity of computed tomography in diagnosis of malignant mediastinal lymph nodes. J Comput Tomogr. T1 lung cancer: prevalence of mediastinal nodal metastases and diagnostic accuracy of CT. References 57 6. T1N0M0 lung cancer: evaluation with CT. Pattern of lymph node metastases in patients with squamous cell carcinoma of the thoracic esophagus who underwent three-field lymphadenectomy. Eur Surg Res.

Hodgkin disease: contributions of chest CT in the initial staging evaluation. Castellino RA. The non-Hodgkin lymphomas: practical concepts for the diagnostic radiolo- gist. Intrathoracic lymph node metastases from extrathoracic neoplasms.

Mediastinal metastases of infradiaphragmatic malignancies. Eur J Radiol. Mediastinal lymph node metastases from gastrointesti- nal carcinoma. Intrathoracic lymph node metastases from extrathoracic carcinoma: the place for surgery.

Ann Thorac Surg. Anatomical bases for the radiological delinea- tion of lymph node areas. Major collecting trunks, head and neck. Radiother Oncol. Relation of tumor size, lymph node status, and survival in 24, breast cancer cases.

Metastatic basal cell carcinoma presenting as unilateral axillary lymphadenopathy: report of a case and review of the literature. Dermatol Surg. Ovarian carcinoma initially presenting as meta- static axillary lymphadenopathy. Gynecol Oncol. Suwatanapongched T, Gierada DS.

CT of thoracic lymph nodes. Part I: anatomy and drainage. Br J Radiol. An evaluation of incidental metastases to internal mammary lymph nodes detected during microvascular abdominal free flap breast reconstruc- tion. J Plast Reconstr Aesthet Surg. Superior diaphragmatic lymph nodes: CT assessment.

J Comput Assist Tomogr. Abdominal Lymph Node Anatomy 3 Lymph node metastasis is frequently seen in most primary abdominal malignant tumors. The tumor cells enter lymphatic vessels and travel to the lymph nodes along lymphatic drainage pathways. The lymphatic vessels and lymph nodes generally accompany the blood vessels supplying or draining the organs. They are all located in the subperitoneal space within the ligaments, mesentery, mesocolon, and extra peritoneum.

Metastasis to the lymph nodes generally follows the nodal station in a stepwise direction—i. The key to understanding the pathways of lymphatic drainage of each individual organ is to understand the ligamentous, mesenteric, and peritoneal attach- ments and the vascular supply of that organ [1].

The benefits of understanding the pathways of lymphatic drainage of each indi- vidual organ are threefold. First, when the site of the primary tumor is known, it allows identification of the expected first landing site for nodal metastases by fol- lowing the vascular supply to that organ [2, 3]. Second, when the primary site of tumor is not clinically known, identifying abnormal nodes in certain locations allows tracking the arterial supply or venous drainage in that region to the primary organ.

Third, it also allows identification of the expected site of recurrent disease or nodal metastasis or the pattern of disease progression after treatment by looking at the nodal station beyond the treated site.

The location of drainage pattern of abdom- inal lymphatics is outlined in Table 3. The accuracy for characterizing malignant lymph nodes based on size criteria Table 3.

Normal-sized lymph nodes can be malignant and enlarged lymph nodes can be nonmalignant see Fig. Harisinghani, ed. Lymph node metastases LNM are rare and generally associated with poor prog- nosis in hepatocellular carcinoma see Fig. The median survival time of patients with single and multiple LNM after surgery was 52 and 14 months, respectively [13]. Table 3. There are several potential pathways for tumor spread, including superficial and deep pathways, below and above the diaphragm.

The superficial lymphatic network see Fig. The drainage of superficial lymphatics can be classified into three major groups: 1. Through the hepatoduodenal and gastrohepatic ligament pathway, it is the most common distribution of lymph node metastasis. The diaphragmatic lymphatic plexus is another important pathway of drainage because a large portion of the liver is in contact with the diaphragm either directly at the bare area or indirectly through the coronary and triangular ligaments.

However, nodal metastasis through this pathway is often overlooked. The anterior diaphragmatic nodes consist of the lateral anterior diaphragmatic group and the medial group, which includes the pericardiac nodes and the subxiphoid nodes behind the xiphoid cartilage.

The nodes in the falciform ligament drain into the anterior abdominal wall along the superficial epigastric and deep epigastric lymph nodes. The epigastric and the subxiphoid nodes drain into the internal mammary nodes 3. The rare pathway for nodal metastasis is along the falciform ligament to the deep superior epigastric node in the anterior abdominal wall along the deep superior epigastric artery below the xiphoid cartilage.

The deep lymphatic network follows the portal veins, drains into the lymph nodes at the hilum of the liver, the hepatic lymph nodes, then to the nodes in the hepatoduo- denal ligament. The nodes in the hepatoduodenal ligament can be separated into two major chains: the hepatic artery chain and posterior periportal chain see Figs. The hepatic artery chain follows the common hepatic artery to the node at the celiac axis and then into the cisterna chyli.

The posterior periportal chain is located posterior to the portal vein in the hepatoduodenal ligament see Fig. Lymphatic Spread of Malignancies 65 a b Fig. The deep pathways follow the hepatic veins to the inferior vena cava nodes and the juxtaphrenic nodes that follow along the phrenic nerve. Tables 3. Long-term survival can be expected after selective lymphadenectomy, especially in patients with a single LNM. On the other hand, efficacy of selective lymphadenectomy for multiple LNM seemed equivocal due to its advanced and systemic nature of the disease [13].

Stomach Gastric cancer is the third most common gastrointestinal malignancy [7]. Lymph node metastasis in gastric cancer is common and the incidence increases with advanced stages of tumor invasion [14]. The lymphatic drainage of the stomach consists of intrinsic and extrinsic systems see Fig. These lymphatic vessels drain into the lymph nodes at nodal stations in the corresponding ligaments and drain into the central collecting nodes at the root of the celiac axis and the superior mesenteric artery [1].

The extent of nodal metastasis as defined by pathologic stag- ing on surgical specimens has been used as prognostic indicators based on the num- ber of positive nodes. Resection of these nodes is defined as D1 category see Fig. They include the left gastric, common hepatic, splenic artery, splenic hilum, proper hepatic, and celiac nodes. Resection of nodes in group 1 and group 2 is defined as D2 category. Group 1: 1 Right cardial nodes, 2 left cardial nodes, 3 nodes along the lesser curvature, 4 nodes along the greater curvature, 5 suprapyloric nodes, 6 infrapyloric nodes.

Group 2: 7 nodes along the left gastric artery, 8 nodes along the common hepatic artery, 9 nodes around the celiac axis, 10 nodes at the splenic hilus, 11 nodes along the splenic artery.

Resection of the three nodal groups and paraaortic nodes is defined as D3 category. Paraesophageal and Paracardiac Nodes The lymph from the distal esophagus and the cardiac orifice of the stomach drains to the paraesophageal lymph nodes around the esophagus above the diaphragm and the paracardiac nodes below the diaphragm. They can spread upward along the esophagus to the mediastinal lymph nodes and along the thoracic duct to the left or right supraclavicular nodes or downward along the esophageal branches of the left gastric artery to the left gastric nodes and the celiac nodes see Fig.

Nodal Metastases in the Gastrohepatic Ligament Tumors arising from the area of the stomach along the lesser curvature and the esophagogastric junction, supplied by the left gastric artery, generally metastasize to the lymph nodes in the gastrohepatic ligament see Fig. The primary nodal group group 1 consists of nodes along the left and right gastric artery anastomosis along the lesser curvature. Group 2 nodes include the nodes along the left gastric artery and vein in the gastropancreatic fold that drain toward the nodes at the celiac axis.

Tumors arising from the area of the stomach in the distribution of the right gastric artery along the lesser curvature of the gastric antrum drain into the perigas- tric nodes and the suprapyloric nodes near the pylorus group 1.

They then drain into the nodes at the common hepatic artery group 2 , from where the right gastric artery originates or the area where the right gastric vein drains into the portal vein.

From these nodes, drainage continues along the hepatic artery toward the celiac axis group 2. The node shows FDG activity on a PET scan curvature form the alternate drainage pathways for the tumors arising from this region. Less commonly they are involved in pancreatic cancer due to retrograde tumor extension from the celiac nodes [1]. Nodal Metastases in the Gastrosplenic Ligament Lymphatic drainage of tumors at the posterior wall and the greater curvature of the gastric fundus spreads to the perigastric nodes group 1 in the superior segment of the gastrosplenic ligament, then follows along the branches of the short gastric artery to the nodes at the hilum of the spleen group 2.

The tumors from the greater curvature of the body of the stomach also spread to the perigastric nodes group 1 and then advance along the left gastroepiploic vessels and drain into the lymph nodes in the splenic hilum group 2. From the splenic hilum, they may spread to the nodes along the splenic artery to the nodes at the celiac axis group 2. Nodal Metastases in the Gastrocolic Ligament Primary tumors involving the greater curvature of the antrum of the stomach in the distribution of the right gastroepiploic artery spread to the perigastric nodes group 1 accompanying the right gastroepiploic vessels that course along the greater curvature of the stomach.

They drain into the nodes at the gastrocolic trunk group 2 see Fig. From there, they may proceed to the celiac axis or the root of the superior mesenteric artery [1].

Inferior Phrenic Nodal Pathways Tumors involving the esophagogastric junction or the gastric cardia may invade the diaphragm as they penetrate beyond its wall. The lymphatic drainage of the perito- neal surface of the diaphragm is via the nodes along the inferior phrenic artery and veins that course along the left crus of the diaphragm toward the celiac axis or the left renal vein [1].

Small Intestine The three most common malignant tumors of the small intestine are lymphoma, ade- nocarcinoma, and carcinoid tumor. The path of regional nodal metastasis follows the vessels of the involved segment to the root of the superior mesentery artery SMA see Fig.

Colorectal 73 Table 3. Lymph node metas- tasis is rare in the tumors of the appendix. Generally, nodal metastasis follows the ileocolic vessels along the root of the mesentery to the origin of the SMA and the paraaortic region [1].

Colorectal Colorectal adenocarcinoma is the third most common cancer and the third most common cause of cancer deaths [7]. Lymph node metastasis is one of the most important prognostic factors in the TNM classification—defining the number of positive nodes in stepwise incremental groups—that correlates with poorer outcome Table 3. Accurate identification of abnormal lymph nodes is important as it aids in preoperative planning of the extent of surgery.

Patients with T1—T2 rectal tumors can be treated with resection alone. If there are nodal metasta- ses or if the tumor is T3 , neoadjuvant treatment is required. It also helps in identi- fying regions of possible recurrence in treated cases, in the clinical setting of increasing carcinoembryonic antigen levels [17—19]. Lymph from the wall of the large intestine and rectum drains into the lymph nodes accompanying the arteries and veins of the corresponding colon and rectum [19—21].

The nodes can be classified according to the location as follows see Fig. Caecum and ascending colon. The lymphatic drainage is via the epicolic nodes and the paracolic nodes, which are seen in proximity with the marginal vessels along the mesocolic side of the colon. From the paracolic nodes see Fig. Transverse colon. The lymphatic drainage is from the epicolic nodes and the paracolic nodes along the marginal vessels to the intermediate nodal group situ- ated along the middle colic vessels and then into the principal node at the root of the SMA see Fig.

Left side of colon and upper rectum. The lymphatic drainage is from the epicolic and the paracolic along the marginal vessels group to the intermediate mesocolic nodes including the left colic nodes, and then to the principal inferior mesenteric artery IMA nodes see Fig.

There are two different lymphatic pathways: one is along the superior hemorrhoidal vessels toward the mesorectum see Figs. Anal tumors usually spread to the superficial inguinal nodes and then to the deep inguinal nodes along the common femoral vessels. From here they ascend to the external iliac, common iliac, and paraaortic groups see Figs. A key pathologic characteristic in determining the stage of disease in colon can- cer is the status of the draining lymph nodes [22].

The criteria for distance between tumor and mesorectal fascia in case of T3 tumors, also applies for mesorectal nodes lying within the mesorectal fat see Fig. If lymph nodes are involved with tumor Stage III disease , 5-fluorouracil—based adjuvant therapy improves survival [23].

However, for node-negative disease stage II disease , the benefits of adjuvant chemotherapy are not well-established. MRI with the use of ultrasmall superparamagnetic iron oxide USPIO contrast agents has a promising role, however further evaluation in rectal cancer needs to be assessed [24]. Because of the nonspecificity on anatomic imaging, additional imag- ing studies and aspiration biopsy are frequently used to establish the diagnosis of metastatic disease before treatment decision.

Retroperitoneal Lymph Nodes Renal, Upper Urothelial, and Adrenal Malignancies Lymphatics draining the kidney are derived from three plexuses: one beneath the renal capsule, the second around the renal tubules, and the third in the perirenal fat. The lymphatic drainage for the proxi- mal ureters is to the paraaortic nodes in the region of the renal vessels and gonadal artery. The middle ureteral lymphatics drain to the common iliac nodes and the lower ureteral lymphatics to the external and internal iliac nodes.

All the iliac nodes drain to the paraaortic nodes, cisterna chyli, and predominantly the left supraclavicular nodes via the thoracic duct. The adrenal lymphatics drain to the paraaortic nodes [1]. Lymphatic Spread of Malignancies 81 a b Fig. Lymphatic spread of renal cell carcinomas RCC is initially to regional lymph nodes. These include nodes along the renal arteries from the renal hilum to the paraaortic nodes at this level see Fig.

Ten to fifteen percent of patients have regional nodal involvement without distant spread. Lymphatic spread may continue above or below the level of the renal hilum, with subse- quent spread to the cisterna chyli and to the left supraclavicular nodes via the thoracic duct.

Occasionally, there is spread from these nodes to the mediastinum and pulmonary hilar nodes [1]. Clustering of three or more nodes in the regional area is also suggestive of metastatic spread.

Urothelial Tumors Periureteral extension from ureteral transitional cell carcinoma TCC is sec- ondary to growth through the ureteral wall and involvement of the extensive lymphatic drainage. The sites of regional lymphatic spread are dependent on the location of the tumor. The paraaortic nodes are involved initially in the renal pelvic and upper ureteral tumors see Fig.

If the origin is from the middle ureter, metastases are to the common iliac nodes, whereas lower ureteral tumors involve the internal and external nodes initially. The iliac nodes drain into the para-aortic nodes. Lymphatics within the wall of the ureter allow for direct extension within the wall [1]. Adrenal Tumors Primary malignant tumors of the adrenal gland arise from the cortex as adrenocortical carcinomas or from the medulla as pheochromocytomas or in the spectrum of the neuroblastoma ganglioneuroma complex.

Most of these tumors spread by lymphatic spread to the para-aortic lymph nodes [1]. Pancreatic Cancer Pancreatic cancer is the second most common gastrointestinal malignancy and is the fifth leading cause of cancer-related death. Up to two thirds may be located in the head of the pancreas. Lymph node metastases are common in pancre- atic and duodenal cancer and they carry a poor prognosis [31, 32].

Lymphatic Spread and Nodal Metastasis 83 Lymphatic Spread and Nodal Metastasis Lymphatic drainage of the head of the pancreas is different from that of the body and tail Table 3.

For practical purposes a prediction assay Gerberick et al. It is that issue E-mail: catherine. Poole, Dorset, UK and were formulated in acetone.

In order to exclude Dosing solutions were prepared volumetrically and imme- dead cells, a separate aliquot of cells from each treatment diately prior to each treatment. A mini- Mice were treated using the exposure regimen of the mum of 10 live lymphocytes, as determined by standard local lymph node assay LLNA as described propidium iodide dye exclusion, was acquired and the previously Kimber and Basketter, ; Kimber et al.

Treat- ments were performed daily for 3 consecutive days. The cells were collected and washed once among draining lymph node cells LNC from vehicle in RPMI growth medium Invitrogen, Renfrewshire, acetone treated control mice.

There was little inter- treatment group basis using trypan blue exclusion and experimental variation in lymph node cellularity, with a haemocytometer. Table 1. In both instances topical exposure to the vehicle acetone acetone was used as the vehicle. Marked increases in cellularity were observed following topical 1 3.

In these two experiments the 4 3. Nevertheless, in each Mean 3. In contrast, treatment ears daily for 3 consecutive days. Five days following the initiation of treat- with BZC, despite stimulating marked lymph node acti- ment, auricular lymph nodes were excised, a single cell suspension prepared vation with respect to increased cellularity, caused in and the cellularity per lymph node determined by trypan blue exclusion.

Thus, for instance, in an earlier series of investi- some instances somewhat lower still. For the ured following exposure of mice to either 0. The Table 2. Five days following the ini- tiation of treatment, auricular lymph nodes were excised, a single cell suspension prepared and the cellularity per lymph node determined by trypan blue exclusion. Results from two independent experiments are shown.

It is with the choice of vehicle. Thus, tation of B data which is less reliant solely on fold decisions about the presence or absence of inherent sen- increases when so much reliance is placed on this sitising potential would be predicated on considerations metric in the LLNA. The primary rationale is that compared with the positive and negative controls.

Why there is that need is Table 3, a fold increase of 1. Examination of the local lymph node assay for use in contact sensitization risk ing lymph nodes. The murine local lymph node assay: a commentary on collaborative trials and new directions.

Food Chem. The local lymph node assay: past, present and future. Contact Derm. Toxicology 63 —



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