This presentation examines the lymphatic dissemination patterns of various neoplasms, including hepatobiliary, gastrointestinal, urological, gynecological, neuroendocrine tumors, lymphoma, melanoma, gastrointestinal stromal tumors (GIST), and sarcomas, utilizing PET/CT, CT, and MRI imaging techniques.

Classification of Lymph Node Metastases:

1. Locoregional Metastases (N): Nodes near the primary tumor within direct lymphatic drainage, considered a local tumor extension. Specific nodal chains depend on tumor location. These nodes are seen as an extension of the tumor and typically involve specific nodal chains, depending on the tumor's location. For example, celiac nodes are associated with gastric cancer, while iliac nodes are connected to gynecological tumors [1,2].
2. Distant Metastases (M): This refers to the involvement of lymph nodes outside the established regional territory, indicating that cancer has spread beyond the initial nodal chains. For instance, in the case of testicular cancer, the spread to lumboaortic nodes is classified as locoregional. However, when the supraclavicular Virchow node is involved, it is considered metastatic, a situation that rarely occurs without previous involvement of the lumboaortic nodes. [3,4].

Typical and Unusual Patterns:

Lymphatic spread differs by tumor type and location, exhibiting clear patterns and some notable exceptions.

1. Typical Patterns: Spread occurs sequentially within the tumor's lymphatic territory, following a sequential order that adheres to the afferent and efferent vessels within the tumoral territory.
2. Unusual Patterns: Lymph nodes may be found in unusual locations due to lymphatic spread from the metastases of a primary tumor or its extension to nearby tissues, ultimately affecting non-regional nodes. For example, an abdominal tumor can cause hilar pulmonary adenopathy if there are lung hematogenous metastases, or prostate cancer invading the rectum can exhibit lymphatic spread similar to rectal cancer.

Patterns of Neoplastic Dissemination

The primary neoplasm will be represented by a blue arrowhead, locoregional metastases by red arrows, and distant metastases by yellow arrows to clarify lymphatic pathways.

1. Esophagus: Regional nodes extend from the lower cervical region to the celiac trunk. All of these nodes are considered regional, regardless of the location of the primary tumor. 

Fig 2: (A) Small node near the celiac trunk. (B) Neoplastic thickening of the middle thoracic esophagus with regional lymph nodes. (C) Periesophageal lymph nodes in the cervical esophagus. (D) Small right peri-esophageal lymph node.

2. Stomach: Regional lymph nodes include perigastric nodes (12 stations) across the ligaments and adjacent to the vessels [1,2].

Fig 3: (A) Tumor of the lesser curvature with regional celiac involvement. (B) Ulcerated tumor of the greater curvature with perigastric nodes in the greater omentum. (C) Hepatoduodenal (regional) and paraaortic (metastatic) nodes. (D) Retroperitoneal nodes below the SMA.

3. Rectum: Lymphatic regional drainage involves the mesorectum's superior, middle, and inferior rectal nodes. The inferior mesenteric axis is considered a regional area, which can appear relatively high on images and should not be mistaken for lumboaortic nodes, as those are metastatic [2,3]. Internal iliac nodes also indicate regional involvement.

Fig 4: (A) Mesorectal nodes, (B) Perirectal and internal iliac lymph nodes. (C) Inferior mesenteric nodes near IMA (D)Presacral inferior mesenteric nodes.

4. Colon: Lymphatic involvement aligns with the tumor's location. For example, ileocolic and middle colic lymph nodes are regional to a right colonic tumor, whereas left colic and inferior mesenteric nodes are regional to a descending colon tumor. Retroperitoneal, retrocrural, and lower cervical nodes are distant metastases.

Fig 5: (A) Ascending colon tumor with ileocolic nodes and (B) middle colic nodes. (C-E) Metastatic retroperitoneal and cervical nodes.

5. Melanoma: Since melanoma can develop in any location, it is essential to identify the specific regional drainage [3,5].

Fig 6: For instance, (A) leg melanomas drain to inguinal nodes, arm melanomas to axillary nodes, (B) skin lumbar tumors to inguinal nodes, (C) neck melanomas to cervical nodes, and (D) dorsal tumors to supraclavicular nodes. (E) When widely disseminated, melanoma can involve lymph nodes throughout the body due to lymphatic metastasis.

6. Renal: Renal cell carcinomas do not show a tendency to spread through the lymphatic system; their preferred route of dissemination is hematogenous, particularly to the lungs and bones, but they can also spread regionally through the renal hilum and lumboaortic nodes, other sites are considered metastatic.

Fig 7: (A) Regional spread may involve the renal hilum and lumboaortic nodes, while metastatic sites include (B) lung nodules and mediastinal lymph nodes. (C) Lymphatic spread is more typical of transitional cell tumors.

7. Prostate:Regional lymphatic involvement progresses systematically, starting from the iliac vessels and their branches upward (external iliac, internal iliac, obturator, and sacral chains[4].

Fig 8: (A) Regional lymphatic spread follows a systematic progression, starting from the iliac vessels and their branches (external iliac, internal iliac, obturator, and sacral chains) [4]. (B) Retroperitoneal and common iliac nodes are distant metastases. (C) Tumors contacting the Denonvilliers fascia may involve mesorectal and inferior mesenteric nodes, while anterior prostate cancers can spread to perivesical lymph nodes, emphasizing the need for accurate presurgical staging.

8. Bladder: Dissemination mirrors that of the prostate, involving the perivesical space and common iliac nodes as regional drainage.

Fig 9: (A) Neoplastic thickening with a regional prevesical node. (B) Internal iliac nodes.

9. “High” Pelvic Neoplasms: Cancers of the cervix, endometrium, ovary, fallopian tube, and peritoneum share regional spread patterns involving para-aortic, iliac, obturator, sacral, and parametrial nodes. Involvement of left lower cervical (IV group) nodes renders them unresectable. Para-aortic nodes above the renal veins (suprarenal) are considered distant metastases in some studies [5,6].

Fig 10: (A) Cervical cancer with bilateral iliac and retroperitoneal involvement. (B) Endometrial cancer with regional right iliac and retroperitoneal involvement. (C, D and E) Ovarian cancer with right iliac, retroperitoneal, and left lower cervical involvement (F) Endometrial cancer with bilateral iliac nodes.

10. “Low” Pelvic Neoplasms: Anal, vulvar, vaginal, penile, and scrotal cancers drain to inguinal nodes as regional sites. As midline neoplasms, they may show unilateral or bilateral lymph node involvement.

Fig 11: (A) Anal cancer with unilateral inguinal lymphadenopathy. (B) Anal cancer with bilateral inguinal, iliac and retroperitoneal lymphadenopathies. (C) Anal cancer with bilateral inguinal involvement. (D) Penile cancer with bilateral inguinal involvement. (E) Vulvar cancer with bilateral inguinal lymphadenopathies.

11. Testicular Cancer: Understanding lymphatic drainage via gonadal veins is essential, as it bypasses the iliac and inguinal nodes, directly affecting the retroperitoneum.

Fig 12: (A) Posterior mediastinal involvement is considered a distant disease. (B) Retroperitoneal regional involvement. (C) Metastatic lower cervical involvement.

12. Summary of retroperitoneal lymphatic dissemination. The retroperitoneal lymphatic dissemination pathways vary depending on the origin of the neoplasm.

Fig 13: Low pelvic neoplasms typically begin spreading through the inguinal lymph nodes and may progress upward. High pelvic neoplasms spread through the iliac lymph nodes as part of their regional drainage. In contrast, testicular cancer bypasses the inguinal and iliac nodes, disseminating directly from retroperitoneal lymph nodes to higher nodal chains in the abdomen and thorax.

13. Pancreas: Their primary location influences the local dissemination of tumors. Tumors in the head and neck show patterns similar to those in distal biliary structures, often involving the superior mesenteric vessels, portal vein, and bile duct. In contrast, tumors located in the body and tail of the pancreas are more likely to affect the perisplenic lymph nodes and surrounding blood vessels. Any node located retroperitoneally below the level of the superior mesenteric artery is classified as metastatic.

Fig 14: (A - C) Cancer of the pancreatic body and tail with regional lymph nodes and non-regional metastases. (D and E) Neoplasm of the pancreatic body with non-regional mesenteric nodes.

14. Gallbladder and Biliary Tract (Perihilar): Regional involvement varies by location, with the hepatic hilum nodes (including the hepatoduodenal and cystic duct nodes) being the most frequently affected.

Fig 15: (A and B) illustrate right intrahepatic cholangiocarcinoma with the involvement of regional hilum nodes. (C and D) depict gallbladder fundus cancer, which shows regional nodes in the hepatic hilum and non-regional retrocrural nodes.

15. Hepatocellular Carcinoma (HCC): The lymphatic spread of this cancer usually follows the hepatoduodenal ligament and can involve the inferior phrenic nodes located between the right diaphragmatic crura and the adrenal gland. In cases of hepatocellular carcinoma (HCC), regional lymphadenopathy can often be observed in the hepatic hilum.

Fig 16: Most of the affected lymph nodes appear hypervascular (A, B, C, D and E). Additionally, a hypervascular node is located anterior to the diaphragm that is not part of the regional lymphatics, as shown in image (F). In the case of pulmonary metastases depicted in image (G), hilar lymph nodes may also be involved, representing non-regional involvement.

16. Gastrointestinal Neuroendocrine Tumors: The lymphatic dissemination of these tumors is influenced by their origin, typically following a classic and orderly pattern. A key characteristic is the presence of classic mesenteric desmoplastic lymphatic involvement.

Fig 17: (A) In this case of a rectal neuroendocrine tumor, somatostatin receptor expression is observed along with the typical spread of rectal cancer involving the mesorectal and internal iliac lymph nodes. (B) A distal ileal neuroendocrine tumor can affect the ileocecal valve and is associated with regional ileocolic lymphadenopathy.

17. Lymphoma: Dissemination can occur anywhere in the body, following two patterns.

Fig 18: (A) In the first case, it is orderly, as seen in left tonsillar lymphoma that has spread to cervical lymph nodes. In contrast, the second case (B)demonstrates a disorganized spread, affecting axillary and inguinal lymph nodes, as well as a spleen lesion.

18. Tumors Without Lymphatic Predilection:

Fig 19: These tumors primarily spread through alternative routes rather than through the lymphatic system.