Carrie L. Fitzgerald, DO, MPH
James A. Brown, MD, FACS
BASICS
DESCRIPTION
• Enlarged nodal tissue in the pelvis and/or retroperitoneum
• Can be regional or generalized
• Definitions vary, but include solitary node ≥1–1.5 cm in short axis, any rounded node >8 mm or multiple nodes >1 cm (1).
• Pelvic lymph nodes (LNs) are generally considered abnormal if >1.3 cm.
• Often discovered incidentally or with imaging performed for tumor staging.
• Usually nonacute, but potentially life threatening.
EPIDEMIOLOGY
Incidence
• Lymphoma is the most frequent malignant tumor in the retroperitoneum. Non-Hodgkin lymphoma (93.7%) occurs more commonly than Hodgkin lymphoma (6.3%).
• Other common causes of retroperitoneal lymphadenopathy are malignancies, infections of retroperitoneal and pelvic organs and external genitalia.
Prevalence
No consistency in literature
RISK FACTORS
• Tumor-associated syndromes:
– Renal cancer:
von Hippel–Lindau (VHL)
Hereditary papillary renal carcinoma (HPRC)
Hereditary leiomyomatosis and renal cell cancer (HLRCC)
Birt–Hogg–Dube (BHD)
Hereditary paraganglioma and pheochromocytoma (HPP)
Tuberous sclerosis complex (TSC)
• Adrenal cancer:
– Gardner syndrome
– Beckwith–Wiedemann syndrome (associated with hemihypertrophy)
– Multiple endocrine neoplasia type 1
– SBLA syndrome (Sarcoma, Breast, Lung, Adrenal carcinoma)
– Li–Fraumeni syndrome
• Urothelial cancer
– Hereditary nonpolyposis colorectal cancer (HNPCC)
– Hereditary retinoblastoma
– Costello syndrome
– Possibly Apert syndrome
• Prostate cancer
– Hereditary breast and ovarian syndrome (HBOS)
• Patients with primary tumors of GI, GU, and GYN tracts and associated risk factors for these malignancies
• Smoking, age, family history, HPV
• Immunosuppression (HIV, autoimmune)
• Lymphadenitis seen with inflammatory/infectious conditions of the pelvis
Genetics
• Ureteral obstruction
• IVC compression +/– lower extremity edema
• DVT
• Await genetics consult for others
• VHL: 3p25-26
• HPRC: 7q31
• HLRCC: Long arm of chromosome 1
• BHD: 17p11.2
• Hereditary paraganglioma and pheochromocytoma (HPP)
• Tuberous sclerosis complex: TSC, TSC1, 9q34.13; TSC2, 16p13.3
PATHOPHYSIOLOGY
• Most adenopathy incidental; may be regional or generalized
• Usually one of five causes: Malignant, infectious, autoimmune, inflammatory (reactive), iatrogenic
ASSOCIATED CONDITIONS
See risk factors
GENERAL PREVENTION
Resolution of primary source
DIAGNOSIS
HISTORY
• Constitutional: Weight loss, night sweats (especially with lymphoma), fatigue, fever
• Local compressive symptoms: Bowel obstruction, hydronephrosis/pyelonephritis/uremia, lower limb edema (vascular/lymphatic compromise)
• Severe infection on perineum/pelvis may result in inguinal/pelvic adenopathy
• History of primary GU, GI, or GYN tumor
• Paraneoplastic syndromes (ie, breast tenderness, anemia, etc.)
• Immunocompromised states raise risk of mycobacterial infection, lymphoma, or Kaposi sarcoma
PHYSICAL EXAM
• Evaluate for peripheral lymphadenopathy (neck, supraclavicular, inguinal, axillary)
• Chest: Clear breath sounds, breast tissue, or tenderness
• Abdominal/pelvic exam: Meta/menorrhagia, palpable mass, bruits, thrills
• GU/GI exam: Testicular mass, right-sided varicocele, penile lesions, digital rectal exam (DRE), perineal cellulitis/abscess, fecal occult blood testing, hematuria, pelvic exam in females
• Skin: Rash, lesions (malignant, benign), ie, melanoma
• Lower extremity edema
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• CBC, ESR, exam of peripheral smear
• Creatinine (for imaging and to check renal function)
• Urinalysis for hematuria
• Urine cytology
• Tumor markers:
– PSA: Prostate cancer
– AFP, β-hCG, LDH: Testicular cancer
– CA-125: Ovarian cancer
– CEA: Colon cancer
Imaging
• May diagnose cause of adenopathy (ie, renal mass)
• Ultrasound: Can pick up larger masses; false-negatives are significant
• CT/MRI: More sensitive than US (1)[A]
– Nodes <7–10 mm considered reactive
– CT generally considered best; use MRI if contrast contraindicated
• PET: Evaluate fibrosis from metabolically active nodes, ie, postchemotherapy testicular cancer, seminoma (2); expanding role (3)
– Some studies show PET can define testicular relapse before CT.
• SPECT: Advances in lymphoscintigraphy have advanced opportunity for LN resection in select GU malignancies (1).
• Bipedal lymphangiography largely replaced by CT and MRI.
Diagnostic Procedures/Surgery
• Nodal tissue exam unless diagnosis is clear (ie, testicular or prostate tumor), then size or function and physiology becomes important (1).
• CT-guided biopsy best way to obtain nodal tissue.
– Not always feasible (ie, proximity to major vessels), open/laparoscopic in select cases
• CT/MRI or SPECT imaging
Pathologic Findings
Numerous, depends on cause (see below)
DIFFERENTIAL DIAGNOSIS
• Tumor
– Primary lymphatic: Lymphoma (non-Hodgkin, Hodgkin, others)
– Secondary: Adrenal, renal, urothelial and nonurothelial bladder or upper tract cancer, prostate, urethral, penile, germ cell, cervical, ovarian, uterine, GI (carcinoid, lymphomas), colorectal, melanoma, Kaposi sarcoma
• Infectious/inflammatory
– Granulomatous: TB, sarcoidosis, histoplasmosis, lymphogranuloma venereum, Castleman disease (angiofollicular LN hyperplasia associated with HIV and human herpesvirus 8 [HHV-8]).
– Nongranulomatous: Viral, bacterial (if abscess in local areas), sinus histiocytosis, retroperitoneal fibrosis
• Other: Neoplastic, non-neoplastic, and cystic retroperitoneal masses (lymphocele, urinoma, hemorrhage) aneurysms
TREATMENT
GENERAL MEASURES
• Wide variety, based on diagnosis of primary disease
• Image-guided needle biopsy, as a 1st-line investigation, is useful in the diagnosis of space-occupying lesions of the retroperitoneum
• Routine lymphadenectomy usually indicated for GU malignancy
MEDICATION
First Line
Based on diagnosis of primary disease
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Open or laparoscopic nodal sampling may be required in select cases
• Lymphadenectomy at time of organ-specific resection indicated in many cases of GU, GYN, and GI malignancy
ADDITIONAL TREATMENT
• Underlying cause must be treated appropriately
• Benign reactive lymphadenopathy can be seen in the presence of malignancy and improves with appropriate treatment
• Lymphadenectomy for malignant lymphadenopathy does not always affect overall survival (4).
Radiation Therapy
For certain causes such as seminoma
Additional Therapies
• In select cases, reimaging for signs of growth or assessing therapeutic response, eg, hormonal therapy for prostate cancer, antibiotics for penile cancer
• Notification of partners if HIV-positive (3)[A]
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
Widely variable
COMPLICATIONS
• Severe lymphadenopathy can result in lower extremity edema, varicocele
• Potential surgical complications of retroperitoneal lymphadenectomy include vascular injury, lymphocele, chylous ascites, ejaculatory dysfunction, and GI complications (pancreatitis, bowel injury/obstruction)
FOLLOW-UP
Patient Monitoring
Based on primary disease
Patient Resources
N/A
REFERENCES
1. Chernyak V. Novel imaging modalities for lymph node imaging in urologic oncology. Urol Clin North Am. 2011;38:471–81.
2. Becherer A. PET in testicular cancer. Methods Mol Biol. 2011;727:225–241.
3. Bouchelouche K, Oehr P. Recent developments in urologic oncology: Positron emission tomography molecular imaging. Curr Opin Oncol. 2008;20:321–326.
4. Bochner BH, Coleman JA, Carver BS, et al. Role of lymphadenectomy in genitourinary cancer. AUA Update Series. 2009;28:205–209.
ADDITIONAL READING
Chen L, Kuriakose P, Hawley RC, et al. Hematologic malignancies with primary retroperitoneal presentation: Clinicopathologic study of 32 cases. Arch Pathol Lab Med. 2005;129(5):655–660.
See Also (Topic, Algorithm, Media)
• Groin/Inguinal Mass
• Lymphadenopathy, Inguinal
• Lymphadenopathy, Pelvic and Retroperitoneal Images 
• Retroperitoneal Mass and Cysts
CODES
ICD9
• 202.80 Other malignant lymphomas, unspecified site, extranodal and solid organ sites
• 567.9 Unspecified peritonitis
• 785.6 Enlargement of lymph nodes
ICD10
• C85.90 Non-Hodgkin lymphoma, unspecified, unspecified site
• K65.9 Peritonitis, unspecified
• R59.0 Localized enlarged lymph nodes
CLINICAL/SURGICAL PEARLS
• General malignancies (testis, penile) have predictable lymphadenopathy pattern of spread.
• Pelvic organ malignancies may have skip lesions to the retroperitoneum.
• Lymphadenectomy may be curative for many urologic and nonurologic malignancies.
• Urinary, bowel, and vascular obstruction possible with advanced lymphadenopathy.
• Inflammatory and infectious conditions may lead to reactive lymphadenopathy.