Causes of Unilateral Inguinal Lymphadenopathy in Adults
Unilateral inguinal lymphadenopathy in adults is most commonly caused by sexually transmitted infections (particularly lymphogranuloma venereum), malignancies (penile cancer, melanoma, gynecologic cancers), or localized infections of the lower extremity/perineum. 1, 2
Infectious Causes
Sexually Transmitted Infections (Most Common in Sexually Active Adults)
- Lymphogranuloma venereum (LGV) is the classic STI presenting with tender unilateral inguinal lymphadenopathy, caused by Chlamydia trachomatis serovars L1, L2, or L3 1
- LGV most frequently affects heterosexual men with unilateral tender inguinal/femoral lymphadenopathy, though women and MSM may present with proctocolitis 1
- The primary genital ulcer at inoculation site is often absent by the time patients seek care, making diagnosis challenging 1, 3
- LGV should be strongly considered in sexually active patients, particularly MSM and HIV-positive individuals, even without other symptoms 4, 3
Other Infectious Etiologies
- Tuberculosis can rarely cause isolated unilateral inguinal lymphadenitis, though bilateral presentation is more typical 5
- Yersinia pseudotuberculosis has been reported as a rare cause of unilateral inguinal lymphadenitis 6
- Localized skin/soft tissue infections of the lower extremity, perineum, or genitalia can cause reactive unilateral inguinal lymphadenopathy 2, 7
Malignant Causes (Critical to Exclude)
Primary Malignancies with Inguinal Drainage
- Penile squamous cell carcinoma is a major consideration, with lymph node involvement being the single greatest prognostic factor for survival 1, 2
- Melanoma of the lower extremity can metastasize to ipsilateral inguinal nodes 2, 7
- Vulvar/anal cancer in women should be considered in the differential 2, 7
- Lower extremity sarcoma may present with inguinal lymphadenopathy 2
- Lymphoma should be considered, particularly if B symptoms (fever, night sweats, weight loss) develop 2
Key Clinical Distinction
- 30-50% of palpable inguinal lymphadenopathy cases are inflammatory rather than malignant, so malignancy should not be assumed without tissue diagnosis 7, 8
- Size >3-4 cm is the strongest predictor of pathology and warrants aggressive diagnostic workup 2, 7
Inflammatory/Reactive Causes
- Foreign body granuloma from penile injection of petroleum jelly or other substances can cause unilateral inguinal lymphadenitis mimicking other pathology 9
- Reactive lymphadenopathy from any lower extremity or perineal inflammatory process 2, 7
Critical Diagnostic Algorithm
Initial Assessment Must Include:
- Examination of genitalia, perineum, lower extremities, and perianal region for primary lesions or infection sources 2, 7
- Documentation of node characteristics: size, number, mobility/fixation, consistency, and relationship to surrounding structures 2, 7
- Sexual history to assess STI risk, particularly for LGV 1, 4
- Assessment for constitutional symptoms suggesting malignancy or systemic infection 2, 7
Diagnostic Workup Priority:
- Fine-needle aspiration (FNA) is the mandatory first diagnostic step for nodes, with 91.7% sensitivity and 98.2% specificity for malignancy 2, 7, 8
- For nodes ≥4 cm, obtain CT abdomen/pelvis with IV contrast before or concurrent with FNA to assess extent and deeper involvement 2
- If FNA is negative but clinical suspicion remains high (heterogeneous appearance, persistent enlargement), proceed to excisional biopsy 7, 8
Common Pitfalls to Avoid
- Do not assume tenderness excludes malignancy—size is a stronger predictor than tenderness 2
- Do not proceed to immediate surgical excision without FNA, as this causes unnecessary morbidity and delays diagnosis 7
- Do not forget to screen for LGV in sexually active patients, as the primary genital lesion is often absent and diagnosis requires specific testing 1, 4
- Do not delay workup in patients with nodes >3 cm, as early diagnosis significantly impacts survival in malignant causes 1, 2