Inguinal Metastases in Cutaneous Malignant Melanoma

Educational disclaimer. This article is a teaching case derived from a historical surgical case series. It is intended for medical education and does not constitute clinical advice for any specific patient. Management of cutaneous melanoma must be individualized, performed within a multidisciplinary team (surgical oncology, medical oncology, dermatology, radiation oncology, pathology), and guided by current society guidelines and local expertise.

Inguinal Metastases in Cutaneous Malignant Melanoma

Introduction

Surgical excision remains the cornerstone of treatment of the primary cutaneous melanoma. The modern role of regional lymph node surgery, however, has fundamentally changed since residency in the 1980s. In clinically node-negative patients, sentinel lymph node biopsy (SLNB) is now used to stage the regional nodal basin rather than to provide a survival benefit by elective dissection (Wong et al., 2018; NCCN v2.2025). In patients with a positive sentinel node, nodal ultrasound surveillance is now an evidence-based alternative to immediate completion lymph node dissection (Faries et al., 2017; Leiter et al., 2019). Therapeutic lymph node dissection (TLND) is reserved for clinically detectable nodal disease, and even in that setting, contemporary practice often begins with neoadjuvant immunotherapy (Patel et al., 2023; Blank et al., 2024). Systemic therapy is no longer reserved for distant disease only: adjuvant anti–PD-1 immunotherapy or adjuvant BRAF/MEK targeted therapy is now standard for resected stage IIB through IV melanoma (Long et al., 2022; Long et al., 2024; Amaral et al., 2025).

The case below describes the historical management of a bulky inguinal nodal recurrence eleven years after primary lower-limb melanoma excision, and the updated discussion summarizes contemporary principles of prognostication, regional nodal surgery, adjuvant and neoadjuvant systemic therapy, and management of advanced disease.

Case report

Eleven years prior to presentation, this 83-year-old female patient, M.H., had undergone excision of a left-foot malignant melanoma. Four years after surgery she developed a swelling in the left groin. The swelling progressively enlarged and became painful, accompanied by swelling of the left lower limb. She also admitted to weight loss. She was asthmatic and hypertensive, with hypertension controlled by oral medications.

Physical examination showed her to be anicteric, with a pulse rate of 80/min and blood pressure 160/100 mmHg. Heart sounds, chest, and abdomen were normal. In her left groin she had an erythematous, tender, 15 × 24 cm mass extending into the upper left thigh. Her left leg was edematous. A grafted site was seen over the medial aspect of the left ankle and foot.

Her investigations showed hemoglobin 10 gm/dL and a white-cell count of 7 × 10⁹/L. Serum urea, electrolytes, and creatinine were normal. Other investigations were:

Test Result Unit Test Result Unit
Gluc 6.3 mmol/L Prot 87 g/L
Albu 34 g/L Glob 53 g/L
Bili(T) 8 μmol/L ALK PHOS 68 IU/L
SGOT 13 IU/L GGT 24 IU/L

Chest X-ray showed an enlarged heart but clear lung fields. Abdominal ultrasonography did not detect intra-abdominal visceral or para-aortic lymph node metastases. Biopsy confirmed metastatic malignant melanoma in the left inguinal lymph nodes.

The patient had advanced melanoma 11 years after excision of the foot primary. She received prophylactic antibiotics and heparin and underwent palliative inguinal lymphadenectomy (Fig 1). The groin wound was left open to heal by secondary intention. She developed marked left lower-limb edema (Fig 2), treated with compression bandaging and elevation. At six-week outpatient follow-up, the groin wound was healing well, although limb edema persisted.
Fig 1: Mass of malignant inguinal
lymph nodes at lymphadenectomy
Fig 2: Lymphadenectomy wound healing by
secondary intention and markedly
edematous left lower limb

Modern equivalent. Today, this patient would undergo full systemic staging with whole-body PET-CT and brain MRI, BRAF mutation testing on the nodal biopsy, and multidisciplinary review (NCCN v2.2025; Amaral et al., 2025). Because she has macroscopic resectable nodal disease (current AJCC 8 clinical stage IIIB/C/D depending on N number and other features), the modern standard pathway for a fit patient would be neoadjuvant immunotherapy — ipilimumab + nivolumab in two cycles, per the NADINA trial (Blank et al., 2024), or pembrolizumab in three cycles, per SWOG S1801 (Patel et al., 2023) — followed by response-driven therapeutic lymph node dissection and tailored adjuvant systemic therapy. In a frail 83-year-old with comorbidities, the choice between this aggressive pathway and a primarily palliative approach (single-agent anti-PD-1 with selective palliative surgery for symptomatic bulk and lymphedema control) is individualized; her actual management then — symptom-directed palliative lymphadenectomy — remains a legitimate option in patients unfit for systemic immunotherapy or surgery with curative intent.

Discussion

1. Staging and prognostic factors

Cutaneous melanoma is now staged using the AJCC 8th Edition TNM staging system (effective 1 January 2018) (Gershenwald et al., 2017; AJCC 8th Edition slide deck). Stages range from 0 (in situ) through IA, IB, IIA, IIB, IIC, IIIA, IIIB, IIIC, IIID, to IV (distant metastatic). T-category cut-points are: T1 ≤ 1.0 mm (with T1a ≤ 0.8 mm non-ulcerated and T1b ≤ 0.8 mm ulcerated or 0.8–1.0 mm of any character); T2 1.01–2.0 mm; T3 2.01–4.0 mm; T4 > 4.0 mm. The historical thresholds of 1.5 mm and 3.5 mm used in earlier literature are no longer in use. Tumor mitotic rate, previously a T1 staging criterion in AJCC 7, was removed from T staging in AJCC 8, though it remains a recorded prognostic variable for risk-stratification tools.

Five-year melanoma-specific survival in AJCC 8 ranges from approximately 99% (stage IA) and 97% (stage IB) through 94% (IIA), 87% (IIB), 82% (IIC), 93% (IIIA), 83% (IIIB), 69% (IIIC), and 32% (IIID), to a historically much poorer figure for stage IV — although stage IV survival has been transformed in the immunotherapy era (Gershenwald et al., 2017; Wolchok et al., 2022).

Established adverse prognostic factors include increasing Breslow thickness, ulceration, higher mitotic rate, lymphovascular invasion, satellitosis or microsatellitosis, head-and-neck or acral location, male sex, older age, and elevated LDH in metastatic disease. Clark’s level of invasion is recorded but is of limited prognostic value once Breslow thickness, ulceration, and other adverse features are accounted for. Histopathologic subtype (superficial spreading, nodular, lentigo maligna, acral lentiginous) retains descriptive value but is less central to staging than in older literature.

2. Biopsy of the primary lesion

A suspicious pigmented lesion should be sampled by full-thickness excisional biopsy with narrow (1–3 mm) clinical margins, oriented to allow subsequent wide local excision and lymphatic mapping (NCCN v2.2025; Amaral et al., 2025). Incisional or punch biopsy is acceptable when excisional biopsy is impractical (e.g., facial, acral, or very large lesions). Shave biopsies should sample to a depth sufficient to obtain accurate Breslow thickness. The histopathology report should document Breslow thickness, ulceration, mitotic rate, growth phase, lymphovascular invasion, microsatellitosis, peripheral and deep margin status, and BRAF mutation status when stage III or IV disease is suspected.

3. Wide local excision and sentinel lymph node biopsy

Wide local excision is performed with margins guided by Breslow thickness — typically 0.5–1 cm for in situ/T1, 1 cm for T2, and 2 cm for T3/T4 — and tailored to anatomic constraints (NCCN v2.2025).

Sentinel lymph node biopsy has replaced elective lymph node dissection. It is recommended for clinically and radiologically node-negative patients with primary melanomas of Breslow ≥ 0.8 mm, or thinner lesions with ulceration or other adverse features (Wong et al., 2018; NCCN v2.2025). Preoperative lymphoscintigraphy with technetium-99m sulfur colloid, combined with intraoperative blue dye and gamma-probe localization, is the standard technique; hybrid radiotracer/dye approaches have the highest identification rate (Faulhaber et al., 2025). Histopathologic evaluation includes serial sectioning and S-100, HMB-45, and Melan-A immunohistochemistry to detect micrometastases.

4. Management of a positive sentinel lymph node

Two landmark randomized trials reshaped the management of patients with a positive SLN. MSLT-II (Faries et al., 2017) and DeCOG-SLT (Leiter et al., 2019) both showed that, for patients with SLN-positive disease, nodal ultrasound surveillance confers melanoma-specific survival equivalent to immediate completion lymph node dissection (CLND), at the cost of a modestly higher rate of nodal recurrence but substantially lower rates of lymphedema (≈ 6% vs ≈ 24% in MSLT-II) and other surgical morbidity. Long-term real-world outcomes confirm the feasibility of surveillance (Cheng et al., 2024, PMC11760195). Nodal ultrasound surveillance — typically every 4 months for the first 2 years, every 6 months for years 3–5, and then annually, paired with appropriate systemic staging — is now the preferred approach for the majority of SLN-positive patients. Completion lymph node dissection remains an option in specific scenarios (high-volume nodal disease on SLN, inability to comply with surveillance, anatomic considerations).

5. Therapeutic lymphadenectomy for clinically detectable nodal disease

For patients with clinically detectable nodal disease — palpable nodes or nodal disease found on imaging — therapeutic lymph node dissection (TLND) is still indicated for local disease control, although the surgical timing is now reframed by neoadjuvant immunotherapy (see Section 6). For the inguinal basin, the principles articulated in classic surgical texts remain relevant:

  • The incision is placed in the line of the groin crease; the limits of subcutaneous dissection are those of the femoral triangle, taken down to the adventitia of the femoral vessels. The segment of the great saphenous vein over the femoral triangle is excised.
  • The upper skin flap is elevated laterally to the anterior superior iliac spine and medially to about half the distance from the pubic tubercle to the umbilicus. The fat between Camper’s fascia and the external oblique aponeurosis is reflected inferiorly to meet the femoral triangle specimen at the inguinal ligament. Cloquet’s node is included in the excised block.
  • Whether to extend the dissection to the iliac and obturator nodes (ilio-inguinal dissection) is selective. When superficial inguinal nodes are pathologically positive, when Cloquet’s node is positive, when there is bulky clinical nodal disease, or when imaging shows pelvic adenopathy, ilio-inguinal dissection is added. When the deep pelvic nodes are involved, prognosis is poor and most patients harbor systemic disease (NCCN v2.2025).
  • Sartorius transposition over the femoral vessels, a closed-suction drain, and postoperative compression bandaging and limb elevation are standard.

In high-volume centers, video-endoscopic inguinal lymphadenectomy (VEIL) and robotic-assisted VEIL have been introduced as minimally invasive alternatives to open dissection, with comparable oncologic completeness and substantially lower wound complication rates (Postlewait et al., 2017; Sávio et al., 2020).

Morbidity of inguinal lymphadenectomy in modern series is dominated by lymphedema (20–50% in open series), wound dehiscence and infection (10–30%), seroma, and venous thromboembolism; chronic lymphedema commonly persists despite optimal compression therapy. These rates are substantially higher than the 12–15% figures cited in earlier series and are a major reason for the shift toward nodal surveillance after positive SLN (Faries et al., 2017).

6. Neoadjuvant immunotherapy for macroscopic stage III disease

For patients with resectable macroscopic stage III melanoma, neoadjuvant immunotherapy is now a new standard of care:

  • SWOG S1801 (Patel et al., 2023) randomized 313 patients with resectable stage IIIB–IV melanoma to three cycles of neoadjuvant pembrolizumab followed by surgery and 15 cycles of adjuvant pembrolizumab versus 18 cycles of adjuvant pembrolizumab alone. Event-free survival was significantly improved with the neoadjuvant-and-adjuvant strategy (2-year EFS 72% vs 49%; HR 0.58).
  • NADINA (Blank et al., 2024; OncLive coverage, 2025) randomized 423 patients with resectable macroscopic stage III melanoma to two cycles of neoadjuvant ipilimumab + nivolumab followed by therapeutic lymph node dissection and response-driven adjuvant therapy, versus immediate TLND followed by 12 cycles of adjuvant nivolumab. Event-free survival was significantly improved with the neoadjuvant arm (12-month EFS 83.7% vs 57.2%; HR 0.32). The “major pathological response”–adapted approach allows many patients to avoid prolonged adjuvant therapy.

Neoadjuvant ipilimumab + nivolumab is now a preferred option in fit patients with macroscopic stage III melanoma (NCCN v2.2025; Amaral et al., 2025).

7. Adjuvant systemic therapy

For resected high-risk melanoma, adjuvant systemic therapy now provides a clinically meaningful reduction in recurrence and, in some settings, in mortality:

  • Adjuvant pembrolizumab is approved for resected stage IIB, IIC, and III–IV melanoma based on KEYNOTE-716 (Long et al., 2022; long-term update, Long et al., 2024) and KEYNOTE-054.
  • Adjuvant nivolumab is approved for resected stage IIB, IIC, III, and IV melanoma based on CheckMate 238 (stage III/IV) and CheckMate 76K (stage IIB/C).
  • Adjuvant dabrafenib + trametinib is approved for resected stage III BRAF V600E or V600K-mutant melanoma based on COMBI-AD, with long-term follow-up demonstrating an approximately 20% reduction in death versus placebo (Long et al., ASCO 2024 LBA9500; Dummer et al., 2020).

Choice between adjuvant anti-PD-1 and adjuvant BRAF/MEK in BRAF-mutant resected stage III disease is individualized based on toxicity profile, comorbidity, and patient preference. Adjuvant non-specific immunotherapy with BCG, Corynebacterium parvum, viral lysates, or transfer factors is no longer used in modern practice.

8. Management of advanced (stage IV) melanoma

Survival in stage IV melanoma has been transformed in the era of checkpoint inhibitors and BRAF/MEK targeted therapy. First-line options for unresectable or metastatic cutaneous melanoma include:

  • Anti–PD-1 monotherapy (nivolumab or pembrolizumab).
  • Nivolumab + ipilimumab combination immunotherapy — highest response rate and durable benefit at the cost of higher immune-related adverse events; in CheckMate 067, median overall survival exceeded 6 years and 5-year overall survival was 52% with the combination versus 44% with nivolumab and 26% with ipilimumab (Wolchok et al., 2022).
  • Nivolumab + relatlimab (anti-LAG-3 + anti-PD-1).
  • BRAF + MEK inhibitor combinations (dabrafenib + trametinib, encorafenib + binimetinib, vemurafenib + cobimetinib) for BRAF V600-mutant disease.

Selected patients benefit from focal therapies (stereotactic radiosurgery for limited brain metastases, palliative radiotherapy for symptomatic bone or visceral metastases, palliative resection for symptomatic, accessible disease), oncolytic immunotherapy (talimogene laherparepvec) for in-transit and selected nodal disease, and isolated limb infusion (ILI) or hyperthermic isolated limb perfusion (HILP) for unresectable in-transit metastatic disease confined to a limb — the modern indication for limb perfusion. The historical view that active treatment of metastatic melanoma is futile in asymptomatic, elderly, or visceral-disease patients no longer reflects standard of care; performance status, comorbidity, and patient preference — not age alone — govern treatment decisions.

9. Surveillance and follow-up

Modern surveillance is risk-stratified by AJCC 8 stage and combines clinical examination of the skin and regional nodes with imaging (CT chest/abdomen/pelvis or PET-CT and brain MRI for high-risk disease) and, for SLN-positive patients on observation, regional nodal duplex ultrasound. Typical schedules call for clinical assessment every 3–6 months for the first 2–3 years, every 6–12 months through year 5, and annually thereafter; high-risk patients require more intensive imaging schedules (NCCN v2.2025; Amaral et al., 2025). Lifelong total-body skin examination is recommended to detect second primary melanomas.

Conclusion

Management of cutaneous melanoma has been fundamentally redefined since the turn of the century. Contemporary care relies on the AJCC 8th Edition staging system; sentinel lymph node biopsy in place of elective lymph node dissection for clinically node-negative T1b–T4 disease; nodal ultrasound surveillance in place of completion lymph node dissection in most SLN-positive patients; therapeutic lymph node dissection (often after neoadjuvant immunotherapy) for clinically detectable nodal disease; adjuvant anti-PD-1 immunotherapy or adjuvant BRAF/MEK targeted therapy for resected stage IIB–IV melanoma; neoadjuvant ipilimumab + nivolumab or pembrolizumab as a new standard for macroscopic stage III disease; and durable, life-prolonging checkpoint inhibitor or BRAF/MEK combinations for stage IV disease. Open inguinal and ilio-inguinal lymphadenectomy retains a central role for bulky regional disease, but minimally invasive video-endoscopic inguinal lymphadenectomy reduces wound morbidity in selected patients. Palliative resection — as performed in the historical case — remains an appropriate option for frail patients with symptomatic, bulky disease who are unsuitable for or unwilling to undergo modern systemic therapy.

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