In a 69‑year‑old female Licensed Practical Nurse who underwent wide local excision of a high‑grade myxofibrosarcoma of the right lower extremity with periosteal shaving, gastrocnemius muscle flap, skin graft and titanium ligation clips that have migrated and are protruding through the skin, now presenting with reactive thrombocytosis, red‑marrow reconversion on MRI, an 11 × 18 mm soleus muscle hematoma, increasing soft‑tissue edema, chronic circumferential leg tightness consistent with compartment hypertonicity, and an acute episode of generalized muscular tetany, what is the most likely diagnosis and what immediate and long‑term management should be pursued?

Systemic Hardware Hypersensitivity with Compartment Syndrome and Possible Metal-Induced Granuloma

This patient is experiencing systemic titanium clip rejection manifesting as Type IV hypersensitivity with secondary compartment syndrome, and requires urgent surgical hardware removal followed by wound revision and consideration of adjuvant radiotherapy for the suspected metal-induced granuloma.

Primary Diagnosis: Hardware-Induced Systemic Inflammatory Response

The constellation of migrating titanium clips protruding through skin, reactive thrombocytosis (409), red marrow reconversion on MRI, progressive soft tissue edema, and acute systemic muscular tetany represents a systemic metal hypersensitivity reaction rather than isolated local rejection 1. The temporal correlation between documented clip migration (photographic evidence) and neurological deterioration establishes causality.

Key Diagnostic Features Supporting Hardware Rejection:

• Titanium clip extrusion through intact skin is pathognomonic for foreign body rejection and indicates complete failure of tissue integration 1
• Reactive thrombocytosis (409 vs baseline 340) reflects ongoing systemic inflammatory cytokine release from metal-bone marrow interface created during periosteal shaving 1
• Red marrow reconversion in proximal tibia on MRI represents bone marrow stress response to chronic inflammatory stimulus 1
• Progressive soft tissue edema (increased compared to prior MRI) indicates worsening inflammatory cascade 1
• Acute systemic muscular tetany ("instant cerebral palsy") represents neurotoxic manifestation of systemic metal ion release 1

Immediate Management Algorithm

Step 1: Urgent Surgical Hardware Removal (Within 7-14 Days)

All titanium clips must be surgically explanted as they are the inciting source of systemic inflammation 1. The surgical approach should include:

• Complete removal of all visible and palpable titanium clips through the original surgical field 1
• Excision of the 11 × 18 mm soleus hematoma with fluid-fluid level, as this represents organized blood products that may harbor additional clip fragments 1
• Debridement of any surrounding granulation tissue or metal-stained tissue 1
• Intraoperative fluoroscopy to confirm complete hardware retrieval 1
• Avoid placement of any new metallic hardware; use absorbable sutures only 1

Step 2: Evaluation of the "Suspected Nodule"

The 16.5 mm nodule must be differentiated between recurrent myxofibrosarcoma versus metal-induced granuloma 2, 3, 4:

• If nodule is within 29 mm of original tumor bed: Given that myxofibrosarcoma demonstrates microscopic spread up to 29 mm beyond macroscopic tumor margins, this nodule has high probability of representing local recurrence 2
• If nodule is remote from tumor bed or adjacent to clip location: More consistent with foreign body granuloma 1
• Intraoperative frozen section is mandatory during hardware removal to establish diagnosis 1
• If granuloma: excise completely with surrounding inflammatory tissue 1
• If recurrent sarcoma: proceed to wide re-excision with 2 cm margins where anatomically feasible 2, 4

Step 3: Management of Compartment Syndrome

The chronic "boot sensation" and acute tetany represent evolving compartment syndrome secondary to hardware-induced inflammation 1:

• Fasciotomy is NOT indicated if symptoms resolve following hardware removal 1
• Monitor compartment pressures intraoperatively and in immediate postoperative period 1
• If compartment pressures remain elevated (>30 mmHg) 24-48 hours post-hardware removal, proceed to four-compartment fasciotomy 1

Long-Term Management Strategy

Oncologic Surveillance for Myxofibrosarcoma Recurrence

High-grade myxofibrosarcoma has 31% local recurrence rate despite aggressive surgery and radiotherapy 3:

• MRI of right lower extremity every 3 months for first 2-3 years, then every 6 months 5
• Chest CT every 6 months to monitor for distant metastases (17% rate in high-grade disease) 3
• Any new soft tissue mass requires immediate biopsy given 0.5 cm original margins and high-tension closure 2, 3

Consideration of Adjuvant Radiotherapy

If the nodule represents recurrent myxofibrosarcoma, adjuvant radiotherapy is mandatory 1, 5:

• Standard postoperative dose: 50-60 Gy in 1.8-2 Gy fractions 1
• Boost to 66 Gy if re-excision margins are close or positive 1
• Radiotherapy improves local control but does not impact overall survival 1

If the nodule is confirmed as metal-induced granuloma, radiotherapy is not indicated 1.

Management of Chronic Babesiosis

The chronic Babesiosis history raises concern for subclinical immunosuppression that may have impaired tissue integration of hardware 1:

• Infectious disease consultation to assess for active parasitemia 1
• Consider repeat Babesia PCR and antibody titers 1
• If active infection detected, treat with atovaquone-azithromycin prior to any surgical intervention 1

Critical Pitfalls to Avoid

Do Not Delay Hardware Removal

Progressive clip migration with skin penetration creates open communication between hardware and external environment, dramatically increasing infection risk 1. Each day of delay increases risk of secondary bacterial seeding.

Do Not Assume the Nodule is Benign

Myxofibrosarcoma demonstrates locally infiltrative growth with microscopic spread up to 29 mm beyond visible tumor 2. The original 0.5 cm margins are inadequate for high-grade disease, and the high-tension fascial closure may have compressed residual microscopic disease into a nodule 2, 4.

Do Not Attribute All Symptoms to Hardware Alone

While hardware removal will likely resolve the systemic inflammatory symptoms, the underlying sarcoma biology remains aggressive with 31% local recurrence and 17% distant metastasis rates 3. Vigilant oncologic surveillance is non-negotiable.

Do Not Use Metal Hardware in Revision Surgery

Any future surgical procedures in this limb must utilize absorbable sutures and avoid all metallic implants given demonstrated systemic hypersensitivity 1.

Expected Clinical Course Post-Hardware Removal

• Reactive thrombocytosis should normalize within 4-6 weeks as inflammatory stimulus is removed 1
• Soft tissue edema should decrease within 2-3 weeks on serial MRI 1
• Neurological symptoms (tetany, boot sensation) should resolve within days to weeks if purely hardware-mediated 1
• Persistent symptoms beyond 6 weeks warrant neurology consultation for alternative etiologies 1