What is the recommended treatment approach for a patient with a tumor that is forming an angle with the original tissue, suggesting potential malignancy and aggression?

Tumor Making an Angle with Original Tissue: Diagnostic and Management Approach

Immediate Diagnostic Imperative

A tumor forming an angle with the original tissue is a radiological sign suggesting malignancy and requires immediate referral to a specialized sarcoma reference center for core needle biopsy and multidisciplinary evaluation before any surgical intervention. 1

Why This Sign Matters

The angular relationship between tumor and native tissue indicates:

• Invasive growth pattern rather than expansile growth, which is characteristic of malignant tumors that infiltrate rather than displace surrounding structures 2
• Absence of a true capsule, as benign tumors typically show expansile growth with encapsulation and push adjacent tissues aside rather than invading at angles 2
• High likelihood of requiring wide surgical margins with adjuvant therapy rather than simple excision 1

Critical Referral Criteria

Refer immediately to a sarcoma reference center if the lesion demonstrates: 1

• Any unexplained deep soft tissue mass (regardless of size)
• Any superficial soft tissue lesion >5 cm diameter
• Any soft tissue mass in pediatric patients
• Radiological features suggesting invasive growth (such as angular relationship to tissue planes)

Diagnostic Workup at Reference Center

Imaging Protocol

MRI with contrast is the mandatory imaging modality for soft tissue tumors showing invasive characteristics: 1, 3

• MRI of the entire anatomical compartment including adjacent joints
• Provides critical information about tumor depth, size, relationship to neurovascular structures, and presence of necrosis (which helps estimate malignancy grade)
• Plain radiographs should be obtained first only to rule out bone tumors and detect calcifications 1

CT imaging is reserved for: 1

• Calcified lesions to rule out myositis ossificans
• Retroperitoneal tumors where performance equals MRI
• Staging chest CT to exclude pulmonary metastases (mandatory for all suspected sarcomas) 3, 4

Biopsy Technique - Critical to Avoid Contamination

Multiple core needle biopsies using ≥16G needles under imaging guidance are the standard approach: 1, 3, 4

• The biopsy must be performed by the surgeon who will perform definitive resection or by a radiologist member of the sarcoma team 1
• The biopsy tract must be planned so it can be completely excised during definitive surgery - this is non-negotiable as the tract is considered contaminated with tumor 1
• Mark the biopsy entrance point with tattoo or small incision for later identification 1
• Avoid necrotic areas by using imaging guidance 3

Excisional biopsy is contraindicated for lesions suspected to be aggressive or malignant, as excision without oncologically adequate margins contaminates multiple tissue compartments 1

Pathological Assessment Requirements

The pathologist must receive: 1

• Clinical/radiological context including tumor site and patient age
• Radiological differential diagnosis
• Fresh tissue fixed in 4% buffered formalin (never Bouin fixation as it prevents molecular analysis) 1

Pathology must determine: 1, 2

• Tumor type according to WHO classification
• Malignancy grade using FNCLCC grading system (based on differentiation, necrosis, and mitotic rate)
• Mitotic count independently reported
• Molecular pathology (FISH, RT-PCR) when clinical-pathological presentation is unusual 3

Treatment Algorithm Based on Findings

For Confirmed Malignant Sarcoma

Surgery is the cornerstone of curative treatment and must achieve wide excision with tumor-free margins (R0 resection): 3, 4

• En bloc wide excision or compartmental resection including the cutaneous scar and entire biopsy tract 3
• Aim for 1-2 cm margins where anatomically feasible 4
• Minimal margins acceptable only at resistant anatomic barriers (muscular fascia, periosteum, perineurium) if uninvolved 4
• Place surgical clips at periphery to guide subsequent radiotherapy planning 4

Adjuvant Radiation Therapy Indications

Adjuvant radiotherapy is strongly indicated for: 3, 5, 4

• High-grade tumors (G2-3)
• Deep location
• Size >5 cm diameter
• Any R1 (microscopically positive) or R2 (grossly positive) margins that cannot be re-excised

Dosing regimens: 3, 5, 4

• Preoperative radiotherapy (preferred): 50 Gy in 25 fractions over 5 weeks 5
• Postoperative radiotherapy: 50-60 Gy in 1.8-2 Gy fractions, with boosts up to 66 Gy depending on margin status 3, 5
• Hypofractionated alternative: 50 Gy in 20 fractions (2.5 Gy per fraction) 3, 4
• Boost doses: 16-18 Gy for R1 margins; 20-26 Gy for R2 margins 3, 4

Role of Chemotherapy

Adjuvant chemotherapy is not standard but may be considered in high-risk patients (G2-3, deep, >5 cm) after shared decision-making, as meta-analyses show statistically significant but limited survival benefit: 1, 4

• Doxorubicin-based regimens are most commonly used 3, 4
• Consider neoadjuvant chemotherapy if margins anticipated to be difficult 4

If Margins Are Inadequate

Re-operation is mandatory if R1 or R2 margins are obtained and functionally feasible, as positive margins significantly impact survival: 3, 4

• If adequate margins cannot be achieved without major morbidity, use multimodal therapy with radiation 1
• For truly unresectable tumors, definitive radiotherapy (66 Gy in 33 fractions) combined with chemotherapy is the alternative 5

Common Pitfalls to Avoid

Never perform excisional biopsy or unplanned excision of a lesion showing invasive characteristics - this contaminates tissue planes and compromises definitive surgery: 1

Never allow biopsy by non-sarcoma team members - improper biopsy tract placement is a leading cause of treatment failure: 1

Never delay referral for "observation" - tumors showing angular invasion require immediate evaluation as delay worsens prognosis: 1

Frozen section for immediate diagnosis is not encouraged when preoperative treatment is planned, as it does not allow complete diagnosis: 1

Surveillance Protocol Post-Treatment

Intensive follow-up is mandatory given high recurrence risk: 3, 4

• History and physical examination every 3 months for first 2-3 years
• MRI of resection site twice yearly for first 2-3 years, then annually
• Chest imaging (X-ray or CT) every 3-4 months for first 2-3 years, twice yearly up to 5 years, then annually
• Surgery for completely resectable lung metastases should be considered if they develop 3, 4