In an adult with unexplained chest tightness and a suspected smooth‑muscle tumor of the bronchial wall or mediastinum, what is the appropriate diagnostic work‑up and management for benign leiomyoma versus malignant leiomyosarcoma?

Diagnostic Work-Up and Management of Smooth Muscle Tumors in the Bronchial Wall or Mediastinum

In an adult with chest tightness and a suspected smooth muscle tumor of the bronchial wall or mediastinum, obtain tissue diagnosis via biopsy with immunohistochemistry (smooth muscle actin, desmin, h-caldesmon positive; CD117, DOG1, CD34 negative) before any definitive treatment, as distinguishing benign leiomyoma from malignant leiomyosarcoma is impossible by imaging alone and fundamentally alters management. 1

Initial Diagnostic Approach

Imaging Evaluation

• CT chest with contrast is the primary imaging modality to assess tumor size, margins, and relationship to adjacent structures 2
• MRI with diffusion-weighted imaging provides superior soft tissue characterization and may help assess malignant features, though it cannot definitively distinguish benign from malignant smooth muscle tumors 3
• Concerning imaging features suggesting malignancy include: larger size, irregular or indistinct margins, heterogeneous appearance, presence of necrosis or cystic spaces, and vascular involvement 2

Mandatory Tissue Diagnosis

• Pre-treatment biopsy is essential and should be performed before any surgical intervention to guide therapeutic decisions 4
• Core needle biopsy or bronchoscopic biopsy (if accessible) should be obtained 1
• Never proceed with resection based on imaging alone, as clinical and radiological criteria cannot reliably differentiate leiomyomas from leiomyosarcomas 4

Histopathologic Diagnostic Criteria

Immunohistochemical Panel (Required)

The diagnosis requires a comprehensive immunohistochemical panel to confirm smooth muscle differentiation and exclude other diagnoses 1:

• Positive markers for smooth muscle tumors:

  • Smooth muscle actin (nearly uniform positivity) 5
  • Desmin (usual positivity) 5
  • H-caldesmon (strongly recommended for confirmation) 6

• Negative markers (to exclude GIST):

  • CD117 (c-kit) must be negative 1
  • DOG1 must be negative (highly specific for GIST, even in CD117-negative cases) 1
  • CD34 should be negative (positive in 70-90% of GISTs) 1

• Additional markers to exclude other diagnoses:

  • S-100 negative (excludes neural tumors like schwannoma) 1

Distinguishing Benign from Malignant

Leiomyosarcoma criteria (any of the following suggest malignancy) 7:

• ≥5 mitoses per 10 high-power fields (most reliable indicator—all tumors with this degree of mitotic activity behave aggressively) 7
• Tumor cell necrosis (closely associated with aggressive behavior even when mitoses are infrequent; benign smooth muscle tumors rarely develop extensive necrosis) 7
• Cellular pleomorphism and atypia (when assessed together with size and cellularity) 7
• Large tumor size (generally >5 cm more concerning) 7

Leiomyoma features:

• Low mitotic activity (<5 mitoses per 10 HPF) 7
• Absence of tumor necrosis 7
• Minimal to no cellular atypia 7
• Well-circumscribed margins 2

Diagnostic Pitfalls

• Nearly 40% of leiomyosarcomas have fewer than 5 mitoses per 10 HPF, so absence of high mitotic activity does not guarantee benignity 7
• Smooth muscle tumor of uncertain malignant potential (STUMP) is a diagnosis used when neither leiomyoma nor leiomyosarcoma can be confidently diagnosed; this diagnosis shows remarkable inter-pathologist variation and may represent low-grade leiomyosarcoma 4
• Uterine criteria for leiomyosarcoma do NOT apply to non-uterine smooth muscle tumors—extrauterine sites require different thresholds 7

Management Algorithm

For Confirmed Benign Leiomyoma

• Complete surgical excision with negative margins is curative 5
• No adjuvant therapy required 5
• Routine surveillance not necessary after complete excision 5

For Confirmed Leiomyosarcoma

• En bloc complete surgical resection with negative margins is the primary treatment 4
• Refer to a sarcoma reference center for multidisciplinary management 1

Adjuvant therapy considerations:

• Adjuvant radiation therapy is NOT routinely recommended following complete resection, as it provides limited value and causes significant short- and long-term toxicities 4
• Radiation may be considered in selected high-risk cases (close/positive margins, local recurrence risk) after multidisciplinary discussion 4
• Adjuvant chemotherapy value is undetermined for localized disease; not standard practice 4

Metastatic/recurrent disease:

• Doxorubicin is the most active single agent for leiomyosarcoma 4
• Gemcitabine/docetaxel combination is an active regimen 4
• Other options include dacarbazine, ifosfamide, trabectedin, and pazopanib in stepwise fashion 4
• Surgery for isolated recurrences or metastases may be considered in selected cases with long disease-free intervals 4

For Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP)

• Complete surgical excision is recommended due to uncertain prognosis 4
• Close surveillance is mandatory given potential for malignant behavior 4
• Shared decision-making with informed patient regarding extent of resection 4

Critical Clinical Caveats

• Avoid any procedures causing tumor spillage (such as piecemeal resection or morcellation) when malignancy cannot be excluded, as this dramatically worsens prognosis if leiomyosarcoma is present 4, 3
• All cases should be referred to a sarcoma reference center for expert pathology review and multidisciplinary treatment planning 1
• Leiomyosarcomas have high local recurrence rates and metastatic potential, particularly to lungs 7
• EBV-associated smooth muscle tumors are a specific subcategory in immunosuppressed patients (AIDS, post-transplant) showing nuclear EBER positivity 5, 8