Are atypical spindle cell mesenchymal tumors benign or malignant?

Atypical Spindle Cell Mesenchymal Tumors: Malignant Potential Assessment

Atypical spindle cell mesenchymal tumors should be considered as having uncertain malignant potential and require comprehensive diagnostic evaluation to determine their biological behavior, as they can display features of both benign and malignant neoplasms. 1

Diagnostic Challenges

• Atypical spindle cell mesenchymal tumors represent a morphologically diverse group of rare lesions that bear striking resemblance to both benign and malignant entities, making their classification particularly challenging 1
• These tumors occur most frequently in children and young adults, but can also affect middle-aged or older adults 1
• The exact biological potential of these tumors is controversial, with some cases demonstrating unexpected lymph nodal metastasis during long-term follow-up despite initially appearing benign 1

Diagnostic Algorithm

Initial Histopathological Assessment

• Evaluate for concerning histological features associated with malignancy: 1
  • Architectural features: asymmetry, lack of circumscription, lack of maturation, ulceration
  • Cytological features: deep dermal mitosis, frequent mitosis, high-grade cytological atypia
  • Host response: brisk tumor-infiltrating lymphocytic infiltrates

Immunohistochemical Assessment

• Perform a set of immunohistochemistry assays to assess malignant potential: 1
  • Dual-color Ki67/MART-1 to identify deep dermal cell proliferation
  • p16Ink4a to detect complete loss of expression
  • HMB45 to identify complete loss of expression

Molecular/Cytogenetic Testing

• For cases with concerning histological or immunohistochemical features, perform: 1
  • Fluorescence in situ hybridization (FISH) with five probes (6p25, 8q24, 11q13, CEN9, and 9p21)
  • Array-based comparative genomic hybridization for comprehensive chromosomal evaluation

Malignant vs. Benign Features

Features Suggesting Malignancy

• Positive FISH for "melanoma pattern" of chromosomal aberrations 1
• Isolated homozygous loss of 9p21 1
• Isolated gain of 6p25 or gain of 11q13 1
• Complete loss of p16 expression 1
• Deep dermal cell proliferation by Ki67/MART-1 1
• Multiple high-risk histological features (asymmetry, deep dermal mitosis, high-grade atypia) 1

Features Suggesting Benign Behavior

• Retention of p16 expression 1
• Absence of chromosomal aberrations on FISH and array-based comparative genomic hybridization 1
• Well-circumscribed borders 1
• Absence of deep dermal mitotic activity 1

Management Approach

• Wide surgical excision with negative margins is the primary treatment of choice for all atypical spindle cell mesenchymal tumors 2
• In cases where wide excision would cause excessive morbidity, a more conservative approach may be considered, but with awareness of increased recurrence risk 2
• Adjuvant radiotherapy should be considered for positive or close surgical margins, tumors in locations where wide excision is not possible, or cases with adverse pathological features 2
• Follow-up should include clinical examination and imaging (typically MRI) of the primary site 2

Special Considerations

• Some atypical spindle cell mesenchymal tumors, like atypical spindle cell/pleomorphic lipomatous tumors (ASCPLT), have locally recurrent potential if incompletely excised but no risk for distant metastasis 3
• ASCPLT can undergo sarcomatous transformation, though the biological significance remains uncertain 3
• For atypical spindle cell lipomatous tumors, the risk of metastatic dissemination is minimal, but there is a non-negligible risk for local recurrence (approximately 13%) 4
• Patients with suspected bone sarcomas should be referred to a specialized sarcoma center before biopsy is performed 5

Common Pitfalls

• Misdiagnosis due to morphological similarity to other spindle cell neoplasms 6
• Inadequate sampling leading to missed areas of malignant transformation 1
• Failure to perform appropriate immunohistochemical and molecular studies 1
• Incomplete excision leading to local recurrence 4
• History of recent injury does not exclude the possibility of a malignant tumor and should not prevent appropriate diagnostic procedures 5