What is a Spindle Cell Neoplasm?
A spindle cell neoplasm is a morphologically diverse group of tumors characterized by elongated, spindle-shaped cells that can arise from various tissue lineages including smooth muscle, fibrous tissue, neural tissue, and other mesenchymal origins, ranging from benign to highly malignant entities. 1
Core Characteristics
Spindle cell neoplasms represent a diagnostically heterogeneous category that presents significant challenges for pathologists due to their overlapping morphologic features despite divergent cellular origins 2. These tumors are defined by their microscopic appearance of elongated cells with tapered ends, rather than by a single tissue of origin 1.
Key Morphologic Features
- Cellular architecture: Spindle-shaped cells arranged in various patterns including storiform (cartwheel-like), fascicular (parallel bundles), or whorled configurations 3, 1
- Nuclear characteristics: Variable from bland, uniform nuclei in benign lesions to marked atypia in malignant variants 3
- Stromal components: May include fibrous, myxoid, or mucinous backgrounds depending on tumor type 1
Classification by Tissue Origin
Smooth Muscle-Derived Tumors
Leiomyomas and angioleiomyomas are benign smooth muscle tumors showing spindle cells in whorled patterns without nuclear atypia, staining positive for smooth muscle actin and vimentin 1. The WHO recognizes these as distinct entities with angioleiomyomas further subclassified into solid, cavernous, and venous subtypes 1.
Fibrohistiocytic Tumors
Dermatofibrosarcoma protuberans (DFSP) is a dermal spindle cell neoplasm with bland cells arranged in storiform or fascicular patterns, typically CD34-positive and factor XIIIa-negative 3. This tumor demonstrates infiltrative growth with potential for local recurrence but rarely metastasizes unless fibrosarcomatous transformation occurs 3.
Atypical fibroxanthoma (AFX) is a low-grade cutaneous spindle cell tumor representing a superficial variant of pleomorphic dermal sarcoma, cured by excision in most cases with metastases in less than 1% 3.
Specialized Anatomic Sites
Renal spindle cell tumors include mucinous tubular and spindle cell carcinoma (MTSCC), a rare entity with intermixed tubules and spindle cells in mucinous stroma, occurring more frequently in women (M:F=1:3-4) and usually following an indolent course 1.
Thymic type A thymomas consist of neoplastic oval or spindle-shaped epithelial cells without atypia or lymphocytes, generally carrying favorable prognosis 1.
Breast spindle cell neoplasms include rare entities like secretory carcinoma with spindle to epithelioid cells, often harboring ETV6-NTRK3 fusion in over 90% of cases 4.
Diagnostic Approach
Essential Immunohistochemistry Panel
A comprehensive immunohistochemistry panel is mandatory for accurate diagnosis, including smooth muscle actin, vimentin, Ki67, CD34, desmin, S100 protein, and cytokeratins 1, 2. The College of American Pathologists recommends immunohistochemistry on all spindle cell neoplasms due to the critical importance of accurate diagnosis in guiding treatment 1.
Molecular Testing
For equivocal lesions, consider FISH, PCR, or conventional cytogenetics to detect characteristic translocations 3. DFSP characteristically shows t(17;22)(q22;q13) resulting in COL1A1::PDGFβ fusion 3. Emerging entities include NTRK-rearranged spindle cell neoplasms and those with EGFR mutations 5.
Malignancy Assessment
Critical features suggesting malignancy include: 6
- Architectural: asymmetry, lack of circumscription, ulceration
- Cytological: deep dermal mitosis, frequent mitoses (>5/10 HPF), high-grade atypia
- Molecular: complete loss of p16 expression, melanoma pattern chromosomal aberrations on FISH
Clinical Significance
Benign Spectrum
Benign spindle cell tumors like leiomyomas and spindle cell lipomas show well-circumscribed borders, absent deep dermal mitotic activity, and retention of p16 expression 1, 6, 7.
Intermediate/Locally Aggressive
DFSP demonstrates infiltrative growth requiring wide surgical margins but metastasizes rarely 3. Atypical spindle cell/pleomorphic lipomatous tumor (ASCPLT) shows local recurrence rates of 10-15% but no documented metastasis 7.
Malignant Variants
Spindle cell sarcomas of bone represent 2-5% of primary bone malignancies, presenting with pain and high fracture incidence, requiring multidisciplinary team management per European Society of Medical Oncology guidelines 1. Spindle cell rhabdomyosarcoma in adults carries poor prognosis with potential for rapid metastasis 8.
Angiosarcoma of the breast represents a particularly aggressive cutaneous spindle cell malignancy with high local relapse risk even with negative margins and high metastatic potential 3.
Common Diagnostic Pitfalls
- Mycobacterial spindle cell pseudotumor can mimic Kaposi's sarcoma and other spindle cell neoplasms, distinguished by acid-fast staining revealing mycobacteria 9
- Fibrosarcomatous transformation in DFSP shows transition to herringbone pattern with increased cellularity, atypia, mitoses (>5/10 HPF), and frequent CD34 loss, requiring referral to sarcoma centers 3
- Anaplastic thyroid carcinoma may show spindle cell morphology requiring discrimination from sarcoma, MTC, or metastatic disease through immunohistochemistry 3
Management Principles
All suspected spindle cell neoplasms require evaluation by pathologists with specific expertise in sarcoma/soft tissue pathology or dermatopathology 3. Patients with suspected bone sarcomas should be referred to specialized sarcoma centers before biopsy 6. Skin sarcomas require joint management between specialist skin cancer MDTs and sarcoma MDTs 3.