What is the role of desmin (immunohistochemical stain) in diagnosing spindle cell neoplasms?

Role of Desmin in Diagnosing Spindle Cell Neoplasms

Desmin serves as a critical immunohistochemical marker that primarily identifies smooth muscle and skeletal muscle differentiation in spindle cell neoplasms, but its diagnostic utility is limited by variable expression patterns and potential pitfalls that require interpretation within a comprehensive immunohistochemical panel.

Primary Diagnostic Applications

Muscle-Derived Tumors

• Desmin positivity strongly supports smooth muscle origin when evaluating spindle cell lesions, particularly in leiomyomas and leiomyosarcomas where positive staining occurs in 92-100% of normal muscle and 12 of 13 leiomyomas 1
• Leiomyosarcomas demonstrate desmin positivity in approximately 69% of cases (18 of 26), making it a useful but not definitive marker for smooth muscle differentiation 1
• True leiomyomas are characterized by positive staining for both smooth muscle actin and desmin, while being negative for CD117, CD34, and S-100 protein, distinguishing them from gastrointestinal stromal tumors (GISTs) 2

Rhabdomyosarcomas

• All rhabdomyosarcomas (31 of 31 cases) and rhabdomyomas (6 of 6 cases) demonstrate desmin positivity, making it highly sensitive for skeletal muscle differentiation 1
• In adult spindle cell rhabdomyosarcomas, desmin stains variably positive in all tested cases, though it should be combined with myf-4 and WT1 for definitive diagnosis 3

Critical Diagnostic Algorithm for Spindle Cell Neoplasms

When Evaluating GISTs vs. Myogenic Tumors

The diagnostic pathway follows this sequence 2:

1. First-line markers: KIT (CD117) and DOG1 for GIST identification

   • If KIT positive → likely GIST (95% sensitivity)
   • If KIT negative → proceed to DOG1 staining

2. Second-line differentiation: When KIT/DOG1 are negative or equivocal

   • Desmin positive → suggests myogenic tumor (leiomyoma/leiomyosarcoma)
   • Desmin negative + S-100 positive → schwannoma
   • Desmin negative + S-100 negative → consider other diagnoses

3. Confirmatory panel: CD34 status helps further differentiate

   • CD34 positive + desmin positive → still favor myogenic tumor
   • CD34 positive + desmin negative → consider GIST or other mesenchymal tumors

Important Diagnostic Pitfalls

False Positive Scenarios

• Spindle cell lipomas can express desmin in 16% of cases (4 of 25), creating potential misdiagnosis as smooth muscle tumors 4
• Myofibroblasts in granulation tissue stain positive for desmin in 2 of 12 cases, and tumor-associated desmoplasia shows desmin positivity in 29 of 67 samples 1
• Benign spindle cell tumors rarely express desmin (1 of 42 cases), but 8 of 89 spindle cell sarcomas show positive staining, limiting specificity 1

False Negative Scenarios

• Approximately 31% of leiomyosarcomas (8 of 26 cases) are desmin-negative, requiring additional markers for diagnosis 1
• Skull base leiomyomas and angioleiomyomas often show negative or variable desmin staining, despite being smooth muscle tumors, though they typically stain positive for smooth muscle actin and vimentin 2

Enhanced Specificity with Complementary Markers

H-Caldesmon for Smooth Muscle Confirmation

• H-caldesmon provides superior specificity for smooth muscle differentiation compared to desmin, showing diffuse staining only in leiomyosarcomas (11 of 11 cases) 5
• Focal h-caldesmon staining (<1% of cells) occurs in only 3 of 26 malignant fibrous histiocytomas and 1 of 11 cellular cutaneous fibrous histiocytomas, demonstrating better discrimination than desmin alone 5
• When desmin is positive in a spindle cell tumor, add h-caldesmon to confirm true smooth muscle differentiation rather than myofibroblastic proliferation 5

Optimal Immunohistochemical Panel

For comprehensive evaluation of spindle cell neoplasms, the following panel is recommended 2:

• Primary markers: Desmin, smooth muscle actin, CD117, DOG1
• Confirmatory markers: CD34, S-100, h-caldesmon
• Additional markers when indicated: Myf-4 and WT1 for rhabdomyosarcoma, SDHB for wild-type GISTs

Technical Considerations

Fixation and Processing Requirements

• Pronase digestion before staining is essential for demonstrating desmin in tissues fixed in formalin, Zenker's, Bouin's, or B5 fixative 1
• Desmin staining is lost or significantly diminished in tissues fixed in absolute ethyl alcohol when pronase is used 1
• Without pronase digestion, positive staining is demonstrated only in alcohol-fixed tissue, creating potential for false-negative results 1

Specificity Limitations

Tumors Where Desmin Should Be Negative

Desmin is consistently negative in 1:

• All epithelia and epithelial tumors
• Normal mesenchymal tissue other than muscle
• Myoepithelial cells (despite their name)

Cross-Reactivity Concerns

• Desmin does not reliably distinguish between smooth muscle and skeletal muscle differentiation, requiring additional markers like fast myosin (though this is unreliable in adults) or myogenin/MyoD1 for skeletal muscle 3
• CD99 and WT1 positivity in rhabdomyosarcomas can create diagnostic confusion, as these markers are not traditionally associated with muscle tumors 3