What is the relationship between a small round cell neoplasm and a right submandibular mass in a patient?

Relationship Between Small Round Cell Neoplasm and Right Submandibular Mass

Yes, a small round cell neoplasm can present as a right submandibular mass, most notably as desmoplastic small round cell tumor (DSRCT), which represents a rare but well-documented primary salivary gland malignancy requiring immediate recognition and aggressive multimodal treatment. 1, 2

Primary Diagnostic Consideration: DSRCT of the Submandibular Gland

DSRCT is the most critical small round cell neoplasm to consider when evaluating a submandibular mass, particularly in young adult patients (typically ages 20-40 years). 1, 2, 3 This highly aggressive malignancy, while classically arising in the abdomen and pelvis, has been documented in the submandibular gland in at least six reported cases. 3

Key Clinical Features

• Age and demographics: Predominantly affects young adults, with reported cases ranging from 24 to 41 years old 2, 3
• Presentation: Painless, unilateral submandibular mass 1
• Imaging characteristics: Hypoechoic mass on ultrasound in the submandibular region 1

Diagnostic Workup Algorithm

Step 1: Initial Tissue Sampling

Fine-needle aspiration (FNA) cytology should be performed first, which will demonstrate variably cohesive clusters of small cells with hyperchromatic nuclei and fine granular chromatin. 3 However, FNA alone is insufficient for definitive diagnosis.

Step 2: Histopathological Examination

Core biopsy or excisional biopsy is mandatory to reveal the characteristic morphology:

• Angulated nests or irregular islands of small round blue cells 2, 3
• Dense desmoplastic or fibromyxoid stroma 1, 2
• Medium-sized tumor cells with hyperchromatic nuclei and moderate cytoplasm 2
• Critical pitfall: Some cases may show large cellular islands with scanty stroma, mimicking conventional salivary gland carcinomas 2

Step 3: Immunohistochemical Panel

A polyphenotypic immunoprofile is pathognomonic for DSRCT and distinguishes it from other small round cell tumors: 4

• Cytokeratin (AE1/3): Positive 2, 3
• Desmin: Positive with characteristic paranuclear dot-like pattern 1, 2, 3
• WT-1: Nuclear positivity 1, 3
• Epithelial membrane antigen (EMA): Positive 3
• CD56: Positive 3
• Neuron-specific enolase: Positive 2

This combination of epithelial, mesenchymal, myogenic, and neural markers is highly specific. 1

Step 4: Molecular Confirmation

EWSR1 gene rearrangement detection by fluorescence in situ hybridization (FISH) is required for definitive diagnosis, with demonstration of the characteristic EWS-WT1 gene fusion by reverse transcriptase polymerase chain reaction providing confirmatory evidence. 1, 2, 3

Differential Diagnosis of Small Round Cell Tumors in Submandibular Region

The differential diagnosis is broad and requires systematic exclusion through immunohistochemistry: 4

Other Small Round Blue Cell Tumors to Consider:

• Merkel cell carcinoma: CK20+, TTF-1+, typically cutaneous origin 4
• Ewing sarcoma: CD99+, EWSR1 rearrangement (but different fusion partner than DSRCT) 5
• Rhabdomyosarcoma: Desmin+ but lacks cytokeratin and WT-1 positivity 4
• Lymphoma: CD45+, B-cell or T-cell markers positive 4
• Small cell carcinoma: TTF-1+ if lung origin, neuroendocrine markers positive 4
• Neuroblastoma: Chromogranin+, synaptophysin+, lacks epithelial markers 4

Benign Submandibular Lesions (Non-Small Round Cell):

• Granular cell tumor: S-100+, vimentin+, composed of large cells with granular cytoplasm (not small round cells) 6
• Oncocytoma: Large cells with abundant eosinophilic granular cytoplasm (not small round cells) 7

Treatment Approach

Comprehensive multimodal therapy is mandatory given the highly aggressive nature of DSRCT, with poor prognosis even with treatment. 1 The treatment protocol should include:

1. Complete surgical resection of the submandibular gland and tumor with negative margins 1, 2
2. Adjuvant chemotherapy as the primary systemic treatment modality 1
3. Radiotherapy as part of the comprehensive anti-tumor regimen 1

Critical Clinical Pitfalls

The most dangerous error is misdiagnosing DSRCT as a conventional salivary gland carcinoma based on morphology alone, which can occur when cellular islands predominate over desmoplastic stroma. 2 This leads to:

• Inadequate surgical margins
• Inappropriate chemotherapy regimens
• Delayed recognition of systemic disease potential

Always perform the complete immunohistochemical panel and molecular testing when encountering any poorly differentiated small cell neoplasm in the submandibular region, particularly in patients under 50 years of age. 1, 2, 3

Tissue preservation is critical: Order FISH for EWSR1 rearrangement at the time of initial biopsy to avoid repeat procedures. 1, 3