- Primary squamous cell carcinoma of the parotid gland (pSCCP):
- Is a rare, aggressive salivary gland malignancy diagnosed only by exclusion:
- After metastatic / secondary spread from a cutaneous or mucosal head and neck SCC, high-grade mucoepidermoid carcinoma, salivary duct carcinoma with squamous differentiation, and direct extension have all been ruled out
- It is a contested entity:
- Contemporary genomic data show that nearly all “parotid SCCs” carry a UV-induced mutational signature indicating cutaneous origin:
- So the great majority of cases coded as primary are in fact metastatic (mSCCP)
- Contemporary genomic data show that nearly all “parotid SCCs” carry a UV-induced mutational signature indicating cutaneous origin:
- Is a rare, aggressive salivary gland malignancy diagnosed only by exclusion:
- Definition and the diagnosis-of-exclusion problem
- True pSCCP is thought to arise from squamous metaplasia of excretory duct epithelium:
- By convention requires no evidence of any other primary squamous source
- True pSCCP is thought to arise from squamous metaplasia of excretory duct epithelium:
- pSCCP and mSCCP are histologically nearly identical:
- Every criterion proposed to favor a primary (e.g., ductal dysplasia) can also occur when metastatic tumor grows along preexisting ducts
- SCC differentiation can also be seen in genetically defined salivary carcinomas :
- NUT carcinoma, high-grade mucoepidermoid carcinoma, basal-type salivary duct carcinoma:
- Further narrowing the space for a “true” primary
- NUT carcinoma, high-grade mucoepidermoid carcinoma, basal-type salivary duct carcinoma:
- Epidemiology
- SCC accounts for roughly 0.3% to 1.5% of salivary gland tumors in classic series:
- Though registry data (which cannot distinguish primary from metastatic) label a much higher share:
- Up to ~ 23% of parotid cancers in one German national study, and ~ 2% of parotid neoplasms at a single institution after strict histologic review
- Registry-based incidence has risen (~ 0.87 to 2.0 per million in SEER over 42 years):
- Paralleling rising cutaneous SCC incidence and an aging population:
- Most likely reflecting misclassified metastatic disease
- Paralleling rising cutaneous SCC incidence and an aging population:
- The German registry found:
- SCC-type parotid cancer was strongly associated with a prior head and neck SCC (adjusted OR 5.48), median interval 365 days:
- Supporting frequent secondary origin
- SCC-type parotid cancer was strongly associated with a prior head and neck SCC (adjusted OR 5.48), median interval 365 days:
- Though registry data (which cannot distinguish primary from metastatic) label a much higher share:
- Typical patient:
- Elderly (7th decade)
- Male predominance:
- Roughly 2:1
- Presentation is often advanced, with a parotid mass, facial nerve dysfunction, and / or cervical nodes:
- The majority present at stage IV
- SCC accounts for roughly 0.3% to 1.5% of salivary gland tumors in classic series:
- Pathohistology and immunohistochemistry:
- Keratinizing to nonkeratinizing infiltrative squamous nests with intercellular bridges / keratinization:
- Keratinization is seen in ~1 in 6 metastatic SCC cases and is rare in the main mimics
- Squamous markers p40, p63, CK5/6 are positive:
- Mucicarmine should be negative:
- Positive mucin points to mucoepidermoid carcinoma
- Mucicarmine should be negative:
- Androgen receptor (AR) and / or HER2 positivity:
- Should raise salivary duct carcinoma with squamous differentiation rather than pSCCP:
- AR / CK7 expression does not exclude SDC
- Should raise salivary duct carcinoma with squamous differentiation rather than pSCCP:
- FNA differential includes:
- Warthin tumor (well-differentiated cases)
- High-grade mucoepidermoid carcinoma
- Salivary duct carcinoma
- UV-signature mutational analysis:
- Is now the most useful ancillary tool to establish cutaneous (metastatic) origin
- Keratinizing to nonkeratinizing infiltrative squamous nests with intercellular bridges / keratinization:
- Work-up:
- The NCCN Head and Neck Cancers guidelines outline evaluation of any parotid mass:
- Complete H&P with full head and neck exam (including mirror / fiberoptic exam), FNA biopsy, and, as clinically indicated, contrast CT / MRI from skull base to clavicle, chest CT, dental / nutrition / speech evaluation, and multidisciplinary consultation
- Because SCC histology mandates excluding a metastatic source:
- Workup should additionally include a thorough cutaneous exam of the face / scalp / ear (cutaneous SCC is the most common tumor to metastasize to the parotid), and an occult-primary / mucosal SCC evaluation when no skin primary is found:
- EUA, direct laryngoscopy, tonsillectomy, chest / abdomen / pelvis CT or FDG-PET/CT, with p16 / HPV and EBV testing
- Workup should additionally include a thorough cutaneous exam of the face / scalp / ear (cutaneous SCC is the most common tumor to metastasize to the parotid), and an occult-primary / mucosal SCC evaluation when no skin primary is found:
- FNA:
- Reliably distinguishes benign from malignant (sensitivity ~ 80%, specificity ~ 97%) and is highly accurate for high-grade cancers
- The NCCN Head and Neck Cancers guidelines outline evaluation of any parotid mass:
- Staging:
- Historically staged with the AJCC 8th edition (2017) TNM for major salivary glands
- T category is size / extraparenchymal-extension based:
- T1 ≤ 2 cm
- T2 > 2 to 4 cm
- T3 > 4 cm and / or extraparenchymal extension
- T4a skin / mandible / ear canal / facial nerve
- T4b skull base / pterygoid plates / carotid encasement)
- An important caveat:
- The newly published AJCC / UICC 9th edition (TNM9) creates a unified salivary-gland-specific system but explicitly excludes squamous cell carcinoma (along with neuroendocrine and basosquamous carcinoma) from salivary gland staging:
- Practically, parotid SCC is therefore staged using the head and neck cutaneous / mucosal SCC or cervical-node / unknown-primary frameworks rather than the salivary-gland schema
- The newly published AJCC / UICC 9th edition (TNM9) creates a unified salivary-gland-specific system but explicitly excludes squamous cell carcinoma (along with neuroendocrine and basosquamous carcinoma) from salivary gland staging:
- Management:
- No prospective trials exist; management is extrapolated from salivary gland and cutaneous / metastatic SCC guidelines and retrospective series
- The consistent message across data sets is that surgery is essential:
- Outcomes without resection are poor
- The core approach for resectable disease is:
- Total (at least superficial) parotidectomy + neck dissection + adjuvant radiotherapy
- Per NCCN for major salivary gland cancers:
- Primary treatment:
- Complete surgical resection, with neck dissection for high-grade and / or T3 to 4 tumors (or clinically N+ disease):
- The facial nerve is preserved when feasible
- Complete surgical resection, with neck dissection for high-grade and / or T3 to 4 tumors (or clinically N+ disease):
- Adjuvant therapy:
- Adjuvant RT is preferred for adverse features:
- High grade, close / positive margins, perineural / neural invasion, nodal metastases, lymphovascular invasion, or high-grade T3 to T4a tumors (SCC qualifies as high grade)
- Adjuvant RT is preferred for adverse features:
- –Unresectable / gross residual disease:
- Definitive RT, or concurrent systemic therapy / RT (category 2B)
- Primary treatment:
- ASCO guidelines:
- Recommend that for advanced (T3 to T4) or high-grade parotid cancers, at least a superficial parotidectomy with removal of additional at-risk parotid tissue be performed (given planned adjuvant RT):
- Balancing oncologic clearance against facial nerve risk:
- There are no data that more aggressive parotidectomy improves survival or locoregional control when adjuvant RT is used
- Balancing oncologic clearance against facial nerve risk:
- Recommend that for advanced (T3 to T4) or high-grade parotid cancers, at least a superficial parotidectomy with removal of additional at-risk parotid tissue be performed (given planned adjuvant RT):
- Prognosis:
- Uniformly aggressive regardless of primary-vs-metastatic classification
- Reported median survival is roughly 13 to 24 months, and 5-year overall survival does not exceed ~ 50%
- Larger tumor size, extraparenchymal extension, nodal metastases, distant metastases, and advanced age independently predict worse survival
- Recurrent disease carries a particularly poor prognosis (median ~14.5 months)
- Secondary (metastatic) parotid SCC has worse survival than true primary salivary cancers and higher rates of facial nerve sacrifice
- References:
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Rodrigo Arrangoiz MS, MD, FACS, FSSO 