Squamous Carcinoma of the Esophagus

Definition

• Malignant epithelial neoplasm of the esophagus demonstrating squamous differentiation

Alternate/historic names for spindle cell variant

• Carcinosarcoma
• Metaplastic carcinoma
• Polypoid carcinoma
• Pseudosarcomatous carcinoma
• Squamous cell carcinoma with spindled component

Diagnostic Criteria

• Most are conventional squamous carcinomas
• Defined based on cytologic atypia and invasion
• Small foci of glandular differentiation are permitted
• Lateral spread (intramucosal metastases) is common (11-16%)
• Second primary SCC is common (14-31%)
• 10% incidence of SCC at other sites also
• Variants (all are rare)
• Basaloid SCC
• Cohesive high grade poorly differentiated squamous carcinoma
• Usually has at least focal squamous differentiation
• High N/C ratio
• Scant amphophilic to basophilic cytoplasm
• High grade nuclei
• High mitotic rate, extensive apoptosis
• Coagulative necrosis common
• Well defined solid sheets, lobules and nests
• Frequent pseudoglandular and cribriform pattern
• No differentiated gland pattern
• Lacks the two cell type pattern of adenoid cystic carcinoma
• Alcian blue positive mesenchymal mucin in pseudoglandular spaces
• PAS/D+ hyaline basement membrane material may compress cells and cords
• Vascular invasion common, perineural invasion uncommon
• Most previously reported adenoid cystic carcinomas of the esophagus are probably basaloid squamous carcinomas
• Behavior not clearly different from SCC NOS
• Spindle cell squamous carcinoma
• SCC with a spindled/mesenchymal component
• SCC may be difficult to identify at edges of specimen or in situ
• Spindled/mesenchymal component highly variable
• May range from uniform and moderately atypical to resembling malignant fibrous histiocytoma
• May exhibit specific differentiation
• Osteosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyoblasts
• Epithelial markers detectable in about 50%
• High molecular weight keratin, p63 more sensitive
• Frequently polypoid (75%)
• 5 year survival not clearly different from SCC NOS
• Verrucous carcinoma
• Exophytic, warty surface
• Must have bland cytology and be well differentiated
• Invasion by smooth prongs of bland squamous cells
• Ragged infiltration not permitted
• Destroys adjacent tissues
• Typically very hard to diagnose histopathologically from biopsies
• Requires clinicopathologic correlation
• Metastases rare
• Adenosquamous
• Admixture of squamous and adenocarcinoma
• Mucoepidermoid
  • Squamoid cells (rarely overtly keratinizing), mucin positive cells and intermediate cells

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 11/29/09

Supplemental studies

Immunohistology

• Basaloid squamous carcinoma

  p63	Positive, usually extensive
  Keratin, including high molecular weight	Positive, varying reports on extent of staining
  S100	25% focal positive
  Actin, including smooth muscle	Negative (one report of 15% focal weak staining)
  p16	Usually negative

• Spindle cell squamous carcinoma (spindle cell component)

  p63	Positive, probably about 50%
  High molecular weight cytokeratin	Positive, probably about 50%
  Low molecular weight cytokeratin	Positive but less sensitive than HMWCK
  Smooth muscle actin	May be positive in spindled tumors NOS, usually focally, (based on similar tumors of ENT sites)
  Actins, desmin, other muscle markers	Depending upon presence and type of differentiation, may be strongly and extensively positive (rare cases)

Differential Diagnosis

Grading / Staging

Grading

• No widely accepted well described, tested grading scheme
• WHO recommendation
• Well differentiated – Large squamous differentiating cells predominate over small basaloid cells
• Poorly differentiated - Small basaloid cells predominate over large squamous differentiating cells
• Moderately differentiated – Intermediate mixtures, should make up about 2/3 of cases
• Undifferentiated
• Grading based on differentiation and cytologic features is not a good predictor of behavior
• Following scheme has been proposed as predictive of 5 year survival (Sarbia 1995)
• Points are allocated as indicated in the table

• Cases are then stratified based on the sum of the two scores
• Group I – 2 or 3 points
• Group II – 4 points
• Group III – 5 or 6 points
• Group IV – 7 or 8 points
• If the complete scheme is not used, it is probably worthwhile to comment on the pattern of invasion and inflammatory response

Staging

• Same TNM for esophageal squamous and adenocarcinomas

Bibliography

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