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Surgical Pathology Criteria

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Squamous Carcinoma of the Esophagus


  • 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


  • 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

Esophageal Basaloid Squamous Carcinoma Esophageal Poorly Differentiated Endocrine (Small Cell Undifferentiated) Carcinoma
Well defined solid sheets, lobules and nests Diffuse permeating pattern of infiltration
Stromal hyalinization common Lacks stromal hyalinization
Frequent intermingling squamous differentiation More than focal squamous differentiation infrequent
Lacks nuclear molding Prominent nuclear molding
Nuclear pleomorphism (at high magnification) Little nuclear pleomorphism
May have distinct but small nucleoli Nucleoli inconspicuous
HMWCK and p63 usually strongly positive HMWCK and p63 negative or focal and weak


Esophageal Basaloid Squamous Carcinoma Esophageal Adenoid Cystic Carcinoma
Frequent intermingling squamous differentiation Squamous differentiation infrequent
Frequent coagulative tumor cell necrosis Necrosis rare
Lacks 2 cell type pattern 2 cell type differentiation (pale ductal and dark basaloid)
Nuclear pleomorphism (at high magnification) Uniform small hyperchromatic nuclei
Frequent mitotic figures Mitotic figures infrequent
p63 diffuse positivity and smooth muscle actin usually negative p63 and smooth muscle actin clearly define a surrounding myoepithelial component
Perineural invasion infrequent Perineural invasion common

Grading / Staging


  • 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






Pattern of invasion Pushing, well defined margins Infiltrating solid cords and bands Small groups of dissociated cells Marked cellular discohesion
Inflammatory response Marked Moderate Slight None
  • 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


  • Same TNM for esophageal squamous and adenocarcinomas


  • Bosman FT, Carneiro F, Hruban RH, Thiese ND (Eds). WHO Classifiication of Tumors of the Digestive System, IARC, Lyon 2010
  • Sarbia M, Becker KF, Höfler H. Pathology of upper gastrointestinal malignancies. Semin Oncol. 2004 Aug;31(4):465-75.
  • Iwaya T, Maesawa C, Tamura G, Sato N, Ikeda K, Sasaki A, Othuka K, Ishida K, Saito K, Satodate R. Esophageal carcinosarcoma: a genetic analysis. Gastroenterology. 1997 Sep;113(3):973-7.
  • Wang ZY, Itabashi M, Hirota T, Watanabe H, Kato H. Immunohistochemical study of the histogenesis of esophageal carcinosarcoma. Jpn J Clin Oncol. 1992 Dec;22(6):377-86.
  • Iyomasa S, Kato H, Tachimori Y, Watanabe H, Yamaguchi H, Itabashi M. Carcinosarcoma of the esophagus: a twenty-case study. Jpn J Clin Oncol. 1990 Mar;20(1):99-106.
  • Guarino M, Reale D, Micoli G, Forloni B. Carcinosarcoma of the oesophagus with rhabdomyoblastic differentiation. Histopathology. 1993 May;22(5):493-8.
  • Osborn NK, Keate RF, Trastek VF, Nguyen CC. Verrucous carcinoma of the esophagus: clinicopathophysiologic features and treatment of a rare entity. Dig Dis Sci. 2003 Mar;48(3):465-74.
  • Sarbia M, Bittinger F, Porschen R, Dutkowski P, Willers R, Gabbert HE. Prognostic value of histopathologic parameters of esophageal squamous cell carcinoma. Cancer. 1995 Sep 15;76(6):922-7.
  • Sarbia M, Verreet P, Bittinger F, Dutkowski P, Heep H, Willers R, Gabbert HE. Basaloid squamous cell carcinoma of the esophagus: diagnosis and prognosis. Cancer. 1997 May 15;79(10):1871-8.
  • Tsang WY, Chan JK, Lee KC, Leung AK, Fu YT. Basaloid-squamous carcinoma of the upper aerodigestive tract and so-called adenoid cystic carcinoma of the oesophagus: the same tumour type? Histopathology. 1991 Jul;19(1):35-46.
  • Li TJ, Zhang YX, Wen J, Cowan DF, Hart J, Xiao SY. Basaloid squamous cell carcinoma of the esophagus with or without adenoid cystic features. Arch Pathol Lab Med. 2004 Oct;128(10):1124-30.
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