Extrapulmonary small cell carcinoma: a clinicopathological study with identification of potential diagnostic mimics

Histopathology. 2012 Sep;61(3):454-64. doi: 10.1111/j.1365-2559.2012.04247.x. Epub 2012 Jun 11.


Aims: To evaluate the clinicopathological features of small cell carcinoma arising outside the lung.

Methods and results: Thirty-seven cases with a pathology diagnosis of extrapulmonary small cell carcinoma (EPSCC) were selected. The clinical notes were reviewed and tumour blocks were selected for a fresh haematoxylin and eosin (H&E) section and immunohistochemical stains. The most common tumour locations were cervix and bladder. Twenty-five cases (68%) were finally diagnosed as EPSCC, nine of which were found with coexisting non small cell carcinoma. Two cases (5%) were diagnosed as large cell neuroendocrine carcinoma (LCNEC) of the cervix. The remainder was classified as 10 poorly differentiated carcinomas (PDCs) (27%). Positive staining for thyroid transcription factor 1 (TTF-1) was noted in nine cases of EPSCC and in none of the cases of PDC (P = 0.034). Synaptophysin immunoreactivity was found in 20 cases of EPSCC and two cases of PDC with neuroendocrine differentiation (P = 0.002), as well as two cases of LCNEC. 34βE12 was positive in eight cases of SCC and two cases of PDC.

Conclusions: Based on this series, EPSCC may be overdiagnosed. Immunohistochemistry for TTF-1, used in combination with synaptophysin, may help to discriminate EPSCC from PDC.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Small Cell / diagnosis*
  • Carcinoma, Small Cell / metabolism
  • DNA-Binding Proteins / biosynthesis
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Synaptophysin / biosynthesis
  • Transcription Factors
  • Young Adult


  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Synaptophysin
  • TTF1 protein, human
  • Transcription Factors