Extrapulmonary Small Cell Carcinoma Workup

Updated: Jun 11, 2021
  • Author: Irfan Maghfoor, MD; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
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Approach Considerations

The diagnostic criteria for extrapulmonary small cell carcinoma (EPSCC) require that the tumor demonstrate histolgic features of small cell carcinoma in the absence of small cell lung cancer (SCLC); thus, biopsy and imaging studies are part of the workup. A paraneoplastic syndrome workup may also be appropriate in certain cases. 


Laboratory Studies

No laboratory investigations aid in the diagnosis of extrapulmonary small cell carcinoma. Most of the laboratory studies done in the workup are to assess end organ function prior to instituting therapy, especially chemotherapy, or to diagnose a suspected paraneoplastic syndrome.

A complete blood count with differential is obtained to assess bone marrow reserve, but it may give clues to bone marrow infiltration by the tumor. Bone marrow infiltration is suspected when peripheral blood displays a leukoerythroblastic picture (ie, red and white blood cell precursors are present).

Blood urea nitrogen and serum creatinine and electrolyte assays are obtained to asses renal function prior to instituting potentially nephrotoxic drugs, as well as to estimate renal clearance of chemotherapeutic agents. In addition, low serum sodium levels and abnormalities in other electrolytes such as potassium may point toward the presence of a paraneoplastic syndrome.

Serum bilirubin and transaminases are measured to assess liver function and to determine appropriate dosing of hepatically cleared chemotherapeutic agents.

Serum calcium is assessed for suspected hypercalcemia and bone metastases.


Imaging Studies

Chest radiography or computed tomography (CT) with or without fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) are required to exclude pulmonary involvement.  

A complete workup should include cross-sectional imaging of the site of origin, as well as of the chest, abdomen, and pelvis for staging. Whole-body imaging with FDG PET/CT may be considered for both staging and assessment of treatment response. [9]



Bone marrow aspiration and biopsy are performed to confirm or exclude bone marrow involvement in case of peripheral blood abnormalities. Some authors recommend that bone marrow biopsy should be done in every patient to confirm limited disease.

Sputum cytology, bronchoscopy, or both are performed to exclude pulmonary origin of small cell carcinoma.

Special tests that may be performed, depending on primary site of origin, include the following:

  • Upper endoscopy: Esophagus

  • Direct laryngoscopy, bronchoscopy, and upper endoscopy: Origin in head and neck region

  • Cystoscopy: Urinary bladder

  • Lower endoscopy: Rectum and large bowel

  • Pelvic examination: Cervix and uterus


Histologic Findings

Extrapulmonary small cell carcinoma histologically consists of sheets of uniform small round cells with scant cytoplasm, dense nuclei, and indistinct nucleoli.

Immunohistochemical stains with silver impregnated stains usually have positive results; however, EPSCC cannot be diagnosed on the basis of immunoreactivity alone. Neural cell adhesion molecule (NCAM or CD56) is the most sensitive neuroendocrine marker. [9]



There is no American Joint Committee on Cancer (AJCC) staging classification for extrapulmonary small cell carcinoma. In the reported literature, extrapulmonary small cell carcinoma is universally staged similarly to small cell carcinoma of lung as limited stage or extensive stage, as follows:

  • Limited stage: Tumor is confined to the organ of origin, with or without regional lymph node involvement. Alternatively, limited stage has also been defined as that encompassed within one radiation port.

  • Extensive stage: Disease has spread to distant organs or beyond regional lymph nodes.