Neuroendocrine tumors

Small cell carcinoma

Last staff update: 4 August 2022

Copyright: 2003-2022,, Inc.

PubMed Search: Small cell neuroendocrine carcinoma lung

Caroline I.M. Underwood, M.D.
Carolyn Glass, M.D., Ph.D.
Page views in 2021: 47,499
Page views in 2022 to date: 31,667
Cite this page: Underwood CIM, Glass C. Small cell carcinoma. website. Accessed August 17th, 2022.
Definition / general
  • Neuroendocrine tumor that arises in the hilum of smokers, with a poor prognosis and no current targeted therapy
Essential features
  • High grade, usually advanced at diagnosis
  • Almost exclusively associated with smoking / tobacco exposure
  • Positive for at least one neuroendocrine marker
  • Oat cell carcinoma
  • Malignant carcinoid
ICD coding
  • ICD-10: C34.90 - malignant neoplasm of unspecified part of unspecified bronchus or lung
  • Lung: central / bronchial / hilar; rarely a peripheral nodule
  • Submucosal growth
  • Metastasis to liver, adrenals, bone, bone marrow, brain; often widespread
  • Arises from neuroendocrine cells of basal bronchial epithelium
  • Smoking (rare in nonsmokers)
Clinical features
  • Biopsy: based on hematoxylin and eosin morphology
Radiology description
Radiology images

Images hosted on other servers:

Right hilar mass

Left hilar mass

Prognostic factors
  • Adverse (Cancer Treat Res 2016;170:301)
    • Continued smoking → chemotherapy resistance
    • Labs: elevated lactate dehydrogenase (LDH), alkaline phosphatase, albumin
    • Metastasis to the liver, bone marrow and brain
    • Presence of paraneoplastic syndromes
  • Favorable (Lung Cancer 2019;130:216)
    • Women
Case reports
Gross description
  • Central or hilar mass
  • White-tan, soft, friable, necrotic (Am J Surg Pathol 2002;26:1184)
  • Peripheral nodules: circumscribed, with fleshy cut surface
Gross images

Contributed by Carolyn Glass, M.D.

Central tumor with bronchial spread

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Hilar mass

Central tumor

Spreading along bronchi

Frozen section description
  • Rarely seen at frozen section due to being diagnosed on cytology and usually treated nonoperatively
Microscopic (histologic) description
  • Round / oval blue cells with minimal cytoplasm; usually small to medium sized
  • Nuclear features: finely dispersed chromatin, no distinct nucleoli, molding, smudging, high mitotic rate
  • Stroma: thin, delicate, scant, fibrovascular
  • Necrosis and apoptosis of individual cells common
  • Patterns: sheets, clusters, ribbons, rosettes, peripheral palisading
  • Other / rarer features (Surg Oncol Clin N Am 2016;25:447)
    • Azzopardi phenomena: basophilic nuclear material lining blood vessel walls
    • Metastatic cells usually have more cytoplasm
    • Scattered giant cells
Microscopic (histologic) images

Contributed by Carolyn Glass, M.D.

Sheets of tumor cells

Crushed blue cells

Cellular morphology




Virtual slides

Images hosted on other servers:

Small cell lung carcinoma

Cytology description
  • Nuclei: oval / elongated, hyperchromatic, absent nucleoli, granular cytoplasm, smooth membrane
  • Scant cytoplasm
  • Pattern: molding, individual cells or loose clusters, crush artifact
  • Necrosis and apoptosis of individual cells and tumor background
  • Hypercellular (Int J Clin Exp Pathol 2010;3:367)
Positive stains
Negative stains
Electron microscopy description
Electron microscopy description

Images hosted on other servers:

Dense core granules

Molecular / cytogenetics description
Sample pathology report
  • Lung, left upper lobe, endobronchial biopsy:
    • Malignant tumor present, consistent with small cell carcinoma (see comment)
    • Comment: Positive immunoreactivity for keratin, CD56 and TTF1 with negative staining for CD45 supports the diagnosis of small cell carcinoma.
Differential diagnosis
Board review style question #1
A 65 year old man presents to the clinic with generalized fatigue for 6 months. He says he has been feeling very down lately and that his mood has had a negative impact on his relationship with his wife of 30 years. He also reports recent acne flares, which he says he has not struggled with since college. He is a 25 pack per year smoker and has hypertension, previously well controlled on his current regimen. Vitals taken today show a BP of 155/95. Physical exam reveals an adipose deposit on the dorsal upper thorax and abdominal striae. A chest Xray reveals a hilar lung mass. Which of the following tumors most commonly produces the paraneoplastic syndrome seen in this patient?

  1. Adenocarcinoma of the lung
  2. Large cell carcinoma of the lung
  3. Small cell lung cancer
  4. Squamous cell lung cancer
Board review style answer #1
C. Small cell lung cancer is associated with paraneoplastic syndromes and one of the most common is Cushing syndrome, as in this patient. This is caused by increased production of adrenocorticotropic hormone by the small cell tumor. Symptoms include weight gain, fatigue, glucose intolerance, moon face, buffalo hump, muscular weakness, skin manifestations (thinning, acne, abdominal striae), psychological symptoms (depression, anxiety, decreased libido), hypertension, increased risk of bone fracture and reproductive symptoms (irregular or absent menstruation in females and erectile dysfunction in males). Other paraneoplastic syndromes associated with small cell lung carcinoma include syndrome of inappropriate antidiuretic hormone secretion and Lambert-Eaton.

Comment Here

Reference: Small cell carcinoma
Board review style question #2
A 59 year old female smoker with no significant past medical history comes to the clinic complaining of dyspnea. She states that a month ago, she began experiencing shortness of breath during her morning 2 mile walk, which she had previously enjoyed without difficulty. Over the last week, she has started becoming short of breath throughout the day and complains of headaches that are not relieved with ibuprofen. When asked about her diet, she says she has decreased her salt intake, as she thinks her face has become swollen. On physical exam, you note edema of the right arm and distention of right sided neck veins. Xray of the chest shows a right sided lung mass at the hilum. Fine needle aspiration of this mass would most likely reveal which of the following?

  1. Granulomas with central necrosis and giant cells
  2. Islands of large eosinophilic cells containing keratin
  3. Nests of cells with large irregular shaped nuclei that are forming glands
  4. Sheets of small round blue cells with finely dispersed chromatin
Board review style answer #2
D. Sheets of small round blue cells with finely dispersed chromatin. Small cell lung cancer is histologically described as small round / oval cells with high nuclear to cytoplasmic ratio. The nuclei have finely dispersed or salt and pepper chromatin and absent nucleoli. Small cell lung cancer is most often located at the hilum and grows along the bronchi. Growth of the tumor can cause compression of the superior vena cava leading to superior vena cava syndrome, characterized by swelling of the face and upper limbs, cough and distention of the neck veins, as venous blood flow is obstructed.

Comment Here

Reference: Small cell carcinoma
Board review style question #3

A 72 year old man was recently diagnosed with small cell lung cancer as shown above. His chest Xray shows a large hilar mass in the left thorax but is negative for pleural effusion. PET scan shows metastasis to 4 lymph nodes in the left thorax but no metastasis to other organs. He has had severe cough and shortness of breath and his labs show hyponatremia. He is anxious about his prognosis and asks about treatment options. How would you stage this tumor and which treatment regimen would you recommend?

  1. Advanced stage: systemic therapy with doxorubicin followed by surgical removal
  2. Limited stage; surgical removal after neoadjuvant radiation and systemic cisplatin therapy
  3. Limited stage: systemic therapy with cisplatin and concurrent radiation therapy
  4. Limited stage: systemic therapy with doxorubicin and concurrent radiation therapy
  5. Limited stage: targeted radiation therapy followed by gene targeted chemotherapy
Board review style answer #3
C. Limited stage: systemic therapy with cisplatin and concurrent radiation therapy. Small cell lung cancer is treated with concurrent radiation and chemotherapy, most often platinum based (like cisplatin). Doxorubicin is an anthracycline chemotherapy and would not be used to treat small cell lung cancer. Surgical removal of these tumors is rare, as they are most often located at the hilum and cannot be effectively removed, even with neoadjuvant chemoradiation therapy. There are currently no genes targetable by chemotherapy. In addition, this patient presents with limited stage disease, as his small cell lung cancer is currently confined to the left hemithorax. If the tumor spread to the right hemithorax, if nonregional lymph nodes became positive, if distant metastasis was present or if he developed a malignant pleural effusion, then this tumor would be advanced stage. However, regardless of the therapy chosen, the overall prognosis for this patient is poor and he should be counseled about the rapid progression of the disease and offered hospice care.

Comment Here

Reference: Small cell carcinoma
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