Case 209 - Discussion

Uploaded: 2008-05-04, Updated: 2008-06-22

  • Immunostains

    • CK: +

    • Synaptophysin: +

    • Chromogranin: +

  • Diagnosis: neuroendocrine carcinoma, large cell type.

Large Cell Neuroendocrine Carcinoma

DEFINITION

  • In the WHO classification, large cell neuroendocrine carcinoma (LCNEC) and large cell carcinoma with neuroendocrine morphology of the lung are both currently classified as subtypes of large cell carcinomas. If the LCNEC is combined with adenocarcinomas, squamous cell carcinomas, or giant cell carcinomas, it was categorized as combined LCNEC. If LCNEC was combined with small cell lung caner , it was classified as combined small cell lung cancer.

CLINICAL FEATURES

  • Accounts for 2% to 3% primary lung cancer;

  • Predominantly male (over 80.0%) in old age;

  • Most of patients (over 94%) are smokers.

GROSS FINDINGS

  • Most large cell endocrine carcinomas of the lung are central and present as well-defined, lobulated tumors.

MICROSCOPIC FINDINGS

  • The morphologic features of large cell neuroendocrine carcinoma include:

    • Organoid, palisading rosettes;

    • High mitotic rates of 11 or more (when 10 high-power fields of 2 mm2 were analyzed);

    • Abundant necrosis;

    • Large polygonal cells (nuclear size is comparable with/or more than] three lymphocytes);

    • Comparatively low Nuclear/Cytoplasm ratios;

    • Coarse or vesicular nuclear chromatin.

    • Frequent nucleoli.

DIFFERENTIAL DIAGNOSES

  • Classic large cell carcinomas: bizarre cells with inflammatory cell infiltration;

  • Large cell carcinoma with neuroendocrine morphology: large cell carcinoma without neuroendocrine differentiation but with neuroendocrine morphology.

  • Small cell carcinoma: monotonous, small round, oval, or spindle, usually less than the size of three small resting lymphocytes, scant cytoplasm, finely granular chromatin, and absent or inconspicuous nucleoli. Large cell neuroendocrine carcinoma: generally large and polygonal with moderate to abundant cytoplasm; nuclear chromatin is coarsely granular and nucleoli are prominent.

  • Modern Pathology (2006) 19, 13581368

     

    LCNEC

    SCLC

     P-value

    Chromogranin

    10/17 (59%)

    8/22 (36%)

    0.1630

    Synaptophysin

    13/17 (77%)

    13/23 (57%)

    0.1910

    CD56

    9/17 (53%)

    21/22 (96%)

    0.0018

  • Modern Pathology (2006) 19, 13581368

     

    CLCC

    LCNEC

    SCLC

    Carcinoid

    P-value

    mASH1

    0/12 (0%)

    10/17 (59%)

    20/23 (87%)

    0/9 (0%)

    <0.0001a

    0.0422b

    NeuroD

    4/12 (33%)

    10/17 (59%)

    3/23 (13%)

    5/9 (56%)

    0.0139

    0.0022

    TTF-1

    4/12 (33%)

    4/17 (24%)

    13/23 (57%)

    0/9 (0%)

    0.0141

    0.0369

    p63

    6/12 (50%)

    3/17 (18%)

    1/23 (4%)

    0/9 (0%)

    0.0028

    0.1657

    p16

    7/12 (58%)

    10/17 (59%)

    21/23 (91%)

    2/9 (22%)

    0.0019

    0.0150

    PTEN

    9/12 (75%)

    5/17 (29%)

    2/23 (9%)

    9/9 (100%)

    <0.0001

    0.0883

    CLCC, classic large cell carcinoma; LCNEC, large cell neuroendocrine carcinoma; SCLC, small cell lung carcinoma

  • Summary of Neuroendocrine Tumor of the Lung

     

    Typical carcinoid

    Atypical carcinoid

    Small cell carcinoma

    Large cell NE carcinoma

    Grade Low grade Intermediate grade High grade High grade
    5-year survival >87% 61% 9 to 25% 27%
    10-year survival >87% 35% 5% 9%
    Age (yrs) 50 54 62 63
    Sex (M:F) 1:1 1:1 2:1 4:1
    Nonsmokers (%) 44 37 0 0
    Organoid pattern Yes Yes   Yes
    Mitoses (/10HPF) 01 210   >10
    Necrosis No Yes Yes Yes
    Nuclear atypia Uncommon Common Prominent Prominent
    Cytoplasm Moderate Moderate Little Moderate to abundant
    Chromatin Finely granular Finely granular Finely granular Finely granular, or coarse
    Nucleoli Inconspicuous Inconspicuous Inconspicuous Prominent
    Regional LN metastasis Up to 15% Up to 50%    
    Distant metastasis Rare Up to 10%    
    Surgery Primary approach Primary approach Controversial If resectable
    Chemotherapy Not proven Not proven Primary approach Promising
    Radiation Not proven Not proven Effective locally Effective locally

IMMUNOHISTOCHEMISTRY AND SPECIAL STAINS

  • In a series of 35 cases:

    • Neuron specific enolase (100% )

    • Chromogranin ( 80% )

    • Leu-7 ( 40% )

    • Synaptophysin ( 40% )

ELECTRON MICROSCOPIC FINDINGS

 

CYTOGENETIC STUDIES

 

TREATMENT AND PROGNOSIS

  • Prognosis is reported as similar to that of small cell carcinomas.

  • Poor prognosis, a 5-year survival rate of 35.3% and a 5-year disease-free survival rate of 27.4%.

REFERENCES

  • Ann Thorac Surg 2003;75:348-352

  • Ann Thorac Surg 2007;84:7027

  • Modern Pathology (2006) 19, 13581368

  • Curr Opin Pulm Med 2002, 8:275280