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Surgical Pathology Criteria

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Thymic Poorly Differentiated Neuroendocrine Carcinoma


  • High grade carcinoma of the thymus demonstrating neuroendocrine differentiation

Diagnostic Criteria

  • Due to their rarity, diagnostic criteria are not clearly defined; use of pulmonary criteria is probably appropriate
    • Small cell (undifferentiated) carcinoma
      • Scant cytoplasm, very high nucleus/cytoplasm ratio
      • Finely granular, stippled chromatin
      • Nucleoli small to absent
      • Nuclear molding
      • Immunohistochemical demonstration of neuroendocrine differentiation not required
    • Large cell neuroendocrine carcinoma requires both morphologic and immunohistologic (or ultrastructural) evidence of neuroendocrine differentiation
      • Morphologic features suggestive of endocrine differentiation (not all are seen in each case)
        • Generally uniform polygonal/cuboidal cells
        • Nesting and/or broad trabeculae with nuclear palisading
        • Rosettes and rosette like structures
      • Demonstration of endocrine differentiation is required
        • Percent of cells required to stain not defined
        • Synaptophysin and chromogranin are the most specific
    • Areas of carcinoid may be seen in both

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 9/24/10

Supplemental studies

Immunohistology and other studies

  • Staining for neuroendocrine markers not required for small cell type
    • When present, it may be faint and focal
  • Synaptophysin and/or chromogranin stains required for large cell type
    • Percent of cells required to stain not defined
  • TTF1 negative
  • Electronmicroscopy reveals neurosecretory granules

Differential Diagnosis

Metastatic Large or Small Cell Neuroendocrine Carcinoma of Lung Primary Thymic Poorly Differentiated Neuroendocrine Carcinoma
History and imaging may reveal primary site History and imaging should reveal no other primary site
TTF1 positive in >90% of lung neuroendocrine carcinomas TTF1 negative (few tested)


Thymic Poorly Differentiated Neuroendocrine Carcinoma Thymic Carcinoid / Well Differentiated Neuroendocrine Carcinoma
Nearly always cytologically malignant Uniform cells with at most mild atypia
No clear cutoff is defined between these two

Grading / Staging


  • By definition, all are poorly differentiated


  • The same TNM proposed for thymomas has been proposed for thymic neuroendocrine carcinomas:
pT1 Completely encapsulated
pT2 Invades through capsule into fat or normal thymus, but not through pleura or pericardium (may be adherent) or into adjacent organs
pT3 Invades through pleura or pericardium or into adjacent organs (great vessels, lung)
pT4 Pleural or pericardial implants
pN1 Metastasis only to anterior mediastinal nodes
pN2 Metastasis to other intrathoracic nodes
pN3 Metastasis to extrathoracic nodes
pM1 With distant metastases
  • From Tsuchiya et al. Pathol Int 1994; 44:506 and Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG eds. World Health Organization Classification of Tumors. Pathology and genetics of tumors of the lung, pleura, thymus and heart. IARC Press: Lyon 2015

Classification / Lists

Intrinsic Tumors of the Thymus

Non-Thymic Neoplasms that May Arise Primarily in the Thymus

  • Hematopoietic
    • Primary mediastinal large B cell lymphoma
    • Extranodal marginal zone lymphoma
    • Precursor T lymphoblastic lymphoma/leukemia
    • Hodgkin lymphoma
  • Germ cell tumors
    • Seminoma (Germinoma)
    • Embryonal carcinoma
    • Yolk sac tumor
    • Teratoma
    • Choriocarcinoma
    • With associated somatic type malignancy
      • Embryonal rhabdomyosarcoma
      • Angiosarcoma
      • Others
    • With associated hematologic malignancy
      • Acute myelogenous leukemia
      • Acute megakaryoblastic leukemia
      • Others

Miscellaneous Thymic Lesions and Conditions


  • Shimosato Y, Mukai K, Matsuno Y. Tumors of the Mediastinum, Atlas of Tumor Pathology, AFIP Fourth Series, Fascicle 11, 2010
  • Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC eds. World Health Organization Classification of Tumors. Pathology and genetics of tumors of the lung, pleura, thymus and heart. IARC Press: Lyon 2004
  • Fukai I, Masaoka A, Fujii Y, Yamakawa Y, Yokoyama T, Murase T, Eimoto T. Thymic neuroendocrine tumor (thymic carcinoid): a clinicopathologic study in 15 patients. Ann Thorac Surg. 1999 Jan;67(1):208-11
  • Moran CA, Suster S. Neuroendocrine carcinomas (carcinoid tumor) of the thymus. A clinicopathologic analysis of 80 cases. Am J Clin Pathol. 2000 Jul;114(1):100-10
  • Moran CA, Suster S. Thymic neuroendocrine carcinomas with combined features ranging from well-differentiated (carcinoid) to small cell carcinoma. A clinicopathologic and immunohistochemical study of 11 cases. Am J Clin Pathol. 2000 Mar;113(3):345-50
  • Moran CA. Primary neuroendocrine carcinomas of the mediastinum: review of current criteria for histopathologic diagnosis and classification. Semin Diagn Pathol. 2005 Aug;22(3):223-9
  • Weydert JA, De Young BR, Leslie KO; Association of Directors of Anatomic and Surgical Pathology. Recommendations for the reporting of surgically resected thymic epithelial tumors. Hum Pathol. 2009 Jul;40(7):918-23
  • Marchevsky AM, Hammond ME, Moran C, Suster S; Members of the Cancer Committee, College of American Pathologists. Protocol for the examination of specimens from patients with thymic epithelial tumors located in any area of the mediastinum. Arch Pathol Lab Med. 2003 Oct;127(10):1298-303
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