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Thymic Well Differentiated Neuroendocrine Carcinoma (Carcinoid and Atypical Carcinoid)

Definition

  • Carcinoma of the thymus exhibiting uniform cytologic features and neuroendocrine differentiation

Alternate/Historical Names

  • Prior to their description in 1972, most were considered variants of thymoma or types of adenoma
  • Atypical carcinoid is included in this category

Diagnostic Criteria

  • Most cells show evidence of neuroendocrine differentiation
    • Synaptophysin and/or chromogranin stains positive in most cases
    • Argyrophil stain positive in nearly all cases
      • Argentaffin negative
    • Neuron specific enolase, PGP9.5 and CD56 are sensitive but not specific
    • Electronmicroscopy reveals neurosecretory granules
  • Most well differentiated neoplasms exhibit characteristic cytologic and architectural features
    • Round regular nuclei
      • Stippled (salt and pepper) chromatin
      • Inconspicuous nucleoli
    • Usually moderate granular eosinophilic cytoplasm
    • Various growth patterns
      • Insular growth pattern
        • Round nests of cells
      • Rosettes and gland-like structures
        • No clear mucinous gland differentiation
      • Trabecular
        • Rows and strands of cells
      • Other occasional to rare patterns
        • Spindle cell
        • Oncocytic
        • Pigmented (melanin or lipofuscin)
        • Angiectatic
        • With amyloid stroma (calcitonin positive carcinoid)
        • With mucinous stroma (acidic, stromal mucin)
    • Sarcomatoid dedifferentiation has been reported in rare cases
    • Sustentacular cells may be seen in occasional cases
  • Punctate necrosis
    • Sharply defined foci of coagulative tumor necrosis
  • Mitotic figures frequently are numerous
    • 2-20/hpf in most cases
  • Nearly all cases would qualify as atypical carcinoid in the lung

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

  • Synaptophysin and/or chromogranin stains positive in most cases
  • Argyrophil stain positive in nearly all cases
    • Argentaffin negative
  • Neuron specific enolase, PGP9.5 and CD56 are sensitive but not specific
  • Somatostatin, ACTH, calcitonin and other secretory products may be identified
  • S100 stains sustentacular cells in occasional cases
  • Electronmicroscopy reveals neurosecretory granules

Differential Diagnosis

Thymoma Thymic Carcinoid / Well Differentiated Neuroendocrine Carcinoma
Immature T cells present Mature T and B cells may be present, but lacks immature T cells
Punctate necrosis very rare Punctate necrosis in nearly all cases
Neuroendocrine markers negative (except CD57) Neuroendocrine markers positive
Rosettes and glands/pseudoglands may be seen in both carcinoid and type A thymoma

 

Thymic Carcinoma Thymic Carcinoid / Well Differentiated Neuroendocrine Carcinoma
Cytologically malignant Uniform cells, at most mildly atypical
Punctate necrosis very rare Punctate necrosis in nearly all cases
Neuroendocrine markers negative (except CD57) Neuroendocrine markers positive
Both may have high mitotic rates

 

Metastatic Carcinoid of Lung Thymic Carcinoid / Well 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 carcinoids TTF1 negative (few tested)

 

Paraganglioma Thymic Carcinoid / Well Differentiated Neuroendocrine Carcinoma
Keratin negative Keratin positive
Punctate necrosis very rare Punctate necrosis in nearly all cases
Both are positive for neuroendocrine markers and may have sustentacular cells

 

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

Grading

  • By definition, all are well differentiated
  • Nearly all thymic carcinoids qualify as atypical carcinoids (using lung criteria) based on an elevated mitotic rate and the presence of necrosis

Staging

  • The same TNM proposed for thymomas has been proposed for thymic neuroendocrine carcinomas:
pT  
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
pN  
pN1 Metastasis only to anterior mediastinal nodes
pN2 Metastasis to other intrathoracic nodes
pN3 Metastasis to extrathoracic nodes
pM  
pM1 With distant metastases
  • From Tsuchiya et al. Pathol Int 1994; 44:506

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

Bibliography

  • 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
  • Gibril F, Chen YJ, Schrump DS, Vortmeyer A, Zhuang Z, Lubensky IA, Reynolds JC, Louie A, Entsuah LK, Huang K, Asgharian B, Jensen RT. Prospective study of thymic carcinoids in patients with multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 2003 Mar;88(3):1066-81
  • 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. Primary neuroendocrine carcinoma (thymic carcinoid) of the thymus with prominent oncocytic features: a clinicopathologic study of 22 cases.  Mod Pathol. 2000 May;13(5):489-94
  • 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, Suster S. Spindle-cell neuroendocrine carcinomas of the thymus (spindle-cell thymic carcinoid): a clinicopathologic and immunohistochemical study of seven cases. Mod Pathol. 1999 Jun;12(6):587-91
  • 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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