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11 July 2013 - Case of the Week #278

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Thanks to Dr. Vaidehi Avadhani, St. Luke's Roosevelt Hospital, New York (USA), for contributing this case and the discussion. To contribute a Case of the Week, follow the guidelines on our Case of the Week page.

December 7, 2013
The Inn at St. John's
Plymouth, Michigan (USA)

Michigan Society of Pathologists
2013 Winter Conference


More information to follow!


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Case of the Week #278

Clinical History:

A 62 year old man with COPD and myelofibrosis presented with shortness of breath. Chest CT showed an anterior mediastinal mass, accompanied by enlarged regional lymph nodes. The mass was excised, and a lymph node dissection was performed.

Gross examination revealed a 3.2 cm nodular mass with a tan white cut surface.

Micro images:

First three images are from mass, image on right is from regional lymph node

What is your diagnosis?


Well differentiated neuroendocrine carcinoma / atypical carcinoid of the thymus gland
The tumor infiltrates into adjacent adipose tissue. Metastatic carcinoma was identified in 2 of 3 lymph nodes.


Left: AE1-AE3, right: synaptophysin

According to the World Health Organization (WHO), thymic epithelial tumors with predominant neuroendocrine differentiation are classified as Neuroendocrine carcinomas (NEC) of the thymus (WHO classification, tumors of the lung, pleura, thymus and heart. IARC Press, 2004: 188, PDF). Thymic neuroendocrine carcinomas are classified as well-differentiated NEC and poorly differentiated NEC.

A. Well differentiated NEC
  a. Typical carcinoid: no necrosis and <2 mitoses per 2 mm2 (10 hpf)
  b. Atypical carcinoid: necrosis present and 2-10 mitoses per 2 mm2(10 hpf)

B. Poorly differentiated NEC:
  a. Large cell NEC: non-small cell NEC with > 10 mitoses per 10 hpf
  b. Small cell NEC: small cell cytology

Neuroendocrine differentiation can be demonstrated by immunohistochemistry (synaptophysin, chromogranin and CD56 positive) or by identification of neurosecretory granules by electron microscopy.

The main differential diagnosis includes:
1. Metastatic pulmonary NEC (TTF1+ may be helpful, Mod Pathol 2013 Jun 21 [Epub ahead of print])
2. Thymic carcinoma with focal neuroendocrine differentiation
3. Nerve sheath tumor: cytokeratin-, chromogranin-, synaptophysin-
4. Paraganglioma: cytokeratin-

Tumor stage has been found to be an important prognostic factor. Due to the rarity of the tumor, well defined guidelines for management are not yet published. However, most studies show that atypical carcinoids of the thymus are aggressive (Semin Diagn Pathol 2005;22:223, Korean J Pathol 2012;46:221). Radical resection of the primary tumor with local lymph nodes is the standard of care.

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