Neuroendocrine tumors of the thymus and mediastinum

Abstract

Neuroendocrine tumors of the thymus (tNET) and mediastinum are very rare neoplasms with scarce available data. All subtypes [typical and atypical carcinoid tumors (TC and AC), large cell neuroendocrine and small cell carcinoma (SCC)] observed elsewhere in the body occur also in the mediastinum and show only few if any organ-specific morphological differences. Although all available data suggest that the broad principles that govern the biology (and hence) the classification of these tumors in general apply also to tNET, there are a few noteworthy peculiarities related e.g., to risk factors, relative frequency and also to molecular genetic features. In this review, we will briefly summarize current knowledge on tNET with a special emphasis on shared and private features in comparison e.g., with pulmonary NET, which have traditionally been regarded the next closely related NET group.

Keywords: Thymus; carcinoid tumor; large cell neuroendocrine carcinoma (LCNEC); neuroendocrine; review; small cell carcinoma (SCC).

Figure 1

Histomorphology of typical carcinoid tumors of the thymus. (A) Low power view shows a vaguely lobulated mass with cystic change; (B) tumor cells in in this example grow in trabecular structures with some perivascular spaces; (C) the neoplastic cells are uniformly small, round to oval with scant and pale eosinophilic cytoplasm, with relatively small, bland nuclei containing fine granular chromatin. Note the numerous delicate blood vessels that are typical for endocrine tumors; (D) ki67-index is below 1% in this case. Overall, there are no specific histological features to suggest that this case is of thymic origin and clinical information is essential. (A-C) Hematoxylin & Eosin; (D) DAB immunohistochemistry on paraffin.

Figure 2

Atypical carcinoid tumor (AC) of the thymus. (A) Low power view showing a solid tumor consisting of small nodules next to an atrophic thymus (upper third of the image); (B) higher magnification shows a small area of tumor necrosis and a cholesterol cleft. Presence of even small foci of unequivocal necrosis places a tumor in the atypical carcinoid category; (C) calcifications are a frequent finding in thymic carcinoid tumors and are thought to be somewhat more frequent than in other organs; (D) this case had 2 mitoses per 10 HPF and a ki67 index of 5%. (A-C) Hematoxylin & Eosin; (D) DAB immunohistochemistry on paraffin.

Figure 3

The morphological spectrum of large cell neuroendocrine carcinoma (LCNEC) of the thymus. (A-C) Example of a LCNEC that retained some features of well-differentiated (carcinoid) tumors; (D-F) example of a LCENC with high grade morphology. (A) Necrosis is not evident at this low power magnification; (B) higher magnification shows multiple foci of blood vascular invasion and (C) several mitoses in one visual field; (D) low power magnification shows a widely invasive tumor; (E) higher magnification shows vascular invasion, high grade nuclear morphology, and several mitoses; (F) the ki67 index in this example was >75%. (A-E) Hematoxylin & Eosin; (F) DAB immunohistochemistry on paraffin.

Figure 4

Morphology of small cell carcinoma (SCC) of the thymus. (A) Low power view shows a widely infiltrative tumor next to a thymic remnant (lower half of the image); (B,C) higher magnification shows the typical small cell morphology with crush artifacts of the vulnerable tumor cell nuclei as well as numerous apoptosis and small foci of necrosis; (D) due to the marked nuclear artefacts, the ki67 index is sometimes difficult to assess, but is usually >70%. This case stained positive for neuroendocrine markers (not shown), although neuroendocrine differentiation is not required for the diagnosis, if the morphology and proliferation rate are adequate. (A-C) Hematoxylin & Eosin; (D) DAB immunohistochemistry on paraffin.