Neuroendocrine tumours (carcinoid tumor)

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Pulmonary neuroendocrine tumors, which include also small cell carcinoma, have been classified by the World Health Organization into the following types: carcinoid tumor, atypical carcinoid tumor, large cell neuroendocrine carcinoma, and small cell carcinoma.
Ultrastructurally, all contain cytoplasmic dense-core granules. They variably stain positive with several immunohistochemical markers: chromogranin A (most specific), synaptophysin, neuron-specific enolase, Leu-7 (CD57). Other peptides may be present, such as ACTH, insulin, calcitonin, gastrin, VIP.

The large cell neuroendocrine carcinoma is composed of large cells with the nuclear features and the organoid growth pattern of a neuroendocrine neoplasm (and immunohistochemical and ultrastructural studies confirm its neuroendocrine nature), whereas the large cell carcinoma with neuroendocrine differentiation is indistinguished by light microscopy from a large cell undifferentiated carcinoma, but it shows immunohistochemical and ultrastructural features of neuroendocrine differentiation. The prognosis for patients with these tumors is poor.

Carcinoid tumor (typical carcinoid tumor)

These neuroendocrine tumors have a low metastatic rate and the prognosis is usually very good. They are usually centrally-located, often with a prominent endobronchial component; they are often covered by an intact respiratory epithelium and, as a result, sputum cytology is often negative.

Cytologic diagnostic features

Loosely cohesive groups and single cells
Acinar or rosette-like structures
Round, columnar or plasmacytoid cells
Uniform, moderately granular nuclei, ‘salt and pepper’ chromatin pattern
Ample eosinophilic cytoplasm
Branching capillaries
Mitoses uncommon

Differential diagnosis

Benign bronchial epithelial cells
Adenocarcinoma
Small cell carcinoma
Atypical carcinoid
Lymphoma
Mesenchimal tumor (spindle cell carcinoid)

Because of their bland, monomorphous appearance, the cells of some carcinoid tumors could be mistaken for benign bronchial cells, but they are less cohesive, have more coarse chromatin and lack cilia. Because of the presence of rosettes in some carcinoid tumors, they could be mistaken for adenocarcinoma, which, however, usually show greater pleomorphism. Lymphoid cells are distinguished from carcinoid tumors because they have less cytoplasm and do not form clusters.

Carcinoid tumors are distinguished from atypical carcinoid and small cell carcinoma by the absence of mitoses and necrosis.

Atypical carcinoid tumor

Atypical carcinoid tumor (well-differentiated neuroendocrine carcinoma) is more aggressive than typical carcinoid tumor.

Cytologic diagnostic features

Cells similar to typical carcinoid
Disorganized growth pattern
Necrosis
Pleomorphism
Mitosis
Prominent nucleoli

NSE

PTH-RP

Carcinoid:

Carcinoid. Cellular aspirate with neoplastic cells seen singly and in tissue fragments. Even at this low power, a few larger atypical cells can be seen (called “endocrine atypia”).

Carcinoid. Loosely cohesive tissue fragments of relatively monotonous cells with minimal nuclear pleomorphism and focal rosette formation. Occasional atypical nuclei can be seen. Note the absence of necrosis and nuclear molding.

Carcinoid. Note the poorly cohesive and small, relatively uniform neoplastic cells with round nuclei, tiny inconspicuous nucleoli, and characteristic “salt and pepper” chromatin distribution.

Carcinoid. Note the numerous neoplastic cells which have lost their cytoplasm, a morphologic finding termed naked nuclei. The nuclei themselves are round to oval with some anisonucleosis, “salt and pepper” chromatin pattern, and small inconspicuous nucleoli.