Fine needle aspirates are suitable for ultrastructural study provided they have been properly procured and processed. Some variation in cell and nuclear size and shape can be appreciated among small cell lung carcinomas by light microscopy and there have been attempts to define subtypes. However, these features generally vary within a particular tumor, and they are influenced by artefactual changes and are consequently not sufficiently reproducible for use as criteria in paraffin sections, nor is there evidence that the suggested subtypes have clinical relevance. Morphometry performed using low magnification electron micrographs has shown that there is an overlap in cell and nuclear size and shape with other lung tumors, but the nuclear-cytoplasmic ratio is significant. The scanty cytoplasm is often strikingly obvious to the electron microscopist.
Organelles are generally sparse.
Cell junctions range from a few small well-formed desmosomes to scattered tiny densities on the apposed cell membranes. The nuclear chromatin is customarily finely clumped and evenly distributed, obscuring small nucleoli, but in a few otherwise typical small cell carcinomas, the chromatin is fine and nucleoli prominent. Neuroendocrine differentiation is manifested ultrastructurally by the presence of dense-core granules. They are consistently small in caliber in small cell lung carcinoma cells, measuring roughly 100 nm and resembling the granules in extrapulmonary neuroendocrine carcinomas and neuroblastomas. In my experience, they are never as plentiful as granules in a typical carcinoid, and are rarely numerous.