Lung Cancer.pdf

Pathologic Evaluation of Lung Cancer 71
carcinomas. Atypical carcinoid is distinguished from typical carcinoid by
the number of mitoses and the presence of necrosis. For this reason, this
distinction may be difficult in small biopsy samples. Atypical carcinoids
may metastasize and cause death (Beasley et al, 2000).
Small Cell Carcinoma. In the past, small cell carcinoma was divided into
oat cell carcinoma; small cell carcinoma, intermediate cell type; mixed
small cell/large cell carcinoma; and combined oat cell carcinoma. However,
these categories lacked prognostic significance, and there was poor
interobserver reproducibility in the assignment of tumors to these categories.
Therefore, in 1998, it was recommended that the terms “oat cell carcinoma”
and “small cell carcinoma, intermediate cell type” be discarded
and that all tumors with pure small cell carcinoma histologic features be
referred to as “small cell carcinoma” (Travis et al, 1998a). The category
“mixed small cell/large cell carcinoma” persisted and was defined as a
tumor with both small cell and large cell carcinoma components, but subsequent
studies failed to confirm the clinical significance of this categorization
and there was poor interobserver reproducibility.
In the recent WHO classification, small cell carcinoma is divided into
small cell carcinoma and combined small cell carcinoma. The term “small
cell carcinoma” is used for tumors with pure small cell carcinoma histologic
features without a NSCLC component. Combined small cell carcinoma
is a mixture of small cell carcinoma and any NSCLC component, including
squamous cell carcinoma, adenocarcinoma, sarcomatoid carcinoma,
or large cell carcinoma—even large cell neuroendocrine carcinoma.
Small cell carcinoma is defined as a malignant tumor composed of
small round to oval cells with scant cytoplasm, ill-defined cell boundaries,
prominent nuclear molding, and nuclei with finely granular chromatin
that either lack nucleoli or have small inconspicuous nucleoli (Figure
4–5). These tumors have a very high mitotic rate (by definition 11 or more
mitoses per 10 high-power fields), and necrosis tends to be extensive.
Small cell carcinoma is distinguished from atypical carcinoid on the
basis of the mitotic rate and the amount of necrosis. Atypical carcinoids
have only up to 10 mitoses per 10 high-power fields, and necrosis tends
to be focal. As small cell carcinomas undergo extensive necrosis, they
show the Azzopardi effect within necrotic areas—i.e., a hematoxyphilic
deposit of DNA from necrotic cells that is encrusted on blood vessel
walls. This effect is uncommon in atypical carcinoids. Neuroendocrine
differentiation is less pronounced in small cell carcinoma as assessed by
both immunohistochemical staining and electron microscopy. Small cell
carcinomas show focal or weak staining for chromogranin and synaptophysin,
while atypical carcinoids show diffuse and strong immunoreactivity
for these markers. On electron microscopy, cytoplasmic dense core
neuroendocrine granules can be seen but are usually sparse in small cell
carcinoma; in contrast, these granules are usually numerous and dif-