LARGE CELL CARCINOMAS OF THE LUNG
Large cell
carcinoma is a malignant epithelial undifferentiated neoplasm lacking glandular
or squamous differentiation and features of small cell carcinoma. It is a
diagnosis of exclusion and includes many poorly differentiated non–small cell
carcinomas. Several variants are recognized, including neuroendocrine
differentiation (large cell neuroendocrine carcinoma [LCNEC]) and basaloid
carcinoma), but it is uncertain if this differentiation is of prognostic or
therapeutic importance. Large cell carcinoma and its variants can only be
diagnosed reliably on surgical material; cytology samples are not generally
sufficient. LCNEC is differentiated from atypical carcinoid tumor by having more
mitotic figures, usually 11 or more per 2 mm2 of viable tumor, and large areas
of necrosis are common. Neuroendocrine differentiation is confirmed using
immunohistochemical markers such as chromogranin, synaptophysin, or CD56.
Patients with LCNEC have a worse prognosis than those with atypical carcinoid
tumors. Large cell carcinoma is associated with cigarette smoking. This cell
type accounted for 4% of all lung cancers in the Surveillance, Epidemiology and
End Results (SEER) database. The SEER database listed the cell type of 24% of
all lung cancers as “other non–small cell.” These other cancers include
non–small cell cancers that pathologists specify as NOS (not otherwise
specified). As treatment moves toward specific treatment for specific cell types,
it will be important for pathologists to classify the histology as accurately
as possible and to decrease the percentages of cases reported as NOS.
The signs and symptoms of this cell type are similar
to those of other non–small cell carcinomas. The most common radiographic
finding is a large peripheral lung mass. Because of the peripheral location,
these cancers may be asymptomatic and detected on an incidental chest
radiograph. Because of the rapid growth of this cell type, the radiographic
lesion may appear rather suddenly (within a few months) or enlarge rapidly.
Diagnostic procedures are similar to those of other
histologic types. Sputum cytology is not generally helpful because of the peripheral location, and
bronchoscopic diagnostic yields are similar to those for peripheral adenocarcinomas
and squamous cell carcinomas (60%-70%). Transthoracic needle aspiration is
diagnostic in the majority of cases. These cancers are usually aggressive
tumors with a strong tendency for early metastases. Nevertheless, surgery is
still the treatment of choice for patients with early-stage disease. Currently,
there is no convincing evidence that patients with LCNEC should be treated differently than those with any other large
cell carcinoma. Patients with stage III and IV disease are treated the same as
those with other non–small cell types. Patients with stage III are treated with
combined chemotherapy and thoracic radiotherapy. Survival is similar to that of
patients with other non–small cell lung cancers, and patients with stage I are
treated with chemotherapy with palliative intent.
