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.