Combined Typical Carcinoid-Adenocarcinoma Lung Tumor
Combined tumors are those with a mixed histologic pattern. Combined neuroendocrine tumors consist of a neuroendocrine component as well as at least one other distinct tumor population. Although combinations of neuroendocrine tumors with non-neuroendocrine carcinomas (NNEC) can occasionally be found in the lungs, the neuroendocrine component of these tumors tends to be small cell lung carcinoma (SCLC) or large cell neuroendocrine carcinoma as opposed to typical or atypical carcinoids. We report a case of combined endocrine tumor of the lung consisting of typical carcinoid mixed with adenocarcinoma, one of only a few reported cases of its kind. Cavazza et al1 were one of the first and only to report a similar finding in 2001.
A 59-year-old white male, 90 packs per year smoker with nonalcoholic steatohepatitis cirrhosis being evaluated for liver transplantation, presented with an incidental right middle lobe 1.6×1 cm nodule with associated right upper lobe (RUL) punctuate nodules (Fig. 1A). Other pertinent history includes non-Hodgkin lymphoma in remission since 2007 and Crohn disease. A positron emission tomography scan revealed hypermetabolic activity with an standardized uptake value of 3.2 and 5.8 in the right middle lobe nodule and RUL punctuate nodules, respectively (Fig. 1B).
Flexible bronchoscopy with radial probe endobronchial ultrasound for guiding RML nodule biopsy followed by RUL and lingular bronchoalveolar lavage was performed. Histopathologic findings were consistent with a typical carcinoid tumor.
On the basis of the consensus recommendation from our multidisciplinary thoracic oncology board meeting, thoracoscopic middle lobectomy with RUL wedge resection and lymph node (LN) dissection followed. Pathology of the RML nodule revealed a combined tumor consisting of 95% typical carcinoid and 5% adenocarcinoma (Figs. 1C, D); the RUL wedge demonstrated necrotizing granulomatous inflammation and LN dissection was negative. The vast majority of the tumor nodule was diffusely and strongly positive for neuroendocrine markers chromogranin-A synaptophysin, and CD56, while weakly coexpressing neuron-specific enolase. The tumor nodule was also diffusely positive for CK-7. The minor glandular component was mostly negative for neuroendocrine markers and positive for CK-7. Bronchial resection margins as well as LNs were negative for malignancy. He is planned to have surveillance imaging with chest computed tomography scan in 3 months, then every 6 months for 2 years and annually thereafter.
Combined neuroendocrine tumors consist of a mixed histologic pattern, with both neuroendocrine and non-neuroendocrine tumor components. Combined neuroendocrine tumors can be further subcategorized by the composition of the neuroendocrine component, which can consist of typical carcinoid, atypical carcinoid, LCNEC, or SCLC.2 In 1 study of 1158 lung tumors, the prevalence of combined neuroendocrine tumors was 1.8% of the total population of resected lung tumors, of which only 2 cases of typical/atypical carcinoid neuroendocrine component were reported.3 Compared with single histology population tumors, combined neuroendocrine tumors with SCLC and LCNEC neuroendocrine components had a significantly greater degree of intratumoral vascular invasion as well as higher grading.3 The presence of SCLC and LCNEC components in these combined tumors led to more aggressive pathologic behavior and significantly influenced outcome. Survival rates for the single histology tumor group were 46% compared with 21% for the combined SCLC or LCNEC/NNEC group.3 The combined SCLC neuroendocrine tumor group prognosis was similar to that of pure SCLC rather than non–small cell carcinoma.3
Given the extreme rarity of combined typical or atypical carcinoid/NNEC tumors, there is no literature examining the clinical and prognostic aspects of patients with combined neuroendocrine tumors of this variety. As more cases of typical or atypical carcinoid/NNEC lung tumors are reported, it is important to compare the behavior and long-term outcomes of this tumor population with that of single histology population tumors.