In 2009, a 42-year-old non-smoking male presented to our hospital for the evaluation of a right lung nodule detected during physical examination. He underwent radical resection of the right lung, and the postoperative pathological report revealed a mucoid adenocarcinoma of the inferior lobe of the right lung (3.5 × 3.0 cm), but no positive lymph nodes (0 of 29; T2aN0M0 stage I). The patient relapsed in 2015. A computed tomography (CT) scan revealed a mass in the superior lobe of the right lung and mediastinal lymph node enlargement. He underwent resection of the residual right lung. Postoperative pathological evaluation and hematoxylin and eosin staining showed different histomorphologies in the primary lung site (mucinous type) (Fig a) and the fourth group of lymph node metastases (solid type, T2N2M0 stage III) (Fig b). Immunohistochemistry indicated a pulmonary origin of both tumors: TTF-1 and Napsin A were positive, and CK 5/6 and P63 were negative. We simultaneously detected ALK and EGFR gene status by reverse transcription-PCR (Amoy, Xiamen, China) in two tumor tissue specimens. The results indicated a positive EML4-ALK rearrangement in tissues and wild EGFR (Fig ). The patient received adjuvant chemotherapy and achieved stable disease.
A 43-year-old Malay man presented to our facility with a three-month history of fever, non-productive cough and weight loss. He was a chronic smoker and had no significant medical history. Results of a physical examination were unremarkable. A chest radiograph revealed a large right lower zone lung lesion, and a subsequent computed tomography (CT) scan of the thorax and abdomen revealed a large heterogeneously enhancing soft tissue mass in the right lower lobe of the lung with intra-cavitary extension into the left atrium via the right inferior pulmonary vein (Figure ). Transthoracic needle aspiration of this mass was suggestive of carcinoma. Surgery was performed for the resection of this mass; a right posterior lateral thoracotomy was performed, followed by a right lower lobectomy. The left atrium was opened at the inferior part of the superior pulmonary vein and the tumor resected with a small cuff of left atrium. The entire tumor and right lower lobe was delivered en bloc, and the left atrial defect subsequently patched. Histology demonstrated a high-grade clear cell sarcomatoid tumor, suggestive of metastatic clear cell renal cell carcinoma, a diagnosis specifically considered by the pathologist. On immunohistochemistry, the lesion was focally positive for epithelial membrane antigen (EMA), CD10 and vimentin, but negative for anticytokeratin CAM5.2, thyroid transcription factor-1 (TTF-1), smooth muscle actin (SMA), S100, HMB-45, Melan-A, Hepar and synaptophysin. However, as no renal lesion was evident on the CT scan (Figure ), a diagnosis of alveolar soft part sarcoma was considered. An additional extensive investigation did not reveal a primary lesion or any other metastatic lesions.\nThen, four months later, our patient developed a subcutaneous mass in his left loin. A CT scan of the abdomen confirmed a large 11 cm tumor occupying nearly the entire right kidney with involvement of the pelvicalyceal system and proximal ureter (Figure ). The tumor also extended into the right renal vein and the inferior vena cava, with a 2 cm soft tissue nodule was seen in the subcutaneous layer of the left flank. Further imaging of the thorax demonstrated multiple lung nodules, a large right pleural-based mass and an enlarged subcarinal lymph node. A bone scan was performed, and suggested involvement of the right humeral head and multiple thoracic vertebrae. Excision biopsy of the subcutaneous nodule was performed, and histology demonstrated a tumor morphologically similar to the initially resected lung lesion, suggestive of a high-grade clear cell renal cell carcinoma with sarcomatoid differentiation (Figure ). On immunohistochemistry, the tumor was strongly positive for vimentin, CD10, focally positive for epithelial membrane antigen, melan-A and negative for TTF-1, S100, inhibin and synaptophysin (Figure ) The positive vimentin and negative inhibin results weighed against the likelihood of an adrenocortical tumor.\nOur patient was given palliative first-line therapy of sunitinib, with initial best response of stable disease. After three cycles of sunitinib, the disease progressed; our patient declined any further therapy and he eventually died 13 months after his initial lung resection.