The incidence of lung adenocarcinoma is increasing year by year, and it has become the most common subtype of lung cancer, accounting for almost 50% of all lung cancers [3]. The 2015 edition of the WHO classification of tumor of the lung reclassifies lung adenocarcinoma based on the growth patterns of cancer: ①preinvasive lesions, including adenocarcinoma in situ and atypical adenomatoid hyperplasia; ②early invasive lesions were named tiny invasive adenocarcinoma; and③ infiltrating adenocarcinoma, including volt wall-like type, acinar type, nipple type, micropapillary type and solid type, and invasive mucinous adenocarcinoma, colloid adenocarcinoma, fetal adenocarcinoma and intestinal adenocarcinoma were introduced [4]. EGFR is a typical driving oncogene in lung adenocarcinoma. The global prevalence of mutations in this gene is still difficult to estimate, and there are great racial differences. According to the literature reports, the incidence of EGFR mutations is 10–15% in Caucasian individuals, 20%-40% in Asian individuals, and even more than 60% in nonsmoking Asian individuals [5]. Therefore, the detection of EGFR gene mutations is not only helpful for the early diagnosis of lung adenocarcinoma patients but also provides a basis for gene-targeted therapy and prognostic evaluation of lung adenocarcinoma.
Pulmonary carcinoid tumorlets are fibrotic nodules formed by hyperplastic pulmonary neuroendocrine cells (PNECs) continuously breaking through the airway mucosal epithelial basement membrane, and the diameter of these nodules is less than 5 mm. If the size of the nodule was greater than or equal to 5 mm, it is diagnosed as a carcinoid tumor. Pulmonary carcinoid tumorlets are a rare disease in primary lung tumors. This disease is often found accidentally in operation or autopsy specimens and is most common in lung inflammation and fibrosis [6].
Pulmonary carcinoid tumorlets have a hidden onset, slow development and lack of specific clinical manifestations. The main symptoms are closely related to the accompanying lung diseases. When hyperplastic PNECs cause tracheal obstruction, stenosis and inflammatory reactions, they can manifest as cough, expectoration, hemoptysis, chest tightness, shortness of breath or progressive dyspnea, and some patients have carcinoid syndromes, such as facial flushing, skin pigmentation, muscle weakness, and diarrhea [7]. Pulmonary carcinoid tumorlets are usually multiple pulmonary nodules that can occur in a single lobe, in multiple lobes, or even in both lungs, and the number ranges from several to dozens [8]. Because of the small volume of these lesions, the common X-ray or CT examination easily leads to missed diagnosis; the different thicknesses of CT may also affect the imaging number of pulmonary nodules, and the disease is often accompanied by some pulmonary disease, which is easy to cause misdiagnosis.
Lung adenocarcinoma and carcinoid tumorlets are two kinds of tumors with different tissue sources. Their coexistence is rarely reported. Only Flynn et al [9] reported a case of right superior lobe carcinoma in the literature in 2004, and low differentiated squamous cell carcinoma, moderately differentiated adenocarcinoma and typical small carcinoid were simultaneously detected in the surgically resected specimen of the right superior lobe.
At the same time, several medical records of lung adenocarcinoma complicated with carcinoids were found. Jung-Legg et al [10] reported a case of three concurrent lung malignant tumors in 1986; two of them were central bronchial carcinoid and peripheral small cell carcinoma in the superior lobe of the right lung, and the third was peripheral adenocarcinoma in the middle lobe of the right lung. Sen et al [11] reported a case of resection of the lower lobe of the left lung in 1998, and adenocarcinoma and typical carcinoid coexisted in postoperative specimens. Metastasis occurred in the ipsilateral hilar lymph nodes, but the metastatic components were composed of well-differentiated adenocarcinoma. Yano et al [12] reported a case of resection of the middle and lower lobes of the right lung in 2002. Pathology confirmed that the tumor in the lower lobe of the right lung was bronchial carcinoid, but the tumor in the middle lobe of the right lung was adenocarcinoma. Nagamatsu et al [13] reported in 2012 a case of adenocarcinoma found in the resection of the superior lobe of the right lung, and carcinoid was detected in the central fibrous scar of the adenocarcinoma. Abbi et al [14] reported a case of a tumor found during resection of the superior lobe of the right lung in 2014. Postoperative pathological examination showed that the tumor was a collision tumor composed of micropapillary adenocarcinoma and typical carcinoid. Saladi et al [15] reported an elderly male cachexia patient with massive pleural effusion in the right lung in 2018. No cancer cells were found in the right pleural effusion puncture. Neoformation was found in the left lower lobe bronchus by bronchoscopy, which was confirmed as carcinoid by pathological biopsy. The cause of pleural effusion was unknown, so thoracoscopic exploration was performed. Multiple pleural nodules were found in the right pleura during the operation, and these nodules were confirmed to be adenocarcinoma by biopsy and gene detection; however, EGFR mutation, KRAS mutation, ALK rearrangement and PD-L1 expression were all negative. The patient was given palliative chemotherapy after the operation. Drpa et al [16] reported a case of adenocarcinoma in stage IIIB found in the right superior lobe that coexisted with bronchial carcinoid of the left lower lobe. Then, the patient underwent gene detection. The adenocarcinoma had an EGFR mutation, while the carcinoids did not have any EGFR mutations. After the patient was treated with erlotinib for 50 months, the adenocarcinoma progressed, but the carcinoid completely disappeared. The patient eventually died of intestinal obstruction due to abdominal metastasis.
This patient was diagnosed with adenocarcinoma in the left superior lobe combined with carcinoid tumorlets in left lower lobe. The two types of lung tumors were located in different lobes, which is very rare. This patient had symptoms of intermittent diarrhea, which may be a manifestation of carcinoid syndrome. However, diarrhea is not serious, and there is no special treatment. The pathological stage of adenocarcinoma of the left superior lobe is IA3 stage(T1cN0M0).
Although the EGFR mutation was positive, but according to the eighth edition of the UICC lung cancer stage, adenocarcinoma of the left superior lobe needs no further treatment and periodic follow-up. We consider that the micronodules of the right lung may also be carcinoid tumorlets. In view of the good prognosis of carcinoid tumorlets, it is recommended that patients do not need radiotherapy and chemotherapy and that close follow-up should be performed. This patient recovered well since the operation follow-up, with no recurrence.
Due to the lack of clinical understanding of microneoplastic carcinoids, misdiagnosis or missed diagnosis can easily occur. Therefore, we should pay attention not only to lump-based lung tumors but also to pulmonary micronodules in the clinic.