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Abstract
Clear cell adenocarcinoma (CCA) of the lungs is no longer referred to as a subtype in recent classifications of lung adenocarcinoma. Like signet ring features, clear cell features are regarded as cytological features rather than histological subtypes. Additionally, in serous fluids, adenocarcinoma metastasis with clear cell features is a diagnostic challenging entity due to other tumors that come to mind first during the differential diagnosis. Here we report a case, diagnosed as CCA of lung metastasis in pleural fluid and evaluated its differential diagnosis.
Keywords: Clear cell morphology, lung adenocarcinoma, metastasis, serous effusions
How to cite this article: Introduction 
Clear cell adenocarcinoma (CCA) is a common histologic type of renal cell carcinoma.[1] However, there are CCAs of non-renal primary sites such as the ovarium and lungs.[2],[3]
CCA of the lungs has been considered a rare subtype of lung adenocarcinoma. However, CCA is no longer referred to as a subtype in recent classifications of lung adenocarcinoma due to a lack of available data with clinical significance.[4],[5],[6]
Like signet ring features, clear cell features are regarded as cytological features rather than histological subtypes.[5],[6]
Additionally, in serous fluids, adenocarcinoma metastasis with clear cell features is a diagnostic challenging entity. Here we report a case, diagnosed as CCA of lung metastasis in the pleural fluid and evaluated its differential diagnosis.
Case Presentation A 76-year-old male patient presented with right flank pain, cough with sputum, and decreased oral intake for 3 weeks. In his medical history, there were hypertension, cerebrovascular disease, and prostatic surgery. In thorax computed tomography (CT), a significant increase in the fluid was observed between the pleural leaves, which filled the right hemithorax completely. The right lung parenchyma could not be evaluated clearly. Approximately 2000 mL of reddish hemorrhagic fluid was drained through the right-sided pleural tube and 10 mL was sent for cytopathologic analysis.
One smear was prepared with the liquid-based cytology (LBC) method and a cell block was obtained. The smear was stained with Papanicolaou (PAP) and slides of cell block were stained with hematoxylin and eosin (H&E). On microscopic examination, tumor cells with large, vacuolized cytoplasm and irregular nuclei, in some with prominent nucleoli were seen in smear and cell block section. In some tumor cells, there was multinucleation and in some of them there was an appearance of a nucleus pushed into a pole of the cell. There were a few mesothelial cells, histiocytes, and mixed-type inflammatory cells [Figure 1]. The tumor cells had a clear cell morphology, and an immunohistochemical panel was performed according to this. Tumor cells were positive for BerEP4, EMA, CK7, and TTF-1. PAX8, CaIX, CD10, RCC, CD117, CK20, CEA, calretinin, and PSAP were all negative [Figure 2] and [Figure 3]. No mucin was detected with mucicarmine staining. A cytological diagnosis of metastasis of carcinoma with clear cell features was signed out with the recommendation of systemic examination of the case, especially the lungs, to find the primary tumor. In the second thorax CT, a hypodense lesion with a size of ~ 11 cm was noted in the lower zone of the right lung.
Figure 1: Tumor cells with large, vacuolized cytoplasm and irregular nuclei, in some with prominent nucleoli. In some of them, there was an appearance of a nucleus pushed into a pole of the cell. Most tumor cells were discohesive, but a few three-dimensional clusters were seen (a and b - PAP × 200, c and d - PAP × 400, LBC)
Figure 2: The appearance of tumor cells in the cell blocks (a - H&E × 200, b - H&E × 400). Positive staining with BerEp4 and CK7 (c - BerEp4 × 200, d - CK7 × 200)
Figure 3: Tumor cells were positive for TTF-1 and EMA, whereas PAX8, RCC, and calretinin were negative (a - TTF-1 × 200, b - EMA × 200, c - PAX8 × 200, d - RCC × 200, e - calretinin × 200) Discussion CCA of the lungs may be seen with subtypes such as solid, acinar, papillary, and micropapillary adenocarcinoma. Although it is not included as a subtype in the World Health Organization (WHO) classification of lung tumors, it is recommended to indicate cases with clear cell features, with its percentages in pathology reports.[5],[6]
In serous fluids, carcinoma metastasis with a clear cell morphology often suggests renal cell carcinoma (RCC). However, other rare neoplasms composed of clear cells must be considered in the differential diagnosis such as clear cell subtype of ovarian/endometrial/prostatic adenocarcinomas and less frequently malignant mesothelioma as well as metastatic RCC. The metastasis of lung adenocarcinoma with clear features is also very rare in serous fluids.[7] In our case, considering that the patient was male, and the specimen was a pleural fluid, the main distinction in diagnosis was made between RCC and lung adenocarcinoma. However, prostate and gastrointestinal system carcinomas and mesothelioma were excluded.
In differential diagnosis, immunohistochemical studies are very helpful. We used calretinin and BerEp4 for distinguishing adenocarcinoma from mesothelial proliferations. WT1, MOC31, and B72.3 can also be used.[8] In the diagnosis of metastatic RCC, PAX8, PAX2, RCC antigen, and CaIX are useful antibodies.[8],[9] In our case at the distinction between lung carcinoma and RCC, we used TTF-1, CD10, PAX8, RCC, and CaIX. Additionally, CEA, CK20, and PSAP were checked immunohistochemically for excluding prostatic and gastrointestinal system carcinomas.
In conclusion, a carcinoma metastasis with clear cell morphology in serous effusions can usually suggest an RCC metastasis, but especially in pleural fluids, lung adenocarcinoma with clear cell features should be kept in mind in the differential diagnosis.
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Conflicts of interest
There are no conflicts of interest.
References 
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/joc.joc_48_22
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