A solitary small brain mass lesion is difficult to diagnose correctly. The important points of differential diagnosis are the density of the lesion, contour of the lesion, and edema of surrounding tissue.

In general, determination of the origin of metastatic malignancies is difficult pathologically. Immunohistochemistry was used to determine this. However, because specific antibodies are a few (such as PSA for prostatic carcinoma), a panel of antibodies are used. Nevertheless, determination of the origin and histological type are frequently difficult.

An immunohistochemical analysis was performed using Dako Envision method (Dako Corp. Glostrup, Denmark), as previously described [3-7]. The immnunohistochemical reagents and results are shown in (Table 1). The immunohistochemistry reveled that the carcinoma cells were positive for four types of pancytokeratins, cytokeratin (CK) 5/6 (Figure 3), CK7 (Figure 4), CK18, CK19, p63 (Figure 5), and Ki-67 (labeling = 78%). They were negative for high molecular weight CK, CK14, CK20, TTF-1, PE10. melanosome, S100 protein, EMA, vimentin, CD34, myoglobin, CEA, p53, desmin, α-smooth muscle actin, chromogranin, synaptophysin, CD56, neuron-specific enolase, CD68, KIT, and PDGFRA.

The positive CK7 and negative CK20 suggested a lung origin, and the cytokeratin profiles and positive CK5/6 and p63 suggested a squamous differentiation. The pathological diagnosis was undifferentiated carcinoma with squamous differentiation probably of lung origin.

Later, systemic CT, MRI and PET were performed, and they detected a small lung tumor (8 mm) in the right apex (Figure 6). The lung biopsy revealed an undifferentiated carcinoma with focal squamous differentiation (Figure 7); the immunohistochemical findings were almost the same as those of the brain tumor (Table 1).

In the present study, the author examined 33 antibodies. The author myself performed these the large number of immunohistochemical staining not only for practical use but also for academic interest. In general, anti-pancytokeratins AE1/3 and CAM5.2 were adequate. The both antibodies detect wide ranges of cytokeratin. The author stained polyclonal and tibody and KL-1 for academic interest. High-molecular weigh cytokeratin (34βE12) and CK5/6 cover squamous epithelium. CK5/6 is used from distinction from mesothelioma. CK7/CK20 patterns were widely used as diagnostic pathology. The use of CK14 was of academic interest, but CK14 is useful in esophageal squamous cell carcinoma. The use of CK18 and CK19 was of academic interest, but these were used for distinction from pancreaticobiliary carcinoma. PE10 and TTF-1 were used as markers of adenocarcinoma of the lung. Melanosome and S100 protein were used from differentiation from epithelioid malignant melanoma. EMA and CKs were used to determine the epithelial nature of the tumor. The mesenchymal markers including vimentin, myoblobin, desmin, S100 protein, α-smooth muscle actin, CD34, and CD68 were used for differentiation from carcinomatoid sarcoma. P63 was used for squamous and transitional cell carcinoma. CEA was used for differentiation from poorly differentiated adenocarcinoma. P53 and Ki-67 was used for the malignant nature of the tumor and for the proliferative fraction. Chromogranin, synaptophysin, CD56, neuron-specific enolase were used to determine the neuroendocrine features of tumor cells. KIT and PDGFRA were used for neuroendocine carcinoma as well as some particular neoplasm. The author stained KIT and PDGFRA, because the author has investigated these molecules and mutational status of these genes.

The brain tumor was pathologically metastatic undifferentiated carcinoma on HE sections in the present case. Immunohistochemically, the tumor was positive for p63, various types of cytokeratin, CK 5/6, suggesting that the carcinoma had squamous differentiation [9-11]. Negative immunoreactions for TTF-1 and PE10 suggest that the tumor had no adenocarcinomatous differentiation [9-11]. The absence of neuroendocrine antigens (chromogranin, synaptophysin, CD56, neuron-specific enolase) suggests that the brain tumor was not neuroendocrine carcinoma such as large neuroendocrine carcinoma. Thus, the author could determine the histological type of the present brain tumor.

The majority of solitary metastasis of brain tumor was lung cancer, gastrointestinal cancers, and breast cancers [12]. In the present study, the CK7 and CK20 pattern suggested a lung cancer together with squamous nature of the tumor [13,14]. Considering the frequency of metastatic brain tumor and the present immunohistochemical study, the author could suggest that the tumor was lung undifferentiated adenocarcinoma with squamous differentiation. In fact, later imaging modalities detected a very small occult lung cancer (8 mm) in the right apex. The lung tumor was found to have the same histology and immunohistochemical findings as the brain tumor. Therefore, the present case was diagnosed as a occult lung carcinoma with a solitary brain metastasis.

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