Primary small cell carcinoma of the pleura: a case report with immunohistochemical and molecular genetic analyses of KIT and PDGFRA genes

Abstract

An extremely rare case of primary small cell carcinoma of the pleura with an emphasis on KIT and platelet-derived growth factor receptor-α (PDGFRA) genes is reported here. A 67-year-old man underwent left testicular orchiectomy because of a testicular tumor. The tumor was immunohistochemically shown to be diffuse large B-cell lymphoma. The patient was treated with chemotherapy and radiation and followed up in our hospital. Eight years after the orchiectomy, the patient (75 years old) developed left pleural tumor and pleural effusion, and a biopsy was performed. The biopsy revealed a medullary malignant tumor consisting of small round and spindle cells. The following three possibilities were considered: recurrent lymphoma, mesothelioma, and small cell carcinoma. Immunohistochemically, the tumor cells were positive for cytokeratin, synaptophysin, CD56, KIT, and PDGFRA, but negative for CEA, cytokeratin 5/6, neuron-specific enolase, chromogranin, CD45, CD3, CD20, CD45RO, CD15, CD30, calretinin, WT-1, B72.3, D2-40, and TTF-1. Therefore, a diagnosis of pleural small cell carcinoma was made. A molecular genetic analysis using PCR-direct sequencing identified no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes. The patient was treated with chemotherapy (cisplatin) and radiation (50 Gray). The present case is the first reported case of primary small cell carcinoma of the pleura with an examination of KIT and PDGFRA expressions and KIT and PDGFRA gene mutations.

Basaloid squamous cell carcinoma of esophagus expressing KIT: A case report with immunohistochemical analysis

“…In general, KIT protein-positive tumors include GIST, acute myeloid leukemia, mast cell neoplasms, germ cell tumors, melanoma, neuroendocrine carcinomas (NEC), large cell neuroendocrine carcinoma (LCNEC), ACC, small cell lung carcinoma (SCLC), and extrapulmonary SmCC [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Of these neoplasms expressing KIT, KIT mutations are shown to be present in GIST [6][7][8][9][10][11]20,22,24,30], germ cell tumors [18,21], and malignant melanoma [19].…”

“…PDGFRA mutations are seen mainly in GIST [6][7][8][9][10][11]22]. In contrast, neuroendocrine carcinomas [13], large cell neuroendocrine carcinomas [11,12], ACC [6,8,9], SCLC [13,31,32], and extra-pulmonary SmCC [12,[14][15][16][17][18][19][20][24][25][26][27] are shown to express KIT and PDGFRA proteins, but no mutations are seen in these genes. Sihto et al [31] insisted that KIT expression in SCLC is due not to KIT gene mutations but to KIT gene amplification.…”

“…A molecular genetic analysis of KIT gene (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) gene was performed by the PCR direct sequencing method, as previously reported [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. The exons of both genes were selected because they are frequent mutation sites .…”

“…Both molecules are transmembranous oncoproteins involved in tumorigenesis of some neoplasms including gastrointestinal stromal tumor (GIST), acute myeloid leukemia, mast cell neoplasms, germ [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. The hot spots of gene mutations are exons 9, 11, 13, and 17 of KIT gene and exons 12 and 18 of PDGFRA gene [6][7][8][9][10][11].…”

Projected focal nodular hyperplasia of the liver with pronounced atypical ductular reaction resembling ductal plate and expressing KIT

“…KIT (CD117) is a receptor tyrosine kinase whose ligand is stem cell factor. KIT is expressed in GIST, 24,25 malignant melanoma, 26,27 germ cell tumor, 28,29 small cell carcinoma 30,31 and other tumors. Bile ductules are known to express KIT and stem cell factor in adult and embryonic livers.…”