Clinicopathological Features and Gene Mutation Analysis of Gastrointestinal Stromal Tumors: A Series of 58 Patients

【Background】In gastrointestinal stromal tumors (GISTs), mutually exclusive gain-of-function mutations of KIT and PDGFRA are associated with different mutation-dependent clinical behavior. The study aims to analyze the characteristics of the clinicopathology and genotypes in GISTs in China.【Methods】All adult patients with GIST located in the stomach or small intestine who underwent surgical resections in the Cancer Hospital, Chinese Academy of Medical Sciences from January 2009 to January 2019 without prior Imatinib(Glivec) treatment were included. Specimens were collected for histopathological examination, and mutations in c-kit and PDGFRα genes were analyzed by PCR and the next generation sequencing(NGS). The clinicopathological characteristics of each gene were also analyzed.【Results】A total of 58 GIST patients was included in the study. Among the genotypes, there were 51(87.9%) c-kit mutations, five(8.6%) PDGFRα mutations, and two(3.4%) wild-type mutations. Among the cell types, there were 40 cases(69.0%) of spindle cell type, three cases(5.2%) of epithelioid cell type, and three cases(5.2%) of mixed cell type. Among the four mutant forms of c-kit exon-11, the most common were point mutation in 16 cases(38.1%), deletion mutation in 13 cases(31.0%), insertion mutation in four cases(9.5%), and mixed mutation in nine cases(21.4%). According to the National Institutes of Health(NIH) risk grade, there were three cases(5.2%) with very-low risk, nine cases(15.5%) with low risk, 19 cases(32.8%) with medium risk, and 23 cases(39.7%) with high risk. There were significant differences in cell types among different gene types(P = 0.022) and significant differences in tumor risk among different mutant forms of c-kit gene exon-11(P = 0.039).【Conclusion】In c-kit mutations, spindle cell type was significantly more than epithelioid cell type and mixed cell type. In PDGFRα mutations, spindle cell type and mixed cell type were prevalent. In wild type, spindle cell type and epithelioid cell type were significantly common. A high risk of deletion mutation and mixed mutation is expected in the c-kit exon-11 mutation form, while the intermediate risk of point and insertion mutations are common.

Cytokeratin-positive interstitial reticulum cell (CIRC) tumor in the lymph node: a case report of the transformation from the epithelioid cell type to the spindle cell type

Background Cytokeratin-positive interstitial reticulum cells (CIRCs), which are a subgroup of fibroblastic reticular cells (FRCs), are known to be present in the lymph nodes. There have been only a few cases of tumors derived from CIRCs. Case presentation We have reported a new case involving a CIRC tumor in a 75-year-old man and reviewed the literature. The resected mediastinal lymph nodes showed epithelial-like proliferation of large atypical round and polygonal epithelioid cells. The tumor cells expressed CK8, CK18, CAM5.2, AE1/AE3, epithelial membrane antigen, vimentin, fascin, and some FRC markers, which is consistent with the diagnosis of a CIRC tumor. Following chemotherapy, the CIRC tumor was observed to have responded very well and became difficult to confirm on imaging, but a small cell lung carcinoma developed 12 months later. Chemoradiotherapy was performed, but the patient passed away 29 months after the initial diagnosis. The autopsy revealed the recurrence of the CIRC tumor, residual small cell lung carcinoma, and a very small latent carcinoma of the prostate. The relapsed CIRC tumor cells had a spindle shape; they were highly pleomorphic and had invaded the superior vena cava. Conclusion We first reported autopsy findings of CIRC tumors and demonstrated the transformation of the tumor from the epithelioid cell type to the spindle cell type.

Spindle cell carcinoma of the breast managed with neoadjuvant AIM: A case report

Spindle cell carcinoma (SpC), also known as metaplastic carcinoma—spindle cell type, is a subtype of metaplastic carcinoma. Metaplastic carcinomas of the breast are rare but are thought to be more aggressive than invasive ductal carcinomas. Due to their rarity, there are few randomized trials that can inform any standardized approaches to treatment. Treatment is instead extrapolated from other types of breast cancer or metaplastic carcinomas of different locations. Here we present the first known case report of a patient with spindle cell carcinoma of the breast successfully treated with a standard sarcoma neoadjuvant regimen of doxorubicin, ifosfamide, and mesna (AIM) that resulted in >99% necrosis of the tumor and negative margins at the time of resection.