A three-month-old baby boy presented with complaints of blood in the stool with a duration of more than half a month. On clinical examination, B-ultrasound results suggested that solid hypoechoic mass was detected in the left lower abdomen, the size was about 6.9×5.0×3.9 cm. Enhanced Computed tomography (CT) showed a 6.3×4.6cm mass in the left lower retroperitoneal (Fig. 1A). The border is clear, showing uneven reinforcement. No other physical abnormalities were found. Blood routine examination revealed that hemoglobin was 63 g/L and the red blood cell count was 2.15×1012/L. The baby's parents and elder sister are in good health and no related neoplastic lesions were found.
Complete resection of the tumor and segmental bowel resection was performed without regional lymphadenectomy in the pediatric surgery department. The tumor located in the left mesentery with invasion into the colon and sigmoid junction. Adjuvant anti-cancer treatment was not undertaken after the operation on account of bad general condition.
Microscopically, under low magnification, tumors are distinctive in their multinodular colon wall involvement with interspersed tracts of colon wall smooth muscle (Fig. 2A), this is often referred to a “plexiform” pattern as reported before. Under high magnification, the tumor cells have mainly epithelioid cytology with a variably eosinophilic cytoplasm. The nucleus is round or oval, and the nucleolus is obvious. Mitotic images were easy to be seen (Fig. 2B). Lymphovascular and nerve invasion was not found under the microscope.
The panel of immune-histochemical stains included CD117, Dog1, CD34, SDHB, S100, SMA, Desmin, Vim, CD99, Fli-1, Syn, EMA, CDK4, Calponion, WT-1, CR, LCA, Myod1, and Ki67. Among them, Vim, CD117, and PDGFR were diffusely and strongly positive (Fig. 2C, D), which supports the diagnosis of gastrointestinal stromal tumors. Besides, the tumor cells lack SDHB expression, but normal intestinal mucosa and vascular elements were positive which verify adequate immunohistochemical detection (Fig. 2E). The remaining immune markers were negative. The Ki-67 labeling index (MIB‑1 index) reached 30% in the area of greatest concentration (Fig. 2F).
Mutational analysis showed a wild-type for KIT and PDGFRA at the five exons examined (KIT exons 9,11,13,17 and PDGFRA exon 18). In addition, all other targets (Her2、EGFR、RET、ROS1、PI3KCA、ALK、KRAS、NRAS and MET) showed no mutation. However, CCND2 amplification and amino acid missense mutation at position 932 of exon 19 of the PTCH1 gene was detected, which may have a significant impact on gene function. At last, we performed SDHB gene sequencing in Jinan Boshang Biotechnology Co. Ltd. Consistent with our expectations, the sequencing of SDHB in tumor showed synonymous mutation at position 169 of exon 1(C-A) (Fig. 3) which may be related to the occurrence and development of this tumor.
On the basis of these findings, the pathological diagnosis of SDH-deficient GIST was established.
Two months later, the baby was brought to our hospital again presented with complaints of cough for two weeks and diarrhea for two days. The results of abdominal color Doppler ultrasound showed that there was much effusion in the abdominal cavity. Abdominal enhanced CT findings suggested that multiple metastases were seen in peritoneum, mesentery, retroperitoneal, left groin and right lower abdominal wall (Fig. 1B). Pulmonary CT suggested double lung inflammatory lesions. Anti-infective treatment was carried out in PICU to correct symptomatic and supportive treatment such as anemia. When the condition improved, the baby left our hospital. After that his parents visited many other children's hospitals and cancer hospitals, however, no treatment options were acquired. In accordance with the advice of Zhongshan First Affiliated Hospital, Imatinib (100 mg‚ once daily) was administered. Because of severe diarrhea, the medicine was withdrawal after 3 weeks. Finally, the baby came back to Shandong Provincial Tumor Hospital to take conservative treatment and ascites to relieve bloating symptoms. Unfortunately, the disease continued to progress, the baby died 5 months after surgery.