Kazuhiko Hirano

Expression of stem cell factor (SCF), a KIT ligand, in gastrointestinal stromal tumors (GISTs) : A potential marker for tumor proliferation

Gastrointestinal stromal tumors (GISTs) show a high incidence of gain-of-function mutations of the c-kit gene, which encodes a receptor tyrosine kinase KIT. This mutation is seen independently of metastasis and/or recurrence of tumors; thus, the factors involved in tumor proliferation rate and malignancy are still not known. Some mesenchymal and epithelial tumors have been reported to co-express KIT and its ligand, stem cell factor (SCF), for autonomous proliferation by the autocrine mechanism. The purpose of this study is to clarify whether GIST cells produce SCF, despite mutated KIT with constitutive activation. Immunohistochemically, we examined the co-expression of KIT and SCF in 36 GIST cases. All cases were found to be KIT-positive, and of these, 21 cases, including four recurrent or metastatic GISTs, showed co-expression of SCF. MIB-1 labeling index was significantly higher, and the average tumor size was larger in SCF-positive cases. By confocal microscopy, KIT was expressed on the cellular membrane, around which SCF was distributed less densely. Western blot analysis revealed that the membrane-bound SCF of 31 kDa was found to be approximately 10 times more abundant than the soluble SCF of 18.5 kDa, suggesting continuous KIT activation. These results indicate that proliferation of GIST cells can be caused not only by the gain-of-function mutation of c-kit, but also by the autocrine mechanism of the SCF/KIT system. Thus, SCF expression would be a useful marker for tumor proliferation.

Leiomyosarcoma with dedifferentiation in a premenopausal patient discovered after uterine artery embolization

Although a hysterectomy is the most common treatment for relieving the symptoms attributable to uterine leiomyomas, uterine artery embolization (UAE) is now being used more frequently as an alternative to a hysterectomy. However, it is difficult to differentiate a leiomyoma from a leiomyosarcoma without performing a pathological examination. Reported herein is a rare case of leiomyosarcoma that showed dedifferentiation of the tumor cells after UAE. A premenopausal 48‐year‐old woman had been suffering from hypermenorrhea for 4 years before visiting the clinic. She underwent UAE for suspected symptomatic leiomyoma. Two months later, dilatation and curettage was performed because of genital bleeding and a necrotic mass was submitted for pathological examination. Three months after curettage, with renewed symptoms, endometrial biopsy was done, which confirmed pleomorphic sarcoma. Metastatic nodes to the lung were also found at that time. Multiple leiomyosarcomas and a leiomyosarcoma showing dedifferentiation of the uterine body were found on pathological examination. The patient had metastatic nodes to the brain later and died of metastatic disease 20 months in total after UAE. This is a rare case of leiomyosarcoma with dedifferentiation and multiple metastases occurring after UAE, suggesting that dedifferentiation could be derived from ordinary leiomyosarcoma and that the traumatic effect of curettage might cause early metastasis. The present case is a warning that careful and detailed evaluation of the uterine tumor are needed before UEA.

Multiple aortic aneurysms complicated by a rupture in the systemic lupus erythematosus: A case report

We report the case of a 61-year-old female who suffered from systemic lupus erythematosus (SLE) and died of a ruptured abdominal aortic aneurysm (AA). She was diagnosed to have SLE at 39 years of age, and was administrated steroids and prostaglandin E(2). From 52 years of age, AA, peripheral arterial occlusion, and multiple organ infarctions appeared repeatedly. At 59 years of age, she was found to be affected by antiphospholipid antibody syndrome (APS). In the following year, expansion of an abdominal AA was identified, but she was given only conservative treatment. In the next year, sudden epigastralgia and dyspnea occurred, and she died. An autopsy revealed multiple AAs up to 11 cm in diameter, one of which showed ruptures, forming a retroperitoneal hematoma. Marked atherosclerosis of the aorta was noted, and she also had aortic dissection accompanied by cystic medial necrosis (CMN). An old myocardial infarction and brain infarction were also confirmed. Although SLE with APS is common, a complication of the disease by CMN, multiple AAs, or ruptured AA has been described in several cases to date. Regarding the etiology of this complicated presentation, we presume synergistic involvement of various factors, such as atherosclerosis and CMN associated with SLE, thrombosis due to APS, and prolonged steroid therapy.

Immature teratoma of the ovary with distant metastases: favorable prognosis and insights into chemotherapeutic retroconversion.

We present a case of a young woman with an immature teratoma of the right ovary that showed systemic metastases. The patient initially experienced abdominal distention at the age of 15 years. Radiographic assessment revealed a right ovarian tumor; thus, right salpingo-oophorectomy was performed, and the resected ovarian tumor showed a multilocular cystic lesion with partially solid areas. Pathologic diagnosis was an immature teratoma, grade 2. As brain, lung, and liver metastases were discovered within 2 years after the operation, sequential resections of the metastatic foci were performed before chemotherapy as well as during the early and late stages of chemotherapy. The resected specimens of each metastatic focus contained histologically more mature elements of the primary immature teratoma and exhibited a decrease in the Ki-67 labeling index, the later the resection was performed. As far as we know, this is the first case of brain metastasis stemming from an immature teratoma of the ovary. In addition, it was highly suggestive that chemotherapy itself was the main etiological factor for the promotion of maturation. The favorable prognosis of this malignant tumor even after brain metastasis was verified by the 10-year-survival of the patient.

Expression of L-type amino acid transporter 1 in various skin lesions

L-type amino acid transporter 1 (LAT1) is a Na(+)-independent neutral amino acid transporter that has an essential role in cell proliferation. Although the involvement of LAT1 in human carcinogenesis has been investigated by immunohistochemistry in various organs, LAT1 expression in skin has not been reported yet. Therefore, in the present study, immunohistochemistry for LAT1 was performed in 15 keratoacanthoma (KA), 10 seborrheic keratosis, 16 Bowens disease, 11 basal cell carcinoma (BCC), and 9 squamous cell carcinoma (SCC) cases as well as 61 normal epidermis as control. It was demonstrated that LAT1 expression limited to the basal layer was occasionally observed in normal epidermis while its expression was significantly decreased in the epithelium of seborrheic keratosis and Bowens disease (P<0.05). By contrast, a significantly higher rate of LAT1 expression was observed in the epithelium of KA, BCC, and SCC than in normal epidermis (P<0.05). Although LAT1 expression was limited to the basal layer or rim of the nests in KA, LAT1 expression was also observed in the center of the nests in BCC and SCC (P<0.001). Thus, LAT1 is differentially expressed in various skin lesions and may be an especially useful marker to distinguish KA from SCC.

Unusual sonographic appearance of synovial sarcoma of the anterior abdominal wall

We report a case of synovial sarcoma in a 58‐year‐old woman arising from the anterior abdominal wall. Sonography demonstrated a large mass with an unusual complex “honeycomb” echotexture. Doppler imaging displayed increased vascularity in the solid parts of the tumor.