Tumor-to-tumor metastasis (TTM) is an uncommon condition. Only a few cases of renal cell carcinoma (RCC) as donor tumor of TTM have been reported in literature, and none of these studies have described RCC metastasizing to synchronous pheochromocytoma (PCC).

The patient was a 54-year-old woman who presented with recurrent dull abdominal pain for six months, which was further aggravated for one more month. Enhanced computed tomography revealed a tumor mass in the right kidney and another mass in the left retroperitoneum/adrenal gland. Histopathology and immunochemistry of resected specimens confirmed the diagnosis of clear cell renal cell carcinoma (CCRCC) of the right kidney, and the left retroperitoneum revealed a typical PCC with CCRCC metastasis. Whole exome sequencing revealed the presence of a c.529A>T somatic mutation of the Von Hippel Lindau (VHL) gene in the metastasized CCRCC, which was also present in the primary right kidney CCRCC, as confirmed by Sanger sequencing. No VHL mutation was detected in the PCC or in normal right kidney tissue. Fluorescence in situ hybridization revealed loss of chromosome 3p in both the primary right kidney CCRCC and CCRCC metastasized to PCC in the left kidney.

This is the first case showing metastasis of CCRCC to PCC, thus leading to tumor-to-tumor metastasis.

• Tumor-to-tumor metastasis
• Clear cell renal cell carcinoma
• Pheochromocytoma
• Von Hippel Lindau somatic mutation
• Case report

Most pituitary tumors are considered benign adenomas, and only 0.1%–0.2% of them present metastasis and are defined as pituitary carcinomas (PCs). Refractory pituitary adenomas (PAs) lie between benign adenomas and true malignant PCs and are defined as aggressive-invasive PAs, characterized by a high Ki-67 index, rapid growth, frequent recurrence, and resistance to conventional treatments. Refractory PAs and PCs are notoriously difficult to manage because of limited therapeutic options. Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis not only during development but also during pathological processes in pituitary tumors. Recently, increasing numbers of preclinical studies and clinical research have demonstrated that anti-VEGF therapy plays an important role in pituitary tumors. The purpose of this review is to report the role of VEGF in the development and pathology of pituitary tumors and the progress of anti-VEGF therapy in pituitary tumors, including refractory PAs and PCs. Previous preclinical studies indicated that cyclin-dependent kinase 5 (CDK5)-mediated VEGF expression might play a crucial role in the development of PAs. Vascular endothelial growth inhibitors have been reported as independent predictors of invasion in human PAs and have been indicated as markers for poor outcome. Furthermore, several studies have reported that angiogenesis decreases tumor sizes in experimental animal models of pituitary tumors. The expression of VEGF is relatively high in PAs; therefore, anti-VEGF therapy has been used in some refractory PAs and PCs. To date, anti-VEGF has been reported as monotherapy, in combination with temozolomide (TMZ), TMZ and radiotherapy, and with pasireotide, which might be a promising alternative therapy for refractory PAs and PCs resistant to conventional treatments. However, the role of anti-VEGF therapy in pituitary tumors is still controversial due to a lack of large-scale clinical trials. In summary, the results from preclinical studies and clinical trials indicated that anti-VEGF therapy monotherapy or in combination with other treatments may be a promising alternative therapy for refractory PAs and PCs resistant to conventional treatments. More preclinical studies and clinical trials are needed to further evaluate the exact efficacy of anti-VEGF in refractory PAs and PCs.

• VEGF
• anti-VEGF
• pituitary carcinomas
• refractory pituitary adenomas
• vascular endothelial growth inhibitor

• Humans
• Intestinal Neoplasms
• Neuroendocrine Tumors
• Pancreatic Neoplasms
• Stomach Neoplasms

• Z99 CA999999 Intramural NIH HHS
• ZIA BC011286 Intramural NIH HHS
• ZIC BC011040 Intramural NIH HHS

Primary clear cell carcinoma of the liver (PCCCL) is a rare and special type of primary hepatocellular carcinoma. However, treatment methods for multiple metastatic PCCCL are lacking. Here, we report the case of a 55-year-old male PCCCL patient with multiple metastatic lesions who was clinically cured by sunitinib-based systematic treatment. This patient was diagnosed with PCCCL in Liver Segment 7, Child–Pugh A liver function, Stage A in November 16, 2009, and received radical excision of the cancer immediately. His disease recurred with multiple metastatic lesions in the liver and other parts of the body, including the retroperitoneal lymph nodes, lung and bilateral adrenal nodules in June 29, 2012. The biopsy results showed that the lung mass was lung metastasis of PCCCL. With Child–Pugh A liver function, Stage C of PCCCL was diagnosed. Sunitinib (37.5 mg, oral, once a day [qd]) in combination with Chinese herbal medicine (CHM) was given. The tumor size steadily reduced, and the lesions were no longer obvious in May 21, 2014. The patient had multiple metastases and is in complete response (CR) state until now. He is considered as clinically cured. From the initial diagnosis of PCCCL, the survival period reached 8 years.

• Chinese herbal medicine
• anti-angiogenesis therapy
• hepatocellular carcinoma
• primary clear cell carcinoma of the liver
• sunitinib

• Adult
• Aged
• Aged, 80 and over
• DNA Methylation/genetics
• Epigenesis, Genetic/genetics
• Female
• Genes, Tumor Suppressor
• Humans
• Male
• Middle Aged
• Multiple Endocrine Neoplasia Type 1/genetics
• Neuroendocrine Tumors/genetics
• Pancreatic Neoplasms/genetics
• Promoter Regions, Genetic/genetics
• Von Hippel-Lindau Tumor Suppressor Protein/genetics