Long-term disease control of a pancreatic neuroendocrine tumor with lanreotide autogel(®): a case report.

The CLARINET study (ClinicalTrials.gov: NCT00353496) showed that somatostatin analogs are able to stabilize tumor growth in patients with intestinal and pancreatic neuroendocrine tumors (NETs). Here, we present a case of NET originating from the pancreatic tail that was treated with lanreotide Autogel(®). A 60-year-old patient underwent resection of a pancreatic NET with splenectomy and distal pancreatectomy. Four months after surgery, there was an increase in chromogranin A levels, along with a hypercaptating lesion of approximately 3.5 cm at the residual part of the pancreatic corpus. Treatment with 30 mg monthly-administered octreotide long-acting release (LAR) was initiated. After 3 months of treatment, a control CT scan revealed diffuse metastases in the liver, although the patient presented no symptoms and liver tests were normal. Due to difficulties with the administration of octreotide LAR, treatment was switched to lanreotide Autogel(®) 120 mg, administered as monthly deep-subcutaneous injections. Progression-free survival, as shown by 3-monthly CT scans, was obtained for 2 years without the need to increase the lanreotide Autogel(®) dose, and the patient reported no side effects. After these 2 years, deterioration of the patient's clinical status and weight loss were observed, along with increased size of the liver lesions and appearance of peritoneal metastases. Chemotherapy treatment with cisplatinum-etoposide was initiated, while the lanreotide Autogel(®) injections were continued. After three chemotherapy cycles, a rapid decline in the patient's quality of life was noted, and she requested discontinuation of the chemotherapy and lanreotide injections. One month later, the patient died due to clinical progressive disease.

Transition of endometrial stromal sarcoma into high-grade sarcoma.

BACKGROUND: Endometrial stromal sarcoma typically is of low grade and hormone-sensitive. Although these characteristics result in an indolent behavior, little data are available on the evolution over time. CASE: We report on two cases where microscopic and immunohistochemic assessment of the tumor on several occasions during 8 and 25 years of follow up enabled us to document a transition of a low-grade into a high-grade malignancy. These were mainly characterized by increased cellular atypia, absence of spiral arterioles and an increased mitotic index and proliferation index (MIB1). Since this transition was related to clinical loss of hormone sensitivity, the therapeutic approach consisting of hormonal treatment in combination with repetitive surgery was switched to chemotherapy only. CONCLUSION: These long-term follow up data provide insight in endometrial stromal sarcoma tumor biology and highlight the importance of sampling recurrent tumors to estimate biologic behavior in order to tailor subsequent treatment.

Cytokeratin-positive meningeal peripheral PNET/Ewing's sarcoma of the cervical spinal cord: diagnostic value of genetic analysis.

Peripheral primitive neuroectodermal tumor (PNET)/Ewing's sarcoma (ES) of the central nervous system is extremely rare and should be differentiated from central PNET and other small blue round cell tumors. We describe a case of a meningeal peripheral PNET/ES of the spinal cord in an 11-year-old boy. Immunohistochemically, the small blue round cell tumor showed expression of epithelial markers and of CD99, thus posing an important differential diagnostic problem with a poorly differentiated synovial sarcoma. Fluorescence in situ hybridization revealed rearrangement of the EWS gene, as seen in peripheral PNET/ES. Peripheral PNET/ES does occur in the central nervous system, but its diagnosis can be extremely difficult on morphologic and immunohistochemical grounds alone. Genetic analysis plays a key role in its distinction from other small blue round cell tumors.

ERBB-2 gene overexpression and amplification in uterine sarcomas.

BACKGROUND: The aim of this study was to determine ERBB-2 (HER-2/neu) gene alterations in different subtypes of uterine sarcomas. METHODS: After central review, representative biopsies were immunohistochemically stained and semiquantitatively scored as negative, weakly (1+), moderately (2+), or strongly (3+) positive. Subsequently, fluorescence in situ hybridization (FISH) was performed on cases with 2+ and 3+ expression. RESULTS: Seventy tumors (52 primaries and 18 recurrent) were evaluated. All 10 adenosarcomas, 21 endometrial stromal sarcomas, and 10 leiomyosarcomas were negative both in the primary and recurrent setting. Twenty-two primary carcinosarcomas were scored. The epithelial component was negative/1+ in 16 (73%), 2+/3+ in five (22.5%) tumors, and could not be evaluated in one case (4.5%), whereas the sarcoma component stained negative/1+ in 21 cases (95.5%) and 3+ (4.5%) in one case. In two recurrent carcinosarcomas, the epithelial component stained 3+ in both cases, whereas the sarcoma component scored negative and 1+. Amplification of the ERBB-2 gene as determined by FISH was observed in 3/7 (43%) carcinosarcomas with 2+ or 3+ overexpression, resulting in an overall 3/22 (14%) amplification rate. One out of four undifferentiated uterine sarcomas stained 2+. ERBB-2 immunopositivity (3+) and ERBB-2 amplification by FISH were confirmed in the recurrent tumor, resulting in a gene amplification rate of 1/4 in undifferentiated uterine sarcomas. CONCLUSION: The current results suggest absence of ERBB-2 overexpression in uterine leiomyosarcoma, uterine adenosarcoma, and endometrial stromal sarcoma, whereas the ERBB-2 gene might have a biologic role in uterine carcinosarcoma and undifferentiated uterine sarcomas.

Transition of epithelial toward mesenchymal differentiation during ovarian carcinosarcoma tumorigenesis.

BACKGROUND: It was the purpose of this study to test the monoclonal theory in ovarian carcinosarcoma. METHODS: Twenty-six women with a diagnosis of ovarian carcinosarcoma were subjected to a clinicopathologic analysis. Biopsies from metastatic lesions obtained at primary surgery and surgery for recurrent disease were reviewed. Special attention was paid to the composition of metastatic lesions and to florid desmoplastic reaction as a potential pitfall for the detection of sarcomatous areas. RESULTS: Biopsies derived from metastatic disease at primary surgery (n = 107) consisted of carcinoma cells only (n = 71, 66%), >50% carcinoma cells (n = 21, 20%), >50% sarcoma cells (n = 13, 12%), or sarcoma cells only (n = 2, 2%). The microscopic analysis demonstrated a preponderance of epithelial cells in the primary setting and suggested the epithelial component to drive the tumor, a finding consistent with the monoclonal theory. Biopsies derived from surgery for recurrent disease (n = 8) consisted of carcinoma cells only (0%), >50% carcinoma cells (n = 1, 13%), >50% sarcoma cells (n = 4, 50%), or sarcoma cells only (37%). Since sarcomatous cells dominated the tumorigenic cell population in the recurrent setting, this analysis revealed a change of the composition of metastatic lesions in time when compared to the data in the primary setting. This change was supported by the observation of a threefold higher incidence of sarcoma-dominated metastatic lesions at interval debulking when compared to primary debulking (24 vs 8%, respectively). The potential of a phenotypic change during ovarian cancer progression was further highlighted by the detection of two cases of carcinosarcoma that presented as a recurrence of epithelial ovarian carcinoma. CONCLUSION: Our results are consistent with the monoclonal theory of ovarian carcinosarcoma histogenesis, but suggest that there is a tendency toward a sarcomatous differentiation during disease progression. These data are important to understand the tumor biology and might have implications for a tailored treatment of ovarian carcinosarcoma.