A Multicenter Randomized Phase II Study of Single Agent Efficacy and Optimal Combination Sequence of Everolimus and Pasireotide LAR in Advanced Thyroid Cancer.

PURPOSE: Aberrant mTOR pathway and somatostatin receptor signaling are implicated in thyroid cancer and offer potential therapeutic targets. We assessed the clinical efficacy of everolimus and Pasireotide long-acting release (LAR) in radioiodine-refractory differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC). PATIENTS AND METHODS: Adults with progressive MTC and DTC untreated or treated with no more than one systemic agent were eligible. The trial was designed to establish the most promising regimen and the optimal combination sequence. Patients were randomized to start treatment with single agent everolimus (10 mg QD; Arm A), pasireotide-LAR (60 mg intramuscular injection, Q4 weeks; Arm B), or the combination (Arm C). At initial progression (PFS1), patients on Arm A or B switched to the combination and continued until progression (PFS2). Efficacy was measured by RECIST criteria. RESULTS: Study enrolled 42 patients: median age 65 years; female 17 (40.5%); White 31 (73.8%), African American 6 (14.3%), others 5 (11.9); DTC 32 (76.2%); MTC 10 (23.8%). There was no objective response by RECIST criteria across the three arms. Median and 1-year PFS1 rates were 8.3, 1.8, 8.1 months and 49.9%, 36.4%, 25.0% for Arms A, B, C, respectively. Median and 1-year PFS2 rates were 26.3, 17.5, 8.1 months and 78.4%, 70.0%, 25% for Arms A, B, C, respectively. The most frequent adverse events were anemia, stomatitis, fatigue, hyperglycemia, and hypercholesterolemia. CONCLUSIONS: The combination of everolimus and pasireotide-LAR showed promising efficacy over single agent. The delayed combination of everolimus and pasireotide-LAR following progression on single agent everolimus appeared intriguing as a combination strategy.

Intravascular lymphoma: an unusual diagnostic outcome of an incidentally detected adrenal mass.

OBJECTIVE: To describe a rare diagnosis of intravascular lymphoma in a patient presenting with an incidentally discovered adrenal mass. METHODS: We describe the patient's clinical history and the findings from biochemical evaluation, radiologic studies, and surgical pathology and review the relevant literature. RESULTS: A 43-year-old woman developed sudden onset of flank pain associated with a flushing sensation and presented to the emergency department where computed tomography showed a 5-cm left adrenal mass. She had normal electrolytes, and serum and urinary test results were negative for pheochromocytoma. A 24-hour urinary cortisol level was minimally elevated, and the midnight salivary cortisol value was within the reference range. Magnetic resonance imaging revealed a 6.5 x 5.8-cm left adrenal lesion that demonstrated moderate T2-weighted signal and gradual delayed enhancement with no drop in signal on out-of-phase images. Since the lesion lacked high intensity and the biochemical testing results did not suggest a pheochromocytoma, it was deemed likely that the mass was a malignant lesion of the left adrenal gland. A laparoscopic left adrenalectomy was performed. Morphologic and immunohistochemical findings were consistent with a large B-cell lymphoma, which by virtue of its near exclusive distribution in vascular spaces, was consistent with the diagnosis of intravascular large B-cell lymphoma. CONCLUSION: Intravascular large B-cell lymphoma should be included in the differential diagnosis of an incidentally detected adrenal mass even though the diagnosis is rare.

Maternal cell microchimerism in newborn tissues.

OBJECTIVES: On the basis of reports of maternal cells being detected in the umbilical cord blood of newborn infants, we tested the hypothesis that maternal cells can migrate out of the circulation into newborn tissues. STUDY DESIGN: We studied autopsy material from 4 newborn infants who never received a blood transfusion and died during the first week of life. The study subjects' diagnoses were trisomy 21 with nonimmune hydrops, 46, XY, 4q+ with multiple congenital anomalies, Potter syndrome, and congenital ichthyosis. Fluorescence in situ hybridization analysis with X and Y chromosome-specific probes was performed on sections of paraffin-embedded tissue, including liver, spleen, thymus, thyroid, and skin. RESULTS: Female cells, as defined by the presence of intact nuclei with two X chromosome signals, were detected in multiple tissue types from all 4 male neonates. The number of female cells varied from 3 to 45 per slide. CONCLUSIONS: Maternal cells enter the fetal circulation and are capable of migration to fetal and neonatal organs. This is of importance with regard to potential consequences of umbilical cord blood transplantation and postnatal development of autoimmune disease.