Cushing's syndrome associated with a nested stromal epithelial tumor of the liver: hormonal, immunohistochemical, and molecular studies

Abstract

Context: Ectopic ACTH syndrome (EAS) is principally associated with aggressive malignant tumors but also with neuroendocrine tumors of good prognosis. Recently, rare nonhepatocytic nested stromal and epithelial tumors (NSET) were characterized by their possible association with Cushing's syndrome of which biochemical and physiopathological features were still incompletely studied. Objective: To describe the clinical and hormonal characteristics of an EAS originating from a liver NSET and further understand the mechanism of cortisol overproduction. Design and setting: This is a clinical case report from the Endocrinology Department of Caen University Hospital, France. Patient and intervention: A 17-year-old female patient was found to have a large liver NSET with mild Cushingoid clinical features and intense biological hypercortisolism but moderate ACTH secretion. Resection of the tumor was curative with a 30-month follow-up. Results: The epithelial component of the tumor coexpressed ACTH mildly, corticotropin-releasing hormone (CRH) strongly, and 11b-hydroxysteroid dehydrogenase at a level comparable with normal human hepatocytes. Conclusions: Liver NSET is a new cause of EAS, which may evoke hypercortisolism by multiple biochemical pathways.

Successful liver transplantation for non‐resectable desmoplastic nested spindle cell tumor complicated by Cushing's syndrome

“…DNSCT is known to occur predominantly in females (67% of reported cases) and occur commonly among children and young adults (range 2‐33 years) as shown in Table . Most of these tumors are discovered incidentally upon abdominal examination or imaging but a few patients present with abdominal symptoms . Cushing's disease secondary to ectopic ACTH has been associated with a significant number of these patients (8 of 36 reported cases; 22%) and responds well to tumor removal and medical adrenal suppression …”

“…In the vast majority of cases, these tumors are discovered incidentally upon imaging or physical examination; however, some patients present with abdominal symptoms as well. Cushing's syndrome due to ectopic production of ACTH has been well described in these patients and responds to medical management and tumor resection . Overgrowth syndromes like Beckwith–Wiedemann syndrome have shown an association with these tumors as well.…”

MANAGEMENT OF ENDOCRINE DISEASE: Cushing’s syndrome due to ectopic ACTH secretion: an expert operational opinion

“…These tumors are very rare, with only around two dozen reported cases (16,80,81,82,83,84,85,86,87,88,89,90,91,92,93). Most cases involve concomitant secretion of CRH and ACTH, although rarer forms of exclusive CRH secretion have been described (80).…”

Calcifying Nested Stromal-Epithelial Tumor of the Liver: An Update and Literature Review

“…6,15 In approximately half of the cases, entrapped, normally formed, mature-appearing bile ducts as well as cords of hepatocytes are seen within the tumor. [4][5][6][16][17][18] Those patients with vascular invasion generally develop tumor recurrence 1 to 6 years later and the presence of vascular invasion is likely related to tumor recurrence. 14 Additionally, the histology of some cases with recurrence reveals areas of sheetlike growth, mitotically active cells, entrapment of normal liver components, extensive necrosis with foamy histiocytes, and occasional multinucleated cells.…”