Characterization of spindle cell component of ferret (Mustela putorius furo) adrenal cortical neoplasms – correlation to clinical parameters and prognosis

Abstract

Adrenal cortical epithelial tumours are common in ferrets. A variant tumour type with prominent spindle cell proliferation has been identified. We characterized these variant tumours with light microscopy and immunohistochemical analysis and correlate these features to clinical parameters and prognosis. We classified 24 ferret adrenal cortical masses with recognizable spindle cell proliferation obtained from the AMC and AFIP databases, based on percentage of spindle cells present and features of malignancy. These masses were separated into hyperplastic nodules and adenomas (both with 1-24% spindle cells), 'mixed' adenomas (>or=25% spindle cells), adenocarcinomas (1-24%) and 'mixed' adenocarcinomas (>or=25% spindle cells). Tumours were evaluated immunohistochemically for smooth muscle actin (SMA) and estrogen receptor (ER) expression. Disease-free interval (DFI) and survival time (ST) were calculated using Kaplan-Meier product limit method. Of 24 cases of spindle cell variant adrenal tumours, one was a hyperplastic nodule, 10 were adenomas, three were 'mixed' adenomas, six were adenocarcinomas and four were 'mixed' adenocarcinomas. The proliferative spindle cell cytoplasm was SMA-positive (smooth muscle myocyte origin). ER positivity, seen in nine of 24 cases, was restricted to adenocarcinomas, 'mixed' adenomas and 'mixed' adenocarcinomas. DFI and ST were significantly reduced in 'mixed' adenocarcinomas or tumours with ER expression. DFI was significantly reduced in tumours with marked smooth muscle. The spindle cell component of these variant adrenal tumours is smooth muscle in origin. The presence of abundant smooth muscle, a more malignant histologic grade ('mixed' adenocarcinomas) and ER expression are significantly positively correlated to both decreased DFI and decreased ST.

Animal models of adrenocortical tumorigenesis

“…In practical terms, however, distinguishing benign and malignant ACTs is often challenging. A separate spindle cell component that expresses smooth muscle actin may be seen in benign or malignant adrenocortical neoplasms in ferrets (Fig 1D), although the prognostic importance of this component is unclear (Gliatto et al, 1995; Newman et al, 2004). …”

Paraplegia in a Domestic Ferret (Mustela Putorius Furo) Secondary to Metastatic Adrenocortical Carcinoma with Myxoid Differentiation

“…9 Previously described variants of adrenocortical carcinomas in ferrets include spindle cell variants and carcinomas with myxoid differentiation. 9,14,15 Adrenocortical carcinomas with myxoid differentiation have been rarely reported in human literature, but have been associated with malignancy. 15,16 This case represents an unusual presentation of adrenal disease in ferrets and is the first report documenting the clinical progression of a ferret with adrenocortical carcinoma with myxoid differentiation.…”

Neoplastic diseases in the domestic ferret (Mustela putorius furo) in Italy: classification and tissue distribution of 856 cases (2000–2010)

“…The morphology of the polygonal neoplastic vacuolated cells strongly resembled adrenal cortical cells, suggesting a possible origin from ectopic adrenal tissue. The documented presence of a spindle cell component within certain adrenal neoplasms likely supports this hypothesis [17, 18], and has been considered both a normal stromal component of the tumours or part of the tumours itself [17, 18]. …”