The Effects of Tumor Location on Diagnostic Criteria for Canine Malignant Peripheral Nerve Sheath Tumors (MPNSTs) and the Markers for Distinction Between Canine MPNSTs and Canine Perivascular Wall Tumors

Abstract

Canine malignant peripheral nerve sheath tumors (MPNSTs) occur not only in the peripheral nervous system (PNS) but also in soft tissue and various organs (non-PNS). The most important diagnostic criterion is proof of peripheral nerve sheath origin. This is difficult in non-PNS MPNSTs, and its differential diagnosis is challenging. Canine perivascular wall tumors (PWTs) also commonly arise in soft tissue. Their histopathological features are quite similar to those of canine MPNSTs, making their differential diagnosis challenging. To elucidate whether the morphological features are applicable to diagnose non-PNS MPNSTs and to demonstrate useful markers for distinction between canine MPNSTs and PWTs, the authors examined 30 canine MPNSTs and 31 PWTs immunohistochemically for S100, nestin, NGFR, Olig2, claudin-1, CD57, PRX, α-SMA, desmin, and calponin. Among canine MPNSTs, the PNS tumors displayed significantly higher S100 and Olig2 expression than the non-PNS tumors. The expression levels of the other markers did not differ significantly, suggesting that the same morphological diagnostic criteria are applicable regardless of their location. The PWT cells displayed significantly weaker immunoreactivity than MPNSTs to markers used except α-SMA and desmin. Cluster analysis sorted most canine MPNSTs and PWTs into 2 distinctly different clusters, whereas 3 MPNSTs and 6 PWTs were assigned to the opposing cluster. These 3 MPNSTs were negative for almost all markers, while these 6 PWTs were positive for only neuronal markers. In particular, NGFR and Olig2 were almost negative in the rest of PWT cases. These findings suggest that NGFR and Olig2 are useful to distinguish these 2 tumors.

Reclassification of 21 Presumptive Canine Peripheral Nerve Sheath Tumors (PNST) Using a Literature-Based Immunohistochemical Panel

“…In a recent study, Olig2 appeared to be a promising diagnostic marker for malignant PNSTs allowing the differentiation between PNSTs and PWTs with a positivity of 90% and 20%, respectively [9]. However, in the present study Olig2 results were quite disappointing, with extensive labelling of normal vessels walls and a 40% positivity recorded among PWTs.…”

“…Although plenty of different antibodies have been tested in the past fi fteen years to help the identifi cation of canine PNSTs [9,[12][13][14], no specifi c immunohistochemical marker has been identifi ed because of the heterogeneous data that emerged from these studies. For this reason a wide panel of reagents is generally used.…”

“…According to the previously published studies, PNST appears to be primarily a "diagnosis of exclusion", with the fi rst distinguishing feature being the negativity to muscle cell markers. Indeed, immunoreactivity for α-SMA and desmin is a quite unusual fi nding in human PNSTs, and specifi cally it was described in one case out of 135 PNSTs [20] and 75 PNSTs [21], while it was never documented for dogs [9,12]. A study on PWT subclassifi cation reports positivity to muscular markers and negativity to S-100 and GFAP as reliable immunohistochemical features to distinguish PWTs from PNSTs [11].…”

“…Therefore, in diagnostic practice a range of potential differential diagnosis is usually provided or a generic diagnosis of soft tissue sarcoma (STS) is made [9,10].…”

“…In particular, S-100, oligodendrocyte transcription factor 2 (Olig2), glial fi brillary acidic protein (GFAP), neuron specifi c enolase (NSE) and nerve growth factor receptor (NGFR) were suggested as PNST markers. Moreover, calponin, desmin and alpha-smooth muscle actin (α-SMA) have been proposed as PWT markers [9,[11][12][13][14]. However, the results of such studies were poorly standardized and no defi nitive diagnostic criteria were established.…”