A man in his late 50s presented with paranesthesia pharynges for 25 days, no obvious dysphagia and any significant health problems. Magnetic resonance imaging (MRI) showed thickening sinus mucosa in the right side of piriform recess, iso-intensity on T1-weighted image, and mild hyper-intensity on T2-weighted image and DW image, with inhomogeneous enhancement. Standard upper endoscopy showed a protruded lesion at 35 cm from the Incisor. Hypopharyngectomy and partial esophagectomy were subsequently performed. The surgical specimen showed a solid tumor in the right dipper, which was involved in the piriform recess with a size of 1.5*1.3cm, and another ulcer focus in the esophagus measuring about 1*0.8cm.
The hematoxylin and eosin (H&E)-stained section showed the tumor was composed of two distinct morphological types. One was a SCC component which had a solid pattern with a small area of squamous cell carcinoma invasion (Fig. 1A、B) and vascular tumor thrombus; the other was an adenocarcinoma with a cribriform and solid growth pattern, interstitial vitreous degeneration and central necrosis were also observed (Fig. 1C), tumor cells showed moderate-to-severe atypia and no clear nerve invasion, mitotic activity were easily seen; There was an abrupt transition between these two components (Fig. 1D).
To further classify the tumor, a panel of immunohistochemical stains was performed. Immunohistochemical analysis revealed that CK7 was positive for the ACC but negative for the SCC component (Fig. 2A), CK5/6 and p63 were diffusely and strongly positive in SCC but patchily positive in ACC (Fig. 2B), p63 was only expressed in the outer luminal surface of the pseudocysts of the ACC component (Fig. 2C), furthermore, CD117 positively showed in the inner luminal surface of the pseudocysts of the ACC component but negative in the SCC component (Fig. 2D), p53 were negative in both of the two components (Fig. 2E); MYB, MYBL1 and NFIB genes detected by in situ hybridization method harbored no gene fusion in ACC components (Fig. 2F).
About 92% of ACC showed positive expression of CD117, which is the valuable factor in diagnosing ACC. CD117 was mainly expressed in the inner luminal surface of the pseudocysts of ACC, however, full-thickness expression could be observed in solid nest of cancer1. In this case, CD117 mainly expressed in the cytoplasm and cell membrane of cancer cell, which is consistent with earlier reports.
Fusion gene of MYB-NF1B leaded by t(6;9) (q22-23;p23-24) translocation is significant discovery for the diagnosis of ACC2–4, but only happened in about 50% of ACC5. According to recent reports, other molecular events such as NOTCH, PI3K signaling pathways, and epigenetic modification and DNA damage repair were also found to play an important role in the tumorigenesis of ACC6, 7. There is no gene fusion observed in this case, implied other mechanisms in the progression of ACC, which conforms to the reports.