To investigate the clinico-pathological characteristics of lacrimal adenoid cystic carcinoma with high-grade transformation (LACC-HGT).

The clinical and pathological data of 8 cases of LACC-HGT were retrospectively analyzed. Among of them, there were 4 males (4 eyes) and 4 females (4 eyes); aged from 19 to 65 years old with a median age of 44.5 years old. Gender, age, first symptoms, tumor size and bone destruction of all patients were recorded, and histopathological characteristics were observed. Immunohistochemical study for P63, SOX10 (SRY-related HMG box 10 protein), cytokeratin 7 (CK7), cluster of differentiation 117 (CD117), Ki-67, MYB, human epidermal growth factor receptor 2 (Her-2) and androgen receptor (AR) was carried out.

Among of these cases, 5 cases had exophthalmos, accounting for 62.5% (5/8); 1 case had swollen eyelids, accounting for 12.5% (1/8); 2 cases had exophthalmos with swollen eyelids, accounting for 25% (2/8). The tumor size was 2 to 5 cm with an average of (3.50±0.92) cm. 6 cases had bone destruction, accounting for 75% (6/8). Follow-up data of 2 cases were incomplete. 4 cases died of the remaining 6 cases with complete follow-up data all who had metastasis, and the metastatic sites included parotid gland, lung, brain, bone and regional lymph nodes. The survival time of the dead patients was 3 to 54 months, with a median survival time of 26 months. 8 cases of masses were all solid, with a maximum diameter of 2 to 5 cm and an average of 3.5 cm. The cut surface of the tumor was gray, solid and medium in texture, and the boundary with the surrounding tissue was not clear. The classic adenoid cystic carcinoma (ACC) area was shown in all 8 cases, of which showed low-grade cribriform structures (2 cases), accounting for 25% (2/8), solid structures (3 cases), accounting for 37.5% (3/8). 3 cases had cribriform and solid mixed structures and solid content>30%, accounting for 37.5% (3/8). The high-grade transformation (HGT) area accounted for 60% to 90% of the total tumor areas. LACC-HGT presented either as solid undifferentiated carcinoma or poorly differentiated adenocarcinoma. Histological examination showed obvious cell atypia, significantly enlarged nucleus, and prominent nucleoli and active mitosis (average 38.75/10 high power field). Nerve invasion (8 cases) and vascular invasion (5 cases) were observed, accounting for 100% (8/8) and 62.5% (5/8), respectively. Desmoplastic reaction (7 cases) and necrosis (6 cases) were found, accounting for 87.5% (7/8) and 75% (6/8), respectively. 4 cases with necrosis were accompanied by calcification. Immunohistochemical staining showed that in ACC region, P63 was expressed in the nucleus of myoepithelial cells in the peritubular and pericribriform areas, and shown in a mottled pattern in the solid nests. CK7 and CD117 were expressed in the luminal facial glands in tubular or cribriform areas, and more diffusely expressed in solid nests. MYB protein was expressed in nuclei of both myoepithelial and glandular epithelium. In HGT areas, P63-positive tumor cells were decreased, even disappeared completely in some areas, and CK7 and CD117 were diffusely and strongly positively expressed. The acinar-derived marker SOX10 was positively expressed in the nucleus, as well as MYB protein. The Ki-67 proliferation index was about 40% to 70% (average 52.5%) in the HGT region, and about 10% to 30% (average 15%) in the classic ACC region. Her-2 and AR were negatively expressed in ACC and HGT regions.

LACC-HGT was showd distinctive histopathological features and poor biological behaviors. Accurate diagnosis should be confirmed based on histopathological and immunohistochemical characteristics, which is significant to guide clinical treatment and prognostic evaluation.