Tracheal ACC is a rare low-grade malignant tumor of the trachea and bronchi. It is most common in the lower third of the main bronchus and can occur at any age with a peak incidence of 40–50 years of age . Because the ventilatory capacity of the trachea is obviously greater than the general actual needs of the body, early small tumors in the trachea can not cause any symptoms of airway obstruction, with only occasional chest tightness, irritant cough, phlegm, or cough blood sputum. For primary tracheal tumor, although fiberoptic bronchoscopy detection rate is low, it is unique for early occult lesions and preoperative pathological diagnosis. In our case, fibrebronchoscopy revealed new organisms on the left and front walls of the lower part of the trachea, extending from 3 cm above the protrusion to the upper left main bronchus. The clinical features of this patient and the presence of fiberglass are very similar to those reported in the literature.
Primary tracheal ACC is a rare, distinctive salivary gland-type malignant neoplasm. The tumor is composed of a dual-cell population of luminal and myoepithelial / basal cells. ACC has three distinct growth patterns: tubular, cribriform and solid. Compared with typical ACC, the solid basaloid variant appears to be a high-grade variant. It is more aggressive, prone to distant metastasis and worse prognosis[2, 3]. The tumor cells in the basaloid variant exhibited moderate to marked atypia and pleomorphism. Increased mitotic activity is also commonly seen. Some of the cells surrounding the solid nests were arranged in a palisade pattern. In our case, in small areas which constituted less than 5% of the neoplasm, inconspicuous glandular lumen or cribriform structure can also be seen. Although very focal, the present of cribriform structures is the key morphological feature for diagnosis [6, 7]. The local cribriform structure can often reveal the nature of adenoid cystic carcinoma.
The two different cell types of ACC can be easily distinguished by immunohistochemistry. The basal layer cells are typically positive for myoepithelial markers (p63, S-100, Calponin), vimentin, whereas the luminal cells exhibit positivity for CK7, EMA, CK5/6 and c-kit (CD117). In our case, the tumor was uniformly positive for CK and CD117, with focal expression of CK7 and CK5/6, while myoepithelial cells were only rarely demonstrable with P63. Previous studies have revealed that the typical dual population of cell types is not always demonstrable in the solid (basaloid) variant of ACC . This is in concordance with our histologic results. The tumor is entirely composed of basaloid cells with only rare foci of myothelial cells. It has been suggested that basaloid cells represent primitive cells. They may be poorly differentiated or undifferentiated tumor cells with the potential of multi-directional differentiation into adenoid, squamous and myoepithelial cell cells. In solid variant of ACC with distinctive basaloid features, solid nests may be scattered with inconspicuous adenoid or sieve structures, which suggesting an undifferentiated or poorly differentiated ACC. Consequently, absence of cells expressing myoepithelial markers does not exclude the diagnosis of solid variant ACC [6, 7].
Series studies have revealed that C-kit gene encodes a glycoprotein receptor called CD117, a member of the tyrosine kinase family. CD117 plays a role in regulating apoptosis, cell differentiation, proliferation, chemotaxis and adhesion through phosphorylation with ligands. CD117 is expressed in 92% of salivary ACC . It is also the basis of differential diagnosis between salivary ACC and other head and neck malignancies. In addition to head and neck, ACC of the breast, trachea, skin and cervix also expressed CD117. Crisi, et al have shown that in classical cribriform or tubular ACC, CD117 is mainly expressed in the inner layer of the cell nest, but CD117 was observed in all the nests in solid variant of ACC with basaloid features. In this case, the expression characteristics of CD117 are the same as those in the literature. The authors believe that in addition to the histological features, ACC as an independent tumor entity, the constant expression of CD117 can be used as an important basis for differential diagnosis from other types of maligancis.
Person, et al confirmed the presence of translocation t(6;9)(q22-23;p23-24) in ACC, which led to the formation of an MYB-NFIB fusion gene and has been identified as a tumor specific cytogenetic abnormality of ACC. The consequence of the translocation leads to overexpression of MYB-NFIB transcripts and activation of MYB target genes involved with cell cycle control, apoptosis, cell adhension, and angiogenesis [6, 10]. The incidence of MYB-NFIB fusion in ACC was 49–57% (mean 54%) and it is highly specific . Detection of MYB rearrangement can be used as a reliable and accurate method for differential diagnosis between ACC and other tumors. In our case, FISH for MYB break-apart assay showed separate red and green signals in more than 30% tumor cells, supporting the diagnosis of solid variant of ACC. However, it should be emphasized that not all ACCs show MYB rearrangement, and a normal FISH pattern does not rule out this diagnosis.
The differential diagnosis includes several other small round tumors [6, 11, 12]. Poorly differentiated squamous cell carcinoma is composed of nests or cords of cells and has pseudoglandular structure without obvious keratinization. Frequently in situ carcinoma of squamous cell is found near the infiltrating area. p63 and CK5/6 are typically diffusely and strongly positive, whereas CD117 is negative. Small-cell (neuroendocrine) carcinoma shows similar features of tightly packed rounded or ovoid cells with hyperchromatic nuclei, scanty cytoplasm and nuclear molding. Markers of neural diffenentiation are variably expressed. CK may show a paranuclear, dot-like expression pattern. Nuclear TTF-1 expression may be prominent in more than 90% of cases, with different degrees of bcl-2 and CD117 positivity. The Ki-67 positive rate is usually more than 50%. Small cell carcinoma is generally free of the typical cribriform structure in adenoid cystic carcinoma. Nonkeratinizing squamous cell carcinoma (SCC) with basaloid features is a highly aggressive tumor with a worse prognosis. It mainly consists of clusters of basal-like cells, which are palisade-arranged around the tumor. CK5/6 and p63 have been shown to be positive in 90–100% of basaloid SCC with CD117 negative. Ewing sarcoma (ES) / primitive neuroectodermal tumor (PNET) cells are usually very bland and monotonous, sometimes with small amounts of clear cytoplasm, and are diffusely membranously positive for CD99. The tumor frequently shows rearrangements of the EWSR1 gene, leading to fusions with FLI1 gene most commonly. Mucosal melanoma is typically diffusely positive for S-100 protein and melanocytic markers. The tumor cells can be arranged in solid, glandular, epithelioma and sarcomatoid. In addition, tracheal ACC also needs to be differentiated from other primary tracheal malignancies, especially tracheal salivary gland-type tumors such as basal cell adenocarcinoma, epithelial-myoepithelial carcinoma.
Because of its growth characteristics, tracheal ACC is prone to local recurrence and distant metastasis. Approach of surgical resection depends on the location of the tumor in the airway. Surgical resection is the optimal management in most of the cases . Howerer, in several studies, surgical resection followed by post-operative adjuvant radiotherapy had a better prognosis and hence a preferred mode of treatment .
In summary, we report a case of solid variant of tracheal ACC with basaloid features. Due to its relatively complex tissue structure and certain limitations in bronchoscopy biopsy, it is concluded that in case of solid aggregates predominated by poorly differentated basaloid cells, primary tracheal ACC should be considered as an important differential diagnosis. Additional immunohistochemistry and molecular techniques could be applied to refine the diagnosis. This case report highlights the significance of various histological patterns and diagnostic modalities in making an accurate diagnosis of primary tracheal ACC at an early stage.