Solid Adenoid Cystic Carcinoma Research Articles

Cell type‐dependent biomarker expression in adenoid cystic carcinoma

AbstractBACKGROUND:Adenoid cystic carcinoma (ACC), a rare and progressive salivary malignancy, is characterized by cellular, morphologic, and clinical heterogeneity. The authors of this report hypothesized that the dual cellular composition of ACC plays an important role in biomarker evaluation, tumor biologic behavior, and response to therapy.METHODS:To investigate the differential localization and expression of the c‐Kit protein and the epidermal growth factor receptor (EGFR) protein, immunohistochemical analyses were performed on tissue arrays that were constructed from 199 tumors, and the results were correlated with clinicopathologic factors.RESULTS:c‐Kit expression was limited to the inner ductal epithelial cells, whereas EGFR expression was limited mainly to the outer myoepithelial cells in the majority of ACCs with tubular and cribriform patterns. In solid ACCs, c‐Kit uniformly was positive, whereas EGFR consistently was negative. A significant statistical correlation was observed between c‐Kit expression and a poor 3‐year outcome, and EGFR expression was correlated with a better 3‐year outcome.CONCLUSIONS:The current findings underscored the importance of cellular subtype localization of biomarkers in the clinical and therapeutic stratification of patients with ACC. Cancer 2010. © 2010 American Cancer Society.

Genetic Profile of Adenoid Cystic Carcinomas (ACC) with High-Grade Transformation versus Solid Type

Background: ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features and to compare results to solid ACC.Methods: Genome-wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, 4 with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), 5 solid ACC. In addition, Ki-67 index and p53 immunopositivity was assessed.Results: ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component.Conclusion: ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC.

Adenoid Cystic Carcinoma With High-grade Transformation

High-grade transformation of adenoid cystic carcinoma (ACC) (previously referred to as dedifferentiation) is a rare phenomenon that does not fit into the traditional ACC grading schemes. The importance and minimal criteria for distinction from solid (grade III) ACC are not well established. We report 11 new cases and review the literature to further define the profile of this tumor. The median age was 61 years (range: 32 to 72 y) with a male predominance (male to female ratio of 1.75:1). The most commonly involved sites were sinonasal (4/11) and submandibular (4/11). Lymph nodes were pathologically positive in 4/7 (57.1%) cases. Distant metastases to the lung (n=2) and soft tissue of the shoulder (n=1) were observed. Five of 9 patients (55.6%) died, all within 5 years with a median overall survival of 12 months. Histologically, ACC with high-grade transformation was distinguished from conventional ACC by nuclear enlargement and irregularity, higher mitotic counts, and the loss of the biphasic ductal-myoepithelial differentiation. Useful supportive criteria were prominent comedonecrosis and fibrocellular desmoplasia. The most common morphologies for the high-grade component were poorly differentiated cribriform adenocarcinoma and solid undifferentiated carcinoma. Micropapillary and squamoid patterns were occasionally present. Ki-67 and p53 labeling indices were elevated in the high-grade components, though c-kit and cyclin-D1 were not. ACC-high-grade transformation is a highly aggressive salivary gland tumor with a variety of histologic patterns. The high propensity for lymph node metastases suggests a role for neck dissection in patients with this rare tumor.

A case of adenoid cystic carcinoma parotid with perineural spread

Adenoid cystic carcinoma (ACC) of salivary glands is a slow growing malignant tumour, characterized by wide local infiltration, perineural spread, a propensity to local recurrence and late distant metastases [1, 7]. ACC is a rare tumour and forms about 1% of all malignant tumours of the oral and maxillofacial region [2]. ACC constitutes about 21.9% of all salivary gland malignancies [3]. ACC has three histopathologic patterns viz. tubular, cribriform and a solid pattern. Solid pattern is associated with increased local recurrence, high metastic rate and higher mortality [4]. We present a case report of solid ACC of parotid salivary gland in a 42 year old female with intracranial extension. Despite good initial response to radiotherapy, patient developed recurrence in the eyelid, orbit, maxilla of the same side and pons. The patient expired within a year of diagnosis.

Differential KIT expression in histological subtypes of adenoid cystic carcinoma (ACC) of the salivary gland

Adenoid cystic carcinoma (ACC) of the salivary gland is characterized by a prolonged but inevitably unfavorable clinical course. Recent studies suggested the transmembrane tyrosine kinase KIT to be involved in ACC pathogenesis. To investigate KIT expression in histologically defined subgroups of ACC and to clarify whether KIT gene copy number gain contributes to KIT overexpression, tumor tissue microarray sections including 55 ACC tumors were analyzed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). The prevalence of positive KIT immunostaining was 89% (49/55). Strong immunostaining of KIT was only found in cribriform and tubular but never in solid subtypes (p=0.02). Average KIT staining intensity was higher in cribriform and tubular (n=37) compared to solid (n=18) ACC subtypes (p=0.005). FISH analysis revealed copy number gains of the KIT gene in 6.1% (3/49) of tumors analyzed. Our results implicate that specific KIT tyrosine kinase inhibitors such as imatinib, might be used in future therapeutic approaches against subgroups of ACC.

Solid adenoid cystic carcinoma of the maxilla: Report of a case

Solid adenoid cystic carcinoma of the maxilla: Report of a case

Myoepithelial Cell Markers in Salivary Gland Neoplasms

We compared the immunoexpression of 5 myoepithelial cell (MEC) markers (alpha-smooth-muscle actin, calponin, h-caldesmon, vimentin, and S-100-protein) using 16 pleomorphic adenomas (PA), 15 adenoid cystic carcinomas (ACC), and 3 epithelial-myoepithelial carcinomas (EMC) of salivary glands. The alpha-smooth-muscle actin was useful for identification of MECs, especially in cribriform and tubular ACC, followed by EMC. Calponin was similar to alpha-smooth-muscle actin, except for polygonal and plasmacytoid cells of PA and for solid ACC, which showed alpha-smooth-muscle actin negative and calponin positive. H-caldesmon was negative. Vimentin immunostained all MEC types, and was negative in luminal cells. S-100 protein was expressed both in the nuclei and cytoplasm of MECs and luminal cells, especially in PA. The best way to identify MEC is using alpha-smooth-muscle actin or calponin, plus vimentin, since in tumors MECs are hardly ever fully differentiated.

A study of the extracellular matrix in salivary gland tumors.

Epithelial-mesenchymal interactions constitute fundamental phenomena in the development and maintenance of the characteristic branching pattern seen in salivary glands. This study was undertaken to discuss the extracellular matrix (ECM) role in morphogenesis and cellular differentiation of salivary gland tumors originating from the intercalated duct. The ECM components, laminin (LN), type IV collagen, fibronectin (FN), and tenascin (TN) were revealed using a streptoavidin-biotin immunohistochemical technique and analyzed in 34 cases of salivary gland tumors: pleomorphic adenoma (PA); myoepithelioma; basal cell adenoma (BCA); polymorphous low grade adenocarcinoma (PLGA); and adenoid cystic carcinoma (ACC). LN and type IV collagen were present in all tumors, confining well-organized duct-like structures, separating them from the stroma, or surrounding cell clusters. In PA and myoepithelioma, the basement membrane (BM) fragmentation was observed through LN and type IV collagen staining around each individual spindle-shaped cell, which was strictly related to the cell modification. Interestingly, BM interruption could not be seen in the malign tumors, however, was frequently augmented in some cases. LN, type IV collagen, and FN were also found in the stroma of all tumors studied, except for the pseudocystic spaces of ACC, which were only delimited by replicated LN and type IV collagen. TN exhibited a variable expression, being more intense in solid ACC. LN and type IV collagen were always present around morphologically well-differentiated duct-like structures in all tumors studied. BM interruption could not be seen in the malign tumors, on the contrary BM production was evident, which is probably related to invasion. FN was present in the stroma of all tumors, but TN was mostly observed in less differentiated and higher degree of malignancy tumors, such as solid ACC.

C-kit Expression Distinguishes Salivary Gland Adenoid Cystic Carcinoma from Polymorphous Low-Grade Adenocarcinoma

Adenoid cystic carcinoma (ACC) is characterized by persistent, relentless growth and a high rate of eventual metastasis. In contrast, polymorphous low-grade adenocarcinoma (PLGA) has a much lower risk of recurrence and rarely metastasizes. The histologic patterns of these two neoplasms can be similar. Expression of c-kit, a transmembrane receptor tyrosine kinase, has recently been reported to be expressed in ACC but not PLGA. Expression of galectin-3, a nonintegrin β-galactosidase–binding lectin, has been reported to be significant in PLGA and decreased in ACC.Formalin-fixed paraffin-embedded tissue from 9 ACC and 14 PLGA were immunostained for c-kit and galectin-3. Cases were scored as 1+ (5–25% positive), 2+ (26–50% positive), or 3+ (>50% positive). C-kit was expressed by 100% of ACC (3+: 7 cases; 2+: 1 case; 1+: 1 case) and by 57% of PLGA (2+: 2 cases; 1+: 6 cases). In all but one ACC, c-kit expression was confined to the inner cell layer. C-kit expression was also noted in the intercalated duct epithelium of the salivary glands and the acinar cells of the lacrimal gland. Galectin-3 was expressed in 8 of 9 cases of ACC and 14 of 14 cases of PLGA.The results of this, the first study to compare c-kit and galectin-3 expression in ACC and PLGA, suggest that c-kit expression characterizes ACC, but not PLGA. Galectin-3 immunohistochemistry does not have a role in the differentiation of ACC and PLGA. C-kit immunostaining may be a valuable adjunctive tool for this differential diagnosis, particularly in the setting of a limited biopsy. Our finding of different patterns of c-kit expression in tubular and solid variants of ACC supports the concept of solid variant ACC as a high-grade tumor, with progression toward an entirely “inner cell” phenotype.

Basal cell adenocarcinoma of the lacrimal gland

PurposeBasal cell adenocarcinoma is a recently recognized entity among malignant tumors of the salivary glands. This entity has not received enough attention among ophthalmologists and ophthalmic pathologists. We recommend that basal cell adenocarcinoma be included in the differential diagnosis of lacrimal gland tumors. DesignCase report. MethodsIn 1988 a lacrimal gland tumor was incompletely removed from the left orbit of a 36-year-old woman and diagnosed as “solid basaloid adenoid cystic carcinoma”. Soon after, an exenteration of the orbit was performed. In 1998, upon review of the initial histopathology, the diagnosis of solid adenoid cystic carcinoma was changed to basal cell adenocarcinoma. Results and main outcome measureThe pathologic findings included nests of basaloid cells with minimal atypia and incomplete palisading around the periphery. The cells were of two types. The first type were large, pale cells with round or oval nuclei, scanty cytoplasm, and ill-defined borders. The other type were smaller cells with hyperchromatic nuclei situated mainly near the periphery of the nests. There was no necrosis or perineural invasion. Mitotic figures were present. Cysts within the nests showed Alcian blue negative contents. Immunohistochemistry showed a positive reaction to cytokeratin and a negative reaction with smooth muscle actin (SMA). ConclusionsThe Alcian blue negative stain, the negative reaction to SMA, and the fact that the patient is still alive 10 years after exenteration favored the diagnosis of basal cell adenocarcinoma. It is essential to differentiate a basal cell adenocarcinoma of the lacrimal gland from the solid basaloid type of adenoid cystic carcinoma, because the former has a better prognosis. Patients with basal cell adenocarcinomas of the lacrimal gland should be closely monitored for local recurrences because this tumor has the tendency to show perineural invasion.

Nucleolar organizer regions in adenoid cystic carcinoma of the salivary glands.

In this study of proliferative activity of adenoid cystic carcinomas (ACCs) with different histological patterns, the argyrophilic staining method of nucleolar organizer regions (AgNORs) was applied to paraffin sections from 25 tumors. Sixteen of the neoplasms showed a mixture of different histological patterns in the same section. The AgNOR numbers in the different histological pattern areas in the same tissue sections of all 16 tumors were lowest in the cribriform, intermediate in the trabecular, and highest in the solid pattern areas. The mean AgNOR number was highest in the solid pattern (3.33 +/- 0.52), and lowest in the cribriform pattern (2.12 +/- 0.43). The results show the order of proliferative activity in the different histological pattern areas of ACC, and explain the previous clinical finding that the prognosis of ACC is poorest in solid pattern ACCs. AgNOR staining appears to be a useful technique for evaluation of the proliferative activity of each histological pattern area of ACC, especially when there are different histological pattern areas in the same tissue section.

An Immunohistochemical Study of the Distribution of Lysozyme, Lactoferrin, α 1-Antitrypsin and α 1-Antichymotrypsin in Salivary Adenoid Cystic Carcinoma

The immunohistochemical expression of lysozyme (Ly), lactoferrin (La), alpha 1-antitrypsin (alpha 1-AT), and alpha 1-antichymotrypsin (alpha 1-Ach) was described, and their distributions were compared to each other in 28 cases of adenoid cystic carcinoma (ACC) of the salivary glands. ACC materials were obtained from the parotid gland (7), the submandibular gland (4), the sublingual gland (8), and minor oral salivary glands (9). Histopathologically, ACC was classified into cribriform (14), tubular (3), and basaloid or solid patterns (11). Positive staining for Ly was found in 1 case of solid ACC in the sublingual gland; La was found in 4 cases (2 cribriform, 1 tubular, 1 basaloid) in the sublinguals (3) and parotid glands (1); alpha 1-AT was found in 6 cases and alpha 1-Ach in 17 cases. The immunohistochemical localization of Ly and La was usually confined to luminal tumor cells of tubulo-ductal structures, irrespective of the pathologic types. Positive staining for alpha 1-AT and alpha 1-Ach appeared in tumor cells of cribriform, tubular and solid ACC. Tumor cells with positive La staining coincided with a positive reaction to alpha 1-AT and alpha 1-Ach, and tumor cells with alpha 1-AT positive deposition were also positive for alpha 1-Ach. The contents of pseudocysts in the cribriform pattern showed a positive reaction to La, alpha 1-AT, and alpha 1-Ach. Of the 28 cases of ACC, positive expressions for Ly, La, alpha 1-AT and alpha 1-Ach were found with a high frequency of alpha 1-Ach staining (17 in 28 cases were positive). In sublingual ACC (8), 7 cases were positive for immunohistochemical reactions. Co-expression or simultaneous expression for Ly, La, alpha 1-AT, and alpha 1-Ach in ACC suggest that tumor cells are protected from proteolysis or degradation.

Solid adenoid cystic carcinoma of the maxilla

Seven cases of solid variant of adenoid cystic carcinoma of the maxilla are reported. Clinical and radiographic characteristics suggest origin within the maxillary alveolar bone. Swelling was minimal and disproportionate to the extensive, diffuse bone destruction universally present. Histologic features were typical of this neoplasm occurring in other sites and consisted of diffusely infiltrating islands of small, closely packed monomorphous cells with sparse cytoplasm, indistinct borders, and small hyperchromatic nuclei. Four of five patients with follow-up data died of their disease. This confirms the lethality of the solid variant. Rationale is presented for considering these malignancies to be of primary intraosseous origin.

New Prognostic Criterion in Adenoid Cystic Carcinoma of Salivary Gland Origin

Adenoid cystic carcinoma (ACC) of salivary gland origin shows histologic patterns (tubular, cribriform, solid) that have been correlated with the clinical course of the disease. Recognition of tubular pattern is generally easy. Discrimination between cribriform and solid types leaves some margin for the pathologist's subjective interpretation because it is essentially based on the amount of gland-like spaces, containing mucinous or hyalinized material, which are present in neoplastic nests. To overcome this problem and with the aim of identifying a more objective basis for prognostic evaluation of cribriform and solid ACC, the authors counted the number of gland-like spaces per square millimeter of tumor, excluding supporting stroma and small areas with the tubular pattern, in a group of tumors similar with regard to therapy, stage of disease, and microscopic evidence of tumor-free surgical margins. According to the authors' data, the number of gland-like spaces per square millimeter of tumor appears to be a reliable and objective measure for prognostic evaluation of cribriform and solid pattern ACC; in particular, the greater the number of gland-like spaces per square millimeter of tumor, the longer the survival of the patient.