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Adenoid cystic carcinoma of the submandibular gland: a 35-year review.

OBJECTIVES: To evaluate the treatment results of adenoid cystic carcinoma (ACC) of the submandibular gland at a single institution during a 35-year period. STUDY DESIGN & SETTING: A retrospective review was performed by examining the records and reviewing the pathology of 22 patients with ACC of the submandibular gland treated at UCLA Medical Center from June 1963 to December 1997. RESULTS: Seven men and 15 women with an age range of 23 to 85 years (median, 48 years) were treated. Surgical intervention was performed in 21 patients. All patients with advanced tumor size, perineural invasion, microscopically positive surgical margins, or regional neck metastases received postoperative adjunctive therapy, primarily radiotherapy. Follow-up varied from 6 months to 181 months (median, 67 months). Disease-free survival at 3, 5, and 10 years was 66%, 57%, and 41% respectively, whereas overall survival was 76%, 70%, and 37%, respectively (note: 5- and 10-year survival rates are not statistically conclusive due to the small sample size). CONCLUSIONS: We report fairly high disease-free survival rates in this patient population and a number of prognostic trends are evident. Early diagnosis, wide surgical intervention, and postoperative radiation are associated with a favorable prognosis. Advanced tumor size, positive surgical margins, perineural invasion, and local recurrence of the tumor are associated with an unfavorable prognosis. EBM RATING: C.

Adult↗

P53, bcl-2 and Ki-67 expression in adenoid cystic carcinoma of the palate. A clinico-pathologic study of 21 cases with long-term follow-up.

Adenoid cystic carcinoma (ACC) is an indolent tumor that pursues a protracted clinical course with recurrences and late metastases. The aim of this study was to investigate immunohistochemically the expression of p53, bcl-2 protein, and Ki-67 in 21 cases of ACC of the palate, all with a minimum of 10 years and a maximum of 22 years of clinical follow-up. These results were also analyzed with regard to different clinical prognoses of the histologic subtypes of ACC. High expression of p53 and bcl-2 was noted in 19 out of 21 ACC cases (90%), in which most tumor cells (from 66% to 99%) proved to be immunopositive. A relation to the histologic types, clinical staging, and survival was not found. Therefore, the high immunoreactivity against these oncoproteins in the same tumor cells suggests that these two oncogenes may be involved since the early stage of carcinogenesis. Loss of function of the p53 protein combined with bcl-2 upregulation might give the tumor cells a double growth advantage, because uncontrolled proliferation is combined with a reduced cell death rate. The interaction with other oncogenes may then trigger a multistep process able to promote tumor progression. The low labeling index Ki-67 was detected in nine out of 21 cases (42%), with a low percentage of tumor cells (from 3% to 15%) being positive, whereas the remaining 12 cases were negative. We found no relation to the histologic types, clinical staging, and survival; however, the low proliferation rate could explain the natural course of tumor.

Adult↗

Establishment and characterization of metastasizing cell lines from a heterotransplanted human adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is a rare malignant tumor of the head and neck occurring in the salivary glands. We established a human ACC line which is serially transplantable in nude mice and designated it as KOA-1. The KOA-1 tumor doubled in 9.3 days and retained the histologic characteristics of a solid pattern of ACC even after 22 serial passages. The KOA-1 metastasized to the lung 2 months after subcutaneous transplantation into nude mice. We further established a subline of KOA-1 by an in vivo selection method and named it KOA-1L3. The KOA-1L3 doubled in 1.3 days and metastasized to the lung within 1 week after subcutaneous transplantation. These tumor lines may serve as a useful model for exploration of the biological behavior and treatment of human ACC.

Animals↗

Central adenoid cystic carcinoma of the mandible: case report and literature review of 16 cases.

Central intraosseous adenoid cystic carcinoma (ACC) of the mandible, formerly known as cylindroma, is a rare neoplasm with only 16 cases reported in the literature. We describe the diagnosis, etiology, and treatment of a central ACC located in the mandibular premolar region. We also review the literature. This case illustrates 2 key facts regarding the diagnosis and etiology of ACC. First, central salivary gland tumors should be considered in the differential diagnosis of cystic lytic lesions in the mandible. Second, even though the origin of this type of tumor is still unknown, the presence of ectopic tissue anterior to the submandibular gland in the submandibular area indicates that this tumor might be made up of ectopic embryogenic inclusions.

Aged, 80 and over↗

Assessment of CD43 expression in adenoid cystic carcinomas, polymorphous low-grade adenocarcinomas, and monomorphic adenomas.

OBJECTIVE: Distinguishing between adenoid cystic carcinoma (ACC), polymorphous low-grade adenocarcinoma (PLGA), and monomorphic adenoma (MA) can occasionally pose a diagnostic challenge. It is of interest to identify a marker that can differentiate between these tumors. CD43 is a sialoglycoprotein that is typically expressed by hematopoietic cells and their derivative neoplasms, although positivity in epithelial tumors has been recently recognized. Our aim was to investigate CD43 immunoreactivity in ACCs, PLGAs, and MAs. STUDY DESIGN: Formalin-fixed paraffin-embedded sections from 40 salivary gland tumors (12 ACCs, 14 PLGAs, and 14 MAs) accessioned from 1989 to 2002 were retrieved from the files at the Department of Pathology, Long Island Jewish Medical Center. Immunohistochemical staining with anti-CD43 monoclonal antibody was performed. RESULTS: Cytoplasmic and membranous immunoreactivity was detected in 12/12 ACCs (100%), 1/14 PLGAs (7.1%), and 3/14 MAs (21.4%). CONCLUSIONS: CD43 appears to be preferentially expressed in salivary gland ACCs compared to PLGAs and MAs. Although the mechanism of this overexpression remains obscure at this time, our results suggest that the use of CD43 immunostaining as an adjunct to histological examination may be helpful in differentiating ACC from its mimics.

Adenocarcinoma↗

Adenoid cystic carcinoma of the Bartholin's gland: report of two cases and review of the literature.

BACKGROUND: Adenoid cystic carcinoma (ACC) of the Bartholin's gland is a rare malignancy of the female genital tract and there have been 62 cases of ACC of the Bartholin's gland in the literature. CASES: Two cases of ACC of the Bartholin's gland are reported. CONCLUSION: There is no consensus on optimal treatment of ACC of the Bartholin's gland. Most commonly, wide local excision and radical vulvectomy with or without lymph node dissection, are performed. More long-term follow up is recommended to evaluate optimal primary treatment and roles of radiotherapy and chemotherapy because ACC of the Bartholin's gland recurs and metastasizes long after primary treatment.

Adult↗

[The value of waiting in spontaneous remission of recurrent tonsillitis without associated adenoid pathology].

In order to assess the rate of spontaneous remission in children with recurrent acute tonsillitis (RAT), we revised the pediatric patients who were seen between 1994 and 1999. For this purpose, 123 cases that were on the waiting list for tonsillectomy under the indication of RAT without associated adenoid disease were selected. Only 23 (18.7%) of the children who were included in the study were removed from the waiting list after a mean time of 9 months because of spontaneous remission of the disease. Thus, there is no justification for claiming that long waiting lists for tonsillectomy are frequently associated with spontaneous remission of RAT.

Acute Disease↗

[CCND1 gene amplification in the adenoid cystic carcinoma of the minor salivary glands].

OBJECTIVE: Adenoid cystic carcinoma (ACC) is a tumour of epithelial origin that represents the most common malignant neoplasm of the minor salivary glands. However, little is known about the genes involved in the development and progression of this tumour. Cyclin D1 gene (CCND1) plays a key role in the control of the cell cycle, and its amplification is described in numerous cancers. The aim of this study is to determine the amplification of the CCND1 gene in the ACC of the minor salivary glands. MATERIALS AND METHODS: A retrospective study was performed on 12 patients with ACC of the head and neck. The amplification of the CCND1 was determined using multiple PCR. RESULTS: Amplification of the CCND1 was found in 4 patients (33.3%). No correlation was found between CCND1 amplification and clinicopathological parameters, although disease-free survival was diminished in patients with amplification. DISCUSSION/CONCLUSIONS: Our study demonstrates for the first time the amplification of the CCND1 gene in ACC. We have found an amplification rate similar to others neoplasms. CCND1 amplification seems to be associated with a poorer prognosis in these tumours, although this needs to be confirmed in larger studies.

Adult↗

[Prognostic factors in adenoid cystic carcinoma of salivary glands].

OBJECTIVE: Adenoid cystic carcinoma (ACC) is a relatively rare tumor which is characterized by its long clinical history, with multiple recurrences and late distant metastasis. The aim of the present study is to show our experience in the management of this tumor and the relationship of different clinico-pathological parameters with its prognosis. MATERIAL AND METHODS: A retrospective study was carried out between 1984 and 2004 in 28 patients with ACC of the salivary glands, analyzing the most outstanding clinico-pathological variables in this tumor related to the prognosis of the tumor and the survival. RESULTS: The overall survival rates at 5, 10 and 15 years were 88%, 69% and 52% respectively. Ten (36%) patients presented local recurrence and 10 (36%) presented distant metastasis (four of which also have local recurrence). Although the differences were not statistically significant, the patients with solid histological subtype (p=0.17), with positive margins status (p=0.2), with perineural invasion (p=0.59), and those treated with surgery alone (p=0.19), presented a worse survival. DISCUSSION/CONCLUSION: Our study confirms that the ACC is a tumor with a high tendency to local recurrence and development of distant metastasis, even long term, which means a close follow-up for life. Nevertheless, it also demonstrates that acceptable survival rates can be obtained with aggressive treatment.

Adolescent↗

Adenoid cystic carcinoma of Bartholin's gland. Case report and review of the literature.

A patient with adenoid cystic carcinoma of Bartholin's gland is reported and the literature relevant to this disease reviewed. The clinical presentation is characterized by a vulvar mass that has existed for a prolonged period prior to the onset of symptoms, usually infection, pain, and burning. Histologically the tumor is characterized by a cribriform pattern and perineural invasion. Electron microscopy confirms the epithelial nature of this lesion. Conclusions concerning therapy are presented, including emphasis on initial radical vulvectomy and the fact that the efficacy of routine lymphadenectomy and adjuvant radiotherapy has not been demonstrated.

Adult↗

Large scale molecular analysis identifies genes with altered expression in salivary adenoid cystic carcinoma.

Salivary gland cancers comprise a heterogeneous group of neoplasms whose biological and clinical characteristics differ considerably from those of mucosal squamous cell carcinomas of the head and neck. One of the most common subtypes, adenoid cystic carcinoma (ACC), is notable for its myoepithelial differentiation, proclivity for hematogenous spread, and slow but progressive clinical course. The molecular alterations that underlie its development and progression are poorly characterized. Here we used oligonucleotide microarray analysis to survey the expression of 8920 different human genes in 15 ACCs, one ACC cell line, and five normal major salivary glands. We observed expression of genes indicative of myoepithelial differentiation, as expected, including those whose protein products are components of basement membranes and extracellular matrix. Other genes that were highly ranked for their expression in ACC were those encoding the transcription factors SOX4 and AP-2 gamma, the latter of which also was overexpressed in ACC relative to 175 other carcinomas from 10 anatomical sites that we had previously profiled. Additional genes, which were highly expressed in ACC compared to the other carcinomas, included casein kinase 1, epsilon and frizzled-7, both members of the Wnt/beta-catenin signaling pathway. Our study documents for the first time the diverse spectrum of genes overexpressed in ACC and highlights gene products and pathways that in the future might be exploited as therapeutic targets for this cancer, which up until now, has shown limited response to chemotherapeutic approaches.

Carcinoma, Adenoid Cystic↗

Stage means more than grade in adenoid cystic carcinoma.

Our experience with 184 previously untreated patients who had adenoid cystic carcinoma of salivary gland origin is reviewed. Retrospective staging was possible in all but nine patients who had minor salivary gland primary tumors. Sixty-three percent of patients were diagnosed as having stage I or stage II disease (stage I, 64 patients; stage II, 47 patients), whereas 43 and 21 patients had stage III and IV tumors, respectively. Grading was as follows: cribriform pattern only (grade 1, 126 patients; 68%), mixed cribriform and solid features (grade 2, 48 patients; 26%), and solid only (grade 3, 10 patients; 5%). Treatment was predominantly surgical (174 patients), and relatively few patients received adjunctive, postoperative irradiation (27 patients). Cumulative 10-year survival was 75%, 43%, and 15% for stage I, stage II, and stage III and IV patients, respectively, and cause-specific survival at 10 years was as high as 94% in patients with stage I disease. Only the clinical stage had a significant impact on survival. Neither survival, regional metastases (16 patients; 11%), nor distant dissemination (64 patients; 43%) was predictable on the basis of tumor grade alone. The prognosis in patients with early stage lesions may be better than has been appreciated.

Adult↗

Distant metastasis in adenoid cystic carcinoma of salivary origin.

BACKGROUND: Adenoid cystic carcinoma (ACC) is an aggressive, often indolent tumor, with a high incidence of distant metastasis (DM). Relatively little has been written about the factors that influence distant spread and subsequent survival because it is uncommon and more than a decade of observation may be required to appreciate the prolonged clinical course in some patients. METHODS: We have retrospectively studied 196 determinate patients who received definitive treatment in our hospital between 1939 and 1986 for ACC in all salivary sites. Inclusion criteria were no prior treatment elsewhere other than excisional biopsy and eligibility for follow-up of at least 10 years. Variables assessed for their impact on distant metastasis included age, gender, site, size, node status, stage, grade, and locoregional treatment failure. RESULTS: Treatment failure occurred in a total of 122 of 196 determinate patients (62%), 74 of whom had DM (38%). This was usually associated with locoregional recurrence (51 patients), but DM was the only indication of failure in 23 whose primary tumor was controlled. Of the 74 patients with known DM, the lung was recorded as the only involved site in 50 patients, lung was involved in addition to other sites in 17, bone metastases alone occured in 5, and the remaining 2 developed disseminated disease. Disease-free intervals varied from 1 month to 19 years (median 36 months) and exceeded 10 years in 9 of 113 patients (8%) with adequate information about treatment failure. Survival with DM was less than 3 years in 54%, but more than 10 yrs in 10% (maximum 16 years). The only significant factors influencing survival were the size of the primary tumor (P <0.0000), local or neck recurrence (P = 0.0006), and the presence of nodal involvement (P = 0.02). CONCLUSIONS: The high incidence of DM with locoregional failure confirms the importance of aggressive initial surgery, combined with irradiation, for high-stage tumors or involved surgical margins. Large tumor size and lymph node involvement, rather than microscopic appearance, were predictive of DM. Considering that lung metastases are usually multiple, and prolonged survival without treatment is not unusual, resection of pulmonary metastases may be hard to justify in ACC patients based on the limited experience thus far reported. Chemotherapy for metastatic ACC is probably best withheld until symptoms appear.

Carcinoma, Adenoid Cystic↗

Acute thoracic inlet obstruction in achalasia with adenoid cystic and squamous cell carcinoma.

Respiratory symptoms due to compression of the trachea by the dilated esophagus in achalasia are extremely rare. A patient is presented whose respiratory manifestations included engorged neck veins and a neck swelling that fluctuated with respiration. He also had two malignant tumors in his dilated esophagus, a squamous cell carcinoma and an adenoid cystic carcinoma.

Acute Disease↗

Adenoid cystic carcinoma of the salivary glands.

Eighty-two patients with adenoid cystic carcinoma treated by a radical course of radiotherapy are reviewed. In 44 cases the tumour arose in the major salivary glands and, of these, 77% had an incomplete surgical excision and 23% had only a tumour biopsy before radiotherapy. Thirty-eight tumours arose in the minor salivary glands and, of these, 18% had an incomplete surgical excision and 82% a biopsy only before treatment. Primary tumour control was achieved in 67% of patients at 5 years. The local control was significantly better in patients who had an incomplete surgical excision: 86% compared with 37% at 5 years. The local control of tumours arising in the major salivary glands is significantly better than that of tumours arising in the minor glands, but this difference is explained by more patients with major gland tumours having had incomplete surgery. For patients treated after only a biopsy, local tumour control was achieved in 37%, demonstrating the radioresponsiveness of this type of carcinoma. No difference in survival was demonstrated in patients with major or minor gland tumours. Despite local tumour control, 43% of patients with major gland tumours died from metastatic disease. The commonest cause of death of patients with minor gland tumours was local failure.

Adult↗

Estrogen receptor assay in polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma of salivary gland origin. An immunohistochemical study.

An apparent relationship between breast cancer and salivary gland cancer has been observed, and there is one report in the literature that describes estrogen receptors in normal salivary gland and salivary gland cancers. With the use of a monoclonal antibody against estrogen receptor protein and the avidin-biotin immunoperoxidase procedure, we were unable to demonstrate estrogen receptors in formalin-fixed paraffin-embedded sections of either polymorphous low-grade adenocarcinoma or adenoid cystic carcinoma of salivary gland origin.

Adenocarcinoma↗

[Adenoid cystic carcinoma of the breast].

OBJECTIVE: To review the clinical presentation and imaging findings of adenoid cystic carcinoma (ACC). MATERIAL AND METHODS: We performed a retrospective study of the period between January 1990 and July 2004, comprising five cases of ACC of the breast, all in women, among 4,036 malignant lesions diagnosed (0.12%). We reviewed the available imaging studies (mammography in all five cases, ultrasound in four, and magnetic resonance in one). We also reviewed the clinical presentation and evolution in all patients. RESULTS: Three patients presented with palpable lesions. Mammographic findings consisted of irregular, ill-defined nodules in three cases, a well-defined rounded nodule in one, and an asymmetrical density in the other. No microcalcifications were observed in any case. Ultrasound examination showed ill-defined polylobulated nodules in three cases and a well-defined, rounded nodule with small cysts inside in the remaining case that showed intense vascularization in the Doppler study. The only case studied by magnetic resonance was seen as a rounded nodule that showed heterogeneous contrast uptake, well-defined margins, and an enhancement curve considered highly suspicious for malignancy. Treatment was tumorectomy together with radiotherapy in all cases. Four patients remain asymptomatic at present (mean follow-up = 64 months) and one presented lung and liver metastes twelve years after the diagnosis of ACC. CONCLUSION: ACC is an uncommon breast tumor with varied radiologic appearance, although moderately or highly suspicious lesions predominate. We consider the absence of microcalcifications in these tumors to be noteworthy. The prognosis is generally good, although the possibility of remote metastasis exists.

Aged↗

The role of p53 mutation and protein expression in primary and recurrent adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is a malignant tumor of salivary gland origin having a propensity for spread by direct extension or perineural invasion with frequent recurrences. Previous reports have shown that tumor behavior is not always predicted by histological pattern or stage. Little is known of the role of p53 tumor suppressor gene mutation and altered protein expression with respect to ACC pathobiology and recurrence. The authors analyzed a group of 14 ACC specimens (seven primary; seven recurrent) from 13 patients treated between 1987 to 1993. Formalin-fixed, paraffin-embedded specimens were reviewed and subjected to, immunohistochemistry (p53, DO-7, DAKO, Nutley, NJ; and WAF-I, Ab-1, Oncogene Sciences, Uniondale, NY) on 4-microm-thick histological sections as a prelude to p53 genotyping. In one case, sequential material representing primary and recurrent tumor was analyzed. Each tumor specimen was topographically genotyped for p53 point mutational change. Minute tissue samples were removed from unstained sections, polymerase chain reaction (PCR) amplified for p53 exons 5 to 8, and then underwent direct DNA sequencing. Six of seven primary ACCs were p53 immunostain negative. Four of seven recurrent (57%) ACCs were p53 immunopositive. These tumors showed varying degrees of p53 immunopositivity ranging from diffuse, intense staining of most tumor cells (n = 1) to interspersed, strongly positive cells mixed with predominantly p53 immunonegative cells (n = 4). All tumors were WAF-I immunostain negative. Two of the most immunopositive recurrent tumors each manifested a single type of p53 point mutation detected by p53 DNA genotyping (p53 exon 5:codon 175 and p53 exon 6:codon 199). In the case in which both primary and recurrent tumor was available, only the recurrent tumor contained point mutational damage. Negative immunostaining for p53 in primary ACC suggests that p53 mutation is not important in early events involving development of this tumor. In contrast, the frequent presence of p53-positive cells and the detection of point mutations in recurrent ACC suggests that p53 alterations are involved in later stages of tumor progression, important in the phenomenon of ACC recurrence.

Adult↗