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PubMed1986

Adenoid cystic salivary gland carcinoma. A histopathologic review of treatment failure patterns.

Seventy-one cases of adenoid cystic salivary gland carcinoma were reviewed according to treatment modality and clinical course. Thirty-six patients (51%) were treated by combined surgery and radiation therapy. The tumors were classified by their histologic patterns into tubular, cribriform, and solid forms. Distant metastases, in 52%, were the most frequent and ominous sources of failure. In 35% of cases, distant metastases developed despite local control at the primary site. In this group, the disease had a more fulminant course with shorter survival. Histopathologically, the cribriform subtype was associated with multiple local recurrences, greater local aggressiveness, and a poorer salvage rate as compared with the tubular subtype. Late onset of local recurrences and distant metastases was especially associated with the cribriform subtype. Overall prognosis in terms of distant metastases and survival was worst for the solid subtype. Control of local disease is best achieved with combined surgery and radiation therapy. The high incidence of distant metastases may not be affected by this regimen. The ultimate outcome of therapy is poorly predicted. Survival appears to be based on the pattern in which distant metastases develop. Overly aggressive and mutilating surgical approaches for these tumors are not recommended in many instances. The need for the development of new, more effective forms of therapy is emphasized.

Aged↗
PubMed1987

The cellular composition of adenoid cystic carcinoma. An immunohistochemical study.

To investigate the cellular differentiation of adenoid cystic carcinomas (ACC), a comparative immunohistochemical study of 12 normal salivary glands and eight specimens of ACC was performed. Antibodies were used against S100 protein (S), keratins (K) of various molecular weights, vimentin (V), muscle-specific actin (A), epithelial-membrane antigen, human milk fat globules, and collagen type IV. A panel of four of these antibodies (SKVA) was identified as the most helpful in characterizing cells in normal salivary glands and ACC. The immunophenotypes depended on the histologic patterns of ACC. Cells in morphologically recognizable duct structures in the cribriform and trabecular areas expressed a phenotype similar to that of the intercalated duct. Cell layers around pseudocysts and occasional cellular islands had an immunophenotype suggesting myoepithelial-cell differentiation. The most clear cut epithelial/myoepithelial bilaminar differentiation was present in areas with a trabecular pattern, in which the layers facing the stroma and the central ductal elements had SKVA phenotypes of myoepithelial and ductal differentiation, respectively. In areas with a reticular pattern, most of the cells showed ductal differentiation. Many of the cells in the cribriform and basaloid regions were immunophenotypically undifferentiated. These results indicate that ACC consists of undifferentiated cells and of cells that are differentiating toward ducts, predominantly intercalated ducts, and toward myoepithelium. These findings support previous observations by electron microscope.

Actins↗
PubMed1990

Adenoid cystic carcinoma of the salivary glands. Management of recurrent, advanced, or persistent disease with hyperthermia and radiation therapy.

Adenoid cystic carcinomas (ACC) of the salivary glands are aggressive tumors characterized by multiple late local recurrences and distant metastases. Current therapy includes wide local excision and high-dose postoperative radiation therapy (XRT) (5400 to 7000 cGy). Despite early aggressive treatment, local recurrence remains a major problem with limited safe and effective therapeutic options available. The excellent local responses obtained in four patients (six sites) with ACC of the head and neck treated either with additional low-dose irradiation (2160 to 3420 cGy) in conjunction with two to five hyperthermia (HT) treatments or with full dose XRT and HT as part of the overall treatment plan are reported. All HT treatments were for 45 minutes once steady state conditions were obtained. Monitored intratumoral temperatures for all treatments achieved average maximum (Tmax), average mean (Tave), and average minimum (Tmin) temperatures of 44.2 degrees C, 41.2 degrees C, and 38.9 degrees C, respectively. A complete response was obtained for all six fields with no significant long-term complications. Two patients remain alive and free of local disease at 42 and 63 months of follow-up. Two patients died--one with metastases (with persistent local control) and one with a local recurrence at 9 and 30 months, respectively, after XRT and HT. This is the first report of HT and low-dose XRT in the management of previously irradiated ACC and suggests a potential role for the use of this modality in the treatment of ACC.

Adult↗
PubMed1990

Intraoral adenoid cystic carcinoma. The presence of perineural spread in relation to site, size, local extension, and metastatic spread in 22 cases.

Twenty-two patients with an intraoral adenoid cystic carcinoma (ACC), initially treated by surgery with or without postoperative radiotherapy, were examined for the presence of perineural spread in relation to primary site, size, local extension, histologic status of the surgical margins, and metastatic spread of the tumor. There seems to be no correlation between perineural spread and the primary site or size of the tumor. However, perineural spread occurred more often in tumors with local extension and in cases with surgical margins with positive results. There seems to be no statistically significant correlation between perineural invasion and distant metastatic disease.

Adult↗
PubMed1991

Adenoid cystic carcinoma of the esophagus. A clinicopathologic study of three cases.

In a group of 245 cases of primary carcinoma of the esophagus the authors found three cases of adenoid cystic carcinoma (ACC). Clinical and pathologic data of those patients (one female and two male; age range, 49-74 years) were analyzed. Tumors were localized in the middle third of the esophagus. One patient lived 15 months after surgery. Another is a case of early ACC who has been living 4.5 years after surgery and is without specific symptoms. The third patient had not had surgery and died 13 months after the onset of dysphagia. An autopsy showed only a locally invasive tumor growing into the surroundings of the esophagus, and regional lymph node metastases without distant parenchymal metastases. These findings support pathologic and biologic similarities between ACC of the esophagus and ACC of the salivary glands. There are synchronous tumors of the esophagus and the vital localization which makes the prognosis of ACC of the esophagus worse than ACC of the salivary glands.

Aged↗
PubMed1991

Adenoid cystic carcinoma of the breast metastatic to the kidney. A clinically symptomatic lesion requiring surgical management.

Adenoid cystic carcinoma (ACC) of the breast is a rare histologic type of breast cancer associated with a good prognosis. A woman who earlier had a pulmonary metastasis surgically resected 6 years postmastectomy developed clinically symptomatic bleeding from a renal metastasis 12 years postmastectomy. An atypical angiographic picture (moderate vascularization) for secondary renal neoplasms was observed. The characteristic histologic features of ACC were present in all specimens; ultrastructural characteristics of ACC were identified in the renal lesion. Successful surgical management of these metachronous solitary metastases demonstrates the therapeutic utility of aggressive management in maintaining disease control of this histologic type of breast cancer.

Breast Neoplasms↗
PubMed1994

Primary adenoid cystic carcinoma of the lung. A clinicopathologic and immunohistochemical study of 16 cases.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare but distinctive salivary gland-type malignant neoplasm that arises infrequently as a primary tumor in the lung. METHODS: The clinical and pathologic features in 16 cases of primary ACC of the lung were reviewed, and immunohistochemical stains on paraffin sections were performed in 7 cases. RESULTS: The patients' ages ranged from 29 to 79 years (mean age, 54 years); 11 were men and 5 were women. Clinically, most patients were seen initially with obstructive symptoms, including cough, wheezing, shortness of breath, and hemoptysis. Eight tumors were in the left lung and eight in the right lung. The lesions were treated by pneumonectomy in seven patients, lobectomy in six, and lobectomy plus chemotherapy in two. One patient was treated with chemotherapy alone after undergoing a diagnostic biopsy that revealed advanced disease. Grossly, most lesions were described as endobronchial and measured from 0.9 to 4.0 cm in greatest dimension; two cases, however, showed poorly circumscribed infiltrative tumors. Histologically, three main growth patterns were identified admixed in various proportions: cribriform (cylindromatous), tubular, and solid. Immunohistochemical study in six of seven cases showed a prominent myoepithelial cell component, as evidenced by immunoreactivity for keratin, actin, and S-100 protein in numerous tumor cells. Clinical follow-up ranging from 2 to 15 years in six patients showed that three were alive and well without evidence of recurrence or metastases at 5, 10, and 12 years, respectively, and three were alive with recurrence at 2, 5, and 15 years, respectively. Three other patients died of unrelated conditions at 2, 7, and 9 years, respectively, after diagnosis. Two patients in the study were seen initially with metastatic spread at the time of initial diagnosis and died 2 months and 1 year later with widespread metastases to lymph nodes, liver, spleen, kidney, and bone despite intensive chemotherapy. CONCLUSIONS: Disease stage at the time of diagnosis may play an important role in predicting the clinical outcome of patients with these tumors. Despite their generally slow and indolent growth in other locations, ACC arising in the lung may in certain cases be more aggressive.

Adult↗
PubMed2005

Therapy strategies for locally advanced adenoid cystic carcinomas using modern radiation therapy techniques.

BACKGROUND: The authors evaluated whether modern photon techniques, such as stereotactic fractionated radiation therapy (FSRT) or intensity-modulated RT, outweighed the biologic advantages of high-linear-energy transfer RT in the treatment of patients with locally advanced adenoid cystic carcinomas (ACC) that infiltrated the skull base or the orbit. METHODS: Between June 1995 and December 2003, 63 patients with ACC were treated with modern RT techniques at the University of Heidelberg. The treatment results achieved with modern photon techniques alone were compared with the results achieved with combined photon RT and a carbon ion boost. Twenty-nine patients (Group A) were treated with a combination of photon RT and a carbon ion boost. Thirty-four patients (Group B) received photon RT alone. RESULTS: The median follow-up was 16 months for Group A and 24 months for Group B. Locoregional control rates at 2 years and 4 years were 77.5% and 77.5% for Group A and 72.2% and 24.6% for Group B, respectively (P = 0.08; log-rank test). Disease-free and overall survival rates at 2 years/4 years were 71.5%/53% and 86.6%/75.8% for Group A and 69.2%/23% and 77.9%/77.9% for Group B, respectively. Rates for severe late toxicity were < 5% for both groups. CONCLUSIONS: Modern RT techniques allowed the safe delivery of high target doses to patients with locally advanced ACC. Late toxicity rates were kept lower compared with the historic neutron therapy data. A combination of modern photon RT and carbon ion RT seemed to be advantageous, with a trend toward higher locoregional control rates compared with modern photon RT alone.

Adult↗
PubMed2005

Promoter methylation of p16INK4a, RASSF1A, and DAPK is frequent in salivary adenoid cystic carcinoma.

BACKGROUND: Promoter methylation is a common mechanism of inactivation of tumor suppressor genes in multiple tumor types. However, little is known about its role in the development of adenoid cystic carcinoma of the salivary gland (ACC). In the current study, the authors investigated whether promoter methylation is common in ACC and whether it may influence ACC development. METHODS: The promoter methylation status of the genes p16(INK4a), RASSF1A, DAPK, and MGMT, which are important in cell growth regulation, apoptosis, and DNA repair, was determined in tissue sections of tumor samples from 60 patients with ACC using methylation-specific polymerase chain reaction. The association between methylation status and patients' clinical and pathologic characteristics were assessed. RESULTS: Of the 60 tumors, DNA methylation of the p16(INK4a) promoter was detected in 28 tumors (47%); the respective values DNA methylation of the RASSF1A, DAPK, and MGMT promoters were 25 tumors (42%), 16 tumors (27%), and 4 tumors (7%), respectively. Forty-six tumors (77%) had DNA methylation in > or = 1 of the 4 promoters, 20 tumors (33%) had DNA methylation in > or = 2 promoters, 6 tumors (10%) had DNA methylation in > or = 3 promoters, and 1 tumor (2%) had DNA methylation in all 4 promoters. RASSF1A promoter methylation was more frequent in high-grade tumors than in low-grade tumors (P = 0.009), in advanced-stage tumors (P = 0.008), and in tumors with metastasis (P = 0.005). CONCLUSIONS: Promoter methylation of p16(INK4a), RASSF1A, and DAPK was common in ACC, and it is possible that such methylation may influence the development of ACC. The high frequency of RASSF1A promoter methylation in high-grade tumors and in tumors with metastasis suggested a role for this gene in the progression of ACC.

Adult↗
PubMed2004

Adenoid cystic carcinoma of the breast diagnosed by fine-needle aspiration.

Fine-needle aspiration cytology remains a useful tool for preoperative diagnosis of breast lesions. We describe a case of adenoid cystic carcinoma (ACC) of the breast detected by ultrasound-guided fine-needle aspiration (FNA). Subsequent histopathology corroborated the diagnosis. ACC is a rare but distinctive neoplasm of the breast that can be accurately diagnosed by FNA. Its infrequent presentation, favorable prognosis, and relatively conservative management in the breast prompt us to reinforce its features.

Aged↗
PubMed2004

Extracellular material in adenoid cystic carcinoma of the salivary glands: a comparative cytological study with other salivary myoepithelial tumors.

The objective of this study was to clarify extracellular materials (ECMs) in adenoid cystic carcinoma (AdCC) and compare these to those found in other salivary gland tumors with myoepithelial differentiation. The ECM was examined with Papanicolaou, May-Grünwald-Giemsa (MGG), and alcian blue stain at pH 2.5. The ECM in AdCC was classified into three types according to their staining patterns: clear, hyalinized, and membrane type. The incidence of clear-type globule material with magenta on MGG was low in other salivary gland tumors with myoepithelial differentiation. The ECM was identified in other salivary gland tumors with myoepithelial differentiation. However, AdCC has the greatest variety of ECM. These findings are useful to understand the character of AdCC and differential diagnosis of the other salivary gland tumors with myoepithelial differentiation.

Aged↗
PubMed2006

Distinguishing adenoid cystic carcinoma from cylindromatous adenomas in salivary fine-needle aspirates: the cytologic clues and their ultrastructural basis.

The utilization of fine-needle aspiration (FNA) biopsy in salivary tumors is hindered by the reluctance of many cytopathologists to report adenoid cystic carcinoma (ACC) because its cylindromatous stroma is observed occasionally in pleomorphic adenoma (PA) and basal cell adenoma (BA), and a diagnosis of ACC results in radical surgery. The aim of this study is to identify dependable features to distinguish the look-alike entities and illustrate their ultrastructural base. We compared 20 cases of ACC to 15 cases of cylindromatous PA and 9 cases of BA. All were direct smears stained with Diff-Quik, hematoxylin and eosin, Papanicolaou, or Ultrafast Papanicolaou (UFP) stain. In addition to the presence of cylindromatous pattern, the amount of cytoplasm in the neoplastic cells and nuclear features were compared. Tissue was dissected from paraffin blocks and processed for electron microscopy in selected cases. The difference in nuclear features can be distinguished in UFP-stained smears and electron microscopy. The nuclei of ACCs were heterochromatic with coarse chromatin and irregular nucleoli, whereas the nuclei of PAs were euchromatic with fine chromatin and small compact nucleoli. The nuclei of BAs were hyperchromatic but finely textured. The cytoplasm of PAs was detectable with every stain at 40x objective, but the cytoplasm of BAs required UFP stain and 100x objective to be detected. The cytoplasm of majority of neoplastic cells of ACCs are invisible, because the thin rim of cytoplasm measured <1 microm ultrastructurally, well beyond the resolution of a light microscope. Rare cohesive fragment of epithelial cells in ACC have scanty blue cytoplasm in UFP stain and can be recognized as ductal cells. In conclusion, in our analysis of salivary tumors with a cylindromatous pattern, the seemingly naked nuclei of neoplastic cells with their coarse nuclear chromatin and irregular nucleoli, as revealed by the UFP stain, reliably distinguished ACC from cylindromatous adenomas.

Adenoma↗
PubMed2006

Extra-salivary gland presentations of adenoid cystic carcinoma: a report of three cases.

Adenoid cystic carcinoma (ACC) is a malignant neoplasm most commonly originating in salivary glands of the head and neck area. When ACC presents outside of these locations, the diagnosis may become more challenging. We describe three cases of ACC presenting in extra-salivary gland sites. Two cases were metastatic; in case 1 the initial presentation was widespread bony metastasis of unknown primary origin. The other metastatic case (case 2) was from a patient presenting with a pleural effusion and a history of previously treated metastatic pulmonary ACC. The pleural effusion cytology was unusual in that exfoliated ACC cells were present in the effusion itself, a rare occurrence. Case 3 was a primary bronchial ACC. In conclusion, ACC can present in various body sites and cytologists must consider this neoplasm when presented with a basaloid carcinoma of uncertain origin.

Aged↗
PubMed1988

Basal-cell adenoma of the salivary gland: a benign adenoma that cytologically mimics adenoid cystic carcinoma.

We describe the fine-needle aspiration cytology of two cases of basal-cell adenoma (BCA) of the parotid gland. Both consisted of groups of small uniform cells with scant cytoplasm and occasional single cells. Small amounts of metachromatic stroma were present in smears from one case. The cytologic and histologic similarities between (BCA) and the solid type of adenoid cystic carcinoma are emphasized. Unequivocal distinction between these two entities may not be possible by cytologic criteria alone.

Adenoma↗
PubMed1984

Isolation of follicular dendritic cells from human tonsils and adenoids. II. Immunocytochemical characterization.

Follicular dendritic cells (FDC) are specialized cells found only within lymphoid follicles. They bind immune complexes and play a role in the presentation of antigen to follicular B cells and in the generation of B cell memory. In the present report the isolation of FDC from human tonsils and adenoids is described. These isolated cells have an unusual spherical arrangement and enclose lymphocytes within extensions of their membranes. Their ultrastructural features are similar to those observed in situ. The reactivity of isolated FDC with a number of monoclonal antibodies was analyzed by immunofluorescence and by immunostaining (at the electron microscopic level) with colloidal gold. In keeping with the results of previous investigations on tissue sections IgM, IgG and IgA (but not IgD) can be detected on the surface of isolated FDC, as can C3b receptors and the FDC-associated antigen detected by monoclonal antibody R4/23. The immunoglobulins associated with FDC are mostly embedded in an electron-dense material. The majority of the lymphoid cells enclosed within the membrane extensions of FDC are of B cell type. These results suggest that isolated FDC may be suitable for further in vitro investigation of their role in the humoral immune response.

Adenoids↗
PubMed1994

Non-random chromosome rearrangements in adenoid cystic carcinoma of the salivary glands.

The chromosomal findings in 10 adenoid cystic carcinomas (ACC) of the salivary glands are described. Clonal numerical deviations as the sole anomaly were detected in four cases and structurally rearranged stemlines and sidelines in four cases. An apparently identical t(6;9)(q23;p21) was found in two tumors; in one case the translocation was part of the abnormal stemline and in the other case it was the sole anomaly in a single variant cell. A similar or identical t(6;9)(q21-24;p13-23) has recently been reported in three of 15 previously published cases of ACC. The three remaining tumors with abnormal stemlines all had rearrangements of chromosome 9, including t(1;9)(q21;p21-22), der(9)i(9)(q10)inv(9)(q12q13), and der(X)t(X;9)(p21;p22-23), respectively. The latter case also had a t(17;18)(p12;q11.2) that was common to both abnormal clones present in this tumor. In addition to other abnormalities, the clone with der(X)t(X;9) also showed a del(6)(q13q21). In two cases fluorescence in situ hybridization (FISH) was used for further characterization of the marker chromosomes. A survey of the present findings together with previous results from 15 ACC clearly demonstrates that rearrangements of 6q21-24 (deletions or translocations in 11 cases), 9p13-23 (translocations in seven cases), and 17p12-13 (translocations in three cases) are recurrent, and often primary, in ACC, and that the t(6;9)(q21-24;p13-23), found in five tumors, is a non-random, primary aberration.

Adult↗
PubMed2002

Immunohistochemical study of epidermal growth factor receptor in adenoid cystic carcinoma of salivary gland origin.

BACKGROUND: Epidermal growth factor (EGF) and its receptor (EGFR) are involved in the development of salivary gland tumors. Recently, treatment modalities for EGFR inhibition have shown an enhanced clinical response in carcinomas of different locations. Adenoid cystic carcinoma (ACC) of salivary gland origin is a malignant tumor with a poor long-term outcome. If salivary gland ACC does exhibit EGFR, then immunotherapy could have a major impact on improving its prognosis. METHODS: The study consisted of 34 samples of formalin-fixed, paraffin-embedded specimens of salivary gland ACC. Specimens were stained with a mouse antihuman monoclonal antibody for immunohistochemical detection of EGFR. Overlying oral mucosa and adjacent normal salivary ducts served as internal controls. Both membrane and cytoplasmic staining were evaluated. Staining score was calculated by multiplying the percentage of positively stained tumor cells by the intensity of the staining. The highest score for a given tumor was equal to 2. RESULTS: In the final analysis, 27 of the 34 specimens were included; 7 were excluded, because the internal control did not reveal any staining. Of these 27 specimens, 23 (85%) stained positively for EGFR with a staining score of 0.05 to 1.8. Three palatal tumors attained the highest scores (one tumor, 1.2, and the remaining two, 1.8). CONCLUSIONS: Most salivary gland ACC stained positively for EGFR, and in some the staining was quite intense. On the basis of the already proven antitumoral effect of agents acting as EGFR inhibitors, it is suggested that patients with ACC might benefit from these agents, especially when surgery has failed or in those with recurrent or metastatic disease.

Adult↗
PubMed2002

Distant metastases of adenoid cystic carcinoma of the salivary glands and the value of diagnostic examinations during follow-up.

BACKGROUND: Adenoid cystic carcinoma (ACC) accounts for approximately 10% of all neoplasms of the salivary glands. Late distant metastases and local recurrences are responsible for a rather low long-term survival rate. AIM: To study the metastasizing pattern of ACC of the salivary glands in 51 patients. METHOD: Fifty-one patients with an ACC in the intraoral/sublingual salivary glands (n = 30), parotid gland (n = 8), submandibular gland (n = 2), maxillary sinus (n = 6), and nasal cavity (n = 5) have been studied. The male-female ratio was 1:1, the mean age was 54.3 (range, 19-81) years. In 30 cases treatment consisted of surgery and radiotherapy. In 13 cases surgery alone was carried out. The average follow-up time was 117.8 (range, 1-171) months. RESULTS: In 28 cases (54.9%) distant metastases occurred, and in 3 patients (5.8%) regional lymph node metastases occurred. In 12 of the 28 patients with distant metastases (42.8%), only the lungs were involved, whereas in 5 of the 28 patients (17.8%), the distant metastases occurred in other organs (eg, bones and brain). In 11 of the 28 patients (39.2%) metastases were found both in the lungs and other organs. Twenty-four of the 51 patients (47.0%) died because of their tumor. The average time between the occurrence of lung metastases and death was 32.3 months and between the occurrence of metastases elsewhere and death 20.6 months. CONCLUSION: Distant metastases of ACC of the salivary glands occur most often in the lungs. Although these lung metastases are the first to occur, these patients die later than patients with distant metastases in other organs. The value of annual chest films or other tests for the presence of distant metastases during follow-up after surgical removal of an ACC seems rather questionable.

Adult↗