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The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation.

PURPOSE: Surgery is the primary treatment for adenoid cystic carcinomas arising from major and minor salivary glands of the head and neck. However, local recurrence is frequent because of the infiltrative growth pattern and perineural spread associated with these tumors. At UTMDACC, we have had a longstanding policy of using postoperative radiotherapy to reduce the risk of local recurrence and to avoid the need for radical surgery; this 30-year retrospective study analyzes the results of this combined modality approach. METHODS AND MATERIALS: Between 1962 and 1991, 198 patients ages 13-82 years, with adenoid cystic carcinomas of the head and neck, received postoperative radiotherapy for known or suspected microscopic residual disease following surgery. Distribution of primary sites was: parotid: 30 patients; submandibular/sublingual: 41 patients; lacrimal: 5 patients; and minor salivary glands: 122 patients. Eighty-three patients (42%) had microscopic positive margins and an additional 55 (28%) had close (< or = 5 mm) or uncertain margins. One hundred thirty-six patients (69%) had perineural spread with invasion of a major (named) nerve in 55 patients (28%). Using radiation techniques appropriate to the primary site, a median dose of 60 Gy (range 50-69 Gy) was delivered to the tumor bed. Follow-up ranged from 5-341 months (median, 93 months). All surviving patients had a minimum of 2 years follow-up. RESULTS: Twenty-three patients (12%) had local recurrences with 5-, 10-, and 15-year actuarial local control rates of 95%, 86%, and 79%, respectively. Fifteen of the 83 patients (18%) with positive margins developed local recurrences, compared to 5 of 55 patients (9%) with close or uncertain margins, and 3 of 60 patients (5%) with negative margins (p = 0.02). Patients with and without a major (named) nerve involved had crude failure rates of 18% (10 out of 55) and 9% (13 out of 143), respectively (p = 0.02). There was a trend toward better local control with increasing dose. This was significant in patients with positive margins, in whom crude control rates were 40 and 88% for doses of < 56 Gy and > or = 56 Gy, respectively (p = 0.006). Actuarial 5-, 10-, and 15-year freedom from relapse rates were 68%, 52%, and 45%, respectively. Base of skull and neck failures were uncommon with or without elective treatment, developing in 2 and 3% of patients, respectively. Distant metastases were the most common type of disease recurrence, developing in 74 patients (37%) of whom 62 (31%) were disease-free at the primary site. CONCLUSIONS: Excellent local control rates were obtained in this population using surgery and postoperative radiotherapy and we recommend this combined approach for most patients with adenoid cystic carcinomas of the head and neck. Perineural invasion was an adverse prognostic factor only when a major (named) nerve was involved. Microscopic positive margins was also an adverse prognostic factor, but even when present, local control was achieved in over 80% of our patients. We recommend a dose of 60 Gy to the tumor bed, supplemented to 66 Gy for patients with positive margins. Despite effective local therapy, one-third of patients fail systemically, and good treatment to address this problem is lacking.

Actuarial Analysis↗

[Thoracic adenoid cystic carcinomas].

Adenoid cystic carcinomas in the trachea are rare, but represent around 40% of all tracheal tumours. Other intrathoracic localisations include the carena or proximal airways. Adenoid cystic carcinoma's growth rate is slow so that it is frequently diagnosed at an advanced stage. Pathological identification may be difficult. Treatment in limited tumours is based upon surgical resection often combined to radiotherapy because of close surgical margins. Radiotherapy dose may vary between 45 and 65 Gy according to margins status. Five-year survival rates of 65-80% have been reported after surgery or surgery and postoperative radiotherapy. Among inoperable patients treated with exclusive radiotherapy for tracheal tumours (including adenoid cystic but also squamous cell carcinomas of poorer prognosis), the recommended delivered dose should be over 60 Gy. Five-year survival rate in these very heterogeneous series may vary between 12 and 27%. Local or metastatic recurrences may occur very lately. They are considered chemo-resistant and targeted therapies may prove to be effective in the future.

Carcinoma, Adenoid Cystic↗

Integrins in metastatic adenoid cystic carcinoma.

Adenoid cystic carcinoma exhibits a diverse clinical behaviour from very localised invasion to widespread metastatases. Recently two adenoid cystic carcinoma cells lines have been isolated and cultured which distinctly show either a low metastatic tendency (Acc-2) or a highly metastatic behaviour (Acc-M). It was hypothesised that these two types of behaviour may at least in part be explained by the different integrin profile on the cells' surface membrane. The integrins represent the largest known family of cell adhesion molecules and a number of tumour cell processes have been shown to be dependant on their integrin expression. Adenoid cystic carcinoma cells of both types were obtained and successfully cultured. These were then subjected to integrin analysis by a number of monoclonal antibodies to alpha(1), alpha(2), alpha(3), alpha(v), alpha(6), beta(1), alpha(v)beta6, alpha(v)beta4 using a fluorescence activated cell sorter. Although there was an apparent difference of integrin expression in the Acc-M group as compared to the Acc-2 group, this was not statistically significant. It is still possible though, that this might account for the differences in behaviour of the two cell lines, and the relationship between integrins, and invasion and metastases in other tumours is discussed. The pattern of integrin expression in Acc may be prognostically significant and useful for treatment planning in the future.

Antibodies, Monoclonal↗

Evaluation of CD25, CD152, Fas-ligand expression in the adenoids of allergic and non-allergic children: a pilot study.

BACKGROUND: The nasal mucosa is the initial site in the upper airways of the host defence against antigen challenge. The lymphatic structure closest to the nasal mucosa is the adenoid. Apoptotic cell death is an important mechanism for maintaining homeostasis in the immune system, and for regulating the fates of lymphocytes following encounters with self and foreign antigens. This process regulates the population of lymphocytes in peripheral lymphoid organs following exposure to various allergens. OBJECTIVES: The objectives of this study were to find evidence for the hypothesis that the development of allergic illness depends on allergic sensitisation in the adenoid. METHODS: In this study, cellular infiltrates in the adenoids of 12 allergic and 13 non-allergic children were evaluated. The number of positive cells for CD4, CD8, CD25, CD152, and Fas-ligand were determined using immunohistochemical stainings and imaging analysis techniques. RESULTS: There was found a higher expression of CD25, CD152 and Fas-ligand in small, activated lymphocytes, especially in the interfollicular area of allergic patients than in the control group. The expression of FasL in activated lymphocytes, as well as in macrophages, was observed. Statistical analysis has shown a significant correlation between expression of CD152 and allergic disease, and a more intense correlation between CD25, CD152 and Fas-ligand and allergic disease. There was no statistically important divergence in the CD4/CD8 ratio in different samples.

Adenoids↗

Search for Herpesvirus 1 and 2 by in situ hybridization in tonsils and adenoids.

OBJECTIVE: Herpes simplex virus (HSV) has been described as cause of acute tonsillitis. It has also been found in nasopharyngeal florid lymphoid infiltrate, mostly composed of CD4+, CD56+ T-cells, simulating lymphoma. In spite of its widespread prevalence in latent form, to the best of our knowledge no study is available on in situ detection of HSV in chronically hyperplastic nasopharyngeal lymphoid tissue. The purpose of the present study was to search for the presence of HSV 1 and 2 in 21 adenoids and 15 tonsils from children (2-12 years of age) in which these organs had been surgically removed due to hypertrophy. METHODS: Paraffin wax-embedded sections from the 36 cases were submitted to the in situ hybridization technique, using the biotinilated probe to Herpes simplex virus 1 and 2 (Pan Path, Amsterdam) and the Rembrandt Universal DISH & HRP Detection Kit (Pan Path, Amsterdam). Positive control consisted of a previously tested Herpes infected lung. RESULTS: In none of the 36 cases studied were positive nuclei detected in adenoid and tonsils, either in lymphoid, in stroma or in epithelial cells, as those seen in the positive control. CONCLUSION: HSV does not seem to be implied in tonsil or adenoid chronic lymphoid hyperplasia. These organs do not seem to harbor the virus latently, or the amount of virus is too low to be detected without amplification methods.

Adenoids↗

Oxidants and antioxidants in tonsillar and adenoidal tissue in chronic adenotonsillitis and adenotonsillar hypertrophy in children.

OBJECTIVE: The aim of the study is to determine the possible role of oxidants and antioxidants in the pathogenesis of chronic adenotonsillitis and adenotonsillar hypertrophy in children. PATIENTS AND METHODS: The children were divided into infection and hypertrophy groups, which were comparable according to age and gender distribution. The infection group was consisted of 20 children with the diagnosis of chronic adenotonsillitis and the hypertrophy group was made up of 19 children with adenotonsillar hypertrophy to whom adenotonsillectomy was performed. Preoperative blood levels of erythrocyte MDA, serum MDA, erythrocyte catalase and serum catalase, and adenoidal and tonsillar tissue levels of MDA and catalase were studied. RESULTS: There were significant increase in tonsil MDA, adenoid MDA, tonsil catalase and adenoid catalase levels in infection group (p<0.05). CONCLUSION: Oxidants and antioxidants are found to have an important role in the pathogenesis of adenotonsillar hypertrophy and chronic adenotonsillitis. These findings strengthen the hypothesis that indicates adenotonsillar hypertrophy and chronic adenotonsillitis are different diseases of the same tissues.

Adenoids↗

Adenoid cystic carcinoma of the head and neck treated by surgery with or without postoperative radiation therapy: prognostic features of recurrence.

PURPOSE: This study sought to review a single-institution experience with the management of adenoid cystic carcinoma of the head and neck. METHODS AND MATERIALS: Between 1960 and 2004, 140 patients with adenoid cystic carcinoma of the head and neck were treated with definitive surgery. Ninety patients (64%) received postoperative radiation to a median dose of 64 Gy (range, 54-71 Gy). Distribution of T stage was: 26% T1, 28% T2, 20% T3, and 26% T4. Seventy-eight patients (56%) had microscopically positive margins. Median follow-up was 66 months (range, 7-267 months). RESULTS: The 5- and 10-year rate estimates of local control were 88% and 77%, respectively. A Cox proportional hazards model identified T4 disease (p = 0.0001), perineural invasion (p = 0.008), omission of postoperative radiation (p = 0.007), and major nerve involvement (p = 0.02) as independent predictors of local recurrence. Radiation dose lower than 60 Gy (p = 0.0004), T4 disease (p = 0.005), and major nerve involvement (p = 0.02) were predictors of local recurrence among those treated with surgery and postoperative radiation. The 10-year overall survival and distant metastasis-free survival were 64% and 66%, respectively. CONCLUSION: Combined-modality therapy with surgery followed by radiation to doses in excess of 60 Gy should be considered the standard of care for adenoid cystic carcinoma of the head and neck.

Adolescent↗

Metastatic adenoid cystic carcinoma to the kidney in a young woman.

The incidence of an adenoid cystic carcinoma on major salivary glands is low, constituting only about 10% to 15% of all parotid malignancies. Cases of delayed metastasis have been reported, but reports of specific renal involvement have not been extensively found. We present the case of a 21-year-old woman with a left renal metastasis from an adenoid cystic carcinoma of the parotid gland that had been surgically treated 7 years previously. The patient underwent successful left radical nephrectomy. During follow-up, the patient developed pulmonary nodules that were metastatic adenoid cystic carcinoma and were surgically excised. At last follow-up, the patient was doing well with no evidence of disease.

Adult↗

Adenoid cystic carcinoma of the cervix.

BACKGROUND: Adenoid cystic carcinoma of the cervix is a rare and aggressive neoplasm for which there are no standardized treatment protocols. CASE: A 38-year-old G3P3 Asian female diagnosed with a stage Ib adenoid cystic carcinoma of the cervix with intermediate risk histologic features received a type III hysterectomy in July 2004. She refused external beam radiotherapy, but agreed to be treated with adjuvant vaginal cuff radiation. She has been closely followed and has no evidence of disease to date. CONCLUSION: Patients with stage Ib adenoid cystic carcinoma of the cervix, especially those with histologic features associated with a higher risk of recurrence, should receive aggressive local therapy, following the guidelines established for similarly staged patients with squamous cell carcinoma of the cervix.

Adult↗

[Otitis medias with effusion: association with the Eustachian tube dysfunction and adenoiditis. The case of the Central Hospital of Maputo].

INTRODUCTION: Although the aetiology of otitis media is known to be multifactorial, adenoids infections and Eustachian tube dysfunction, have been frequently associated with the incidence of middle-ear effusion. Middle-ear effusion cases are frequent in Maputo, Mozambique, and very often insertion of tympanostomy tubes and adenoidectomy alone or with amigdalectomy have been used to treat these cases and to prevent further episodes. The objective of this study is to describe the association of these factors with otitis medias with effusion in patients that visit the Otorrinolaringology department (ENT) at the Central Hospital of Maputo (HCM), as well as to describe the clinical and epidemiological profile of these patients. PATIENTS AND METHODS: A cross sectional study was conducted. 4157 clinical files of all patients who made their first visit to the ENT department at the HCM, with otitis media during a period of 4 years (1995 to 1998). RESULTS: 23.3% of patients who visited the ORL service of Maputo with otitis media, are children under 3 years; the major proportion of otitis media with effusion was observed in children aged from 3 to 7 years old (49.2%). In boys under, otitis media with effusion is strongly associated with the history of adenoiditis and/or Eustachian tube dysfunction (OR=9.53) and in older patients (OR=12.26). CONCLUSION: The proportion of otitis media with effusion increases more evidently in patients with disfuntion tube syndrome. Other factor that can be important in patients under seven, is the presence of adenoiditis.

Adenoids↗

Primary cutaneous adenoid cystic carcinoma of the eyelid.

PURPOSE: To report a case of primary cutaneous adenoid cystic carcinoma involving the eyelid. METHODS: We examined a 70-year-old woman with an 18-month history of a gradually enlarging, blue-colored mass in the medial third of the right upper eyelid. Excisional biopsy and additional resection of the medially infiltrated margin resulted in tumor-free edges. Superior cervical and orbital evaluations were performed. RESULTS: Histopathologic evaluation revealed a primary cutaneous adenoid cystic carcinoma. No gland pathology was documented. No tumor recurrence has been noted. CONCLUSION: Primary cutaneous adenoid cystic carcinoma, an uncommon tumor of the skin, should be added to the differential diagnosis of eyelid tumors.

Aged↗

Spinal metastasis of submandibular gland adenoid cystic carcinoma: a case report.

BACKGROUND: Adenoid cystic carcinoma is a rare malignant tumor of the salivary glands, with pulmonary metastasis being the most common site of distant metastasis. CASE DESCRIPTION: The author reports an unusual case of intradural adenoid cystic carcinoma metastasis of the lumbar spine in a patient with recent prostate carcinoma suffering from progressive back pain. The primary submandibular tumor was resected 7 years before the appearance of the spine metastasis, and a prostatic carcinoma had been detected 1 year before. The patient died of systemically advanced disease a few months after surgical decompression. CONCLUSION: Late submandibular gland adenoid cystic carcinoma recurrence may present as an intradural lumbar spine metastasis. The case further displays difficulty in diagnosis and differentiation of metastasis in case of metachronous tumors.

Carcinoma, Adenoid Cystic↗

Multiple brain metastases from adenoid cystic carcinoma of the parotid gland. Case report and review of the literature.

BACKGROUND: Adenoid cystic carcinoma is a slow-growing malignant tumor occurring in the head and neck. Intracranial involvement usually results from direct skull invasion from adjacent primary sites. To our knowledge, this is the first reported case of multiple brain parenchymal metastases manifesting with hemorrhage. CASE DESCRIPTION: A 60-year-old male experienced sudden onset of hemiparesis caused by an intracerebral hematoma in a brain metastasis from adenoid cystic carcinoma. The primary parotid tumor was treated 15 months before the appearance of the brain metastases. The hemorrhagic metastasis was resected, and cranial irradiation was performed. The brain metastasis had increased cellular atypism compared with the primary tumor. The patient remained well and free of neurologic dysfunctions until 5 months after the radiotherapy was completed; he died of systemically advanced disease 8 months after the craniotomy. CONCLUSION: Hematogeneous brain metastases of adenoid cystic carcinoma are quite rare and cannot be distinguished from those of other cancers radiologically. We assume that the intratumoral hemorrhage is related to the tendency of the tumor to spread around the vessels. Although radiation therapy is not curative, it is beneficial in controlling tumor regrowth.

Bacteremia↗

Adenoid cystic carcinoma of the lacrimal sac.

Adenoid cystic carcinoma is the most common epithelial malignancy of the lacrimal gland and minor salivary glands. Its occurrence in the lacrimal drainage system is extremely rare. A 57-year-old woman presented with epiphora and a mass in the lacrimal sac, which proved to be an adenoid cystic carcinoma. Histologically, it appeared to arise from the wall of the lacrimal sac, and both the lacrimal gland and maxillary antrum were uninvolved by tumor. Despite aggressive surgical intervention, recurrence and metastasis developed. Adenoid cystic carcinoma must be considered in the differential diagnosis of epiphora.

Biopsy↗

Adenoid cystic carcinomas of the lacrimal gland in childhood and adolescence.

OBJECTIVE: To see if there is a correlation between histologic features of these tumors and final outcome. DESIGN: A small series of cases of adenoid cystic carcinomas of the lacrimal gland in patients 18 years of age or younger were evaluated. PARTICIPANTS: A total of 11 cases of adenoid cystic carcinoma of the lacrimal gland in patients 18 years of age or younger found in the registry of Ophthalmic Pathology at the Armed Forces Institute of Pathology were studied. INTERVENTION: Histologic material obtained by excision of lacrimal gland tumors was evaluated for different morphologic parameters. Clinical follow-up information was reviewed. MAIN OUTCOME MEASURES: All cases were evaluated for proportion of a basaloid histologic pattern: necrosis, hemorrhage, mitotic count, and perineural, vascular, intraosseous, leptomeningeal, and optic nerve invasion. These parameters were examined for an association with the clinical follow-up that was obtained for eight of the patients (mean follow-up, 10 years; range, 2-14 years). RESULTS: Most of the patients were female (M:F = 2:9). Mean age was 14 years (range, 6.5-18 years). Of the patients with follow-up, 5 (62.5%) of 8 survived. Estimated survival rate at 15 years was 58% (Kaplan-Meier analysis). Survivors had 25% or less basaloid histology. Necrosis, hemorrhage, perineural invasion, and mitotic count were less prominent in survivors than in those who died of disease. Vascular invasion was seen only in fatal cases. CONCLUSIONS: Young patients with adenoid cystic carcinomas have a better prognosis than do adult patients, which may be due to their tumors having less aggressive histologic features.

Adolescent↗

Velopharyngeal insufficiency and articulation impairment in velo-cardio-facial syndrome: the influence of adenoids on phonemic development.

Velo-cardio-facial syndrome is the most common contiguous gene disorder in humans and constitutes 8% of patients with clefts of the secondary palate. Speech disorders, including severe hypernasality and articulation impairment have been documented as among the most common clinical manifestations of the disorder. A series of 36 consecutive patients with VCFS ranging in age from 3 to 14 years, all confirmed to have a 22q11.2 deletion, were studied to determine specific risk factors associated with VPI and articulation impairment. Factors studied included palatal clefting, hypotonia, platybasia, and adenoid size. The factor that correlated most strongly with speech disorders was adenoid hypoplasia or absence, a common manifestation in the syndrome. It is hypothesized that early identification of the absence or hypoplasia of the adenoids can result in the implementation of appropriate therapy plans to avoid severe disorders of speech intelligibility.

Abnormalities, Multiple↗

Detection of Epstein-Barr virus and subsets of lymphoid cells in adenoid tissue of children under 2 years of age.

Epstein-Barr virus (EBV) has been closely associated with undifferentiated nasopharyngeal carcinoma (NPC) and T/NK nasal non Hodgkin lymphoma. Nevertheless, the presence of EBV in non neoplastic lymphoid tissue of the nasopharynx has been rarely investigated. In a previous study by our group, using in situ hybridization to detect EBV in adenoids of children (2-13 years old) resected because of nasal obstruction due to hypertrophy, we found EBV genome in 72% of the cases. It was now intended to study the frequency of EBV expression in adenoids from children that underwent surgical removal, belonging to a lower age group (1-2 years old). It was also intended to establish which lymphoid subsets are involved in this infection. Adenoidal paraffin sections from 21 patients aged 1-2 years old (mean 1.6 years), 15 males and six females were submitted to double labeling: in situ hybridization with EBER 1/2 probes to detect EBV and immunohistochemistry to determine the lymphocyte typing of EBV-positive cells (CD20 for B-lymphocytes, CD3 for T-lymphocytes and CD56 and CD57 for NK-cells). Among 21 patients, seven showed positive lymphoid cells for EBV (33%). In almost all cases, EBV-positive cells were also CD20-positive. Some EBV-positive cells showed no labeling with any of the lymphoid markers, but in no instance they were positive for CD3, CD56 or CD57. This study confirms the preferential infection of B-lymphocytes by EBV, which in some instances can down regulate the expression of CD20.

Adenoids↗

Adenoidal tissue mass as a clinical guide of disease evolution in vertically HIV-1 infected children.

INTRODUCTION: it is known that in early-stage HIV-induced disease there is a discrepancy between the levels of viral burden and virus replication in peripheral blood versus lymphoid organs. HIV disease is active in the lymphoid tissue throughout the period of clinical latency. However, it is not known how long term progression of HIV infection is influenced by short-term changes in the adenoidal size. OBJECTIVE: To assess the reliability of adenoidal-nasopharyngeal (AN) ratio in predicting clinical evolution of pediatric HIV infection. METHODS: lateral radiographs of the nasopharynx in 94 Caucasian children born to HIV-1-infected mothers ranged from 6 months to 15 years (60 children infected with HIV-1 and 34 without HIV infection), and in a control group of 692 normal children were evaluated to obtain the AN ratio in order to identify the relationship of AN profiles with different stages of the disease. Patients were rated regarding their clinical and immunological status according to the Center for Disease Control Classification. RESULTS: statistically significant differences between the groups of HIV-1-infected children, seroreverters and controls in the AN ratio were found (P < 0.001). Moreover, significant differences were also found in individual children that correlated with clinical progression. CONCLUSION: examination of radiographic changes in adenoidal size by AN ratio in relation to clinical status during one year period in the whole group showed strong prognostic value. These findings may have important implications in the design of therapeutic strategies.

Adenoids↗