Immunohistochemical distribution of CD9 in parotid gland tumors

OBJECTIVE: CD9 is a member of the tetra-membrane-spanning glycoprotein family called tetraspanin. CD9 suppresses breeding and motion in some types of cancer cells. At present, the expression of CD9 in the salivary gland has not yet been elucidated. METHODS: We examined the expression of CD9 not only in the normal salivary glands of human embryo and adults but also in the parotid gland tumors using immunohistochemical staining. RESULTS: CD9 was not detected in embryos at 18 weeks of gestation, but was observed at 24 weeks in the salivary gland. CD9 was constantly detected in the adult normal parotid gland. In benign parotid gland tumors, CD9 was present in the 11 of 16 pleomorphic adenomas, every Warthin tumors (18/18) and basal cell adenoma (1/1). In contrast, positive staining for CD9 in malignant parotid tumors was observed in only the case of mucoepidermoid carcinomas. Neither acinic cell carcinomas or adenoid cystic carcinomas did show positive reaction in examined cases. The localization of CD9 was also observed in intercalated duct cells. CONCLUSION: There was a statistically significant reduced expression of CD9 in malignant parotid gland tumors as compared to benign parotid gland tumors (P = 0.003).     

DNA ploidy and proliferative activity in salivary gland tumours]

DNA ploidy and S-Phase fraction (SPF) of 279 salivary gland tumours were analysed using high-resolution DNA flow cytometry. All 229 benign neoplasms were diploid while 12 of 50 malignant tumours showed cell populations with aneuploid DNA content. The SPF values of diploid malignancies were significantly higher if compared with pleomorphic adenomas but did not differ from that of the zystadenolymphoma (Warthin tumour) group. While aneuploidy represents a distinct indicator of malignancy SPF values are of minor relevance for dignity assessment in salivary gland tumours.     

Two-Phase Helical Computed Tomography Study of Salivary Gland Warthin Tumors: A Radiologic Findings and Surgical Applications

Objectives

The goal of this study was to define the radiologic characteristics of two-phase computed tomography (CT) of salivary gland Warthin tumors and to compare them to pleomorphic adenomas. We also aimed to provide a foundation for selecting a surgical method on the basis of radiologic findings.

Methods

We prospectively enrolled 116 patients with parotid gland tumors, who underwent two-phase CT preoperatively. Early and delayed phase scans were obtained, with scanning delays of 30 and 120 seconds, respectively. The attenuation changes and enhancement patterns were analyzed. In cases when the attenuation changes were decreased, we presumed Warthin tumor preoperatively and performed extracapsular dissection. When the attenuation changes were increased, superficial parotidectomy was performed on the parotid gland tumors. We analyzed the operation times, incision sizes, complications, and recurrence rates.

Results

Attenuation of Warthin tumors was decreased from early to delayed scans. The ratio of CT numbers in Warthin tumors was also significantly different from other tumors. Warthin tumors were diagnosed with a sensitivity of 96.1% and specificity of 97% using two-phase CT. The mean operation time was 38 minutes and the mean incision size was 36.2 mm for Warthin tumors. However, for the other parotid tumors, the average operation time was 122 minutes and the average incision size was 91.8 mm (P<0.05).

Conclusion

Salivary Warthin tumor has a distinct pattern of contrast enhancement on two-phase CT, which can guide treatment decisions. The preoperative diagnosis of Warthin tumor made extracapsular dissection possible instead of superficial parotidectomy.     

Flow cytometric analysis of DNA content and Ki-67-positive fractions in the diagnosis of salivary gland tumors

To explore the utility of flow cytometry (FCM) for the diagnosis of histopathology of salivary gland tumors, fresh materials taken at surgery from 23 Warthin’s tumors, 57 pleomorphic adenomas, and 14 malignant tumors were analyzed for DNA ploidy and proliferative cell activities, including S-phase fraction (SPF), G2- plus M-phase fraction (G2M), and Ki-67-positive fraction. To facilitate this study, glands were taken from all major salivary sites and minor glands in the head and neck. DNA aneuploidy was not detected in the benign tumors. Nine of 14 malignant tumors showed DNA aneuploidy. The percentage of SPF or G2M of the malignant tumors was significantly higher than those of the benign tumors. The percentage of Ki-67-positive fraction of pleomorphic adenomas was comparable to that of malignant tumors and was significantly higher than that of Warthin’s tumors. Ki-67 of 20% as a cut-off had a sensitivity of 88%, specificity of 100%, and accuracy of 91% for differentiating pleomorphic adenomas from Warthin’s tumors. In analyzing DNA content and proliferative activities by FCM, we could distinguish among the three major histopathologies of salivary gland tumors. Warthin’s tumors showed low SPF+G2M with low Ki-67, pleomorphic adenomas had low SPF+G2M with high Ki-67, and malignant tumor showed high SPF+G2M with high Ki-67. The high percentage of the Ki-67-positive fraction seen in pleomorphic adenomas may reflect their potential biological aggressiveness manifested as tumor recurrence or malignant transformation. Received: 26 June 1997 / Accepted: 5 November 1997     

Diagnosis management of Warthin tumour: clinical presentation, fine needle cytology and MRI

OBJECTIVES: Warthin tumour is the second most frequent benign tumour of the parotid gland after pleomorphic adenoma. The aim of this retrospective study was to define clinical, cytological and MRI characteristics in order to work out a therapeutic strategy. MATERIAL AND METHOD: During the period May 1991-January 2003, 53 patients with Warthin tumors were treated in our institution. Clinical data were reported from medical records reviewing. Histological diagnoses were compared with FNAB and MRI results. RESULTS: Warthin tumours represented 13% of all parotid lesions of our series. Mean age of patients was 58 year-old. Sex ratio was 3.8 men and 1 woman. Sensitivity of FNAB for Warthin tumour diagnosis was 75% while positive predictive value was 71%. Six cases of false positive patients were reported: 2 acinic cells carcinomas, 2 pleomorphic adenomas, 1 dermoid cyst, 1 branchial cyst. CONCLUSIONS: Surgical management is based on partial parotidectomy that may be adapted to the tumour location. Because of elderly patients, benign nature and low risk of malignant transformation of Warthin tumours, one might prompt to adopt a conservative strategy, avoiding surgery in some cases. Despite diagnosis of Whartin tumour on FNAB and MRI, one must be cautious in recommending conservative treatment in order to avoid ignoring a surgical tumour.     

Masses of the salivary gland region in children

BACKGROUND: Noninflammatory masses of the salivary gland region in children are extremely rare. Therefore, very few published individual and institution-based experiences exist. DESIGN: Retrospective chart review from 1990 through 1997. SETTING: University-based children's hospital. DESIGN: Patients 18 years of age or younger with a tumor in the salivary gland region. Masses of infectious origin were excluded. Hemangiomas and lymphangiomas were tallied for relative incidences only. RESULTS: Three hundred twenty-four consecutive cases of salivary gland masses were found: 192 hemangiomas (59.2%), 89 lymphangiomas (27.5%), and 43 (13.3%) solid masses. No significant difference was found between the age at presentation of the patients with benign solid tumors and the patients with malignant solid tumors (mean + SEM age, 7.2 + 0.7 years). Sixty-one percent of the masses were found in the parotid region; 18% were localized to the submandibular gland region; and the remaining 21% were located in a minor salivary gland site. The most common benign perisalivary masses were pilomatrixomas (20.9%), followed by pleomorphic adenomas (11.6%). The most common malignant masses were mucoepidermoid carcinomas (9.3%), followed by rhabdomyosarcomas (7.0%). Treatment was individualized to the disease. Twenty-two patients had adequate data for follow-up analysis (mean + SEM follow-up, 30.0 + 8.4 months). Four patients (18.2%) experienced recurrent or residual disease and were alive with disease at last follow-up, and 100% of our population demonstrated disease-specific survival at last follow-up. CONCLUSIONS: Vascular lesions outnumber solid tumors of the salivary gland region. The most common salivary tumors were pleomorphic adenomas, followed by mucoepidermoid carcinomas. Although certain solid salivary masses may demonstrate locally aggressive behavior, the overall prognosis is favorable. Arch Otolaryngol Head Neck Surg. 2000;126:1435-1439     

Extra-major salivary gland pleomorphic adenoma of the head and neck: a 10-year experience and review of the literature

Pleomorphic adenomas, or benign mixed tumors, make up 65% of all salivary gland tumors. They also can be found as solid tumors in other parts of the head and neck region, such as the auditory canal, the eyelids, and the orbital area. In this study, we investigated extra-major salivary gland pleomorphic adenomas of the head and neck region retrospectively at a tertiary care center. Between March 1998 and June 2009, 37 patients underwent primary surgery for extra-major salivary gland pleomorphic adenoma of the head and neck. The duration of symptoms, radiographic findings, operative procedures, and pathologic findings were documented. Of the 37 patients enrolled, 22 were male and 15 were female, with a median age of 57?years. Tumors were found in the soft palate, hard palate, nasopharynx, orbital area, trachea, buccal mucosa, cheek, nasal septum, upper lip, lower eyelid, and external auditory canal. Cellular variant of the pleomorphic adenoma was found in four patients, while the remaining patients presented with the classic variant. No myxoid subgroup was noted in our study. Carcinoma ex pleomorphic adenoma was observed only in one patient for whom radical surgery was performed. Twenty-eight patients (76%) had long-term follow-ups, with the average follow-up period being 4.5?years. Local recurrence was observed in three patients, and they underwent revision surgery during the follow-up period. Our results indicate that extra-major salivary gland pleomorphic adenomas are most commonly found in the soft palate. Wide excision was the treatment of choice, although its efficacy might be compromised with cosmetics and functional structures of the head and neck. Therefore, long-term follow-up of patients is necessary.     

Simultaneous primary pleomorphic adenoma in parotid gland and minor salivary gland in the parapharyngeal space

The majority of salivary gland tumours present as a single mass in one gland. Sometimes multiple primary neoplasms can be seen in more than one salivary gland. The most common tumour is Warthin's tumour. Multiple primary pleomorphic adenomas are extremely rare. Most of them are in the major salivary glands. The author reports the first case of simultaneous pleomorphic adenomas in the parotid gland and minor salivary gland at the parapharyngeal space.     

Pleomorphic adenomas in the materials of the Department of Otolaryngology of the Academy of Medical Sciences in Poznań

In the years 1958-1997 were surgically treated in the Department of Otolaryngology Karol Marcinkowski University of Medical Sciences in Poznań 365 patients with pleomorphic adenomas. Majority of the tumors originated of the major salivary glands was parotid gland (273 cases). The given materials confirms the viewpoint that enucleation in the pleomorphic adenomas of the parotid salivary gland--based on total removal of the tumor together with the capsule and pouch constitute a completely sure surgical procedure.     

Constitutive (HO-2) and inducible (HO-1) haem oxygenase in pleomorphic adenomas of the human parotid: an immunocytochemical study

This study examines the expression HO-1 and HO-2 isozymes in human parotid pleomorphic adenomas. They are members of the heat shock protein family, and are thought to play a role in the regulation of tumoral blood flow. Immunocytochemistry using antibodies specific for HO-1 and HO-2 were undertaken in 12 pleomorphic adenoma specimens, all sections of which contained adjacent normal salivary tissue. Normal salivary gland acini and ducts displayed significantly stronger immunoreactivity for HO-2 compared to tumour cells (p < 0.001). Expression for HO-1 was minimal in both normal salivary gland acini and tumour cells with no difference (p = 1.000). However, positive staining for HO-1 was seen in normal salivary ducts and in pleomorphic adenomas showing ductal differentiation. In conclusion, this is the first study to examine the expression of HO-1 and HO-2 within normal salivary glands and pleomorphic adenomas. Our findings suggest that HO may be implicated in the pathogenesis of salivary pleomorphic adenomas.     

Myoepithelial carcinoma ex-pleomorphic adenoma of the parotid gland

INTRODUCTION: Myoepithelial carcinoma accounts for less than 1% of salivary gland malignant tumors. It may develop de novo or, in approximately 50% of the cases, from a pleomorphic adenoma. OBSERVATION: A 57-year-old man with a history of a pleomorphic adenoma of the parotid treated surgically 6 years earlier, presented with a 2 cm tumor mass, palpable in the scar region. The histological examination and immunohistochemical study revealed a low-grade myoepithelial carcinoma. The patient had no complementary treatment. He presented 5 years later with a 2 cm parapharyngeal recurrence which was resected. There was no evidence of recurrent tumor or of distant metastasis at 4 year follow-up. DISCUSSION: Although myoepithelial cells are often predominant in pleomorphic adenomas, carcinomas developing in pleomorphic adenomas show in most cases a glandular differentiation and myoepithelial carcinomas are rare. Currently the diagnostic criteria, the prognosis, and the management of myoepithelial carcinomas are not well documented. Invasive carcinomas developing in pleomorphic adenoma are known to be highly aggressive neoplasms and myoepithelial carcinomas ex-pleomorphic adenoma seem to have a better prognosis. Our reported case was characterized by the weak aggressiveness of the lesion.     

Simultaneous pleomorphic adenomas of the right parotid and ipsilateral submandibular glands

A case of simultaneous pleomorphic adenomas of the right parotid and ipsilateral submandibular glands was reported. The patient was a 68-year-old woman who had a ten-year history of an otherwise asymptomatic non-enlarging mass in the parotid gland and a slowly enlarging mass in the submandibular gland. Microscopically, the parotid tumor consisted of predominant spindle-shaped cell proliferations with myxoid stroma in places. The submandibular gland tumor showed tubular and trabecular formations with stroma consisting of hyalinized fibrous connective tissues. Simultaneous pleomorphic adenomas in the salivary glands are so rare that only 23 cases can be found in the literature. Additionally, only five tumors occurring simultaneously in the parotid and submandibular glands are reported in the literature. Our case seems to be the sixth of simultaneous pleomorphic adenomas of the parotid and submandibular glands.     

Marginally excised parotid pleomorphic salivary adenomas: risk factors for recurrence and management. A 12.5‐year mean follow‐up study of histologically marginal excisions1

Marginally excised parotid pleomorphic salivary adenomas: risk factors for recurrence and management. A 12.5‐year mean follow‐up study of histologically marginal excisions The aim of the study was to identify recurrence risk factors in surgically excised parotid pleomorphic salivary adenomas. We reviewed the case histories and histological findings for all cases of marginal or inadequate excision of pleomorphic salivary adenomas at the Royal Hallamshire Hospital, Sheffield, UK, between 1980 and 1995. A total of 83 cases with complete records were identified, with a mean follow‐up period of 12.5 years. The histological slides were reviewed in each case. The overall recurrence rate was 6.0%. Where tumour was present at the margin, recurrence occurred in 17.6% of cases. However, cases conventionally regarded as marginally excised and likely to recur (tissue margin < 1 mm) showed recurrence in only 1.8% of cases. Intraoperative capsular rupture, microscopic capsular invasion by tumour and several other surgical factors were not predictive of recurrence. Adequate excision of pleomorphic salivary adenomas, in the sense of minimal recurrence risk, does not require more than a fraction of a millimetre of surrounding tissue. Only pleomorphic salivary adenomas with tumour actually at the excision margin require prolonged follow‐up or consideration of radiotherapy. Provided that the tumour can be removed intact, the surgical approach for pleomorphic salivary adenomas should be guided by the need to preserve vital structures rather than by an attempt to remove a cuff of normal tissue with the tumour.     

erbB-2/Her-2 gene amplification and overexpression in parotid gland tumors

Summary Proto-oncogenes represent a family of normal cellular genes that were identified on the basis of their similarity to genetic sequences with known tumorigenic + or transforming potential. Accumulating evidence links alterations in either the structure, copy number, or expression of one or another of these genes to neoplasia. One such gene, called erbB-2/Her-2 was found amplified in an adenocarcinoma of the human salivary gland and has also been found associated with primary human breast cancer. Patients with multiple copies of the gene have had a shorter overall survival. In the present study, 21 tumors of the parotid gland were examined by Southern and Northern blot hybridization for amplification and possible overexpression of the erbB-2/Her-2 oncogene. Normal parotid gland tissue was used as negative control. The parotid gland lesions comprised 7 pleomorphic adenomas, 5 squamous cell carcinomas, 4 cases of chronic fibrotic sialadenosis, 3 mucoepidermoid carcinomas as well as 1 lymphoma and 1 cystadenolymphoma. Gene amplification was found in 1 of the pleomorphic adenomas, with 2 tumors showing a significant overexpression of the erbB-2/Her-2 oncogene. Because 3–5% of all pleomorphic adenomas undergo malignant transformation, close follow-up of patients is currently underway.     

Pleomorphic adenoma of minor salivary glands

Pleomorphic adenoma, a benign tumor often seen in ENT practice, arises either from minor as well from major salivary glands. 5-14% of tumors occur in minor glands. Sixteen cases of minor salivary gland pleomorphic adenomas are studied. Eight of them originate from the oral cavity: 6 from the palate, one from the lower lip and one from the cheek. Two oral adenomas were malignant. In 4 patients tumors occur in the nasal cavity and in two other patients--in the neck. The clinical and pathological features of these patients are presented. Special attention is given to malignant transformation and the rate of recurrence of the tumors.     

Evaluation of proliferating activity of pleomorphic adenoma arising from the salivary glands--using anti BrdU monoclonal antibody

Salivary gland tumors present diverse histopathological aspects and show various biological behavior. At present, the immunohistological method using anti-BrdU monoclonal antibodies, which was originated in the field neurosurgery, has been tried extensively in various fields of medicine. Using this method, the authors have attempted to detect biological characteristics of salivary gland tumor tissues, especially those of pleomorphic adenomas. The labelling index (L.I.) is defined as the percentage of the labelled cells (proliferating cells) in the tumor tissue. In order to confirm the usefulness of the L.I. for measuring the proliferating activity of tumor tissue, an investigation was conducted with respect to squamous cell carcinomas of the head and neck, excluding salivary gland tumors. The results indicate that the L.I. is highly correlated with the differentiation of these carcinomas. In salivary gland tumors, values of the L.I. are also higher for benign tumors than for normal or inflammatory tissues and the values were even higher for malignant tumors. Values of the L.I. are low for pleomorphic adenomas, which are the majority of salivary gland tumors, as well as for other benign tumors. However considerable individual variabilities, are bound for pleom. ad. and the values of the L.I. are markedly high in some cases. These high values are particularly common in patients with whom strong positivity in Ga scintigraphy, or primary growth in the submandibular glands are found. The localization of proliferating cells shows a characteristic pattern in each type of tumor tissue. In pleomorphic adenomas, proliferating cells are sporadically distributed but the main growth is located at the site of the epithelioid proliferative region, excluding the duct-forming locus. However, the overall proliferating activity of myxochondromatous tumors is not generally low, and the proliferating activity is not particularly high in the region of infiltrating is the capsule.     

A causal relationship between chromosomal rearrangements and the genesis of salivary gland pleomorphic adenomas

Summary The results of chromosome analyses performed on 50 pleomorphic salivary gland adenomas in Germany are summarized herein and compared with those obtained on 100 adenomas studied in Sweden. In both series, characteristic or even specific structural chromosomal rearrangements involving either chromosome 8 or 12 were found that allowed the cytogeneticist to distinguish between subgroups. However, the significantly higher percentage of tumors with chromosome abnormalities in the adenomas examined in Germany is particularly noteworthy. In the near future, cytogenetic investigations together with molecular methods will allow investigators to describe basic mechanisms for the development of pleomorphic adenomas in terms of oncogenetics.     

A case of pleomorphic adenoma of the parotid gland metastasizing to a mediastinal lymph node

OBJECTIVE: Pleomorphic adenomas are the most common salivary gland tumors and are typically cured with complete surgical excision. There are rare reports, however, in which these histologically benign tumors have inexplicably metastasized to distant sites. We present a case of a patient who presented, 27 years after excision of a parotid pleomorphic adenoma, with a recurrence in the parotid bed and a mediastinal metastasis. STUDY DESIGN: Case report. METHODS: A 43-year-old woman presented with a mass in the right parotid bed 27 years after excision of a pleomorphic adenoma of the parotid. The patient's presentation, workup, and final diagnosis of benign metastasizing pleomorphic adenoma will be discussed, along with a pertinent review of the literature. RESULTS: A diagnosis of recurrent pleomorphic adenoma was made from a fine needle aspiration biopsy of the right parotid mass. On subsequent computed tomographic scan, chest images revealed an incidental left mediastinal mass, which also proved to be a pleomorphic adenoma on computed tomography-guided fine needle aspiration biopsy. The patient underwent a completion parotidectomy and sternotomy with excision of the mediastinal mass. Examination of the pathology specimens confirmed a diagnosis of pleomorphic adenoma in both the parotid bed and the mediastinum. No histologic characteristics of malignancy were seen in either specimen; therefore, a diagnosis of benign metastasizing mixed tumor was rendered. CONCLUSION: Benign metastasizing pleomorphic adenoma is a rare and controversial but distinct clinical entity. Although the definition of the term benign precludes metastatic disease, these tumors do not demonstrate any malignant features yet metastasize to distant sites. It remains to be determined whether these benign metastasizing pleomorphic adenomas are really low-grade salivary malignancies.     

A causal relationship between chromosomal rearrangements and the genesis of salivary gland pleomorphic adenomas

The results of chromosome analyses performed on 50 pleomorphic salivary gland adenomas in Germany are summarized herein and compared with those obtained on 100 adenomas studied in Sweden. In both series, characteristic or even specific structural chromosomal rearrangements involving either chromosome 8 or 12 were found that allowed the cytogeneticist to distinguish between subgroups. However, the significantly higher percentage of tumors with chromosome abnormalities in the adenomas examined in Germany is particularly noteworthy. In the near future, cytogenetic investigations together with molecular methods will allow investigators to describe basic mechanisms for the development of pleomorphic adenomas in terms of oncogenetics.