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ORIGINAL ARTICLE
Year : 2010  |  Volume : 47  |  Issue : 4  |  Page : 424-429
 

A retrospective study of 18 cases of adenoid cystic cancer at a tertiary care centre in Delhi


1 Department of Radiotherapy & Oncology, Maulana Azad Medical College and Lok Nayak Hospital, Bahadur Shah Zafar Marg, New Delhi - 110 002, India
2 Department of Pathology, Maulana Azad Medical College and Lok Nayak Hospital, Bahadur Shah Zafar Marg, New Delhi - 110 002, India

Date of Web Publication4-Dec-2010

Correspondence Address:
K Sharma
Department of Radiotherapy & Oncology, Maulana Azad Medical College and Lok Nayak Hospital, Bahadur Shah Zafar Marg, New Delhi - 110 002
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.73571

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 » Abstract 

Context: Adenoid cystic carcinoma (ACC) is a rare neoplasm that usually arises from the salivary, lacrimal, or other exocrine glands. It is characteristically locally infiltrative in nature and has a tendency toward local recurrence, high propensity for perineural invasion, and prolonged clinical course. Aim: To analyze the presentation and natural history of cases of adenoid cystic tumors of salivary glands in our institution; and to compare with the existing literature. Design and Setting: Retrospective study at the Department of Radiotherapy. Materials and Methods: Data on 18 patients of ACC of the salivary glands treated between 2004 and 2008 were reviewed with respect to clinical presentation, stage, and histology. Results: There were 8 cases of major salivary gland tumors (47%), of which 2 were in the submandibular and 6 were involving the parotid. Ten patients (53%) had minor salivary gland involvement. Two patients had metastasis at the time of presentation. All patients underwent surgery. Radiotherapy was delivered to 16 patients and chemotherapy to 6 patients (concurrent, n = 3 and adjuvant, n = 3) and no adjuvant therapy was given to 2 patients. All patients were alive at a median follow-up of 3 years. No patient developed local or distant failure during the study duration. Conclusion: ACC has locally aggressive behavior. Radiotherapy adjuvant to surgery improves local control in locally advanced disease. Longer follow-up is mandatory in view of incidence of late metastasis.


Keywords: Adenoid cystic carcinoma, natural history, salivary gland neoplasms


How to cite this article:
Sharma K, Rathi A K, Khurana N, Mukherji A, Kumar V, Singh K, Bahadur A K. A retrospective study of 18 cases of adenoid cystic cancer at a tertiary care centre in Delhi. Indian J Cancer 2010;47:424-9

How to cite this URL:
Sharma K, Rathi A K, Khurana N, Mukherji A, Kumar V, Singh K, Bahadur A K. A retrospective study of 18 cases of adenoid cystic cancer at a tertiary care centre in Delhi. Indian J Cancer [serial online] 2010 [cited 2017 Feb 26];47:424-9. Available from: http://www.indianjcancer.com/text.asp?2010/47/4/424/73571



 » Introduction Top


Adenoid cystic carcinoma (ACC), also known as "cylindroma" was first described by Theodar Billroth in 1859. ACC is commonly classified with the salivary gland tumors, although it may arise in any site where mucous glands exist. These tumors account for <1% of head and neck neoplasms and 10% of salivary gland tumors. [1] Half of these tumors occur in glandular areas other than the major salivary glands, mainly in the hard palate, but they may also arise in the tongue and other minor salivary gland locations. [1],[2],[3],[4],[5],[6],[7],[8] ACC is the most common malignancy of the submandibular gland.

In some cases, ACC may arise in other primary sites, such as the skin, breast, cervix, prostate gland, external auditory canal, nasopharynx, lacrimal glands, vulva, esophagus, and trachea. [5],[6],[7]

These tumors have a slight female predisposition (female to male ratio 3:2), [8],[9],[10],[11] and most individuals are diagnosed with the disease in the fourth to sixth decades of life. There is no distinct risk factor that predisposes patients toward this malignancy. Various studies have shown chromosomal abnormalities and genetic deletions occurring in samples of ACC. There is some evidence that the p53 tumor suppressor gene is inactivated in advanced and aggressive forms of this neoplasm. No specific molecular abnormalities that underlie this disease process are known. [12]

The diagnosis is made by histologic analysis of a biopsy or resection specimen of a tumor mass. Treatment was defined from physical examination, imaging, staging and histology. Recurrences are usually identified by radiographic imaging techniques, such as computed tomography (CT). This article reviews the presentation and natural history of these tumors in our institute for comparison with existing literature.


 » Materials and Methods Top


During the study duration from August 2004 to February 2008, 18 patients with ACC of the salivary glands registered in the Department of Radiotherapy were chosen for this study. All patients whose treatment began before the start of this period were excluded from the present study. Patients were classified according to their clinical stage, based on the 1998 criteria of the Union Internationale Contre le Cancer (UICC). All patients had preoperative CT scans performed to map the extent of the disease.

Diagnoses were made on the basis of histopathologic samples; preoperatively by means of either fine-needle aspiration or incisional biopsy. All of the patients then underwent surgery with a curative intent. Positive or narrow margins, perineural invasion or more aggressive histologic subtypes (generally the solid type) were the criteria for determining the need for postoperative radiotherapy, and this was employed in 16 cases.


 » Observations and Results Top


In our series, patients were between 20 and 80 years of age at the time of diagnosis. Sixty percent of the patients presented in the 3rd and 4th decade of life [Table 1]. Female patients outnumbered male patients. Two patients presented with lung metastasis. Lymph node metastasis was documented only in 2 patients. In 8 patients, the tumor was present in major salivary glands. Ten patients (56%) had minor salivary gland tumors. The primary tumor was located in the parotid glands in 6 patients (33%), submandibular glands in 2 patients (11%), palate in 2 (11%), and maxillary sinus in 3 (17%). Other sites included base of tongue and buccal mucosa in 5 patients (28%). Pain at the site of the primary tumor was reported in 5 patients (28%). Swelling at the time of presentation was noticeable in 14 patients (78 %). There was a high incidence of perineural invasion in 5 patients (28%). The majority of patients (50%) presented in stage III followed by stage IV (33%). Only 3 patients had stage II disease. Five patients had positive resection margins with infiltration of the surrounding structures.
Table 1a: Patient characteristics
Table b: Treatment schedules (n 16)


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The imaging scans accurately depicted the extent of the primary lesion and none of the scans underassessed the stage of the tumoral lesions, as confirmed by intraoperative findings.

Sixteen patients received postoperative adjuvant radiotherapy due to high risk features [Table 1]. Median delay between surgery and radiotherapy was 6 weeks. Eleven patients received 50 Gy/25 fractions/5 weeks with conventional fractionation. Five patients were given 60 Gy/30 fractions/6 weeks in conventional fractions in view of positive resection margins. Radiotherapy was delivered by cobalt 780E machine. Generous radiation portals were used to cover the cranial nerve pathways to the base of the skull.

Chemotherapy was delivered in only 6 patients. Three patients were given concurrent cisplatin 30 mg/m [2] weekly. Three patients received chemotherapy based on Cyclophosphamide and Adriamycin adjuvant to radiotherapy [Table 1].

All patients were alive at a median follow-up of 3 years and there was no local or distant relapse during this study duration.


 » Discussion Top


Salivary gland ACC has indolent behavior, but is prone to late local recurrence. [9],[10] The management is based on the clinical stage, histopathologic subtype, and ancillary imaging examinations, including CT scans.

The usual peak incidence of ACC is between 50 and 60 years of age. The tumors seldom occur before the age of 30 years, which is consistent with our study in which most patients presented in the third and fourth decades and no patient presented before the age of 30 years. [11],[13] There was a slight female predominance among the cases, which was similar to the available literature. [8],[9],[10] Major salivary glands were affected more than the minor salivary glands. Among the major salivary glands, the parotid gland was the one most frequently affected, which was in contrast to the literature where submandibular gland was more commonly involved. [9],[10] In the present series, there were no cases of ACC in the sublingual glands, which could be attributed to a smaller sample size.

ACC usually occurs as a largely asymptomatic, nonulcerated submucosal mass. Diagnosis is often delayed; and most patients even with metastatic disease are relatively asymptomatic for long periods. Signs and symptoms depend largely on the site of the tumor. Early lesions of the salivary glands present as painless slowly growing masses of the mouth or face. Advanced tumors may present with pain and/or nerve paralysis. [7],[13],[14],[15] Similarly in our review, pain was present only in 5 patients, whereas 14 patients (82%) had painless swelling at presentation. The majority of patients had a longstanding history of more than 6 months.

The clinical course is often prolonged and there is propensity for perineural invasion, and there is a tendency for local recurrence. [1],[13],[17],[18],[19] Local recurrence and pulmonary metastasis are frequent even after curative resection. Positive margins and neural invasion suggest recurrence and have a negative influence on survival. The relatively short follow-up in our series meant that there were few distant metastases contrary to the existing literature. [13]

Another unusual feature of ACC is the low incidence of metastases to regional lymph nodes. Only 2 patients in our review had lymph node metastasis. [20] Distant metastasis is the most common presentation of treatment failure. Lung is the most common site of metastasis, with the liver being the second most common site. Bone metastases usually indicate a fulminant clinical course. No liver and bone metastasis were encountered in our review, which may be attributed to a shorter follow-up.

ACC has a distinctive microscopic appearance, which is characterized by abnormal nests or cords of epithelial cells surrounding or infiltrating ducts and glandular structures within the affected organ. [21],[22],[23] Classically, it consists of 3 subtypes histologically cribriform (cylindromatous), tubular, and solid [Figure 1], [Figure 2], [Figure 3], [Figure 4]. The most predominant and frequent is the cribriform pattern. It is characterized by nests of tumor cells containing numerous sharply outlined luminal spaces and sometimes containing mucinous secretions in their lumen. The solid pattern has the tendency to grow predominantly extraluminally and to more likely metastasize. The tubular subtype has the best prognosis; and solid subtype carries the worst prognosis.
Figure 1: Perineural invasion (H and E, ×400)

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Figure 2: Trabecular and tubular pattern of adenoid cystic carcinoma (H and E, ×100)

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Figure 3: Cystic dilatation of the glands (H and E, ×400)

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Figure 4: Solid pattern of adenoid cystic carcinoma (H and E, ×100)

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The clinical differential diagnosis consists largely of other benign and malignant neoplasms that arise in these locations. These include benign mixed tumor, mucoepidermoid carcinoma, and polymorphous low-grade adenocarcinoma (PLGA). The major histologic differential diagnosis in the minor salivary glands is between ACC and PLGA, which share many features. In other sites, ACC may be confused on histologic grounds with a variant form of squamous carcinoma known as basaloid squamous carcinoma. [24]

Surgical resection is the mainstay therapy. Postoperative radiotherapy is advocated to decrease the risk of local recurrence. Postoperative radiotherapy significantly improves regional control in the pN+ neck (86% vs 62% for surgery alone). Terhaard et al have recommended postoperative radiotherapy with a dose of at least 60 Gy for patients with T3-T4 tumors, incomplete or close resection, bone invasion, perineural invasion, and pN+. In unresectable tumors, a dose of at least 66 Gy has been advisable. [25]

A few specialized centers offer neutron beam therapy, which may be more effective than conventional radiation therapy. In a retrospective study by Huber comparing radiotherapy with neutrons, photons, and a photon/neutron mixed beam in patients with advanced ACC of the head and neck, fast neutron radiotherapy provided higher local control rates than a mixed beam and photons in advanced, recurrent, or incompletely resected ACC. Neutron radiotherapy can be recommended in patients with a bad prognosis with gross residual disease, with unresectable tumors, or inoperable tumors. The type of radiation did not impact survival, which is dominated by the high number of distant metastases. [26]

There appears to be no effective chemotherapy for ACC, although some patients may receive palliation. There is paucity of literature relating to chemotherapy for ACC due to the rarity of these tumors. Koopot et al reported some improvement with oral cyclophosphamide in a patient with pulmonary metastases. [27] A review was conducted in 1977 at the M.D. Anderson Hospital, Texas, of its 25-year experience of patients with malignant neoplasms of the major salivary glands. [28] Of 671 patients, 43 (6%) received single-agent chemotherapy. Four partial responses (10%) were observed in 39 evaluable trials. Three of 6 patients treated with an anthracycline and 1 of 2 treated with hexamethylmelamine (altretamine) responded. Of 23 evaluable trials with multiple-agent chemotherapy, responses occurred in 1 of 4 patients who received cyclophosphamide and lomustine and in 1 of 3 who were treated with Ftorafur, methotrexate, lomustine, and BCG (Bacillus Calmette-Guιrin).

Administering the combination of drugs of cyclophosphamide, Adriamycin and cisplatin, Creagan et al noted an overall response rate of 50% in 16 patients. [29] Cisplatin also had been administered by the intra-arterial route to patients with ACC, and all the 4 patients showed some response. [30]

A study of the combination of doxorubicin, cisplatin, and cyclophosphamide has confirmed its activity in ACC and is found to be of value as an induction treatment. Dimery et al treated 17 patients with salivary gland carcinomas with a combination of fluorouracil, doxorubicin, cyclophosphamide, and cisplatin. Among the 7 patients with ACC were 3 partial responses, 2 minor responses, and 2 with stationary disease. [31],[32] A report from Turin University of 27 patients, including 10 with ACC, found some superiority for multiple-agent regimens with an overall response rate of 45%. [33] In a study conducted by Vermorken et al, epirubicin was used to treat 20 patients with ACC. Objective regression was seen in 2 (10%) patients, but symptomatic improvement occurred in a majority of the patients. All the patients had documented progressive disease before treatment, and 10 (50%) showed disease stabilization with a median time to progression of 16 weeks. [34]

Several clinical trials are examining the effects of relatively new chemotherapeutic drugs (paclitaxel, gemcitabine, and others) alone, or in combination with other drugs. Ongoing trials are evaluating lapatinib in ACC, but it has not been found to be promising.

Early perineural and hematologic spread is common. Local recurrences and distant metastases (especially to the lung) are common and sometimes arise years after the primary tumor has been diagnosed and treated. Unlike most carcinomas, most patients with ACC survive for 5 years, only to have tumors recur and progress. In a recent study of a cohort of 160 ACC patients, disease-specific survival was 89% at 5 years but only 40% at 15 years. Therefore, these patients require long-term follow-up. As is true of ACC primary tumor, distant metastases are occasionally stable and slow-growing. For these patients, long-term follow-up is essential because of the possibility of late hematologic metastasis, especially among high risk patients. Poor prognostic signs at the time of initial surgery are a solid growth pattern, perineural invasion of major nerves, and/or positive margins after histopathologic examination.


 » Conclusion Top


We conclude from this study that ACC is predominantly a disease of the middle aged with a slight female predominance. Most patients present with painless mass lesions, with less than a quarter of patients presenting with pain. Distant metastases or even lymph node spread was not common in this study; however, distant metastasis is the most common cause of disease recurrence even after 10 years of completion of treatment. Complete surgical excision is the treatment of choice. Postoperative radiotherapy is indicated in cases of close or positive margins, residual disease, lymph node involvement, perineural spread, as well as very large primary. These cases generally have a poorer prognosis; hence, the need for postoperative radiation therapy. Multi-agent chemotherapy offers palliation in patients with advanced, recurrent and metastatic disease. Long-term survival in these patients is generally excellent even in patients with metastatic disease due to the indolent nature of both primary and metastatic lesions. However, in this study, in view of the short follow-up of less than 5 years, long-term survival as well as progression free survival could not be evaluated. All our patients remained free of disease at the time of compilation of the results. Further long-term follow up is required.

 
 » References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

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