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CASE REPORT
Year : 2017  |  Volume : 6  |  Issue : 3  |  Page : 185-188

Carcinoma ex-pleomorphic adenoma of submandibular salivary gland: A case report and review of literature


1 Department of Otorhinolaryngology (ENT), K S Hegde Medical Academy, Nitte University, Mangalore, Karnataka, India
2 Department of Pathology, K S Hegde Medical Academy, Nitte University, Mangalore, Karnataka, India

Date of Web Publication25-Sep-2017

Correspondence Address:
Vadisha Srinivas Bhat
Department of Otorhinolaryngology, K S Hegde Medical Academy, Mangalore - 575 018, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2277-8632.215518

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  Abstract 

Pleomorphic adenoma (PA) is the most common benign neoplasm affecting the major salivary glands. It is more common in parotid gland and sometimes occurs in submandibular and other minor salivary glands. Carcinoma ex-pleomorphic adenoma (CXPA) is the malignant transformation of a primary or recurrent PA. Here, we report a case of CXPA of submandibular salivary gland with metastasis in the cervical lymph nodes. He was treated with excision of the mass with radical neck dissection, followed by adjuvant radiotherapy.

Keywords: Adjuvant radiotherapy, carcinoma ex-pleomorphic adenoma, excision, lymph node metastasis, submandibular salivary gland


How to cite this article:
Bhat VS, Biniyam K, Aziz AA, Yeshwanth SK. Carcinoma ex-pleomorphic adenoma of submandibular salivary gland: A case report and review of literature. J NTR Univ Health Sci 2017;6:185-8

How to cite this URL:
Bhat VS, Biniyam K, Aziz AA, Yeshwanth SK. Carcinoma ex-pleomorphic adenoma of submandibular salivary gland: A case report and review of literature. J NTR Univ Health Sci [serial online] 2017 [cited 2020 Apr 9];6:185-8. Available from: http://www.jdrntruhs.org/text.asp?2017/6/3/185/215518


  Introduction Top


Pleomorphic adenoma (PA) is the most common benign neoplasm of the salivary glands. They are usually found in the parotid gland, but they can also arise in the submandibular, sublingual, and minor salivary glands.[1],[2] They present as a slow growing painless mass. Malignant transformation occurs in 5-25% untreated patients.[3] There are three subtypes of malignant PA: Carcinoma ex-pleomorphic adenoma (CXPA), carcinosarcoma, and metastasizing PA. The most common subtype is CXPA which develops in primary or recurrent PA.[3] The likelihood of malignant transformation increases with the duration of the lesion.[1] The optimal treatment is wide local excision with or without postoperative radiotherapy. We report a case of CXPA of the submandibular gland, with metastasis in cervical lymph nodes. He was treated with excision of the gland along with radical neck dissection followed by postoperative adjuvant radiotherapy.


  Case Report Top


A 65-year-old male patient presented with a swelling in the left submandibular region for last 7 years. The swelling was initially small in size and slow growing but started growing rapidly in last 6 months. The swelling was painless. He did not have difficulty in swallowing or breathing. On examination, there was a firm, nontender swelling measuring 9 cm × 6 cm with lobular surface in left submandibular area. The swelling was mobile and skin over the swelling was normal and pinchable [Figure 1]. There were three firm mobile lymph nodes palpable in level IB and two in level II region, each measuring about 1 cm × 1 cm in size. Oral cavity and oropharynx were within the normal limits. Indirect laryngoscopy examination was within normal limits.
Figure 1: Clinical photograph of the patient with left submandibular mass

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Ultrasonography of the neck revealed well defined, encapsulated mass of mixed echogenicity in left submandibular region. Multiple enlarged levels II and III lymph node were noted. Fine-needle aspiration cytology (FNAC) of the mass revealed tiny clusters of tumor cells with pleomorphic hypochromatic nuclei and vague acinar pattern with occasional giant cells. Cytological features were suggestive of poorly differentiated adenocarcinoma. Computed tomography (CT) scan revealed lobulated large heterogeneously enhancing mass measuring 11 cm × 7 cm in left submandibular salivary gland with central necrosis [Figure 2]. Necrotic lymph nodes were seen in ipsilateral levels I, II, III, and V region [Figure 3]. Thorax and abdominal viscera were within normal limits.
Figure 2: Computed tomography scan neck axial view showing lobulated large heterogeneously enhancing mass in left submandibular salivary gland with central necrosis

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Figure 3: Computed tomography scan neck axial view showing cervical lymph nodes

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Wide excision of left submandibular mass with left radical neck dissection was performed under general anesthesia. Postoperative period was uneventful. The resected specimen measured 12 cm × 8 cm × 6 cm in size. The cut surface of the mass showed grey white solid tumor with areas of hemorrhage and necrosis [Figure 4]a. Histopathological examination of the specimen showed epithelial and chondromyxoid stromal component accompanied with myoepithelial cells with foci displaying pleomorphic tumor cells arranged in tubulo-alveolar pattern favoring the diagnosis of CXPA [Figure 4]b and [Figure 4]c. Metastatic deposits of the tumor were seen in 40 of the 43 lymph node isolated with radical neck dissection [Figure 4]d. Adjuvant radiotherapy of 66 Gray was given. Patient is under follow-up for last 1 year and he is in good general health status and there is no evidence of loco-regional recurrence of the disease.
Figure 4: (a) Gross specimen showing a partially encapsulated, ill-defined variegated tumor comprising of grey white areas, hemorrhage and necrosis with adjacent compressed normal salivary gland tissue. (b) Microphotograph of pleomorphic adenoma component displaying both epithelial and chondromyxoid stromal component accompanied with myoepithelial cells (H and E stain, ×10). (c) Microphotograph of other foci displaying pleomorphic tumor cells (arrow) arranged in tubulo-alveolar pattern favoring carcinoma ex-pleomorphic adenoma (H and E stain, ×10). (d) Microphotograph of cervical lymph node showing metastatic deposits of the tumor (H and E stain, ×10)

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  Discussion Top


Pleomorphic adenomas are common benign neoplasm of the major salivary glands. They are usually found in the parotid gland but they can also arise in the submandibular, sublingual, and minor salivary glands. They sometimes undergo malignant transformation. Malignant changes in PA have been associated with a long tumor duration, tumor recurrence after excision, advanced age, and a large tumor size.[4] Malignant transformation of PA occurred in 5-25% untreated patients.[3] Malignant derivatives of PA are classified into three groups: CXPA, carcinosarcoma, and metastasizing PA.[5] CXPA comprises the vast majority of malignant mixed tumors.[5] It develops in 6% of all PAs. These tumors represent 3.6% of salivary gland neoplasm, and 11.6% of all malignant neoplasm of the salivary gland. They are mainly seen in major salivary glands. Occurrence in the minor salivary gland is uncommon accounting for <7% of all cases.[6] CXPA is found predominantly in the sixth to eighth decades of life and is slightly more common in females.[7]

Carcinoma ex-pleomorphic adenoma can be asymptomatic as most of the tumors are not invasive and often have similar clinical presentations as PA. Pain usually results from local extension of the neoplasm into adjacent soft tissues or bone. Patients with long-standing mass are frequently become alerted when there is rapid enlargement of the mass, pain, or other clinical symptoms.[7] Since the presenting symptoms are similar to those of a benign PA, it is important that the high index of suspicion is required.

Imaging is essential before planning the treatment. CXPA may have various CT appearances: It may be similar to a PA with no evidence of malignancy, it may occur with focal necrosis, wall irregularity, or infiltrating margins or it may have an entirely aggressive CT appearance.[8],[9] In our case, the CT scan showed a heterogeneously enhancing mass with central necrosis.

Sensitivity and specificity of fine-needle aspiration biopsy in the diagnosis of malignant character of PA were 60% and 46% respectively.[3] High-grade salivary adenocarcinoma that is difficult to classify should raise the suspicion of possible CXPA.[10] In our case, FNAC was showing poorly differentiated adenocarcinoma, while the histopathology of the excised specimen was diagnostic of CXPA.

The proportions of adenoma and carcinoma components determine the macroscopic features of the tumor. When the PA component is dominant, the tumor has grayish solid appearance. This is due to hyalinization and calcification in the stroma. When the malignant components are dominant, the tumor shows areas of necrosis and hemorrhage.[7]

Carcinoma ex-pleomorphic adenoma is composed of a mixture of PA and carcinoma on microscopic examination.[7] Since CXPA is histologically composed of both benign and malignant components, false negative diagnosis of the malignant component of the tumor, even by open biopsy, is frequent due to sampling error or misinterpretation. False negative diagnoses of malignant mixed tumors on biopsy have been reported in the literature.[9],[11]

The majority of CXPA develop from epithelial components of PAs that display aggressive behavior. Lewis et al. in an analysis of 73 cases of CXPA noted that the carcinomatous component made up more than 50% of the cancer in 84% of cases.[10] Zbären et al. in an analysis of 19 CXPA cases, reported that the carcinomatous components made up <33% of the tumor in 21% of cases, between 33% and 66% in 37% of the cases and >66% in 42% of the cases.[12] In certain cases, the carcinomatous component occupies the entire neoplasm without any features of the PA component. In such instance, the detection of the PA component depends on previous biopsy, clinicopathologic correlation or additional sectioning of the specimen.

Stodulski et al. found the most common malignant component in CXPA was adenocarcinoma.[3] Sometimes, the component may be adenoid cystic carcinoma, mucoepidermoid carcinoma, or salivary duct carcinoma. The other less common histological subtypes are acinic cell carcinoma, epithelial-myoepithelial carcinoma, basal cell carcinoma, myoepithelial carcinoma, squamous cell carcinoma, and clear cell carcinoma.[7],[12] Some cases of CXPA with metastasizing PA have been reported in the literature.[13]

Carcinoma ex-pleomorphic adenoma metastasize regionally and in distant areas, such as the lungs, hilar and cervical lymph nodes, bone, and central nervous system.[9],[14] It is reported that CXPA involves regional nodes with a frequency nearly equal to the distant metastatic rate.[9] Olsen and Lewis reported that metastasis occurred regionally in 56% and distantly in 44% of patients. In our case, there was metastasis in the cervical lymph nodes, with 40 of the 45 lymph nodes isolated in the Radical neck dissection specimen showed metastasis.[10],[14]

The survival rate for CXPA is reportedly worse than most salivary gland malignancies.[7] Prognostic parameters are recurrence, capsular invasion >9 mm, and metastasis.[15] Loco-regional recurrences are considered to be a major prognostic factor for patients with CXPA. Olsen and Lewis reported local recurrence in 23% of patients and regional recurrence in 18% of patients with CXPA. The prognosis after detection of progression or recurrence is poor, with a median survival of <1 year.[14]


  Conclusion Top


Carcinoma ex-pleomorphic adenoma of the submandibular gland is rare. Long standing PA may undergo malignant transformation into CXPA. The best method of prevention of CXPA is early and radical removal of all major salivary glands tumors. Surgery followed by postoperative radiotherapy improves life in patients with CXPA with lymph node metastasis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Mendenhall WM, Mendenhall CM, Werning JW, Malyapa RS, Mendenhall NP. Salivary gland pleomorphic adenoma. Am J Clin Oncol 2008;31:95-9.  Back to cited text no. 1
    
2.
Ariyoshi Y, Shimahara M, Konda T, Tsuji M. Carcinoma ex pleomorphic adenoma of the sublingual gland: A case report. Int J Oral Sci 2012;4:50-3.  Back to cited text no. 2
    
3.
Stodulski D, Rzepko R, Kowalska B, Stankiewicz C. Carcinoma ex pleomorphic adenoma of major salivary glands — a clinicopathologic review. Otolaryngol Pol 2007;61:687-93.  Back to cited text no. 3
    
4.
LiVolsi VA, Perzin KH. Malignant mixed tumors arising in salivary glands. I. Carcinomas arising in benign mixed tumors: A clinicopathologic study. Cancer 1977;39:2209-30.  Back to cited text no. 4
    
5.
Gnepp DR. Malignant mixed tumors of the salivary glands: A review. Pathol Annu 1993;28:279-328.  Back to cited text no. 5
    
6.
Furukawa M, Suzuki H, Matsuura K, Takahashi E, Suzuki H, Tezuka F. Carcinoma ex pleomorphic adenoma of the palatal minor salivary gland with extension into the nasopharynx. Auris Nasus Larynx 2001;28:279-81.  Back to cited text no. 6
    
7.
Antony J, Gopalan V, Smith RA, Lam AK. Carcinoma ex pleomorphic adenoma: A comprehensive review of clinical, pathological and molecular data. Head Neck Pathol 2012;6:1-9.  Back to cited text no. 7
    
8.
Som PM, Brandwein MS. Salivary glands. In: Som PM, Curtin HD, editors. Head and Neck Imaging. St. Louis: Mosby; 2003. p. 2070.  Back to cited text no. 8
    
9.
Akan H, Yildiz L, Unal R. Carcinoma ex pleomorphic adenoma of the minor salivary gland with pulmonary metastasis. Diagn Interv Radiol 2008;14:3-5.  Back to cited text no. 9
    
10.
Lewis JE, Olsen KD, Sebo TJ. Carcinoma ex pleomorphic adenoma: Pathologic analysis of 73 cases. Hum Pathol 2001;32:596-604.  Back to cited text no. 10
    
11.
Yoshihara T, Tanaka M, Itoh M, Ishii T. Carcinoma ex pleomorphic adenoma of the soft palate. J Laryngol Otol 1995;109:240-3.  Back to cited text no. 11
    
12.
Zbären P, Zbären S, Caversaccio MD, Stauffer E. Carcinoma ex pleomorphic adenoma: Diagnostic difficulty and outcome. Otolaryngol Head Neck Surg 2008;138:601-5.  Back to cited text no. 12
    
13.
Matsushima M, Ohara R, Ishida M, Kanao K, Shimokawa R, Nakajima Y. Carcinoma ex pleomorphic adenoma of the submandibular gland with renal metastases composed exclusively of metastasizing pleomorphic adenoma. Int Cancer Conf J 2012;1:116-20.  Back to cited text no. 13
    
14.
Olsen KD, Lewis JE. Carcinoma ex pleomorphic adenoma: A clinicopathologic review. Head Neck 2001;23:705-12.  Back to cited text no. 14
    
15.
Tortoledo ME, Luna MA, Batsakis JG. Carcinomas ex pleomorphic adenoma and malignant mixed tumors. Histomorphologic indexes. Arch Otolaryngol 1984;110:172-6.  Back to cited text no. 15
    


    Figures

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



 

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