- Pleomorphic adenoma
Pleomorphic adenomais a benign neoplastic tumor of the salivary glands. It is the most common type of salivary gland tumorand the most common tumor of the parotid gland. It derives its name from the architectural pleomorphism (variable appearance) seen by light microscopy. It is also known as "Mixed tumor, salivary glandtype", which describes its pleomorphic appearance as opposed to its dual origin from epithelial and myoepithelial elements.
The tumor is usually solitary and presents as a slow growing, painless, firm single nodular mass. Isolated nodules are generally outgrowths of the main nodule rather than a multinodular presentation. It is usually mobile unless found in the palate and can cause atrophy of the
mandibular ramuswhen located in the parotid gland. When found in the parotid tail, it may present as an eversion of the ear lobe. Though it is classified as a benign tumor, pleomorphic adenomas have the capacity to grow to large proportions and may undergo malignant transformation, to form carcinoma ex pleiomorphic adenoma, a risk that increases with time. Although it is "benign" the tumor is aneuploid, it can recur after resection, it invades normal adjacent tissue and distant metastases have been reported after long (+10 years) time intervals.
Histologically, it is highly variable in appearance, even within individual tumors. Classically it is biphasic and is characterized by an admixture of polygonal
epithelialand spindle-shaped myoepithelialelements in a variable background stroma that may be mucoid, myxoid, cartilaginous or hyaline. Epithelial elements may be arranged in duct-like structures, sheets, clumps and/or interlacing strands and consist of polygonal, spindle or stellate-shaped cells (hence pleiomorphism). Areas of squamous metaplasia and epithelial pearls may be present. The tumor is not enveloped, but it is surrounded by a fibrous pseudocapsule of varying thickness. The tumor extends through normal glandular parenchyma in the form of finger-like pseudopodia, but this is not a sign of malignant transformation.
The tumor often displays characteristic chromosomal translocations between chromosomes #3 and #8. This causes the PLAG gene to be juxtaposed to the gene for Beta-catenin. This activates the catenin pathway and leads to inappropriate cell division.
The diagnosis of salivary gland tumors utilize both histopathological sampling and radiographic studies. Histopathological sampling procedures include
fine needle aspiration(FNA) and core needle biopsy (bigger needle comparing to FNA). Both of these procedures can be done in an outpatient setting. Diagnostic imaging techniques for salivary gland tumors include ultrasound, computer tomography(CT) and magnetic resonance imaging(MRI).
Fine needle aspiration biopsy (FNA), operated in experienced hands, can determine whether the tumor is malignant in nature with
sensitivityaround 90% [Cohen EG; Patel SG; Lin O; Boyle JO; Kraus DH; Singh B; Wong RJ; Shah JP; Shaha AR. Fine-needle aspiration biopsy of salivary gland lesions in a selected patient population. Arch Otolaryngol Head Neck Surg 2004 Jun;130(6):773-8. PMID 15210562] [Batsakis JG; Sneige N; el-Naggar AK. Fine-needle aspiration of salivary glands: its utility and tissue effects. Ann Otol Rhinol Laryngol 1992 Feb;101(2 Pt 1):185-8. PMID 1739267] . FNA can also distinguish primary salivary tumor from metastatic disease.
Core needle biopsy can also be done in outpatient setting. It is more invasive but is more accurate compared to FNA with diagnostic
accuracygreater than 97% [Wan YL; Chan SC; Chen YL; Cheung YC; Lui KW; Wong HF; Hsueh C; See LC. Ultrasonography-guided core-needle biopsy of parotid gland masses. AJNR Am J Neuroradiol 2004 Oct;25(9):1608-12. PMID 15502149] . Furthermore, core needle biopsy allows more accurate histological typing of the tumor.
In terms of imaging studies, ultrasound can determine and characterize superficial parotid tumors. Certain types of salivary gland tumors have certain sonographic characteristics on ultrasound [Bialek EJ; Jakubowski W; Karpinska G. Role of ultrasonography in diagnosis and differentiation of pleomorphic adenomas: work in progress. Arch Otolaryngol Head Neck Surg 2003 Sep;129(9):929-33. PMID 12975263] . Ultrasound is also frequently used to guide FNA or core needle biopsy.
CT allows direct, bilateral visualization of the salivary gland tumor and provides information about overall dimension and tissue invasion. CT is excellent for demonstrating bony invasion. MRI provides superior soft tissue delineation such as perineural invasion when compared to CT only [Koyuncu M; Sesen T; Akan H; Ismailoglu AA; Tanyeri Y; Tekat A; Unal R; Incesu L. Comparison of computed tomography and magnetic resonance imaging in the diagnosis of parotid tumors. Otolaryngol Head Neck Surg 2003:129:726-32. PMID 14663442] .
Overall, the mainstay of the treatment for salivary gland tumor is surgical resection. Needle biopsy is highly recommended prior to surgery to confirm the diagnosis. More detailed surgical technique and the support for additional
adjuvantradiotherapy depends on whether the tumor is malignant or benign.
Generally, benign tumors of the parotid gland are treated with superficial or total parotidectomy with the latter being the more commonly practiced due to high incidence of recurrence [Stennert E; Guntinas-Lichius O; Klussmann JP; Arnold G. Histopathology of pleomorphic adenoma in the parotid gland: a prospective unselected series of 100 cases. Laryngoscope 2001 Dec;111(12):2195-200. PMID 11802025] . The
facial nerveshould be preserved whenever possible. The benign tumors of the submandibular glandis treated by simple excision with preservation of mandibular branch of the trigeminal nerve, the hypoglossal nerve, and the lingual nerve[Leonetti JP; Marzo SJ; Petruzzelli GJ; Herr B. Recurrent pleomorphic adenoma of the parotid gland. Otolaryngol Head Neck Surg 2005 Sep;133(3):319-22. PMID 16143173] . Similarly, other benign tumors of minor salivary glands are treated similarly.
Malignant salivary tumors usually require wide local resection of the primary tumor. However, if complete resection cannot be achieved, adjuvant radiotherapy should be added to improve local control [Ganly I, Patel SG, Coleman M, Ghossein R, Carlson D, Shah JP. Malignant minor salivary gland tumors of the larynx. Arch Otolaryngol Head Neck Surg. 2006 Jul;132(7):767-70. PMID 16847187 ] [Terhaard CH; Lubsen H; Rasch CR; Levendag PC; Kaanders HH; Tjho-Heslinga RE; van Den Ende PL; Burlage F. The role of radiotherapy in the treatment of malignant salivary gland tumors. Int J Radiat Oncol Biol Phys 2005 Jan 1;61(1):103-11. PMID 15629600 ] . This surgical treatment has many sequellae such as cranial nerve damage,
Frey's syndrome, cosmetic problems, etc.
Warthin's tumor- monomorphic adenoma
* [http://brighamrad.harvard.edu/Cases/bwh/hcache/75/full.html Harvard]
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