Pleomorphic Adenoma

Epidemiology

• Most common salivary gland tumor overall (~50% of all salivary gland tumors)
• Annual incidence: ~2.4-3.05 per 100,000 population
• Most common between the 3rd and 6th decade; average age of presentation is 45 years
• Slightly more common in women
• Distribution by gland:
  • Parotid gland: >80% of cases (most common site); represents ~65% of all parotid tumors
  • Submandibular gland: less common
  • Minor salivary glands: ~40% of intra-oral minor salivary gland tumors; most common site within the oral cavity is the hard palate

Clinical Features

• Slow-growing, painless, firm, mobile, well-defined solitary mass
• Gradual progression over many years - can reach enormous proportions if untreated
• When arising from the deep lobe of the parotid, it may present as a paratonsillar bulge
• Occasionally presents as metachronous or synchronous tumors
• Warning signs of malignant transformation: sudden increase in size, facial nerve palsy, pain, fixation

Macroscopic (Gross) Appearance

• Rounded or ovoid, well-demarcated mass, several centimeters in greatest dimension
• Variably encapsulated - capsule may be thick and fibrotic, attenuated, or even incomplete (especially on the palate)
• Cut surface: gray-white with myxoid and blue translucent chondroid areas
• May have areas of cystic change and calcification
• Protuberant pericapsular nodules may be seen, sometimes attached by a slender pedicle - these are key surgical pitfalls

Microscopic (Histological) Appearance

1. Ductal (epithelial) and myoepithelial cells - arranged in ducts, acini, tubules, strands, or sheets
2. Chondromyxoid stroma - loose myxoid tissue with islands of cartilage, and rarely foci of bone

• Oval, epithelioid, spindle-shaped, plasmacytoid, and clear cells in variable proportions
• Well-formed ducts lined by cuboidal-to-columnar luminal cells with an underlying layer of small, deeply chromatic myoepithelial cells
• Islands of well-differentiated squamous epithelium may be present
• No epithelial dysplasia or significant mitotic activity in benign cases

• Metaplastic changes (squamous, lipomatous, osseous, neuroid, angiomatoid)
• Degeneration (cystic change, infarction, mineralization, hyalinization)
• Various growth patterns mimicking other tumors (adenoid cystic carcinoma-like, basaloid, clear cell, etc.) - this can make diagnosis from limited FNAB samples difficult

• Luminal cells: CK7 (strong and diffuse)
• Myoepithelial cells: p63, S-100, SOX10, SMA

Histology Images

Pleomorphic adenoma histology. (A) Low-power: encapsulated tumor adjacent to normal salivary gland. (B) High-power: epithelial and myoepithelial cells within chondroid matrix. - Robbins Pathologic Basis of Disease, Fig. 13.6

Histology showing double-layered ducts and strands of myoepithelial cells invested by a myxoid matrix (H&E, medium magnification). - Scott-Brown's Otorhinolaryngology

Surgical Considerations and Recurrence

• Treatment: complete surgical excision with a cuff of normal surrounding tissue (superficial or total parotidectomy with facial nerve preservation)
• Enucleation alone is inadequate and must be avoided - risks:
  • Detaching pericapsular pseudopods/nodules (which remain in the field as nidi for recurrence)
  • Capsular rupture, especially with predominantly myxoid tumors, which can spill semi-fluid tumor throughout the operative field
• Recurrence rates:
  • After simple enucleation: ~25%
  • After wider excision with cuff: ~4%
  • Recurrences are typically multifocal due to seeding
• For oral cavity pleomorphic adenomas: transoral excision is appropriate

Malignant Transformation: Carcinoma Ex Pleomorphic Adenoma

• Overall risk: ~6% (Scott-Brown's) - Robbins cites 2% at <5 years rising to nearly 10% at >15 years
• Clinical warning signs: rapid growth, pain, facial nerve palsy, fixation
• Risk factors for transformation:
  • Older patient age
  • Male sex
  • Long duration of tumor
  • Multiple recurrences
  • Deep lobe parotid location
• Histology: usually adenocarcinoma or undifferentiated carcinoma
• Prognosis: 30-50% mortality at 5 years - among the most aggressive salivary gland malignancies
• Carcinogenesis associated with frequent attempts at removal of recurrent benign disease - yet another reason to get the surgery right the first time

Summary Table

Part 1: TNM Staging of Salivary Gland Tumors (By American Joint Committee)

Primary Tumor (T)

Nodal Involvement (N)

Distant Metastasis (M)

Stage Grouping

Part 2: Pleomorphic Adenoma - Oral Pathology Perspective

Introduction

• Most common salivary gland tumor overall
• Term "pleomorphic adenoma" was coined by Willis, referring to the unusual histological pattern of the lesion
• The morphologically diverse appearance is its pathognomonic (defining) feature
• Derived from a mixture of ductal and myoepithelial elements
• It is the only tumor showing remarkable diversity both between different tumors AND within different areas of the same tumor

Why "Mixed Tumor"?

• Fibrous areas
• Hyalinised areas
• Chondroid (cartilage-like) areas
• Myxoid areas
• Epithelial cells with metaplasia

Other Names for Pleomorphic Adenoma

• Iceberg tumor
• Endothelioma
• Branchioma
• Enchondroma
• Enclavoma

Histogenesis and Pathogenesis

Two Main Theories:

• Reserve cells of the intercalated duct differentiate into ductal and myoepithelial cells
• These then undergo mesenchymal metaplasia (transforming into cartilage, bone, etc.)
• The intercalated duct reserve cell is the histogenetic precursor of pleomorphic adenoma

• Any neoplastically altered epithelial cell can differentiate in multiple directions (multidirectionally)
• Origin is NOT necessarily restricted to intercalated duct and myoepithelial cells

Clinical Features (beginning)

Sex and Age

• Women to men ratio: 6:4 (slight female predominance)
• Most common in the 4th to 6th decades, but can occur in young adults and children

Site

• Parotid gland: 90% of cases
• Lower pole of the superficial lobe of the parotid is the most commonly affected specific site
• Intraoral: palatal gland and lip
• Upper lip and buccal mucosa are very uncommonly affected

Appearance (partially visible)

• Palatal tumors present as smooth-surfaced, dome-shaped lesions
• Ulceration may be present (text cut off at the bottom of the page)

Pleomorphic Adenoma - Clinical Features (continued from previous page)

Mobility

• Palatal tumors are IMMOBILE - due to their location and tight microanatomy of the palate
• Lip and buccal mucosa tumors are MOBILE
• Parotid tumors are typically mobile (as seen in Fig. 17.18 - the elderly patient with a large parotid swelling)

Symptoms

• Starts as a small, painless, quiescent (quiet) nodule
• Slowly increases in size, sometimes intermittently (not constantly growing)
• Patient is usually aware of it for months to years before seeking help
• If neglected, can grow to a very large size (as shown in the photo - a man with a massive parotid tumor)

Shape

• Small tumor: round or oval
• As it grows: becomes lobulated (multi-nodular)

Size

• Parotid tumors can reach cricket ball size or larger, weighing in pounds
• Intraoral tumors: usually not more than 1-2 cm in diameter

Surface

• Surface is smooth
• Sometimes bosselated (covered in boss-like bumps)
• Occasionally crossed by deep furrows

Consistency

• Firm and rubbery to feel
• Sometimes cystic degeneration may be present (giving a softer feel)

Histopathological Features

Macroscopic (Gross) Appearance

• Encapsulated lesion with firm to rubbery consistency
• Minor salivary gland tumors may not have a well-defined capsule
• Cut surface shows a classic "cut potato" appearance - a key descriptive hallmark
• May be associated with:
  • Small cystic areas
  • Mucoid areas
  • Hemorrhagic areas

The "cut potato appearance" is a classic exam answer for the gross appearance of pleomorphic adenoma.

Microscopic Appearance

• Well-circumscribed and encapsulated
• May show infiltration of the capsule by tumor cells (especially palatal tumors, which show infiltration of capsule beneath the epithelial surface)
• Considerable variation in arrangement of epithelial and stromal components between different areas of the same tumor

1. Epithelial Cell Component

• Consists of: epithelial duct-like cells, polygonal cells, cuboidal cells, spindle cells
• Arranged in: sheets, clumps, islands, or interlacing strands
• Cuboidal cells show duct-like arrangement
• Duct-like spaces may contain eosinophilic coagulum and mucoid material
• Epithelial cells resembling squamous cells have distinct intercellular bridges
• Cystic spaces are uncommonly seen

2. Myoepithelial Cell Component

• Few stellate cells or spindle cells = myoepithelial cells
• Variable morphology
• Have rounded eccentric nucleus
• Have eosinophilic hyalinized cytoplasm - resembling plasma cells
• These are called plasmacytoid cells (or hyaline cells)
• Hyaline cells also seen with dense eosinophilic cytoplasm

Plasmacytoid (hyaline) myoepithelial cells are a characteristic feature of pleomorphic adenoma.

3. Stromal (Mesenchymal) Component

• Stromal changes are highly variable
• Believed to be produced by myoepithelial cells (text cuts off here)
• Typically includes: myxoid, chondroid (cartilage-like), hyalinized, and occasionally osseous (bone) areas

Summary of Key Points from This Page

Stromal (Mesenchymal) Component - Continued

What the stroma contains:

The presence of chondroid (cartilage) in a salivary gland tumor is a hallmark of pleomorphic adenoma, because cartilage does not normally exist in salivary glands. It is produced by the metaplastic activity of myoepithelial cells.

Special Terminology Based on Predominant Component

Histological Types of Pleomorphic Adenoma

(Foot and Frazel Classification, 1954)

This classification matters clinically: Principally myxoid tumors are the most dangerous during surgery - they are semi-fluid and capsular rupture during removal can spill tumor cells, leading to multifocal recurrence.

Figure Descriptions (Histology Images on This Page)

• D = Duct-like spaces
• E = Eosinophilic material filling the ducts
• M = Mucous acini (peripherally placed)
• C = Capsule surrounding the tumor

• Chondroid (cartilage-like) areas within the stroma - the blue/grey material that is characteristic of pleomorphic adenoma

• D = Ductal spaces filled with eosinophilic material
• C = Chondroid areas clearly visible adjacent to ducts

• C = Chondroid areas
• SM = Squamous metaplasia - islands of squamous epithelium within the tumor (another hallmark feature)

Quick Summary of This Page

Stromal component of Pleomorphic Adenoma:
├── Myxoid material (most common stromal element)
├── Hyalinized CT
├── Chondroid / cartilage islands ← KEY FEATURE
├── Osteoid / bone (rare)
└── All produced by MYOEPITHELIAL CELLS

Special names:
├── Epithelial dominant → Cellular adenoma
└── Myoepithelial dominant → Myoepithelioma

Histological types (Foot & Frazel 1954):
1. Principally myxoid
2. Equal myxoid + cellular
3. Predominantly cellular
4. Extremely cellular