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BDS 3rd Year - Oral Pathology University Exam Answers

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LONG ESSAY QUESTIONS

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Q1. Define and Classify Odontogenic Cysts. Discuss in detail Clinical, Histological and Radiographic Features of Radicular Cyst.

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DEFINITION OF ODONTOGENIC CYST

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CLASSIFICATION OF ODONTOGENIC CYSTS

I. INFLAMMATORY ODONTOGENIC CYSTS

1. Radicular cyst (Periapical cyst)
2. Residual cyst
3. Paradental cyst (Inflammatory collateral cyst)

II. DEVELOPMENTAL ODONTOGENIC CYSTS

1. Dentigerous cyst (Follicular cyst)
2. Odontogenic keratocyst (OKC)
3. Lateral periodontal cyst
4. Gingival cyst
5. Glandular odontogenic cyst (Sialo-odontogenic cyst)
6. Calcifying odontogenic cyst (Gorlin cyst / CCOT)
7. Orthokeratinized odontogenic cyst

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RADICULAR CYST (PERIAPICAL CYST)

DEFINITION

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PATHOGENESIS

Dental caries → Pulpitis → Pulp necrosis
        ↓
Periapical inflammation → Periapical granuloma
        ↓
Proliferation of epithelial rests of Malassez (in periodontal ligament)
        ↓
Epithelial lining forms around inflammatory focus
        ↓
Accumulation of fluid due to osmotic pressure gradient
        ↓
RADICULAR CYST

• The rests of Malassez are dormant epithelial remnants in the periodontal ligament - they are stimulated to proliferate by inflammatory mediators (prostaglandins, interleukins) from necrotic pulp.
• Fluid accumulates inside the epithelial cavity due to the osmotic pressure created by breakdown products (cholesterol crystals, cellular debris).

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CLINICAL FEATURES

• Residual cyst - radicular cyst that remains after extraction of the offending tooth
• Lateral radicular cyst - arises from lateral accessory root canals

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RADIOGRAPHIC FEATURES

1. Shape: Well-defined, round to oval radiolucency
2. Location: Surrounds the apex (periapical) of a non-vital tooth
3. Borders: Well-corticated (thin, radio-opaque white line around margin)
4. Size: Typically 5mm to 2cm; can grow very large
5. Unilocular: Always unilocular (single chamber)
6. Lamina dura: Loss of lamina dura at root apex
7. Root resorption: Uncommon but may occur
8. Adjacent teeth: Displacement and divergence of roots of adjacent teeth

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HISTOPATHOLOGICAL FEATURES

A. Lining (Epithelium)

• Stratified squamous non-keratinized epithelium of variable thickness (key feature)
• The epithelium is derived from rests of Malassez
• May show arcading/anastomosing epithelial strands in actively growing phase
• Epithelium shows spongiosis and infiltration by neutrophils (in inflamed areas)

B. Connective Tissue Wall

• Dense fibrous connective tissue with chronic inflammatory infiltrate (lymphocytes, plasma cells, macrophages)
• Acute inflammatory cells (PMNs) in areas of active infection
• Russell bodies (hyaline bodies, Lentz bodies) - plasma cell-derived immunoglobulins
• Cholesterol clefts - needle-shaped empty spaces (dissolved cholesterol) surrounded by foreign body giant cells - PATHOGNOMONIC for radicular cyst
• Hemosiderin deposits (yellow-brown granules)
• Hyaline bodies (Rushton bodies) - curved, linear eosinophilic deposits in the epithelial lining - characteristic of radicular cyst

C. Lumen Contents

• Straw-colored fluid (in aspiration)
• Cholesterol crystals
• Cellular debris
• Epithelial desquamation

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DIFFERENTIAL DIAGNOSIS

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TREATMENT

1. Small cysts - Root canal treatment (RCT) of the offending tooth ± periapical surgery
2. Larger cysts - Enucleation + extraction or RCT
3. Very large cysts - Marsupialization (Partsch operation) followed by enucleation
4. Residual cysts - Surgical enucleation

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Q2. Define and Enumerate OPMDs. Discuss Etiology, Clinical Features, Histopathological Features and Malignant Transformation of Oral Submucous Fibrosis (OSF).

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DEFINITION OF OPMDs

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ENUMERATION OF OPMDs (WHO Classification)

1. Leukoplakia
2. Oral Submucous Fibrosis (OSF)
3. Erythroplakia
4. Oral Lichen Planus (erosive/atrophic forms)
5. Actinic (Solar) Cheilitis
6. Palatal changes associated with reverse smoking
7. Oral lupus erythematosus
8. Discoid lupus erythematosus
9. Dyskeratosis congenita

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ORAL SUBMUCOUS FIBROSIS (OSF)

DEFINITION

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ETIOLOGY

1. Areca Nut (Betel Nut) - PRIMARY CAUSE

• Arecoline (alkaloid in areca nut) is the main culprit
• Arecoline stimulates fibroblasts to produce excess collagen
• Simultaneously inhibits collagenase, preventing collagen degradation
• Net result: Collagen accumulation and submucosal fibrosis
• Pan masala (areca nut + lime + tobacco) accelerates the process
• Gutkha consumption is strongly linked to OSF in India

2. Tobacco

• Tobacco chewing enhances oxidative stress and fibroblast stimulation
• Tannins in tobacco stimulate fibrosis

3. Nutritional Deficiencies

• Deficiency of iron, vitamins (especially B complex, C), zinc
• Malnutrition alters mucosal immunity

4. Immunological Factors

• Autoimmune component - elevated serum immunoglobulins
• Increased CD4:CD8 ratio in lesional tissue
• Elevated HLA-DR3, HLA-A10 association reported

5. Genetic Factors

• Familial predisposition; certain HLA types are susceptible
• Cytochrome P450 enzyme polymorphisms

6. Chili Peppers / Spicy Food

• Capsaicin in chilies causes mucosal irritation, contributing to chronic inflammation

7. Viral Factor

• Human papillomavirus (HPV) - suggested but not proven as a major factor

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CLINICAL FEATURES

Stages (Clinical Staging by Pindborg / FIGO modification):

Subjective Symptoms:

• Burning sensation in the mouth (earliest symptom - aggravated by spicy foods)
• Inability to whistle or blow out candles
• Reduced mouth opening (trismus) - hallmark symptom
• Difficulty chewing, swallowing (dysphagia), and opening mouth
• Dryness of mouth

Objective Signs:

• Blanching of oral mucosa - marble-white or milky appearance (due to reduced vascularity)
• Fibrous bands palpable in buccal mucosa, soft palate, labial mucosa, tongue
• Inter-incisal distance reduced (normal = 35-45mm; OSF = may be <20mm in advanced cases)
• Uvula may become fibrotic and shrunken ("bud-like" uvula)
• Soft palate - may be involved with reduced mobility
• Lips - may show leathery, hard texture
• Tongue - depapillation, reduced mobility
• Concomitant leukoplakia or erythroplakia in ~25% of cases (increases malignant risk)

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HISTOPATHOLOGICAL FEATURES

Stage I - Very Early

• Edematous fibrous connective tissue
• Fine, delicate collagen fibers
• Mild chronic inflammatory infiltrate in subepithelial region
• Epithelium: normal or mild atrophic change

Stage II - Early

• Increased fibroblast activity
• Collagen fibers begin to thicken and become dense
• Moderate chronic inflammatory cells (lymphocytes, plasma cells)
• Juxta-epithelial collagen fibers showing early hyalinization
• Atrophic epithelium with occasional dysplastic changes

Stage III - Moderately Advanced

• Dense hyalinized collagen fibers replace normal connective tissue
• Marked reduction in vascularity (obliterative endarteritis)
• Moderate-to-severe chronic inflammatory infiltrate
• Muscle degeneration in deeper tissues (key feature)
• Epithelial atrophy with epithelial dysplasia in many cases
• Loss of rete ridges OR elongated thin rete ridges

Stage IV - Advanced

• Dense, avascular, acellular homogeneous hyalinized collagen
• Minimal inflammatory cells
• Severe epithelial atrophy - epithelium is very thin
• Degeneration of underlying muscle fibers (myositis with atrophy)
• Frank carcinoma in-situ or invasive carcinoma may be seen

1. Epithelial atrophy (loss of rete ridges)
2. Juxta-epithelial hyalinization of collagen
3. Dense fibrosis of submucosal tissue
4. Chronic inflammatory infiltrate
5. Obliteration of minor salivary glands
6. Muscle degeneration
7. Epithelial dysplasia (in advanced cases)

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MALIGNANT TRANSFORMATION

• OSF carries a malignant transformation rate of 7-13% over a period of 10-20 years
• OSF is considered a high-risk OPMD
• Most common transformation: to Oral Squamous Cell Carcinoma (OSCC)
• Commonly develops in buccal mucosa (the most common site of OSF)

1. Presence of epithelial dysplasia on histology
2. Concomitant leukoplakia or erythroplakia
3. Long duration of disease
4. Advanced clinical stage
5. Tobacco use combined with areca nut
6. Presence of HPV co-infection

• Chronic hypoxia due to obliterative changes in vasculature
• Arecoline induces DNA damage and chromosomal instability
• Accumulation of reactive oxygen species (ROS)
• Mutations in tumor suppressor genes (p53, p16)
• Upregulation of pro-oncogenic pathways

• Cessation of areca nut / gutkha habit (most important)
• Intralesional steroids (triamcinolone)
• Micronutrient supplementation (vitamins A, C, E, lycopene)
• Mouth opening exercises (physiotherapy)
• Surgical intervention: fibrotomy + skin/amnion graft in advanced trismus
• Regular follow-up every 3-6 months with biopsy if suspicious change

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SHORT NOTES QUESTIONS

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A. BITE MARKS IN FORENSIC ODONTOLOGY

1. Human bite marks - oval or elliptical marks with 6 upper + 6 lower anterior tooth impressions
2. Animal bite marks - differ in arch width, tooth morphology

• Bite marks can be left on skin of victims, foodstuffs (apple, chocolate, cheese), and other materials
• They serve as class and individual characteristics for identification

1. Photography - standard scale photographs (ABFO No. 2 scale used)
2. Swabbing - DNA from saliva on bite mark
3. Casting - vinyl polysiloxane/silicone impressions
4. Transparencies and overlays - comparison with suspect's dental casts

• Shape of the arch
• Spacing and size of individual teeth
• Rotations, missing teeth, wear facets
• ABFO (American Board of Forensic Odontology) guidelines used
• DNA analysis of saliva enhances bite mark evidence reliability

• Can be used to include or exclude suspects
• Bite mark evidence has been used in landmark criminal cases
• Limitations: skin distortion, bruising, post-mortem changes
• Uniqueness of dentition is the scientific basis

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B. ROOTLESS TEETH (DENTIN DYSPLASIA TYPE I / ROOTLESS TEETH)

• Teeth appear clinically normal in color, shape, and size
• Both primary and permanent teeth are affected
• Teeth are excessively mobile due to short roots
• Early exfoliation is common
• Teeth may present with multiple periapical abscesses and cysts without obvious carious involvement (due to obliterated pulps)
• Also called Rootless teeth or Shields Type I Dentin Dysplasia

• Short conical or absent roots (rootless or near-rootless appearance)
• Completely obliterated or crescent-shaped pulp chambers in permanent teeth
• In primary teeth: small pulp remnants visible as "thistle-tube" or "chevron" shaped pulp chambers
• Multiple periapical radiolucencies (cysts/granulomas) common

• Normal coronal dentin
• Root dentin shows atypical dentin formation with inclusion of soft tissue and cells
• Irregular dentin tubules
• Whorled pattern of dentin in roots

• Type I (Radicular) - normal crowns, abnormal short roots, obliterated pulp
• Type II (Coronal) - also called Dentin Dysplasia Type II - affects pulp morphology (thistle-tube shape) with normal root length

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C. UNICYSTIC AMELOBLASTOMA

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• Usually asymptomatic unless secondarily inflamed
• May present as a painless swelling of the jaw
• Often resembles a dentigerous cyst clinically
• Sometimes associated with an unerupted tooth (commonly 3rd molar)

• Unilocular radiolucency with well-corticated borders
• Frequently surrounds or is associated with the crown of an unerupted tooth
• Indistinguishable radiographically from a dentigerous cyst or other odontogenic cysts

1. Columnar or cuboidal basal cells lining the cyst
2. Palisading of the basal cell layer
3. Polarization of basal cell nuclei AWAY from the basement membrane (reverse polarity)
4. Hyperchromatism of basal cell nuclei
5. Subnuclear vacuolization of cytoplasm of basal cells
6. Loosely aggregated stellate cells (stellate reticulum-like) above the basal layer

• Type I (Luminal): Ameloblastomatous changes confined to luminal surface only - BEST PROGNOSIS
• Type II (Intraluminal): Intraluminal proliferation into the lumen (plexiform pattern)
• Type III (Mural): Ameloblastomatous epithelium invades the fibrous wall - WORST PROGNOSIS (behaves like conventional ameloblastoma)

• Simple/Type I and II: Enucleation alone is adequate (conservative)
• Type III (Mural invasion): Resection like conventional ameloblastoma required
• IMPORTANT: The entire specimen must be processed histologically to rule out mural invasion

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D. MUCOEPIDERMOID CARCINOMA

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• Low-grade: Painless, slowly enlarging mass; may appear bluish/cystic (mucous cells)
• High-grade: Rapid growth, pain, facial nerve involvement, skin fixation, cervical lymphadenopathy

1. Mucous cells - large, foamy, vacuolated cytoplasm; filled with mucin; PAS-positive; form cystic spaces
2. Epidermoid (squamous) cells - squamous differentiation, intracellular bridges
3. Intermediate cells - small, basaloid, precursor cells; form the bulk of high-grade tumors
4. Clear cells - may be seen
5. Mucin-filled cystic spaces in low-grade tumors

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E. CANDIDIASIS (ORAL CANDIDIASIS)

• Immunosuppression (HIV/AIDS, organ transplant, chemotherapy)
• Diabetes mellitus (impaired neutrophil function)
• Prolonged antibiotic use (alters oral flora)
• Corticosteroid use (topical or systemic)
• Xerostomia (reduced saliva)
• Denture wearing (especially complete dentures - Denture stomatitis)
• Infancy and old age
• Nutritional deficiencies (iron, zinc, folate)

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PRIMARY ORAL CANDIDIASIS:

1. Pseudomembranous candidiasis (Thrush): White, creamy, curd-like plaques that can be wiped off leaving an erythematous, bleeding surface; seen in infants, HIV patients
2. Erythematous (Atrophic) candidiasis: Red, painful lesions; seen with antibiotics ("antibiotic sore mouth") or denture wearers

1. Chronic pseudomembranous - persistent thrush
2. Chronic atrophic (Denture stomatitis) - erythema under denture-bearing area
3. Chronic hyperplastic (Candidal leukoplakia) - white patches that CANNOT be wiped off, commonly at commissures; highest risk of malignant transformation among candidal variants
4. Median rhomboid glossitis - diamond-shaped erythematous area at midline of dorsum tongue

SECONDARY ORAL CANDIDIASIS: Associated with systemic diseases.

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• Hyphae and pseudohyphae invading the superficial epithelium (PAS stain - deep magenta red; Grocott-Methenamine Silver stain)
• Superficial necrotic layer of fibrin, desquamated epithelial cells, PMNs
• Subepithelial inflammatory infiltrate (lymphocytes, neutrophils)
• In chronic hyperplastic type: epithelial dysplasia may be present

• Clinical appearance
• Smear with Gram stain or PAS stain showing budding yeast cells and pseudohyphae
• Culture on Sabouraud's dextrose agar (cream-colored colonies)

• Topical: Nystatin suspension/lozenges, Clotrimazole
• Systemic: Fluconazole (drug of choice for moderate-severe), Itraconazole, Amphotericin B
• Correct predisposing factors

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F. HYPERPARATHYROIDISM (ORAL AND SKELETAL MANIFESTATIONS)

• Elevated PTH → Elevated serum calcium → Low serum phosphate
• Alkaline phosphatase elevated
• Hypercalciuria

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1. Brown Tumor (Osteoclastoma-like lesion):

• Characteristic oral/jaw lesion of hyperparathyroidism
• Most commonly in mandible, followed by maxilla, clavicle, ribs
• Appears as a painful, expanding radiolucent lesion
• Contains multinucleated giant cells with hemorrhage and hemosiderin (hence brown color)
• Resolves after treatment of hyperparathyroidism
• Must be differentiated from central giant cell granuloma (identical histology but different etiology)

1. Generalized Osteoporosis:

• Loss of bone density; ground glass appearance of jaw bones on radiograph

1. Loss of Lamina Dura:

• Classic radiographic sign - normal lamina dura around teeth becomes indistinct or disappears

1. Jaw Bone Changes:

• Coarsening of trabecular pattern
• Expansion and thinning of cortical plates

• Loss of lamina dura
• Ground glass appearance of bone
• Brown tumor = well-defined unilocular/multilocular radiolucency
• "Salt and pepper" skull on lateral skull X-ray

• Numerous multinucleated osteoclast-like giant cells in a background of mononuclear spindle cells
• Foci of hemorrhage and hemosiderin deposits (explains brown color)
• Fibrous stroma

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G. REGRESSIVE ALTERATIONS OF TEETH

1. ATTRITION

• Definition: Loss of tooth structure due to tooth-to-tooth contact (normal masticatory function or parafunctional habits like bruxism)
• Affects occlusal/incisal surfaces primarily
• Physiological in elderly; pathological in bruxism
• Histologically: Sclerotic dentin, irregular secondary dentin deposition, reduced pulp size

2. ABRASION

• Definition: Pathological loss of tooth structure due to friction from an exogenous mechanical agent
• Causes: Incorrect brushing technique (most common), pipe smoking, occupational habits
• Site: Cervical abrasion (V-shaped notch at CEJ) due to toothbrush abrasion
• Histologically: Cut dentinal tubules; sclerosis

3. EROSION

• Definition: Chemical dissolution of tooth substance by acids NOT produced by bacteria
• Extrinsic causes: Citric acid in fruits/drinks, carbonated drinks
• Intrinsic causes: Gastric acid in GERD, bulimia nervosa
• Affects smooth, cupped-out surfaces; palatal surfaces of maxillary incisors in GERD/bulimia
• Histologically: Dissolution of hydroxyapatite; widened dentinal tubules

4. ABFRACTION

• Definition: Loss of tooth structure at the CEJ due to lateral occlusal stress causing flexure
• V-shaped or wedge-shaped notch at cervical area

5. INTERNAL RESORPTION

• Definition: Destruction of dentin from within the pulp chamber/canal by odontoclasts
• Appears radiographically as a "pink spot" (resorbed dentin shows through enamel)
• Often asymptomatic; found on routine radiograph
• Pulp is vital but inflamed
• Treatment: Root canal therapy

6. EXTERNAL RESORPTION

• Definition: Resorption of tooth structure from the external surface
• Causes: Periapical inflammation, trauma, excessive orthodontic force, reimplantation of avulsed tooth, cysts/tumors adjacent to root
• Types: Inflammatory, replacement (ankylosis), cervical (invasive cervical resorption)

7. HYPERCEMENTOSIS

• Excessive deposition of cementum on root surface
• Seen in Paget's disease, periapical inflammation, occlusal trauma

8. SECONDARY/REPARATIVE DENTIN

• Deposited in response to irritation (caries, attrition) - acts as a defense mechanism
• Irregular dentin with fewer/irregular tubules

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H. VERRUCOUS CARCINOMA

• Strongly associated with tobacco use - particularly smokeless tobacco (snuff dipping, tobacco chewing)
• HPV (types 6, 11, 16, 18) has been isolated from some lesions but precise role unclear
• Combination of tobacco and areca nut in South Asia
• Chronic mucosal irritation

• Buccal mucosa (most common)
• Gingiva / alveolar ridge
• Hard palate
• Larynx (another common site outside oral cavity)

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• Exophytic, warty, white or grey papillary/pebbly surface lesion
• Classically described as a "cauliflower-like" or "shaggy" white surface
• Slow-growing but locally aggressive
• Base is firm and indurated
• May appear as a large fungating mass over time
• Usually painless unless secondarily infected
• Regional lymph node metastasis is rare (this distinguishes it from conventional SCC)
• Locally destructive - can invade bone

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1. Well-differentiated squamous epithelium with exophytic and endophytic components
2. Broad, blunt, pushing rete ridges extending into connective tissue (no single-cell infiltration)
3. Minimal cytologic atypia - cells appear well-differentiated with abundant eosinophilic cytoplasm
4. Parakeratotic crypts - keratin-filled crevices between papillary projections (characteristic)
5. Heavy lymphocytic infiltrate at the pushing border (host immune response)
6. NO destructive/infiltrating invasion pattern (this is the KEY feature distinguishing from conventional SCC)
7. Hyperkeratosis and acanthosis of epithelium

• Conventional SCC (shows individual cell keratinization, infiltrative borders, atypia)
• Papillary SCC
• Verruca vulgaris (HPV koilocytes present)
• Proliferative Verrucous Leukoplakia

• Wide surgical excision is the treatment of choice
• Radiation therapy is relatively contraindicated (risk of anaplastic transformation)
• Prognosis is generally GOOD - low rate of metastasis
• Mohs surgery for recurrent cases

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I. IRON DEFICIENCY ANEMIA (Oral Manifestations)

• Chronic blood loss (GI bleed, menorrhagia)
• Inadequate dietary intake
• Malabsorption (celiac disease, post-gastrectomy)
• Increased demand (pregnancy, infancy)

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1. Iron deficiency anemia
2. Dysphagia (due to esophageal webs)
3. Atrophic oral mucosa with glossitis and angular cheilitis

• Recurrent aphthous ulcers (can be precipitated by iron deficiency)
• Increased susceptibility to oral infections (candidiasis)
• Impaired wound healing

• Epithelial atrophy - reduced epithelial thickness
• Loss of rete ridges
• Elongated, thin basal cells
• Subepithelial inflammatory infiltrate

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J. HISTOPATHOLOGY WITH DIAGRAMS

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J(i). CALCIFYING ODONTOGENIC CYST (COC / GORLIN CYST)

• Variable age (infant to elderly); peak incidence in 2nd decade
• Equal sex distribution
• Site: Intraosseous (most common) > extraosseous (peripheral); Maxilla slightly more common; anterior jaws (incisor-canine region) most frequent
• Painless swelling; variable growth rate
• Variable clinical behavior - some behave as simple cysts, others as aggressive neoplasms

• Unilocular or multilocular radiolucency
• Well-demarcated borders
• Irregular calcifications (ghost cell calcifications) within the lumen - radiopaque foci
• May be associated with an unerupted tooth or an odontoma

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1. A distinct layer of ameloblast-like columnar basal cells with reverse nuclear polarity (nuclei polarized away from basement membrane) - similar to ameloblastoma
2. Above basal layer: loosely arranged stellate reticulum-like cells
3. Ghost cells - pale eosinophilic, anucleate (enucleated) cells with a preserved cell outline that resemble "ghost" of the original epithelial cell. These undergo calcification over time. They may appear as:

• Single scattered ghost cells
• Large masses of ghost cells

1. Calcification within the ghost cell masses - may be dystrophic or actual hard tissue formation (dentinoid)
2. Dentinoid / Dysplastic dentin may be found adjacent to the basal layer (characteristic)

• Fibrous capsule
• Areas where ghost cells extruded into connective tissue cause a foreign body giant cell reaction
• Inflammatory infiltrate (lymphocytes, plasma cells)
• Calcifications in wall

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LUMEN
  |
  |  Ghost cells (pale, anucleate, calcified)
  |  ↓ ↓ ↓ ↓
══════════════════════════════════  ← Stellate reticulum-like cells
|  ○  ○  ○  Ghost cells  ○  ○   |
══════════════════════════════════
[Columnar ameloblast-like basal cells, palisaded, reverse polarity]
══════════════════════════════════  ← Basement membrane
  Dentinoid / Dysplastic dentin (sometimes)
  ↓
  Fibrous connective tissue wall
  (with foreign body giant cells where ghost cells penetrate)

• Generally benign with good prognosis after enucleation and curettage
• Can be associated with other odontogenic tumors (ameloblastoma, adenomatoid odontogenic tumor, calcifying epithelial odontogenic tumor)
• Rare recurrence after conservative enucleation

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J(ii). ADENOID CYSTIC CARCINOMA (ACC)

• Minor salivary glands (most common overall - palate most common single site)
• Submandibular gland (2nd most common major gland)
• Parotid gland
• Also occurs in lacrimal gland, breast, skin, lung, trachea

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• Slow-growing but relentlessly progressive mass
• Pain is a prominent early feature (due to perineural invasion) - differentiates from most other salivary tumors
• Facial nerve paralysis (in parotid tumors) due to perineural spread
• Numbness/paraesthesia (sensory nerve involvement)
• Long clinical course with tendency for multiple recurrences over many years

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1. CRIBRIFORM PATTERN (Most Common, Grade 1)

• Islands of uniform basaloid tumor cells arranged with characteristic "Swiss cheese" or punched-out pseudocystic spaces
• Pseudocysts contain basophilic mucin (sialomucin) or eosinophilic hyaline material (basement membrane-like material)
• NOT true glandular spaces - hence "pseudo-cysts"
• Cells are small, dark, uniform with scant cytoplasm
• Surrounding hyalinized stroma

2. TUBULAR PATTERN (Grade 1)

• True glandular lumina lined by two cell types:
• Inner luminal cells (ductal differentiation, positive for EMA/CEA)
• Outer abluminal/myoepithelial cells (S100, smooth muscle actin positive)
• Better prognosis

3. SOLID PATTERN (Grade 3, Worst Prognosis)

• Solid sheets or nests of basaloid cells
• Minimal to no pseudocysts
• Higher mitotic activity, comedo necrosis may be seen
• >30% solid component = Grade 3 - most aggressive

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            CRIBRIFORM (Swiss cheese) PATTERN
       ┌─────────────────────────────────┐
       │                                 │
       │   [ISLAND of basaloid cells]    │
       │                                 │
       │  ○  ○  ○  ○  ○  ○  ○  ○       │  ← Pseudocysts
       │ ○ ○ ○ [CELLS] ○ ○ ○ ○ ○       │    (mucin-filled
       │  ○  ○  ○  ○  ○  ○  ○  ○       │     or hyaline
       │                                 │     material)
       └─────────────────────────────────┘
               Hyalinized stroma
       
    Small, dark, uniform basaloid cells
    Perineural invasion (KEY FEATURE)
    Basement membrane deposits within pseudocysts

1. Basaloid tumor cells - small, uniform, dark-staining nuclei
2. Cribriform "Swiss cheese" pattern - most characteristic
3. Perineural invasion - seen in majority of cases; HALLMARK of ACC
4. Hyalinized stroma
5. Two cell types: ductal cells + myoepithelial cells

• EMA, CEA (ductal cells)
• S100, SMA, p63 (myoepithelial cells)
• CD117 (c-KIT) positive
• MYB-NFIB fusion (t6;9 translocation) - molecular marker

• Grade 1: Tubular + cribriform only (no solid areas)
• Grade 2: Cribriform predominant + <30% solid
• Grade 3: >30% solid pattern

• Deceptively slow course but poor long-term prognosis
• 5-year survival: 70-75%; 10-year survival: 40% (drops dramatically)
• Distant metastasis common (lungs most frequent) - even without lymph node involvement
• Lymph node metastasis is less common than distant spread (opposite to most carcinomas)
• Perineural spread causes local recurrence despite wide excision

• Wide surgical excision with clear margins
• Adjuvant radiation therapy (postoperative) - improves local control
• Chemotherapy for metastatic disease (limited efficacy)

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