Diseases of the Salivary Glands

Overview

3 paired MAJOR glands(parotid, submandibular, sublingual) + numerous MINOR glands. Parotid=PURELY SEROUS. Submandibular=mixed, predominantly serous. Sublingual=mixed, predominantly mucous. Ducts: intercalated(low cuboidal)→intralobular(tall columnar)→secretory(simpler). Saliva: lubrication+amylase+antibacterial.

Salivary flow disturbances

SIALORRHOEA(ptyalism, ↑flow) — stomatitis, teething, mental retardation, schizophrenia, neuro disturbance, ↑gastric secretion, sialosis.

XEROSTOMIA(↓flow) — Sjögren’s, sarcoidosis, mumps parotitis, Mikulicz’s syndrome, megaloblastic anaemia, dehydration, drugs(antihistamines/antihypertensives/antidepressants).

Sialadenitis (acute or chronic, chronic MORE common)

Etiology:

1. Viral — COMMONEST inflammatory salivary lesion = MUMPS(school-age children). Triad: epidemic parotitis + orchitis-oophoritis + pancreatitis. ±testicular/pancreatic atrophy. CMV in infants (less common)
2. Bacterial/mycotic:
   • ACUTE — infectious fevers, postop parotitis(ascending infection), debility, old age, dehydration
   • CHRONIC — recurrent OBSTRUCTIVE(calculi/sialolithiasis, stricture, surgery, injury) or NON-OBSTRUCTIVE(hyposalivating drugs, irradiation, congenital duct malformation); chronic inflammatory disease(TB, actinomycosis, rare)
3. Autoimmune:
   • SJÖGREN’S SYNDROME — triad: dry eyes(keratoconjunctivitis sicca)+dry mouth(xerostomia)+rheumatoid arthritis
   • MIKULICZ’S SYNDROME — salivary+lacrimal gland inflammatory enlargement+xerostomia

Morphology: swelling, capsule-limited. Acute=redness/pain/tenderness/purulent discharge. Chronic=firm fibrous swelling. Micro: acute viral(mumps)=acinar swelling/vacuolation, ductal degeneration, interstitial oedema, fibrinoid collagen degeneration, dense mononuclear infiltrate. Chronic/recurrent=↑interstitial lymphoid tissue, progressive secretory loss→fibrosis.

Tumours

Parotid(85%)=COMMONEST site overall. PARADOX: parotid tumours mostly BENIGN(65-85%) but other major/minor gland tumours mostly show HIGHER MALIGNANT rate(35-50%) — RULE OF THUMB: rarer the site, higher malignancy chance. Origin: mostly ductal+myoepithelial cells, few from acini. Recurrent parotid tumours→facial palsy+scarring risk (anatomic proximity).

A. Benign tumours

Adenomas — 2 groups: pleomorphic vs monomorphic.

PLEOMORPHIC ADENOMA (mixed salivary tumour) — COMMONEST major(60-75%)+minor(50%) gland tumour; commonest parotid tumour. Women, 3rd-5th decade. Solitary, smooth, nodular, painless, slow-growing, below/front of ear.

Morphology: Gross=circumscribed, pseudoencapsulated, rounded/multilobulated, firm, 2-5cm, bosselated. Cut surface=grey-white/bluish, variegated, semitranslucent, mostly solid ±small cysts, soft mucoid. Micro=genuinely MIXED: epithelial(ducts/acini/tubules/sheets, ductal cuboidal/columnar+myoepithelial polygonal/spindle, PAS+ mucin, ±squamous metaplasia) IN stromal matrix(mucoid/myxoid/chondroid=PSEUDOCARTILAGE, actually modified myoepithelial product per S-100+). IHC: epithelial(cytokeratin/EMA/CEA)+myoepithelial(actin/vimentin/S-100) BOTH positive.

Prognosis: notorious RECURRENCE (years later) — incomplete removal(facial nerve proximity), multifocality, pseudoencapsulation, surgical implantation. Rare benign metastasis possible; malignant transformation also possible (see below). “Benign” ≠ low surgical stakes here.

Monomorphic adenomas (no mesenchyme-like tissue):

• WARTHIN’S TUMOUR (papillary cystadenoma lymphomatosum/adenolymphoma) — ~8% parotid neoplasms. MEN, 4th-7th decade. From parotid ductal epithelium in adjacent/intraparotid lymph nodes. Gross: encapsulated, round/oval, smooth; cystic spaces+milky fluid+papillary projections. Micro: eosinophilic epithelial glandular/cystic/papillary component + LYMPHOID STROMA(±germinal centres)
• OXYPHIL ADENOMA (oncocytoma) — benign, slow-growing, major glands, oncocytes(granular eosinophilic, mitochondria-rich = “mitochondrioma”)
• Other: myoepithelioma(pure myoepithelial), basal cell adenoma(resembles skin BCC), clear cell adenoma

Misc benign: fibroma, lipoma, neurilemmoma, neurofibroma, haemangioma, lymphangioma (rare mesenchymal).

B. Malignant tumours

MUCOEPIDERMOID CARCINOMA — MOST COMMON malignant salivary tumour overall (major+minor). Parotid+palatal minor glands commonest sites. Age 30-60, but ALSO commonest malignant salivary tumour in CHILDREN/ADOLESCENTS. MOST COMMON radiation-induced malignant salivary tumour. Gross: circumscribed, NOT encapsulated, 1-4cm. Micro: graded low/intermediate/high; 4 cell types(mucin-producing/squamous/intermediate/clear); well-diff=mucinous predominant, poor-diff=solid/infiltrative.

MALIGNANT MIXED TUMOUR — 3 entities:

1. Carcinoma ex pleomorphic adenoma — commonest(3-5%). RED FLAG: long-standing slow adenoma suddenly accelerates+becomes painful±facial palsy. Later age(6th decade) than typical PA(4th-6th). More often in RECURRENCES than primary. Gross: poorly circumscribed, infiltrating, ±haemorrhage/necrosis/cystic degeneration. Micro: typical PA areas + malignant areas(anaplasia, hyperchromatism, nucleoli, mitoses, invasion)
2. Carcinosarcoma — rare
3. Metastasising mixed salivary tumour — rare

ADENOID CYSTIC CARCINOMA (cylindroma) — highly malignant via PERINEURAL infiltration (notorious despite sometimes bland histology — local recurrence along nerve sheaths long after apparent complete excision). Micro: CRIBRIFORM appearance, duct/myoepithelial cells with fenestrations/cystic spaces, PAS+ basophilic material.

Acinic cell carcinoma — rare, resembles serous cells, sheets/acini, basophilic granular cytoplasm, variable atypia.

Adenocarcinoma — resembles elsewhere; variants: mucoid, clear-cell, papillary cystadenocarcinoma.

Epidermoid carcinoma — rare, SCC features, infiltrates skin+facial nerve EARLY.

Undifferentiated carcinoma — highly malignant, anaplastic, unclassifiable.

Misc: melanoma, sebaceous carcinoma, lymphoma, fibrosarcoma, leiomyosarcoma. Metastatic involvement common(esp. epidermoid carcinoma, melanoma).

Clinical relevance

Parotid paradox = rarer site→higher malignancy chance rule of thumb. Pleomorphic adenoma recurrence tendency = pseudoencapsulation+multifocality+facial nerve proximity explains why benign≠low-stakes here. Carcinoma ex pleomorphic adenoma = clinical red flag(sudden growth/pain/facial palsy in stable mass)→urgent reassessment. Adenoid cystic carcinoma’s perineural invasion = explains clinical notoriety despite sometimes bland grade — margins+long follow-up disproportionately important.

Overview

Three paired major salivary glands (parotid, submandibular, sublingual) plus numerous minor glands scattered through the oral mucosa. The parotid is purely serous; the submandibular is mixed but predominantly serous; the sublingual is mixed but predominantly mucous. Ducts drain: intercalated portion (low cuboidal), intralobular ducts (tall columnar), secretory ducts (simpler epithelium). Saliva lubricates swallowing/speech and carries amylase and antibacterial properties.

Salivary Flow Disturbances

Sialorrhoea (ptyalism) — increased salivary flow, from stomatitis, teething, mental retardation, schizophrenia, neurological disturbance, increased gastric secretion, or sialosis (uniform, symmetric, painless glandular hypertrophy).

Xerostomia — decreased salivary flow, associated with Sjögren’s syndrome, sarcoidosis, mumps parotitis, Mikulicz’s syndrome, megaloblastic anaemia, dehydration, and drugs (antihistamines, antihypertensives, antidepressants).

Sialadenitis

Salivary gland inflammation, acute or chronic (chronic is more common).

Etiology:

1. Viral infections — the commonest inflammatory salivary lesion, particularly of the parotid, is mumps in school-age children — a triad of epidemic parotitis, orchitis-oophoritis, and pancreatitis; testicular/pancreatic involvement may cause atrophy. Less commonly, cytomegalovirus affects the parotid in infants/young children.
2. Bacterial and mycotic infections:
   • Acute sialadenitis: acute infectious fevers, acute postoperative parotitis (ascending infection up the parotid duct), general debility, old age, dehydration.
   • Chronic sialadenitis: recurrent obstructive type (calculi/sialolithiasis, stricture, surgery, injury causing repeated ascending-infection attacks); recurrent non-obstructive type (hyposalivating drugs, irradiation, congenital ductal malformation); chronic inflammatory disease (tuberculosis, actinomycosis, other mycoses, rare).
3. Autoimmune disease:
   • Sjögren’s syndrome — triad of dry eyes (keratoconjunctivitis sicca), dry mouth (xerostomia), rheumatoid arthritis.
   • Mikulicz’s syndrome — inflammatory enlargement of salivary and lacrimal glands with xerostomia.

Morphology: gland swelling, usually capsule-limited. Acute stage — local redness, pain, tenderness, purulent ductal discharge. Chronic stage — firm fibrous swelling. Micro: acute viral (mumps) — acinar epithelial swelling/vacuolation, ductal epithelial degeneration, interstitial oedema, collagen fibrinoid degeneration, dense mononuclear infiltrate. Chronic/recurrent — increased interstitial lymphoid tissue, progressive secretory tissue loss, replacement fibrosis.

Tumours of the Salivary Glands

Both major and minor glands give rise to varied benign/malignant tumours. Parotid gland (85%) is the commonest site overall; 65–85% of parotid tumours are benign, while 35–50% of other major/minor gland tumours are malignant. Most tumours originate from ductal lining epithelium and myoepithelial cells, a few from acini. Recurrent parotid tumours often cause facial palsy and scarring from repeated surgery, given their anatomic location.

A. Benign Salivary Gland Tumours

Adenomas — two major groups: pleomorphic and monomorphic.

Pleomorphic adenoma (mixed salivary tumour) — the commonest tumour of major (60–75%) and minor (50%) glands; commonest parotid tumour. More common in women, 3rd–5th decades. Solitary, smooth, nodular, painless, slow-growing; commonly below/in front of the ear.

Morphology: Gross — circumscribed, pseudoencapsulated, rounded (sometimes multilobulated), firm, 2–5 cm, bosselated surface; cut surface grey-white/bluish, variegated, semitranslucent, mostly solid with occasional small cysts; soft mucoid consistency. Micro — genuinely “mixed”/pleomorphic appearance: epithelial elements (ducts, acini, tubules, sheets, strands of ductal/myoepithelial cells; ductal cells cuboidal/columnar, myoepithelial cells polygonal/spindle-shaped; PAS-positive epithelial mucin in duct lumina; focal squamous metaplasia/keratinisation) set in a stromal matrix of mucoid/myxoid/chondroid tissue (pseudocartilage — actually modified myoepithelial cell product, confirmed by S-100 positivity; true cartilage/bone occasionally seen). IHC: epithelial markers (cytokeratin, EMA, CEA) and myoepithelial markers (actin, vimentin, S-100) both positive.

Prognosis: notorious for recurrence, sometimes years later — from incomplete removal (facial nerve proximity), multiple tumour foci, pseudoencapsulation, and surgical-field implantation. Though entirely benign, rare cases metastasise distantly with benign histology preserved; actual malignant transformation can also occur (see malignant mixed tumour below).

Monomorphic adenomas — benign epithelial tumours without mesenchyme-like tissue:

• Warthin’s tumour (papillary cystadenoma lymphomatosum, adenolymphoma) — ~8% of parotid neoplasms; more common in men, 4th–7th decades; rarely submandibular/minor gland. Likely arises from parotid ductal epithelium within adjacent/intraparotid lymph nodes. Gross: encapsulated, round/oval, smooth; cut surface shows slit-like/cystic spaces with milky fluid and papillary projections. Micro: epithelial parenchyma (glandular/cystic, papillary, eosinophilic epithelium lining, ± mucous goblet cells/sebaceous differentiation) plus a lymphoid stroma (often with germinal centres).
• Oxyphil adenoma (oncocytoma) — benign, slow-growing, major glands; large cells with granular eosinophilic cytoplasm (oncocytes) in sheets/acini/tubules; also called “mitochondrioma” for the mitochondria-driven granularity.
• Other uncommon forms: myoepithelioma (purely myoepithelial cells, tubular/alveolar/trabecular), basal cell adenoma (resembles cutaneous basal cell carcinoma), clear cell adenoma (spindle/polyhedral clear cells).

Miscellaneous benign tumours: rare mesenchymal tumours — fibroma, lipoma, neurilemmoma, neurofibroma, haemangioma, lymphangioma.

B. Malignant Salivary Gland Tumours

Mucoepidermoid carcinoma — the most common malignant salivary gland tumour (major and minor glands). Parotid (major) and palatal minor glands are commonest sites. Age 30–60, but also the commonest malignant salivary tumour in children/adolescents; the most common radiation-induced (especially therapeutic) malignant salivary tumour. Gross: circumscribed but not encapsulated, 1–4 cm. Micro: graded low/intermediate/high by differentiation and invasiveness; composed of mucin-producing, squamous, intermediate, and clear cells — well-differentiated tumours are mucinous-cell-predominant; poorly-differentiated tumours are more solid/infiltrative.

Malignant mixed tumour — three distinct entities:

1. Carcinoma ex pleomorphic adenoma (carcinoma arising in benign mixed tumour) — commonest (3–5%).
2. Carcinosarcoma — rare.
3. Metastasising mixed salivary tumour — rare.

Carcinoma ex pleomorphic adenoma: a long-standing slow adenoma suddenly accelerates in growth, becomes painful, ± facial palsy. Malignant transformation occurs later (6th decade) than typical pleomorphic adenoma age (4th–6th decades); more often in recurrences than the primary tumour. Gross: poorly circumscribed, infiltrating margin, ± haemorrhage/necrosis/cystic degeneration. Micro: typical pleomorphic adenoma areas plus malignant areas showing anaplasia, nuclear hyperchromatism, large nucleoli, mitoses, invasive growth — any usual salivary carcinoma type may develop within a pleomorphic adenoma.

Adenoid cystic carcinoma (cylindroma) — highly malignant from its typical perineural infiltrative nature. Micro: cribriform appearance — duct-lining/myoepithelial cells in duct-like structures/masses with fenestrations/cyst-like spaces containing PAS-positive basophilic material.

Acinic cell carcinoma — rare; acinic cells resembling normal serous cells, in sheets/acini, basophilic granular cytoplasm; atypia ranges from bland to overtly malignant.

Adenocarcinoma — resembles adenocarcinoma elsewhere; variants: mucoid, clear-cell, papillary cystadenocarcinoma.

Epidermoid carcinoma — rare; squamous cell carcinoma features (keratin, intercellular bridges); commonly infiltrates skin and involves the facial nerve early.

Undifferentiated carcinoma — highly malignant, anaplastic, unclassifiable.

Miscellaneous malignant tumours: melanoma, sebaceous carcinoma, lymphoma, fibrosarcoma, leiomyosarcoma (all resembling their counterparts elsewhere). Metastatic involvement of major glands/adjacent nodes is also common, especially from epidermoid carcinoma and malignant melanoma.

Clinical Relevance

• The parotid’s benign-predominance-but-most-common-site paradox (85% of tumours occur here, yet 65–85% of parotid tumours are benign) versus the minor/other-gland reversal (35–50% malignant) is a genuinely useful rule of thumb: the rarer the gland site for a tumour to arise in, the higher the chance it’s malignant.
• Pleomorphic adenoma’s recurrence tendency despite being entirely benign is directly explained by its anatomic and histologic features (pseudoencapsulation, multifocality, facial nerve proximity limiting resection margins) — this is why “benign” doesn’t mean “low surgical stakes” for this specific tumour.
• Carcinoma ex pleomorphic adenoma is the clinical red flag to watch for in any long-standing parotid mass: sudden growth acceleration, new pain, or new facial palsy in a previously stable, slow-growing lump should prompt urgent reassessment for malignant transformation.
• Adenoid cystic carcinoma’s perineural invasion pattern explains its clinical notoriety despite sometimes appearing histologically bland — it recurs locally along nerve sheaths long after apparent complete excision, making margins and long-term follow-up disproportionately important compared to its grade.

• Classification tree of salivary gland tumours (benign: pleomorphic/monomorphic adenomas vs malignant: mucoepidermoid/adenoid cystic/acinic cell/etc.)
• Pleomorphic adenoma’s mixed epithelial-plus-stromal architecture shown as a labelled cross-section
• Warthin’s tumour cross-section showing the epithelial papillary-cystic component against its lymphoid stroma

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