Tadrous P.J. Diagnostic criteria handbook in histopathology: a surgical pathology vade mecum

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Alimentary Tract 129

Multiple sections to exclude dentine (otherwise = ameloblastic ﬁbro-dentinoma or ameloblastic ﬁbro-

odontome if enamel has formed over the dentine)

d/dg – !do not call this ameloblastoma – because unnecessarily radical surgery will result

Squamous Odontogenic Tumour

Islands / strands of bland squamous epithelium with no peripheral palisading

± Keratin, ± cystic areas, ± dystrophic Ca

(but no amyloid)

d/dg SCC: bland cytology

d/dg ameloblastoma: no palisading

d/dg Pindborg tumour: no amyloid / round masses of calcium / anisonucleosis

Calcifying Epithelial Odontogenic Tumour (Pindborg)

Sheets / cribriform structures / nests of squamoid epithelium ± intercellular bridges

Anisonucleosis with even chromatin

Mitoses uncommon

Hyaline amyloid amongst the epithelium (rounded masses, may calcify)

Clear Cell Odontogenic Tumour

Elderly, aggressive tumour

Cords and nests of clear cells and basaloid cells

Mitoses ++

No amyloid, calcium or mucus but glycogen is present

d/dg clear cell tumours of salivary gland / clear cell ameloblastoma / Pindborg tumour

Primary Intraosseous Carcinoma

Usu. in mandible and usu. SCC

d/dg odontogenic tumours

d/dg metastasis esp. RCC

d/dg ameloblastoma / adamantinoma (q.v.)

Fibro-osseous Lesions

Cementoblastoma: osteoblastoma at root of tooth (well-circumscribed, see p. 335)

Ossifying ﬁbroma: clearly deﬁned margin on X-ray, well-circumscribed

Fibrous dysplasia: poorly deﬁned margin on X-ray (for features, see p. 334)

Periapical cemental dysplasia

Oral Fibrous Polyps

Fibroma of the lip: uninﬂamed un-orientated collagen bundles (i.e. they go in all directions)

Fibrous epulis: inﬂamed vertically oriented collagen bundles continuous with underlying corium

Pyogenic granuloma: inﬂamed lobular capillary growth ± ulceration

Denture-assoc

hyperplasia: simple lobulated hyperplastic polyp around denture edges

Giant cell ﬁbroma: large stellate stromal myoﬁbroblasts ± multinucleation

and ossiﬁcation may occur in the stroma of any of these

Dysplasia in Squamous Oral Mucosa

Grading is based on less-severe changes cf. CIN in the cervix (particularly for mild dysplasia)

Rete peg elongation alone is not an arch. feature of dysplasia (cf. bulbous / ‘drop’-shaped rete pegs)

Mild:  basal cell crowding with bulbous rete pegs and mild atypia (no need for ↑mitoses)

Moderate:  bulbous rete ± lateral projections (i.e. 2

◦

nodules of basal cells extending laterally)

 mild to moderate cytological atypia, suprabasal mitoses

 changes extend to the middle

(but do not completely ﬁll the basal and spinous layers)

Severe:  atypia ﬁlls the basal and spinous layers (but need not extend to the surface, else =

CIS)

 cytological atypia is worse than in moderate dysplasia ± atypical mitoses

 changes extend to upper

(but surface cell nuclei may be normal)

d/dg chronic candidiasis (incl. median rhomboid glossitis): see ‘Pseudoepitheliomatous Hyperplasia

(PEH) in the Oral Cavity’, p. 133

d/dg lichen planus: if dysplasia is present with LP call it ‘dysplasia with a lichenoid reaction’ not LP

d/dg koilocytic atypia (HPV) occurs (esp. with HIV) but is not considered dysplasia in the mouth

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Alimentary Tract 130

SCC of Oral Mucosa

‘Microinvasive’ is not deﬁned in terms of a depth measurement but as invasion to only the most

superﬁcial regions beneath the BM

Verrucous carcinoma: criteria are as for skin (see p. 285)

d/dg: PEH ± granular cell tumour (a deeper Bx may be needed to reveal this) / other cause

d/dg: papillary hyperplasia of the palate: this shows nodular ﬁbroplasia and irregular cross-sections of

deep broad rete pegs with parakeratosis ± PEH with pseudo-‘pearls’ (! do not call it SCC)

d/dg necrotising sialometaplasia (vide infra): SCC rarely occurs on the hard palate

d/dg: lichenoid reactions (drugs, LP, discoid LE) cause irregularity of the basal layers and inﬂam

SCC rarely arises on the dorsum of the tongue (unlike d/dg chronic Candida / granular cell tumour)

Salivary Glands

Pleomorphic Salivary Adenoma (PSAd)

Pathognomonic features

◦

Chondromyxoid stroma

◦

Plasmacytoid myoepithelial cells (also seen in myoepithelioma)

◦

‘Streaming’ pattern of myoepithelial cells (like a ‘swarm of bees’)

◦

Thick, ﬂuffy elastic bands (centrally – shown well by EVG)

Prognostic features

Margins

The more the matrix the more the recurrence risk

The more the cells the more the malignancy risk

Immuno

Epithelium: CEA, PSA, EMA +ve

Myoepithelium: calponin (for other myoepithelial cell markers, see p. 18)

Low Ki-67 LI (1.6% cf. >20% for d/dg AdCC)

Malignancy and pleomorphic salivary adenoma

Metastatic PSAd is a complication of surgery

Carcinoma ex PSAd:  any salivary CA that doesn’t ﬁt a standard type think CA ex PSAd (do EVG)

 any type (except acinic cell) may occur

 prognosis depends on whether the tumour is:

◦

In situ (↑/abnormal mitoses, coagulative necrosis, expansile nodule, widespread atypia

)or

◦

Invasive (distance of invasion from the PSAd capsule [some quote 8mm, others 5 to 6mm as

the threshold for prognostic change], grade and type are all important features to assess)

Myoepithelioma of Salivary Gland (and Myoepithelial Carcinoma)

Well-circumscribed

Solid, myxoid and reticular architectures

Myoepithelial cells may be: spindled, plasmacytoid, epithelioid or clear (rare)

Spindle morphology is commonest in parotid with plasmacytoid in minor glands

± Small ducts (<10% of tumour)

Immuno: S100, GFAP & CK14 +ve (and other myoepithelial markers – see p. 18)

Malignancy (= myoepithelial carcinoma):  invasion

 ↑ proliferation:  mitotic count >7/10 hpf

 Ki-67 LI >10%

Basal Cell Adenoma (and Basal Cell Adenocarcinoma)

Major salivary glands; two subtypes (membranous and non-membranous)

Two cell types:

◦

small dark with scant cytoplasm,

◦

larger with amphophil cytoplasm

Cell nests surrounded by PAS +ve BM material (± peripheral palisading)

Variant: Non-membranous:

 M=F, rarely recur or become malignant

 well-circumscribed, nests/trabeculae

 cells are admixed with dark ones tending to the periphery of the nests

if atypia is mild then it is called ‘atypical PSAd’ rather than ‘carcinoma ex PSAd’

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Alimentary Tract 131

 ± ducts and whorled eddies of epithelial cells

 variably cellular stroma contains S100 +ve spindle cells

Variant: Membranous:

 MF, multicentric,

recur locally,

become malignant

 unencapsulated, multinodular jigsaw pattern architecture

 the PAS +ve BM material around islands and blood vessels is thick and hyaline

 50% assoc

with dermal cylindroma / spiradenoma / other skin adnexal tumours

Malignancy: invasiveness (= basal cell adenocarcinoma)

d/dg adenoid cystic carcinoma: AdCC has more cytological atypia and mitoses and does not have

epithelial whorled eddies and is not palisaded

Canalicular Adenoma

Small

Interconnecting strands of bilayered small, dark epithelial cells

Loose vascular stroma

No pleomorphism, mitoses or invasion (! but multifocality can mimic invasion)

Immuno: strongly and diffusely S100 +ve

d/dg adenoid cystic carcinoma: AdCC has true invasion and only focal or weak S100 +ve

Oncocytoma / Oncocytosis / Multinodular Oncocytic Hyperplasia (MNOH)

PMHx of radioRx

Round central nuclei with distinct nucleoli

Granular cytoplasm: DPAS −ve, PTAH +ve



cf. d/dg acinic cell carcinoma

Prone to infarction → squamous metaplasia with ‘reparative’ nuclear atypia (!d/dg SCC)

Malignancy:  invasiveness

 coagulative tumour cell necrosis (not infarction)

 abnormal mitotic ﬁgures

 (atypia beyond the reparative type expected)

Adenoid Cystic Carcinoma (AdCC)

Minor > major glands esp. palate, breast, bronchial glands (d/dg spread from salivary gland)

Invasion (esp. perineural invasion)

Cylindroma-like BM thickening around islands of basaloid cells with cribriform cystic spaces (acini)

Basaloid acini are ‘inverted’ i.e. contain acid mucin (often with a central neutral mucin blob)

Basaloid cells have angular hyperchromatic nuclei with a degree of pleomorphism

True epithelial tubules are also admixed with central neutral mucin

Immuno: +ve for c-kit (membranous), p63 (nuclear), S100 (focal, weak)

Solid variant:  focally jagged islands of basaloid cells (not palisaded)

 ± small ducts within the basaloid islands

 ± coagulative tumour cell necrosis

 d/dg basal cell adenoma: (vide supra)

Salivary Duct Carcinoma

Usu. major gland in middle aged

Like high grade ductal carcinoma of the breast with comedo DCIS. In salivary glands this comedocar-

cinoma is considered to be an invasive component (unlike in the breast)

Immuno: +ve for EMA, PSA, CEA, GCDFP15, ± PgR; −ve for ER and myoepithelial components

d/dg metastatic carcinoma: breast 1

◦

must be excluded clinically

d/dg high grade MEC: esp. if more than sparse mucin is present

Polymorphous Low Grade Adenocarcinoma (PLGA, Terminal Duct Carcinoma)

Usu. minor salivary glands

Cells are rounded / oval; nuclei are uniform with ﬁnely speckled chromatin ± PTC-like vacuoles

‘Architectural diversity’ (ducts, cribriform, ILC-like, diffuse inﬁltration)

Capsular, vascular and perineural invasion (the latter may be ‘targetoid’)

Immuno: triad of EMA, S100, vimentin +ve

Papillary variants are more aggressive

d/dg AdCC:  cytology (AdCC has angular, hyperchromatic nuclei with pleomorphism)

 proliferation fraction by MIB1: <10% for PLGA, >10% for adenoid cystic

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Alimentary Tract 132

Acinic Cell Carcinoma

May be bilateral

Microcystic / thyroid follicular / solid arch. with regimented marginal nuclei cf. oncocytic

Granular cytoplasm: DPAS +ve, PTAH −ve



tumours

Stromal lymphoid follicles

Good prognosis subtype:  well-circumscribed

 microcystic



throughout

 lymphoid follicles

Mucoepidermoid Carcinoma (MEC)

Any age, major/minor salivary gland, tracheobronchial tree, jaw bones

Macro: solid ± cystic areas

Micro: inﬁltrative as irregular islands (solid ± cystic with mucin) and variable stromal ﬁbrosis and

inﬂammation (? due to a reaction to extravasated mucin)

Three cell types:

◦

epidermoid (intercellular bridges but keratin rare),

◦

intermediate,

◦

mucus cells

Low grade:  well-developed mucus cells and cysts make up a large proportion of the tumour

(intracystic spaces account for >10% of tumour area by Evans’ criteria [not counting

stroma and areas occupied by extravasated mucin])

 squamoid features not well developed (bridges hard to demonstrate, no keratin)

 ﬁbroinﬂammatory stroma prominent

High grade:  mostly solid

 squamoid features well developed ± minor keratinisation (full keratinisation and

pearls still rare)

 mucus cells (necessary for diagnosis) – may need DPAS/mucicarmine to show them

 aggressive invasion pattern plus at least one of the following

 ‘other high grade features’: high grade cytological atypia, ↑mitoses (>4 per 10 hpf),

tumour necrosis, perineural / vascular / bony invasion

Intermediate Grade: EITHER a) some minor cystic areas and well-developed mucus cells OR b) predom.

composed of intermediate cells with aggressive invasion but no ‘other high grade features’

Variant: Sclerosing MEC has paucicellular keloidal central scarring with inﬂammatory aggregates

mixed with tumour islands at periphery (!d/dg benign inﬂammatory lesion)

d/dg poorly diff adenocarcinoma, SCC or ASC: see p. 92

d/dg Warthin or PSAd with squamous differentiation

d/dg salivary cystadenoma / cystadenocarcinoma

d/dg mucocoele (vs. low grade MEC)

d/dg salivary duct carcinoma with mucus cells (vs. high grade MEC)

Mucus Clear Cell Tumours of Salivary Glands

MEC

Variants of salivary duct carcinoma

Non-mucus Clear Cell Tumours of Salivary Glands

Monomorphic: 1. Epithelial: Hyalinising Clear Cell Carcinoma

2. Myoepithelial: Myoepithelioma / carcinoma

Dimorphic: Epithelial myoepithelial carcinoma  well-circ., lobules, organoid, low grade

 clear cells glycogen +ve

 epithelial (eosinophilic) cells DPAS +ve

Metastatic: RCC, thyroid, melanoma, SCC with clear cell change

Clear cell variants of: Acinic (DPAS +ve, PTAH −ve) or Oncocytic (DPAS −ve, PTAH +ve) tumours

Myoepithelial Sialadenitis = Lymphoepithelial Sialadenitis (MESA / LESA) = Autoimmune Sialadenitis

Old name = benign lymphoepithelial lesion; assoc

with autoimmune / CTD

Early:  duct dilates

 light / focal inﬁltrate of duct epithelium by B-cells with centrocyte-like morphology (Cc-

like cells) that merge with the mantle zones of the surrounding follicles

 duct surrounded by lymphoid tissue with follicles and germinal centres

 plasma cells also present (esp. around the ducts)

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Alimentary Tract 133

Later: ducts condense with obliteration of the lumen to leave solid nests of epithelial, myoepithelial

and B-cells (epimyoepithelial islands) – highlighted by CK immuno

The earliest change of transformation to MALToma (MZL) is the presence of a pale zone of clear Cc-

like cells around the duct or epimyoepithelial island. These cells loose there mantle B-cell phenotype

(IgD +ve, IgM +ve) to display a marginal zone phenotype (IgD −ve, IgM +ve).

Non-Autoimmune Sialadenitis (e.g. due to duct obstruction)

Lymphocytic inﬁltration of the ducts is mild and there are scarce/no LEL (cf. d/dg LESA)

Ducts may contain PMN, calculus +/ squamous metaplasia

Main inﬂammation is in the acini

Late changes = acinar atrophy, stromal ﬁbrosis ± heavy chronic inﬂammation ± germinal centres.

These can cause a hard palpable gland (= K¨uttner’s tumour in the submandibular gland)

Some forms of K¨uttner’s tumour may have IgG4 +ve plasma cells (see multifocal ﬁbrosclerosis)

Necrotising Sialometaplasia

Usu. minor glands, ischaemic aetiology (post radiation / FNA or adjacent to infarction, etc.)

Lobular architecture is preserved

Extensive squamous metaplasia of both ducts and acini

Inﬂammation ± granulation tissue / residual infarction

PEH of overlying squamous epithelium (e.g. in palatal lesions)

d/dg SCC: retained lobular architecture goes against SCC, and metaplastic ducts may retain lumena

Oral Hairy Leukoplakia

Due to EBV; seen in immunosuppression regardless of HIV status

Hyperkeratosis and acanthosis with minimal / no underlying inﬂammation

Ballooning degeneration of keratinocytes ± intranuclear ground glass inclusions / beaded nuclei

± Koilocytic atypia (may also be due to d/dg HPV)

d/dg chronic biting, Candida, maceration, white sponge naevus

Pseudoepitheliomatous Hyperplasia (PEH) in the Oral Cavity

Chronic hyperplastic candidosis incl. median rhomboid glossitis: more usually this gives broad-based

enlargement of the rete with atrophy over the connective tissue papillae but PEH may occur: look for

PMN ± microabscesses and fungal hyphae on PAS

Granular cell tumour (esp. tongue)

Necrotising sialometaplasia (esp. palate, looks like a ‘malignant ulcer’ clinically) – vide supra

Papillary hyperplasia of the palate (usu. due to poorly ﬁtting or continuously worn dentures) – vide

supra

d/dg SCC: SCC is rare on the dorsum of the tongue and hard palate and shows abrupt squamous

differentiation / keratinisation (not maturation from a basal layer like PEH) – see also p. 285

Cystic Lesions of Salivary Glands

Warthin’s tumour:

 bilayer of oncocytic epithelium (inner columnar often with nuclei towards lumen, outer

cuboidal)

 ± squamous (! d/dg atypical squamous metaplasia is not SCC), mucous, ciliated metaplasia

 stroma may be lymphoid rich or poor (esp. in the elderly)

 malignancy in epithelium: SCC / poorly diff carcinoma / MEC

 malignancy in stroma: any lymphoma that affects LNs

Benign lymphoepithelial cyst (= ‘simple cyst’):

 lining is branchial-type (squamous +/ respiratory +/ columnar +/ cuboidal)

 wall contains reactive lymphoid tissue ± follicles

 no epimyoepithelial islands

Cystic LESA:

 instead of contracting to form epimyoepithelial islands, some ducts dilate → multicystic

Cystic lymphoid hyperplasia of HIV:

 LESA variant with Cc-like B-cells inﬁltrating cyst lining ± epimyoepithelial islands

 multiple cysts lined by squamous epithelium (or cuboidal / columnar / respiratory)

 undulating appearance to the epithelial lining

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Alimentary Tract 134

 ﬂorid HIV-type lymphoid reaction in the wall:

 follicular hyperplasia (± ‘naked follicles’ i.e. without mantles)

 folliculolysis, plasmacytosis, etc. (for more details,

see p. 119)

Cystic MALToma: can develop in cystic LESA

Cystic MEC:

 d/dg benign lymphoepithelial cyst (see box):

 d/dg mucocoele: vide infra, also mucocoeles are

very rare in major salivary glands

MEC has more mucous cells cf. squames

MEC shows solid areas

MEC has a mixture of cell types

MEC is inﬁltrative

Cystic metastatic carcinoma: d/dg cystic SCC vs. benign lymphoepithelial cyst vs. keratocystoma

Keratocystoma: multiple benign squamous cysts usu. in a major gland and without mucous cells, lobular

arch. or skin adnexa (cf. d/dg trichoadenoma / dermoid / SCC / necrotising sialometaplasia)

Papillary cystic acinic cell carcinoma: (see ‘Acinic Cell Carcinoma’, above)

Cystadenoma (papillary cystadenoma):

 major / minor glands, slow growing and painless

 single / multicystic

 dense ﬁbrotic stroma

 cysts lined by attenuated ductal epithelium ± papillary projections

 bland nuclei, mitoses scant / absent

 ± metaplasias (mucous, oncocytic, squamous)

 d/dg salivary duct ectasia

 d/dg cystic MEC (solid areas, inﬁltrative, mixed cell types)

 d/dg cystadenocarcinoma (invasion)

Cystadenocarcinoma (papillary cystadenocarcinoma):

 major and minor glands, asymptomatic, low grade malignancy

 single / multicystic with great variation in cyst size within any given tumour

 ﬁbrotic / sclerotic / desmoplastic stroma

 single layer to pseudostratiﬁed cuboidal / columnar cells

 prominent nucleoli and mild to moderate atypia

 invasion into surrounding parenchyma is the diagnostic feature

 d/dg papillary cystic acinic cell carcinoma and salivary cystadenoma (q.v.)

Polycystic disease of the parotid (dysgenetic disease):

 retained lobular architecture

 honeycomb multicystic dilatation of lobules

 cysts contain ﬂocculant material

Sclerosing polycystic adenosis:  lobular architecture retained

 variably-sized cysts

 adjacent cellular areas resembling sclerosing adenosis of the

breast

Retention mucocoele: (usu. in minor salivary glands) has an intact epithelial lining

Extravasation mucocoele: (usu. in minor salivary glands)

 small ones may collapse to a muciphagic granuloma otherwise you see...

 a pool of mucin with peripheral foamy M,

 ± lined by granulation tissue / ﬁbrosis

 large cysts may have a rim of compressed M (! do not confuse for an epithelial lining)

 sublingual gland extravasation mucocoeles lying to one side of the frenulum can be large and

are known as ranula. They may dissect the deep soft tissues of the head and neck (→plunging /

dissecting ranula) and excision of sublingual gland is required for cure

Oesophagus

Reﬂux Oesophagitis (part of Gastro-Oesophageal Reﬂux Disease – GORD)

Basal layer hyperplasia (alone this may be normal / physiological)

Oedema / spongiosis

↑ IELs, eosinophils, PMN

↑ Height of papillae into upper

of epithelium

Superﬁcial engorged capillaries

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Alimentary Tract 135

± Peptic ulceration

d/dg: pemphigus, etc.: in systemic skin disease the changes are usu. in mid to upper oesophagus

d/dg: HSV, candidal or CMV oesophagitis

d/dg ! beware local reﬂux changes adjacent to carcinoma (.

. do levels if clinically ? CA)

d/dg adult eosinophilic oesophagitis is favoured by dysphagia (cf. heartburn), M>F, age <45, rings &

lack of hiatus hernia on endoscopy, l.p. ﬁbrosis & eos., many intraepithelial eos. (≥20–25 in 1 hpf or

≥15 in ≥2 hpf), eos. abscesses; (important because Rx is allergen exclusion rather than antacids)

Progressive Systemic Sclerosis (PSS) ± CREST Syndrome

Intimal thickening and elastosis of arteries

Submucosal ﬁbrosis and atrophy of smooth muscle

GORD

Achalasia of the Cardia

Maybe1

◦

(idiopathic ?autoimmune) or 2

◦

(e.g. to neoplasia, sarcoid, vagotomy, MEN 2b, etc.)

Distal constrict

: loss of myenteric plexus neurons ± patchy ﬁbrosis, lymphocytic & eos. inﬂam

Lewy bodies

Proximal dilatation: ﬁbrosis, muscularis propria hypertrophy ± severe GORD ± ulceration

Other 2

◦

changes incl.: BO, haemorrhage, Candida, SCC

d/dg Chagas’ disease: T. cruzi amastigotes (≈ Leishmania) in intracellular ‘cysts’ seen in early stages

Barrett’s Oesophagus (BO)

Def

: Classical BO: > 3cm from GOJ shows any of:

cardiac mucosa this is a combined

—–

atrophic fundic mucosa

⎫

⎬

⎭

endoscopic and

intestinal metaplasia histological diagnosis

Short-segment BO: < 3cm but only i.m. is allowed

Ultra-short-segment BO = i.m. within the SCJ

Classical and short:  assoc

with reﬂux (gastro-oesophageal acid, SI contents and bile)

 CagA +ve H. Pylori may be protective

Ultrashort  not necessarily assoc

with reﬂux or classical BO

 assoc

with H. Pylori gastritis (may be a form of carditis)

Histodiagnosis of BO

Deﬁnite: native oesophageal structures

juxtaposed to metaplastic glandular mucosa

Conditional:

(on endoscopy)

 inﬂammation in disorganised gastric mucosa

 intestinal metaplasia (only the presence of i.m. is a deﬁnite cancer risk)

Other features: a reduplicated m.m. (new component superﬁcial to old) ± hyperplastic polyps

Soft Tissue Tumours

Carcinosarcoma (d/dg inﬂammatory pseudotumour – see Chapter 21: Soft Tissues)

Inﬂammatory ﬁbroid polyp (vide infra)

Granular cell tumour (± PEH – don’t mis-diagnose as SCC)

Leiomyoma (d/dg GIST):  arise from muscularis propria / m.m. / vessels

 <5cm and unencapsulated (1–2mm ones are ‘seedling leiomyomas’)

 histology as for leiomyoma elsewhere

 d/dg very rare leiomyosarcoma: >5cm, necrosis, mitoses >5/10 hpf

 d/dg diffuse leiomyomatosis: adolescents, hereditary associat

Glandular Dysplasia

No universally agreed criteria to distinguish low grade from high grade (see also p. 127)

Cytology alone cannot distinguish dysplasia from invasive carcinoma (.

. need histology)

High grade should be corroborated by an ‘expert’ (at least double reporting) or 2

the term ‘Barrett’s epithelium’ refers to simple tall columnar mucinous epithelium (± goblet cells) with thin and irreg. (partially

beaded) apical mucin that may occur in BO – this term is best avoided given the current clinicopathological deﬁnitions of BO and

given that some people use the terms ‘Barrett’s epithelium / metaplasia / oesophagus’ interchangeably in the literature

i.e. oesophageal ducts (with a stratiﬁed squamoid lining) and submucosal glands (≈ minor salivary glands)

not necessarily intestinal metaplasia

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Alimentary Tract 136

Low grade:

 cytology equivalent to mild / moderate dysplastic colonic adenoma

 nuclei ovoid or pencil-like and usu. stratiﬁed (but often mild or not full-thickness)

 architectural abnormalities are usu. mild

High grade: (some require these changes to be present in > 1 or 2 crypts to qualify as high grade)



EITHER cytology ≈ severely dysplastic colonic adenoma AND/OR severe arch. abnormalities

 rounded nuclei with open chromatin and prominent nucleoli which may be irregular

 the nuclear arrangement is more disorganised than just stratiﬁed

 more severe arch. changes (budding, complexity, etc.)

 50% have co-existent invasive carcinoma, esp. if there is a nodule or ulcer on endoscopy

BCDA: has both arch. complexity and dysplasia-type cytological atypia but with surface

maturation

Immuno: AMACAR +vity may suggest neoplasia (–vity means nothing), p53 is controversial

Features causing problems in diagnosis: (usu. false positive)

 ↑ size of proliferative zone

 variable position of proliferative zone in different types of metaplasia (gastric vs. intestinal)

 change to intestinal-type epithelium (esp. a patch of intestinal metaplasia in an otherwise

gastric area)

 inﬂammation esp. acute (→ ‘indeﬁnite for dysplasia’) or reactive (chemical) gastritis-type

 surface re-epithelialisation with squamous mucosa: may mask the underlyingdysplastic glands

(difﬁcult because there is no glandular surface to help assess loss of maturation)

 artefacts e.g. cross-cutting, variable thickness or staining, etc. (consider ‘indeﬁnite for dys-

plasia’)

 d/dg Isaacson lesions (esp. Type II vs. SCC) – see p. 127

Management:  Indeﬁnite early → (3 month) re-endoscopy after Rx for inﬂammation

 Low grade → close F/U with endoscopies

 High grade → laser/photodynamic/submucosal resection/surgery

Squamous Dysplasia

Same criteria as squamous dysplasia elsewhere (except oral cavity)

Low grade if <1/2 the epithelial thickness involved, high grade if >1/2

d/dg ! exclude inﬂammatory atypia these have vesicular nuclei with nucleoli (may be irregular

d/dg ! exclude regenerative atypia

⎫

⎪

⎬

⎪

⎭

or elongated) and normal mitoses. Dysplasia has ↑ NCR,

hyperchromasia, mitoses ++ (that may be abnormal)

and disturbed cytoarchitecture

Oesophageal Carcinoma

Main 1

◦

types: SCC, adenoCA, SmCC, ASC: grade by worst area (well/mod./poorly diff./undiff)

Invasion of submucosal lymphatics results in ‘skip’ lesions away from any macroscopic main lesion

d/dg SCC vs. PEH (esp. when 2

◦

to granular cell tumour)

Neoadjuvant Rx (Pre-op ChemoRx ± RadioRx)

Mucin pools, keratinous nodules and effects of chemoRx/radioRx on benign tissues may be seen

Only viable tumour epithelial cells allow diagnosis of residual tumour for staging purposes (apoptotic

cells or mucin/keratin alone do not count) – multiple levels and CK immuno may be used to detect viable

epithelial cells. (See also ‘Neoadjuvant Rx (Pre-op RadioRx ±ChemoRx)’ in ‘Colorectal Carcinoma’)

Other Nodular / Mass Lesions and Cysts

Squamous papilloma: ﬁliform arch., hyperplastic non-dysplastic squamous epithelium ±HPV changes

Adenoma (see ‘Adenomatous Polyp (Gastric Adenoma)’, p. 138) – may occur as part of Barrett’s

dysplasia

Minor salivary gland-type tumours arising from oesophageal glands

◦

tumours: melanoma, breast carcinoma, testicular tumours, etc.

Glycogenic acanthosis

Fibrovascular polyp: usu. lined by squamous epithelium but not ﬁliform (cf. papilloma)

Cysts: duplication, bronchogenic, pseudodiverticular, etc.

? a role for F/U endoscopy i.e. conservative – always check local Mx protocols with clinicians

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Alimentary Tract 137

Stomach

Chronic Gastritis (Usual Types)

A) atrophic: body, PA, ECL-cell hyperplasia / tumourlets. Assoc

with i.m., adenoma, adenocarcinoma

B) bacterial (HLO): mention presence and severity of chronic inﬂam

, activity (= intraepithelial PMN),

i.m., atrophy, lymphoid follicles, HLOs, dysplasia and malignancy. HLOs are assoc

with activity, 2

◦

lymphoid follicles, i.m. & MALToma.; intestinal metaplasia is associated with adenocarcinoma

C) chemical / reactive (due to alcohol, bile reﬂux, NSAID, etc.): foveolar hyperplasia, ﬁbrosis, oedema,

vertical smooth muscle in l.p., superﬁcial vascular ectasia and sparse chronic inﬂam

.GAVE= ﬂorid

type C gastritis

Lymphocytic Gastritis and Collagenous Gastritis

↑ T-cells in both l.p. and epithelium (≥ 25 per 100 epithelial cells)

Small mature T-cells with pericellular clear halo

± Aphthae

‘collagenous gastritis’ if there is a subepithelial collagen band (>10 thick)

Assoc

with: coeliac, Crohn’s, H. Pylori, lymphoma, adenocarcinoma, HIV and idiopathic

Eosinophilic Gastritis

Eosinophils predominate throughout the l.p.

l.p. ﬁbrosis

Assoc

with allergies, parasites, CTD, Crohn’s and idiopathic

Granulomatous Gastritis

Infective: H. pylori, TB, fungi, Whipple’s, syphilis, etc.

Sarcoidosis

Crohn’s (also has patchy acute inﬂam

± ﬁssures / ulcerat

± eos. ± submucosal lymphoid aggregates

± focal destruction of glands by T-cells [= focally enhanced gastritis ≈ focal lymphocytic gastritis])

Foreign body-type (assoc

with erosions or peptic ulcer)

Idiopathic (= ‘isolated’) or rarer speciﬁc causes

Alcoholic Gastropathy (Haemorrhagic Gastropathy, Portal HT Gastropathy)

‘Snakeskin’ appearance at endoscopy may be seen (vascular changes) – fundal predominance

Superﬁcial mucosal haemorrhages ± haemosiderin

Adjacent oedema

Usu. lacks inﬂammation

d/dg Erosive ‘Gastritis’: this is similar and is commonly seen in very ill patients (stress-related)

Intestinal Metaplasia (i.m.)

Assoc

with ↑ risk of carcinoma – esp. in incomplete types and esp. in type III.

Goblet cells contain both neutral and acid (either sialo or sulpho) mucin

Complete i.m. (type I): goblet cells surrounded by intestinal absorptive cells (± Paneth / NE cells)

Incomplete i.m. (types II and III): goblet cells surrounded by altered columnar mucinous cells (altered

such as to have acid mucin and in smaller amounts cf. normal gastric mucin cells).

Subtyping is based on the columnar (not goblet) cell acid mucin: sialo = type II, sulpho = type III

(also known as type IIa and IIb respectively)

M´en´etrier’s Disease

Protein-loosing hypertrophic gastric body fold disease. Progressive in adults / self limiting in a child

Massive body / fundus foveolar hyperplasia with cystic glands deeper

Mucus plugs in glands

Atrophy of chief and parietal cells (.

. ↓ gastric acid unlike ZE syndrome)

d/dg infection (esp. CMV)

d/dg ZE Syndrome: ECL-cell hyperplasia, parietal cell hyperplasia and pancreatic / duodenal gastrinoma

→ hypergastrinaemia (unlike M´en´etrier)

d/dg hypertrophic hypersecretory gastropathy (very rare)

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Alimentary Tract 138

Fundic Gland Polyp

Usu. fundal mucosa and average size <5mm

Cystically dilated fundic glands

Bland, often attenuated epithelium in cysts

Assoc

with: idiopathic, long term gastric acid suppression, FAP (dysplasia common)

Inﬂammatory Fibroid Polyp

Macro: smooth submucosal mass that may ulcerate, usu. <5cm, occurs in upper & lower GIT

Submucosal vascular granulation tissue with variable inﬂammatory inﬁltrate

Perivascular hypocellular zones

Variable n˜o. of eosinophils (but not peripheral eosinophilia)

± Leiomyoma / Schwannoma-like areas with nuclear palisading

Immuno: CD34 +ve, >95% are −ve for c-kit

Peutz-Jeghers Polyp – See p. 149

Hyperplastic Polyp (Regenerative Polyp)

Usu. junctional mucosa and average size 1cm (if >2cm have ↑ risk of dysplasia / carcinoma)

Cystic ± branching foveolar hyperplasia and ‘onion skin’ concentric arrangement of glands

Stromal oedema ++, ± inﬂam

, smooth muscle ﬁbres extend up around gland aggregates

Bland epithelium ± inﬂam

atypia / ulceration (! d/dg focal dysplasia / CA which may also occur)

Dysplasia (Flat / Non-Polypoid)

Usual features of dysplasia extending to the surface in the absence of complicating factors

Low grade: cytological features not marked, mitoses normal, architecture minimally disturbed

High grade: marked cytological +/ arch. atypia, abnormal mitoses

May occur within i.m. (goblets may loose polarity) or apart from i.m. but is often assoc

with i.m.

Immuno: p53 nuclear +vity and Ki-67 extending to the surface epithelium favour dysplasia

d/dg (complicating factors): sig. PMN inﬁltrate, foveolar hyperplasia, granulation tissue, ulcer slough

d/dg chemoRx / radioRx atypia shows surface maturation, preserved polarity, cytoplasmic

eosinophilia/vacuoles, microcystic arch. in deeper glands, normal mitoses present in normal distribution

(also p53 −ve & Ki-67 restricted to usual proliferative zones), no i.m. nearby

Adenomatous Polyp (Gastric Adenoma)

Usu. sessile, solitary and antral and may be large (few cm) ± nearby intestinal metaplasia

Arch.: tubular, villous and TV ± underlying non-dysplastic cystic gastric glands

Cytology: mild / moderate / severe dysplasia (criteria are as for colonic adenomas)

± intestinal differentiation (absorptive, goblet, NE and Paneth cells) which may predominate

Invasive foci: single cell inﬁltration / solid areas / back-to-back cribriform areas

Must assess completeness of excision

d/dg hyperplastic / other polyps: presence of dysplasia and intestinal differentiation in adenomas

Gastric Carcinoma: Classiﬁcation, Grading and Typing

Laur´en’s classiﬁcation of gastric carcinoma:

 intestinal (tubules/papillae ± solid foci, cuboidal / columnar cytoplasm, basal nuclei)

 diffuse (inﬁltrative polygonal cells, often signet ring). Signet ring cells usu. have acid mucin

cf. the neutral mucin of benign gastric epithelium hence the use of an ABDPAS for screening

gastric biopsies (! but some signet ring carcinomas have purely neutral mucin).

 mixed / unclassiﬁed (Carneiro’s classiﬁcation is similar but subdivides the unclassiﬁed group

into solid [cords and islands] and mixed [diffuse plus intestinal / solid – the smallest component

being ≥5% of the tumour] subtypes)

Ming’s classiﬁcation of gastric carcinoma:

 expansile margin with discrete nodules (better prog. unless early gastric cancer)

 inﬁltrative (worse prognosis unless early gastric cancer)

Mucin-based (intra and extracellular) classiﬁcations (e.g. intracellular mucin with Goseki):

 mucin poor: better prog. (Goseki group1–well-formed tubules, 3 – poorly-formed tubules)

 mucin-rich: poorer prog. (Goseki group2–well-formed tubules, 4 – poorly-formed tubules)

WHO classiﬁcation:

 by predominant pattern: papillary, tubular, mucinous, signet ring, special types (vide infra)

 widely believed to be prognostically useless