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

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Alimentary Tract 139

Grading: UK National Dataset method is based on the most poorly diff. area as:

 poorly diff: i.e. diffuse / signet ring / non-cohesive tumours

 other: usu. intestinal type / cohesive growth pattern

Grading: WHO method is based on the proportion of tumour composed of glands:

 well diff: >95%

 moderately diff: 50–95%

 poorly diff: <50%

Types of gastric carcinoma other than typical intestinal-type adenocarcinoma:

 signet ring carcinoma (WHO def

requires >50% signet ring type)

 mucinous carcinoma (WHO def

requires >50% mucinous type)

 SCC, ASC, SmCC, ChC, carcinosarcoma and spindle cell carcinoma

 medullary carcinoma (>50% is poorly diff, lymphoid stroma, lack of ﬁbrous tissue)

 anaplastic carcinoma with extensive PMN inﬁltration

 malignant rhabdoid tumour (vimentin +ve)

 hepatoid (bile canaliculi & AFP +ve, typical adenocarcinoma foci elsewhere)

 metastatic (very rare, may be multiple, usu. submucosal centric and arise by lymphatic or

blood spread from: melanoma, breast, thyroid, testis, lung, oesophagus and elsewhere)

Differential Diagnosis of Signet Ring Carcinoma of Stomach (esp. on Frozen Section)

ILC of the breast

Signet ring carcinoma from other 1

◦

sites: e.g. prostate, bladder, cholangiocarcinoma, etc.

Malakoplakia (variant with non-mineralised PAS +ve bodies), muciphages or xanthelasma

Signet ring lymphoma / mesothelioma / melanoma / ovarian stromal tumour / uterine leiomy-

oma/sarcoma / amphicrine MTC, signet ring morphology in CNS tumours (oligodendroglioma and

ependymoma)

Neuroendocrine Pathology of the GIT

The following criteria and terms relate to the upper GIT but some apply them in the colon also

Hindgut (rectosigmoid) carcinoids are different. They arise in the submucosa, are usu. trabecular and

poor prognostics are: invasion of muscularis propria, size >1 cm (add esp. if >2 cm), lymph/blood

vasc. invasion, tumour ulceration, mitotic count.

d/dg includes glomus tumour, paraganglioma and adenocarcinoma

NE cell hyperplasia

Def

: ↑ numbers of NE cells within a pre-existing gland / crypt:

Conﬁned to the mucosa (by deﬁnition)

May be linear or nodular with nodules no wider than the width of a normal gland / crypt (sometimes

called ‘micronodules’ hence ‘micronodular hyperplasia’)

Each nodule surrounded by BM

Adenomatoid hyperplasia =≥5 micronodules close to each other with interposed BM

NE Cell Dysplasia (= pre-carcinoid)

Fusion of micronodules with loss of intervening BM

Micronodules enlarge beyond the size of a normal gland / crypt

Total size >0.15 mm but <0.5 mm in max. 

± Cytological atypia

± Microinvasion of the lamina propria

Microcarcinoid (= Tumourlet)

Def

: NE-proliferation >0.5mm , the upper measurement limit is not deﬁned but it must be conﬁned

to the mucosa and not macroscopically (clinically / endoscopically) visible

Carcinoid

Def

: a well diff. NE-proliferation >0.5mm  which either:

◦

invades the muscularis mucosae or

◦

is large enough to be macroscopically visible (clinically / endoscopically).

The following is a guide to aggressiveness but the terms ‘benign’, ‘borderline’ and ‘malignant’ are best

avoided since all carcinoids are potentially malignant

‘Benign’: <1cm , no angioinvasion, tumour limited to mucosa / submucosa

‘Borderline’: either

◦

<1cm with angioinvasion but limited to mucosa / submucosa or

◦

1–2cm, no angioinvasion, limited to mucosa / submucosa

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Mucinous carcinoid / goblet cell carcinoid: more aggressive cf. other carcinoids and is probably a form

of argyrophil adenocarcinoma (for details, see ‘Appendix’, p. 152)

Atypical carcinoid: any of the following:

◦

necrosis (usu. punctate, not extensive)

◦

mitoses >2/10 hpf

◦

cytological atypia (e.g. prominent nucleoli)

‘Malignant’: any of the following:  functioning tumour (NE peptide effects)

 1–2cm with angioinvasion

 >2cm without angioinvasion

 invades the muscularis propria or beyond

Types of upper GI / gastric carcinoid

Any type of carcinoid may have a sub-population of cells expressing any other NE peptide

The four main types of NE cell (and tumours) in the stomach / upper GI are:

◦

ECL-cell (histamine, 5-HT or no product in carcinoids):

 proliferate in response to hypergastrinaemia (any cause)

 d/dg EC-cell: ECL-cell is +ve for VMAT-2, CgA, Grimelius; −ve for serotonin and argentafﬁn

 gastric ECL-cell carcinoids occur usu. in the proximal stomach and are typed as:

Type I: assoc

with ↑gastrinaemia 2

◦

to chronic atrophic gastritis



usu. multiple, small & arise on a

Type II: assoc

with ↑gastrinaemia without atrophy e.g. MEN 1/ZE background of ECL-cell hyperplasia

Type III: sporadic and more likely to be solitary & show features of malignancy / atypia (vide supra)

◦

EC-cell (serotonin) tumours occur in the distal duodenum, acinar pattern

◦

G-cell (gastrin) proximal duodenum, trabecular, may cause ZE syndrome, ± MEN-1

◦

D-cell (somatostatin) → somatostatinoma (50% have NF-1):

 periampullary, glandular/acinar pattern, psammoma bodies

 immuno/stains: somatostatin +ve, ! CgA / Grimelius may often be negative

 d/dg: well diff adenocarcinoma (! esp. on FS) but somatostatinoma has low grade NE nuclei,

low/absent mitoses & somatostatin +ve immuno

Gastrointestinal Stromal Tumour (GIST)

Occur in any part of GI tract (and 7% are extra GI: mesenteric ones have worse prog. cf. omental)

Spindle cell type:

 variable cellularity

 interlacing bundles / whorls of uniform spindle cells with blunt nuclei

 ± paranuclear vacuole

 ± multinucleated ‘wreath’ cells

 ± prominent vascularity

 ± neural features (e.g. palisaded nuclei)

 ± skeinoid ﬁbres (extracellular globoid / curvilinear collagen aggregates)

 stroma may be hyaline or myxoid

 ± foci of liposarcoma / chondrosarcoma / RMS

Epithelioid type:

 sheets / nests

 rounded / vacuolated / clear / epithelioid / plasmacytoid cells

 variable nuclear atypia to (very rarely) frank pleomorphism with large nucleoli

 ± multinucleated tumour cells

 thought to have worse prognosis cf. spindle type but is indolent if part of Carney triad

Gastrointestinal autonomic nerve tumour (GANT):

 a non-myogenic GIST of either spindle / epithelioid type

 diagnosis depends on ultrastructural features (processes, synapses, vesicles, etc.)

 often has peritumoural lymphoid inﬁltrates (similar to some deep Schwannomas)

 possibly worse prog. cf. other GISTs but no longer necessary to separate out this sub-type

Immuno +ve: c-kit (membrane accentuation), DOG-1 (useful for CD117 −ve GIST – some of these

also respond to Glivec



), CD34, CD171 (in 75%); nestin, (± neural +/ smooth muscle markers),

PDGFR (as for DOG-1 but also +ve in 25% of desmoids)

Carney triad =

◦

epithelioid GIST,

◦

pulmonary chondroma and

◦

non-adrenal paraganglioma

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d/dg (c-kit [CD117] is +ve in many things – see also p. 16 – do not use Ag retrieval):

 leiomyoma / sarcoma: c-kit −ve, CD171 −ve, desmin +ve,ERmaybe+ve (−ve in GIST)

 cellular Schwannoma of the GIT

/ MPNST: c-kit −ve, S100 +ve; nestin & CD171 rarely +ve

 ﬁbromatosis: c-kit +ve (but with cytoplasmic blob [myoﬁbroblast] pattern not membranous),

PDGFR ±ve, CD171 & CD34 −ve; (! don’t mis-call a post-op desmoid ‘recurrent GIST’)

 inﬂammatory ﬁbroid polyp: CD34 +ve (like GIST), eosinophils (see p. 138)

 SFT: triad of CD99, Bcl-2, CD34 +ve; some are also c-kit +ve (see p. 324)

 spindle cell carcinoma and mesothelioma: CK +ve (rare in GISTs) and −ve for c-kit and CD34

 glomus tumour (vs. epithelioid GIST) – see pp. 285–286

Prognosis (NB: it is good practice never to report a GIST as ‘benign’):

 good prognostics are:  spindle type with only smooth muscle markers

 any type with only neural markers

 <1cmand incidental ﬁnding (these may be truly benign)

 gastric or omental site

 bad prognostics are:  frank invasion (= malignant, whatever the mitotic count / size)

 recurrence after Rx: abdominal cavity and liver commonest sites

 pleomorphism is irrelevant to prognosis in epithelioid tumours

 grading ∝ size and mitotic count but SI GISTs may be more aggressive for any given size

 any tumour >10cm or with >10/50 hpf mitoses is high risk (see Figure 11.2)

 if it has >20–50 mitoses / 50 hpf it is considered very high grade

(< 5 cm)

(< 2cm)

0510

very

low

intermediate

high

Mitotic Count (per 50 hpf)

Size of maximum dimension (cm)

FIGURE 11.2 GIST risk groups.

Based on Fletcher et al. 2002 and Wong

et al. 2003.

Lymphoma

See also Chapter 10: Lymphoreticular.

Small intestinal MALToma:

 LEL are less prominent & DLBCL transformation more common (cf. gastric)

 multifocality and stage are important prognostics

 solid sheets of blasts = DLBCL (Bcl-2 & p53 may be prognostic)

Others: EATL, IPSID, EBV-assoc

high grade B-cell (HIV / PTLD), Burkitt’s, FCL

in general, anywhere in the alimentary tract, heterotopias are distinguished from metaplasias by the presence of gastric parietal or

chief cells or pancreatic acinar cells or adrenocortical cells

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Post-Colectomy Ileitis (= Pre-stomal ileitis or Neoterminal ileitis)

Occurs months to years post colonic surgery (for UC, colonic carcinoma or other causes), FM

Wall thickening ± stricture

Patchy variable acute and chronic inﬂam

± ulcerat

, ﬁssures and TLA but no granulomas or bugs

d/dg Crohn’s disease: but in post-colectomy ileitis there is a history of colectomy, CPC and review

of past specimens conﬁrms UC or show no evidence of Crohn’s, granulomas are absent and TLA are

limited to areas of deep mucosal ﬁssuring/activity

CIBD

Duodenum: focal aggregates of PMN in the l.p. and epithelium may be the only sign in Crohn’s

TI: patchy active inﬂam

and UACL are typical of Crohn’s and strongly favour Crohn’s over UC

TI: the ‘backwash ileitis’ of UC occurs with right-sided UC and shows diffuse superﬁcial activity (no

erosions or deep ulcers and no UACL) – it is not a contraindication to the formation of a pouch.

Lower GI

Infective Colitis

General bacterial colitis

Oedema

Mild to moderate inﬂammation, PMN dominant

Inﬂammation tends to be more superﬁcial in the mucosa and surface epithelium

Cryptitis with preserved architecture (except amoebic colitis)

Beaded crypt absceses (‘string of pearls’ sign)

Crypt withering (also seen in radioRx effect and ischaemia)

Microgranulomas (≥ 5M) away from inﬂamed crypts – esp. in Salmonella / Campylobacter

Haemorrhage

Tufting of surface epithelium (may be antibiotic-related)

Resolution (i.e. it goes away on F/U)

Entamoeba Histolytica

Crypt distortion

‘Flask-shaped’ ulcers (have overhanging edges)

Amoebae have pale-staining spherical nuclei (unlike M nuclei that are darker and bean-shaped)

Amoebae have engulfed RBC (unlike non-pathogenic Entamoeba coli)

Amoebae stain magenta with DPAS – sensitive method to detect them – and are CD68 –ve

d/dg carcinoma (macro / radiology) and UC (histology)

Clostridium difﬁcile

(Pseudomembranous Colitis)

Multiple discrete foci of disrupted crypts

Affected crypts are dilated superﬁcially

A ‘volcanic spray’-like exudate forms a ‘mushroom cloud’ pseudomembrane of cellular debris, ﬁbrin,

mucus and inﬂam

cells (! similar exudate can occur in SRUS – need to see underlying mucosa)

Intervening mucosa is normal

d/dg ischaemic colitis, severe CIBD / defunctioned UC, CMV, Shigella, E. coli, (rarely) acute CC

d/dg PMC may also be caused by drugs, e.g. gold, not just antibiotic-assoc

C. difﬁcile infection

Chronic idiopathic Inﬂammatory Bowel Disease (CIBD)

Common pitfalls in diagnosis

Pericryptal cells (pseudogranulomas)

Muciphage collections (pseudogranulomas)

Cryptolytic lesions (foreign-body-type granuloma adjacent to a crypt that has spilled its mucin) seen in:

UC, diversion colitis, pouchitis, diverticular disease-assoc

colitis, etc.; usu. in superﬁcial l.p.

Isolated crypt abscesses (can be seen adjacent to focal lesions / other situations)

Branching crypts (seen at normal innominate grooves and in any situation of regeneration / growth)

Normal chronic ‘inﬂam

’ and NE cells of the caecum; normal rectal NE cells (vs. NE cell hyperplasia)

‘Atrophy’ at the anorectal margin (normal histology)

Infective colitis (esp. amoebic / CMV)

NB: difﬁcile is a Latin word of four syllables (di-ﬁ-chi-lay) – not French

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Alimentary Tract 144

Ischaemic colitis

Beh¸cet’s, peritumoural and diverticular disease-associated colitis (esp. d/dg Crohn’s disease)

Post-colectomy ileitis (!do not call it Crohn’s disease in a patient with established UC) – see p. 143

Diversion reaction / colitis

Ileoanal pouch changes

Drug-induced colitis e.g. bowel prep colitis (esp. d/dg Crohn’s) or cholestyramine / polystyrene

colitis

Failure to correlate clinical information and macroscopic appearances / distribution with histology

Per-operative diagnosis of CIBD (incl. FS)

Used during some ileoanal pouch-forming procedures because Crohn’s disease is a contra-indication

Determine: Crohn’s disease / UC / don’t know (not ‘indeterminate colitis’ q.v.)

Macro appearances at surgery helps (see macro features of Crohn’s disease and UC, below)

FS from:  the largest LN – granulomas? (be wary of pitfalls and acceptable criteria)

 full-thickness lesional bowel – characteristic features present?

 full-thickness ‘normal’ interlesional bowel – is disease truly patchy?

Ulcerative Colitis (UC)

Macro:  diffuse involvement of diseased colon from distal to proximal (± backwash ileitis)

 speciﬁc skip lesions can occur (appendix & caecal patch) ± rectal sparing if treated

Micro (mucosal):

 crypt distortion (!beware of nearby causes e.g. ulcers, lymphoid aggregates, innominate

grooves)

 surface villosity

 chronic inﬂam

: diffuse throughout the full thickness of the mucosa and length of the Bx and

continuous throughout the involved segment (except with the UC skip lesions vide supra);

tends to be worse distally

 acute activity (PMN in the 1.p [esp. if >100 per mm] / cryptitis / crypt abscesses): this is

diffuse but patchiness can occur

◦

at the junction of involved and uninvolved bowel and

◦

cases of treated UC

 mucin depletion (associated with activity, weak feature)

 cryptolytic granulomas and muciphage collections may be seen in UC

 quiescent UC:  the lamina propria may be hypocellular

 distortion and atrophy (crypt bases do not reach the m.m.)

 NE cell hyperplasia and Paneth cell metaplasia

 patchiness of disease severity is OK for UC (as opposed to patchiness of disease presence in

Crohn’s) as not all sites may be at the same degree of severity of inﬂam

. Finding quiescent

UC in between two active biopsies is OK. Finding completely normal bowel in between two

diseased biopsies is not (consider Crohn’s or other d/dg, however, fulminant UC may be patchy

with rectal sparing)

 the rectal mucosa in UC may return to histological normality esp. after Rx .

. a normal rectal

Bx does not exclude UC

Micro (transmural / resection): diffuse inﬂammation can occur transmurally at sites of ulceration

Crohn’s disease

Macro:  SI involvement ± colon favours Crohn’s (but isolated Crohn’s colitis is possible)

 fat-wrapping, serosal exudate, thickening of bowel wall, strictures, ﬁstulae

 skip lesions, ﬁssures, snail-track ulcers, cobblestone mucosa, etc.

 Abnormalities are worst on the mesenteric aspect

Micro (mucosal Bx ± submucosa):

 there is less crypt distortion and less mucin depletion (cf. UC)

 patchiness of inﬂam

– both acute and chronic, both within and between biopsies, esp. sin-

gle crypt abscesses ﬂanked by normal crypts. Completely normal intervening biopsies in a

series

 epithelioid granulomas, esp. when multiple, small (<200), between crypts and abutting the

muscularis mucosae (d/dg infective microgranulomas, cryptolytic lesions, pseudogranulomas)

 patchy lamina propria ﬁbrosis and oedema (d/dg ischaemia which is favoured by mucosal

capillary telangiectasia and siderophages – but these are not always seen)

 disproportionate submucosal inﬂam

(not assoc

with an ulcer)

 the typical Crohn’s aphtha begins at the crypt base as a triangular (‘mountain-top’) ulcer

pointing upwards sending a stream of PMN up the crypt and often overlying a lymphoid

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aggregate (see Figure 11.3). Fissures

develop as continuations of the angles

at the base of the ulcer. The adjacent

mucosa is normal. It is useful in d/dg

UC but is not speciﬁc for Crohn’s.

Micro (transmural / resection):

 inﬂam

is transmural with patchy dis-

crete lymphoid aggregates, seen esp.

running along serosa

 granulomas (following lymphatics) are

found in two-thirds of cases; ± granulo-

matous lymphovasculitis

 ﬁbrosis and oedema (±submucosal lym-

phangiectasia & neuronal hyperplasia –

not seen in UC – ± perineural chronic

inﬂam

)

 deep ﬁssures (esp. if narrow, lined by

inﬂam

and arising from the base of

Crohn’s-like aphthae)

 well-formed, sarcoid-like epithelioid

granulomas in draining lymph nodes

help establish the diagnosis esp. in per-

operative frozen section

d/dg TB is favoured by conﬂuent granulomas,

caseous necrosis or ≥10 granulomas per Bx

d/dg Crohn’s-like reaction (macro & micro) lim-

ited to a DD segment or peritumoural

d/dg idiopathic granulomatous appendicitis: only the appendix is affected, no other signs of Crohn’s

d/dg Beh¸cet’s colitis: deep/perforating ileocaecal ulcers or colitis histologically identical to Crohn’s

d/dg focal inﬂam

may occur in inﬂam

polyps or anastomotic lines and does not favour Crohn’s

FIGURE 11.3 Crohn’s aphtha

Indeterminate Colitis (IC)

Only diagnose when small bowel disease has been excluded clinically and whole colon sampling is

available (colectomy or multiple biopsies)

Using CPC and Bx ﬁndings try to qualify IC with a probable aetiology: UC, Crohn’s (subserosal

lymphoid aggregates unrelated to ulcers or gross skip lesions), other (e.g. infective / obstructive),

unknown

IC should be considered a temporary diagnosis pending F/U whenever possible

Acute type IC

A conﬁdent pre-op Bx diagnosis of UC should not be overruled by indeterminate resection ﬁndings

Macro:  usu. acute severe segmental colitis affecting the middle 1/3 of the colon

 ulceration ± extensive denudation ± toxic megacolon

 ± transverse ﬁssures

Micro:

 non-cryptolytic/non-foreign-body granulomas exclude IC (esp. if beyond the mucosa)

 undermining ulcers with adjacent mucosa showing normal / minimal architectural or inﬂam-

matory response (pronounced and diffuse architectural distortion favours UC)

 ﬁssuresmaybe transmural but are ‘V’-shaped (cf. thinner in Crohn’s disease) and showminimal

adjacent inﬂam

(more prominent in Crohn’s)

 myocytolysis with capillary engorgement in paraﬁssural muscularis propria

 transmural inﬂam

is diffuse (cf. aggregates in Crohn’s) and restricted to areas of severe

ulceration

Non-acute type IC

A conﬁdent endoscopic / pre-op Bx diagnosis should not be overruled by subsequent IC ﬁndings

Micro (if normal colonoscopy): abnormalities not sufﬁcient for diagnosis of microscopic colitis

Micro (if abnormal colonoscopy): features not diagnostic of a speciﬁc colitis e.g. UC, Crohn’s, drugs,

ischaemia, infection, diverticular disease-assoc

colitis, etc.

d/dg non-speciﬁc colitis (vide infra)

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Alimentary Tract 146

Non-Speciﬁc Colitis and Focal Active Colitis

Only diagnose non-speciﬁc chronic colitis if:

 you can’t suggest even a probable aetiology and

 features similar to IC (Non-Acute) but IC is not diagnosable due to limited sampling

Diagnosis should come with a recommendation for F/U or further investigation

Focal active inﬂam

with no other abnormality (= focal active colitis), incl. no evidence of chronicity

(unlike non-speciﬁc colitis) is also non-speciﬁc and may be due to infection, drugs, ischaemia, etc.

Microscopic Colitis (Lymphocytic Colitis [LC] / Collagenous Colitis [CC])

Prolonged watery diarrhoea with (nearly) normal endoscopy. Assoc

with coeliac disease

Transverse colon (cf. sigmoid) may be the most sensitive Bx site for diagnostic features

Lymphoplasmacytic inﬁltrate of the lamina propria

Epithelial damage (ﬂattening, detachment, ↑lymphocytes (≥20 per 100 enterocytes in LC)

Collagen band (strands parallel to the lumen, 7–90 thick, may contain vessels) – in CC only (! may

also get collagen band in other things e.g. metaplastic polyps – so use multiple criteria, as usual)

PMN may be seen in LC / CC (some say that mild crypt distortion is also allowed)

d/dg PMC vs. severe acute CC (quite rare, use CPC)

d/dg amyloidosis vs. CC: surface epithelial damage in CC; CR +vity & CPC in amyloid

Diverticular Disease-Associated Colitis

Four main types occur (possibly together):

◦

lumenal narrowing → obstructive colitis proximal to the diverticular disease (DD) segment

◦

impacted stools → localised ischaemia (= crescentic fold colitis)

◦

more diffuse inﬂam

affects the whole DD segment – segmental colitis

◦

redundant fold prolapse → inﬂammatory myoglandular polyp-like change (≈ ‘cap polyp’)

Mild forms of crescentic fold and segmental colitis show:  mild diffuse chronic inﬂammation

 surface pus / erosions

 normal architecture

Severe forms can mimic CIBD with gland distortion, crypt abscesses, TLA, etc.

d/dg CIBD:

 DD colitis tends to be around the mouths of the diverticula, sparing the intervening mucosa

 UC or Crohn’s affecting only the sigmoid is unusual

 TLA in DD colitis tend to radiate out from an affected diverticulum unlike Crohn’s

Obstructive Colitis

Varies from mild superﬁcial ulceration to severe (resembling indeterminate colitis)

Haemorrhage and congestion in adjacent mucosa

The 2–3cm of mucosa immediately proximal to the obstruction is spared

Ischaemia

Acute changes include ulceration and haemorrhagic necrosis starting with the most superﬁcial layers

of the mucosa (earliest changes) to deeper (with more prolonged / severe ischaemia)

Long term ischaemia: stromal haemosiderosis and changes similar to d/dg chronic radiation enteritis

(q.v.) but without the atypical stromal ﬁbroblasts and vessel wall damage

Amyloid

Usu. 2

◦

(to Crohn’s, RhA, etc.)

d/dg collagenous colitis (vide supra): lack of surface epithelial cell damage goes against CC

d/dg collagen in systemic sclerosis / myopathies in the muscularis propria (do CR / SAP immuno)

Endometriosis

Endometrial glands and stroma (do CD10 if necessary) – unlike d/dg colonic carcinoma

May inﬁltrate all layers the bowel wall

May give radiological and clinical features suggestive of malignancy

! d/dg carcinoma – overcalling endometriosis as carcinoma is the main danger

d/dg SRUS

d/dg colitis cystica profunda (but endometrial glands are not mucinous)

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d/dg Crohn’s (clinically, due to adhesions, deformity and ﬁbrosis with PR bleeding of endometriosis)

d/dg ischaemia (due to intermittent bleeding and pain and ﬁbrosis with haemosiderin on histology)

Diversion Proctocolitis

Lymphoid hyperplasia and diffuse chronic inﬂammation = diversion reaction

+ Aphthae and acute inﬂammation = diversion colitis

Lumenal narrowing and thickening of the submucosa and muscularis propria



do not imply

± Occ. well-formed mucosal epithelioid granulomas (controversial) Crohn’s

Microcarcinoids

Involution (if severe may preclude re-anastomosis):

 excessive adipose inﬁltration of submucosa and muscularis propria

 mucosal atrophy

Normal architecture unless prior CIBD

UC / indeterminate colitis:

(get worse after diversion)

 transmural lymphoid aggregates .

. a diagnosis of Crohn’s must not

 ﬁssures



be based solely on the histology

 granulomas (incl. in LN) of the defunctioned rectum

 pseudomembranous colitis (PMC)

Crohn’s disease:

(gets better)

 ↑ ﬁbrosis

 granulomas hyalinase (± Schaumann bodies)

Ileal Reservoirs and Pouchitis (= Chronic Relapsing Acute Pouchitis)

↑Chronic inﬂam

& a degree of crypt hyperplastic villous atrophy is normal but

Subtotal villous atrophy (colonization

= Type C mucosa) is a minor risk factor for dysplasia →F/U

Active pouchitis clinical: diarrhoea, blood, pain, contact bleeding on endoscopy

Active pouchitis histol.: acute inﬂammation, surface erosion and focal superﬁcial ulceration – UC-like

d/dg exclude: infection, prolapse, ischaemia (i.e. ischaemia as a 1

◦

cause of the pathology [e.g. due to

surgical complications])

d/dg Crohn’s disease:

 any single feature of Crohn’s may be present in the pouch without Crohn’s being the cause

of it:

 granulomas (esp. in lymphoid follicles) – but granulomas in SI beyond the pouch

favour Crohn’s

 vertical ﬁssures (usu. seen in relation to ruptured deep crypt abscesses / anastomoses)

 ﬁstulae (e.g. colovesical)

 .

. a ﬁrst diagnosis of Crohn’s should never be made on pouch histology alone

St Mark’s pouchitis score (score acute and chronic features separately) – based on Shepherd et al.

(1987) – see table 11.1:

TABLE 11.1 St Mark’s pouchitis score

Acute: (add PMN and ulceration scores to get a total score out of 6)

Score PMN Infiltrate Ulceration

0 absent absent

1 (mild) restricted to surface epithelium and focal

superﬁcial

2 (moderate) + crypt abscesses (occasional)

3 (severe) + crypt abscesses (numerous) widespread & deeper

Chronic: (add chronic inﬂammatory cell and atrophy scores to get a total score out of 6)

Score Cellular Infiltrate Villous Atrophy

0 normal normal architecture

1 (mild) focal minor anomalies

2 (moderate) partial

3 (severe) more extensive subtotal

∗

‘restricted to surface epithelium’ includes cryptitis

Melanosis Coli (Pseudomelanosis)

Lipofuscin 2

◦

to chronic apoptosis

Anthraquinones, NSAID, etc.

d/dg haemosiderosis (ischaemia) and brown bowel syndrome (muscle)

‘colonization’ (colonic phenotypic change) also connotes a change in mucin type to colonic

JWBK208-11 December 8, 2007 16:3 Char Count= 0

Alimentary Tract 148

Drug Reactions (incl. NSAID)

PMC or acute self limiting colitis (e.g. with antibiotics)

Ulceration ± superﬁcial PMN inﬁltrates

Melanosis / Microscopic colitis

Ischaemia (incl. stricture & diaphragm disease)

Crypt apoptoses

Eosinophil inﬁltrates

Speciﬁcs:  Bowel Prep Colitis: focal proximal active colitis (d/dg Crohn’s)

 Cholestyramine or Polystyrene sulphonate: can mimic CIBD (ZN +ve crystals)

 Barium Granuloma: blue-grey / light green ‘foamy’ Mφ with birefringent crystals

(stain red with rhodizonate – as does Pb, Zn, Sr and Hg)

Chemotherapy / Radiation

NB: vitamin B12 / folate deﬁciency show similar cytological atypia to chemoRx changes

Early changes

Ulceration and mucosal necrosis

Apoptoses

Epithelial cells may show a syncytial-like appearance

Marked cell enlargement with nuclear atypia d/dg dysplasia / carcinoma:

 gland architecture is preserved

 nuclear abnormalities too bizarre for neoplasia forming such good glands

 NCR not markedly increased (esp. given degree of nuclear atypia)

 cytological atypia also present in surrounding endothelial and stromal cells

 no mitoses (except in normal numbers and in their normal locations)

 no inﬁltrative growth

Later changes

Chronic ulceration

Fibrosis / stricture / adhesions



d/dg Crohn’s disease (! in this regard note that there have

± Chronic inﬂam

in lamina propria been case reports of radiation-assoc

granulomas)

Hyaline ﬁbrosis of the lamina propria

Crypt loss (and ‘withering’) with single large dark crypts standing out (regenerative hyperplasia)

Radiation ﬁbroblasts (plump, vesicular nuclei, binucleate forms, etc.)

Colitis cystica profunda is also assoc

with radioRx

Vascular changes: ectatic capillaries, endarteritis obliterans, foamy M accumulation with hyaline

change in vessel walls

Squamous Metaplasia in the Rectum (causes)

Upgrowth from the anus 2

◦

to distal rectal ulceration

Repeated self-induced trauma by insertion of foreign objects

Radiation-induced

Persistent chronic inﬂammation (e.g. in UC)

Common Variable Immunodeﬁciency (CVID)

Lack of plasma cells in l.p., ± Cryptosporidia, etc., ± MALToma

± Nodular lymphoid hyperplasia ± granulomas. See p. 351 for more detail.

Graft vs. Host Disease (GVHD)

In the ﬁrst 3 weeks post BMTx it is impossible to differentiate from pre-BMTx chemoRx changes

Apoptoses in basal enterocytes, chronic inﬂammatory cells are few

± More extensive necrosis and ulceration and PMN

Crypt loss with NE gravestones and regenerative crypt distortion

Fibrosis of lamina propria (helps to distinguish from d/dg UC) ± transmural ﬁbrosis

d/dg: ↑apoptoses of crypts is also seen in HIV, CMV, drugs / viruses, chemoRx, radioRx

Angiodysplasia (of Upper or Lower GIT)

Ectatic veins in the submucosa (may extend through to subserosa and become conglomerated)

Communicate with ectatic capillaries in l.p. (not always seen but diagnose with caution if not seen)

Arterial component seen if severe (but diagnosis should not be made in those with angiomas)

Bleeds are assoc

with age, true diverticula (those with all muscle coats), aortic stenosis, etc.