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

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Skin 299

Granuloma annulare (GA)

Plasma cells, palisaded M and lymphocytes around necrobiotic collagen

Dermal mucin +ve; giant cells are rare

Variants: perforating (superﬁcial), subcutaneous, diffuse (seen in DM)

Rheumatoid nodule

Like GA but larger and deeper

Usu. only found in seropositive cases of RhA (.

. check CPC before diagnosing it)

Paraprotein-associated xanthogranuloma with necrobiosis

Xanthogranulomatous inﬂammation separated by necrobiotic collagen

May extend deep (clin d/dg incl. Weber-Christian disease)

Urticaria

Clinically ‘hives’

Perivascular oedema (easiest to see in superﬁcial vessels cf. deep)

Telangiectasia (incl. ↑ lymphatic channels)

Later get a sparse perivascular inﬂam

cell inﬁltrate (eos. ± PMN early → mononuclear later)

Urticarial Vasculitis

Like urticaria but with evidence of vasculitis

Subtle vasculitis (leukocytoclasia and ﬁbrinoid change)

d/dg: consider CTD esp. LE, RhA

Cuteneous Mastocytosis

Incl.: urticaria pigmentosa, maculopapular and diffuse cutaneous mastocytosis, solitary mastocytoma

Infantile: lightly pigmented macules, regress; Adult: more pigment ± telangiectasia, no spontaneous

regression, systemic involvement common. May present as bullous lesions

Epidermis: ↑pigmentation of the basal layer

Papillary dermis: mast cells (some spindled) may form sheets / nodules / perivasc. cuffs ± eosinophils

Nodular lesions may extend to subcutis (typically in solitary mastocytoma)

Superﬁcial lymphohistiocytic inﬁltrate (esp. adults)

Variant: bullous mastocytosis – subepidermal split with festooning

Actinic Reticuloid

Chronic photodermatitis of elderly men. Reversible. Pruritic, thick, red skin (d/dg MF)

Multinucleated stellate myoﬁbroblasts (may be worrying) ± granulomatous inﬂam

Actinic damage and mixed, deep dermal inﬁltrate incl. eosinophils.

Lymphocytes may be atypical (d/dg MF)

Psoriasiform acanthosis, little epidermotropism, ± Pautrioid collections (d/dg MF)

Lymphomatoid Papulosis (LyP)

Clin.: M>F, 30s, continuing eruption of self-healing ulcerating papules

Histology looks like a lymphoma:

 dense inﬁltrate of atypical lymphocytes that are:

 epidermal ulceration / necrosis

 vascular endothelial proliferation

Willemze type: A) large cells, moderate-abundant cytoplasm, RS-like (CD30 +ve), mixed cellularity

B) more monomorphic S´ezary/MF-like cells with occasional large cells

C) like A but anaplastic lymphoma histol. (sheets of large cells, less mixed cellularity)

lichenoid superﬁcially

perivascular deeply

wedge-shaped rarely

Granuloma Faciale

Dense (band-like and perifollicular) superﬁcial mixed inﬂam

cell inﬁltrate with Grenz (clear) zone

Nuclear dust

One of the ‘ﬁbrosing vasculitis’ group (includes erythema elevatum diutinum – EED)

d/dg erythema elevatum diutinum: EED has more PMN and dust (i.e. a frank LCV is more obvious),

has less of a Grenz zone and is dapsone sensitive

d/dg isolated ﬁbrosing vasculitis: this may be present without either granuloma faciale or EED

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Skin 300

Pernio (Chilblains)

Papillary dermal oedema and superﬁcial and deep lymphocytic vasculitis 2

◦

to cold exposure

Lupus Pernio

Sarcoid of the skin of the face

d/dg acne rosacea (= granulomatous reaction around vellus hair follicle infundibulae)

Sweet Syndrome (Acute Febrile Neutrophilic Dermatosis)

Clin.: red plaques ± pustules assoc

with resp. infection, pregnancy, AML, other cancers, etc.

Papillary dermal oedema (± vesiculation)

Band of reticular dermal PMN with leukocytoclasia ± RBC extravasat

but no frank vessel damage

Later mononuclear cells become more numerous

d/dg: pyoderma gangrenosum, cellulitis, dermis near abscess/folliculitis, granulomatous vasculitides

Pustules in the Skin

Intraepidermal: subcorneal pustular dermatosis, bullous impetigo, drugs, psoriasis, HSV / VZV

Intradermal: pustular contact dermatitis, pustulosis palmaris et plantaris, pemphigus vegetans

Caseation in the Skin

Lupus miliaris disseminatus facei – caseating dermal granulomas (may be assoc

with TB)

Bazin disease – calves of adolescent girls with a positive tuberculin test

TB (! d/dg granulomatous rosacea may have necrotising or sarcoidal granulomas focally as a reaction

to sebaceous material)

Deposits in the Skin

Amyloid

Lichen amyloidosus: itchy, raised rash, rare in Caucasians; epidermal hyperplasia, mild chronic inﬂam

± pigmentary incontinence, amorphous small amyloid globules in the papillary dermis, ± basal vac-

uolar change, ± dyskeratoses; d/dg: lichen simplex chronicus, colloid milium, hyalinoses

Macular amyloidosis is similar to lichen amyloidosus but without epidermal hyperplasia

◦

localised nodular amyloidosis: larger masses in the dermis or around vessels

Colloid milium

Clin: sporadic (elderly, actinic) or familial (young, hyalinosis); 1–2mm semi-translucent papules

Rounded cracked hyaline masses in the superﬁcial dermis, may stain like amyloid (d/dg is clinical)

Calcium

Calcinosis cutis: amorphous mass of calciﬁc material ± giant cell reaction at periphery. Look for

underlying CTD / other cause of dystrophic Ca

before calling it ‘idiopathic’. Idiopathic scrotal

calcinosis is a subtype that may show the remnants of an epidermal cyst lining in serial sections

Calciphylaxis: serious necrotising lesion of dermis and subcutis usu. assoc

with ↑PTH/CRF and caused

by ﬁbroblastic endarterial occlusion of small and medium-sized vessels with Ca

in their walls

Elastic

Elastic globules (blue autoﬂuorescence in UV light) may be a normal ﬁnding in some circumstances

Actinic elastosis (may have a giant cell response = annular elastolytic giant cell granuloma)

Hyalinoses / metabolic disorders

Pattern may be globular, vascular, or extensive dermal deposits of a variety of materials e.g. familial

amyloid, Russell and colloid bodies, colloid milia, ﬁbrinoid, cryoglobulins, BM material (porphyrias)

Massive cutaneous hyalinosis: deep dermal and subcutis nodules composed of monoclonal  light

chains but not in amyloid form

Juvenile hyaline ﬁbromatosis: d/dg keloid in children

Gout: uric acid deposits (may dissolve out of sections)

Dermal mucins: myxoedema, LE, scleroedema, etc.

Cutaneous Leishmaniasis

May see an ulcerating granulomatous lesion extending deeply (± ﬁbrinoid necrosis)

± Little double-dots in the macrophages (esp. on Giemsa – see Chapter 23: Infection and Immunity)

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Skin 301

Morphoea / PSS

Early: endothelial swelling and a lymphoplasmacytic inﬁltrate (perivascular, peri-eccrine and at dermo-

subcutis junction) with horizontal ﬁbroplasia of mid and deep dermis

Later: scarring (loss of rete) and adnexal atrophy, no mucin, pilosebaceous units are usu. absent

In late stages inﬂam

is sparse but may persist at the periphery of the lesion / around eccrine coils

May affect subcutis (as a sclerotic septal panniculitis)

d/dg scleroedema, scleromyxoedema / lichen myxoedematosus (vide infra)

d/dg lichen sclerosus: band-like inﬁltrate, epidermal basal lamina damage, site (see p. 215)

d/dg scarring (traumatic): consider the history, cellularity ± haemosiderin / foamy M

Eosinophilic fasciitis (Shulman’s syndrome)

Clin. diagnosis: PB eosinophilia, skin lesions (spare the face) ± pain. Also seen with the L-tryptophan

eosinophilia-myalgia syndrome. Morphoea profunda is clinicopathological overlap (usu. ANA +ve)

Mixed chronic inﬂam

of the deep fascia ± skeletal muscle

May expand the intralobular septa of subcutis and involve the deep dermis

Variable eosinophils (may be absent, not required for diagnosis) and plasma cells (esp. perivascular)

Scleromyxoedema / Papular Mucinosis (Lichen Myxoedematosus)

Scleromyxoedema has papules and conﬂuences while papular mucinosis has only papules

Assoc

with paraprotein / monoclonal gammopathy

Mucin in upper third of the dermis

↑ Mast cells and ﬁbroblasts

Scleroedema (= Scleredema)

Clin.: adults, upper back, non-pitting woody thick skin; post URT infection / assoc

with DM

↑Collagen (hypocellular) of normal pattern and with interspersed mucin (subtle) ±trapped adipocytes

d/dg morphoea / PSS: scleroedema has mucin and no scarring (rete ﬂattening, adnexal atrophy)

d/dg nuchal-type ﬁbroma: same histology but more localised; esp. on back of neck ± Gardner’s

medium-sized vessels also involved

subcutis as well as dermis involved

Leukocytoclastic Vasculitis (LCV)

Clinically ‘palpable purpura’ in dependent areas (limbs / buttocks); associated with

Malignancy

Autoimmune disease

Infection

Drugs/viruses

Immune complex mediated acute vasculitis of dermal venules

PMN in vessel wall and karyorrhexis ± RBC extravasation / haemosiderin

Usu. no systemic vasculitis except with Henoch-Sch¨onlein purpura (= arthralgia, GI bleeds, GN)

Direct IF: IgG and C3 in vessel wall, but immuno may be −ve in old lesions (> 24h)

Thrombosis and ﬁbrinoid necrosis (NB: seborrhoeic dermatitis can give leukocytoclasia without these)

Anetoderma (= macular atrophy: loss of elastin in upper and mid dermis) may have LCV early on but

more typically shows a mild mononuclear inﬁltrate.

Also get a small vessel vasculitis in PAN and Wegener’s but:

Other causes incl. EED and HSV (for more information, see p. 71)

Lymphocytic Vasculitis

Def

: perivascular / intramural lymphocytes and extravasation of erythrocytes

Pigmented purpuric dermatoses e.g. lichen aureus (that has a band-like inﬁltrate, Grenz zone and ≈

normal epidermis) and others (which have a perivascular inﬁltrate, spongiosis and exocytosis): these

all have superﬁcial / papillary dermal haemosiderin (cf. d/dg stasis dermatitis)

Toxic erythema (clin. rash assoc

with pregnancy, food, drugs, viruses, etc.)

Rickettsial or viral exanthem (viruses can also result in LCV, e.g. around an HSV blister)

Pernio, PLEVA and PLC (see p. 300 and p. 298)

Drug eruption, CTD and Beh¸cet’s (can all also result in LCV)

Sclerosing vasculitides: isolated, EED and granuloma faciale (see p. 299)

Pyoderma gangrenosum: a non-speciﬁc chronic ulcer with PMN predominating in the dermis but

mononuclear/granulomatous inﬂam

may predominate deeply (into the subcutis). Any vasculitis is

often 2

◦

. May begin as coalescence of folliculitis. Occurs isolated or with various systemic diseases

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Skin 302

Parapsoriasis

Large plaque parapsoriasis = early (patch stage) MF:

 papillary dermal oedema and psoriasiform acanthosis

 atypical lymphocytes in papillary dermis and epidermis (without spongiosis)

Small plaque parapsoriasis = chronic superﬁcial dermatitis (a mild psoriasiform eczema without a

thinned suprapapillary plate, PMN exocytosis, prominent papillary dermal capillaries or ↑mitoses)

Pagetoid Reticulosis

Strictly epidermal MF

Solitary lesion (= Woringer-Kolopp disease), otherwise it’s probably not Pagetoid reticulosis

T-cells are usu. CD30 +ve, CD4/8/neither +ve,  ±ve

Excellent prognosis

Primary Cutaneous CD30 +ve Large T-cell Lymphoma

Def

◦

large cells should comprise ≥30% of the neoplastic population

◦

≥75% of the large cells must be CD30 +ve

◦

exclude systemic disease by CPC

Not children (i.e. rare in children)

Not EMA (i.e. usu. EMA −ve)

Not ALK (i.e. usu. ALK t(2;5) −ve)

The tumour is usu. localised but upto 10% cases have nodal involvement

A solitary, non-regressing lesion resembling LyP (A or B) on histology is called ‘Anaplastic lymphoma,

LyP-like’ – it is considered a ‘borderline lesion’

Pseudoepitheliomatous hyperplasia may be ﬂorid (! d/dg SCC)

Other CD30 Positive Inﬁltrates

Transformed tumour stage MF (a bad prognostic)

LyP of Willemze type A

◦

CD30 +ve ALCL (ALK and EMA +ve and clinical LNp)

HL in the skin

B-Cell and Other Lymphomas

d/dg reactive hyperplasia (e.g. insect bite, Borrelia burgdorferi, post vaccination / injection / acupunc-

ture, hypersensitivity to heavy metals, idiopathic): Lymphomas may show destruction of adnexa and a

deep-predominant pattern of inﬁltration (a weak feature); lymphocyte morphology, immuno and CPC

also help. (For more on skin lymphomas and d/dg hyperplasia, see p. 110)

Follicular Mucinosis

Children: benign, lymphocytes and eosinophils

Adults: mycosis fungoides, cerebriform lymphocytes

Borderline Lesions (Borderline Cutaneous T-cell Proliferations)

LyP of Willemze type C

LyP-like ALCL (i.e. anaplastic lymphoma, LyP-like subtype thereof)

Pannus Adiposus

Panniculitis

Any cause may show fat necrosis, Ca

and lipogranulomatous inﬂam

and some may ulcerate

There is variable overlap in the site of the inﬂam

between septal and lobular types ∝ the stage of

disease

Weber-Christian disease

Clin: relapsing febrile nodular panniculitis – it is a diagnosis of exclusion (see d/dg)

Mixed inﬂam

but PMN and lobular predominant panniculitis without abscess formation

Later: microcysts of free fat may develop and may discharge to the surface; may get dense ﬁbrosis

d/dg: LE, 

AT↓, cold/trauma/factitial or histiocytic cytophagic panniculitis, other speciﬁc cause

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Skin 303

Septal panniculitis

Erythema nodosum: PMN and lymphocytic inﬂam

expand septa →granulomatous inﬂam

→ﬁbrosis

-1-antitrypsin deﬁciency: PMN inﬂam

and dissolution of collagen → adipose lobules ‘ﬂoat’ in pus

Sclerotic types: deep morphoea, eosinophilic fasciitis and ischaemic liposclerosis

d/dg deep extension of necrobiotic diseases, infections or vasculitis

Lobular panniculitis

Pancreatic panniculitis: basophilic ring adipocytes (anucleate) and calciﬁcation

Lupus panniculitis: basophilic ring adipocytes, lymphocytic + plasma cell inﬂam

, septal mucin ±

overlying lupus

Granulomatous vasculitis: nodular vasculitis = erythema induratum (if evidence of TB = Bazin’s)

PAN (PMN and ﬁbrinoid necrosis in vessels) / calciphylaxis (calciﬁcation of small vessels)

Subcutaneous fat necrosis of the newborn child / sclerema neonatorum } vide infra

Mixed lobular / septal panniculitis

Cold/trauma-induced (incl. factitial) panniculitis: ± PMN, haemorrhage, Ca

, foreign/faecal matter

Infection: direct mycobacterial infection, gummatous syphilis

Abnormal cell inﬁltrates: Rosai-Dorfman disease, TCL (panniculitis-like, angiocentric, etc, −p. 114),

histiocytic cytophagic panniculitis (= haemorrhagic panniculitis with haemophagocytic syndrome:

may see ‘bean bag cells’ = M with engulfed lymphocytes, RBC and other cell fragments)

Granulomatous, other: Crohn’s, sarcoid (d/dg WG, Churg-Strauss syndrome, etc.)

Sclerema Neonatorum

Clin.: lardaceous sick baby, fatal, IEM

Needle clefts containing crystals but no or minimal inﬂammation / fat necrosis

Widened septa

Subcutaneous Fat Necrosis of the New Born

Clin.: nodules on cheeks, buttocks, rest of body. Good health, benign, ? birth trauma related

Needle clefts, basophilic fat necrosis, giant cell inﬂammation, focal calcium deposits

Blistering Diseases

Overview Mnemonic

Pemphi(gus/goid)

Erythema multiforme (see p. 297)

Herpetiformis (DH) et al. (linear IgA disease and chronic bullous dermatosis)

Epidermolysis bullosa acquisita / congenita

Porphyrias

Some others (HSV / VZV, pompholyx / pustular disorders, bullous variants e.g. of LP, LE, etc.)

The Pemphigus Group

Acantholysis → intraepidermal blisters; may involve adnexal epithelium, ± Nikolsky sign

Direct IF (on perilesional skin): IgG ± C3 in intercellular spaces

Indirect IF

shows circulating Ab to keratinocyte surface glycoproteins (e.g. desmoglein 1 in foliaceous

or desmoglein 3 in vulgaris); disease severity ∝ titre (.

. used for monitoring)

Pemphigus vulgaris

Clin.: middle-aged onwards; blister and erosions at mucocutaneous junctions and intertriginous areas

May be extensive and life threatening if not Rx (currently with steroids / immunosuppression)

Suprabasal split → rounded cavity cells and ‘tombstone’ appearance of remaining basal cells

Early: spongiosis of lower epidermis (± eos.); late: mixed dermal chronic inﬂam

Healing results in >1 layer of cells beneath the split/erosion and epidermal downgrowths (‘villi’)

Pemphigus vegetans

Neumann type starts as pemphigus vulgaris, Hallopeau type starts as suprabasal acantholytic clefts

In both types the lesions heal with verrucous epidermal hyperplasia with pronounced villi

Intraepidermal eosinophils and eosinophil abscesses

the patient’s serum is applied to a section of monkey oesophagus or normal human skin (from a donor) then labelled with ﬂuorescent

anti-human Ig to reveal any Ig in the patient’s serum that may have bound to the tissue

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Skin 304

Pemphigus foliaceous

Younger (patients), better (prognosis) and higher (split – at stratum granulosum) cf. vulgaris

Pemphigus erythematosus

Clin.: mild form of foliaceous resembling LE but localised to the head and neck; ±MG and thymoma

Direct IF: intercellular deposits and a Lupus band

Benign familial chronic pemphigus (Hailey-Hailey disease)

Clin.: AD, 20–30 years, intertriginous areas affected

Micro: epidermis shows ‘dilapidated brick wall’ acantholysis, IF is −ve

Differential diagnosis of pemphigus

Actinic / post radioRx acantholysis

Darier’s disease = multiple keratosis follicularis (KF) – see p. 282 under ‘Acanthoma’

Warty dyskeratoma = solitary KF – see p. 282 under ‘Acanthoma’

Grover’s disease (transient acantholytic dermatosis): small areas of acantholysis (!.

. do levels) that may

resemble Darier’s, SD, pemphigus or Hailey-Hailey disease

Subcorneal pustular dermatosis (SPD): pustules (± spongiform .

. d/dg psoriasis), ± acantholysis

IgA pemphigus is an SPD subtype with direct IF showing intercellular IgA (not IgG)

Bullous impetigo (no acanthosis cf. d/dg SPD, a Gram stain may show bugs)

Older lesions of dermatitis herpetiformis (DH) (d/dg IgA pemphigus)

Scabies (scabies may produce circulating bullous pemphigoid Ags) – diagnosis requires ﬁnding the

mite, eggs/shells or faeces in the burrow which is mostly intracorneal (→ intraepidermal at the

end)

Viruses: HSV / VZV (blister/pustule ± inclusions ± underlying LCV) or pox (± pilosebaceous units)

Acantholytic SCC (vs. vegetans which lacks atypia and shows eosinophil abscesses)

Psoriasis (vs. foliaceous but this is more of a clinical similarity cf. histological)

Paraneoplastic acantholysis: esp. seen with NHL / CLL / Castleman / thymoma / sarcomas this shows

+ve indirect IF on rat bladder (unlike the pemphigus group)

Necrolytic erythemas: shows d/dg psoriasis-like spongiform pustules and parakeratosis with intra-

cellular oedema just below the stratum granulosum. Examples are: necrolytic acral erythema (HCV),

acrodermatitis enteropathica (AR Zn deﬁciency), pellagra (deﬁciency of niacin / tryptophan), necrolytic

migratory erythema (glucagonoma)

Incontinentia pigmenti (p. 297) and drug-induced pemphigus can be distinguished by CPC

Widespread

Oral (and other) mucosae

Limbs

Flexors

The Pemphigoids

Bullous pemphigoid

Clin.: elderly; steroid responsive, large, tense bullae distributed:

Subepidermal split and dermal eosinophils

Direct IF: IgG and C3 at the DEJ at the lamina lucida – take Bx from a small new lesion

Indirect IF: circulating IgG  to an extracellular glycoprotein in the BM zone of the DEJ

 to an intracellular keratinocyte hemidesmosome (70–100%)

 severity NOT ∝ titre

Cicatricial pemphigoid

Clin.: chronic, scarring mucosal disease (esp. oral / oesophageal / conjunctival)

Direct IF: linear IgG in the DEJ

Indirect IF: rarely shows circulating Ig (only 10% of cases)

Differential diagnosis of pemphigoid

Herpes gestationis, DH, chronic bullous dermatosis } vide infra

EBA: use the salt split skin test (see p. 305, under EBA) or the alcohol-ﬁxed indirect IF test (pemphigoid

antigenicity is destroyed but EBA is preserved)

Bullous variants of: lichen planus, amyloidosis, mastocytosis, drug/arthropod reaction and LE

Herpes Gestationis (Pemphigoid Gestationis)

Clin.: itchy, vesicular eruption; pregnancy / puerperium; recurs; ± miscarriage

Subepidermal split (due to basal cell necrosis) and eosinophils ++

Direct IF: linear C3 at the DEJ at the lamina lucida (in 100% of cases)

Indirect IF: circulating IgG (herpes gestationis factor, HGF)

HGF ﬁxes C3 at the DEJ in normal human skin in vitro

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Skin 305

Dermatitis Herpetiformis

Clin.: chronic, young adults, widespread groups of itchy (dapsone sensitive) papules and vesicles, usu.

symmetrical, gluten sensitive jejunopathy (75%) but only a minority have malabsorption clinically

Associations: HLA B8, DR3 and DQw2

Subepidermal split with PMN and oedema in dermal papillae tips, the PMN may form microabscesses

Older lesions show acantholysis, eosinophils, vasculitis → d/dg pemphigus (esp. IgA pemphigus)

Direct IF: granular IgA (includes J-chain .

. is dimeric and possibly from gut)

Indirect IF: no circulating Abs – but serology is usu. +ve for IgA-class anti-tTG Abs

Immuno EM: deposits just below the lamina densa (at the anchoring ﬁbrils)

Linear IgA Disease (Adult Type) and Chronic Bullous Dermatosis of Childhood – see Table 20.1

TABLE 20.1 Linear IgA disease or chronic bullous dermatosis?

Linear IgA Disease Chronic Bullous Dermatosis

Feature (Adult Type) of Childhood

clinical idiopathic / drug-induced self limiting (usu. gone by age 8)

histology similar to DH similar to DH

assoc

s low incidence of HLA B8 & gluten sensitivity assoc

with HLA B8 but not gluten sensitivity

direct IF linear IgA linear IgA

indirect IF no circulating Ab circulating Ig common

Epidermolysis Bullosa Acquisita (EBA)

Clin.: adults, trauma → blisters on wrists, ﬁngers, feet

Associations: Autoimmune disease / amyloid; Bowel disease (CIBD); Cancers

Subepidermal split: non-inﬂam

with festooning (d/dg porphyria) or inﬂam

(d/dg DH, pemphigoid)

Direct IF: linear IgG and C3 at DEJ (Bx non-blistered skin – e.g. peri-lesional – else ↑false −ve)

Indirect IF: circulating Ig is uncommon (only 25% of cases)

Immuno EM: deposits just below the lamina densa (Abs target type VII collagen)

d/dg bullous pemphigoid (do split skin test): apply patient’s serum to normal skin split with 1M NaCl

then label with anti-human IgG labelled Ab. In pemphigoid IgG binds to the epidermal part of the split

skin. In EBA it binds to the dermal part. (See also the alcohol-ﬁxed indirect IF test, p. 304)

The Porphyrias

Clin.: photosensitive cutaneous disease in all types (except acute intermittent porphyria)

Accumulation of PAS +ve material (= type IV collagen) around dermal blood vessels and DEJ

Non-inﬂam

split at DEJ, dermal papillae project into cavity (i.e. ‘festooning’) ± actinic damage

Direct IF: IgG passively entrapped within the PAS +ve material (i.e. not immune-mediated)

RadioRx (Effects of Ionising Radiation)

Acute Radiation Effects (up to 6 months post exposure)

Clin.: epilation / erythema →radiodermatitis (erythema, inﬂam

, dry desquamation) →radiation burn

(wet desquamation, vesicles, ulceration); the extent of these changes will depend on the dose

Epidermis: spongiosis, intraepidermal ± DEJ vesicles → conﬂuent epidermal necrosis and ulceration

with upper dermal ﬁbrin deposition (≈ second degree thermal burn)

↓ Mitoses, loss of hair shafts, follicular keratin plugs

Swelling of epithelial and endothelial cells with ↑ apoptoses

Upper dermal oedema, capillary dilatation, arteriolar ﬁbrin thrombi, ↑melanin pigment

Mixed diffuse dermal inﬂam

(incl. PMN and eos.) ± exocytosis

Chronic Radiation Effects

Clin.: poikiloderma (due to thin epidermis variable melanocyte enzyme activity and capillary ectasia)

Epidermis: variably atrophic with ﬂattening of rete pegs ± dyskeratosis, basal/sub-basal vacuolation

Atypia of basal keratinocytes ± melanocytes (! some report occasional atypical mitoses)

Papillary and reticular dermis replaced by irregular hyaline ﬁbrosis (pale on H&E) with ﬁbrillary

interstitial ﬁbrinoid and prominent elastosis (can go deep and incl. subcutis – unlike d/dg solar elastosis)

Atypical ﬁbroblasts: plump, angular, amphophil cytoplasm, vesicular nuclei ± binucleate forms

Dermal capillary ectasia, anisochromasia of plump endothelial cells, arteriolar hyaline, endarteritis

obliterans of larger vessels (usu. scant) and ﬁbrinoid necrosis (usu. 2

◦

– e.g. near ulcers)

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Skin 306

Chronic ulcers have a ﬁbrinopurulent base but little or no granulation tissue

± Pigmentary incontinence, ± siderophages (but not dermal inﬂam

unless 2

◦

pathology is present)

Patchy destruction of pilosebaceous units → bulbous scars near plugged infudibula / arrector pili

Radiation Atypias and Neoplasia

Benign cytomegaly may occur at any time in any cell type: NCR is normal, irreg. nuclear membrane

(not thickened), cytoplasmic +/ nuclear vacuolation, multinucleation, bizarre shapes, irreg. staining

Epidermal dysplasia (AK-like) occurs after some years and SCC after 15–20 years (on average)

Atypical vascular lesions (similar to those described in the breast – see p. 320) and d/dg angiosar-

coma: both may be multiple and occur after 1–20 years (average 3 years for benign, 6 years for

malig.)

Hobnail haemangioma-like vascular lesions (conﬁned to dermis – unlike angiosarcoma):

 wedge-shaped ‘proliferations’ (but no mitoses and Ki-67 is −ve) – thin end of wedge is deep

 dilated (usu. empty) vascular spaces superﬁcially, more slit-like deeper

 plump ±hyperchromatic endothelium (but no multilayeringor other angiosarcoma-likeatypia)

 ± small papillaroid intralumenal stromal projections (d/dg Dabska’s tumour in children – but

that is often subcutaneous with a lymphoid inﬁltrate and dilated channels with ﬂorid tuftings

[the adult equivalent is reteform haemangioendothelioma – this has ﬂatter branching spaces])

Immunodeﬁciency

Graft vs. Host Disease (GVHD)

Clin.: skin changes, hepatic dysfunction and diarrhoea

Aetiology: congenital (maternal lymphocytes) / acquired (post BMTx, liver, SI, lung and kidney Tx)

Acute graft vs. host skin reaction (GVHR) starts in the 1

3 months post Tx and is important because

it precedes hepatic and GIT involvement (early Rx gives best chance of survival):

 papillary dermis:  sparse lymphocytic inﬁltrate and exocytosis (otherwise the changes

could be due to radiation)

 RBC extravasation and siderophages (but no true vasculitis)

 Civatte bodies (are not, in themselves, diagnostic of lichenoid change)

 ± PMN and eosinophils

 epidermis:

Grade 1: vacuolar interface change – starts at deep tips of rete ridges and hair follicles

Grade 2: dyskeratosis ± satellite cell necrosis (= ‘satellitosis’ – lymphocytes partly

surround an apoptotic cell)

Grade 3: sub-epidermal clefting (due to coalescence of necrotic keratinocytes)

Grade 4: complete sloughing (loss) of necrotic epidermis

 d/dg: viral exanthem, fungal infection, chemo/radioRx effect .

. use CPC and exclude speciﬁc

pathogens by appropriate stains

 d/dg: TEN (and other members of the erythema multiforme group):

 can be impossible to differentiate (need CPC ± serial [in time] Bx with immuno)

 PMN favour GVHR

 pilosebaceous involvement favours GVHR (eccrine occurs in both)

 immuno:  NK cells (CD16, CD56) in the epidermis favour GVHR over TEN

 T-cell:M ratio: ♦ purely M favours lymphocyte depleted GVHR over TEN

♦ mixed, M predominant or 1:1 favours TEN over GVHR

♦ mixed, T-cell predominant favours GVHR over TEN

Chronic: (usu. after 100 days)

 early lichenoid stage: like LP (may also occur in acute GVHR, either way it’s a bad prognostic)

 late sclerotic stage: epidermal atrophy and ↑ pigment, thickened dermis, loss of adnexa

HIV / AIDS and the Skin

Acute HIV exanthem (micro: just a perivascular lymphohistiocytic inﬁltrate)

Eosinophilic folliculitis:

 pruritic reaction to infundibular Ag, may indicate advanced HIV (low CD4 count)

 early: lymphocytes and eos. in sebaceous duct / infundibular region →mixed exocytosis and

spongiosis

 later: ﬂorid perifollicular inﬂam

→ ﬁbrosis

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Skin 307

(Staphylococcal) folliculitis

Seborrhoeic dermatitis (± dyskeratosis, leukocytoclasia and plasma cells in HIV)

Psoriasis

LP (hypertrophic)

Photosensitivity (chronic actinic dermatitis, photosensitive granuloma annulare, hyperpigmentation)

HIV interface dermatitis: vacuolar degeneration ++, no eosinophils / neutrophils

KS: prognosis ∝ HIV disease activity and level of immunosuppression (see pp. 322–323)

T-cell lymphomas (cf. EBV-related DLBCL elsewhere); MF is rare .

. consider CD8 +ve mimic

Opportunistic infections (often occur with a low CD4 count – <150 cells/l):

 oesophageal candidiasis; cutaneous Histoplasma, Cryptococcus and Candida (the commonest)

 CMV, giant and verrucous molluscum, persistent herpes (HSV and VZV have the same his-

tology)

 atypical mycobacteria

Oral hairy leukoplakia: prognosis is poor if CD4 count is >300 (see p. 133)

Bacillary angiomatosis (more often multiple cf. d/dg pyogenic granuloma – see p. 319)

Nodular / Norwegan scabies (! d/dg resemble pseudolymphoma): see p. 304 (under ‘Differential diag-

nosis of pemphigus’) and p. 349

Drug eruptions: photosensitive / lichenoid with eosinophils / erythema multiforme group

Immune Reconstitution Disease Syndrome (IRDS – due to HAART) – CMV and erosive HSV

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