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

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Soft Tissues 319

Tufted Angioma (Angioblastoma of Nakagawa)

Capillary lobules with pericytes

‘Cannon ball’ ‘buckshot’ distribution in the dermis and subcutis

Crescentic ‘semilunar’ spaces (? lymphatic) surround the lobules

There is no signiﬁcant spindle population

Stains: reticulin shows a ‘vasoformative’ pattern (i.e. tubules)

Intramuscular Haemangioma (= Intramuscular Angioma [if lymphatics are present])

Clin.: may be painful, usu. restricted to one site or muscle group

Vessels ++, of all types and in various proportions (capillary, cavernous, arterial, venous ±lymphatic)

Mature adipose tissue may be a prominent component

d/dg intramuscular lipoma: angioma is too vascular for a lipoma and contains a variety of vessel types

d/dg angiomatosis of soft tissues: angiomatosis clinically affects >1 site or muscle group

Angiomatosis (Bacillary)

Clin.: assoc

with AIDS/post Tx; sites: dermal / oral / aural polyp, liver / spleen peliotic lesions

Lobular growth, rounded capillary channels, plump endothelial cells } (cf. d/dg KS)

PMN in clumps throughout (not just near an ulcerated surface as in d/dg pyogenic granuloma)

Interstitial granular amphophil debris (=Warthin-Starry +ve bacteria Bartonella henselae +/ quintana)

Angiomatosis (of Soft Tissues)

Clin.: child/adolescent, limbs, involves any depth from dermis to bone, large contiguous areas

Mature fat surrounds proliferating vessels

Subtypes:

◦

irregular veins with incomplete muscle; cavernous and capillary vessels

◦

small capillaries only and sparse feeder vessels

d/dg AVM: no arteries in angiomatosis

d/dg intramuscular haemangioma: vide supra

Angiomatosis (of Lung Septa)

Assoc

with pulmonary veno-occlusive disease (VOD) – see p. 88

Angiomatosis (of Lymph Nodes = Vascular Transformation of LN Sinuses)

A reactive sinus vessel proliferation 2

◦

to lymphovenous obstruction

Spindled proliferation with maturation

Maturation takes the form of capillary ectasia – usu. most marked at the periphery of the LN

Arch. is preserved and it lacks well-formed fascicles (cf. d/dg KS)

Angiomatosis (of Breast)

Clin.: large (present as a mass), locally recurrent but not pre-malignant and do not metastasise

Diffuse involvement of the interlobular stroma (spares the TDLU – unlike d/dg angiosarcoma)

Variably dilated channels (mixture of empty and blood-ﬁlled) that do not get smaller at the periphery

Channels may anastomose but endothelium is ﬂattened and not atypical (cf. angiosarcoma)

d/dg angiosarcoma shows:

 endothelial atypia (hyperchromasia / tufting / mitoses / nucleoli) ± high grade areas (solid

foci, necrosis)

 destructive invasion (e.g. it inﬁltrates and overruns the TDLUs)

 a more heterogeneous density of channels throughout the lesion

 maturation towards the periphery (calibre of vascular spaces decreases down to capillary

)

d/dg AVM: angiomatosis has no signiﬁcant smooth muscle component

d/dg PASH: PASH is lined by CD34 (not CD31) +ve and Bcl-2 +ve stromal cells, not endothelium

d/dg perilobular haemangioma: this may have focal atypia and anastomoses but is well circumscribed

and does not show destructive invasion (it is called ‘haemangiomatosis’ if multiple)

d/dg atypical haemangioma (vide infra)

d/dg atypical vascular lesions post radioRx (vide infra)

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Atypical Haemangioma (of the Breast)

Small (<2cm ), benign lesions with vaguely lobular arch., stromal mast cells and organising thrombi

± Feeder vessels nearby / within the lesions

Atypia = anastomosing channels, local ‘invasive’ margins (not encapsulated) and focal endothelial

hyperchromasia / hyperplasia (usu. in regions of organising thrombi)

Subtypes: cavernous, compact capillary (d/dg pyogenic granuloma), combined, capillary budding (has

some solid spindle areas – d/dg KS)

d/dg angiosarcoma: no destructive invasion, solid areas, necrosis, blood lakes or large tumours 2cm

d/dg angiolipoma: angiolipoma vessels are concentrated at the periphery of a fat lobule

Atypical Vascular Lesions post RadioRx (of the Breast)

Small benign lumps (usu. < 1cm ) conﬁned to dermis (or to a ﬁbrous nodule if parenchymal – rare)

Well-circ. but not encapsulated and variable stromal chronic inﬂam

cell inﬁltrate (lymphocytes and

plasma cells)

Empty, angulated, variably-sized channels, some of which may anastomose ± dissect collagen

Spaced-out, plump single (rarely focal 2) layered endothelium ± hyperchromasia but no other atypia

d/dg angiosarcoma: unlike angiosarcoma, these are small, lack diffuse skin change / ‘bruise-like’

discoloration clinically and lack invasion, blood lakes or signiﬁcant cytological atypia (tufting, mitoses,

nucleoli)

Pleomorphic Hyalinising Angiectatic Tumour (PHAT)

A low grade malignancy with an aptly descriptive name (for immuno see Schwannoma, ancient, d/dg)

Also ± perivascular ﬁbrin, perilesional lymphocytes, Ca

, Fe and intranuclear cytoplasmic inclusions

d/dg: ancient Schwannoma, simplastic haemangioma, MFH (the latter is more mitotic)

Stuart-Treves Syndrome (Stuart-Treves Lymphangiosarcoma)

Occurs in lymphoedematous arms following axillary radioRx for breast carcinoma

Solid, epithelioid and papillary endothelial formations

Unlike post radioRx angiosarcoma, it occurs outside the radiation ﬁeld

Angiosarcoma

Clin.: blue/black (‘bruise-like’), affects any tissue, liver, skin (e.g. face and scalp of the elderly), breast

(can be bilateral and usu. deep in the breast if 1

◦

or affects the breast skin if 2

◦

to radioRx)

Macro: haemorrhagic and often several cm in size

Destructive inﬁltration by anastomosing angular channels with atypical endothelium (hyperchromatic,

± tufting / mitoses / nucleoli) ± extravasation ‘blood lakes’ in higher grades

Better differentiated at periphery of lesion (i.e. the channels get smaller and have lower grade histology)

Grade according to worst area (only useful for breast lesions): Mitoses

Grade 1: upto 2 layers, tufting, dissecting and anastomosing channels

Grade 2: papillary and solid spindle cell areas

Grade 3: mostly solid, necrosis

Variants: haemorrhagic (blood lakes ++), epithelioid, granular and sclerosing

Immuno:  +ve for CD31, CD34, FVIIIRA, vimentin

 −ve for Melan-A, HMB45, ALK, CEA, thyroglobulin, Hep Par 1, HMW CK

 ±ve for LMW CK (CAM5.2 is +ve in ≈ 33% of cases), S100 (≈ 8%), c-kit (≈ 50%)

d/dg benign vascular lesions in general, but these:

 are usu. < 2cm in max.



 may have a nearby muscular vessel (but some epithelioid angiosarcomas also have a feeder

vessel)

 may have smooth muscle in the walls of the vascular channels (but some angiomatoses don’t)

 spaces are not anastomosing (but this is a weak feature with many exceptions – vide supra)

d/dg speciﬁc entities:

 Kaposi sarcoma vs. solid (spindle cell) angiosarcoma: angiosarcoma has dissecting, ramiﬁed

channels and signiﬁcant cytological atypia whereas KS has minimal atypia (except the African

endemic form) and curved fascicles with simple channels. CPC is also helpful

 sinusoidal haemangioma: sieve-like back-to-back dilated vessels ± hyperchromasia, no inva-

sion

 atypical vascular lesions post radioRx (vide supra)

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 grade 1–2 angiosarcoma occurring in infancy (in liver, spleen, lungs or bone) is called ‘infantile

haemangioendothelioma’ but some use this term to be synonymous with cellular haemangioma

in the skin or Kaposiform haemangioendothelioma (described on p. 322)

 angiomatoid variant of anaplastic thyroid carcinoma may have anastomosing channels con-

taining blood and +vity for FVIIIRA and vimentin .

. look for focal better diff tumour foci

and use CPC

 haemorrhagic angiosarcoma vs. choriocarcinoma

 sclerosing angiosarcoma vs. ﬁbromatosis / other sarcoma (cells arranged in branchingbilayered

strands favour angiosarcoma)

 angiomatosis, haemangiomatosis and atypical haemangiomas (pp. 319–320)

 carcinoma, anaplastic lymphoma and melanoma vs. epithelioid angiosarcoma (vide infra)

 Masson’s tumour: this is usu. entirely intravascular and is a hyalinepapillary form of organising

thrombus with single-layered, non-atypical endothelium. However, it may arise secondarily in

any other 1

◦

vascular lesion.

 reactive angioendotheliomatosis: loose irregular lobules of non-atypical capillaries (usu.) in

the dermis

 benign lymphangioendothelioma: dissects the dermal collagen but has empty channels and

no endothelial atypia

Epithelioid Angiosarcoma

Clin.: older adults (MF), skin, deep soft tissue (incl. muscle – an otherwise rare site for angiosarcoma)

An origin from the edge of a larger vessel may be seen (a feeder vessel)

Solid sheets of large epithelioid cells (vesicular nucleus and large eosinophilic nucleolus)

Small foci of more typical angiosarcoma (if more extensive call it ‘angiosarcoma with epithelioid

areas’)

Mitoses ++, ± necrosis, haemorrhage

Vacuoles (containing occ. RBC, not mucin)

Vasoformative (tubular) reticulin pattern

Immuno: CD31 +ve, ± LMW CK +ve (HMW CK −ve), ± focal EMA +ve (but usu. −ve): see

‘Angiosarcoma’, above, for more

d/dg all epithelioid malignant neoplasms (incl. mesothelioma): endothelial immuno ± EM, RBC vac-

uoles and retic pattern are the most helpful distinguishing features

d/dg epithelioid haemangioendothelioma: angiosarcoma does not have the centrifugal architecture of

haemangioendothelioma, for other features in the d/dg vide infra

Epithelioid Haemangioendothelioma

Adult, multicentric (except in soft tissues), arises from medium-sized vein/artery; may metastasise

Cords / sheets of polygonal cells in myxohyaline stroma ± plump spindle cell fascicles

Eosinophilic hyaline cytoplasm, inconspicuous nucleoli

Cytoplasmic vacuoles (more evident that in epithelioid angiosarcoma)

Vasoformative (tubular) reticulin pattern (smaller and more broken-up cf. epithelioid angiosarcoma)

Low mitotic count (≤2/10hpf)

Immuno: CD31 +ve ± SMA +ve, CK +ve (but CEA and EMA −ve)

Malignant change: focally solid and more pleomorphic, but mitoses are still few

d/dg: carcinoma (esp. sclerosing cholangiocarcinoma): different immuno, vacuoles contain RBC not

mucin, also carcinomas have worse cytology

d/dg epithelioid sarcoma: but epithelioid sarcoma has a sheet-like growth pattern, is −ve for CD31 and

FVIIIRA, is +ve for EMA, CK and CD34 and does not have RBC in its cytoplasmic vacuoles

d/dg KS but the spindle cells are plumper than KS and have eosinophilic hyaline cytoplasm

d/dg epithelioid angiosarcoma: haemangioendothelioma has cords, fewer solid areas, more obvious

vacuoles,↓ mitoses, smaller cells, small nucleoli, more myxohyaline stroma and a centrifugal growth

pattern around a central vessel

d/dg intravascular bronchioalveolar tumour – it is the same tumour, but in the lungs

d/dg myxoid chondrosarcoma

Haemangiopericytoma (HPC)

Clin.: age ≈ 40 years (d/dg synovial sarcoma occurs younger), assoc

with Castleman’s disease

Sites: thigh, retroperitoneum, head and neck, trunk (d/dg synovial sarcoma prefers the extremities)

Stubby spindle cells with scant cytoplasm and oval nuclei with dispersed chromatin

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Open vascular spaces, some biﬁd or ‘staghorn’

Immuno: +ve for CD34, vimentin, ± focal actin (but usu. −ve); −ve for CD31, CK, S100

Diagnosis of exclusion:

 must have an HPC pattern and single cell reticulin everywhere

 must be negative for muscle, nerve sheath and epithelial markers

‘Benign’ variant: no necrosis or pleom. and low mitotic count (< 1/20 hpf) – but some still metastasise

Signs of aggression: necrosis, trabecular arch., mitoses, pleomorphism, vascular invasion

d/dg:

 synovial sarcoma: has an epithelial component (or nested reticulin if monophasic)

 HPC-like tumour, sinonasal: site, more rounded cells, no pleomorphism, mitoses rare

 glomus tumour: organoid features and SMA +ve

 myopericytoma / myoﬁbromatosis: MSA +ve cells are orientated around the vascular channels

 haemangiopericytic meningioma shows focal transition to benign meningioma (but meningeal

HPC exists)

 solitary ﬁbrous tumour: shows other growth patterns

 thymoma, type A: other features of thymoma are present (see pp. 95–96)

 clear cell sugar tumour: clear (PAS +ve) cells and positive for CD34, S100, HMB45

 mesenchymal chondrosarcoma: focal cartilage islands

 RMS or liposarcoma (because HPC may have focal myxoid areas or alveolar architecture)

Intimal Sarcoma

Large vessels of adults (e.g. aorta, pulm. arteries and venae cavae), embolic effects, poor prog.

A spindle sarcoma arising from the intima

Immuno: vimentin +ve but other markers are variable / −ve

Kaposiform Haemangioendothelioma

Clin.: usu. infants / children, no HIV, die from a consumptive coagulopathy (Kaserbach-Merritt)

Site: deep soft tissues (esp. peripancreatic retroperitoneum), skin in older patients

Inﬁltrative lobular growth pattern (lobules may be large .

. not obvious on core Bx)

Criss-crossing curved to straight fascicles (shorter cf. KS and simpler than spindle cell haemangioma)

DPAS +ve globules may be present

Microthrombi are common

Well-formed capillary areas may be present

Short narrow vascular spaces lined by attenuated slender cells with dark nuclei (like normal endothe-

lium) are interspersed among the spindle cells (not seen in KS)

Pericytes (MSA +ve) are present to abundant (cf. KS)

d/dg KS – vide infra, also KS is nodular (not lobular) and is rare in deep soft tissues and in infants

d/dg angiosarcoma – haemangioendothelioma lacks a dissecting pattern or cytological atypia

Kaposi Sarcoma (KS)

Multifocal, skin / visceral sites, HIV, HHV8 (nuclear positivity by immuno)

Early lesions are polyclonal later becoming monoclonal

Three main stages: Patch (≈ ‘granulation tissue like’ histology), Plaque, Nodule

Nodular (i.e. expansile with altered stroma peripherally – oedema / ﬁbrosis with concentric collagen)

Criss-crossing, curved, fascicles of spindle cells

Simple slit-like spaces (appear reteform / sponge-like if cut transversely), spaces contain RBC

Minimal cytological atypia

DPAS +ve hyaline globules (intra and extracellularly)

Interspersed lymphoplasmacytic inﬁltrate and haemosiderin

CD34 +ve spindle cells (all tumour cells are +ve cf. spindle cell haemangioma)

Pericytes (MSA +ve) are sparse or absent

Well-developed capillaries may be present (esp. at the periphery or in the angiomatous variant)

Lymphangiomatous variant KS (dilated empty channels) lacks endothelial multilayering / atypia (cf.

d/dg angiosarcoma) or focal smooth muscle (cf. benign lymphangioendothelioma) and has stromal

spindle cells and plasma cells / inﬂam

unlike those differentials

Skin KS may have a collarette of epidermis mimicking d/dg pyogenic granuloma

d/dg microvenular haemangioma: unlike KS this well-circ lesion with sclerotic collagen has many

branching small vessels, pericytes, invasion of the arrector pili and lacks a KS-like inﬂam

component

d/dg KS may be clinically confused for acroangiodermatitis (an exaggerated form of stasis dermatitis)

For other d/dg see the features of the other vascular entities described above.

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TABLE 21.1 The 5 main clinical forms of KS

◦

Classical (Kaposi, 1872)

◦

Endemic

Westerners / Eastern European Jews

Sub-Saharan Africa

Indolent

Males

Elderly males

Aggressive lower leg lesions / Classical-like / Systemic

Lower leg lesions

Die from other causes

Assoc

with tumours esp. lymphomas

◦

Lymphadenopathic

◦

Tx-Associated

Rapidly fatal

Long-term immunosuppression

African children

Aggressive cf. classical

Widespread LNp, no skin lesions

Fatal in 30%

Skin and systemic involvement

◦

AIDS-Associated

Male homosexuals

Die from other complications of AIDS

Multiple purple patches/plaques (usu. on upper body, palate and viscera)

Miscellaneous

Synovial Sarcoma

Extremities of young adults / chest wall, chemosensitive (esp. in children), cytogenetics: t(X;18)

Stromal changes: ﬁbrosis, hyaline, Ca

, mast cells, haemangiopericytoma-like vessels

Biphasic  short, stubby, spindle cells closely compacted together with pericellular reticulin

 nuclei: ovoid, open chromatin ± nuclear overlapping

 epithelial: 1. elongated glands, +ve for mucicarmine / DPAS

2. small nests (show up as packeted reticulin cf. pericellular)

 haemangiopericytomatous architecture

 herring bone / alternating hyper and hypocellular areas

Monophasic:  more common (×2) and usu. spindle type but may be epithelial

 reticulin packets (sufﬁcient to make the diagnosis if the clinical ﬁts)

 EM: may show microvilli-lined spaces as evidence of epithelial differentiation

Synovioblastic synovial sarcoma: poor prognosis variant, ↑cellular, pleomorphic spindle cells, rhabdoid

cells / small blue round cells, mitoses ++, ± necrosis

Calcifying synovial sarcoma: good prognosis variant, has calciﬁcation ++

Grading:

Low: > 50% glandular, <15 mitoses /10 hpf → low risk (100% 3YS)

High: < 50% glandular, > 15 mitoses/10 hpf → high risk (40% 3YS)

Prognostics: metastasis-free survival is better with the SYT-SSX2 translocation cf. SYT-SSX1

Immuno: triad

◦

Bcl-2 +ve,

◦

EMA (EMA and CK are at least focally +ve in spindle and epithelial

cells) and

◦

CD99 ±ve (membranous, in the spindle cells); S100 ±ve; −ve for CD34, desmin, MSA

d/dg: HPC, ﬁbrosarcoma, MPNST, mesenchymal chondrosarcoma, leiomyosarcoma, KS

Alveolar Soft Part Sarcoma

Clin.: young, thigh (or head and neck in children); slow malignant course with late metastases

Nests of uniform cells with central dyscohesion ± rhabdoid / clear cell change ± solid foci

Large eosinophilic cells with large nucleoli; ±AB and DPAS +ve cytoplasmic basophilic crystalloids

Mitoses and pleomorphism are only focal but haemorrhage and necrosis may be prominent

Peritumoural vascular invasion

Immuno: nuclear TFE3 +vity is ≈speciﬁc (! but also +ve in granular cell tumours and some childhood

RCC); desmin, MSA, NSE and S100 are all ±ve; −ve for CgA, synaptophysin, HMB45, Melan A,

CK, EMA

d/dg RCC / melanoma (more pleomorphic), malig. granular cell tumour, paraganglioma, PEComa,

ACC

Clear Cell Sarcoma of Tendon and Aponeuroses (Malignant Melanoma of Soft Parts)

Clin.: young, ankle / foot

Fascicular and nested (retic) inﬁltration by clear cells with vesicular nuclei and prominent nucleoli

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Wreath-like giant cells / melanin

Immuno: +ve for S100, HMB45, NSE

d/dg superﬁcial CCSTA vs. cutaneous melanoma: lack of junctional activity in overlying skin

d/dg epithelioid MPNST: CCSTA is HMB45 +ve and has t(12;22)

Epithelioid Sarcoma

Clin.: young, hand / wrist, extensive local spread ± mets to scalp, LN, lung

Commonest sarcoma of hand and forearm (followed by alveolar RMS and synovial sarcoma)

Subcutis / deeper, attached to tendon / aponeurosis

Nodules / multinodular conglomerates of epithelioid cells (± myoid/spindle cells), pleomorphism is

mild, ± intracytoplasmic vacuoles and cleft-like spaces (d/dg vascular lesion), ± rhabdoid inclusions

Granuloma-like: bland tumour cells with central hyaline or necrosis and peripheral lymphocytes

Stroma is dense collagenous (incl. intercellular collagen) ± chondroid / osteoid

Immuno +ve for: CK (e.g. AE1/AE3), vimentin and EMA +ve; CD34 ±ve

Immuno −ve for: CD31, CD68, S100, FVIIIRA, CEA

d/dg granulomas, vascular neoplasm, RMS, rhabdoid tumour, epithelioid Spitz: immuno may help

d/dg carcinoma: CD34 +vity is rare in carcinomas and there is no epidermal component (cf. 1

◦

SCC)

Worse prognosis if >5cm or proximal variant (esp. perineum / pelvis)

Proximal variant:  sheet-like growth of larger cells with vesicular nuclei, no necrosis

 more pleomorphism (carcinoma-like) and rhabdoid inclusions

 d/dg extra-renal rhabdoid tumour (vide infra) / carcinoma

Extra-Renal Rhabdoid Tumour

Clin.: young, aggressive (? related to solid / proximal variant epithelioid sarcoma)

Round epithelioid cells, vesicular nuclei and prominent nucleoli, hyaline globular (rhabdoid) inclusions

Immuno: +ve for CK, vimentin and EMA (like RCC and epithelioid sarcoma)

d/dg rhabdoid differentiation in other tumours

Solitary Fibrous Tumour (Localised Fibrous Tumour)

Mesothelial or 1

◦

soft tissue (interstitial dendritic cell origin – like spindle cell lipoma)

Well-circumscribed but not usu. encapsulated – may entrap adjacent structures

A variety of patterns is characteristic:

◦

patternless pattern: parallel ‘ropey’ collagen

◦

wavey neuroid

◦

storiform / herring bone

◦

haemangiopericytomatous

Stromal degenerations (myxoid, hyaline, etc.): useful in d/dg synovial sarcoma

± Amianthoid ﬁbres (as in palisaded myoﬁbroblastoma, p. 312)

Immuno:  +ve for the triad of CD34, CD99, Bcl-2; vimentin +ve, (c-kit ±ve)

 −ve for S100, CK, SMA, desmin, FXIIIa, collagen IV, (CD34 in high grade malig.

SFT)

 NB: CD34 and vimentin are characteristic of the interstitial dendritic cell

Variant: calcifying ﬁbrous pseudotumour:  SFT which has ‘burnt out’ (i.e. no spindle cells)

 collagen and psammoma bodies may be present

d/dg: adenoﬁbroma, synovial sarcoma (see p. 94), NF, Schwannoma, MFH, ﬁbrosarcoma, HPC

Malignant SFTs have 2–50% of nuclei +ve for p53 (cf. ≤1%

in benign) and a Ki-67 LI of 1-45% (cf. ≤2% in benign)

Malignancy:  inﬁltrative margins (! not just entrapment)

 hypercellularity

 pleomorphism

 necrosis

 mitoses >4/10 hpf

Grading malignant SFT (NB: intermediate grade shows features in between high and low):

 lowgrade: predom. pushing border and elongated bland nuclei; they show obviousSFT patterns

and collagen and p53/Ki-67 are at the low end of the malignant range. CD34 is usu. +ve

 high grade: extensively inﬁltrative with plump, pleomorphic, hyperchromatic nuclei; SFT

patterns and collagen are not well developed and p53/Ki-67 are at the upper end; CD34 is

often −ve

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Juvenile Xanthogranuloma

Multinucleated GC (esp. Touton type – peripheral vacuoles surround a ring of nuclei)

Does not inﬁltrate the epidermis

May inﬁltrate muscle and deep structures

May have lots of eosinophils (d/dg HX – do immuno to see if histiocytes are of the Langerhans type)

Immuno: non-X histiocytes are +ve for CD68, 

AT, lysozyme and CD31 and −ve for CD1a and

S100

Malignant Fibrous Histiocytoma (MFH)

Sites: soft tissues (extremities/retroperitoneum) / bone (30% are 2

◦

to Paget’s/radiation/cartilage

tumours)

Variants:  Myxoid (most ‘myxoid MFH’ are now regarded as high grade myxoﬁbrosarcoma)

 Angiomatoid (youths, indolent, termed angiomatoid ﬁbrous histiocytoma by the WHO)

 Giant cell MFH has many osteoclast-like (i.e. bland) giant cells

 Inﬂammatory (retroperitoneal, big xanthomatoid cells / virocytes, PMN, d/dg

CA mets)

 Common type (Storiform Pleomorphic) focally seen in all variants except angiomatoid

 Skin (= AFX): slow growing, locally recurrent, mets uncommon

Storiform pattern (i.e. variably curved bundles of spindle cells radiating from a central hub)

Variably pleomorphic spindle cells and ‘malignant histiocyte’-like cells, ±multinucleated tumour cells

Usu. much collagen, lipid-laden M, ± osteoclast-like giant cells

Immuno: MFH is a diagnosis of exclusion, MSA and CD68 may be +ve but a deﬁnitive immunophe-

notype should result in classiﬁcation of the lesion as a poorly diff sarcoma of that type

Angiomatoid type: nodular, subcutaneous and usu. have a rich lymphoplasmacytic component (.

. d/dg

LN), blood spaces lack endothelium, relatively bland eosinophilic spindle cells ± haemorrhage (d/dg

KS), few mitoses; immuno ±ve for CD68, desmin and MSA (= HHF-35, not SMA)

d/dg: ﬁbrosarcoma, MPNST, monophasic synovial sarcoma, spindled metastasis (esp. in bone e.g. from

carcinoma of the bronchus, kidney or anaplastic thyroid carcinoma)

d/dg: many cases of storiform pleomorphic MFH may be poorly differentiated versions of liposarcoma

(better prognosis), RMS (worse prognosis) or leiomyosarcoma

d/dg: many cases of ‘giant cell MFH’ may be giant cell rich osteosarcomas or leiomyosarcomas

d/dg: see also ‘Some Soft Tissue Lesions with a Storiform Pattern’, p. 327

Atypical ﬁbroxanthoma (AFX)

Skin (esp. head and neck), circumscribed, ± collarette, actinic background, usu. lacks a Grenz zone

Highly pleomorphic cells (or non-pleom. variant), mitoses ++ (incl. atypical ones), various patterns

Adnexa may be entrapped but usu. not inﬁltrated (an inﬁltrative deep margin goes against a diagnosis

of AFX)

Necrosis, vascular or perineural invasion or deep subcutaneous spread suggest a more malignant

sarcoma

Immuno: SMA ±ve, CD68 ±ve, −ve for pan CK and S100

d/dg melanoma, leiomyosarcoma and sarcomatoid SCC must all be excluded before making the diag-

nosis

d/dg atypical DF: this is not UV-related, has a background typical of a DF and is FXIIIa +ve

TABLE 21.2 Immuno of DF vs. DFSP

FXIIIa CD34

DF +ve −ve

DFSP −ve +ve

Dermatoﬁbrosarcoma Protruberans (DFSP)

Dermal, extends into subcutis with cells parallel to the surface to surround adipocytes (‘lace-like’)

Arch: asymmetrical, storiform pattern throughout, ± Grenz zone

Bland spindle cells, mitoses uncommon (usu. <5/10 hpf)

Overlying epidermis is thinned / ulcerated

Immuno: CD34 +ve, FXIIIa −ve, p53 +ve, SMA −ve

Variant: Bednar: heavily melanin pigmented dendritic cells

throughout (cf. haemosiderin in DF)

Variant: ﬁbrosarcomatous (>5% of tumour shows ↑mitoses, fascicular architecture and cytological

atypia ± CD34 +vity)

Variant: giant cell ﬁbroblastoma (young, superﬁcial, uni and multinucleated cells line pseudovasc.

spaces)

Variants: myxoid, diffuse, fascicular, sclerotic, atrophic (d/dg DF), DFSP-MFH (aggressive)

d/dg AFX: DFSP has bland cytology and few mitoses (except aggressive variants)

d/dg DF:  epidermal changes in DF (not seen in DFSP)

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 admixed foam cells, multinucleated giant cells and inﬂam

cells favour DF

 pattern and extent of subcutis involvement

 DF is more symmetrical, only focally storiform and contains birefringent collagen

Dermatoﬁbroma / Benign Fibrous Histiocytoma (DF / BFH)

Dermal, ± minimal extension into subcutis as radiating spikes perpendicular to the surface

Bland spindle cells, mitoses are uncommon

Overlying epidermis: acanthosis ± BCP-like pattern or basaloid proliferations resembling BCC

Junction with normal dermis shows inﬁltration of spindle cells around hyalinised collagen bundles

Foamy M (called BFH when these are prominent), giant cells, inﬂam

cells ± haemosiderin

Immuno: CD34 −ve, FXIIIa +ve (but may be −ve towards the centre of sclerotic lesions), SMA ±ve,

p53 −ve

Variant: cellular (may reach into the superﬁcial subcutis and have small central necrotic foci)

Variant: aneurysmal (may evolve into a haemosiderotic DF or ‘sclerosing haemangioma’):

 cellular DF with blood-ﬁlled spaces (d/dg KS), mitoses may reach upto 10/10 hpf

 immuno: desmin +ve (other muscle markers −ve)

 d/dg haemangioma:  the blood spaces are not endothelial-lined in DF

 characteristic DF peri-collagen inﬁltration at the periphery

Variant: atypical DF (‘with monster cells’) has sparse mitoses and no necrosis; d/dg AFX (q.v.)

Variant: subcutaneous (well-circumscribed, monomorphic, ± vasc. invasion, CD34 ±ve)

Variants: keloidal (d/dg juvenile hyaline ﬁbromatosis), lipidised, epithelioid, DF with true BCC, etc.

d/dg DFSP (see under DFSP) / scar / keloid / stasis change in lower leg

d/dg storiform collagenoma (collagen ++, ﬁbroblasts are rare, similar lesions occur in Cowden’s

syndrome)

d/dg basaloid epidermal changes can be confused for BCC if the underlying DF is not recognised

d/dg pleomorphic ﬁbroma is hypocellular (unlike atypical DF) with haphazard collagen and some very

atypical cells – but mitoses are rare; there is no actinic association

Perivascular Epithelioid Cell Tumour (PEComa)

May be benign or malignant and occur at ≈ any site; exclude tuberose sclerosis clinically

Macro: well circ. lobulated solid white ﬂeshy tumour ± ﬁbrous bands (contain hyalinised vessels)

Epithelioid and spindled components (one may predominate), clear or eosinophilic cytoplasm, nuclei

are bland or focally pleom. ± eosinophilic intranuclear inclusions or prominent nucleoli but usu.

amitotic if benign); rich sinusoid-like microvasculature ± extravasated RBC; variable hyalinisation

Stains: PAS +ve, DPAS −ve

Immuno: +ve for HMB45 (usu. strong, diffuse) ± actins and desmin (usu. in spindled areas) ±CD68,

± CD10, c-kit (membranous, but usu. <50% of cells stain). Melan-A and CD34 may be patchy +ve

or −ve. CK, vimentin, S100, calretinin, CD31 and AFP are all −ve.

EM: cytoplasmic membrane-bound vesicles containing variably dense granular material 350–750 nm

, glycogen and some features of smooth muscle ± cytoplasmic rhomboid crystals. No melanosomes

or premelanosomes

Features correlated with malignancy: haemorrhage / necrosis, local invasion, nuclear pleomorphism

(esp. in epithelioid cells), only one cell type (esp. if myomatous) and mitoses ++

d/dg: melanoma (should be S100 +ve), GIST (not usu. pleomorphic and HMB45 is −ve), uterine

stromal tumour or epithelioid leiomyosarcoma (lack strong diffuse HMB45), rhabdoid tumour (HMB45

−ve, CK and desmin +ve in epithelioid cells, typical EM), other clear cell sarcomas (q.v.)

Lesions in the differential diagnosis of ‘Myxoma’

It helps to know:

◦

age, sex, site;

◦

is it totally myxoid or cellular with myxoid areas (the latter suggests

a myxoid variant – vide infra);

◦

if totally myxoid what is the vascular density / pattern?

Cardiac myxomas (see p. 79)

Superﬁcial angiomyxoma (see pp. 317–318 and see all the entities in the d/dg list under that entry)

Chordoma and soft tissue myxopapillary ependymoma (see pp. 184) – esp. if near the sacrum

Cellular myxoma (low grade myxoid neoplasm with recurrent potential) has pseudolipoblasts

Myxoma of the jaw: spindle/stellate cells with intermeshing branched processes ±odontogenic epithe-

lium

Myxolipoma (is a myxoid variant of spindle cell lipoma)

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Angiomyxoma of deep soft tissues (similar histology to aggressive angiomyxoma of the vulva - q.v.)

Juxta-articular myxoma: d/dg low grade myxoﬁbrosarcoma may be difﬁcult (CPC, esp. site, helps)

Intramuscular myxoma: sparse vasculature (focally increased), pseudolipoblasts ± muciphages

Ganglion cyst (may have cellular myxoid foci outside the cyst wall–!donotover-interpret)

Nerve sheath myxoma (= a myxoid PNST)

Ossifying ﬁbromyxoid tumour: extremities, late middle-age, variable atypia, thick acellular ‘capsule’

Low grade ﬁbromyxoid sarcoma: ! d/dg nodular fasciitis. See p. 311

Myxoﬁbrosarcoma: WHO requires ≥50% of the tumour to have the typical highly vascular stroma with

curvilinear vessels; grading ∝ mitotic count, presence of solid cellular areas and necrosis

d/dg myxoid variant of otherwise cellular tumours:

 DFSP, MPNST, GIST, MFH, etc.

 chondrosarcoma: has hyaluronidase resistant myxoid (unlike most other myxoid lesions), !

S100 is often −ve

 liposarcoma, synovial sarcoma, leiomyosarcoma

Sarcomas 2

◦

to Radiation Exposure

Most occur ≥2 years post exposure (some use this as a deﬁning requirement)

Osteosarcoma, angiosarcoma, MFH, ﬁbrosarcoma, chondrosarcoma, synovial sarcoma, mesothelioma,

MPNST

(Fibromatoses, carcinomas, haematolymphoid and CNS neoplasms also occur post radiation)

Some Soft Tissue Lesions with a Storiform Pattern (at least focally)

Mycobacterial pseudotumour

DF, DFSP, SFT, MFH / AFX, ovarian ﬁbroma, metaphyseal ﬁbrous defect / non-ossifying ﬁbroma

Sarcomatoid mesothelioma and carcinoma, malignant meningioma (d/dg 1

◦

intracranial SFT)

GIST, smooth muscle tumours, vascular tumours, FDC sarcoma, spindle/desmoplastic melanoma

Sarcomas that may be Positive for Cytokeratins

PNST

Epithelioid sarcoma

Angiosarcoma (and epithelioid haemangioendothelioma)

Rhabdoid tumour

Leiomyosarcoma (esp. of deep soft tissues)

Synovial sarcoma (focal groups)

Sarcomas that Metastasise to Lymph Nodes

Synovial sarcoma

MFH

Myxoﬁbrosarcoma

Epithelioid sarcoma

Tumours which Commonly Mimic Spindle Sarcomas

Spindle cell SCC, sarcomatoid RCC, anaplastic thyroid carcinoma

Sarcomatoid mesothelioma

Melanoma

Fasciitides, myositis ossiﬁcans, myoﬁbroblastic proliferations and pseudotumours

Grading of Soft Tissue Sarcomas

The NCI and FNCLCC are the most common systems (for details, see Graadt van Roggen, 2001)

Grade ∝ tumour type, mitotic count and % necrosis (only valid if no prior chemoRx/radioRx)

Form many tumours, the type alone deﬁnes the grade; examples from the NCI system are:

G1 =infantile ﬁbrosarcoma, well-diff/myxoid liposarcoma, epithelioid haemangioendothelioma, MPNST

with <6/10 hpf mitoses

G2 = any non-G3 tumour with necrosis at <15%

G3 = RMS, ASPS, mesenchymal chondrosarcoma, Ewing/PNET, any other sarcoma with >15%

necrosis

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