Determining Etiology:Contents 6.1 Overview 71 6.2 A Cutaneous Ulcer in Which the Clinical Diagnosis Is Not Established 72 6.2.1 Possibilities of Histologic Picture 72 6.2.2 Intravascula
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42 Schwaegerle SM, Bergfeld WF, Senitzer D, et al
Pyo-derma gangrenosum: a review J Am Acad Dermatol
1988; 18 : 559–568
43 Phillips TJ, Salman SM, Rogers GS: Nonhealing leg
ulcers: A manifestation of basal cell carcinoma J Am
Acad Dermatol 1991; 25 : 47–49
44 Harris B, Eaglstein WH, Falanga V: Basal cell
carci-noma arising in venous ulcers and mimicking
gran-ulation tissue J Dermatol Surg Oncol 1993; 19 :
150–152
45 Brodell RT, Wagamon K: The persistent nonhealing
ulcer Could it be basal cell carcinoma? Postgrad
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46 Blank AA, Schnyder UW: Squamous cell carcinoma
and basal cell carcinoma within the clinical picture
of a chronic venous insufficiency in the third stage.
Dermatologica 1990; 181 : 248–250
47 Ackroyd S, Young AE: Leg ulcers that do not heal Br
Med J 1983; 286 : 207–208
48 Pierard G, Fumal I, Pierard-Franchimont C: Cold
in-juries In: Freedberg IM, EisenAZ, Wolff K, Austen
KF, Goldsmith LA, Katz SI (eds) Fitzpatrick’s
Der-matology in General Medicine, 6th edn New York:
McGraw-Hill 2003; pp 1211–1220
49 Karmody AM, Powers SR, Monaco VJ, et al: ‘Blue toe’
syndrome: An indication for limb salvage surgery.
Arch Surg 1976; 111 : 1263–1268
50 Freund NS: Cholesterol emboli syndrome following
cardiac catheterization Postgrad Med 1990; 87 :
55–60
51 Morton RS: The treponematoses In: Champion RH,
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1998; pp 1237– 1275
52 Ohtsuka T, Yamakage A, Yamazaki S: Digital ulcers
and necroses: novel manifestations of angiocentric
lymphoma Br J Dermatol 2000; 142 : 1013–1016
53 Russwurm R, Hagedorn M: Lichen ruber ulcerosus.
Hautarzt 1989; 40 : 233–235
54 Parodi A, Ciulla P, Rebora A: An old lady with
scar-ring alopecia and an ulcerated sole Ulcerative
li-chen planus Arch Dermatol 1991; 127 : 407–410
55 Micalizzi C, Tagliapietra G, Farris A: Ulcerative
li-chen planus of the sole with rheumatoid arthritis.
Int J Dermatol 1998; 37 : 862–863
56 Barbarulo AM, Metha N, Bucalo B, et al: Recurrent
disseminated herpes zoster and cytomegalic
peri-anal ulcer: a case report and review of the literature.
Cutis 2001; 67 : 43–46
57 Pariser RJ: Histologically specific skin lesions in
dis-seminated cytomegalovirus infection J Am Acad
Dermatol 1983; 9 : 937–946
58 Rodot S, Lacour JP, Elslande L, et al: Ecthyma
gan-grenosum caused by Klebsiella pneumoniae Int J
in-62 Brandt O,Abeck D, Breitbart E, Ring J: Perianal tismus gangraenosus Hautarzt 1997; 48 : 199–202
ergo-63 Baptista AP, Mariano A, Machado A: Peranal ulcers caused by ergotamine-containing suppositories Ac-
66 Senti G, Schleiffenbaumb B, Dummera R: Vaginal cers as initial presentation of subacute myelomono- cytic leukemia Dermatology 1999; 199 : 346–348
ul-67 Magro CM, Crowson AN: Cutaneous manifestations
of Behçet’s disease Int J Dermatol 1995; 34 : 159–165
68 Slutzki S, Bogokowsky H,Gilboa Y, et al: induced skin necrosis Int J Dermatol 1984; 23 : 117–119
Coumadin-69 Defranzo AJ, Marasco P, Argenta LC: duced skin necrosis of the skin Ann Plast Surg 1995;
leish-73 Hay RJ, Adriaans B: Bacterial infections In: pion RH, Burton JL, Burns DA, Breathnach SM (eds) Rook/Wilkinson/Ebling Textbook of Dermatology, 6th edn Oxford: Blackwell Scientific Publications 1998; pp 1097–1179
Cham-74 Odom BO, James WD, Berger TG (eds) Bacterial fections In: Andrews’ Diseases of the Skin: Clinical Dermatology, 9th edn Philadelphia: WB Saunders 2000; pp 307–357
in-75 Tsao H, Swartz MN, Weinberg AN, Johnson RA: Soft tissue infections; erysipelas, cellulitis and gangre- nous cellulitis In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI, Fitzpatrick TB (eds) Fitzpatrick’s Dermatology in General Medi- cine, 5th edn New York: McGraw-Hill 1999; pp 2213– 2231
76 Irvine AD, Bruce IN, Walsh M,et al: Dermatological presentation of disease associated with antineu- trophil cytoplasmic antibodies: a report of two con- trasting cases and a review of the literature Br J Der- matol 1996; 134 : 924–928
77 Weninger W, Kain R, Tschachler E, et al:
Microscop-ic polyangiitis with eosinophilia- an overlap drome or separate disease entity? A case report and review of the literature Hautarzt 1997; 48 : 332–338
syn-78 Peterson LL: Hydralazine-induced systemic lupus erythematosus presenting as pyoderma gangreno-
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79 Skaria AM, Ruffieux P, Piletta P, et al: Takayasu
arter-itis and cutaneous necrotizing vascularter-itis
Dermatol-ogy 2000; 200 : 139–143
80 Frances C: Dermato-mucosal manifestations of
Beh-çet’s disease Ann Med Interne (Paris) 1999; 150 :
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81 Schlesinger IH, Farber GA: Cutaneous ulceration
re-sembling pyoderma gangrenosum in the primary
antiphospholid syndrome: a report of two
addition-al cases and review of the literature J La State Med
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82 Helm KF, Peters MS, Tefferi A, et al: Pyoderma
gan-grenosum-like ulcer in a patient with large granular
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27 : 868–871
83 Massa MC, Doyle JA: Cutaneous cryptococcosis
simulating pyoderma gangrenosum J Am Acad
Dermatol 1981; 5 : 32–36
84 Ryan TJ, Burnand KG: Diseases of the veins and
ar-teries – leg ulcers In: Champion RH, Burton JL,
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of Dermatology, 5th edn Oxford: Blackwell
Scientif-ic PublScientif-ications 1992; pp 1963–2013
85 Weinberg AN, Swartz MN: Miscellaneous bacterial infections with cutaneous manifestations In: Freed- berg IM, EisenAZ, Wolff K, Austen KF, Goldsmith
LA, Katz SI and Fitzpatrick TB (eds) Fitzpatrick’s Dermatology in General Medicine, 5th edn New York: McGraw-Hill 1999; pp 2257–2273
86 Gwakrodger DJ: Mycobacterial infections In: Champion RH, Burton JL, Burns DA, Breathnach SM (eds) Rook/Wilkinson/Ebling Textbook of Derma- tology, 6th edn Oxford: Blackwell Scientific Publica- tions 1998; pp 1181–1214
87 Dowd PM: Reactions to cold In: Champion RH, ton JL, Burns DA, Breathnach SM (eds) Rook/Wil- kinson/Ebling Textbook of Dermatology, 6th edn Oxford: Blackwell Scientific Publications 1998;
Bur-pp 957– 972
88 Kalter DC, Rudolph A, McGavran M: Livedo laris due to multiple cholesterol emboli J Am Acad Dermatol 1985; 13 : 235–242
reticu-89 Ramos-e-Silva M, Rebello PF: Leprosy Recognition and treatment Am J Clin Dermatol 2001; 2 : 203–211
Chapter 5 Determining Etiology
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Trang 3Determining Etiology:
Contents
6.1 Overview 71
6.2 A Cutaneous Ulcer in Which
the Clinical Diagnosis Is Not Established 72
6.2.1 Possibilities of Histologic Picture 72
6.2.2 Intravascular Occlusion 72
6.2.3 Vasculitis 76
6.2.4 Other Histologic Patterns 79
6.2.5 Insufficient Histologic Data 80
6.3.4 ‘Unexpected’ Histologic Findings
in Certain Types of Cutaneous Ulcers 82
6.4 Suspected Malignancy 82
6.4.1 When Should Malignancy Be Suspected? 82
6.4.2 Epithelioma as a Primary Lesion 83
6.4.3 Epithelioma Developing
in a Long-Standing Cutaneous Ulcer 83
6.5 An Ulcerated Nodule or Plaque 84
6.5.1 Ulcers Developing Within a Nodule
or a Plaque 84
6.5.2 Granulomatous Histologic Pattern 84
6.5.3 Seeking an Infectious Cause 84
In most cases, routine blood tests should beperformed for every patient presenting with acutaneous ulcer where the diagnosis is not es-tablished These routine workups, which gener-ally include tests such as erythrocyte sedimen-tation rate, complete blood count, and bloodchemistry, may direct the physician towards theetiology in certain cases In many other situa-tions with cutaneous ulcers, the anamnesis andphysical examination may suggest the need for
a more specific and focused investigation.For example, an ulcer suspected of being re-lated to hemolytic anemia requires the perfor-mance of a blood smear, which may reveal sick-led cells, spherocytes, etc
Similarly, when a connective-tissue disease
is suspected, the workup should include tory parameters such as anti-nuclear factor,rheumatoid factor, cryoglobulin level, or anti-neutrophil cytoplasmic antibody (ANCA)
labora-In cases of cutaneous ulcers, histologic imens may provide valuable information re-garding their etiology The histologic hallmark
spec-of a cutaneous ulcer is dictated by its medical
definition, namely, the absence of epidermis and
the partial or complete absence of dermis Yet
the question is not whether there is an ulcer butwhat the underlying pathology is Therefore,the biopsy should not be taken from the ulceritself, but rather from an area adjacent to the ul-cer margin, covered by dermis and epidermis;where specific histologic features may be iden-tified
06_071_088 01.09.2004 13:57 Uhr Seite 71
Trang 4In order to cover all the clinical possibilities
that may derive from the histology of a
cutane-ous ulcer, a broad knowledge of
dermatopa-thology is required Nevertheless, our purpose
here is not to review the entire gamut of
cur-rently available dermatopathological
knowl-edge, but to relate only the most practical
clini-cal implications arising from histologic
fea-tures of cutaneous ulcers
A biopsy should be considered from an
ulcer’s margin under the following
condi-tions:
5An ulcer in which the clinical
diag-nosis is not established:when
histo-ry, physical examination and theulcer’s appearance do not provide aconcrete diagnosis i.e., when there is
no clinical clue, or when one wants
to confirm a suspected/doubtful agnosis
di-5A non-healing ulcer:Biopsy should
be considered when dealing with anulcer that does not heal within three
to four months of optimal treatment
This is subject to the clinical set-up(see below)
5Suspected malignancy:when the
ulcer is suspected of being nant/cancerous Under these cir-cumstances, a biopsy should be per-formed as early as possible
malig-Each of the above possibilities is discussed
below
6.2 A Cutaneous Ulcer in Which
the Clinical Diagnosis
Is Not Established
6.2.1 Possibilities of Histologic Picture
Sometimes, neither the history nor the physical
examination provides any clues to assist in
arriving at a diagnosis A biopsy from an areaadjacent to the ulcer margin should be done, inorder to obtain diagnostic clues
This chapter deals with those topics that arespecifically relevant to the histopathology ofskin ulcers, such as intravascular occlusion orvasculitis In addition, we shall discuss the steps
to be taken if the histologic specimen does notprovide sufficient diagnostic information
6.2.2 Intravascular Occlusion
Intravascular occlusion may manifest in
sever-al forms, depending on the pathologic processleading to occlusion Conditions characterized
by intravascular occlusion are listed inTable 6.1
Coagulopathies are common forms of vascular occlusion [1, 2] In these cases, intra-vascular occlusion is reflected histologically bythe presence of fibrin thrombi within the lumen
intra-of blood vessels (Fig 6.1) Fibrin thrombi pear as amorphous eosinophilic material inhematoxylin and eosin (H&E) stain; they may
ap-be more obvious in a periodic acid-Schiff (PAS)stain In severe forms of coagulopathy, areas ofcutaneous necrosis may be observed [2].Fibrin thrombi may be accompanied byunique features such as cholesterol clefts incholesterol emboli (Fig 6.2) or calcium deposi-tion in calciphylaxis (Fig 6.3) Other histologicfeatures may also be involved in intravascularocclusion For example, in sickle cell anemia,blood vessels are occluded by the sludging ofsickled erythrocytes [3, 4] (Fig 6.4)
Note that intravascular occlusion and thepresence of fibrin thrombi within the lumen ofblood vessels may variably appear in vasculiticprocesses as well Yet, vasculitis also has uniquecharacteristics, such as the infiltration of whiteblood cells within the wall of blood vessels oractual signs of damage to the vessel wall (seeSect 6.2.3) In this section, we present condi-
tions of intravascular occlusion which are not
accompanied by vasculitis
In some cases, the clinical diagnosis isstraightforward and the histology simply com-plements the history and physical examination
Chapter 6 Biopsy and Laboratory Investigation
72
6
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Trang 5Fig 6.1.
A fibrin thrombus within
the lumen of a blood vessel
Table 6.1.Intravascular occlusion
Trang 6For instance, the diagnosis of coumarin
necro-sis may be reached when anamnenecro-sis confirms
intake of the drug a few days before ulceration
Similarly, cutaneous ulcers and splenomegaly
in a young patient raise the possibility of
hemo-lytic anemia
6.2.2.1 Histologic Features
In conditions such as coagulopathies, nemias, or anti-phospholipid syndrome, thehistopathologic features may be similar, and anaccurate diagnosis cannot be established bybiopsy alone On the other hand, in other condi-tions, specific histologic features may assist indetermining the ulcer’s etiology
dysprotei-Chapter 6 Biopsy and Laboratory Investigation
Trang 7Histologic clues such as those mentioned
be-low should be sought (presented in Schema
6.1):
5Microcalcifications in small to
me-dium sized vessels:This histologicfinding appears in calciphylaxis It
is well demonstrated by a Von Kossastain [17–19]
5Bizarre forms of red blood cells:
Bi-zarre forms of red blood cells such
as sickled erythrocytes or tes may be found within capillaries
spherocy-in ulcers caused by hemolytic mia; extravasation of red blood cellsmay be seen [3, 4, 11]
ane-5Cholesterol clefts:Cholesterol
em-boli are characterized by the ence of cholesterol clefts within thefibrinous material [20–22] Note thatthe absence of typical cholesterolclefts does not necessarily rule outthe diagnosis of cholesterol emboli[25, 26] It may be difficult to locateand identify cholesterol emboli, and
pres-a deep biopsy mpres-ay be needed [2]
6.2.2.2 Other Histologic Clues
Atrophie Blanche In the initial stages ofatrophie blanche, the entity might still not beidentified by histology; i.e., fibrin thrombiwithin blood vessels may be the sole finding.However, more severe cases may present fea-tures such as infarction with hemorrhage or aninflammatory infiltrate In late atrophic lesions,
a thin epidermis is usually seen, and the dermisbecomes sclerotic [2, 13]
Stain Type.The type of stain used may giveand clues for diagnosis: Precipitated cryoglob-ulins appear bright red with PAS stain, whileother fibrinoid depositions, caused by otherprocesses, tend to stain lighter [2] As men-tioned above, deposition of calcium withinblood vessels, as appears in calciphylaxis, may
be identified by using the Von Kossa stain [19]
Trang 85Anti-thrombin III level
5Resistance to activated protein C
5Analysis of DNA to factor V Leiden
Although the scheme for histological
identifi-cation shown in Fig 6.5 is quite comprehensive,
we have encountered isolated cases of
cutane-ous ulcers with fibrin thrombi in which,
follow-ing thorough investigation, a definite etiology
could not be identified
6.2.3 Vasculitis
Fully developed vasculitis is characterized
by the following histologic features [1] (seeFig 6.6):
5Infiltration of white blood cellswithin the wall of blood vessels
5Deposits of fibrin within the walland lumen of blood vessels
5Extravasation of red blood cells –secondary to injury of the bloodvessels
Other signs of damage to the wall may bepresent, such as the degeneration of collagenfibers, and the necrosis of endothelial cells andsmooth muscle cells
A special type of vasculitis that manifests
unique features is leukocytoclastic vasculitis,
the hallmark of which is the presence of morphonuclear cells and fragmented nuclei,usually termed ‘nuclear dust’
poly-Note that when vasculitis results in the mation of cutaneous ulcers, we expect to identi-
for-fy a form of necrotizing vasculitis in the
histo-logic specimen, showing necrotic areas with
Chapter 6 Biopsy and Laboratory Investigation
Trang 9significant damage to blood vessels and
sur-rounding tissues
The literature is replete with a wide range of
different classifications of vasculitic lesions,
and there is no one accepted classification
Most authors present differing specific
classifi-cations
Tables 6.2, 6.3, and 6.4 present a reasonable
and convenient classification of types of
vascu-litis that tend to be associated with ulceration
These tables are based, in part, on the following:
1 Classification of vasculitis, as presented by
A.B Ackerman [1]
2 Classification of the vasculitis syndromes, as
presented by A.S Fauci [27] in Harrison’s
Principles of Internal Medicine
3 The definitions of vasculitis as delineated by
the Chapel Hill Consensus Conference in 1992
[28, 29]
Accurate identification of the subtype of
vas-culitis is determined by the following data:
5Type of vessel involved (arterial
system versus venous system)
5Size of vessel involved (e.g.,
postca-pillary venule)
5Type of infiltrate: neutrophilic?
lym-phocytic?
5Presence or absence of
leukocytoc-lasis (fragmented neutrophilic clei)
nu-Table 6.3 presents conditions associated withsmall-vessel leukocytoclastic vasculitis
In some cases of vasculitis, the pathologywill not be obvious in a given histologic speci-men The lesion may be in its early stages, whenthe vasculitic process may not yet be evident Inother cases, the specific site from which the bi-opsy was taken will not reflect the pathologyaccurately Therefore, if a histologic specimen isnot diagnostic, the biopsy should be repeated.Grunwald et al [33] have shown that directimmunofluorescence is a very sensitive test,which may confirm the presence of vasculitis inconditions where routine histologic specimenssometimes fail to do so (e.g., in the early and re-solving stages of the vasculitic process)
Where there is histologic evidence of litis, the following laboratory workup should
vascu-be considered, depending on the clinical up:
set-5Erythrocyte sedimentation rate
5Complete blood count
Vasculitis: note the damaged vessel
wall, infiltrated by inflammatory
cells
t
t
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Trang 105p-antineutrophil cytoplasmic
anti-body (pANCA)
5Serum markers for malignancy
5Chest X-ray
5Abdominal ultrasound
5Fecal occult blood testing
In some cases, even after extensive tion, no definite explanation for the vasculitiscan be found Such cases remain defined asidiopathic vasculitis, in which a specific diseasemay become apparent at a later date
investiga-Chapter 6 Biopsy and Laboratory Investigation
78
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t
Table 6.2.Cutaneous ulcers characterized by vasculitis
Vasculitis induced by an exogenous stimulus:
Other vasculitic processes
쐌 Vasculitis associated with malignancy
쐌 Nodular vasculitis (erythema induratum)
쐌 Erythema elevatum diutinum
is not necessarily associated with vasculitis Lesions in Behcet’s disease may appear without histologic evidence
of vasculitis [32].
d Mixed cryoglobulinemia may be associated with several systemic or infectious diseases such as rheumatoid thritis, Sjögren's disease, chronic lymphocytic leukemia and hepatitis C.
ar-06_071_088 01.09.2004 13:57 Uhr Seite 78
Trang 116.2.4 Other Histologic Patterns
In some cases, a unique histologic pattern may
be seen (e.g., a specific type of tumor, or a cific inflammatory process), which provides anaccurate diagnosis Yet, there is a huge range ofpossible causes of skin ulcers Hence, manydiagnoses may be revealed in a histologic spec-imen obtained from a cutaneous ulcer A broadknowledge of dermatopathology is needed toidentify all the histologic possibilities
spe-The classic textbooks of dermatopathologydeal with this issue very well
5Histologic Diagnosis of Inflammatory Skin Diseases: An Algorithmic Method Based on Pattern Analysis (A B Ackerman)
5Lever’s Histopathology of the Skin (Elder, Elenitsas, Jaworsky and Johnson)
6.2
t
Table 6.3.Small vessel leukocytoclastic vasculitis a, b
Vasculitis induced by an exogenous stimulus:
Vasculitis associated with malignancy
a More detailed discussions regarding vasculitis and its classification can be found in dermatopathology texts We
do wish to make the point, however, that although in most of the conditions listed in the above table the trate is largely neutrophilic, in certain types of vasculitis there is typically a lymphocytic vasculitis (e.g., in col- lagen diseases such as SLE and some cases of drug-induced vasculitis or arthropod bites [1, 2].
infil-b Erythema elevatum diutinum also manifests small vessel leukocytoclastic vasculitis [28].
Table 6.4.Cutaneous ulcers in which medium-sized
vas-culitis or large cell vasvas-culitis may be identified a, b
a Wegener’s granulomatosis presents as
leukocytocla-stic vasculitis of small vessels together with vasculitis
of large venous vessels [1].
b Polyarteritis nodosa may present as leukocytoclastic
vasculitis of small vessels and as large vessel arterial
vasculitis [1].
06_071_088 01.09.2004 13:57 Uhr Seite 79
Trang 12Note that in most cases, the presence of
inflam-matory cells within the histologic section
can-not be used as a diagnostic clue, except where a
unique pattern of distribution is identified Any
cutaneous ulcer is subject to inflammatory
pro-cesses, independent of its primary basic
pathol-ogy These inflammatory responses may
mani-fest (but not necessarily) as infiltrations of
var-iable numbers of inflammatory cells within the
superficial dermis, usually around blood
ves-sels Sometimes, the inflammatory infiltrate
re-sults from superficial secondary infection and
has no etiologic significance Nevertheless, in
some cases, a unique pattern of distribution of
inflammatory cells (e.g., numerous plasma cells
in syphilis, or a granulomatous pattern) may
provide important diagnostic clues A detailed
discussion of inflammatory patterns would
en-tail covering the entire field of
dermatopathol-ogy, and is beyond the scope of this chapter
6.2.5 Insufficient Histologic Data
Sometimes the histologic data do not seem to
provide even the slightest diagnostic clue In
such a case, it is advisable to thoroughly scan the
entire slide and biopsy specimen to see if it
sho-ws certain specific histologic characteristics
such as fibrin thrombi, vasculitis, a
granuloma-tous pattern (detailed below), or some other
specific pattern If this step does not provide
further clues, another biopsy from a different
area of the same ulcer should be considered,
sin-ce there may be considerable variation among
different specimens taken from the same ulcer
When certain conditions are suspected, a
bi-opsy containing deep dermis and subcutaneous
tissue should be considered For example, in
polyarteritis nodosa and nodular vasculitis, a
superficial biopsy may not reveal the presence
of vasculitis Similarly, as suggested in the
sec-tion on vasculitis, direct immunofluorescence
of a tissue specimen from the ulcer margin may
confirm the diagnosis of vasculitis
Figure 6.7 summarizes the approach to the
diagnosis of ulcers when the history and
physi-cal examination do not lead to a diagnosis It
includes the main histologic findings and their
clinical implications
6.3 A Non-Healing Ulcer
6.3.1 The Various Histologic Patterns
Biopsy should be considered when dealing with
an ulcer that does not heal within 3–4 months
of optimal treatment (depending on the clinicalset-up) In these cases, additional parametersmay influence the decision as to whether the ul-cer should be sampled For example, when theaffected area is too close to a bone (i.e., an ulcerlocated over the anterior tibia), it may beappropriate to postpone the biopsy for a while,giving the ulcer a longer period of time to heal.Classical examples of non-healing ulcers arethose where the clinical features suggest the di-agnosis of a ‘venous ulcer’ or an ‘ischemic ulcer’
in a patient with peripheral arterial disease Inthese cases, it is not the role of the histologicspecimen to establish a diagnosis Diagnoses ofsuch cases are based on physical examinationand specific tests such as Doppler flowmetry ofleg arteries or Doppler ultrasonography of thelower limb venous system
In such cases, the main purpose of the biopsy
is to confirm that the ulcer, which appears to bebenign, is not, in fact, caused by some otherunderlying process such as malignancy Occa-sionally, histologic data may direct the physiciantowards other conditions such as infectious pro-cesses or pyoderma gangrenosum The histolog-
ic possibilities of non-healing ulcers are
(fi-5A variable degree of inflammation
5Presence of hemosiderin
5Extravasation of red blood cells
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06_071_088 01.09.2004 13:57 Uhr Seite 80
Trang 13Fig 6.7.Algorithm for laboratory workup when clinical diagnosis has not been established
Fig 6.8.The possible histologic patterns, in the case of a non-healing ulcer
06_071_088 01.09.2004 13:57 Uhr Seite 81
Trang 14The presence of fibrin cuffs is considered to be
a typical histologic finding in venous ulcers
These are organized structures composed of
fi-brin, laminin, fibronectin, tenascin, collagen,
and trapped leukocytes [35] It is suggested that
high venous pressure results in dermal leakage
of fibrinogen with subsequent formation of
pericapillary fibrin layers [35] Pericapillary
fi-brin is positively stained by Martius scarlet
blue Its presence may be also confirmed by
di-rect immunofluorescence [36]
Falanga et al [36] documented the presence
of pericapillary fibrin in 14 (93%) of 15 patients
with venous ulceration but in only one of 14
pa-tients (7%) who had cutaneous ulcers of other
etiologies Burnard et al found that
pericapil-lary fibrin can be found in the skin of patients
with venous insufficiency, whether the skin is
ulcerated or not [37] However, cuffing can be
seen if appropriate staining has been carried
out, provided that its structure has not been
de-stroyed by an inflammatory response, which
frequently accompanies ulceration
Note that fibrin cuffs may be seen in
diabet-ic ulcers, including ischemdiabet-ic diabetdiabet-ic ulcers
[38] and in pressure ulcers [39] However, while
in venous insufficiency the fibrin is organized
in concentric lamellae, in diabetic ulcers the
fi-brin tends to appear as fragmented and diffuse
deposits [38]
6.3.3 The Histologic Characteristics
of Ischemic Ulcers
The narrowing or occlusion of blood vessels
can be seen in diabetic ulcers and ischemic
ulcers as a result of thickening of the blood
ves-sel wall [38] This process is caused by an
abnor-mal proliferation of endothelial cells or smooth
muscle cells [38] Narrowing or occlusion of
blood vessels may also be seen as a result of
ath-erosclerotic disease
These processes involve only blood vessels of
the deep plexus, and these histologic
character-istics are not seen within the superficial plexus;
therefore, most punch biopsies, which are
rela-tively superficial, will not reveal the above
Malignancy may be suspected under the lowing circumstances:
fol-5When an ulcer arises within aprominent, heavily infiltrated nod-ule or tumor (e.g., ulceration ofmelanoma or a cutaneous lesion oflymphoma)
5When granulation tissue extendsbeyond the ulcer margin: this mayoccur in basal cell carcinoma (BCC)
or squamous cell carcinoma (SCC)[40]
5When specific characteristic tures are observed, such as the typi-cal pearly border of a BCC
fea-Chapter 6 Biopsy and Laboratory Investigation
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