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CORRESPONDENCE
bone marrow recovery could also exhibit unusual properties.
These functional changes could lead to a release of cytokines
and an upregulation of expression of some adhesion molecules such as a4-integrin, all changes that might promote
adhesion of neutrophils to vessel walls, damage to the
endothelium, diapedesis and accumulation in some areas
such as the dermis.11,12 The earliest phase of this recovery is
probably ongoing while the peripheral count still shows a
sometimes deep granulocytopenia, the functional properties
of these first neutrophils being more important than their
absolute number. This theory could also possibly apply to
usual cases of Sweet’s syndrome, where a rapid increase in
neutrophil count by bone marrow stimulation for various
reasons could explain both the usual high neutrophil count
and the unusual behaviour of these highly stimulated cells. A
similar mechanism has been suggested by some authors to
account for cases of Sweet’s syndrome occurring during
myelodysplastic syndromes.13 Finally, a similar pathogenesis
could also be hypothesized for ATRA-induced ND, as ATRA is
a potent stimulator of some neutrophil functions.
Department of DermatologyPhlebology and *Laboratory of
Pharmacovigilance, CHRU
Montpellier, Hôpital Saint-Eloi, 80
Avenue Augustin Fliche, 34295
Montpellier cedex 5, France
E-mail: o-dereure@chu-montpellier.fr
O.Dereure
D.Hillaire-Buys*
J-J.Guilhou
References
1 von der Driesch P. Sweet’s syndrome. J Am Acad Dermatol 1994;
31: 535–56.
2 Roujeau JC. Neutrophilic drug eruptions. Clin Dermatol 2000; 18:
331–7.
3 Ross HJ, Moy LA, Kaplan R, Figlin RA. Bullous pyoderma gangrenosum after granulocyte colony-stimulating factor treatment.
Cancer 1991; 68: 441–3.
4 Park JW, Mehrotra B, Barnett BO et al. The Sweet syndrome
during therapy with granulocyte colony-stimulating factor. Ann
Intern Med 1992; 116: 996–8.
5 Johnson ML, Grimwood RE. Leukocyte colony-stimulating factors.
A review of associated neutrophilic dermatoses and vasculitides.
Arch Dermatol 1994; 130: 77–81.
6 van Kamp H, van den Berg E, Timens W et al. Sweet’s syndrome
in myeloid malignancy: a report of two cases. Br J Haematol 1994;
86: 415–17.
7 Richard MA, Grob JJ, Laurans R et al. Sweet’s syndrome induced
by granulocyte colony-stimulating factor in a woman with congenital neutropenia. J Am Acad Dermatol 1996; 35: 629–31.
8 Lewerin C, Mobacken H, Nilsson-Ehle H, Swolin B. Bullous pyoderma gangrenosum in a patient with myelodysplastic syndrome
during granulocyte colony-stimulating factor therapy. Leuk
Lymphoma 1997; 26: 629–32.
9 Levi I, Raanani P, Shalmon B et al. Acute neutrophilic dermatosis
induced by all-trans-retinoic acid treatment for acute promyelocytic leukemia. Leuk Lymphoma 1999; 34: 401–4.
10 Aractingi S, Mallet V, Pinquier L et al. Neutrophilic dermatoses
during granulocytopenia. Arch Dermatol 1995; 131: 1141–5.
11 Spiekermann K, Roesler J, Emmendoerffer A et al. Functional
features of neutrophils induced by G-CSF and GM-CSF treatment:
differential effects and clinical implications. Leukemia 1997; 11:
466–78.
12 Johnston B, Kubes P. The a4-integrin: an alternative pathway for
neutrophil recruitment? Immunol Today 1999; 20: 545–50.
13 Reuss-Borst MA, Pawelec G, Saal JG et al. Sweet’s syndrome
associated with myelodysplasia: possible role of cytokines in the
pathogenesis of the disease. Br J Haematol 1993; 84: 356–8.
The importance of skin biopsy in the diverse clinical
manifestations of cholesterol embolism
DOI: 10.1111/j.1365-2133.2004.06000.x
SIR, Cholesterol embolism (CE) is a multisystemic disorder
characterized by release of cholesterol crystal emboli from
eroded atherosclerotic plaques of the aorta or large feeder
arteries.1–6 These lead to ischaemia and rarely cause infarction in tissue distal to the emboli. CE may occur spontaneously or after precipitating factors such as vascular surgery,
angiographic procedures, or anticoagulant and thrombolytic
therapies.7 Although many organs may be targets of emboli,
the most commonly involved organs are the skin and kidneys.
We report a series of 52 patients where cutaneous lesions
suggested a diagnosis of renal CE in 50 (96%) and skin biopsy
provided the correct diagnosis in 27 patients (52%).
We surveyed 52 nephrology in patients consulting between
1989 and 1999 (44 men and eight women; mean age
68 years). The diagnosis of CE was made on clinical grounds
alone in seven of 52 patients (13%). They presented a typical
triad comprising a precipitating event, acute or subacute
renal failure and ischaemic peripheral changes such as
cutaneous lesions on the lower extremities, gastrointestinal
bleeding or neurological involvement. The disease was
spontaneous in 11 patients (21%); a triggering factor was
identified in 41 patients (79%), such as angiography (50%),
anticoagulant treatment (21%) and aneurysm resection
(15%). Acute renal failure occurred in 18 patients (35%),
subacute renal failure in 29 patients (56%) and chronic and
stable renal failure in five patients (9%). Cutaneous lesions,
which usually came before the onset of renal symptoms,
occurred in 50 patients (96%). Patients had one or more
characteristic skin lesions such as redness on the toes (79%)
(Fig. 1a), livedo reticularis of the lower limb and abdomen
(38%), or gangrene of the extremities (15%), leading to
amputation of a portion of the lower extremity in three
patients; two patients also showed ulceration of the scrotum
and penis. The two patients without cutaneous lesions had a
spontaneous form of renal cholesterol crystal embolization
presenting as a chronic and stable renal impairment.
Skin biopsy provided the correct diagnosis in 27 patients
(52%). The histological features of CE are highly characteristic, showing an occlusion of the lumen of small arteries and
arterioles by atherosclerotic material. As the lipids are
dissolved by the techniques used for preparation of the tissue
for histological examination, the cholesterol crystals may be
identified within lumina of small vessels by the presence of
multiple, biconvex, needle-shaped clefts that remain after
2004 British Association of Dermatologists, British Journal of Dermatology, 150, 1212–1234
CORRESPONDENCE
1231
most definitive method of diagnosing renal cholesterol crystal
embolization. However, during the acute phase of the disease
many patients may be too ill to proceed with this invasive
procedure. Moreover, as cholesterol crystal embolization is a
patchy process, a focal lesion can elude histological examination.8 Random muscle biopsy from the lower extremities
may also have a high diagnostic yield, but the sensitivity of
this procedure has never been evaluated. In contrast, biopsy
of characteristic cutaneous lesions represents a more easily
accessible site and may yield a positive diagnosis in many
cases.9 Cutaneous manifestations such as livedo reticularis,
gangrene, cyanosis, ulceration, nodules and purpura are the
most common signs of systemic cholesterol crystal embolization, and were found to occur in 35–90% of patients with CE
in previous studies.2,9,10 In our series typical skin lesions
occurred in a greater number of patients (50 of 52 patients)
than in previous studies because we looked for early
cutaneous manifestations of CE and found 79% of our
patients to have redness on the toes. Early recognition of CE
skin lesions is not easy because lesions are often asymptomatic and weak, but looking for these is essential for early
diagnosis of CE. Therefore, skin biopsy should be considered
the best choice for histological diagnosis, because it is a simple
and noninvasive procedure that avoids the increased morbidity of renal biopsy.
Figure 1. (a) Extent of redness on the toes. (b) Well-demarcated
cholesterol crystals may be identified within the lumen of a small
vessel.
cholesterol has dissolved during fixation (Fig. 1b). Percutaneous renal biopsy was performed in only four patients (8%).
In two patients with a stable and chronic renal impairment,
histological confirmation was obtained by nephrectomy
specimens because of renal carcinoma in both cases. In four
patients (8%), CE was confirmed histologically in the less
likely target organs such as gastrointestinal tissue (stomach
and colon) obtained on endoscopy. In one patient, who had
an associated haematological disorder, the histological diagnosis was made when an iliac crest bone marrow biopsy
showed cholesterol crystal emboli. Autopsy was the sole
means of histological diagnosis in three patients. All patients
had been followed for at least 2 years. The 1- and 2-year
survival rate, estimated using Kaplan–Meyer actuarial
curves, was 69% and 61%, respectively. Death was due to
cardiac causes, gastrointestinal ischaemia and stroke.
Diagnosis of CE requires a high index of suspicion because
the typical triad may be absent and clinical manifestations
can be nonspecific. Renal biopsy should be considered the
Department of Dermatology, Azienda
A.M.Manganoni
Spedali Civili, P.le Spedali Civili 1,
M.Venturini
25123 Brescia, Italy
F.Scolari*
*Division of Nephrology and
G.Tucci
Department of Pathology,
F.Facchetti
Spedali Civili and
S.Graifemberghi
University, Brescia, Italy
P.G.Calzavara-Pinton
E-mail: dermatologia@
spedalicivili.brescia.it
References
1 Kassirer J. Atheroembolic renal disease. N Engl J Med 1969; 280:
812–18.
2 Fine MJ, Kapoor W, Falanga V. Cholesterol crystal embolization: a
review of 221 cases in the English literature. Angiology 1987; 38:
769–84.
3 Lye WC, Cheah JS, Sinniah R. Renal cholesterol embolic disease.
Case report and review of the literature. Am J Nephrol 1993; 13:
489–93.
4 Saleem S, Lakkis FG, Martinez-Maldonado M. Atheroembolic renal disease. Semin Nephrol 1996; 16: 309–18.
5 Colt HG, Begg RJ, Saporito JS et al. Cholesterol emboli after cardiac catheterization: eight cases and review of the literature.
Medicine 1988; 67: 389–400.
6 Dahlberg P, Frecentese D, Cogbill T. Cholesterol embolism:
experience with 22 histologically proven cases. Surgery 1989;
105: 737–46.
7 Scolari F, Bracchi M, Valzorio B et al. Cholesterol atheromatous
embolism: an increasingly recognized cause of acute renal failure.
Nephrol Dial Transplant 1996; 11: 1607–12.
8 Flory CM. Arterial occlusion produced by emboli from eroded
aortic atheromatous plaques. Am J Pathol 1945; 21: 549–65.
2004 British Association of Dermatologists, British Journal of Dermatology, 150, 1212–1234
1232
CORRESPONDENCE
9 Falanga V, Fine MJ, Kapoor WN. The cutaneous manifestations
of cholesterol crystal embolization. Arch Dermatol 1986; 122:
1194–8.
10 Thadhani R, Camargo C, Xavier R et al. Atheroembolic renal
failure after invasive procedures. Natural history based on 52
biopsy-proven cases. Medicine 1995; 74: 350–8.
Eccrine porocarcinoma and eccrine poroma arising
in a scar
DOI: 10.1111/j.1365-2133.2004.05997.x
SIR, Malignant tumours occurring at scar sites have long been
reported in the literature. Most of them are squamous cell
carcinomas and basal cell carcinomas. To our knowledge,
eccrine porocarcinoma and eccrine poroma have not yet been
described in association with scars. We report a case of
eccrine porocarcinoma and eccrine poroma arising from a
scar on the right foot.
A 74-year-old woman had had paralysis of the lower half of
the body for more than 50 years from spinal injury due to
tuberculosis. She had scars caused by skin infections due to
osteomyelitis and recurrent decubitus on the lower legs and
feet. She presented with a partly ulcerated, fresh, red nodule
surrounded by a brownish macule, 5 cm in diameter, situated
within a scar on the anterior surface of her right foot
(Fig. 1a). In addition, there was a slightly elevated, reddish
but partly white nodule surrounded by a brown macule, 4 cm
in diameter, situated in a scar on the posterior surface of her
right foot (Fig. 1b).
Histology of the nodule on the anterior surface of her right
foot revealed a tumour composed of cords and broad columns of
generally small basal-like cells extending into the dermis from
the epidermis. The tumour cells were arranged irregularly and
showed moderate atypia. The cells had large, hyperchromatic,
irregularly shaped nuclei and some of them were multinucleated. Atypical mitotic figures were also seen. Ducts and small
cysts were also seen within the tumour nests (Fig. 2a,b). The
tumour cells stained positive with periodic acid–Schiff, alcian
blue, epithelial membrane antigen, cytokeratin 7 (Fig. 2c) and
carcinoembryonic antigen (Fig. 2d). However, diastase digestion, cytokeratin 20, S-100 protein and gross cystic disease
fluid protein-15 were negative in the tumour cells. Based on
these clinical and histopathological findings, the tumour on the
anterior surface of the right foot was diagnosed as an eccrine
porocarcinoma arising from a scar.
Histopathologically, the nodule on the posterior surface of
the right foot showed nests and islands of uniformly small
basaloid cells, which were sharply demarcated from the
adjacent keratinocytes. Broad, anastomosing cords and solid
columns and nests of large cells extended into the dermis to
varying levels. Duct-like structures were also found. The
tumour was diagnosed as an eccrine poroma that occurred in
association with a scar.
Carcinomas are well known to arise frequently from a burn
scar, and such carcinomas are termed Marjolin’s ulcers. Skin
malignancies are thought to occur in association not only
Figure 1. (a) Anterior view of the right leg upon initial examination.
Note a partly ulcerated, fresh, red nodule surrounded by a brownish
macule (arrow). (b) On the posterior surface of the right foot there
was a slightly elevated, reddish nodule surrounded by a brownish
macule (arrow).
Figure 2. Histopathological features of the eccrine porocarcinoma on
the anterior surface of the right foot. (a) The tumour was composed of
cords and broad columns of basaloid cells extending into the dermis
from the epidermis. Irregular-shaped ducts and small cysts were seen
within the tumour columns (haematoxylin and eosin; original magnification · 40). (b) The cells had large, hyperchromatic, atypical
nuclei (haematoxylin and eosin; original magnification · 200). (c)
The tumour cells forming ductal structures were positive for cytokeratin 7 (original magnification · 120). (d) Carcinoembryonic
antigen was also positive in the wall of irregular ducts (original
magnification · 120).
with burn scars, but also with scars in chronically inflamed or
traumatized skin. Among such malignant tumours, squamous cell carcinomas occur most frequently in association
2004 British Association of Dermatologists, British Journal of Dermatology, 150, 1212–1234