Full text of DOI:10.1067/mjd.2000.110043

Brief reports 867
J AM ACAD DERMATOL
VOLUME 43, NUMBER 5
Multiple pseudolymphomas caused by
Hirudo medicinalis therapy
Josef Smolle, MD, Lorenzo Cerroni, MD, and Helmut Kerl, MD Graz, Austria
Therapy with medicinal leeches (Hirudo medicinalis) is now frequently applied in plastic surgery and in the
management of chronic venous insufficiency. We observed a patient in whom firm, brown-red, pea-sized
papules developed at each site where leeches had been applied on the lower legs. Histology,
immunohistology, and molecular analysis of T-cell receptor and immunoglobulin heavy chain gene
rearrangement proved these lesions to be follicular pseudolymphomas. (J Am Acad Dermatol 2000;43:867-9.)
he medicinal leech (Hirudo medicinalis) has
been used for medical purposes for about
T
3000 years.1 In the past decade, this remedy
has become popular again. Particularly in plastic and
reconstructive surgery, H medicinalis treatment has
been proven to be effective in avoiding necrosis of
congested skin flaps.2-4 Furthermore, H medicinalis
is used for the treatment of venous insufficiency.5 In
both indications, the release of hirudin, an antihe-
mostyptic agent, together with effective sucking of
venous blood and subsequent spontaneous bleeding
are considered to be the responsible therapeutic
mechanisms.5 In addition, hirudin derivatives can
also be produced by gene technology and are cur-
rently tested in systemic therapy for vascular occlu-
sive disease.6
FPO
Side effects of H medicinalis therapy are consid-
ered to be rare. Scarring and local bacterial infection
have been reported.4,7-9
CASE REPORT
A 56-year-old woman presented with multiple
lesions on both lower legs, which had appeared sev-
eral weeks after she had received H medicinalis
treatment because of chronic venous insufficiency
with varicosis, edema, tenderness, and hyperpig-
mentation.
Fig 1. Multiple firm, brown nodules on the lower legs sev-
eral weeks after therapy with medicinal leeches.
Several pea-sized, firm, brown-red cutaneous
nodules could be observed on both lower legs (Fig
1). In some nodules, small areas of central scarring
were evident. A biopsy was performed on one of
these lesions.
Histologic examination showed a superficial and
deep nodular dermal infiltrate (Fig 2) with germinal
center formation (Fig 3). These showed a regular
morphology and presence of so-called tingible body
macrophages and a normal mantle zone. The infil-
trate outside germinal centers consisted of lympho-
cytes admixed with a few eosinophilic granulocytes
and plasma cells. In the center of the lesion, the
upper and mid dermis was replaced by scar tissue.
Immunohistology performed with a standard 3-step
immunoperoxidase technique10 showed a nodular
From the Department of Dermatology, University of Graz.
Reprint requests: J. Smolle, Department of Dermatology, University
of Graz, Auenbruggerplatz 8, A-8036 Graz, Austria.
Copyright © 2000 by the American Academy of Dermatology, Inc.
0190-9622/2000/$12.00 + 0 16/54/110043
doi:10.1067/mjd.2000.110043

868 Brief reports
J AM ACAD DERMATOL
NOVEMBER 2000
Fig 2. Nodular dermal infiltrate with germinal centers.
Scar tissue in the upper and mid dermis. (Hematoxylin-
eosin stain; original magnification ×50.)
Fig 4. CD21+ follicular dendritic cells within a germinal
center. (Biotin-streptavidin-peroxidase stain; original
magnification ×100.)
Fig 3. Lymph follicle with well-defined germinal center
and mantle zone. (Hematoxylin-eosin stain; original mag-
nification ×250.)
arrangement of the B lymphocytes (CD20+) with
presence of CD21+ follicular dendritic cells (Fig 4)
within well-circumscribed germinal centers. T lym-
phocytes (CD3+) were found around the B-cell
areas, scattered within germinal centers, and in
interstitial distribution. The proliferation rate within
germinal centers, as detected by MIB-1 antibody, was
more than 90% (Fig 5). Outside germinal centers
only a few cells were positive for MIB-1. B-lympho-
Fig 5. High proliferative activity (MIB-1-positive nuclei) in
a germinal center. (Biotin-streptavidin-peroxidase stain;

Brief reports 869
J AM ACAD DERMATOL
VOLUME 43, NUMBER 5
REFERENCES
cyte clusters expressed κ and λ immunoglobulin
light chains at equal amounts. Analysis of T-cell
receptor and immunoglobulin heavy chain gene
rearrangement was carried out with a standard poly-
merase chain reaction technique on routinely fixed,
paraffin-embedded sections of tissue,11 using
primers described previously.12,13 With both sets of
primers a polyclonal smear could be observed, indi-
cating that a monoclonal population of lymphocytes
was not present in the infiltrate.
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As a therapeutic measure, intralesional treatment
with corticosteroids led to gradual clearing of the
skin lesions.
DISCUSSION
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Buncke HJ. Intestinal flora of the medicinal leech Hirudinaria
manillensis. J Reconstr Microsurg 1994;10:83-5.
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Smolle J. Simultaneous localization of calcitonin mRNA and
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LM. A simplified method of detection of clonal rearrangements
of the T-cell receptor gamma chain. Diagn Mol Pathol 1992;1:
173-9.
13. Wan JH,Trainor KJ, Brisco MJ, Morley AA. Monoclonality in B cell
lymphoma detected in paraffin wax embedded sections using
the polymerase chain reaction. J Clin Pathol 1990;43:888.
14. Hovmark A, Asbrink E, Olsson I.The spirochetal etiology of lym-
phadenosis benigna cutis solitaria. Acta Derm Venereol
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Cutaneous pseudolymphomas with germinal cen-
ters are known to occur because of systemic med-
ications, after arthropod bites, and in conjunction
with Borrelia burgdorferi infection.14,15 To our
knowledge, this is the first report of cutaneous fol-
licular pseudolymphomas occurring after medicinal
leech therapy. The specific association with H medi-
cinalis in this case was supported by the presence of
skin lesions only at sites of previous leech therapy.
Whether this pseudolymphomatous reaction was
due to substances released from the leech or to an
infectious agent inoculated during the treatment,
however, remains to be determined.
In our patient cutaneous follicular B-cell lym-
phoma and marginal zone lymphoma could be ruled
out because of the presence of regular germinal cen-
ters with tingible body macrophages and distinct
mantle zone, and of the demonstration of polyclon-
ality of the infiltrate at both immunohistologic and
molecular levels.10 Furthermore, the high prolifera-
tion rate of the germinal center cells is a feature typ-
ical of reactive follicles.10
15. Kerl H, Smolle J. Pseudolymphomas of the skin. In: Friedman RJ,
Rigel DS, Kopf AW, Harris MN, Baker D, editors. Cancer of the
skin. Philadelphia: WB Saunders; 1991. p. 408-18.
In conclusion, pseudolymphomas seem to be a
rare but noteworthy side effect of medicinal leech
therapy.