General light microscopic findings of dermatoborreliosis 
DERMATOP ATHOLOGIC DIAGNOSIS 
OF L YME BORRELIOSIS 
S. Hodl, H. P. Soyer and R. R. Miillegger 
ABSTRACT 
The goal of this study was to determine the general light microscopic findings which lend support to the 
histopathologic diagnosis of the main cutaneous manifestations of Lyme Borreliosis. Their diagnostic criteria 
are delineated and illustrated. 
In culminating lesions of erythema migrans and acrodermatitis chronica atrophicans, a peculiar connective 
tissue reaction includes an increase in the number of fibroblasts, proliferation of collagen fibers, and 
interstitial mucinous edema. The cellular infiltrates are patchy perivascular in erythema migrans and either 
patchy and/or band-like in acrodermatitis chronica atrophicans. They consist of lymphohistiocytic cells with a 
variable admixture of plasma cells. The damage to elastic (and even collagen) fibers occurs in early 
acrodermatitis chronica atrophicans and is reflected by the phenomenon of elastophagocytosis. Reduction or 
lack of pilosebaceous units is a constant finding. In advanced lesions of acrodermatitis chronica atrophicans, 
a thinning of the dermal breadth is noticed, resulting from a decrease in collagen and elastic fibers. 
Fibrous nodules and morphea-like conditions are characterized by excessive farmation of collagen. Borrelial 
lymphocytoma exhibits two different patterns of infiltration, accompanied by dermal fibrosis and increased 
numbers of fibroblasts. Recent tick bites show a predominantly neutrophilic infiltrate. 
By applying the results of this synoptic study, histopathologic diagnosis of dermatoborrelioses should be 
possible without the absolute necessity of clinical correlation. 
KEY WORDS 
Lyme borreliosis, synoptic dermatopathologic diagnosis, recent tick bite, erythema migrans, borrelial 
lymphocytoma, acrodermatitis chronica atrophicans, elastophagocytosis, fibrous nodules, morphea-like conditions 
INTRODUCTION 
Notwithstanding the various laboratory techniques 
( e.g. ELISA, immunofluorescence assay, immunoblot, 
PCR (1)) far diagnosing cutaneous borrelial disorders, 
the correlation of clinical and pathological findings 
acta dermatovenerologica A.P.A. Vol 5, 96, No 3-4 
remains the first step towards the diagnosis of these 
endemic dermatoses. Apart from atypical forms, the 
gross appearance of the major dermatoborrelioses 
allows far a spot diagnosis in most instances. It bas 
been stated that the histopathologic features are of 
little diagnostic value without the demonstration of 
123 
General light microscopic findings of dermatoborreliosis 
Fig. l. Recent tick bite les ion ( # 7978/92, H & E, 
scanning power view ): Intraepithelial blister, diffuse 
upper and middermal and perivascular deep dermal 
neutrophilic infiltrate. 
spirochetes (2). However, these agents are difficult 
to detect in biopsy specimens, even when appropriate 
staining methods are used (2,3). Histopathologic 
changes taking place during the course of dermato-
borrelioses are a further diagnostic challenge in the 
assessment of these disorders. 
This group of diseases is caused by various strains 
of borrelia, however, these organisms may share 
pathologic sequelae in the infected skin. The goal 
of this study was to determine the general light 
microscopic findings which lend support to the 
histopathologic diagnosis of dermatoborrelioses. 
MATERIAL AND METHODS 
We analyzed histologic specimens of erythema 
(chronicum) migrans (EM) (41 cases), borrelial 
lymphocytoma (BL) (5 cases), acrodermatitis chronica 
atrophicans (ACA) (82 cases), fibrous nodules (5 
124 
Fig. 2. Tick bite lesion, one day old (# 10991/89, H 
& E x 50): Vertical zone of densely packed sclerotic 
collagen bundles below tick fragments. Perivascular 
lymphocytic infiltrates with admixture of neutrophils. 
cases) and morphea-like changes ( 4 cases). Three 
cases of recent tick bites were also included. Ali 
histopathologic descriptions and illustrations are either 
of H & E or Orcein and Mowry-stained paraffin-
embedded skin biopsy specimens. 
RESULTS AND DISCUSSION 
TICK BITE 
The recent tick bite lesion exhibits an intraepidermal 
blister at the site of the bite injury, containing 
erythrocytes and nuclear debris and a superficial 
and deep dermal infiltrate mainly composed of 
mature neutrophils and admixed lymphocytes, 
histiocytes and a few eosinophils (Fig. 1). This 
predominantly neutrophilic infiltrate discriminates the 
tick bite from the sting reactions resulting from 
most other insects such as mosquitoes, bedbugs or 
Sarcoptes scabiei, in which eosinophils are preeminent. 
acta dermatovenerologica A.P.A. Vol 5, 96, No 3-4 
General light microscopic findings of dermatoborreliosis 
Fig. 3. Erythema migrans (# 17328/93, H & E, 
scanning power view ): Moderate superficial and deep 
perivascular predominantly lymphocytic infiltrate. Interstitial 
edema, proliferation of fibroblasts and collagen throughout 
the dermis. Lack of pilosebaceous units. 
In older tick bite lesions a few days old, the injury 
site is marked by a vertical zone of densely packed, 
thickened, sclerotic collagen bundles within the dermis. 
Neutrophils or their nuclear remnants are interspersed 
between the bundles (Fig. 2) . 
DERMATOPATHOLOGY OF LYME 
BORRELIOSIS 
ERYTHEMA (CHRONICUM) MIGRANS 
The clinically fully developed lesion consists 
histologically of a flattened, yet cytologically normal 
epidermis. The salient histological findings are fibrosis 
of the reticular dermis, interstitial edema in both 
the papillary and reticular dermis, increased numbers 
of fibroblasts and extensive loss of pilosebaceous 
units. Smooth muscle remnants of the arrector pili 
may be present, whereas the sudoriferous glands are 
acta dermatovenerologica A.P.A. Vol 5, 96, No 3-4 
Fig. 4. Bomlial lymphocytoma (# 19744/95, H & E 
x 50): Diffuse infiltration of the upper and mid dermis 
with small lymphocytes and admixture of medium-sized 
lymhoid cells. 
mostly preserved. A moderately dense, patchy, 
superficial and deep infiltrate, composed mainly of 
lymphocytes with admixed histiocytes, arranged around 
dilated vessels, nerves, and eccrine glands is commonly 
seen (Fig. 3). The histopathologic diagnosis of EM 
can be made on the basis of a picture encompassing 
all the above-mentioned morphologic components. 
However, a subtle clinico-pathologic correlation is 
often required. 
BORRELIAL L YMPHOCYTOMA 
(L YMPHADENOSIS CUTIS BENIGNA) 
The earlobes and the areolae of the mamillae are 
the sites of predilection for BL. However, it also 
occurs in the face or in the axillary and genital 
regions. The gross appearance is characterizea by 
either a solitary or an aggregate of soft reddish or 
bluish-red nodules. 
125 
General light microscopic findings of dermatoborreliosis 
Fig. 5. Borrelial lymphocytoma (# 31658/93, H & E 
x 50): Dense nodular lymphocytic infiltrate surrounding 
germinal centers of medium-sized lymphoid cells (follicular 
type). 
Two main histopathologic pattems can be diffe-
rentiated according to the pattem of infiltration and 
the type of cells involved. The more common 
histopathologic type reveals a dense nodular or 
diffuse pattern of infiltration which usually occupies 
the upper and mid dermis. The infiltrate is composed 
of small, mature lymphocytes and a variable admixture 
of clustered, medium-sized lymphoid cells with pale-
staining indented nuclei and plasma cells (Fig. 4) . 
The component of pale-staining lymphoid cells may 
predominate, resulting in a polymorphic appearance 
of the infiltrate, thus making the distinction from 
malignant lymphoma difficult. The connective tissue 
background shows fibrosis, interstitial edema and 
increased numbers of fibroblasts. The latter features 
are obscured in the less common follicular type of 
BL, which is characterized by a dense, nodular 
lymphocytic infiltrate surrounding germinal centers 
of medium-sized, pale-staining polymorphic lymphoid 
cells. This pattern of infiltration mimics secondary 
126 
Fig. 6. Acrodermatitis chronica atrophicans, infiltrative 
edematous stage. Edema and bright red injlammation 
on the back of the hand (G.M., 58 year-old Jemale). 
For corresponding histology see Fig. 7a and b. 
lymph node follicles. The borders between the abutting 
units are effaced and the infiltrate occupies the 
entire reticular dermis, extending into the subcutaneous 
fat in places. The papillary dermis is spared from 
the infiltrate, but displays a conspicuous edema and 
dilated capillaries (Fig. 5). It should be mentioned 
that transitions between these two histopathologic 
pattems may occur. 
ACRODERMATITIS CHRONICA 
ATROPHICANS 
ACA arises as a primary well demarcated, bright 
red swelling, mainly located on the extremities. 
After months or years, the infiltrative edematous 
stage gradually progresses into the atrophic stage of 
advanced disease. At this point, ACA exhibits markedly 
thinned, diaphanous, wrinkled, glossy skin with whitish 
and reddish-violaceous hues. Therefore, two different 
pictures corresponding to the two stages in the 
acta dermatovenerologica A .P.A. Vol 5, 96, No 3-4 
General light microscopic findings of dermatoborreliosis 
Fig. 7. Acrodermatitis chronica atrophicans (# 5651/95, H & E). 
a) Subepidermal band-like lymphohistiocytic infiltrate (xl00) . 
b) Elastophagocytosis: Elastic fibers (arrows) within the cytoplasm of a multinucleated giant cel! (x 1000). 
Fig. 8. Sclerodermiforme condition in acrodermatitis 
chronica atrophicans (# 12250/91, 
H & E x 100): Epidermal atrophy and markedly 
thickened dermis with densely packed hyalinized collagen, 
increased number of fibroblasts and focal lymphoplasma-
cellular infiltrates. 
acta dermatovenerologica A.P.A. Vol 5, 96, No 3-4 
course of ACA must be considered. Occasionally, 
fibrous nodules and morphea-like conditions coincide 
within atrophic skin over the dorsal aspects of the 
elbows, metacarpus and knees. 
INFILTRATIVE EDEMATOUS STAGE OF 
ACRODERMATITIS CHRONICA 
ATROPHICANS: 
The architectural pattern is either composed of 
subepidermal, band-like and/or patchy perivascular 
infiltrates. The latter are present throughout the 
dermis in a chiefly top-heavy pattern. The band-like 
pattern may be accompanied by necrosis of basal 
keratinocytes and vacuolar alteration at the dermo-
epidermal interface, as seen in lichen planus. The 
infiltrate is basically lymphohistiocytic, but plasma 
cells participate in variable numbers. The dermis 
itself shows fibrotic collagen, separated by interstitial 
mucinous edema and a markedly increased number 
of fibroblasts. 
In rather rare cases of ACA (3 out of 58 patients 
in our histology files 1994 - 1995) the microscopic 
substrate discloses the mechanism of elastic fiber 
damage. From a clinical viewpoint, it is more often 
observed in the culminating inflammatory stage, as 
depicted in Fig. 6. However, it may also be 
encountered in the early, atrophic stage, when the 
lesions stili contains a moderate perivascular, lympho-
plasmacellular infiltrate, i.e. in a not fully „burned 
out" lesion. The process of elastic fiber daipage 
may be distinctly seen in lesions where the upper 
dermal band-like infiltration type of ACA is present. 
Large histiocytic cells with abundant eosinophilic 
127 
General light microscopžc findings of dermatoborreliosis 
cytoplasm and one or more (multiple) palestaining 
nuclei are found focally within this infiltrate as well 
as in places within deeper parts of the dermis. 
These large cells occur either singly or in clusters 
in the formation of granulomas. A conspicuous 
finding is the presence of grayish or greenish fibers 
or their destroyed remnants lying within the cytoplasm 
of these multinucleated giant cells. This strongly 
suggests that phagocytosis of elastic ( elastophagocytosis) 
or collagen fibers is taking place. Fibers may be 
clearly seen to extend from the cytoplasm, beyond 
the cell border, into the surrounding connective 
tissue (Fig. 7a + b). 
ATROPHIC STA.GE OF ACRODERMATITIS 
CHRONICA ATROPHICANS: 
As the lesion gradually becomes flaccidly atrophic, 
the epidermis is reduced to a few layers and shows 
complete loss of rete ridges. Subepidermal lichenoid 
or sparse upper and middermal perivascular and 
perineural lymphoplasmacellular infiltrates surrounding 
dilated blood vessels are nearly pathognomonic 
features. The breadth of the dermis is remarkably 
decreased and edema separates the collagen bundles. 
When applying the orcein ( elastica) stain, the elastic 
fibers are markedly decreased or entirely absent. An 
increased number of fibroblasts, some with bizarre 
configurations, can be seen interstitially. Single large 
mono- or binucleated cells with engulfed fragments 
of fibers are found here and there. The sweat 
glands are preserved, whereas pilosebaceous units 
are greatly reduced or completely absent. 
FIBROUS NODULES 
The fibrous nodules are commonly found on the 
dorsal aspects of the elbows, metacarpus, knees or 
on the ankles Guxtaarticular location) and consist of 
a dome-shaped, slightly red mass with a cartilaginous 
consistency. Their histopathologic correlate is the 
presence of coarse hyalinized collagen bundles within 
the middle and deep dermal parts of the broadened 
dermis. Occasionally the mass lies in the subcutis. 
Fibrous nodules display either anion-like, interlacing 
or cartwheel patterns, as may be observed in some 
fibrohistiocytic tumors or in sclerosing fibroma. A 
striking histopathologic finding is the markedly 
increased number of fibroblasts within the areas of 
proliferated collagen fibers. Sparse lymphocytic 
infiltrates with admixed plasma cells can be seen 
around small blood vessels in the subepidermal part 
and at the periphery of the peculiar collagen 
128 
formations. There is a complete lack of cutaneous 
adnexa when the lesion is confined to the dermis. 
MORPHEA-LIKE AND SCLERODERMIFORME 
CONDITIONS 
Grossly, these conditions appear as whitish or 
ivory-colored plaques or sheets of indurated, tightly 
fitting, scleroderma-like skin, located mainly on the 
lower leg and instep. Thus, the range of joint 
mobility may be limited. The disorder develops 
gradually within a period of several months. 
Under scanning magnification, the plaques reveal 
a thinned out, flattened epidermis and a noticeably 
thickened, sclerotic dermis with superficial and deep, 
inflammatory infiltrates. The excessively broadened 
dermis contains compact homogeneous hyalinized 
collagen and a considerably increased number of 
fibroblasts which entrap collagen bundles in a pattern 
similar to the structure of a dermatofibroma. The 
inflammatory infiltrates are characterized by sheet-
like or perivascular interstitial celi aggregations. The 
latter are composed of lymphocytes and plasma 
cells as well as sporadic eosinophils. Remnants of 
hair follicles may be present (Fig. 8). The subcutaneous 
fat _ is largely replaced by sclerotic collagen. 
CONCLUSION 
Although the major cutaneous entities of Lyme 
Borreliosis may be diagnosed by their gross appe-
arance at first glance, correlation with histopathologic 
features is mandatory to establish an unequivocal 
diagnosis in these disorders . This procedure is 
especially important in atypical manifestations. Our 
study of a large series of skin biopsy specimens, 
taken from the main tickborne dermatoses, show 
that the representative histopathologic findings are 
as follows: 
l. Recent tick bites show a predominantly neutrophilic 
infiltrate at the site of the bite injury and, thus, 
differ from reactions to other insect stings with 
largely eosinophilic infiltrates, such as mosquitoes, 
bedbugs, etc. (4,5). 
2. A peculiar connective tissue reaction can be 
observed in culminating lesions of EM and ACA. 
This reaction includes a noticable increase in the 
number of fibroblasts, proliferation of collagen fibers 
and an interstitial mucinous edema throughout the 
dermis. The edema consists of acid mucopoly-
saccharides (Mowry stain). The cellular infiltrates 
acta dermatovenerologica A.P.A. Vol 5, 96, No 3-4 
General light microscopic findings of dermatoborreliosis 
exhibit a patchy, perivascular arrangement in EM 
and either patchy and/or band-like lichenoid patterns 
in ACA (6). The dominant inflammatory cells are 
lymphohistiocytic with a variable admixture of plasma 
cells. The damage to elastic (and even collagen) 
fibers is discernible in a few lesions of lichenoid 
ACA. Stretched fibers or their destroyed fragments 
are found within the cytoplasm of large epitheloid 
or multinucleated giant cells, representing elastopha-
gocytosis. A reduction in or lack of pilosebaceous 
units is a constant finding. In advanced lesions of 
ACA a considerable thinning of the dermal breadth 
is noticed, resulting from a decrease in collagen and 
elastic fibers. In the end, the elastic fibers are 
completely absent as is the cellular infiltrate (,,burned 
out" lesion). A lack of pilosebaceous units is a 
remarkable finding in both entities as well as in the 
following conditions. 
3. Fibrous nodules (7,8) and morphea-like conditions 
in ACA (9,10) are characterized by excessive formation 
of collagen, either in an anion-like, matted fascicular 
or pronounced sclerosing manner. The perpetual 
presence of borrelia organisms may play a role in 
the peculiar reaction of the affected tissue (3). 
4. BL shows two different patterns of infiltration: i) 
nodular or diffuse spread of small lymphocytes with 
admixed medium-sized lymphoid cells. ii) a follicular 
pattern mimicking secondary lymph node follicles 
(11). 
By applying the results of this synoptic study, the 
histopathologic details of a suspicious lesion should 
supply ample information to diagnose the entire 
spectrum of dermatoborrelioses without the absolute 
necessity far clinical correlation. 
REFERENCES 
l. Mi.illegger RR, Zochling N, Schli.ipen EM et al. 
Polymerase chain reaction control of antibiotic 
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1990. 
3. De Koning J, Tazelaar DJ, Hoogkamp-Korstanje 
JAA, Elema JD. Acrodermatitis chronica atrophicans: 
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4. Ackerman AB. Histologic diagnosis of inflammatory 
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10. Mi.illegger RR, Hofmann-Wellenhof R, Soyer 
HP, Hodl S. Concurrent acrodermatitis chronica 
atrophicans and circumscribed scleroderma in a temale 
farmhelper. Acta Dermatovenerol Alpina Pannonica 
et Adriatica 1994; 3: 115-19. 
11. Kerl H, Kresbach H. Lymporetikulare Hyperplasien 
und Neoplasien der Haut. In: Doerr W, Seifert G, 
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AUTHORS' ADDRESSES 
Stefan Hodl, MD, professor of dermatology, Department of Dermatology, University of Graz, 
School of Medicine, Auenbruggerplatz 8, A-8036 Graz, Austria 
H. Peter Soyer, MD, professor of dermatology, same address 
Robert R. Mi.illegger, MD, assistant professor of dermatology, same address 
acta dermatovenerologica A.P.A. Vol 5, 96, No 3-4 129