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152 DISC
Veterinary Dermatology 2000, 11, 1316

Subepidermal linear alignment of mast cells in

inammatory dermatoses of the dog
KARYN E. BENINGO,* DANNY W. SCOTT,*{ and HOLLIS N. ERB{
*Departments of Clinical Sciences, {Biomedical Sciences, and {Population Medicine and Diagnostic Science,
College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
(Received 17 July 1998; accepted 29 September 1998)

Abstract A recent study demonstrated that 47.7% of dogs with Malassezia dermatitis had a subepidermal
linear alignment of mast cells (SLAM). A retrospective histopathological study was conducted on 419 canine
skin biopsies to determine if a SLAM was present in other inammatory diseases. Cases examined included
dogs with demodicosis, sarcoptic mange, dermatophytosis, pemphigus foliaceus, pemphigus erythematosus,
discoid lupus erythematosus, systemic lupus erythematosus, erythema multiforme, dermatomyositis,
staphylococcal pyoderma, primary seborrhea, arthropod bites, contact hypersensitivity, ea bite
hypersensitivity, atopy, and food hypersensitivity. Three cases (3/419, 0.7%) were identied with SLAM.
The diagnoses for these cases were atopy (1/23, 4%) with a secondary bacterial folliculitis (1/136, 0.7%),
pemphigus erythematosus (1/18, 6%), and discoid lupus erythematosus (1/16, 6%). Based on this study,
SLAM is signicantly more common in Malassezia dermatitis than in other inammatory diseases.
Keywords: dermatitis, dog, histopathology, mast cells, skin.

INTRODUCTION
A subepidermal linear alignment of mast cells
(SLAM) was rst reported in West Highland White
terriers with epidermal dysplasia and Malassezia
dermatitis.1 A more recent histopathologic study
revealed this SLAM to be present in 47.7% (95%
condence interval [36.8, 58.7]) of dogs with Malassezia dermatitis.2 It has been hypothesized that this
SLAM represents a hypersensitivity to the fungal
antigens.1,2 The authors are unaware of any other
studies that have looked for this histological nding.
The purpose of this study was to determine if the
SLAM is found exclusively with Malassezia dermatitis or if this alignment is seen in other inammatory
dermatoses of the dog.

sezia dermatitis (irregular epidermal hyperplasia, parakeratotic hyperkeratosis, diuse epidermal spongiosis,
lymphocytic exocytosis, and the presence of supercial
perivascular to interstitial dermatitis wherein lymphocytes were the predominant inammatory cell type).13,4
2 A denitive diagnosis was possible based on history,
clinical signs, biopsy, response to treatment, and, where
applicable, additional tests (e.g. intradermal skin
testing, hypoallergenic diet trial).

Correspondence: D. W. Scott.
Reprints will not be available.

We attempted to select dermatoses that represented

dierent aetiologic categories (infections, parasitisms,
allergies, autoimmune and immune-mediated disorders, keratinization disorders, etc.) and dierent
histopathological reaction patterns (folliculitis, intraepidermal pustular dermatitis, perivascular dermatitis,
interstitial dermatitis, interface dermatitis, etc.) (Table
1). An additional 11 biopsies from normal dog skin
were also reviewed. All of the biopsy samples had
been submitted in formalin, routinely processed,
sectioned at 4 mm, and stained with haematoxylin
and eosin (H&E) and acid orcein Giemsa (AOG). For
the purpose of this study, all of the slides that were
reviewed were stained with AOG in order to more
readily visualize mast cells. The slides were examined
by one of the authors (K.E.B.) and any biopsy
specimen that demonstrated SLAM was recorded,
and corroborated by the other author (D.W.S.).
In order to be considered a SLAM, the mast cells
had to be in a discrete row immediately below the
basement membrane zone of the epidermis and hair
follicle outer root sheaths.1 Subepidermal mast cells

# 2000 Blackwell Science Ltd

13

MATERIALS AND METHODS

A retrospective study of canine skin biopsies submitted to the Diagnostic Laboratory and the
Dermatology Service at the Cornell College of
Veterinary Medicine from January 1987 to December
1997 was performed. Slides were included in this
study if they satised the following criteria:
1 Yeast were not present in the biopsy specimens nor was
there suggestive histopathological evidence of a Malas-

152 DISC
14

K. E. Beningo, D. W. Scott and H. N. Erb

that were components of perivascular or interstitial

inammatory inltrates were not included.
Exact binomial 95% condence intervals were
calculated (Epi Info 6 v 6.04b, 1997, Centers for
Disease Control and Prevention) for all syndromespecic fractions.
RESULTS
Four hundred and nineteen cases with supercial
inammation were reviewed. Of these cases, 71 had
two dierent inammatory diseases based on clinical
ndings and histopathological reaction patterns (Table 1). Only three cases (3/419, 0.7%, 95% condence
interval [0.1, 2.1]) had SLAM (Fig. 1). The diagnosis
for the three cases were atopy (1/23, 4%, [0.1, 22])
with a secondary bacterial folliculitis (1/136, 0.7%,
[0.02, 4.03]), pemphigus erythematosus (1/18, 6%,
[0.1, 27]), and discoid lupus erythematosus (1/16, 6%,
[0.2, 30]) (Fig. 1). None of the skin biopsies from the
11 normal dogs had SLAM (0%, [0, 28]) (Fig. 2).
DISCUSSION
Mast cells store and produce many inammatory
mediators.3,57 They are important in immediate
hypersensitivity diseases and are distributed throughout the body in connective tissue.5 In normal and
atopic dog skin, mast cells are more numerous
around supercial blood vessels and adnexae (Fig.
2).3,8,9 Increased numbers of perivascular and periadnexal mast cells have also been reported in dogs
Table 1. Canine dermatoses examined for the presence of linearly
aligned subepidermal mast cells
Diagnosis

No. of
cases*

No. (%) of cases

with SLAM{

Staphylococcal infection
Demodicosis
Pemphigus foliaceus
Primary seborrhea
Dermatophytosis
Atopy
Dermatomyositis
Pemphigus erythematosus
Discoid lupus erythematosus
Erythema multiforme
Sarcoptic mange
Flea bite hypersensitivity
Systemic lupus erythematosus
Food hypersensitivity
Contact hypersensitivity

136
79
77
40
34
23
22
18
16
13
11
8
6
3
1

1
0
0
0
0
1
0
1
1
0
0
0
0
0
0

(0.7%)
(0.0%)
(0.0%)
(0.0%)
(0.0%)
(4%)
(0.0%)
(6%)
(6%)
(0.0%)
(0.0%)
(0.0%)
(0.0%)
(0.0%)
(0.0%)

*Seventy-one of 419 cases had two dierent diseases based on

clinical ndings and histopathological reaction patterns. Sixty-four
dogs had a bacterial infection secondary to primary seborrhea,
atopy, pemphigus foliaceus, ea bite hypersensitivity, sarcoptic
mange, dermatophytosis, food hypersensitivity, dermatomyositis,
pemphigus erythematosus, and discoid lupus erythematosus. Seven
dogs had various combinations of food hypersensitivity, atopy,
sarcoptic mange, and ea bite hypersensitivity.
{SLAM = subepidermal linear alignment of mast cells.
# 2000 Blackwell Science Ltd, Veterinary Dermatology, 11, 1316

Figure 1. Photomicrograph of skin from a dog with discoid lupus

erythematosus. Mast cells form a discrete row below the basement
membrane zone of the epidermis (AOG, 6400).

with bacterial pyoderma.10 Although inammatory

dermatoses are very common in the dog, and mast
cells are often reported to be present in increased
numbers in skin biopsy specimens,4 the precise
localization of the mast cells within the dermatoses
is rarely specied. Normal dog skin contains 412
mast cells per high-power microscopic eld and there
is no signicant dierence between mast cell numbers
at dierent skin sites.3,11,12
Mast cell heterogeneity has been demonstrated in
dog skin. At least two types of mast cells are
recognized (connective tissue or typical and mucosal
or atypical) which can be distinguished by their
staining properties in dierent xatives and by the
response to antigen in vivo.3,8,13,14-3 Both subsets are
present in dog skin. Connective tissue mast cell
granules exhibit metachromasia with Giemsa, toluidine blue, alcian blue, or AOG stains. Mucosal mast
cells are believed to account for one-third of the mast
cells in skin. Their granules contain chondrodroitin
sulphate and do not exhibit metachromasia unless
special xatives (e.g. lead acetate) are used.5,8,11,1315
In our study, similar to the previous studies of
Malassezia dermatitis, the biopsy specimens had been
xed with formalin and stained with AOG. Hence,
the mucosal mast cells were not accounted for.
However, because most laboratories examine for-

152 DISC
Subepidermal mast cells in dogs

15

dermatitis, the prevalences of SLAM in these other

dermatoses are signicantly lower.
In conclusion, SLAM can occasionally be seen in
canine dermatoses of immune-mediated nature.
However, this SLAM is seen much more commonly
with Malassezia dermatitis and, when present, should
always prompt a search for these organisms and their
associated histopathological reaction pattern.2
REFERENCES

Figure 2. Photomicrograph of normal dog skin. Mast cells are

found in a perivascular location (AOG, 6400).

malin-xed tissue, this was not a major practical

consideration. In addition, the authors are unaware
of any dermatoses wherein connective tissue or
mucosal mast cells are known to be preferentially
increased or decreased in numbers.
In order to see what eect dierent aetiologic
categories and histopathological reaction patterns might
have on the occurrence of a SLAM, we attempted to
select from a variety of these. Based on our ndings, the
occurrence of a SLAM was not inuenced by aetiology
or histopathological reaction pattern.
It has been speculated that SLAM may be the
result of a hypersensitivity reaction to a fungal
antigen.1,2 In this study, none of the cases of
dermatophytosis exhibited SLAM. Therefore, if the
above hypothesis is true, then dermatophytes (unlike
yeast) do not appear to be able to provoke this type
of host response.
In this study, only one case of atopy (4%), one case
of pemphigus erythematosus (6%), and one case of
discoid lupus erythematosus (6%) had SLAM. These
dermatoses would appear to have little in common,
other than their immune-mediated aetiopathogenesis.
Their histopathological reaction patterns are quite
dierent. These percentages are small when compared
to dogs with Malassezia dermatitis (47.7%).1,2
Because none of their condence intervals overlap
with the condence interval for SLAM in Malassezia

1. Scott, D.W., Miller, W.H. Jr. Epidermal dysplasia and

Malassezia pachydermatis infection in West Highland
White terriers. Veterinary Dermatology 1989; 1: 2536.
2. Mauldin, E.A., Scott, D.W., Miller, W.H. Jr, Smith, C.A.
Malassezia dermatitis in the dog: a retrospective
histopathological and immunopathological study of 86
cases 199095. Veterinary Dermatology 1997; 8: 191202.
3. Scott, D.W., Miller, W.H. Jr, Grin, C.E. Muller and
Kirk's Small Animal Dermatology. 5th edn. W.B.
Saunders, Philadelphia, 1995: 3517.
4. Gross, T.L., Ihrke, P.J., Walder, E.J. Veterinary
Dermatopathology. A Macroscopic and Microscopic
Evaluation of Canine and Feline Skin Disease.
Mosby-Year Book, Inc., St. Louis, 1992: 10272.
5. Tizard, I.R. Veterinary Immunology: an Introduction,
5th edn. W.B. Saunders, Philadelphia, 1996: 34651.
6. Fitzpatrick, T.B., Eisen, A.Z., Wol, K., Freedberg,
I.M., Austen, K.F. Dermatology in General Medicine ,
4th edn. McGraw-Hill, Inc., New York: 1993: 35973.
7. Jorden, R.E. Immunologic Diseases of the Skin.
Appleton and Lange, Norwalk: 1991: 6371.
8. Becker, A.B., Chung, K.F., McDonald, D.M., Lazarus,
S.C., Frick, O.L., Gold, W.M. Mast cell heterogeneity
in dog skin. Anatomical Record 1985; 213: 47780.
9. Olivry,
T.,
Naydan,
D.K.,
Moore,
P.F.
Characterization of the cutaneous inammatory
inltrate in canine atopic dermatitis. American
Journal of Dermatopathology 1997: 19: 47786.
10. Rojko, J.L., Hoover, E.A., Martin, S.L. Histologic
interpretation of cutaneous biopsies from dogs with
dermatologic disorders. Veterinary Pathology 1978; 15:
57989.
11. Nimmo Wilkie, J.J., Yager, J.A., Eyre, P., Parker,
W.M. Morphometric analyses of the skin of dogs with
atopic dermatitis and correlations with cutaneous and
plasma histamine and total serum IgE. Veterinary
Pathology 1990; 27: 17986.
12. Kristensen, S. A study of skin disease in dogs and cats.
I. Histology of the hair skin of dogs and cats. Nordisk
Veterinaer-Medicin 1975; 27: 593603.
13. Becker, A.B., Chung, K.F., McDonald, D.M., Lazarus,
S.C., Frick, O.L., Gold, W.M. Cutaneous mast cell
heterogeneity: response to antigen in atopic dogs.
Journal of Allergy and Clinical Immunopathology
1993; 78: 93742.
14. de Mora, F., Garcia, G., Ferrer, L., Arboix, M. Canine
cutaneous mast cells dispersion and histamine secretory
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15. Mehregan. A.H. Pinkus' Guide to Dermatohistopathology, 4th edn. Appleton-Century-Crofts, Norwalk:
1986: 524.
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152 DISC
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K. E. Beningo, D. W. Scott and H. N. Erb

Resume Une etude recente a demontre que 47.7% des chiens presentant une dermatite a Malassezia avaient
un alignement lineaire sous-epidermique de mastocytes (SLAM). Une etude histopathologique retrospective a
ete conduite sur 419 biopsies cutanees de chiens pour determiner la presence d'un SLAM dans d'autres
dermatoses inammatoires. Les cas inclus regroupaient des chiens sourant de demodecie, de gale
sarcoptique, de dermatophytie, de pemphigus foliace, de pemphigus erythemateux, de lupus erythemateux
disco de, de lupus erythemateux systemique, d'erytheme polymorphe, de dermatomyosite, de pyodermite, de
seborrhee idiopathique, de piqures d'arthropodes, d'allergie de contact, d'atopie et d'allergie alimentaire.
Trois cas (3/419, 0.7%) ont ete identies avec un SLAM. Il y avait un cas d'atopie (1/23, 4%) avec une
folliculite bacterienne secondaire (1/136, 0.7%), un cas de pemphigus erythemateux (1/18, 6%), et un cas de
lupus erythemateux disco de (1/16, 6%). En se basant sur cette etude, le SLAM est signicativement plus
frequent dans les dermatites a Malassezia que dans les autres dermatoses inammatoires. [Beningo, K. E.,
Scott, D. W. et Erb, H. N. (Alignement sous-epidermique lineaire de mastocytes dans les dermatoses
inammatoires du chien.) Veterinary Dermatology 2000; 11: 1316.]
Resumen Un estudio reciente demostraba que el 47.7% de los perros con dermatitis por Malassezia ten an
una disposicion linear subepidermica de mastocitos (SLAM). Se realizo un estudio histopatologico
retrospectivo sobre 419 biopsias cutaneas caninas para determinar si se observaba una SLAM en otras
enfermedades inamatorias. Los casos examinados inclu an demodicosis, sarna sarcoptica, dermatotosis,
pengo foliaceo, pengo eritematoso, lupus eritematoso discoide, lupus eritematoso sistemico, eritema
multiforme, dermatomiositis, pioderma estalococica, seborrea primaria, picaduras de artropodos,
hipersensibilidad por contacto, hipersensibilidad por picadura de pulga, atopia e hipersensibilidad
alimentaria. Tres casos (3/419, 0.7%) fueron identicados con SLAM. Los diagnosticos para estos casos
fueron atopia (1/23, 4%) con foliculitis bacteriana secundaria (1/136, 0.7%), pengo eritematoso (1/18, 6%) y
lupus discoide eritematoso (1/16, 6%). Basado en este estudio, SLAM es signicativamente mas frecuente en
dermatitis por Malassezia que en otras enfermedades inamatorias. [Beningo, K. E., Scott, D. W. y Erb, H. N.
(Disposicion linear subepidermica de mastocitos en dermatosis inamatorias del perro.) Veterinary
Dermatology 2000; 11: 1316.]
Zusammenfassung In einer kurzlich unternommenen Studie wurde die subepidermale lineare Ausrichtung
von Mastzellen (SLAM) bei 47.7% der Hunde mit Malassezia Dermatitis demonstriert. Um festzustellen, ob
SLAM bei anderen entzundlichen Hauterkrankungen vorliegt, wurde eine ruckblickende histopathologische
Studie mit 419 kaninen Hautbiopsien durchgefuhrt. Untersuchte Falle waren Hunde mit Demodikose,
Sarcoptesraude, Dermatophytose, Pemphigus foliaceus, Pemphigus erythematodes, diskoidem Lupus
erythematodes, systemischem Lupus erythematodes, Erythema multiforme, Dermatomyositis,
Staphyolokokkenpyodermie, primarer Seborrhoe, Arthropodenbisse, Kontaktallergien, Flohbissallergien,
atopischer Dermatitis und Futteruberreaktionen. Drei Falle (3/419, 0.7%) mit SLAM wurden idenziert. Die
Diagnose dieser Falle war atopische Dermatitis (1/23, 4%) mit sekundarer bakterieller Follikulitis (1/136,
0.7%), Pemphigus erythematodes (1/18, 6%) und diskoider Lupus erythematodes (1/16, 6%). Die Studie
ergibt, dass SLAM bei Malassezia Dermatitis signikant hauger vorkommt als in anderen entzundlichen
Hauterkrankungen. [Beningo, K. E., Scott, D. W. und Erb, H. N. (Subepidermale lineare Ausrichtung von
Mastzellen bei entzundlichen Hauterkrankungen des Hundes.) Veterinary Dermatology 2000; 11: 1316.]

# 2000 Blackwell Science Ltd, Veterinary Dermatology, 11, 1316