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Mehregan Supplement

Report
Oxford, UK
International
IJD
Blackwell
?0011-9059
Science,
Journal
Ltdof Dermatology
2002

Assessment of histologic criteria in the diagnosis of mycosis


fungoides

Histologic
Naraghi
Supplement
et criteria
al.
in mycosis fungoides

Zahra Safee Naraghi, MD, Hassan Seirafi, MD, Mahin Valikhani, MD, Forshad Farnaghi, MD,
Susan Kavusi, MD, and Yahya Dowlati

From Razi Hospital, Tehran University of


Medical Sciences, Tehran, Iran
Correspondence
Zahra Safee Naraghi, MD
Razi Hospital
Tehran University of Medical Sciences
Tehran
Iran
E-mail: SuKavusi@yahoo.com

Abstract
Background The histologic diagnosis of early mycosis fungoides (MF) can be difficult to
establish in many instances because the subtle changes observed in patches of MF are also
present in many inflammatory dermatoses.
Methods To assess the frequency and significance of many of these histologic parameters, we
retrospectively reviewed 50 slides from patients with documented MF in patch, plaque, and
tumor stages. The diagnosis of MF was unequivocally established either by the progression of
patients to advanced stages of the disease or by indubitable histologic findings. In the second
phase of the study, we compared the histologic parameters observed in 24 patch stage MF
patients with those in 24 non-MF patients. The non-MF group were patients whose pathologic
pattern was suspicious for MF, but who definitely did not have MF on clinical grounds. The two
groups were matched by histologic pattern. Two different observers evaluated the slides and the
intensities of 32 histologic parameters were graded on a four-point scale to minimize the
subjective variability in the histologic reports.
Results On univariate analysis, the following parameters achieved significance in
distinguishing MF from non-MF: Pautriers microabscesses, haloed lymphocytes, disproportionate
epidermotropism, epidermal lymphocytes larger than dermal lymphocytes, hyperconvoluted
lymphocytes in the epidermis and dermis, absence of dyskeratosis, and papillary dermal fibrosis.
None of these features proved to have additional discriminating power on multivariate analysis.
Conclusions The efficacy of single histologic features in the diagnosis of early MF is generally
poor and, to discriminate MF from its inflammatory simulators, a combination of cytologic and
architectural features must be used.

Introduction
The histologic diagnosis of early stages of mycosis fungoides
(MF) may be difficult in many instances: early patches of
MF may show only subtle histologic changes that can easily
be confused with those of inflammatory dermatoses.1 In
approximately half of patients, biopsies are diagnostic of
MF from the outset, but, in many patients, histologic findings
are only suggestive of MF and repeat biopsies over time with
clinicopathologic correlation will clarify the correct diagnosis.2,3
Another problem is the low agreement rate in reporting
biopsies suggestive of MF among dermatopathologists due to
a lack of specifically defined histologic criteria.4
Immunophenotyping and T-cell receptor gene rearrangement
studies by polymerase chain reaction have been utilized as
adjunctive techniques to provide additional useful information
in difficult cases; however, the immunophenotypic aberrations
2003 The International Society of Dermatology

seen in advanced stages of MF may not be found in patches,2,5


and molecular biopsy techniques can only detect T-cell
receptor gene rearrangement in 50 80% of patches and
plaques of MF.1,68 A combination of clinical course, histologic
findings, and these adjunctive techniques remains the gold
standard in the diagnosis of MF.2,3
A number of recent studies have emphasized the importance
of many of the subtle histologic findings as clues to the correct
diagnosis of MF.1,3,9 Ackerman10 noted that four histologic
patterns in the context of infiltrates composed mainly of
lymphocytes should suggest a diagnosis of patch/plaque of
MF: spongioticlichenoid, psoriasiformlichenoid, spongiotic
psoriasiformlichenoid, and psoriasiformnodular. He also
reported four parameters as diagnostic criteria of early MF:
exocytosis with a paucity of spongiosis, solitary lymphocytes
lined up along the basal layer, epidermal lymphocytes larger
than dermal lymphocytes, and papillary dermal fibrosis
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Mehregan Supplement Report Histologic criteria in mycosis fungoides

within a lichenoid infiltrate. Shapiro and Pinto3 observed


sparse, superficial, perivascular or interstitial infiltrate of
lymphocytes in the early stages of MF, in addition to slight
epidermotropism with minimal spongiosis and lymphocytes
along the basal layer of the epidermis. They also emphasized
the importance of lymphocytic atypia within the epidermis.
Smoller et al.,9 in 1995, stated that haloed lymphocytes were
the most robust factor indicative of MF. Other significant
parameters included: Pautriers microabscesses, disproportionate epidermotropism, epidermal lymphocytes larger than
dermal lymphocytes, hyperconvoluted epidermal lymphocytes,
and lymphocytes aligned within the basal layer. They concluded
that a combination of specific histologic criteria may be
used to establish a diagnosis of MF without the need for
immunophenotyping in the majority of cases.
The European Organization for Research and Treatment
of Cancer (EORTC)1 recently declared that the only feature
which yielded independent diagnostic information in MF was
medium to large cerebriform lymphocytes in the epidermis or
in clusters in the dermis, because the major clue to the diagnosis of MF was the identification of neoplastic cells. They
also noted that the efficacy of single histologic criteria in the
diagnosis of MF was generally poor and concluded that a confident diagnosis of MF could be achieved using a constellation
of cytoarchitectural features. In 1999, Guitart et al.4 proposed
a grading system based on the sequential evaluation of major
and minor criteria at different magnifications in order to
increase the agreement rate among dermatopathologists in
reporting biopsies suspicious of MF. In order to assess the
frequency and significance of different histologic parameters
in Iranian MF patients, we conducted our study.
Materials and methods
We conducted our study in two phases. In phase I, we assessed
the frequency of a series of histologic parameters in 50 slides from 30
patients in different stages (patch, plaque, and tumor) of MF. In phase
II, we compared these histologic criteria in 24 patients with documented
patches of MF with those in 24 non-MF patients in order to evaluate
the significance of each parameter in the diagnosis of early MF.
The diagnosis of MF in all patients was unequivocally
established by either the progression of patients from the patch
stage of MF to the more advanced plaque or tumor stage, or by
indubitable histologic findings pathognomonic for MF. All patients
included in the study had medical records at Razi Hospital and
were undergoing treatment for their disease.
Each slide was evaluated separately by our reference
dermatopathologists (Z. S. Naraghi, MD, and S. Kavusi, MD) by
light microscopy, and each histologic parameter was graded on a
four-point scale, as defined in Table 1. In phase II, the slides of MF
and non-MF patients were mixed and reviewed in a blind manner.
We assessed the histologic pattern,10 density and location of the
dermal infiltrate at low power ( 10). At intermediate power ( 40),
International Journal of Dermatology 2003, 42, 45 52

all of the cytoarchitectural parameters were evaluated, except for


nuclear detail and atypia of lymphocytes, which were reviewed at
high power ( 100). Cell counts in the epidermis and dermis (for
example, number of haloed lymphocytes or eosinophils) were
performed in five different fields from the most dense areas and the
mean value was recorded for each. Features such as spongiosis,
dermal edema, parakeratosis, and papillary dermal fibrosis were
graded as the percentage of specimen involved.9 Disproportionate
epidermotropism was graded according to the ratio of the highest
degree of epidermotropism to spongiosis.9 Pautriers
microabscess was defined as a cluster of at least four atypical
lymphocytes within a single intraepidermal vacuole. The dermal
infiltrate was monomorphous if more than 75% of the infiltrate was
composed of lymphocytes and granulomatous if clusters of
epithelioid histiocytes or giant cells were detected. Lymphocytes
were graded as small (nucleus, < 5 m), medium (nucleus,
5 9 m), or large (nucleus, 10 12 m). Mitosis was present if
more than three mitoses were detected per five high power fields
(> 3/5 100). Vasculopathy was defined as the presence of
extravasated red blood cells and/or swollen endothelial cells
and/or thick vessel walls.
Our non-MF group was composed of patients who definitely
did not have MF on clinical grounds and follow-up, but whose
histologic pattern was suspicious for MF. Patients in the MF
and non-MF groups were matched by histologic pattern10 (i.e.
lichenoid, spongioticlichenoid, psoriasiform).
Data were entered on a computer file and statistically analyzed
using the SPSS package to obtain frequency tables and cross
tables. A univariate analysis was performed on each criterion in
phase II by chi-squared and Fischers exact test, and the sensitivity
and specificity were calculated for each parameter. A multivariate
analysis was performed on factors that gained significance in the
univariate analysis by logistic regression.

Results
The results of the histologic evaluation of 50 slides from 30
patients in patch, plaque, and tumor stages of MF are summarized in Table 2.
We reviewed 24 slides from patch stage MF, 18 from
plaque stage MF, and eight from tumor stage MF; 60% of the
patients were males.11 The patients ages in the different
groups are given in Table 3. There were five cases below
30 years of age in patch stage MF, confirming that MF is not
a disease exclusively of older individuals, but also affects
young patients.12
The results of the second phase of our study are summarized
in Table 4. The P value for each parameter is recorded and the
sensitivity and specificity of all criteria are noted in Table 4.
In univariate analysis, we found that the degree of
epidermotropism, Pautriers microabscesses, haloed
lymphocytes, disproportionate epidermotropism, larger
epidermal lymphocytes, hyperconvoluted lymphocytes in the
2003 The International Society of Dermatology

Naraghi et al.

Histologic criteria in mycosis fungoides Mehregan Supplement Report

Table 1 Grading of histologic parameters


Parameter

1+

2+

3+

4+

Atrophy
Acanthosis
Parakeratosis
Spongiosis
Intensity of epidermotropism
Pautriers microabscesses
Haloed lymphocytes
Disproportionate
epidermotropism
Epidermal > dermal
lymphocytes
Hyperconvoluted
epidermal lymphocytes
Dyskeratosis
Intensity of
dermal infiltrate
Eosinophils
Plasma cells
Histiocytes
Hyperconvoluted
dermal lymphocytes
Papillary fibrosis
Dermal edema
Telangiectasia
Perieccrine lymphocytes
Follicular mucinosis
Follicular infiltration
Vasculopathy
Mitosis
Pattern of
epidermotropism
Basal layer

None
None
None
None
None
None
None
None

Mild
Mild
< 10%
< 10%
1 5/40
Present/40
1 5/40
Mild

Moderate
Moderate
10 50%
10 50%
6 10/40

6 10/40
Moderate

Severe
Severe
> 50%
> 50%
> 10/40

> 10/40
Severe

None

10% larger/100

10 50% larger/100

> 50% larger/100

None

1 5/100

5 10/100

> 10/100

None
Sparse

1 5/40
Mild perivascular
or lichenoid
1 5/40
1 5/40
1 5/40
1 5/100

6 10/40
Dense lichenoid

> 10/40
Very dense or deep

6 10/40
6 10/40
6 10/40
6 10/100

> 10/40
> 10/40
> 10/40
> 10/100

< 10%
< 10%
< 1 vessel
1 5/40
< 10%
1 5/40
Present
Present (> 3/500)
Pagetoid

10 50%
10 50%
1 3 vessels
6 10/40
10 50%
6 10/40

Mixed

> 50%
> 50%
> 3 vessels
> 10/40
> 50%
> 10/40

Perivascular

Diffuse vacuolar
change

Pattern of
dermal infiltrate
Location of
dermal infiltrate

Focal vacuolar
change
Lichenoid

Papillary dermis

Papillary and upper


reticular dermis

Papillary and
reticular dermis

Monomorph
Small
Spongiotic
Lichenoid
Psoriasiform
Spongioticlichenoid
Spongiotic
psoriasiform
Lichenoid
psoriasiform
Spongioticlichenoid
psoriasiform

Polymorph
Small, medium

Granulomatous
Small, medium, large

Dermal infiltrate
Dermal lymphocytes
Pattern

None
None
None
None
None
None
None
None
None
None
None
None
Single lymphs
in basal layer
Intact

epidermis and dermis, absence of dyskeratosis, and papillary


dermal fibrosis were the most significant discriminators
between MF and its inflammatory simulators, emphasizing
the importance of both cytologic and architectural features in
the diagnosis of MF.3
2003 The International Society of Dermatology

Papillary and
reticular dermis
and subcutis

On multivariate analysis by logistic regression, none of the


histologic criteria found to be important diagnostically by
univariate analysis had additional discriminatory power.
In reviewing the slides of 50 MF patients, we encountered all of the major inflammatory patterns described by
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Mehregan Supplement Report Histologic criteria in mycosis fungoides

Table 2 Frequency of histologic parameters (phase I)


Parameter

Patch % > 2+

Plaque % > 2+

Tumor % > 2+

Total % > 2+

Atrophy
Acanthosis
Parakeratosis
Spongiosis
Pautriers microabcesses
Haloed lymphocytes
Disproportionate epidermotropism
Epidermal > dermal lymphocytes
Hyperconvoluted epidermal lymphocytes
Dyskeratosis
Intensity dermal infiltrate
Eosinophils
Plasma cells
Histiocytes
Hyperconvoluted dermal lymphocytes
Papillary dermal fibrosis
Dermal edema
Telangiectasia
Perieccrine lymphocytes
Follicular mucinosis
Follicular infiltration
Vasculopathy
Mitosis
Pattern of epidermotropism
Single basal
Pagetoid
Mixed
Basal layer
Intact
Focal vacuolar
Diffuse vacuolar
Pattern of dermal infiltrate
Perivascular
Lichenoid
Location of dermal infiltrate
Papillary dermis
Papillary and upper reticular dermis
Papillary and reticular dermis
Papillary and reticular dermis
and subcutaneous fat
Deep reticular dermis
and subcutaneous fat
Dermal infiltrate
Monomorphous
Polymorphous
Granulomatous
Dermal lymphocytes
Small
Small, medium
Small, medium, large
Pattern
Spongiotic
Lichenoid
Psoriasiform
Spongioticlichenoid
Spongioticpsoriasiform
Lichenoidpsoriasiform
Spongioticlichenoidpsoriasiform

41.7
66.7
54.2
54.2
37.5
87.5
75
41.7
62.5
29.8
87.5
29.2
25
75
83.3
95.8
66.7
100
13
0
45.8
25
0

22.2
77.8
77.8
72.2
66
94.4
83
61.1
83.3
44.4
94.4
72.2
44.4
100
77.8
88.9
61.1
83.3
17.6
22.2
55.6
50
33.3

25
75
87.5
75
12.5
10
50
25
75
0
100
87.5
62.5
87.5
100
62.5
37.5
87.5
83.3
37.5
87.5
50
62.5

32
72
68
64
44
92
74
46
72
26
92
54
38
86
84
88
60
92
22
14
56
38
22

79
8
12.5

33
28
39

62.5
25
125

60
18
22

12.5
62.5
25

22
44
33

62.5
0
37.5

24
46
30

54
46

39
61

54
21
25
0

22
33
33
11

0
0
25
62.5

34
22
28
14

12.5

71
29
0

55.5
28
16.5

25
75
0

58
36
6

83
17
0

67
33
0

25
62.5
12.5

68
30
2

4
58
12.5
8
4
12.5
0

0
28
17
28
5
11
11

12.5
25
12.5
12.5
25
0
12.5

4
42
14
16
8
10
6

International Journal of Dermatology 2003, 42, 45 52

0
100

40
60

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Naraghi et al.

Histologic criteria in mycosis fungoides Mehregan Supplement Report

Table 3 Age of patients


Age

Patch

Plaque

Tumor

Total

Range (years)
Mean (years)

17 77
47.2

30 78
57.2

42 75
58.7

17 78
52.7

Ackerman.10 The most common pattern was lichenoid


(42%), followed by spongioticlichenoid and psoriasiform.
Focal or diffuse vacuolar change was detected in 76% of slides.
The results of our histologic review are recorded in Table 2.
Discussion
In this study, we systemically evaluated many of the criteria
previously reported to be useful in distinguishing MF from its
inflammatory simulators.9 By strictly defining the criteria
before initiating a comparison, we tried to minimize the
inter- and intraobserver disagreement that often accompanies
qualitative and semiquantitative histologic evaluations.4,13,14
Attempts to enhance diagnostic sensitivity with the use of
immunophenotyping have proven to be of some value,5,9 but
the loss of T-cell common antigens useful in confirming the
presence of a neoplastic infiltrate most commonly occurs in
plaque and tumor stages, stages in which histopathologic
diagnosis is less challenging.2
Although some authorities have reported the loss of CD-7
to be helpful in identifying MF, others have not found the
absence of CD-7 to be a reliable feature in differentiating MF
from inflammatory diseases.2 The polymerase chain reaction
technique is used to assess T-cell clonality in biopsies suspicious
for early MF. Clonal T-cell receptor- gene rearrangements
were detected in 77% of suspected MF specimens in a recent
report by Murphy et al.8 T-cell receptor gene rearrangements
could be detected in 50 80% of documented patches and
plaques.15 Moreover, when indeterminate lesions were
analyzed, the clonality dropped to as low as 19%.5 Also, the
demonstration of a clonal T-cell proliferation does not
necessarily establish a diagnosis of a malignant process, such
as MF.2,9 These results indicate that clinicopathologic
correlation remains the gold standard in the diagnosis of MF.
In our study, upward migration of lymphocytes into the
epidermis (epidermotropism) was found in all MF patients,
but also in 80% of inflammatory diseases; it is therefore a
sensitive, but nonspecific, parameter. Disproportionate
epidermotropism was significantly more specific (92%),
although not as sensitive. Our results are in agreement with
those of Smoller et al.,9 indicating that epidermotropism is a
crucial feature for the diagnosis of early MF. The most
frequent pattern of epidermotropism in the MF group was the
linear arrangement of single cells in the basal layer (seen in
80% of cases), but because lymphocytes were also detected in
2003 The International Society of Dermatology

the lower one-third of the epidermis in 87.5% of non-MF


patients, this pattern was not a specific marker for MF. In
contrast, a pagetoid pattern was not detected in any of the
inflammatory disorders, and was therefore a specific, but not
sensitive, feature. Haloed lymphocytes were detected in
87.5% of patients with MF, but also in 33% of the control
group. Prominent haloed cells (> 6/40) were found in only
25% of MF patients. Our study supports the impressions of
Ackerman10 and Smoller et al.9 that haloed lymphocytes are
highly indicative of MF. Pautriers microabscesses were only
detected in patches of MF and never in its inflammatory simulators; therefore, it proved to be a significant discriminator
on univariate analysis, similar to haloed lymphocytes and disproportionate epidermotropism, although they were detected
in only 37.5% of patches of MF, similar to that reported by
Smoller et al.9
The most specific feature in the epidermis was the presence
of lymphocytes that were larger than dermal lymphocytes, in
addition to Pautriers microabscesses. This feature was also
typical of MF, and not seen in any inflammatory condition.9
It was readily detectable (epidermal lymphocytes > 10%
larger than dermal lymphocytes) in 30% of patches of MF.
Hyperconvolution of intraepidermal lymphocytes also
proved to have discriminating power, although it was not a
particularly common feature (62.5%).9
We observed areas of atrophy adjacent to acanthotic areas
in 12.5% of patches, a histologic clue suggestive of MF.3
Spongiosis was more common in the non-MF group and, in
those MF patients in which spongiosis was observed, it was
almost always of a mild degree. Microvesiculation was
absent in 96% of patches of MF. It is a sensitive criterion and
identical to the results of the EORTC.1 We should emphasize
that, although mild degrees of spongiosis do not exclude
MF, the presence of microvesiculation is exceedingly rare.
The absence of dyskeratosis (79%) proved to be another
discriminating factor.
Eosinophils and plasma cells were uncommon in the dermal
infiltrates of patches of MF, but plasma cells were detected
more frequently in MF patients than in those with inflammatory dermatoses. Dermal hyperconvoluted lymphocytes were
commonly detected in patches of MF (83%), but not in the
control group, proving to be a specific discriminating factor in
the univariate analysis. This observation is emphasized by the
report of the EORTC1 which declared that the presence of
medium to large cerebriform cells in the epidermis or in clusters in the dermis is the single most useful histopathologic
marker in establishing a diagnosis of early MF.
Dermal infiltration was more dense in MF patients. In 96%
of patches, the infiltrate was composed mainly of small
lymphocytes, but medium lymphocytes were found in 16%
of patients, usually mixed with small cells; 71% showed a
monomorphic dermal infiltrate. We obtained a result between
that reported by Nickoloff,16 who observed a monomorphous
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Table 4 Univariate analysis

Parameter
Atrophy
Acanthosis
Parakeratosis
Spongiosis
Pautriers microabscesses
Haloed lymphocytes
Disproportionate epidermotropism
Epidermal > dermal lymphocytes
Hyperconvoluted epidermal lymphocytes
Dyskeratosis
Intensity dermal infiltrate
Eosinophils
Plasma cells
Histiocytes
Hyperconvoluted dermal lymphocytes
Papillary fibrosis
Dermal edema
Telangiectasia
Perieccrine lymphocytes
Follicular mucinosis
Follicular infiltration
Mitosis
Pattern of epidermotropism
Single basal
Pagetoid
Mixed
Basal layer
Intact
Focal vacuolar
Diffuse vacuolar
Pattern of dermal infiltrate
Perivascular
Lichenoid
Location of dermal infiltrate
Papillary dermis
Papillary and upper reticular dermis
Papillary and reticular dermis
Papillary and reticular dermis and subcutis
Dermal infiltrate
Monomorphous
Polymorphous
Granulomatous
Dermal lymphocytes
Small
Small, medium
Medium
Pattern
Spongiotic
Lichenoid
Psoriasiform
Spongioticlichenoid
Spongioticpsoriasiform
Lichenoidpsoriasiform
Spongioticlichenoidpsoriasiform

International Journal of Dermatology 2003, 42, 45 52

Patch MF > 2+
(%)

Non-MF > 2+
(%)

Sensitivity
(%)

Specificity
(%)

P
value

41.7
66.7
54.2
54.2
37.5
87.5
75
41
62.5
20.8
87.5
29.2
25
75
83.3
95.8
66.7
100
13
0
45.8
0

50
50
33.3
75
0
33.3
8.3
0
25
70.8
75
29.2
12.5
91.7
12.5
50
87.5
91.7
15
0
63.6
0

42
67
54
54
37.5
87.5
75
41
62.5
21
87.5
29
25
75
83
96
67
100
13
0
46
0

50
50
67
25
100
67
92
100
75
29
25
71
87.5
8
87.5
50
12.5
8
85

36

0.77
0.38
0.24
0.22
0.002
0
0
0.001
0.019
0.001
0.46
1
0.46
0.24
0
0.001
0.168
0.489
0.712

0.14

79
8
12.5

87.5
0
12.5

79
8
12.5

12.5
100
87.5

0.35

12.5
62.5
25

20.8
29.1
50

12.5
62.5
25

79
71
50

0.067

54
46

58
42

54
46

42
58

54
21
25
0

37.5
25
33
4

54
21
25
0

62.5
75
67
96

0.49

71
29
0

62.5
37.5
0

71
29
0

37.5
62.5

0.76

83
12.5
4

0
100
100

0.113

83
12.5
4
4
58
12.5
8
4
12.5
0

100
0
0
4
58
12.5
8
4
12.5
0

2003 The International Society of Dermatology

Naraghi et al.

infiltrate in 33% of patches and plaques, and that obtained by


the EORTC,1 which detected a monomorphous infiltrate of
lymphocytes to be a sensitive criterion (91.7%).
In 75% of patch stage MF, dermal infiltration was confined
to the papillary and upper reticular dermis. No involvement
of the subcutis was observed in our MF patients; 37.5% of
patches showed a purely lichenoid pattern and 20% showed
an atrophic lichenoid pattern at low magnification. Other
commonly observed gross patterns in decreasing order were
psoriasiform (12.5%) and lichenoidpsoriasiform (12.5%).
Shapiro and Pinto3 reported similar findings. This emphasizes
the common occurrence of interface changes in MF patients,2,17
found in 87.5% of our cases of MF.
Dermal edema and vasculopathy were neither sensitive
nor specific for MF. Severe dermal edema was not observed
in the MF group. In contrast, papillary dermal fibrosis was a
sensitive feature (96%), with the observation of either fine or
coarse bundles of collagen, and it achieved statistical significance as a discriminating factor. This is similar to the results
reported by Smoller et al.9 and Ackerman.10 They also
pointed out that dermal fibrosis was a feature of late atrophic
patches or plaques and was not encountered in early patches.
Mitoses were not detected in patches of MF, showing that
lymphocytic mitotic activity is not increased in early lesions of
MF.9 In addition, none of our MF patients had any evidence
of follicular mucinosis, but folliculotropism was detected in
about one-half of patients. Eccrine gland involvement was
reported in 13% of patch stage MF.
Pautriers microabscesses, haloed lymphocytes, disproportionate epidermotropism, larger epidermal lymphocytes,
hyperconvoluted lymphocytes in the dermis and epidermis,
absence of dyskeratosis, and papillary dermal fibrosis achieved
significance as discriminating factors between MF and its
inflammatory simulators on univariate analysis; however,
none of these features showed additional distinguishing power
on multivariate analysis by logistic regression. It is counterintuitive that the diagnosis produced by multiple histologic
features does not demonstrate a unique criterion for discriminating MF from non-MF. There may be two reasons for this.
First, covariation of our significant features (on univariate
analysis) and their high correlation may exhaust the discriminating power of the other. Second, the relatively small sample
size; with a larger sample size, some features might emerge as
significant factors.
Based on the data presented here, we conclude that there
are some histologic features, such as Pautriers microabscesses,
haloed lymphocytes, disproportionate epidermotropism,
larger epidermal lymphocytes, absence of dyskeratosis,
hyperconvoluted dermal and epidermal lymphocytes, and
papillary dermal fibrosis, that can be used to discriminate MF
from its inflammatory simulators. In order to diagnose MF
confidently, we must use the constellation of cytologic and
architectural parameters proposed. The gold standard in the
2003 The International Society of Dermatology

Histologic criteria in mycosis fungoides Mehregan Supplement Report

diagnosis of MF is clinicopathologic correlation, and the


efficacy of single histopathologic features in the diagnosis of
early MF is generally poor.1
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lymphoma: Refinement in the application of controversial
histologic criteria. Dermatol Clin 1999; 17 (3): 601 614.
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fungoides/Sezary syndrome. A review of 222 biopsies
including newly described patterns and the earliest
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4 Guitart J, Variakojis D, et al. Histologic criteria for the
diagnosis of early mycosis fungoides: Proposal of a grading
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5 Bergman R, Faclieru D, Sahar D, et al. Immunophenotyping
and T-cell receptor gamma gene rearrangement analysis as
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7 Delfau-Larue MH, Patrella T, Lahet C, et al. Value of
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8 Murphy M, Signoretti S, Kadin ME, et al. Detection of
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9 Smoller BR, Bishop K, Glusac E, et al. Reassessment of
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10 Ackerman AB. Histologic Diagnosis of Inflammatory Skin
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11 Morales Suarez-Varela MM, Llopis Gonzalez A,
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12 Elder D. Levers Histopathology of the Skin. Philadelphia:
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13 Burg G, Zwingers T, Feller AC, et al. Interrater and
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14 Santucci M, Biggeri A, Feller AC, et al. Accuracy,
concordance, and reproducibility of histologic diagnosis in
cutaneous T-cell lymphoma: an EORTC cutaneous
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(4): 497 502.
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15 Tok J, Szabolcs J, Silvers DN, et al. Detection of clonal


T-cell receptor & chain gene rearrangements by PCR and
denaturing gradient gel electrophoresis (PCR / DGGE) in
archival specimens from patients with early CTCL.
Correlation of histologic findings with PCR / DGGE. J Am
Acad Dermatol 1998; 38: 453.

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Naraghi et al.

16 Nickoloff BJ. Light microscopic assessment of 100 patients


with patch / plaque stage mycosis fungoides. Am J
Dermatopathol 1988; 10: 469 477.
17 Guitart J, Peduto M, Caro WA, et al. Lichenoid changes
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2003 The International Society of Dermatology

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