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Mycosis fungoides:
criteria for histopathologic diagnosis
Flavia
Flavia CB
CB Lisboa,
Lisboa, Sueli
Sueli Carneiro,
Carneiro, Juan
Juan Piñeiro-Maceira
Piñeiro-Maceira
Sector of Dermatology and Department of Pathology-HUCFF/U FRJ and Post-Graduation Course, School of Medicine,
Universidade Federal do Rio de Janeiro, Brazil
INTRODUCTION
Mycosis fungoides (MF) is a T cell cutaneous lymphoma (CTCL) characterized by patch, plaque and tumor stages, and erythroderma during its evolution. The
diagnosis of the patch stage is often difficult, clinically and histopathologically, because patients with patch stage mycosis fungoides present erythematous
patches or plaques minimally infiltrated resembling inflammatory lesions, that may persist for a long time. The histologic findings of such stage are subtle. The
same difficulty is seen in patients with erythroderma.1,2
Figure 1:
Photomicrography of
initial lesion (patch stage).
Epidermotropism of lymphocytes and
discrete mononuclear infiltrate
in the dermis (HE, 100X)
Frequently many biopsies taken over a long period of time are necessary before a definitive diagnosis can be
reached.3 On the other hand, established plaque-stage MF rarely causes difficulties in its clinical or
4
histopathological diagnosis.
OBJECTIVE
To identify the most relevant criteria for the histopathologic diagnosis of mycosis fungoides, specially in the
patch stage and in the erythrodermic form, through the observation of the histopathologic features present in
patients with a clinical evolution characteristic of the disease.
Figure 2:
Photomicrography of
initial lesion (patch stage).
Irregular acantosis and
dense mononuclear infiltrate
occupying the dermis (HE, 100X)
MATERIAL AND METHODS
Sixty-five patients with the histologic diagnosis of mycosis fungoides were recovered from the files of the
Department of Pathology of HUCFF/UFRJ in the period of 1978-1998. After reviewing their records, 27 patients
were included in the study. All of them had the diagnosis of MF confirmed by clinical evolution. Major
characteristic aspects of the patients and material and summarized in tables 1, 2, 3 and 4.
Forty two hematoxilin-eosin-stained skin sections were evaluated for the presence of parakeratosis, acanthosis, epidermal atrophy, dyskeratosis,
spongiosis, exocytosis, disproportionate epidermotropism, Pautrier's microabscess, basal layer damage, papillary fibrosis, papillary edema,
telangiectasia, perieccrine lymphocytes, follicular epidermotropism, epithelioid granulomas and eosinophils, haloed lymphocytes, single basal
lymphocytes and dermal and epidermal lymphocytes with hyperconvoluted nuclei.
Figure 5: Photomicrography of erythrodermic form.
Hyperconvoluted nuclei lymphocyte
in the epidermis (HE, 1000X)
Figure 4: Photomicrography of erythrodermic form.
Irregular acantosis and discrete mononuclear infiltrate
in the dermis (HE, 100X)
Figure 6: Photomicrography of erythrodermic form.
Hyperconvoluted nuclei lymphocytes
in the dermis (HE, 1000X)
RESULTS
Figure 3:
Photomicrography of erythrodermic form.
Parakeratosis, irregular acantosis,
disproportionate epidermotropism of
lymphocytes and mononuclear infiltrate
occupying the dermis (HE, 100X)
Figure 7: Photomicrography of eryhtrodermic form.
Halloed lymphocytes with hyperconvoluted nuclei aligned
in the basal layer (HE, 1000X)
Table 1: Relation between number of patients
and skin samples available for the study
according to clinical diagnosis
Hyperconvoluted nuclei lymphocytes within the epidermis (81,25%) and haloed lymphocytes
(75,0%) were the most frequent findings in the patch stage. In the erythrodermic form,
disproportionate epidermotropism was seen in 92,3% of the cases. Hyperconvoluted nuclei
lymphocytes within the epidermis and dermis appeared in equal proportions (88,46%), while the
haloed lymphocytes were seen in 84,61%. Pautrier microabscesses were seen only in about one
fourth of the cases
Initial phase
Erythrodermic form
Total
Patients Skin samples
9
16
18
26
27
42
Figure 8: Photomicrography of initial lesion.
Pautrier's microabscess (HE, 400X)
Table 2: Number of patients according to inclusion criteria
Disease form
Evolution to
tumoral lesions or
spread of the
disease
Initial
Erythrodermic
Total
3
12
15
Follow up for at least 5
years, with typical
evolution, although
without disease
progression
6
6
12
Total
9
18
27
The prevalence of each criteria is represented in Graphic 1, for both initial and erythrodermic forms.
Granulomas
Table 3: Clinical and epidemiological aspects
of initial phase patients
Dermal edema
Erytrodermic form
Telangiectasia
Age of
N Sex disease
onset
Initial phase
Eosinophils
Exocytosis
1
F
61
Spongiosis
2
F
40
Dyskeratosis
Epidermal atrophy
3
M
49
8
M
62
13
M
60
15
M
71
18
F
60
20
F
61
Parakeratosis
Graphic 1:
Prevalence of histopathological
criteria in both forms of MF studied.
Acantosis
Perieccrine lymphs
Papillary fibrosis
Pautrier's microabscess
Single basal lymphs
21
Haloed lymphs
Convoluted dermal lymphs
M
27
Age at the Follow up
time of
duration Evolution
Death
diagnosis
(years)
Improved with
63
5
N
topical treatment
Worsened with
44
4
N
tumoral lesions
Improved with
55
5
N
topical treatment
Worsened with
63
2
N
tumoral lesions
Worsened with
62
2
N
tumoral lesions
Improved with
71
7
N
topical treatment
Improved with
65
10
N
topical and systemic
treatment
Improved with
63
5
N
topical treatment
Improved with
34
7
topical and systemic
N
treatment
M: male; F: female; N: no; Y:yes
Convoluted epidermal lymphs
Table 4: Clinical and epidemiological aspects of erythrodermic patients
Age of Age at the Follow up
N Sex disease time of
duration Evolution
onset diagnosis (years)
Improved with topical and systemic
4 M
47
47
5
treatment
5 M
38
39
1/dez
Spread of the disease
6 M
82
82
2
S zary cells on peripheral blood
Improved with topical and systemic
7
F
29
62
13
treatment
9 M
45
51
8
Improved with systemic treatment
10 M
56
76
1/dez
Spread of the disease
11
M
63
63
11
Improved with systemic treatment
12 M
74
79
5
Worsened with tumoral lesions
23
F
50
67
1/dez
S zary cells on peripheral blood
25 M
59
63
5
S zary cells on peripheral blood
26 M
66
72
1
Worsened with tumoral lesions
28 M
53
54
1/dez
S zary cells on peripheral blood
Improved with topical and systemic
29 M
61
62
7
treatment
31
F
65
66
2
Worsened with tumoral lesions
Bone marrow infiltration by
32 M
65
70
6
hiperconvoluted lymphocytes
33 M
53
53
3
CNS infiltration
36 M
82
83
4
S zary cells on peripheral blood
Improved with topical and systemic
37
F
68
71
5
treatment
Death
N
Y
N
N
N
Y
N
Y*
N
N
Y
Y
N
N
N
Y
Y
N
M: male; F: female; N: no; Y: yes; *non-MF related death
Disproporcionate exocytosis
10
20
30
40
50
60
70
80
90
100
DISCUSSION
Cutaneous T cell lymphomas, especially mycosis fungoides, are subject of update discussion, mostly about their pathogeny,
classification and diagnostic criteria. The recent proposed classifications5,6 and the debates about the applicability and the
reproducibility of criteria suggested by them7,8 prove such affirmative.
We performed a systematic study in which we could confirm the sensibility of important histological criteria, as referred in the
3,4,9,10,11
literature.
Specially in erythrodermic forms, hyperconvoluted dermal lymphocytes and disproportionate epidermotropism
11
may be considered of great importance, as described earlier. Despite these results, the absence of these criteria in a small part of
the skin samples show that sometimes even the most prevalent criteria will not be seen in initial and erythrodermic forms of MF.
Pautrier's microabscesses were considered specific findings by Smoller et al,3 since they are present almost exclusively in cases of
11,12
MF, although, these abnormal lymphocyte collections within the epidermis are present in the minority of cases of MF. They were
seen only in about 25% of our cases. It seems that they are a specific finding, but not a sensible one, and thus are not necessary for
the diagnosis of MF.
We believe that in any patient with a clinical picture suggestive of mycosis fungoides, the presence of such prevalent histologic
findings, can make the diagnosis possible, even in initial and erythrodermic forms. On the other hand, the absence of the
histological findings can not exclude the diagnosis in a clinical suggestive setting.
REFERENCES
CONCLUSIONS
Disproportionate epidermotropism, hyperconvoluted nuclei lymphocytes (within
the epidermis and dermis), halloed lymphocytes and a dermal infiltrate with
eosinophils are the most relevant histopathologic findings in patch stage and
erythrodermic mycosis fungoides.
E-mail: [email protected]
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