Case report

zary syndrome with concomitant pulmonary

An unusual Se
localization: aggressiveness of folliculotropic form
Charlotte Brugiere1,2, MD, Andrea Stefan1,2, MD, Veronique Salaun3, MD, Francois
Comoz4, MD, Karine Campbell5, MD, Sylvain Chantepie3, MD, and Laurence Verneuil1,2,
MD, PHD

1
Department of Dermatology, CHU de
Caen, Caen, France, 2Medical School,
 de Caen Basse-Nomandie,
Universite
Caen, France, 3Department of
Haematology, CHU de Caen, Caen,
France, 4Department of Pathology, CHU de
Caen, Caen, France, and 5Department of
Pulmonary, CHU de Caen, Caen, France

Correspondence
Laurence Verneuil, MD, PHD
Dermatology Department, CHU Caen,
Avenue Georges Clemenceau, F-14033
Caen, France
E-mail: verneuil-l@chu-caen.fr
Conflicts of interest: None.

Introduction

Case report

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous

group of non-Hodgkin lymphomas arising from T cells
that home to and persist in the skin.1,2 Mycosis fungoides
(MF) and Sezary syndrome account for approximately
65% of CTCL.3 They were considered as different stages
in the same disease, but recent genetic and phenotypic
studies suggest that they arise from two distinct T-cell
subsets.4,5
Folliculotropic MF, a follicular variant of classic MF, is
discussed separately because of its distinct clinicopathological features3 and a more aggressive clinical course,
with poorer prognosis than in classic MF.6 It is characterized by folliculotropic infiltrates, often sparing the epidermis, and clinically by follicular papules, comedones, cysts
of preferentially head and neck areas, or by alopecia. It is
frequently refractory to usual therapies.6
Sezary syndrome is an aggressive clinical entity
associated with poor prognosis and a median survival of
23 years. Folliculotropic Sezary syndrome, a clinical variant, is exceptional, and we report a case of folliculotropic Sezary syndrome with a concomitant pulmonary
localization.

We report a 64-year-old man with a 1-month history

of pruritic erythroderma, which covered more than
80% of the body surface area and was associated with
infiltrated leonine facies, follicular papules of the head
and neck, alopecia of the scalp (Fig. 1a), and palmoplantar keratoderma. Cervical, axillary, and inguinal
lymphadenopathy were detected. Skin biopsy showed
no epidermotropism but follicular mucinosis was
confirmed by alcian blue staining (Fig. 1b) and lymphocyte aggregates composed of small- to intermediate-sized
lymphocytes with irregular nuclei (Fig. 1c) expressing
CD3/CD4/CD5 with a loss of CD7 and CD8 around
the hair follicles. An abnormal cutaneous T-cell population expressing CD2/CD3/CD4/CD5 with a loss of CD7
and CD26 expression was evidenced using flow cytometric immunophenotyping. Inguinal lymphadenectomy
showed localization of a malignant lymphoproliferative
T-cell population.
In the blood and inguinal lymphadenectomy, using
flow-cytometric immunophenotyping, the same T-cell
population was detected. The white blood cell count
showed 6.0 9 109/l lymphocytes with 1200/mm3 Sezary

2014 The International Society of Dermatology

International Journal of Dermatology 2016, 55, 8184

81

82

Case report

Brugie re et al.

An unusual folliculotropic Sezary syndrome

(a)

(b)

(c)

Figure 1 Clinical and histological data

of our patient. (a) Infiltrated leonine
facies with alopecia of the scalp and
follicular papules of the head. (b)
Follicular mucinosis and aggregates of
lymphocytes around hair follicles;
alcian blue staining, 9 200. (c) Smallto intermediate-sized lymphocytes
with irregular nuclei at the lower part
of the hair follicle bulb; hematoxylin
eosinsafran staining, 9 400

cells and a CD4/CD8 ratio at 41. HTLV-1 detection was

negative.
A computed tomography scan showed bilateral reticular infiltrates, and bronchoalveolar fluid analyses, using
flow-cytometric immunophenotyping, detected the same
abnormal T-cell population CD2+/CD3+/CD4+/CD5+/
CD7 /CD8 /CD26 as in the skin, blood, and lymph
node. No red blood cell was detected in the bronchoalveolar fluid, excluding blood contamination. The same
T-cell clone was detected in the skin, blood, lymph nodes,
and bronchoalveolar fluid.
These data were characteristic of a folliculotropic
Sezary syndrome with a concomitant pulmonary localization, corresponding to a T4N2M1B2 stage, clinical
stage IVB. There was no other extracutaneous infiltration.
Despite intensive treatment with cyclophosphamide/
doxorubicin/vincristine/prednisone started immediately in
our patient, he died five months after the diagnosis due
to an acute respiratory distress syndrome probably secondary to the progression of pulmonary lymphoma.
International Journal of Dermatology 2016, 55, 8184

Discussion
Sezary syndrome characterized by a folliculotropism (folliculotropic Sezary syndrome) is exceptional with only eight
cases previously reported713 (Table 1). In our patient,
aggressiveness was remarkable with concomitant pulmonary lymphoma localization at the onset of disease. Currently, as in our case, a quick extracutaneous involvement
has been described in four of nine patients (44%) with folliculotropic Sezary syndrome, showing a strong aggressiveness when a folliculotropism is present7,8,13 (Table 1). This
fact suggests that factors other than therapeutic resistance
alone, which was recorded in folliculotropic MF,14,15 could
be involved in this agressiveness. The T lymphocytes found
in the folliculotropic form of CTCL could be characterized
by greater visceral tropism. This raises the question of the
molecular and functional characteristics of these T lymphocytes and the possibility of a common target in hair follicles
and certain organs. Studies have shown that chemokine
receptors are likely to be involved in the skin tropism that
characterizes CTCL.16,17 Molecular study characterizing
2014 The International Society of Dermatology

Brugie re et al.

5 months
At the diagnosis
Yes

Lung

At the diagnosis
Bone marrow

ND
ND, in life after 5 years
ND, in life after 2 years
In life

< 1 year

5 months
Bone marrow

Yes
Yes
Yes
Yes

Follicular dermatosis, nodules, alopecia

Erythroderma, follicular papules, leonine facies
Erythroderma, follicular papules, alopecia
Erythroderma, follicular papules, leonine facies,
keratoderma
Erythroderma, follicular papules, leonine facies,
keratoderma, alopecia
F
M
M
M

2 years
ND
ND
5 months

Our case, 2012

Jang13

Mehta7
Gerami12

zary syndrome
Se
zary syndrome
Se
zary syndrome
Se
Cutaneous CD30+ folliculotropic
zary
lymphoma with circulating Se
cells
zary syndrome
Se
zary syndrome
Se
zary syndrome
Se
zary syndrome with
CD25+ Se
CD30+ large cell transformation
zary syndrome
Se
Westfried9
Rivers10
LeBoit11
Tremeau-Martinage8

M
M
F
M

Follicular papules, keratoderma

Erythroderma, nodules, small milia, alopecia
Erythema, follicular papules, alopecia
Follicular papules

Yes
No
Yes
Yes

Bone marrow

Survival
Sex
Type of folliculotropic lymphoma

2014 The International Society of Dermatology

Case report

and comparing T lymphocytes of folliculotropic CTCL and

T lymphocytes of non-folliculotropic CTCL could be
investigated.

Cases reported

Table 1 Reported cases of folliculotropic S

ezary syndrome

Cutaneous data

Adenopathy

Extracutaneous
involvement

Time to visceral
involvement

An unusual folliculotropic Sezary syndrome

Acknowledgements
We wish to thank A. Swaine, who reviewed the English
language.
References
1 Olsen E, Vonderheid E, Pimpinelli N, et al. Revisions to
the staging and classification of mycosis fungoides and
Sezary syndrome: a proposal of the International Society
for Cutaneous Lymphomas (ISCL) and the cutaneous
lymphoma task force of the European Organization of
Research and Treatment of Cancer (EORTC). Blood
2007; 110: 17131722.
2 Girardi M, Heald PW, Wilson LD. The pathogenesis
of mycosis fungoides. N Engl J Med 2004; 350:
19781988.
3 Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC
classification for cutaneous lymphomas. Blood 2005; 105:
37683785.
4 Campbell JJ, Clark RA, Watanabe R, et al. Sezary
syndrome and mycosis fungoides arise from distinct T-cell
subsets: a biologic rationale for their distinct clinical
behaviors. Blood 2010; 116: 767771.
5 van Doorn R, van Kester MS, Dijkman R, et al.
Oncogenomic analysis of mycosis fungoides reveals major
differences with Sezary syndrome. Blood 2009; 113: 127
136.
6 van Doorn R, Scheffer E, Willemze R. Follicular mycosis
fungoides, a distinct disease entity with or without
associated follicular mucinosis: a clinicopathologic and
follow-up study of 51 patients. Arch Dermatol 2002;
138: 191198.
7 Mehta A, Dhungel BM, Khan MF. Mycosis fungoides/
Sezary syndrome: report of an unusual case. J Cutan
Pathol 2006; 33(Suppl. 2): 1215.
8 Tremeau-Martinage C, Gorguet B, Lamant L, et al.
[CD30 positive pilotropic lymphoma]. Ann Dermatol
Venereol 1999; 126: 434438.
9 Westfried M, Rosenthal JC, Coppola A, et al. Sezary
syndrome presenting as a follicular dermatosis. Cutis
1982; 29: 394396.
10 Rivers JK, Norris PG, Greaves MW, et al. Follicular
mucinosis in association with Sezary syndrome. Clin Exp
Dermatol 1987; 12: 207210.
11 LeBoit PE, Abel EA, Cleary ML, et al. Clonal
rearrangement of the T cell receptor beta gene in the
circulating lymphocytes of erythrodermic follicular
mucinosis. Blood 1988; 71: 13291333.
12 Gerami P, Guitart J. Folliculotropic Sezary syndrome: a
new variant of cutaneous T-cell lymphoma. Br J
Dermatol 2007; 156: 781783.

International Journal of Dermatology 2016, 55, 8184

83

84

Case report

An unusual folliculotropic Sezary syndrome

13 Jang MS, Kang DY, Han SH, et al. CD25+ folliculotropic

Sezary syndrome with CD30+ large cell transformation.
Australas J Dermatol 2012; doi: 10.1111/ajd.12000.
[Epub ahead of print].
14 Benner MF, Jansen PM, Vermeer MH, et al. Prognostic
factors in transformed mycosis fungoides: a retrospective
analysis of 100 cases. Blood 2012; 119: 16431649.
15 Agar NS, Wedgeworth E, Crichton S, et al. Survival
outcomes and prognostic factors in mycosis fungoides/
Sezary syndrome: validation of the revised International
Society for Cutaneous Lymphomas/European

International Journal of Dermatology 2016, 55, 8184

Brugie re et al.

Organisation for Research and Treatment of

Cancer staging proposal. J Clin Oncol 2010; 28:
47304739.
16 Wu XS, Lonsdorf AS, Hwang ST. Cutaneous T-cell
lymphoma: roles for chemokines and chemokine
receptors. J Invest Dermatol 2009; 129: 11151119.
17 Yagi H, Seo N, Ohshima A, et al. Chemokine receptor
expression in cutaneous T cell and NK/T-cell lymphomas:
immunohistochemical staining and in vitro chemotactic
assay. Am J Surg Pathol 2006; 30: 11111119.

2014 The International Society of Dermatology