An unusual Sézary syndrome with concomitant pulmonary localization: aggressiveness of folliculotropic form

Authors


  • Conflicts of interest: None.

Introduction

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 Sézary 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 features[3] 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]

Sézary syndrome is an aggressive clinical entity associated with poor prognosis and a median survival of 2–3 years. Folliculotropic Sézary syndrome, a clinical variant, is exceptional, and we report a case of folliculotropic Sézary syndrome with a concomitant pulmonary localization.

Case report

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.

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, × 200. (c) Small- to intermediate-sized lymphocytes with irregular nuclei at the lower part of the hair follicle bulb; hematoxylin–eosin–safran staining, × 400

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 × 109/l lymphocytes with 1200/mm3 Sézary 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 Sézary 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.

Discussion

Sézary syndrome characterized by a folliculotropism (folliculotropic Sézary syndrome) is exceptional with only eight cases previously reported[7-13] (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 Sézary syndrome, showing a strong aggressiveness when a folliculotropism is present[7, 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 and comparing T lymphocytes of folliculotropic CTCL and T lymphocytes of non-folliculotropic CTCL could be investigated.

Table 1. Reported cases of folliculotropic Sézary syndrome
Cases reportedType of folliculotropic lymphomaSexCutaneous dataAdenopathyExtracutaneous involvementTime to visceral involvementSurvival
Westfried[9]Sézary syndromeMFollicular papules, keratodermaYes  2 years
Rivers[10]Sézary syndromeMErythroderma, nodules, small milia, alopeciaNo  ND
LeBoit[11]Sézary syndromeFErythema, follicular papules, alopeciaYes  ND
Tremeau-Martinage[8]Cutaneous CD30+ folliculotropic lymphoma with circulating Sézary cellsMFollicular papulesYesBone marrow< 1 year5 months
Mehta[7]Sézary syndromeFFollicular dermatosis, nodules, alopeciaYesBone marrow5 monthsND
Gerami[12]Sézary syndromeMErythroderma, follicular papules, leonine faciesYes  ND, in life after 5 years
 Sézary syndromeMErythroderma, follicular papules, alopeciaYes  ND, in life after 2 years
Jang[13]CD25+ Sézary syndrome with CD30+ large cell transformationMErythroderma, follicular papules, leonine facies, keratodermaYesBone marrowAt the diagnosisIn life
Our case, 2012Sézary syndromeMErythroderma, follicular papules, leonine facies, keratoderma, alopeciaYesLungAt the diagnosis5 months

Acknowledgements

We wish to thank A. Swaine, who reviewed the English language.

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