Mycosis fungoides/Sezary syndrome:report of an unusual case

Introduction: Sezary syndrome (SS) is an uncommon form ofcutaneous T cell lymphoma (CTCL) with a classical triad oflymphadenopathy, characteristic circulating lymphoma cells (Sezarycells) and erythrodermatous skin involvement with classical mycosisfungoides (MF)-like histological picture.Case report: A 32-year-old woman presented with this classicaltriad; however, her skin involvement, histologically, was in theform of folliculotropic MF, rather than the usual classical formof MF.Conclusions: In the vast majority of cases, the cutaneous involvementin SS resembles conventional MF, histologically. One case ofCD30-positive CTCL with pilotropic MF has been reported. However,English literature does not describe any case of SS with folliculotropicMF with typical immunophenotype of SS thus far. We presumethat this case represents the first report of SS with folliculotropicMF histologically, displaying the typical CD30-negativeimmunophenotype.

Mehta A, Dhungel BM, Khan MFF. Mycosis fungoides/Sezarysyndrome: report of an unusual case.J CutanPathol 2006; 33 (Suppl. 2): 12–15.#BlackwellMunksgaard 2006.

Anurag Mehta, Bal MakundaDhungel and Mohd. FawadFarooq Khan

Department of Pathology, Armed ForcesMedical College, Pune, Maharastra, India

B. M. Dhungel, Department of Pathology, ArmedForces Medical College, Pune, Maharastra, IndiaMobile: þ91 9822777640e-mail: drbmdhungel@druknet.bt

Accepted for publication September 28, 2005

Mycosis fungoides (MF) and Sezary syndrome (SS)are the most common clinical variants of cutaneousT-cell lymphoma.1 SS is a rare disease defined his-torically by the triad of erythroderma, generalizedlymphadenopathy, and the presence of neoplastic Tcells (Sezary cells) in skin, lymph nodes, and periph-eral blood.1,2 The histological features in SS aresimilar to those in classical MF albeit of patch orplaque stage.3,4 Several studies have identified aconsistent pattern of chromosomal abnormalities inSS identical to that in MF, suggesting that bothconditions represent parts of spectrum of the samedisease with a similar pathogenesis.1 Patients withMF and SS have varying risks for disease progres-sion or death. SS is an aggressive clinical entityassociated with poor prognosis and median survivalof 2–3 years.5,6

MF is an extranodal non-Hodgkin’s lymphomasof T-cell origin with primary cutaneous involve-ment. Apart from the classical Alibert–Bazin typeof MF with characteristic epidermotropism, manyclinical and/or histologic variants have been

reported.1,2 The histologic variants, i.e. (a) folliculo-tropic MF (MF with or without associated follicularmucinosis), (b) pagetoid reticulosis, and (c) granulo-matous slack skin, have distinctive clinicopathologicfeatures and prognosis and hence are classified sepa-rately in the WHO-EORTC classification of cuta-neous lymphomas with primary cutaneousinvolvement.2 Folliculotropic MF is a variant ofMF characterized by the presence of folliculotropicinfiltrates, often with sparing of the epidermis, andpreferential involvement of the head and neck area.Most cases show mucinous degeneration of the hairfollicles (follicular mucinosis) and are traditionallydesignated as MF-associated follicular mucinosis.7–9

Similar cases, but without follicular mucinosis, havebeen reported as folliculocentric or pilotropic MF.10

Upregulation of intercellular adhesion molecule-1(ICAM-1) on follicular epithelium with ligand recep-tor binding to lymphocyte function-associatedantigen-1 (LFA-1)-positive folliculotropic lymphomacells is thought to be responsible for the lymphocyte-homing mechanisms in folliculotropic MF.11 In

J Cutan Pathol 2006: 33 (Suppl. 2): 12–15 Copyright # Blackwell Munksgaard 2006Blackwell Munksgaard. Printed in Singapore

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most cases, the neoplastic T cells have a CD3þ,CD4þ, and CD8– phenotype as in classical MF.Recent studies described the prognosis of patientswith folliculotropic MF as similar to that of classicaltumor-stage MF, but significantly worse than that ofpatients with classical plaque-stage MF.2,8 The mostimportant clinical predictive factors for survivalinclude patient age, T stage, and the presence ofextracutaneous disease.12

Case report

A 32-year-old female presented with generalizedintense itching of 4-month duration and red raisedlesions all over the body of 1-month duration.A history of swelling of feet and face and fever of7-day duration was also elicited. Examination oflesions on the face revealed multiple, tender, poly-sized, erythematous maculo-papular lesions, andnodules ranging from 0.5 to 2 cm in diameter cov-ered with fine non-adherent scales (exfoliation)(Fig. 1A). Multiple discrete symmetrical erythema-tous/hyperpigmented, maculopapular lesions, fewcoalescing to form plaques, were noted on the trunk,buttocks and limbs; however, the body folds werespared. Likewise, large numbers of erythematous/cop-pery maculo-papular lesions were observed over thepalms and soles. Additionally, the patient exhibitedtemporo-parietal alopecia, follicular dermatosis,madarosis, and generalized lymphadenopathy.Pathological examination of skin biopsy sample

showed nodular aggregates of lymphocytes, principallyaround hair follicles and sweat glands with invasion oftheir epithelium leading to their destruction. A cleargrenz zone between nodular infiltrate of lymphocytesand epidermis was observed, and the epidermis wasfree of epidermotropism (Fig. 1B). The infiltrate wascomposed of small-to-intermediate-sized lymphocytes,with irregular and highly indented cerebriform nuclei(Fig. 1C). Immunohistochemistry showed that thenodular aggregates were strongly positive for CD3,CD4 (clone1F6 for paraffin sections), CD5, andCD45RO and were negative for CD20, thus confirm-ing their T-cell lineage. The neoplastic infiltrate dis-played negativity for CD7, and 5% of the cells showedsurface-membrane positivity for CD8 (clone 4B11 forparaffin sections). The lymphocytes were also negativefor CD30, thus ruling out primary cutaneous CD30-positive T-cell lymphoproliferative disorders.Peripheral blood smear showed atypical lympho-

cytes with highly indented cerebriform nuclei similarin morphology to those seen in the skin biopsy, com-prising 42% of all lymphocytes and 22% of total leu-kocytes (Fig. 1D). The total leukocyte count was6.2 � 109/l, with relative lymphocytosis (55%),thereby yielding atypical lymphocyte count of

1.36 � 109/l. The CD4/CD8 ratio in the blood was4 : 1 (Becton Dickinson FACS count). The bone mar-row biopsy exhibited marrow infiltration by small irre-gular lymphocytes, either singly or as micronodules(Fig. 1E). The infiltrate showed morphological andimmunohistochemical features similar to that of theskin biopsy. Further, a lymph node biopsy was doneto stage the disease and a diffuse involvement by afore-mentioned infiltrate, with similar morphological andimmunophenotypic features to that of the skin and thebone marrow was documented (Fig. 1F).As this case fulfilled the existing criteria of WHO/

EORTC for the diagnosis of SS, a final diagnosis ofSS with histological picture of MF (folliculotropicvariant) was rendered.

Discussion

Although MF and SS are thought to be closelyrelated malignant CTCLs, their relation to eachother has not yet been fully defined. The presenceof the same T-cell receptor rearrangements in theneoplastic cells from SS, MF, and large-cell lym-phoma show that they were derived from a commonT-cell clone.1,2 SS presents with erythroderma,which may be associated with marked exfoliation,edema, and lichenification, and which is intenselypruritic.2 In some patients, in addition to general-ized erythroderma, plaques or tumors indistinguish-able from those of MF are also seen, as in ourcase.13 Rare presentations as follicular dermatosis,bullous lesions, leukoderma, and eczematous derma-titis have been reported.14,15 The present case isinteresting in that cutaneous involvement was alsoin the form of follicular dermatosis with pronouncedalopecia and madarosis, an uncommon presentationas gleaned from existing literature.Clinical, histological, and hematological criteria

for the diagnosis of SS have been described.16,17 Inrare cases, MF can progress over years to decades toSS as a part of natural evolution of the disease.18 Inpresent case, SS was considered a better diagnosisthan MF progressing to SS, as the historical triad ofclassical features was observed at first presentation.Moreover, the patient had short preceding course ofbarely 4 months. It also fulfilled the InternationalSociety for Cutaneous Lymphomas (ISCL) criteriaof Sezary cell count of at least 1000 cells/mm3 inthe peripheral blood. Moreover, the lymphoma cellsof the skin, lymph node, and the bone marrow wereof the same immunophenotype and showed loss ofCD7 antigen. The CD4/CD8 ratio in the periph-eral blood was raised in our case (4 : 1), againstdiagnostic criteria of more than 10 : 1. The clonalitydetermination using TCR rearrangement beingbeyond the scope of this laboratory, phenotypic

Mycosis fungoides/Sezary syndrome: report of an unusual case

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similarity of the infiltrate in the skin, peripheralblood, bone marrow, and lymph node with aberrantloss of CD7 was used as an indirect evidence ofclonality. The peripheral count of Sezary cells(>1000/mm3) and aberrant loss of any T-cell anti-gen (CD7 in present case) along with other cytomor-phological and immunophenotypic criteria isminimal for the diagnosis of SS.2

In our case, the cutaneous involvement was in theform of folliculotropic MF histologically, rather than

the usual classical form of MF as described inthe literature. Tremeau-Martinage et al.19 havedescribed one case of pilotropic lymphoma withCD30-positive circulating Sezary cells. In our case,however, the infiltrate was CD30 negative, andclassical SS immunophenotypes were exhibited bylymphoma cells. Thus, this could be the first case ofCD30-negative SS with cutaneous involvement inthe form of folliculotropic variant of MF to bereported thus far. A differential diagnosis of adult

A B

C D

E F

Fig. 1. A) Diffuse erythematous maculopapular lesion – abdomen. B) Nodular folliculotropic infiltrate without epidermotropism; hematoxylin

and eosin (H&E), �40. C) Small-to-medium-sized atypical lymphocytic infiltration of follicular epithelium; H&E, �400. D) Sezary cells in

blood film; MGG, �1000. E) Micronodular infiltrate in the bone marrow; H&E, �40. F) Diffuse effacement of the lymph node architecture

by atypical lymphocytic infiltrate; H&E, �40.

Mehta et al.

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T-cell leukemia/lymphoma (ATLL) was also enter-tained initially, however, in the absence of hypercal-cemia, osteolytic lesions on skeletal survey, highperipheral count, epidermotropism of the neoplasticinfiltrate, morphological pleomorphism, and neg-ative serology for HTLV-I and -II by enzyme-linkedimmunosorbent assay (Orgenics, Yavne, Israel), thediagnosis was ruled out. Further, South-Asia is not anendemic area for ATLL, and the incidence of HTLV-I and -II is very low in India.20,21

The dermatopathologic findings in cases of SS thatarise in patients without a previous diagnosis of MFhave not been well characterized. The histologicalfeatures in SS are non-specific and similar to thosein classical MF of patch or plaque stage.3,4 However,the cellular infiltrates in SS are more often monoto-nous, and epidermotropism may sometimes beabsent.22 In our case, the infiltrate did not show anyepidermotropism, but it was predominantly arounddermal appendages with a clear grenz zone betweenthe nodular infiltrate and the epidermis. The prog-nosis of patients with SS is generally poor, with amedian survival between 2 and 3 years. Moreover,the skin involvement in the form folliculotropic MFmakes them less accessible to skin-targeted therapiesdue to the deep, follicular, and perifollicular localiza-tion of the neoplastic infiltrates.2

Conclusion

SS is an uncommon CTCL. In the vast majority ofcases, the cutaneous involvement resembles conven-tional MF histologically. One case of CD30-positiveCTCL with pilotropic MF has been reported.However, English literature does not describe anycase of SS with folliculotropic MF and the typicalimmunophenotype of SS. We presume that this caserepresents the first report of SS with folliculotropicMF histologically, which displays the typical CD30-negative immunophenotype.

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