Case Report

T-Cell Receptor-g in Gamma-Delta PhenotypeCutaneous T-Cell Lymphoma Can

Be Accompanied by Atypical Expressionof CD30, CD4, or TCRbF1 and an Indolent

Clinical CourseHarina Vin,1 Rakhshandra Talpur,1 Michael T. Tetzlaff,2 Madeleine Duvic1

Clinical Practice Points

� Diagnosis of cutaneous gamma-delta T-cell lym-phoma (CGDTCL) using clinical findings alone isnearly impossible because of the resemblance of theskin lesions to other diseases on the cutaneous T-celllymphoma (TCL) spectrum.

� The wide spectrum of clinical and histological pre-sentations of the CGDTCL patients presented hereinchallenges the notion of CGDTCL as a distinct entitywith universally poor prognosis, because clinical pre-sentation and pathology can overlap with other cuta-neous TCLs with less aggressive clinical courses.

� In consideration of our data in cases 1, 3, 5, 6, 7, and9, we conclude that T-cell receptor (TCR)-g expres-sion alone does not condemn patients to aggressive

progression of CGDTCL because the TCRg-positive(TCRgþ) finding can be accompanied by markers thatare typical of less aggressive disease, namely CD30,CD4, or bF1 expression.

� CD30 expression in particular can be used quitesuccessfully as a therapeutic target and CD4þ casesrespond better to skin-directed regimens than CD4�

cases.� Additionally, we show in cases 2 and 4 that even whena classic CGDTCL immunophenotype is present, earlyaggressive therapy can still induce an indolent clinicalcourse, which highlights the importance of earlyCGDTCL diagnosis, often requiring multiple biopsies.

Clinical Lymphoma, Myeloma & Leukemia, Vol. 14, No. 6, e195-200 ª 2014 Elsevier Inc. All rights reserved.Keywords: Gamma-delta T-cell lymphoma, Non Hodgkins lymphoma, Peripheral T-cell lymphoma

Subcutaneous T-cell lymphoma, T cell receptor

IntroductionCutaneous gamma-delta T-cell lymphoma (CGDTCL) is a rare

form of T-cell lymphoma that usually exhibits an aggressive clinicalphenotype. To further characterize the histopathologic and clinicalfeatures of CGDTCL we identified a retrospective case series of9 patients from our database. As has been reported elsewhere1, the

1Department of Dermatology2Department of PathologyThe University of Texas M.D. Anderson Cancer Center, Houston, TX

Submitted: Mar 29, 2014; Revised: Jun 7, 2014; Accepted: Jun 17, 2014; Epub:Jun 23, 2014

Address for correspondence: Madeleine Duvic, MD, Department of Dermatology,M.D. Anderson Cancer Center, Pickens Tower, FCT11.6078, 1515 Holcombe Blvd,Unit 1453, Houston, TX 77030Fax: 713-745-3597; e-mail contact: mduvic@mdanderson.org

2152-2650/$ - see frontmatter ª 2014 Elsevier Inc. All rights reserved.http://dx.doi.org/10.1016/j.clml.2014.06.024

clinical features were heterogeneous, and the diagnosis of CGDTCLwas based on extensive immunophenotypic characterization,including T-cell receptor (TCR)-g expression. The novel finding ofthis study is the presence of unusual immunophenotypical profiles inmost of these patients, including CD4-postive (CD4þ), CD30þ orTCR-bF1þ, which are typical of less aggressive cutaneous T-celllymphoma (TCL). In the minority of cases, with the classicCGDTCL immunophenotype profile, aggressive therapy initiatedearly induced resolution of lesions in 1 patient. Our data suggest thatCGDTCLs diagnosed according to TCRg expression are not alwaysassociated with the aggressive phenotype. These findings call intoquestion the diagnostic power of TCRg alone as a marker ofCGDTCL, especially in cases where certain immune markers are alsopresent. The presence of these markers might explain the indolentdisease course in these patients.

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Gamma-Delta Phenotype Cutaneous T-Cell Lymphoma

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The gd TCLs are lymphomas that express gd TCRs2 and arerare, aggressive cancers. Primary CGDTCL accounts for < 1% of allcutaneous TCLs.3 gd TCLs originate from gd T-cells, whichregulate inflammation and epidermal homeostasis.4 Lesions ofCGDTCL are typically disseminated with diffuse skin involvement2

and reported median survival time from diagnosis ranges from15 months to 31 months.1,5

Cutaneous gamma-delta T-cell lymphoma is characterized bythe expression of CD3 and CD2 with variable CD7 expression.2

Activated gd T-cells might express CD56, associated with naturalkiller cells, and also might express cytotoxic markers such as T-cellintracellular antigen-1 (TIA-1) and granzyme B.2 The classicCGDTCL tumor cells do not express ab T-cell chains and thus donot stain for TCR-bF1 and are often double-negative for CD4and CD8.6 Immunophenotypic diagnostic criteria for CGDTCLare not unequivocally established, and range from absence of abTCR expression to positive immunohistochemistry of TCRg.

Materials and MethodsWe retrospectively reviewed the medical records of 9 patients

with the gd T-cell lymphoma phenotype, diagnosed based onclinical features and skin biopsies expressing TCRg. Their de-mographic characteristics, clinical courses, histopathologic features,and response to treatment were summarized, along with polymerasechain reaction (PCR) results for TCR rearrangements.

ResultsDemographic Characteristics

In this case series of 9 patients, 4 were male and 5 were femalewith a median age of 57.5 (range 1.5 to approximately 88) years atthe time of diagnosis. Four patients had hypertension, 3 had irri-table bowel syndrome, and 2 had hypothyroidism. History of cancer

Table 1 Demographic Characteristics, Initial Presentation, and Lesi

Case Race SexInitialLesion

InitialSuspicion Initial Locat

1 Caucasian F N e U/l calf

2 Chinese M Pa E Unspecified

3 Caucasian F R MF, Ps Diffuse (bod

4 Black F Pa MF U/l thenar emin

5 Black M P MF Back

6 Middle-Eastern F P e U/l lower leg

7 Caucasian M Pa E, Ps, CD B/l extremitie

8 Caucasian M P E, MF U/l hip

9 Black F P PA, MF, Ps B/l buttocks, eabdomen

Age listed is age at diagnosis, based on time of TCRg-positive biopsy.Abbreviations: B/l ¼ bilateral; CD ¼ contact dermatitis; E ¼ eczema; F ¼ female; M ¼ male; MF ¼Ps ¼ psoriasis; R ¼ rash; SC ¼ subcutaneous; TCR ¼ T-cell receptor; U/l ¼ unilateral.

- Clinical Lymphoma, Myeloma & Leukemia December 2014

was present in 2 cases. Case 3 had a history of marginal zone B-celllymphoma of the spleen and lymph nodes, and case 4 had a historyof cervical cancer. Previous skin problems were present in case 5(history of psoriasis), case 8 (history of melanoma and actinickeratosis), and case 9 (history of mycosis fungoides [MF], lichensimplex chronicus, and alopecia).

Presenting SymptomsData are summarized in Table 1. The presenting symptom was

a papular rash in 3 cases, erythematous patches in 3 cases, asubcutaneous nodule in 1 case, and a diffuse, papulosquamousMF-like rash in 1 case. In 1 of the cases (case 4) with a papularrash, the lesions were initially small and eventually developed intolarger and ulcerated tumors. Interestingly, 3 patients initiallyattributed their papules to insect bite-like lesions. The intervalbetween onset of symptoms and diagnostic biopsy was generally> 1 year (range, 1-121 months, median 43.3 months). Most ofthe initial lesions (n ¼ 6) presented on the extremities with thenext most common presenting site being the trunk (n ¼ 4). Only1 case (case 9) began on the face, and no cases had initialinvolvement of the scalp.

Skin LesionsAs the disease progressed, the most common site of involvement

continued to be the extremities (n ¼ 9), followed by the trunk(n ¼ 6). Three patients also developed lesions on the face and/orscalp. All patients eventually developed lower limb involvementand 7 had concurrent upper limb involvement.

Case 1 had subcutaneous nodular lesions, which persisted. Otherpatients’ lesions became patches, plaques, or a combination, and5 of the other 8 patients experienced ulceration. In general, thepatches and plaques were erythematous (n ¼ 5), with 3 patients

on Descriptions

ionAge,Years

Lesion atDiagnosis Areas Affected Ulcer

64 SC nodules B/l l lower leg; U/l upperarm and buttock

No

1.5 Violaceous patches/plaques

B/l legs and buttocks;U/l ankle and upper arm

No

y) 88 Plaques and scalypatches

B/l extremities and trunk;U/l axilla and ear

Yes

ence 51 Patches, plaques,violaceous papules

U/l breast, nostril, pubis,heel, lower leg

Yes

39 Hyperpigmentedplaques and patches

Total body Yes

74 Plaques and ulcer U/l lower extremity, flank,arm; both buttocks

Yes

s 42 Patches with centralclearing and plaques

Extremities only No

82 Thick, erythematousplaques and tumors

U/l hip, flank, lower leg,soles

Yes

ye, 42 Hypopigmentedpatches

B/l diffuse body; U/l scalp No

mycosis fungoides; N ¼ subcutaneous nodule; P ¼ patch; Pa ¼ papule; PA ¼ pityriasis alba;

Harina Vin et al

having violaceous plaques. Two of the patients’ plaques were spe-cifically noted to have ill-defined borders (1 of these had induration,the other had central clearing) and 1 had lesions that were well-demarcated.

Clinically, the diagnosis was suspected to be MF in 5 cases. In5 cases, the clinical presentation was initially suspicious for eczemaor psoriasis. Data are summarized in Table 1.

Pathologic FeaturesAll 9 patients had 1 or more lesional skin biopsies taken from

characteristic skin lesions. In all but 3 cases, the biopsy resultsinitially supported other dermatologic conditions, making it clearthat multiple biopsies were needed to obtain the correct diagnosis.The final diagnosis of gd T-cell lymphoma was established ac-cording to the histopathological and immunohistochemical findingsof the biopsy tissue—specifically, TCRgþ and TCRbF1�. TCRgþ

is important to note because TCR-silent lymphomas exist, whereexpression of ab and gd are both negative.7,8

All cases exhibited an atypical lymphoid infiltrate involving thedermis (n ¼ 3), epidermis (n ¼ 1), or both (n ¼ 3), with 2 casesinvolving the dermis and subcutaneous tissue. In 7 cases there wasepidermotropism, which is a diagnostic criteria for MF. Case 1 wasthe only case with a subcutaneous granulomatous infiltrate withadmixed tumor cells characterized by hyperchromatic nuclei andscant eosinophilic cytoplasm. The tumor cells ranged from small(n ¼ 6) to medium (n ¼ 6) to large (n ¼ 2), with many casesshowing a range of cell sizes. Two cases showed extravasation ofred blood cells. Of note, histopathologically, case 7 lacked someof the typical features of CGDTCL, such as conspicuous dysker-atotic keratinocytes. Complete pathological descriptions are notedin Table 2.

Immunophenotyping of the infiltrates was available for all of the9 cases. The atypical lymphocytes were positive for CD3. All 9 caseshad positive staining for TCR-gamma chain but 3 of these hadconcurrent expression of bF1, with the remaining 6 patients char-acterized as bF1�. It is believed that expression of TCRab orTCRgd heterodimers is mutually exclusive,9 so these 3 patients didnot fit the generally accepted clinical standards and are puzzling. Ofthe 8 samples tested for CD30, 6 were positive to varying degrees.Interestingly, the infiltrates were CD8þ in 4 patients and CD4þ in3 patients. Of the 5 patient samples tested, none were Epstein-Barrvirus-positive, which is consistent with previous reports.3 Granzyme

Table 2 Pathological Descriptions of Diagnostic Biopsy Tissue

Case Infiltrate Depth EDT

1 Granulomatous with lymphocytes SC, D No

2 Lymphocytes with irregular nuclear contours D, E Yes

3 Atypical lymphocytes SC, D Yes

4 Atypical lymphocytes with cytologic atypia D, E Yes

5 Atypical lymphocytes with syringotropism D NA

6 Lymphocytes, rare germinative centers D Yes

7 Lymphocytes with mild cytologic atypia NA Yes

8 Atypical lymphocytes with hyperchromatic nuclei D, E Yes

9 Atypical lymphocytes with mild cytologic atypia D Yes

Abbreviations: D ¼ dermis; E ¼ epidermis; EDT ¼ epidermotropism; L ¼ large; M ¼ medium; MF

B and TIA were coexpressed in 6 of the patients tested. Case 7 againlacked definitive expression of cytotoxic markers. CD5 expressionwas positive in 3 of 6 patients and CD7 expression was positive in3 of 8 patients.

T-cell receptor g chain gene rearrangement analysis was per-formed using PCR and detected in all 7 tested patient biopsies.TCR-g amplicons used the V-gamma 1 family only in 2 cases, theV1,2 family in 1 case, the V1,3 family in 1 case, and the V1,2,3family in another. Of these, 3 were also positive for rearrangementsin TCR-b. Data are summarized in Table 3.

Treatment and ResponseAverage survival from onset of symptoms was 87.4 months (7.3

years) and average survival from date of diagnosis was 9.8 months.The 9 CGDTCL patients are still living, and 1 is in completeremission.

In 8 of the patients, initial treatment was topical steroids andwas ineffective in all as monotherapy. Oral prednisone was effectivein treating the subcutaneous nodules when combined with bexar-otene in case 1. The histone deacetylase (HDAC) inhibitor vor-inostat was used in cases 5 and 8. Although there was an excellentresponse to vorinostat in case 5, the medication was unfortunatelydiscontinued because of an increase in creatinine level. AnotherHDAC inhibitor, romidepsin, provided some clinical benefit forthis patient although not as dramatic as with vorinostat.

Cutaneous chemotherapy with topical nitrogen mustard wasprescribed in 2 cases as an adjuvant therapy with limited response.In general, nitrogen mustard served to stabilize or improve existinglesions but did not prevent formation of new lesions. Cases 1, 5, 8,and 10 underwent therapy with the oral retinoid X receptor,bexarotene, but only half of the patients experienced the clinicalbenefit of either flattened lesions or reduced erythema.

Multi-agent chemotherapy is often used to treat CGDTCLbecause of its aggressive behavior.10 When oral chemotherapy failedin case 5, intravenous chemotherapy with gemcitabine providedno response. Aggressive treatment was initiated in case 2 becauseof the age of the patient. He had no response to cyclophosphamide,doxorubicine, vincristine and prednisone (CHOP) with bleomycinbut a complete response to Berlin-Frankfurt-Munster (BFM) ther-apy with non-Hodgkin lymphoma Berlin-Frankfurt-Münster-95(NHL-BFM-95) that was partially stabilized with gemcitabine.Case 4 was also treated aggressively because of her definitive

Cell Size Previous Biopsies

S/M aB-panniculitic TCL; granulomatous MF

S/M None

S/M, L None

M/L Pagetoid reticulosis type TCL; CD8þ lymphoproliferative TCL

NA MF

S, M, L Granuloma annulare

S Contact dermatitis, MF

NA MF in 3 biopsies

S/M MF

¼ mycosis fungoides; S ¼ small; SC ¼ subcutaneous; TCL ¼ T-cell lymphoma.

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Table 3 Immunophenotypic Summary of Diagnostic Biopsy Tissue Infiltrate

Case CD3 CD5 CD7 CD4 CD8 CD56 CD30 EBER GZB TIA-1 bF1 TCR-gTCR-bPCRa

TCR-gPCRa

1 þ þ þ þ þ þ S � þ þ þ þ No Yes

2 þ � þ � þ � � NA � NA � þ No Yes

3 þ NA � � þ NA þ � NA � � þ Yes Yes

4 þ � NA � � þ R NA þ þ � þ No Yes

5 þ þ þ þ þ NA R � þ þ þ þ Yes Yes

6 þ þ � þ � þ R � þ þ þ þ Yes Yes

7 þ � � þ � � NA NA þ þ � þ NA NA

8 þ NA � � � NA � NA NA NA � þ No Yes

9 þ NA � � � þ þ NA þ þ � þ NA NA

Abbreviations: EBER ¼ EBV-encoded RNA; GZB ¼ Granzyme B; PCR ¼ polymerase chain reaction; R ¼ rare; S ¼ significant; TCR ¼ T-cell receptor; TIA1 ¼ T-cell intracellular antigen-1.aNo indicates no rearrangement detected, yes indicates rearrangement detected.

Gamma-Delta Phenotype Cutaneous T-Cell Lymphoma

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CGDTCL immunophenotype; she underwent chemotherapy withrescue stem-cell transplant and completed only 2 cycles of ritux-imab, cyclophosphamide, vincristine, doxorubicin, dexamethasone,methotrexate, cytarabine (R-hyper-CVAD) with alternating meth-otrexate and cytarabine before having complete resolution of skinlesions. In all patients who received targeted radiation therapy,palliation of the lesions was achieved.

Targeted anti-CD30 therapy with brentuximab vedotin (BV) wasinitiated for the MF-like lesions in case 3 after radiation of a tumor.There was a partial response but after 7 treatments the drug wasstopped because of Grade 2 neuropathy. Because BV might have asynergistic effect with chemotherapy,11 this could be a usefultherapy for CD30þ CGDTCLs. Case 10 also had diffuse CD30staining but has not received BV.

Complete treatment and response summaries are listed inTable 4. Although not included in this table, the benefits of woundmanagement in these patients cannot be understated. In severalpatients, Burrow’s solution soaks and whirlpool therapy providedimprovement, and treatment of secondary infection is assumed tohave prevented further complications.

DiscussionCutaneous gd TCL is a rare malignancy consisting of a clonal

population of mature, activated gd T cells with a cytotoxicphenotype.12 Most cases of CGDTCL in the literature appear at amedian age of 42 years with a female predominance.13 Five-yearsurvival is not reached in classic CGDTCL patients.10 Our reportshows 9 cases of relatively indolent courses of CGDTCL evidencedby longer than expected survival from date of presentation.

The classically described immunophenotype of CGDTCL isCD3þ, CD4�, CD5�, and CD8� with variable expression ofCD7 and CD56. Cytotoxic markers, granzyme B and TIA-1, areusually positive, and TCR-bF1 is negative. In the larger study fromGuitart et al, all cases expressed at least 1 cytotoxic marker, eitherTIA-1 or granzyme B.1 Interestingly, they also noted that TIA-1þ

and CD5� were associated with overall mortality and granzymeBþ and CD5� was associated with shorter time to death. All 9of our patients had the unifying finding of TCRg positivity.However, other immunohistochemical findings varied greatly.Despite that the immune phenotypes of some cases exhibit features

- Clinical Lymphoma, Myeloma & Leukemia December 2014

of non-CGDTCL cutaneous TCLs, we believe that these areindolent CGDTCLs rather than mimickers of less aggressive TCL.Not only are our cases TCRgþ but the clinical presentations ofour cases make other cutaneous TCLs less likely.

CD30 expression is rarely reported in cases of CGDTCL butwas diffusely present in 2 of our patients’ tumor cells and presentin 8 of 9 patients’ lesions. The classic primary CD30þ lym-phoproliferative disorders are lymphomatoid papulosis (LyP) andcutaneous CD30þ anaplastic large-cell lymphoma (C-ALCL),both of which have excellent prognosis.14,15 It is unlikely thatour 2 CD30þ patients have either of these diseases, however,because they do not fit the generally accepted clinical standards.The most common presentation of C-ALCL is ulcerated tumorsor nodules and the most common presentation of LyP is multipleself-regressioning pink, red, or brown papules and nodulesof < 1.5 to 2.0 cm.14 Neither of these presentations was typicalof any of our cases. It is possible that the diffuse CD30þ in case 3and 9, plus the rare, scattered CD30þ atypical lymphocytes in5 other cases, is contributing to their more indolent-courseCGDTCL, although our small sample size is far too small todraw prognostic conclusions. To our knowledge, CD30þ cuta-neous TCL with gd-phenotype is rare. Again, drawing compar-ison to Guitart et al, CD30þ was observed in only 1 of 45patients.5 Concerning their patient with atypical gd T cells andCD30 expression, they observed that the lesions also presentedwith an indolent clinical course but concluded that the lesionsrepresented a variant of LyP rather than CGDTCL. Regardless,in our 2 CD30þ cases, therapy with the anti-CD30 agent BVwas beneficial in resolving lesions for 1 patient and has just beenstarted in the other patient.

The typical profile of CGDTCL is CD4�CD8� and thisphenotype, when seen with TCRg, is associated with moreaggressive disease than CD4þ TCLs.16 CD4þ cells in TCL areassociated with nonaggressive behavior in MF and under theprovisional category of primary cutaneous CD4þ small/medium-sized pleomorphic T-cell lymphomas,17 although pleomorphicTCL would not be on the differential for a clinical presentationsuspected to be CGDTCL. We were able to exclude MF andpleomorphic TCL based on the constellation of clinical presentationand histopathologic and immunophenotypic findings. Clinically,

Table 4 Chronological Treatment Summary and Response toTreatment

Case Treatment Response1 Clobetasol NR

Bexarotene NR

Bexarotene and prednisone PR

Prednisone taper Relapse

2 CHOP and bleomycin (2 cycles) NR

NHL-BFM-95 (4 cycles) CR, then relapse

Gemcitabine Stable

Gemcitabine and clobetasol PR

3 Triamcinolone and hydrocortisone NR

Radiation therapy: axilla LR

Brentuximab and bleach baths PR

Brentubimab discontinued midcourse(peripheral neuropathy)

Relapse

Radiation therapy: scalp LR

Radiation therapy: neck, perineum,inner thigh

LR

4 Clobetasol NR

R-hyper-CVAD alternating withmethotrexate, cytarabine

CR and PIH

5 Clobetasol and triamcinolone NR

Vorinostat PR

Vorinostat and narrow band UVB PR

Vorinostat decreased (increased creatinine) Relapse

Bexarotene NR

Vorinostat discontinued Relapse

Gemcitabine (3-4 cycles) NR

Romidepsin PR

Total skin electron beam therapyand whirlpool

PR

6 Triamcinolone PR, then relapse

Radiation therapy and nitrogen mustard LR, then relapse

Burrrow’s solution soaks NR

EPOCH CR, then relapse

EPOCH Current

7 Steroids NR

Triamcinolone (discontinued,allergic reaction)

NR

Nitrogen mustard PR

Nitrogen mustard and bleach baths PR

8 Bexarotene PR

Bexarotene decreased (hyperlipidemia) Relapse

Bexarotene and vorinostat PR

Low dose skin electron beam PR

Whirlpool PR

Bexarotene only PR, Relapse

Table 4 (Continued)

Case Treatment Response

9 Steroids NR

Narrow band UVB PR

Narrow band UVB discontinued(photosensitivity)

Relapse

Nitrogen mustard Stable

Bexarotene PR, relapse

Abbreviations: CHOP ¼ cyclophosphamode, doxorubicin, vincristine and prednisone;EPOCH ¼ etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin; LR ¼ localresponse; NHL-BFM-95 ¼ non-Hodgkin lymphoma Berlin-Frankfurt-Münster-95; NR ¼ noresponse; PIH ¼ Post inflammatory hyperpigmentation; R-hyper-CVAD ¼ rituximab, cyclo-phosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine; UVB ¼ultraviolet B phototherapy.

Harina Vin et al

the predilection of lesions on the extremities compared with on thetrunk and buttocks points to CGDTCL over MF. Histologically,a major difference is presence of CD4þCD8� infiltrate along witha lack of TCRg in MF.14 Taken together, these features supporta diagnosis of CGDTCL in our patients despite the apparently

indolent course involving MF-like plaques. CD4 positivity inCGDTCL is rare in the literature; in a reported study of 53CGDTCL patients, only 4 were CD4þ,1 making our group veryunique. As with CD30 expression, we believe that CD4 expressionin TCRgþ CGDTCL patients is likely a contributor to the moreindolent course. Alternatively, it is possible that these patientsrepresent MF with aberrant expression of TCRg. Notably, in ourpatients, lesions that presented like MF tended to respond to skin-directed skin regimens faster than the other lesions.

Despite the belief that TCRb and TCRg expression aremutually exclusive, the double-positive phenomenon we see in3 of our patients is not unique. TCRbF1 and TCRg double-positive neoplastic cells were reported in lesional biopsies inanother study in 1 of 5 CGDTCL patients and 3 of 5 LyPpatients.18 Among the double-positive cases presented byRodríguez-Pinilla et al,18 all 3 LyP patients had diffuse CD30expression and the CGDTCL patient had low CD30 expression.In our double-positive cases, CD30 expression was low. Thisfurther supports the diagnosis of CGDTCL in our 3 patientswith TCRg expression alongside bF1 expression, but possiblyexplains why the progression of disease is less aggressive, similarto LyP.

ConclusionTaken together, the novel finding of single markers displaying

atypical expression in CGDTCL cases might be the most impor-tant contributing factor to the less-than-expected aggressiveness ofthe TCLs reported herein. Specifically, expression of CD30, CD4,or bF1, despite TCRg staining, might explain the indolent courseof cases 1, 3, 5, 6, 7, and 9. The remaining cases (2, 4, and 8) aremore puzzling because they display the expected immunopheno-type of aggressive CGDTCL yet the patients were treated andachieved at least a partial response. Their indolent courses might beexplained by the aggressive therapy they received, initiated soonerafter diagnosis. In those 2 cases, treatment with NHL-BFM-95and R-hyper-CVAD, respectively, induced complete resolutionof lesions.

DisclosureThe authors have stated that they have no conflicts of interest.

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