1012 Letters
MAY 2016
mastocytosis, and 3 were not specified. We also
stained normal skin (n ¼ 17) for mast cell tryptase
and PD-L1 for comparison.
The finding of strong, diffuse PD-L1 staining was
identified in all mastocytosis specimens (n ¼ 16)
(Fig 1). Additionally, staining of MC was strong for all
cases of mastocytosis, regardless of subtype. In 3
biopsies (25%), the MC appeared to be darker along
the leading edge of the infiltrate. Normal skin bi-
opsies displayed very weak to no staining for PD-L1.
Here we demonstrate increased expression of PD-
L1 in MC proliferations. PD-L1 is expressed on various
tumor cells, such as melanoma and lung cancer, and
enhances immune evasion.4 PD-L1 expression in
melanoma demonstrated a worse prognosis and
blockade of the PD-1/PD-L1 interaction diminished
tumors.5 Therefore, antiePD-L1 blockade may be
therapeutic in treatment-resistant mast cell disease.
In conclusion, our findings provide evidence of
expression of PD-L1 in MC proliferations of mastocy-
tosis. Blockade of the PD-1/PD-L1 interaction may
prove to be a useful therapeutic modality in advanced
MC disease. The most common adverse reactions of
antiePD-1 pathway therapy identified include mild
fatigue, rash, and pruritus. Additional studies are
required to evaluate the role of PD-L1 in MC disease.
Lawrence F. Kuklinski, BA,a and Jinah Kim, MD,
PhDa,b
Department of Pathologya and Department of
Dermatology,b Stanford University, California
Funding sources: None.
Conflicts of interest: None declared.
Correspondence to: Jinah Kim, MD, PhD, Stanford
University, Department of Pathology and Derma-
tology, MC 5324, Stanford, CA 94305
E-mail: jinahkim@stanford.edu
REFERENCES
1. Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of
anti-PD-L1 antibody in patients with advanced cancer. N Engl J
Med. 2012;366:2455-2465.
2. Akin C, Metcalfe DD. Systemic mastocytosis. Annu Rev Med.
2004;55:419-432.
3. Lim KH, Tefferi A, Lasho TL, et al. Systemic mastocytosis in 342
consecutive adults: survival studies and prognostic factors.
Blood. 2009;113:5727-5736.
4. Dong H, Strome SE, Salomao DR, et al. Tumor-associated
B7-H1 promotes T-cell apoptosis: a potential mechanism of
immune evasion. Nat Med. 2002;8:793-800.
5. Hino R, Kabashima K, Kato Y, et al. Tumor cell expression of
programmed cell death-1 ligand 1 is a prognostic factor for
malignant melanoma. Cancer. 2010;116:1757-1766.
http://dx.doi.org/10.1016/j.jaad.2015.09.029
J AM ACAD DERMATOL
Expression of T-bet and GATA-3 in early
mycosis fungoides and spongiotic dermatitis
To the Editor: T helper (Th) cells play a major role in
the immune response through collaboration be-
tween T and B lymphocytes. Th1 and Th2 CD41T
cells are differentiated by cytokines that they secrete.
Th1 lymphocytes produce IFN and IL2, while Th2
cells secrete IL4, IL5, IL6, IL10 and IL13. CD81T
cytotoxic (Tc) cells were also found to be subdivided
into Tc1 and Tc2, and their activation results in the
production of INF.1 T-bet is a Th1 lineage commit-
ment transcription factor required for na€ıve CD81
T cells differentiation. In contrast, GATA-3 is a Th2
lineage commitment transcription factor. Both T-bet
and GATA-3 expression affect the balance of Th1/
Th2 cells.2
Early mycosis fungoides (MF) demonstrates an
increase in IL2 and INF, which is a Th1 profile,3
whereas in contact dermatitis, both Th1 and Tc1
play a rule in pathogenesis.4 The diagnostic utility
of T-bet and GATA-3 specific markers in MF and
inflammatory dermatosis mimics was recently
investigated,5 and it was suggested that a predom-
inance of T-bet T cells in the epidermis supports a
diagnosis of patch stage MF over dermatitis. In an
attempt to validate their findings, we assessed the
ratio of T-bet and GATA-3 expression via immuno-
histochemical staining, using both dual staining
CD3/T-bet and CD3/GATA-3 and single staining for
T-bet and GATA-3 in 10 consecutive cases each of
spongiotic dermatitis and patch-stage MF retrieved
from the files of Ackerman Academy. The MF cases
were typical of patch stage disease clinically and
histologically. They were characterized by the
presence of band-like and superficial epidermo-
tropic lymphocytes of hyperchromatic atypical
lymphocytes with underlying papillary dermal
fibrosis. In contrast to the prior report, we found
no significant differences between the groups or in
staining of the epidermotropic T cells and the
underlying dermal infiltrate within each group
(Fig 1). Both T-bet and GATA-3 were strongly
expressed in both spongiotic dermatitis and MF,
with higher expression in microabcesses in cases of
MF for both markers. Both T-bet and GATA-3 did
not distinguish between spongiotic dermatitis and
patch-stage MF (Table I). However, within the
cases of spongiotic dermatitis, we found signifi-
cantly higher expression of GATA-3/CD3 compared
with T-bet/CD3 (P ¼ .011; Friedmann test-
Bonferroni corrections) but this differential staining
was not noted in MF. We found single staining
easier to interpret, compared with dual staining
with CD3. The bright red CD3 stain made it more
J AM ACAD DERMATOL Letters 1013
VOLUME 74, NUMBER 5

Fig 1. Expression of GATA-3/CD3 and T-bet/CD3 in spongiotic dermatitis and mycosis

fungoides (MF). A, GATA-3/CD3 nuclear expression in reactive lymphocytes in spongiotic
dermatitis (original magnification: 3200); B, Nuclear expression of GATA-3/CD3 in epidermo-
tropic atypical lymphocytes in MF (original magnification: 3200); C, Nuclear expression of
T-bet/CD3 in reactive lymphocytes in spongiotic dermatitis (original magnification: 3200);
D, Expression of T-bet/CD3 in nuclei of atypical epidermotropic lymphocytes in MF (original
magnification: 3200).

Table I. Percentage of positive lymphocyte expression of T-bet and GATA-3 in mycosis fungoides (MF) and
spongiotic dermatitis
MF Spongiotic dermatitis
Markers Median Minimum Maximum Median Minimum Maximum P value
GATA-3/CD3 63 30 90 75 50 90 .579
GATA-3 50 5 75 50 33 75 .971
T-bet/CD3 55 20 75 35 20 50 .075
T-bet 29 5 75 38 10 75 .631

difficult to interpret differences in T-bet or GATA-3
staining. It should also be noted that single staining
with GATA-3 is more difficult to interpret in the
epidermis than in the dermis because of staining of
epidermal nuclei (Fig 2).
While the investigators had a clear preference
for single staining, no significant difference was
found between the methods in regard to the results
(P ¼ 1.000 for GATA-3/CD3 compared with GATA-3
alone in MF, and P ¼ .500 in spongiotic dermatitis,
1014 Letters
Fig 2. Single staining of GATA-3 (A) and T-bet (B) in case of mycosis fungoides (MF). Note the
easy interpretation of T-bet staining, and difficulty in case of GATA-3 due to the brown
background staining of the epidermis (original magnification: 3200).
P ¼ .414 for T-bet/CD3 compared with
T-bet alone in MF, and P ¼ 1.000 in spongiotic
dermatitis, using the Friedmann test-Bonferroni
corrections). Interobserver concordance between
authors ranged from moderate in cases of spongi-
otic dermatitis expressing T-bet/CD3 (r ¼ 0.636;
P ¼ .048); to weak for staining for spongiotic
dermatitis with GATA-3/CD3 (r ¼ 0.298;
P ¼ .403), and MF with either GATA-3/CD3
(r ¼ 0.496; P ¼ .145) and T-bet/CD3 (r ¼ 0.297;
P ¼ .405) using the Spearman rho. This would
be expected given the background staining of
epidermal nuclei with GATA-3, which make the
stain more difficult to interpret. While the original
investigators studied a somewhat larger sample (31
vs. 20), the most important findings of our study
(ie, the difficulty in interpretation of the stains) is
independent of sample size. Our findings suggest
that these stains may have limited value in actual
practice.
Amira Elbendary, MBBCh, MSc,a,b Kruti Parikh,
BS,c Inas Elattar, DrPH,d Jonathan Truong, HTL,
QIHC, BS,a and Dirk M. Elston, MDa
Ackerman Academy of Dermatopathology, New
York, NYa; Dermatology Departmant, Kasr Alainy
Faculty of Medicine, Cairo University, Cairo,
Egyptb; Rutgers Robert Wood Johnson Medical
School, Piscataway, NJc; Department of Biostatis-
tics and Cancer Epidemiology, National Cancer
Institute, Cairo University, Cairo, Egyptd
Supported by: None.
Conflict of interest: None declared.
Correspondence to: Dirk M. Elston, MD, Ackerman
Academy of Dermatopathology, 145 E 32nd St,
10th Fl, New York, NY 10016
E-mail: elstond@musc.edu
J AM ACAD DERMATOL
MAY 2016
REFERENCES
1. Farrar JD, Asnagli H, Murphy KM. T helper subset
development: roles of instruction, selection, and transcrip-
tion. J Clin Invest. 2002;109:431-435.
2. Oestreich KJ, Weinmann AS. Transcriptional mechanisms that
regulate T helper 1 cell differentiation. Curr Opin Immunol.
2012;24(2):191-195.
3. Saed G, Fivenson DP, Naidu Y, Nickoloff BJ. Mycosis fungoides
exhibits a Th1-type cell-mediated cytokine profile whereas
Sezary syndrome expresses a Th2-type profile. J Invest
Dermatol. 1994;103:29-33.
4. Wang B, Fujisawa H, Zhuang L, et al. CD4_ Th1 and CD8_ type 1
cytotoxic T cells both play a crucial role in the full development
of contact hypersensitivity. J Immunol. 2000;165:6783-6790.
5. Hsi AC, Lee SJ, Rosman IS, et al. Expression of helper T cell
master regulators in inflammatory dermatoses and primary
cutaneous T-cell lymphomas: diagnostic implications. J Am
Acad Dermatol. 2015;72(1):159-167.
http://dx.doi.org/10.1016/j.jaad.2015.12.004
Joint complaints correlate with increased
serum IgE levels in patients hospitalized for
moderate-to-severe psoriasis: A single center
retrospective study
To the Editor: Psoriasis is a chronic-relapsing inflam-
matory cutaneous disorder characterized by
abnormal epidermal proliferation and nail alter-
ations. Involvement of the joints is the most promi-
nent extracutaneous manifestation of this condition.
In order to evaluate factors predicting joint com-
plaints in patients hospitalized for moderate to severe
psoriasis, a retrospective cross-sectional study was
conducted in a tertiary academic Dermatology Clinic.
After institutional board approval, the medical
files of 117 patients with psoriasis hospitalized be-
tween January 2007 and December 2011 were
reviewed. Sixty-three parameters (Supplemental
Table I; available at http://www.jaad.org) were stud-
ied with univariate analysis (F-test, verified with
Student t-test for continuous and 2- or Fisher’s exact
test for categorical factors), employing SPSS