Pediatric Dermatology Vol. 30 No.

2 192–198, 2013

Pediatric Follicular Mucinosis: Presentation,

Histopathology, Molecular Genetics,
Treatment, and Outcomes over an 11-Year
Period at the Mayo Clinic
Ali Alikhan, M.D.,1 John Griffin, M.D.,1 Nicholas Nguyen, M.D.,
Dawn Marie R. Davis, M.D., and Lawrence E. Gibson, M.D.

Department of Dermatology, Mayo Clinic, Rochester, Minnesota

Abstract: Follicular mucinosis (FM) and folliculotropic mycosis fun-

goides (MF) are rare in children, and data regarding long-term outcomes
are limited. We sought to describe clinical and histopathologic findings of
children with FM with and without MF, as well as treatments administered
and clinical outcomes. We conducted a retrospective chart review of
patients younger than 22 years (at time of diagnosis) with a biopsy
demonstrating FM who were seen in the Dermatology Department at the
Mayo Clinic from September 1, 1999, to September 1, 2010. Eleven patients
(six male, five female) ages 11 to 19 years at the time of diagnosis met
the inclusion criteria. Follow-up data were available for 10 patients, with a
mean duration of 4.9 years. The head, neck, and extremities were the most
common sites of involvement, and lesions were follicular-based papules
(18%), scaly alopecic patches and plaques (45%), or a combination of the
two (36%). Overall, three patients were confirmed to have MF. T-cell
receptor gene rearrangement demonstrated clonality in two cases and was
equivocal in one case. Treatments included topical corticosteroids, topical
retinoids, oral minocycline, and, in patients with MF, ultraviolet light and
topical bexarotene. Lesions resolved completely in seven patients,
partially in one, and not at all in two (no follow-up data on one patient).
Of the three patients with MF, two had complete resolution, and one has
intermittent flares. To our knowledge, no patients developed other
lymphoproliferative disorders. FM in children is rare. A histopathologic
diagnosis of FM does not equate to folliculotropic MF in all cases. Most
patients responded to treatment with topical steroids, topical retinoids, or
phototherapy. In our series of patients, the disease ran a benign course.

Address correspondence to Ali Alikhan, M.D., Mayo Clinic,

Department of Dermatology, 200 First Street SW, Rochester, MN
55905, or e-mail: alikhan.mirza@mayo.edu.
1
Both authors contributed equally to the manuscript.

DOI: 10.1111/pde.12019

192 © 2012 Wiley Periodicals, Inc.


Follicular mucinosis (FM) is a cutaneous disease of
unclear etiology defined histopathologically accord-
ing to the deposition of mucin within the outer root
sheath and sebaceous glands of the pilosebaceous
unit. The clinical findings are variable, but typical
manifestations include an acute or subacute eruption
on the head or neck composed of plaques that are
hypopigmented, eczematous, or composed of flesh-
colored, follicular papules (1,2). In 1957 Pinkus
described what he called “alopecia mucinosa” in six
patients demonstrating alopecia overlying follicular
papules within plaques clinically and follicular mucin
deposition histopathologically (1). After observing
the concomitant development of alopecia mucinosa
and mycosis fungoides (MF) in select patients, Braun-
Falco classified alopecia mucinosa into two types: a
primary or idiopathic type unrelated to lymphoma
and a secondary type seen in the setting of lymphoma
(3). In 1959 Jablonska et al (4) proposed the term
“follicular mucinosis” as a synonym for alopecia
mucinosa. In 1969 Emmerson (5) described three
patterns of FM: head and neck lesions in young adults
that clear spontaneously in months to years, general-
ized lesions in slightly older patients that have a
chronic relapsing course over several years, and
lesions associated with a malignant lymphoprolifera-
tive disorder in adults. Boer et al (6) proposed
relinquishing the terms “follicular mucinosis” and
“alopecia mucinosa” in favor of “epithelial mucino-
sis” and “mycosis fungoides with epithelial mucino-
sis” because they felt that the previous terms were
confusing. “Epithelial mucinosis,” which may be
encountered in a host of conditions, was introduced
“to designate findings histopathologically of deposits
of mucin in infundibular, follicular, and sebaceous
epithelium.” “Mycosis fungoides with epithelial muc-
inosis” describes a “specific expression of mycosis
fungoides fulfilling criteria for mycosis fungoides,
clinically and histopathologically, in addition to
deposits of mucin being present in infundibular,
follicular, and sebaceous epithelium” (6).
FM is rare in children. Although most cases have a
benign prognosis, associations with MF (6,7) and
Hodgkin’s lymphoma (8–10) have been described. A
standardized therapeutic ladder does not exist. Ther-
apies described for primary FM include antimalarials;
topical, intralesional, or systemic corticosteroids;
dapsone; indomethacin; interferon alpha-2b; inter-
feron gamma; minocycline; oral isotretinoin; ortho-
voltage radiation; or ultraviolet A light with or
without psoralens (2). Therapy for FM secondary to
MF is aimed at the underlying lymphoma. Despite
advances in our ability to diagnose MF at earlier
Alikhan et al: Pediatric Follicular Mucinosis 193
stages, the precise criteria for diagnosis, especially in
this age group, remain problematic and controversial.
Therapy remains anecdotal. To expand our experi-
ence with this difficult problem, we report 11 pediatric
cases of FM from the Department of Dermatology at
the Mayo Clinic. In doing so, we will describe the
clinical and histopathologic findings, treatment, and
outcome of FM in children.
METHODS
A review of our dermatopathology files (searching all
cases in which “follicular mucinosis” was mentioned
in the final diagnostic report) identified 11 cases of
FM in patients younger than 22 years (at the time of
diagnosis) from September 1, 1999, to September 1,
2010. Clinical and follow-up information about each
patient was collected using our electronic medical
records system. If a patient had not been seen for
more than 1 year (7 of 11 patients), a telephone
interview was conducted to assess his or her outcome,
as well as other relevant clinical information; we were
able to reach 6 of the 7 patients.
In cases in which photographs, hematoxylin and
eosin (H&E)-stained sections, and immunohisto-
chemical-stained sections were available, three of the
authors (LEG, JRG, and AA) obtained and reviewed
them. Some patients also had frozen tissue specimens
submitted for T-cell receptor (TCR) gene rearrange-
ment studies using Southern blot analysis or poly-
merase chain reaction (PCR) at the time of diagnosis;
these results were reviewed as well. Approval for the
study was obtained from the Mayo Clinic Institu-
tional Review Board.
RESULTS
Eleven patients met our inclusion criteria (Table 1)
(six male, five female, ages 11 to 19 years, mean age
14.9 years). Clinical follow-up from the onset of
disease ranged from 1.3 to 10.4 years (mean
4.9 years). There were no follow-up data for one
patient. Histopathology was available for review in 7
of the 11 patients (the slides from the remaining 4
patients had been returned to the referring institu-
tions); the results are summarized in Table 1.
Clinically the lesions varied widely in distribution
and appearance (Figs. 1 and 2). The head, neck, and
upper extremities were the most frequent sites of
involvement. All three patients with MF had involve-
ment of the extremities. The appearance of the lesions
took on primarily three forms: follicular-based pap-
ules (n = 2; 18%), scaly alopecic patches and plaques
TABLE 1. Clinical, Histologic, Molecular, Treatment, and Outcome Characteristics
Age,
Case Sex years Pathology
1 F 17 Mucin near hair shaft,
lymphocytic follicular
inflammation
2 M 14 2 follicles involved, 1 +
mucin, lymphocytic
inflammation,
acanthosis, mild
spongiosis
3 M 11 3 biopsies:
1) small amount of
mucin, acanthosis, mild
spongiosis, lymphocytic
inflammation (CD4
predominant, CD2, CD3
and CD5 (+) perifollicular
T-cell infiltrate with partial
loss of CD7)
2) large amount of mucin,
acanthosis, eosinophils,
no epidermotropism
3) moderate amount of
mucin, no epidermotropism,
perivascular eosinophils
present
4 M 13 2 biopsies:
small amount of mucin,
acanthosis and
parakeratosis, no
spongiosis or
epidermotropism,
eosinophils present
5 F 19 Medium amount of mucin,
acanthosis, multiple
follicles involved, no
epidermotropism,
eosinophils present
T-cell
receptor Morphology
N/A Nummular plaques with
superficial scale and pink
center (2–4 cm diameter)
N/A Confluent scaling plaque on
scalp with seborrhea-like
scale
Multiple 1- to 2-cm
erythematous nummular
plaques with slight scale
and hypopigmentation on
face
Nummular plaques with
alopecia and follicular
prominence on right
shoulder and arm
Clonal Erythematous scaly patches,
(skin tissue, some of which are
PCR) hypopigmented
Equivocal Follicular papules (lichen
(skin tissue, spinulosa-like) and scaly
unknown plaques with alopecia
method)
No clone Alopecic scaly plaque
(skin (1.5 cm 9 3.5 cm diameter)
tissue,
PCR)
Total
Location and follow-up
distribution Treatment(s) Outcome time
Right arm and right TMC 0.1% cream twice Resolved 10 yrs,
anterior shin daily 5 mos
Scalp, cheeks, nose, Desonide 0.05% cream Resolved 8 yrs,
forehead, right (face) twice daily, 9 mos
shoulder and arm fluocinolone 0.01%
solution and selenium
sulfide 2.5% shampoo
(scalp) daily,
triamcinolone 0.1%
cream (trunk) twice daily
Face, chest, back, Minocycline 100 mg twice CTCL at 2 yrs
hips, scalp, upper daily and topical tretinoin outset;
extremities, lower 0.1% cream initially currently
extremities, Subsequently, tretinoin resolved
shoulders 0.1% cream stopped,
minocycline continued,
194 Pediatric Dermatology Vol. 30 No. 2 March/April 2013
and bexarotene 1% gel
daily and NB-UVB (three
times per week) started
Currently on no
medications because of
resolution
Papules on trunk and Ammonium lactate cream, Persistent 9 mos
extremities, desonide 0.05% cream on arms
plaques on twice daily, natural and legs
extremities, hair sunlight
loss on occipital
scalp and lateral
eyebrows
Left forehead above Desonide 0.05% cream Resolved 10 yrs,
eyebrow twice daily initially 3 mos
Subsequently, clobetasol
0.05% cream twice daily
and triamcinolone
intralesionally as needed
because desonide was
ineffective
Subsequently, 6 wks of
oral isotretinoin (stopped
TABLE 1. Continued

Total
Age, T-cell Location and follow-up
Case Sex years Pathology receptor Morphology distribution Treatment(s) Outcome time

because of dryness and no

benefit)
Finally, bexarotene 1% gel
twice daily
6 M 18 Not available for review Clonal (skin Alopecic scaly patch Right upper eyebrow Pimecrolimus 1% cream Unknown None
tissue, (3 cm 9 3 cm diameter) twice daily (also given
Southern tretinoin 0.1% cream
blot) prescription if
pimecrolimus ineffective)
7 M 11 Large amount of pooled Equivocal Several scaly plaques Left upper back, left Bexarotene 1% gel daily and CTCL at 2 yrs,
mucin, folliculotropism (skin tissue, (1 cm 9 1 cm to anterior shoulder, excimer laser twice a week outset; 3 mos
and syringotropism, PCR); no 4 cm 9 4.5 cm diameter) right arm lesions
suspicious for pilotropic clone resolved
MF present in and flared
Initial blood intermittently
immunohistochemical sample
evaluation showed
predominance of
CD3+ and CD4+
T-lymphocytes
invading hair follicles,
with loss of CD7 and
CD8, but these slides
were not available for
review
8 M 19 Not available for review Clonal Alopecic plaque with Right volar forearm Clobetasol 0.05% cream CTCL at 4 yrs,
(skin follicular accentuation twice daily, handheld NB- outset; 9 mos
tissue, (~3 cm) UVB device currently
PCR) resolved
9 F 14 Not available for review N/A Coalescing papules Left forehead above Desoximetasone topically Resolved 4 yrs,
surrounded by eyebrow initially (unknown dose 7 mos
hypopigmentation or frequency)
Subsequently, minocycline
100 mg daily and
tazarotene 0.1% cream
twice daily
10 F 16 Not available for review N/A Erythematous plaques with Face, limited to Desonide 0.05% cream Resolved 4 yrs,
slight prominence of hair cheeks and right twice daily 3 mos
follicles and vellus hair upper eyebrow
growth
11 F 12 Spongiosis, no other N/A Dermatitic, lichenified Buttocks, posterior Hydrocortisone 2.5% cream Improved 15 mos
notable findings patches and erythematous thighs, popliteal under wet dressing over 12 to 15
excoriated papules fossae, forearms, occlusion twice daily mos, then
right dorsal hand recurred on
face, legs, and
arms
Alikhan et al: Pediatric Follicular Mucinosis

N/A, test not performed; NR, not recorded; wks, weeks; yrs, years; CD3+ mos, months; CTCL, cutaneous T-cell lymphoma.
195
196 Pediatric Dermatology Vol. 30 No. 2 March/April 2013
A A
B C
Figure 1. A 14 year-old girl with idiopathic follicular
mucinosis (patient 9 in Table 1) with a 2-month history of
coalescing papules surrounded by hypopigmentation on the
forehead. She also had acne vulgaris and was treated with
minocycline and tazarotene. The plaque resolved within
several months and did not recur (A). Microscopic
examination revealed perivascular lymphocytic infiltrate
and involvement of two follicles, one with a mild
lymphocytic infiltrate in the outer root sheath epithelium
and both with 1+ mucin. There is mild overlying spongiosis
and no eosinophils (B) (hematoxylin and eosin, original
magnification 109). Colloidal iron stain highlights the
intrafollicular mucin (C).
(n = 5; 45%), or a combination of the two (n = 4;
36%). None of the three patents with MF had
peripheral lymphadenopathy on examination, and
all were Stage IA according to the Mycosis Fungoides
Cooperative Group staging system and the updated
International Society of Cutaneous Lymphomas/
European Organization of Research and Treatment
of Cancer staging system.
Slides were available for review for two of three
patients with MF. Microscopically these cases of MF
did not demonstrate clear cytologic atypia, a band-
like lymphocytic infiltrate along the epidermis, or
Pautrier’s microabscesses in the epidermis or upper
follicle as in classic MF. In one patient there was
significant folliculotropism and syringotropism.
T-cell receptor gene rearrangement was available
for six patients. The clinician or pathologist in cases
suspicious for MF ordered testing. Three cases
Figure 2. An 11-year-old boy with folliculotropic mycosis
fungoides developed widespread eczematous plaques
that were unresponsive to typical treatments for dermatitis.
The plaques progressed over 6 months to a psoriasiform
appearance; subsequent infiltration lead to peau d’orange
changes (A). A dense perifollicular lymphocytic infiltrate in
conjunction with pools of intrafollicular mucin is noted
(B) (hematoxylin and eosin, original magnification 49).
CD3, CD4, and CD5 staining highlights the lymphocytes;
CD7 and CD8 are markedly low Iimmunohistochemical
staining, original magnification 59). Molecular genetic
studies using polymerase chain reaction demonstrated
clonality. CD, cluster of differentiation.
demonstrated clones, two were equivocal, and one
did not demonstrate a clone. Two clonal cases and one
equivocal case were associated with MF. One clonal
case did not follow up, so it is difficult to comment on
progression. One equivocal case and the case that did
not demonstrate clonality were not associated with
MF. Peripheral blood smear was performed on two
patients with MF (patients 3 and 8 in Table 1); Sézary
cells were not demonstrated.
A wide range of therapies were employed, includ-
ing topical retinoids, oral minocycline, and topical
corticosteroids. In patients with MF, ultraviolet light
therapy and topical bexarotene were also employed.
Overall, three patients had histopathologic findings
consistent with MF. The other seven did not develop
MF. There were no follow-up data for one patient. As

of the most recent follow-up, lesions have resolved
completely in seven patients, partially in one, and not
at all in two (no follow-up data on one patient). Of the
three patients with MF, two had complete resolution
and one has intermittent flares that are controlled
with topical bexarotene and excimer laser.
DISCUSSION
Follicular mucinosis in children is not generally
indicative of MF. In only 3 of the 11 patients was
FM associated with MF, although follow-up was not
available for one patient. Furthermore, two of the
three patients with MF no longer have clinical lesions.
Of the lymphoproliferative disorders, FM is most
frequently associated with MF, although the inci-
dence varies considerably between studies, ranging
from 9.4% to 60% (5,8,11–16). Other lymphoprolif-
erative disorders have been reported in patients with
FM, including Hodgkin’s disease (16–18), chronic
lymphocytic leukemia (16), cutaneous B-cell lym-
phoma (19), acute myeloblastic leukemia (20), adult
T-cell leukemia–lymphoma (21), and chronic myelo-
monocytic leukemia (22). To our knowledge, no
patients in our study developed any other lympho-
proliferative disorders.
Given the strong association with MF, controversy
exists as to whether FM represents a neoplastic
process or a clonal inflammatory condition. Some
authors have proposed that FM, MF, and folliculo-
tropic MF (FMF) represent conditions along a
continuous spectrum, with FM being a variant of
MF that follows an indolent clinical course (6,23). Of
greater significance is that proponents and opponents
of this theory agree that no clinicopathologic criteria
can reliably distinguish between primary and second-
ary FM. In most cases of FM associated with a
lymphoproliferative disorder, patients develop FM
and MF concomitantly, although lymphocytic malig-
nancy may also arise several years after the diagnosis
of FM (15,20,24–26). Brown et al (27) state that, in the
majority of cases, MF manifests within 5 years after
the onset of FM. In our study, all three patients with
MF demonstrated findings of MF in conjunction with
FM on their initial biopsy (which demonstrated FM).
Recently it has been suggested that clonal FM with
a TCR gene rearrangement may be associated with
the development of cutaneous malignancy, although
this has not been firmly substantiated. Brown et al
(27) reported seven patients younger than 40 years of
age with primary FM, of whom five had clonal TCR.
Patients were followed for a mean of 10.3 years with
none progressing to MF; in two of the patients,
Alikhan et al: Pediatric Follicular Mucinosis 197
complete remission was observed (both had clonal
TCR). Other studies have also demonstrated no
progression of FM to MF despite the presence of
clonal TCR (28). In contrast, two of three patients in
our study who had clonal TCR had MF, and the third
was lost to follow-up.
It is generally accepted that, in patients with limited
disease (primarily of the head and neck) at the time of
presentation, the condition typically runs a benign
course (29). In a study of 33 individuals with FM,
initial lesions were on the head and neck in 44% and
on the trunk or extremities in 56% of those with MF,
but were on the head and neck in 58% and on the
trunk or extremities in 42% of those without MF (16).
Our data are consistent with prior studies in this
regard—all patients with MF had involvement of the
extremities. Additionally, patients in whom the
lesions did not resolve typically had more areas of
involvement.
Taken together, our data, as well as data from
previous studies, indicate that FM is not equivalent
to MF in children. The majority of our patients with
histologic findings of FM did not have evidence of
MF. Of those who had MF, all were diagnosed on
initial biopsy, all had several anatomic sites of
involvement, and all had clonal or equivocal TCR
gene rearrangement studies. On a positive note, two of
three individuals with MF have completely cleared
their disease, whereas the third continues to experi-
ence flares that are controlled well with nonsystemic
agents. This study adds further credence to approach-
ing this finding in children with caution and conser-
vative therapy. It appears that the addition of
molecular genetics studies to those of routine histo-
pathology and careful clinicopathologic correlation is
warranted and may be helpful. Even in cases of
confirmed MF, there is no evidence in this study to
support aggressive therapy that may, in the long term,
bring about immune alterations.
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