Full text of DOI:10.1111/j.1346-8138.2002.tb00252.x

The Journal of Dermatology
Vol. 29: 214–220, 2002
Proliferating Trichilemmal Cyst: Report of Two Cases,
One Benign and the Other Malignant
Seema Sethi and Usha Rani Singh
Abstract
Proliferating trichilemmal cyst (PTC) is a rare but morphologically distinct tumor that
usually arises on the scalp of elderly women. We report two cases of PTC, one benign and
the other malignant. PTCs are well circumscribed, subepidermal lesions and demonstrate
a uniform histologic pattern with varying degrees of cytological atypia. Malignant prolifer-
ating trichilemmal cyst (MPTC) has features in common with benign proliferating
trichilemmal cyst (BPTC), including a central area of abrupt keratinization and hyper-
plastic squamous epithelium forming solid areas. The diagnosis of MPTC is essentially
based on histological features. The presence of a high mitotic rate, atypical mitosis, severe
nuclear pleomorphism, and tumor invasion of the adjacent tissues are the essential histo-
logical features of malignancy in these unusual tumors. The therapeutic approach in ma-
lignant cases is the same as that in the treatment of BPTC: surgical removal with a wide
clear margin. However, even with adequate resection, both tumors tend to recur locally.
Abbreviations: MPTC: malignant proliferating trichilemmal cyst; BPTC: benign
proliferating trichilemmal cyst; PTC: proliferating trichilemmal cyst; TC: trichilemmal
cyst
Key words: proliferating trichilemmal cyst; trichilemmal keratinization; malignant
proliferating trichilemmal cyst
the first description by Maurer in 1895 went
unnoticed. Trichilemmal keratinization is
Introduction
Proliferating trichilemmal cyst, also re-
ferred to as proliferating trichilemmal
tumor (1), is derived from the outer root
sheath of the hair follicle and is nearly al-
ways a single lesion; rarely are there two
PTCs (2). They preferentially arise in areas
of dense follicle concentration (3). About
characterized by a gain in the bulk and ver-
tical diameter of the cells, which generally
loose their nuclei and keratinize without the
formation of keratohyaline granules. Such
keratinization is observed in that part of the
isthmus of the anagen hair where the outer
root sheath is no loger covered by the inner
root sheath. Similar keratinization appears
also in the trichilemmal sac, surrounding
the lower end of catagen hair, thus produc-
ing the telogen bulb. The two intradermal
lesions which show trichilemmal keratiniza-
tion are the trichilemmal cyst and proliferat-
ing trichilemmal cyst. Focal immunohisto-
chemical reactivity for CD34, a marker for
outer root sheath differentiation, has been
detected (6).
9
0% of the cases occur on the scalp, with a
residual 10% occurring mainly on the back.
More than 80% of the patients are women,
most of them elderly (4).
In 1969, Pinkus (5) drew attention to the
existence of trichilemmal keratinization;
Received May 31, 2001; accepted for publication
January 15, 2002.
Department of Pathology, University College of
Medical Sciences and Guru Teg Bahader Hospital,
Shahdara, Delhi-110095, India.
About 30 well documented cases of so
called malignant proliferating trichilemmal
cyst have been reported.
Reprint requests to: Seema Sethi, M.D., 107, Old
Gupta Colony, Delhi-110009, India

Proliferating Trichilemmal Cyst
215
Fig. 1. Gross morphology of benign proliferat-
ing trichilemmal cyst
Fig. 2. Section showing skin with a cyst in the
dermis lined by proliferated squamous epithe-
lium with squamous eddy (arrow) (H & E
×20)
Fig. 3. High power view of Figure 2 showing
basal palasading of cells, squamous eddies
(
arrow head), dyskeratosis (thin arrow), and
trichilemmal keratinization (T) (H & E ×100)
Case Report
Case 1
An otherwise healthy 52-year-old male pre-
sented for the first time with a history of swelling
over the scalp of 1-year duration, gradually in-
creasing in size. A detailed clinical history was
taken. On examination, a single swelling mea-
suring 5 cm in diameter with a smooth surface
and soft consistency was seen on the scalp. It was
painless and not adherent to the underlying
bone. No lymph nodes were palpable in the
neck. A clinical diagnosis of sebaceous cyst was
made. The tumor was excised, and the tissue
sent for histopathological examination.
Fig. 4. Gross appearance of malignant prolifer-
ating trichilemmal cyst
Grossly, the tumor was predominantly cystic,
well circumscribed, and filled with yellowish
brown necrotic material. The solid portion had
a honeycomb configuration (Fig. 1). It was cov-
ered with hairy skin and had a margin of normal
tissue all around. Histopathologically, the lesion
was in the dermis, well circumscribed, and sur-

2
16
Sethi and Singh
Fig. 5. Section from the tumor showing nuclear
plemorphism, hyperchromatism, and mitosis
Fig. 6. Section from tumor showing atypical mi-
totic figure (H & E × 400).
(
H & E ×200).
clear cells were also seen. Trichilemmal kera-
tinization was observed on the internal border
of the wall lining the cysts, but it also appeared
in the form of whorls looking like squamous ed-
dies in the walls of the cyst and inside the lob-
ules. The stroma showed a mild mononuclear
inflammatory infiltrate. The overlying epidermis
was normal. All the surgical margins were free of
the tumor. A diagnosis of benign proliferating
trichilemmal cyst was made. The patient was
asymptomatic at six months follow up.
Case 2
Fig. 7. Section from tumor margin showing vas-
A 60-year-old female presented with a scalp
swelling of 4 years duration that had gradually
increased in size, and discharged foul smelling
material. On examination, there was a single, ul-
cerated blue-red tumor 5 cm in diameter and
rubbery firm in consistency on the parietoccipi-
tal region. It was not fixed to the underlying
bone, and there was no lymphadenopathy. The
lesion was diagnosed as sebaceous cyst and was
excised. The tissue was set in 10% formalin for
histopathological examination. Grossly the
tumor was nodular, circumscribed, and protrud-
ed through ulcerated hairy skin. It was rubbery
firm in consistency. On the cut surface, it was
predominantly solid tan brown in color with soft
friable areas (Fig. 4). The small cystic areas were
filled with cheesy material.
cular invasion (H & E × 20)
rounded by compressed collagen (Fig. 2). The
cyst was lined by stratified squamous epithelium,
which showed trichilemmal keratinization and
was filled with keratin with an area of hemor-
rhage and cholesterol clefts. In the wall of the
cyst, there was epithelial proliferation forming
lobules of squamous epithelium with central
trichilemmal keratinization and separated by fi-
brous tissue septa. The basal layer of the epithe-
lium was composed of small cells, which showed
palisading near the basement membrane. These
cells became larger as they matured and pro-
ceeded towards the center, undergoing mainly
trichilemmal keratinization without forming
keratohyaline granules and occasionally form-
ing dyskeratotic cells (Fig. 3). Scattered foci of
Microscopically, the morphology was the
same as in Case 1 but, in addition, showed the
following features. The lesion was ulcerated and

Proliferating Trichilemmal Cyst
217
covered by necrotic debris. It was predominantly
solid and had a nodular architecture separated
by bands of fibrous tissue. The nodules were
composed of proliferated squamous epithelium
forming spaces filled with keratinous material
and necrotic debris. At places, the cells lining
the nodules were highly pleomorphic, had mod-
erate amounts of cytoplasm and large nuclei
with irregularly clumped chromatin, some show-
ing prominent nucleoli. There was increased mi-
totic activity with atypical mitotic figures (Figs. 5,
Rapid enlargement of the lesion has been
reported after trauma or spontaneously (2)
and has indicated malignant transformation
according to some authors (14). Clinically,
size, ulceration, duration since presence,
and growth pattern do not differentiate a
benign from malignant lesion.
PTC is an uncommon neoplasm showing
trichilemmal keratinization, which occurs
normally in the stratified epithelium of the
outer root sheath of the hair follicle and
where, keratinized cells are produced with-
out the formation of keratohyalin. Some au-
thors have suggested that PTC arises from
preexisting TC. In 2% of pilarcysts, single or
multiple foci of proliferating cells have been
observed (15).
Brownstein et al. (4) studied 56 cases of
PTC (and 50 cases of TC as comparison). In
many PTCs, areas indistinguishable from
uncomplicated TC were found, and some
uncomplicated TC contained foci of hyper-
plasia indistiguishable from PTC. A spec-
trum was observed from TC with minimal
hyperplasia to full blown proliferating TC.
Similarities between TC & PTC, identifica-
tion of intermediate stages between the two,
and the occasional association of these two
conditions suggest that PTC is a complica-
tion of TC; it would seem likely that trauma
and inflammation induce occasional TC to
proliferate. A similar view is held by other
authors (2, 7, 15, 16). However, PTC can
also occur de novo without a preexisting le-
sion (2). Although considered biologically
benign, they may be locally aggressive (7),
recur (3, 11, 15, 18), and metastasize (16,
18–20) to lymph nodes and internal organs
(19).
6
). The cells still showed maturation towards the
center of the cyst by forming trichilemmal type
of keratinization. In these areas, the basal cells
did not show palisading. Dyskeratosis, clear cell
changes squamous eddies were more conspicu-
ous. The margins of the lobules showed infiltra-
tion into the surrounding stroma by cords of
atypical tumor cells. Vascular and lymphatic in-
vasion was also seen (Fig. 7). There was a foreign
body type giant cell reaction and a dense
mononuclear inflammatory infiltrate into the
surrounding stroma with formation of lymphoid
follicles in areas. The remaining epidermis was
unremarkable. One of the resected surgical mar-
gins showed involvement by the tumor. A diag-
nosis of malignant proliferating trichilemmal
cyst was made. The patient was lost to follow up.
Discussion
Proliferating trichilemmal cyst is thought
to arise from a preexisting ordinary
trichilemmal cyst following trauma and in-
flammation (2, 4). A PTC is often lobulated
and can undergo ulceration (2, 7). Usually
located on the scalp, but can also occur on
other sites such as the wrist (3), chest (3),
elbow (8), vulva (9), mons pubis (10), and
buttock (10). The size of the lesion as re-
ported in the literature can vary from 0.4 cm
to 10 cms in greatest diameter (4), but can
grow as large as 25 cms in largest dimension
Saida et al. (16) described the three
stages in the oncological development of
trichilemmal tumor. Trichilemmal cyst,
being the adenomatous stage, proliferating
trichilemmal cyst, the epitheliomatous
(
11). Ulceration can occur over the lesions,
mostly following trauma, and discharge foul
smelling, doughy, whitish material. The le-
sion can be present from 4 months to 50
years (2). About 84% of patients are greater
than 50 years of age (12), with females in-
volved predominantly (2–4, 10, 11, 13).
stage, and
malignant proliferating
trichilemmal tumor, the carcinomatous
transformation of PTC. The presence of
frankly malignant cells intimately associated
with more typical areas of trichilemmal dif-

2
18
Sethi and Singh
ferentiation suggests the possibility that
pilar tumors may progress through a series
of stages to malignant transformation (14,
from PTC were seen.
Sleater et al. (21) studied the prolifera-
tion index measured by immunohistochem-
ical staining with Ki-67 along with the mitot-
ic count and DNA ploidy in four cases of
PTC which were benign on histology. Two of
the cases had numerous mitotic figures and
were non-diploid. These showed greater Ki-
67 positively, whereas the other two, which
showed fewer mitotic figures, were diploid.
Herrero et al. (26) performed CD34 im-
munohistochemical reactivity in three cases
of malignant proliferating trichilemmal cyst
and found no reactivity [CD34 is a marker
of outer root sheath differentiation and has
been detected in PTC (7)]. Loss of reactivity
of CD34 was considered to be a conse-
quence of the undifferentiated phenotype
of most tumor cells. All three tumors had
malignant features on histology; two of the
three were aneuploid. PCNA reactivity and
mitotic count showed that the pleomorphic
tumor cell population was highly prolifera-
tive, indicating aggressive behaviour.
Hashimoto et al. (30) performed DNA
ploidy analysis by flow cytometry on ten
specimens of trichilemmal carcinoma, five
PTCs, and six TCs. Nine of the ten
trichilemmal carcinoma and two of the five
PTCs were aneuploid. Takata et al. (31), in a
case of trichilemmal carcinoma which they
thought began in the wall of a PTC, isolated
DNA from micro dissected areas of the PTC
and carcinoma respectively, and performed
PCR-based microsatellite loss heterozygosity
(LOH) analysis as well as p53 gene sequenc-
ing. LOH analysis showed that PTC retained
chromosome arm 17p (where the p53 gene
resides and showed a nonsense mutation in
both samples), whereas carcinoma was asso-
ciated with loss of this allele. In the observa-
tions made by various authors, as stated
above, the cases which were malignant on
histology only showed increased prolifera-
tion index, aneuploid DNA content, and
loss of CD34 reactivity.
1
7, 20–24). Headington (22) proposed the
term “malignant proliferating trichilemmal
tumor” for the malignant variant of prolifer-
ating trichilemmal cyst. The diagnosis of
malignancy is based on morphology and cy-
tology (25, 26) by the presence of pleomor-
phism, atypia, mitosis, atypical mitosis, and
invasion of the stroma (2–4, 7, 10, 11, 13, 15,
1
7, 18, 20, 24, 27). Cases with no atypia may
exhibit aggressive behaviour and vice versa
3, 28), and the biological behaviour of PTT
is not related to its histological appearance
29).
Rutty et al. (24) studied cell proliferation
(
(
in two cases of trichilemmal cyst, three cases
of PTC, and one trichilemmal carcinoma by
using immunohistochemical staining
against proliferating cell nuclear antigen
(
PCNA) and correlated these results with
the DNA content using flow cytometry. His-
tologically, two were trichilemmal cyst, one
trichilemmal cyst with early proliferative
changes, one proliferating trichilemmal
cyst, one PTC with early malignant changes
and one overt carcinoma. Two cases of TC
and one PTC showed nuclear PCNA stain-
ing confined to the basal layer, a pattern
similar to that seen in normal skin. In the
tumor containing overt carcinoma, areas of
residual PTC showed the same staining pat-
terns as a benign neoplastic basal layer. In
contrast, the cells of the invasive component
showed an increase in the numbers of posi-
tive cells. PTC with focal early malignant
changes also showed an increase in positive
nuclear staining in these areas. DNA con-
tent of TC and PTC was diploid. The DNA
content in overt carcinoma and in PTC with
early malignant changes was aneuploid.
This confirms the hypothesis that morpho-
logical malignancy in pilar tumors is accom-
panied by increased cell proliferation and
DNA aneuploidy, supporting Mehregan et
al. (14) and multistep theory of Saida et al.
Ackerman and co-workers (32, 33) called
PTC a proliferating follicular cystic neo-
plasm (PFCN), and later they came to con-
(
16). In our Case 1, areas characteristic of
TC and, in Case 2, areas indistinguishable

Proliferating Trichilemmal Cyst
219
sider that PTC is a kind of squamous cell
carcinoma and called it proliferating
trichilemmal cystic squamous cell carcino-
ma (PTCSCC) because it displays architec-
tural, cytopathologic, and biologic charac-
teristics of a malignant neoplasm. They
called it a squamous cell carcinoma, be-
cause some cohesive neoplastic cells show
signs of aberrant cornification in the form
of dyskeratotic cells and parakeratosis.
There was no indication of any other kind
of differentiation. They also stress that PTC-
SCC is malignant right from its inception
and not malignant transformation. It has
also been difficult for some authors (4, 32)
to differentiate squamous cell carcinoma
from PTC. Jaworski (28) described features
for diagnosing malignant PTT; these includ-
ed the presence of abnormal mitosis,
marked cellular pleomorphism, infiltrating
margins, and ploidy status. After our review
of the literature, we also feel that PTC devel-
ops from TC and MPTC from PTC but that
MPTC can also arise de novo.
The benign counterpart of PTCSCC has
been called “proliferating trichilemmal cys-
tic acanthoma” by Mones et al. (33) because
of its architecture and cytological features.
Aggregations of neoplastic cells are relative-
ly uniform in size and shape and ker-
atinocytes rather than spinal cells predomi-
nate consistently in the center of the aggre-
gation. The nuclei of cells are not crowded,
are monomorphous, and practically never
in mitosis. The epithelium lining the cysts is
the same as in conventional trichilemmal
cyst.
recommend immunohistochemical staining
for proliferation markers, CD34 immunore-
activity, and DNA ploidy to predict its bio-
logical behavior, and we intend to keep the
patient on close follow up.
Our Case 2 of a 60-year-old female with an
ulcerated scalp swelling of 4 years duration
was morphologically and cytologically ma-
lignant, and we would prefer to call it malig-
nant proliferating trichilemmal tumor (or
PTCSCC, as a distinct variant of SCC).
References
1
2
) Hanau D, Grosshans E: Trichilemmal tumor un-
dergoing specific keratinization: Keratinizing
trichilemmoma, J Cutan Pathol, 6: 463–475, 1979.
) Baptista AP, Silva LGE, Born MC: Proliferating
trichilemmal cyst, J Cutan Pathol, 10: 178–187,
1983.
3) Holmes EJ: Tumors of lower hair sheath: Com-
mon histogenesis of certain so-called “sebaseous
cysts”, acanthomas and “sebaceous carcinomas”,
Cancer, 21: 234–248, 1968.
4
) Brownstein MH, Arluk DJ: Proliferating
trichilemmal cyst: A simulant of squamous cell
carcinoma, Cancer, 48: 1207–1214, 1981.
5
6
) Pinkus H: “Sebaceous cysts” are trichilemmal
cysts, Arch Dermatol, 99: 544–555, 1969.
) Poblet E, Jimenez-Acosta F, Rocamora A:
QBEND/ 10 (anti-CD34 antibody) in external
root sheath cells and follicular tumors, J Cutan
Pathol, 21: 224–228, 1994.
7) Hendricks DL, Liang MD, Borochovitz D, Miller
T: A case of multiple pilar tumors and pilar cysts
involving the scalp and the back, Plast Reconstr
Surg, 87: 763–767, 1991.
8
) Patterson JW: Infundibular and trichilemmal
keratinization of a pilar tumor, Cutis, 36: 330–
332, 1985.
9
) Buchler DA. Sun F, Chuprevich T: A pilar tumor
of the vulva, Gynecol Oncol, 6: 479–486, 1978.
1
1
0) Janitz J, Weidersberg H: Trichilemmal pilar tu-
mors, Cancer, 45: 1594–1597, 1980.
1) Dabska M: Giant hair matrix tumor, Cancer, 28:
701–706, 1971.
Our Case 1 was a non-ulcerated cystic le-
sion of one year’s duration over the scalp of
a 52-year-old male; grossly, the tumor was 5
cm in diameter and predominantly cystic
with one area in the wall showing a honey-
combed growth. Microscopically, it showed
cysts of various sizes lined by stratified squa-
mous epithelium with a bland morphology
showing trichilemmal keratinization. As per
Mones et al., it would be PTCSCC (well dif-
ferentiated) or PTC acanthoma, which is
very rare. We would prefer to call it PTC and
12) Sau P, Graham JH, Helwig EB: Proliferating ep-
ithelial cysts: Clinicopathological analysis of 96
cases, J Cutan Pathol, 22: 394–406, 1995.
1
3) Reed RJ, Lamar LM: Invasive hair matrix tumors
of the scalp, Arch Dermatol, 94: 310–316, 1966.
4) Mehregan AH, Lee KC: Malignant proliferating
trichilemmal tumors. Report of three cases, J
Dermatol Surg Oncol, 13: 1339–1342, 1987.
1
1
1
5) Leppard BJ, Sanderson KV, Wells RS: Hereditary
trichilemmal cyst, Clin Exp Dermatol, 23–32, 1977.
6) Saida T, Oohara K, Hori Y, Tsuchiya S: Develop-

2
20
Sethi and Singh
ment of a malignant proliferating trichilemmal
cyst in a patient with multiple trichilemmal cysts,
Dermatologica, 166: 203–208, 1983.
tases, Am J Dermatopathol, 19: 536–539, 1997.
26) Herrero J, Monteagudo C, Ruiz A, Llombart-
Bosch A: Malignant proliferating trichilemmal
tumors: a histopathologic and immunohisto-
chemical study of three cases with DNA ploidy
and morphometric evaluation, Histopathology, 33:
542–546, 1998.
27) Jawroski R: Unusual proliferating trichilemmal
cyst, Am J Dermatopathol, 9: 459–461, 1987.
28) Jawroski R: Malignant trichilemmal cyst, Am J
Dermatopathol, 10: 276–279; 1988.
29) Arico M, Noto G, Pravata G, et al: Proliferating
trichilemmal tumor: Morphometeric evaluations
in 4 cases, in Panconesi E (ed), Dermatology in Eu-
rope, Blackwell, Oxford, 1991, pp 810–813.
30) Hashimoto Y, Matsuo S, Iizuka H: A DNA-flow
cytometeric analysis of trichilemmal carcinoma,
proliferating trichilemmal cyst and trichilemmal
cyst, Acta Derm Venerol (Stockh), 74: 358–360, 1994.
31) Takata M, Rehman I, Rees JL: A trichilemmal
carcinoma arising from a proliferating trichilem-
mal cyst: The loss of the wild type p53 is a critical
event in malignant transformation, Hum Pathol,
29: 193–195, 1998.
32) Ackerman AB, de Viragh PA, Chongchitnant N:
Proliferating follicular cystic neoplasm; in Neo-
plasms with Follicular Differentiation, Lea &
Febinger, Philadelphia, 1993, pp 551–570.
33) Mones JM, Ackerman BA: Proliferating
trichilemmal cyst is squamous-cell carcinoma,
Dermatopathol: Practical and Conceptual, 4; 295–
310, 1998.
1
1
1
7) Weiss J, Heine M, Grimmel M, Jung EJ: Malig-
nant proliferating trichilemmal cyst, J Am Acad
Dermatol, 32: 870–873, 1995.
8) Mori O, Hachisuka H, Sasai Y: Proliferating
trichilemmal cyst with spindle cell carcinoma,
Am J Dermatopathol, 12: 479–484, 1990.
9) Amaral AL, Nascimento AG, Goellner JR: Prolif-
erating pilar (trichilemmal) cyst. Report of two
cases, one with carcinomatous transformation
and one with distant metastases, Arch Pathol Lab
Med, 108: 808–810, 1984.
0) Penden JC: Carcinoma developing in sebaceous
cysts, Ann Surg, 128: 1136–1147, 1948.
1) Sleater J, Beers B, Stefan M, et al: Proliferating
trichilemmal cyst. Report of 4 cases, two with
nondiploid DNA content and increased prolifer-
ating index. Am J Dermatopathol, 15: 423–428,
2
2
1
993.
2
2
2) Headington JT: Tumors of the hair follicle, A re-
view, Am J Pathol, 85: 480–514, 1976.
3) Swanson PE, Marrogi AJ, Williams DJ, et al: Tri-
chiolemmal carcinoma. Clinicopathologic study
of 10 cases, J Cutan Pathol, 19: 100–109, 1992.
4) Rutty GN, Richman PI, Liang JH: Malignant
change in trichilemmel cysts: A study of cell pro-
liferation and DNA content, Histopathology, 21:
2
2
4
65–468, 1992.
5) Park BS, Yang SG, Cho KH: Malignant proliferat-
ing trichilemmal tumor showing distant metas-