TUMORS OF LOWER HAIR SHEATH

C o m m o n Histogenesis of Certain So-called Sebaceous Cysts,

Acanthomas and Sebaceous Carcinomas
ELIZABETH
J. HOLMES,
MD

Under the terms trichochlamydocyst and trichochlamydocarcinoma is proposed a new unifying concept of the histogenesis of certain so-called sebaceous,
keratinous and pilar cysts (cystic wens) and of proliferating epidermoid cysts
and sebaceous carcinomas (solid wens). T h e majority of these lesions occur
on the scalps of elderly women. Morphologically and histochemically their
origin can be traced to the lower external root sheath of the terminal hair
follicle rather than to sebaceous glands. I n addition, a hitherto unrecognized
lesion of the scalp, trichochlamydoacanthoma, is described for the first time and
compared to its counterpart of other body regions, the keratoacanthoma. It,
like keratoacanthoma, possesses a central keratin-filled crater but comprises
instead lower externaI hair sheath epithelium as well as upper sheath or
epidermal epithelium. Trichochlamydocarcinomas, the solid tumors of lower
sheath origin, although usually non-aggressive, are occasionally capable of
metastasis. I t is not possible to predict by histologic or cytologic criteria their
probable behavior so that a margin of normal tissue should accompany their
excision.

RICHOCHLAMYDOCYST (HAIR SHEATH CYST)

is the term proposed for those wens

widely known previously as sebaceous cysts.
They and epidermal cysts have long been confused with each other; however, as early as
1930, Broders and Wilson6 separated their
keratoma or epidermal cyst from sebaceous
cysts not only microscopically but by the
strong odor given off from sebaceous cysts
but not from keratomas! In a study of 566
cysts in 1943 Warvi and Gates38 found that
all but ten were epidermal and filled with
laminated keratin. In the same year Love and
Montgomery22 wrote that epithelial cysts
should be distinguished from sebaceous cysts,
milia and steatocystoma multiplex. On the
From King County Hospital and University of
Washington Medical School Departments of Pathology,
Seattle, Wash.
Address for reprints: Elizabeth J. Holmes, MD,
Department of Pathology, King County Hospital, 325
Ninth Avenue. Seattle, Wash. 98104.
Supported in part by grant T 419 from the American Cancer Society.
The author thanks Dr. James L. Bennington, Assistant Professor of Pathology, University of Washington
and Pathologist-in-Chief, King County Hospital, for
providing information leading to the inclusion of
case 7 in the series of trichochlamydocarcinomas and
Dr. Robert G. Parker, Professor of Radiology, University of Washington Medical School, for providing the
clinical photographs of case 7.
Received for publication April 21, 1967.

other hand, KligmanlQin 1964 stated that the

sebaceous cyst was nothing more than a variety of keratinous cyst, for which McGavran
and Binningtonz4 in 1966 proposed an outer
hair sheath origin. The present investigation
undertakes to substantiate this origin and further limit it to the lower outer root sheath.
Trichochlamydoacanthoma is the term proposed for a hitherto undescribed hair sheath
tumor of the scalp probably confused in the
past with keratoacanthoma of other body regions. Previously only five keratoacanthomas
have been recorded in the literature as having occurred on the scalp. Jenkins according
to Whiteley16 reported one pitch wart on
the scalp in an analysis of 158 treated lesions
of the head and neck in gas and tar workers;
however, the histology was not illustrated.14
Rook32 recorded 3 cases of keratoacanthoma
of the scalp and Baer and Kopfl had one but
there were no histologic illustrations for these
four cases either. The lack of previous h i s
tological details prompted the ensuing case
report.
Trichochlamydocarcinoma is the term proposed for those solid tumors of the scalp of
hair sheath origin which clinically have the
appearance of wens until late in the course of
the disease. The true incidence of these relatively rare tumors is difficult to estimate be-

2 34

TUMORS
OF LOWER
HAIRSHEATH
Holmes
235
cause of the previous lack of recognition of 45 females for epidermal cysts and only 4 men
and agreement as to their histogenesis. I t is to 28 women for trichochlamydocysts. Epiderquite likely that in the past they have been mal cysts occurred on all areas of the body
confused with pi lo matrix om as^^ and other tu- including the beard region and the perineum,
mors as well.
often said to be sites for sebaceous cysts;
Jones1? in 1966, apparently was the first to however, all 32 trichochlamydocysts occurred
recognize that all of his proliferating epi- on the hairy scalp. Only one epidermal cyst
dermoid cysts (trichochlamydocarcinomas) of the 127 occurred on the scalp. This was
were derived from a sebaceous type of epi- a case of a 12-year-old boy who developed a
thelium and that they usually occurred on the lump on his head after trauma at age 6.
scalp of elderly women. He reported nine
Both the contents and epithelial lining
cases of the less aggressive type of trichoch- cells of trichochlamydocysts stained positively
lamydocarcinoma. It is the purpose of the for neutral fat and glycogen. T h e contents
present report to present arguments for the and lining epithelium of epidermal cysts were
lower outer hair sheath histogenesis of these negative for neutral fat and glycogen. Both
solid tumors of the scalp and to call attention, types of cysts gave a negative test for citrulline.
although most are indolent carcinomas, to the
Morphology: T h e lining epithelium of epiexistence of the more aggressive types with dermal cysts had an appearance similar to
that of either the surface epiderm or the epithe potential of metastasis.
thelium of the pilosebaceous canal (Fig. 1,
2).
T h e lining was topped by a keratohyalin
MATERIALS
AND METHODS
granular cell layer and laminae of keratin.
All of the cysts of the skin in the slide files T h e gross appearance was that of a thinof King County Hospital for the 5 years from walled cyst with densely packed white flakes
1961 through 1965 were reviewed and classi- of keratin. Usually sebaceous glands were not
fied into two groups, epidermal cysts and tri- a part of the wall but occasionally they occhochlamydocysts, depending on the presence curred as shown in Fig. 2 A. O n the other
or absence of a keratohyalin granular cell hand, the lining epithelium of trichochlamylayer. T h e clinical entities of milia and stea- docysts bore a striking resemblance to the
tocystoma multiplex were not separated out outer root sheath of the hair club (the lower
since microscopically they appeared to be portion of the hair follicle sheath in telogen
merely smaller variants of epidermal cysts stage just prior to shedding of the hair). At
with which they were grouped. Stored paraffin this stage, the outer root sheath of the hair
blocks of both types of cysts were obtained as appeared saw-toothed at its inner cellular
were the blocks of the trichochlamydoacan- margin because of the retraction of the lower
thoma and of four cases of trichochlamydo- follicle toward the surface of the skin during
carcinoma. From these blocks newly cut sec- catagen (Fig. 1). This same saw-toothing
tions were made and stained by the periodic could be seen frequently in trichochlamydoacid-Schiff (PAS) technique before and after cysts (Fig. 3 B).
diastase. Other sections were subjected to a
T h e gross appearance of trichochlamydonew histochemical method for citrulline.12
cysts was that of thick-walled cysts with yellow
In six instances wet tissue was available for brown thick layers of keratin in contrast to
fat stains. Accordingly, frozen sections of two the white thin flakes of epidermal cysts. Miepidermal cysts, one trichochlamydocyst and croscopically also, the keratin was denser and
three trichochlamydocarcinomas were stained more homogeneous than the separate laminae of epidermal cysts (Fig. 2 A, 3 A). Often
for neutral fat with Sudan IV.
a vitreous membrane surrounded the trichochlamydocyst as it normally did the lower hair
TRICHOCHLAMYDOCYSTS
VS. EPIDERMAL
CYSTS
follicle (Fig. 3 B). A vitreous membrane was
Results: There were 159 cysts of the skin; not found around sebaceous glands. Occas127 were epidermal cysts and 32 were tricho- ionally such a cyst might acquire focally a
chlamydocysts. T h e age range for epidermal keratohyalin granular layer similar to the
cysts was from 8 weeks to 88 years with an process of keratinization of a mucous memaverage age of 50. T h e range of trichochla- brane but it was never the characteristic and
mydocysts was from 27 to 87 years with an universal finding that it was in epidermal
average age of 60. There were 82 males and cysts.
No. 2

236

CANCER
February 1968

Vol. 21

FIG. 1. Telogen phase hair follicle. Squarnous outer root sheath of upper follicle (above
attachment of sebaceous gland) has keratohyalin granular layer in contrast to lower follicle
which contains the hair club and has no granular layer. Hair matrix below the club is beginning anagen phase downgrowth and will soon produce another hair to replace the shed club
(H and E, ~ 1 5 0 ) .

physical examination a keratotic, depressed

lesion with elevated edges measuring 1.2cm
in diameter was noted on the hairy scalp, and
excised.
Morphology: T h e lesion was an epithelial
neoplasm possessing a central keratin-lined
fossa with marginal, overhanging lips of normal skin (Fig. 5). T h e configuration was quite
similar to a keratoacanthoma; however, unlike keratoacanthoma there were two distinct
varieties of stratified squamous epithelium
lining the central crater. One was the usual
epidermal type with a keratohyalin granular
cell layer. Alternating with this were foci of a
keratin-producing epithelium without a granTRICHOCHLAMYDOACANTHOMA
ular layer (Fig. 5, 6). From these latter foci,
Case report: A 49-year-old Negro man en- long tortuous, canalized, epithelial tubes extered King County Hospital on July 16, 1964 tended downward to the depths of the dermis
in a comatose state, having been found in his (Fig. 5). This configuration was reminiscent
apartment with gas escaping from the stove. of distorted hair follicles without hair matrix
No other history was available since the pa- or hair.
tient suffered permanent brain damage. On
T h e epithelium itself was quite similar in

T h e finding of a sebaceous gland opening

into a large epidermal cyst was somewhat unusual.19 T h e finding of an early anagen hair
complete with dermal papilla burrowing
into a large trichochlamydocyst was distinctly
unusual if not unique in recorded dermatopathologic literature thus far. Fig. 4 illustrates
such a hair. I n addition, Fig. 4 illustrates one
of the several undeveloped hair germs found
budding from various foci of the cyst wall.
Some of these hair germs possessed dermal
papillae while others, such as the one illustrated, did not.

No. 2

TUMORS
OF LOWER
HAIRSHEATH

Holiizes

237

FIG. 2. Epidermal cyst. A, epithelium of cyst wall with attached sebaceous gland resembles
epithelium of the upper hair follicle of Fig. 1 (H and E, ~ 1 5 0 ) B
. (inset), gross appearance of
the sectioned cyst ( ~ 2 ) .

appearance to that of the outer root sheath of

the lower hair follicle or to that of trichochlamydocysts (sebaceous cysts). Furthermore,
the root sheath epithelium lining the crater
produced a denser keratin than the adjacent
epidermal basket-weave type (Fig. 6 ) . This
was similar to the difference in appearance
of the keratins of trichochlamydocysts and
epidermal cysts. Both keratins were negative
histochemically for citrulline and therefore
not of inner root sheath derivation.12
Periodic acid-Schiff reaction before and after diastase demonstrated that the outer root
sheath epithelium contained large amounts of
glycogen both in the crateriform lining and in
the tubular downgrowths. Wet tissue was not
available for neutral fat stains; however,
some of the cells lining the tubules had
the clear cell appearance associated with glycogen and neutral fat content in trichochlamydocysts (Fig. 7).
Another histologic finding of importance
was the absence of basal layer pigmentation of
the lower root sheath epithelium in the tri-

chochlamydoacanthoma. In normal hair follicles the lower outer root sheath is nonpigmented, its basal layer containing only
amelanotic melanocytes. At the level of the
entrance of the sebaceous gland the upper
hair follicle abruptly becomes pigmented as
it changes to a n epidermal type of epitheli ~ m . This
~ ? same abrupt change between the
two epithelial components of the crateriform
lining of the trichochlamydoacanthoma was
strikingly apparent in this dark-skinned individual (Fig. 5 , 6 ) .

TRICHOCHLAMYDOCARCINOMA-CASE
REPORTS
AND MORPHOLOGY
Case 1. ES-84.
This Caucasian woman
entered the hospital for excision of multiple
cysts of the scalp on November 8, 1961. One
was a solid round tumor measuring 1.5 cm
in diameter which had been shelled out. Microscopically the tumor consisted of a squamous epithelial proliferation in a fibrous
stroma resembling that of Fig. 8 A or the
epithelium lining trichochlamydocysts. T h e

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CANCER
Februaiy 1968

VOl. 21

FIG. 3. Trichochlamydocyst. A (lower), epithelium shows clear cell change that may be interpreted erroneously as sebaceous metaplasia. These cells are positive for both glycogen and
neutral fat (H and E, X300). B (left inset), another portion of the cyst wall resembles the
lower follicle epithelium of Fig. 1. Note also the underlying vitreous membrane (H and E,
~ 3 0 0 ) .C (right inset), gross appearance of the sectioned cyst with keratin scooped from one of
the halves (X2).

No. 2

TUMORS
OF LOWER
HAIRSHEATH

Holnzes

239

FIG. 5. Trichochlamydoacanthoma. Note the central keratin-filled crater with overhanging

normal skin margins. Long tortuous tubes of lower outer root sheath epithelium extend from
the crater into the dermis (H and E, ~ 1 4 ) .

patient died ly2 years later of unrelated

cause and without evidence of recurrence.
This Caucasion woman
Case 2. AM-68.
had excision of multiple cysts of the scalp on
February 7, 1964. One was solid, measuring
2 cm in diameter, and microscopically resembled case 1. T h e patient subsequently was lost
to follow-up.
Case 3. FE-78. This Caucasian man entered the hospital in 1960 for excision of a
single solid scalp nodule measuring 3.5 x 4
x 4.5 cm with a small amount of normal
surrounding tissue. Histologically the lesion
resembled case 1. When the patient was last
seen two years later, there was no evidence
of recurrence.
This Caucasian woman
Case 4. MC-76.
was seen first on February 18, 1963 for the
removal of a 2.5 x 4 cm oval nodule present
in the scalp for 5 years. It was simply shelled
out. Microscopically, the tumor resembled
that of Fig. 8 A and extended to the surgical
margins. Re-excision was recommended but
refused by the patient. Approximately 3 years
later, on June 9, 1966, the patient submitted
to the removal of a densely scarred-in re-

growth of the tumor measuring 2.5 cm. in

greatest diameter. O n cut section, half of the
lesion was cystic and the other half solid (Fig.
8 B). Microscopically the recurrence was similar to the original. I t comprised anastomosing islands of squamous epithelium with
central degeneration and necrosis. I n some of
the central areas the debris reminded one of
the contents of trichochlamydocysts. Sudan
IV and periodic acidschiff stains, before and
after diastase, were positive for neutral fat
and glycogen in both the viable epithelium
and necrotic centers. There was an occasional
mitotic figure in the basilar layers of epithelium.
This Causasian woman
Case 5. RO-72.
entered the hospital on January 24, 1966 for
the excision of a slowly growing solid tumor
of the scalp of unknown duration measuring
1.6 x 2.5 x 2.9 cm. Grossly it was a circumscribed solid lesion which had been only
shelled out (Fig. 9 B). T h e histologic appearance was variable. A large portion of the
tumor comprised clear cell formations having
a striking resemblance to the clear cells of
the lower outer hair sheath in anagen phase
(Fig. 9 A, 9 C). These areas like the lower

FIG.4. Trichochlamydocyst. A , different cyst from that of Fig. 3 shows anagen hair cone with
underlying dermal papilla on the left and budding hair germ without dermal papilla on the
right (H and E, ~300).B (inset), enlargement of anagen hair of Fig. 4A (H and E, ~ 7 5 0 ) .

240

CANCERFebruary 1968

FIG. 6. Trichochlaniydoacanthoma. Lining epithelium

ufiper outer hair sheath (epidermal) epithelium with
granular cell layer and (2) lower outer hair sheath
granular layer. Note basket-weave keratin of epidermal
sheath (H and E, X300).

VOl. 21

oE crater is of two distinct types: (1)

basal pigmentation and keratohyalin
epithelium without pigmentation or
variety vs. solid keratin of lower hair

outer hair sheath contained large amounts of

neutral fat and glycogen. Other areas of the
tumor demonstrated a greater cellular pleomorphism with disparity in nuclear size and
shape. This was particularly prominent in the
dark cell areas which were also positive for
fat and glycogen. A most interesting finding
in the tumor was the presence of a thickened
vitreous-like membrane around the tumor islands such as is seen normally surrounding
the lower sheaths of hair follicles (Fig. 10).
A few more mitotic figures were found in this
tumor than in case 4. I n spite of the shellingout of this tumor and its histologic cancerous
appearance, it has not recurred as of February 16, 1967, one year following its removal.

of an expansile one rather than infiltrating;

however, microscopically there was an area
of individual-cell infiltration of stroma among
the areas of solid squamous islands (Fig. 1 1
A). I n this infiltrating area, vitreous membrane was again recapitulated as in case 5.
Mitotic figures were quite numerous in the
infiltrative area (Fig I1 B) and glycogen was
present in the squamous portions of the tumor. Wet tissue was not available for fat
stains. I n spite of the large size of the lesion
a n d the areas of histologic dedifferentiation,
there was no metastasis to the removed lymph
node. T h e patient died 70 days later of
pneumonia without evidence of residual tumor.

Case 6. NK-82.
This Caucasian woman
underwent surgical excision in 1959 of a solid
ulcerated mass of the occipital scalp measuring 3.5 x 9 x 12 cm. There were several
cysts of the scalp also present. I n addition,
an occipital-nuchal lymph node was excised.
Grossly the margins of the growth were
rounded, the tumor having the appearance

Case 7. JW-65.
This Caucasian woman
gave the history of a lesion which first began
in the scalp 14 years prior to her admission
to the hospital in April 1963. At first she had
developed a cyst on top of her head which
was cauterized and seemed to disappear.
Shortly thereafter, a recurrence about 2 cm
in diameter was removed surgically. I n 1959

No. 2

TUMORS
OF LOWER
HAIRSHEATH

Holmes

24 I

FIG. 7. Trichochlamydoacanthoma. Epithelial nests of lower hair sheath epithelium in the

dermis contain clear cells such as are sometimes seen in trichochlamvdocvsts. Keratinization is
accomplished without a granular cell layer (H and E, ~7.50).
I

a regrowth of the tumor measured 4 x 5 cm.

Treatment was refused by the patient until
April 24, 1963 when, because of chronic blood
loss, she submitted to the removal of a solid
ulcerated lesion measuring 2 x 10.5 x 11
cm (Fig. 12 B). The tumor had eroded the
outer table of the skull over a 5 x 9 cm area
but not the inner table. Grossly the margins
of the tumor were rounded. Microscopically
the lesion comprised islands of clear cells
with a few islands of dark cells as well. Fat
and glycogen were present in the tumor epithelium. Mitoses were not numerous and there
were no individual-cell infiltrating areas such
as in case 6. dn spite of its apparent histologic
differentiation, the tumor had metastasized to
an excised preauricular lymph node. The
lymph node was completely replaced by tumor which faithfully reproduced vitreous
membranes in its desmoplastic stroma (Fig.
12 A).
Subsequently the lesion recurred and grew
to its original size on 3 occasions following
x-ray-induced regressions (Fig. 12 C). Besides
the large lesion on the scalp at present, the
patient has a small nodule, less than 1 cm
in diameter, in the middle of her forehead.

DISCUSSION
The origin of epidermal cysts has been ascribed to (1) epidermal inclusions secondary to trauma, (2) rudimentary epithelial
rests and (3) obstruction to the outer portion
of the orifice of the hair f0llicle.~7The latter
mode of origin is an attractive hypothesis particularly for the epidermal cyst of Fig. 2 not
only because it has been the mode of origin
of some of the skin cysts of hairless micez6but
because of the single focus of sebaceous gland
attachment to the cyst wall. Otherwise one
would have to postulate the de novo development of the sebaceous gland from a traumatic
inclusion or an epithelial rest; however, it
seems unlikely that epithelium possessing such
a developmental potential would produce no
more than one sebaceous gland.
I n contrast, the trichochlamydocyst of Fig. 4
has multiple hair germs in addition to the
anagen hair budding from it so that the c y s ~
epithelium in this case must possess the ability to form hair in conjunction with nearby
dermal papillae of the mesoderm. That both

242

CANCER
February 1968

VOl. 21

FIG. 8. Case 4. Recurrent trichochlainydocarcinoina. A, relatively benign appearing dark cell

squamous pattern resembles telogen phase of lower outer hair sheath (H and E, x300). B
(inset), gross appearance of the sectioned recurrent tumor (x2).

epithelium and mesoderm are needed for the

development of hair has been well estab1ished;Zp 5 however, it has not been established
definitely whether the hair germ induces formation of the dermal papilla or vice versa
since they appear at about the same time in
embryonal development25 and in wound healing.2, 5
Oliver29 observed the regeneration of dermal papillae of normal size after their surgical
removal from rat vibrissal follicles. Even the
entire lower third of the hair root including
the matrix could be removed and small dermal papillae would form as long as outer hair
sheath epithelium remained intact. This and
the fact that the trichochlamydocyst of Fig. 4
has several dermal papillae associated with its
budding hair germs provide favorable evidence for epithelial induction of stroma. T h e
opposite postulate, that several papillae induced the formation of one cyst, is less tenable.
T h e mechanism of formation of tricholamy-

docysts is still open to speculation. T h e reason why all of them in the present series and
92% in another recent seriesz4 occurred on
the scalp is unknown. T h e situation is probably analogous to the preponderance of eccrine poromas on the palms and soles over
that of other parts of the body. Perhaps the
greater density of hair follicle population of
the scalp above that which obtains for the
rest of the body25 might be a factor. Also the
long anagen (proliferative) phase of the hair
cycle of the scalp7 might exert an influence
on the development of dormant rests, traumatic inclusions or occluded hair follicles, as
the case might be.
T h e preponderance of women over men
with trichochlamydocysts and trichochlamydocarcinomas suggests that the lanugo hair
follicle of the bald scalp is as unlikely to
produce these tumors as are the follicles of
other nonterminal hairy areas. Indeed it is
unusual to see a wen in the scalp of a bald
man. When it occurs, however, one might

No. 2

TUMORS
OF LOWER
HAIRSHEATH

Holmes

243

FIG. 9. Case 5. Trichochlamydocarcinoma. A (left), microscopic clear cell appearance of the

tumor resembles anagen phase lower outer hair sheath (H and E, ~ 3 0 0 ) .B (right upper inset),
gross appearance of the sectioned tumor (xl). C (right lower inset), lower portion of a normal
anagen hair follicle for comparison with tumor at the left (H and E, ~ 3 0 0 ) .

speculate that it began before balding was

complete in the area.
T h e finding that the epithelium of hair
sheath tumors contains neutral fat and glycogen as do sebaceous glands does not necessarily support a sebaceous gland origin of
the tumors. T h e lower outer root sheath of
the hair follicle is also positive for these substances. Montagna et al. have shown experimentally that the cells of the external sheath
differentiate into sebaceous cells in normal
mice in which sebaceous glands have been
totally extirpated with methylcholanthrenein-benzene.26 Furthermore, in hairless mice,
the cysts of the skin arise from several sources but, regardless of their source, undergo
first a sebaceous (fatty) transformation and
later form corneal laminae.e T h u s fatty transformation is evidently a secondary change or
a n inherent property of human trichochlamydocysts too.
Likewise, some of the trichochlamydocar-

cinomas showed an extensive clear cell change

similar to that of anagen phase hair follicles.
T h e induction of vitreous membranes by
these tumors further supports their lower
sheath origin. Vitreous membranes even were
produced in the desmoplastic stroma of the
metastatic lesion and served to differentiate a
clear cell metastasis of this type from any
other. T h e negative test for citrulline in these
tumors as well as in epidermal cysts indicates
that the keratin they contain is not derived
from the inner root sheath of the hair follicle
as it is in pilomatrixomas12 but is a product of
epiderm in the case of the epidermal cyst and
of the outer root sheath in the case of the hair
sheath tumors.
Trichochlamydoacanthoma, like trichochlamydocysts and carcinomas, will probably be
a lesion found mostly on the hairy scalp and
only exceptionally on other areas bearing
terminal hairs. It should not be confused histologically with hair folliculoma of other skin

244

CANCER
Fe brunry 1968

VOl. 21

FIG. 10 Case 5. Trichochlamydocarcinoma. Dark cell area of the tumor with nuclear
morphism. Note the caricature of vitreous membrane produced by the stroma (H and E, x??
:;

areas. Folliculoma consists of a central invagination of epidermis with many small hairproducing follicles entering it20 whereas trichochlamydoacanthoma does not produce
hair in its abortive follicles. Neither should
the lesion be confused with nevus epitheliomatosus sebaceus capitis, which consists of
rudimentary hair anlagen, cysts and sebaceous glands and does not possess a central
keratin-filled fossa.40
I t is likely that trichochlamydoacanthoma
of the scalp is related to keratoacanthoma of
other body regions since they share the property of a central keratin-lined fossa opening
onto the suface of the skin. Hutchinson13 in
1896 probably first described keratoacanthoma although he did not clearly differentiate
it from indolent skin cancer. Subsequently,
Ferguson-Smith36 in 1939 recorded the first
case of multiple primary squamous cell carcinoma with spontaneous healing. Credit for
the suggestion in 1936 that keratoacanthoma
is derived from the hair follicle is generally
accorded to MacCormack and Scarff,33 although it is now known that these lesions may

occur on nonhairy areas of the body as well.

I t has been repeatedly demonstrated that
keratoacanthoma is usually derived from the
outer root sheath of the upper third of the
hair follicle and contiguous surface epithelium.lO.33 Support for this site of origin has
come from the finding of early lesions and
from finding transitions from upper follicular
epithelium to tumor.i,9,18,2* Line11 and
M5nsson21 in 1957 illustrated a monstrous
follicle with a central horny core surrounded
by a proliferating upper follicular epithelium
sending off a few extensions into the surrounding dermis. They considered this to be
a n early stage of keratoacanthoma. I n contrast, Headington and Frenchll in 1962 illustrated a monster follicle quite like the configuration of the preceding one but without
a central keratin-filled fossa. Instead the proliferation consisted of clear cells or lower
sheath cells and they considered this to be the
early stage of their solid clear cell tumors
which they called tricholemmomas. Whether
these tricholemmomas are the naturally occurring counterparts of Ghadiallyslo experi-

No. 2

TUMORS
OF LOWER
HAIRSHEATH

Holmes

24 5

FIG. 11 Case 6. Trichochlamydocarcinoma. A, anaplastic area of tumor with areas of vitreous

membrane stroma (H and E, 2300). B (inset), mito& figure present in anaplastic area (H and
E, x750).

mentally produced type 2 and 3 keratoacanthomas which were solid tumors without
connections to surface epiderm and derived
from the deeper part of the hair follicle is
conjectural. In this connection, Whiteley39 in
1957 showed that the usual type of keratoacanthoma with a central keratin-filled crater
opening onto the skin occurred experimentally
during the anagen growth phase of the hair
cycle while the deeply placed tumors appeared
during the quiescent telogen phase.
Experimentally papillomas are the usual lesions produced on glabrous skin;lO however,
keratocanthoma-like lesions have been produced from the interfollicular areas of the
skin of chickens34 and occur naturally on the
glabrous skin in the human syndrome of multiple self healing epitheliomata of FergusonSmith. This syndrome may even involve the
mucous membranes.34 Yet, according to
Whiteley,3Q the lesions of keratoacanthoma
have a distribution related to the length of
the period of hair growth and are found most
frequently on the face and ears and to a lesser

extent on the scalp where telogen phase is

shortest. This distribution of lesions may be
explained by the fact that during a long telogen phase the hair germs are close to the surface and would be within reach of the carcinogenic agent39 and act as a reservoir for
3Q Keratoacanthomas are rare on glabrous
skin because carcinogens do not remain on
surface epithelium as long as they do in hair
follicles.l0,33 Thus keratoacanthomas and carcinomas in pitch workers arise on the hairy
skin of the forearm and hand but not on the
palm even though the latter comes into more
direct contact with the ~arcin0gen.l~
A synthesis of the facts would lead one to
believe that although the hair follicle may act
as a reservoir for carcinogens and thus take
part in the formation of keratoacanthoma,
upon other occasions, it must be the surface
epithelium which is stimulated to proliferate.
Certainly it must be the surface epithelium
that produces the rare glabrous skin tumors
and laryngeal mucous membrane tumors of
the Ferguson-Smith syndrome. Likewise it also

246

CANCER
February 1968

VOl. 21

FIG. 12 Case 7. A (left), Preauricular lymph node containing a clear cell metastasis. Note
the vitreous membranes produced by the stroma of the lymph node (H and E, ~300).B (upper
right inset), clinical appearance of the tumor before surgical excision. C (lower right inset),
clinical appearance of the tumor following second regrowth after surgery and first regrowth
after x-ray therapy.

may be mainly responsible for some of the

tumors of hair-bearing skin, the surface epithelium of which has been demonstrated to
retain its embryonal potential of hair formation. This is exemplified by the massive regeneration of pilosebaceous units which occurs yearly from the regenerated skin of deer
antlers.3 It also occurs experimentally in
wound healing where the wound has been
prevented artificially from contracting and
covering itself with old instead of new skin
and hair follicles.2~6 In a tumorous proliferation the epidermis may merely stop short of
complete hair formation after producing infundibular epithelium of the upper hair follicle. This proliferation then would take the
form of a keratoacanthoma with its own grotesque infundibulum (central keratin-lined
fossa).
The unusual finding reported by Worringer
and Laugiel-41 that a regressing keratoacanthoma in one instance was capable of producing complete pilosebaceous units merely

indicates the embryonal potential of the crateriform epithelium and not its usual behavior.
Just as keratoacanthoma might be considered a tumorous proliferation which stops
short after the production of the infundibulum of the hair follicle, trichochlamydoacanthoma may be considered a tumorous
proliferation of the surface epiderm which
goes one step further and produces outer root
sheath epithelium of the lower hair follicle.
This would not be a surprising form of neoplasia for the specialized skin of the scalp to
take in view of its highly characteristic propensity for producing other tumors of the
lower follicle such as trichochlamydocysts and
carcinomas.
T h e stated incidence of carcinomas arising
in skin cysts varies from 0.5% to 9.20/,.17Coll i w 8 in a review of the literature to 1936,
found that 91% of the malignant cysts were
located in the scalp. This figure strongly reinforces the impression that these lesions of

No. 2

TUMORS
OF LOWER
HAIRSHEATH

Holnzes

247

the scalp probably represent a different en- but none metastasized. Likewise, Peden30 retity from those reported elsewhere on the ported 13 cases of squamous cell carcinoma
body with the exception perhaps of those arising in sebaceous cysts. Of the seven in
from other regions bearing terminal hairs. the scalp only one recurred 2 years after
Lack of good photomicrographs in the lit- excision. The two cases of metastasizing leerature hinders adequate interpretation of sions he reported were not in the scalp. Nurmwhat the other 9% of lesions represent. There- berger28 in 1938 reported two cases of carfore, they will not be considered further. Only cinoma arising in epithelial cysts with
the scalp lesions of previous authors will be generalized metastasis; however, neither case
considered.
was a scalp tumor.
The sex incidence of trichochlamydocarThe only case of probable metastasizing
cinomas is heavily weighted toward the fem- trichochlamydocarcinoma in the literature is
inine side judging from the few published one of the two cases of scalp tumors reported
series where these lesions are classified as to by Seff and Berkowitz35 in which there were
age, site and sex. Jones17 reported seven of several recurrences with enlarged neck nodes
eight cases to be in women. Bishops,4 Ped- and death due to carcinomatosis. T o this, the
ens30 and the present series each had six present case series adds one recurring and one
women in seven cases and Lund23 recorded two metastasizing tumor in seven.
cases in women. Thus the ratio of women to
Certainly metastasis is rare in trichochlamymen reported having this tumor is 31:4 or docarcinoma. Does this mean that there are
almost 8:l. This figure is quite close to the two categories of solid scalp tumors, a trichoratio of 7:l of women to men found for tri- chlamydoadenoma as well as carcinoma? It
chochlamydocysts in the present series. The may be tempting to draw a dividing line beaverage age in Jones17 series was 65 and in tween those solid tumors with, and those
the present series is 75.
without, cellular anaplasia; however, of the
Like trichochlamydocysts, trichochlamydo- present series case 4 without anaplasia recurcarcinomas occur most often in the scalps of red and case 5 with anaplasia did not. Furelderly women but, when a nodule does occur thermore, the huge tumor of case 6 with the
in the masculine scalp, it has the same chance greatest anaplasia of all did not metastasize
of being cancerous as it does in a woman. as did the same sized lesion of case 7 having
Taking the present cases of trichochlamydo- less anaplasia. Therefore, it is difficult to precarcinoma which occurred during the same dict behavior on a histologic or even a size
5-year period in the same hospital as did the basis with the present limited number of retrichochlamydocysts, the figures are 32:3 or ported cases.
over 1O:l ratio of benign to malignant tuFor this reason, for treatment all solid
tumors of the scalp should be considered
mors,
The criteria for malignancy of these solid potentially dangerous and enlarging wens
tumors of the scalp of hair sheath origin has of the scalp should be viewed with suspicion
varied with different authors. Of Jones17 nine since generally in clinical wens there is a
cases, which all occurred on the scalp with one to ten chance of malignancy if only in the
the exception of 1 case without any clinical sense of progressive growth and eventual inhistory, all presented a rather benign histol- vasion of the skull. The chance of metastasis
ogic appearance similar to the present case may not be very great but the possibility does
4 (Fig. 8 A). Most of his patients tumors had exist. At the time of surgery incision of the
been present for many years. After excision scalp nodule should tell the surgeon whether
there was one definite and one possible recur- he is dealing with a trichochlamydocyst which
rence in the series. From this, Jones17 con- may be simply shelled out or a trichochlamycluded that the tumors were benign but that docarcinoma which should be removed with
progression to a true malignant epithelioma some of the surrounding tissue to prevent
remained a possibility. Also Lund23 who clas- recurrence.
sified these tumors as subepidermal acanthomas considered them benign without metasCONCLUSIONS
tasizing potential.
On the other hand, Bishop4 in 1931 reTrichochlamydocysts, trichochlamydoacported 11 epidermoid carcinomas arising in anthoma and trichochlamydocarcinoma are
sebaceous cysts. Seven were in the scalp, tumors derived from the lower outer root

248

CANCER
February 1968

sheaths of hair follicles, particularly of the

scalp and occur predominantly in elderly
women. Trichochlamydoacanthoma is a singular rare tumor never having been reported
before the present case. Since the lesion was
excised, it is not known whether, like its

Vol. 21

counterpart, keratoacanthoma of other body

regions, it is capable of regression. Trichochlamydocarcinoma should not be shelled out
like trichochlamydocysts but should be removed with a margin of the surrounding tissue to prevent recurrence.

REFERENCES
1. Baer, R. S., and Kopf, A. W.: Keratoacanthoma.
In Year Book of Dermatology, 1962-1963 series. Chicago, The Year Book Publishers, pp. 7-41.
2. Billingham, R. E.: A reconsideration of the
phenomenon of hair neogenesis, with particular reference to the healing of cutaneous wounds in adult
mammals. In T h e Biology of Hair Growth, W. Montagna and R. A. Ellis, eds. New York, Academic Press,
1958; pp. 451-468.
3. _ _ , Mangold, R., and Silvers, W. K.: T h e
neogenesis of skin in the antlers of deer. Ann. N.1.
Acad. S C ~83:491-498,
.
1959.
4. Bishop, E. L.: Epidermoid carcinoma in sebaceous cysts. Ann. Surg. 93:109-112, 1931.
5. Breedis, C.: Regeneration of hair follicles and
sebaceous glands from the epithelium of scars in the
rabbit. Cancer Res. 14: 575-579, 1954.
6. Broders, A. C., and Wilson E.: Keratoma-a
lesion often mistaken for sebaceous cyst. Surg. Clin.
N. Am. 10:127-130, 1930.
7. Calnan, C. D., and Haber, H.: Molluscum sebaceum. J. Path. Bact. 69:61-66, 1955.
8. Collins, D. C.: Carcinoma originating in sebaceous cysts. Canad. Med. Assn. J . 35:370-372, 1936.
9. Fisher, B. K., and Elliott, G. B.: On the origin
of keratoacanthoma-Reflections on an unusual lesion.
Canad. Med. A m . I. 93272-273, 1965.
10. GhadiaIly, F. N.: T h e role of the hair follicle
in the oricrin and evolution of some cutaneous neoplasms of man and experimental animals. Cancer 14:
801-816, 1961.
11. Headington, J. T., and French, A. J.: Primary
neoplasms of the hair follicle. Arch. Derm. 86:430-441,
1962.
12. Holmes, E. J.: A histochemical test for citrulline
of the carbamido-diacetyl reaction to
-Adaptation
histologic sections with positive results in pilomatrixomas (calcifying epitheliomas). J. Histochem. Cytochem.
In press.
13. Hutchinson, J.: Records of the demonstrations
at the clinical museum-The crateriform ulcer-microscopic examination. Arch. Surg. 7:88-89, 1896.
14. Jenkins, W.: Dermatoses among Gas and T a r
Workers. Bristol, J. Wright & Sons, 1948 (quoted by
Calnan).
15. Idem. (quoted by Ghadiallylo).
16. Idem. (quoted by Whiteley30).
17. Jones, E. W.: Proliferating epidermoid cysts.
Arch. Derm. 94:ll-19, 1966.
18. Kalkoff, K. W., and Macher, E.: Zur Histogenese
des Keratoakanthoms. Hautarzt 128-15, 1961.
19. Kligman, A. M.: T h e myth of the sebaceous
cyst. Arch. Derm. 89: 253-256, 1964.
20. -:
Neogenesis of human hair follicles. Ann.
N.Y. Acad. Sci. 83:507-511, 1959.
21. Linell, F., and Mlnsson, B.: Molluscum pseudocarcinomatosum. Acta Radiol. 48:123-140, 1957.
22. Love, W. R., and Montgomery, H.: Epithelial
cysts. Arch. Derm. 47:185-196, 1943.

23. Lund, H. Z.: Tumors of the Skin; Sec. 1, Fax.

2. Washington, D. C., Armed Forces Institute of Pathology, 1957; pp. 246-247.

24. McGavran, M. H., and Binnington. B.: Keratinous cysts of the skin-Identification and differentiation
of pilar cysts from epidermal cysts. Arch. Derm. 94:
499-508, 1966.
25. Montagna, W.: Summary. In T h e Biology of
Hair Growth, W. Montagna and R. A. Ellis, eds. New
York, Academic Press, 1958; pp. 487-500.
26. , Chase, H. B., and Melaragno, H. P.: T h e
T h e formation of cysts and
skin of hairless mice-I.
the distribution of lipids. J . Invest. Derm. 19:83-94,
1952.
27. Montgomery, H.: Dermatopathology, vols. I and
11. New York, Hoeber Medical Division, Harper and
Row, 1967.
28. Nurmberger, W.: Die Epithelcysten des ausseren
Haut und die aus ihnen hervorgehenden Geschwiilste.
Frankf. 2. Path. 52:488-472, 1938.
29. Oliver, R. F.: Histological studies of whisker
regeneration in the hooded rat. J. Embryol. Exp.
M o ~ p l i .16231-244, 1966.
30. Peden, J. C.: Carcinoma developing in sebaceous
cysts. Ann. Surg. 1136-1147, 1948.
31. Rigdon, R. H.: Histopathogenesis of keratoacanthoma induced with methylcholanthrene. Arch.
Derm. 81:381-387, 1960.
32. Rook, A.: Rapport-KCrato-acanthome et Ctats
pseudocarcinomateux voisins. Lausanne, IX Congres.
Assoc. Derm. Syph. Langue Franc., 1956; pp. 221-231.
33. -and Champion, R. H.: Keratoacanthoma
(National Cancer Institute Monograph 10). Washington,
D.C., U.S. Government Printing Office, 1963; pp. 257274.
34. Rossman, R. E., Freeman, R. G., and Knox,
J. M.: Multiple keratoacanthomasA case study of the
eruptive type with observations on pathogenesis. Arch.
Derm. 89:374-381, 1964.
35. Seff. I., and Berkowitz. S.: Carcinomatous depeneration of sebaceous cysts. Surg. Gynec. ObstetT023:
469-473, 1916.
36. Smith, J. F.: A case of multiple primary squamous-celled carcinoma of the skin in a young man,
with spontaneous healing. Brit. J . Derm. 46:267-272,
1934.
37. Staricco, R. G.: T h e nielanocytes and the hair
follicle. J . Invest. Derm. 35:185-194, 1960.
38. Warvi. W. N., aud Gates, 0.: Epithelial cysts
and cystic tumors of the skin. A m . J. Path. 19:765-783,
1943.
39. Whiteley, H. J.: T h e effect of the hair growth
cycle on experimental skin carcinogenesis in the rabbit.
Brit. J . Cancer 11:196-205, 1957.
40. Wolters, M.: Uber einen Fall von Naevus epitheliomatosus sebaceus capitis. Arch. Derm. Syph. 101:
195-208, 1910.
41. Woringer, F., and Laugier, P.: NCoformation
pilo-sbbacCe dans une cicatrice de kbrato-acanthome.
Ann. Anat. Path. 435544560, 1959.