COL Purnima Sau, M.D., MC, USA,* COL George P. Lupton, M.D., MC, USA,t
and James H. Graham, M.D.$
Background. Pilomatrix carcinoma, a malignant
variant of pilomatrixoma, is extremely rare. The authors
report 20 patients with pilomatrix carcinoma and review
the pertinent literature.
Methods. Tumors showing histologic features of pi-
lomatrix carcinoma were selected from the files of the
Armed Forces Institute of Pathology. Clinical data of the
20 selected patients were reviewed, and follow-up infor-
mation was obtained. Sections stained with hematoxylin
and eosin were studied in all patients. Special stains were
used in selected patients.
Results. Pilomatrix carcinomas were asymptomatic
dermal and subcutaneous masses with a predilection for
the posterior neck and back. Tumors varied in size, from
1-10 cm (mean, 4 . 6 cm), and occurred more often in mid-
dle-age men, with a ma1e:female ratio of 4 : l (mean age, 45
years). Histologically, pilomatrix carcinomas are charac-
terized by sheets and islands of proliferating atypical ba-
saloid cells with an infiltrating border. Transition to
squamous cells, clear cells, areas of necrosis and mitoses
often are seen. Keratinization with formation of keratin
cysts, shadow cells, and trichohyalin and keratohyalin
granules are found in all tumors, in conjunction with cal-
cification and foreign body giant cell reaction, just as are
seen in benign pilomatrixoma. Follow-up of 17 patients
revealed local recurrence in 10 (59%), with multiple re-
currences in 3. One patient had pulmonary metastasis,
and one died of extensive local spread of the tumor.
Conclusion. Pilomatrix carcinomas are locally ag-
gressive tumors that have a tendency to recur, especially
when they are incompletely excised. Greater anaplasia
and deep soft tissue infiltration were associated with a
higher incidence of recurrence and death. Wide excision
is the preferred treatment. The role of radiation therapy
is unclear. Cancer 1993: 71:2491-8.
Key words: pilomatrixoma, pilomatrix carcinoma, basa-
loid cells, shadow cells, clear cells.
Pilomatrixoma was first described in 1880 by Malherbe
and Chenantais’ as a ”calcifying epithelioma” that was
thought to be derived from the sebaceous gland. In
1949, Lever and Griesemer2 suggested that the origin of
the tumor was hair matrix cells. Forbis and Helwig3 re-
viewed a series of 228 patients in 1961 and proposed
the currently accepted name of ”pilomatrixoma.”
Pilomatrixomas are slow-growing, benign dermal
or subcutaneous tumors, 0.5-5.0 cm in diameter. How-
ever, most such tumors measure 1-3 cm.2 These tumors
are found most frequently in young age groups. Forty
percent of the tumors occur in individuals younger than
10 years of age, and more than 60% are diagnosed dur-
ing the first two decades of life. The ma1e:female ratio is
approximately 2:3. The tumor involves (in decreasing
frequency) the head, upper extremity, neck, trunk, and
lower e~tremity.~ Light and electron microscopic and
histochemical studies support the hair matrix origin of
this t ~ m o r . ~ , ~ , ~ , ~
The malignant variant of pilomatrixoma (piloma-
trix carcinoma) is extremely rare. Only 24 patients have
been reported in the literature. We report 20 patients
with pilomatrix carcinoma, one of whom has been pre-
viously reported. This study was done to delineate the
histologic features, differentiate them from their benign
counterpart, determine the clinical and biologic behav-
ior, and recommend appropriate therapy.
Materials and Methods
From the *Department of Dermatology and Pathology, Walter
Reed Army Medical Center, Washington, DC; the tDepartment of
Dermatopathology, Armed Forces Institute of Pathology, Washing-
ton, DC; and the $Division of Dermatopathology, Department of Pa-
thology, Scripps Clinic and Research Foundation, La Jolla, California.
The opinions or assertions contained herein are the private
views of the authors arid not to be construed as official or as reflecting
the views of the U.S. ,4rmy or the Department of Defense.
Address for reprints: Purnima Sau, M.D., Dermatology Service,
Walter Reed Army Medical Center, Washington, DC 20307-5001.
Accepted for publication November 23, 1992.
All tumors designated as pilomatrixoma (702 patients),
adnexal tumor and adnexal carcinoma (650 patients),
and adnexal tumors of pilar origin (98 patients) were
retrieved from the files of the Armed Forces Institute of
Pathology. Tumors with histologic features of piloma-
trixoma that exhibited unusual features, such as exces-
sive basaloid cell proliferation, cytologic atypia, deep
soft tissue infiltration, rapid growth, and recurrence,
were studied. Twenty patients were selected from this
CANCER April 25, 2993, Volume 71, No. 8
group. Available clinical data were reviewed. A ques-
tionnaire was sent to the contributing physicians and to
the patients to obtain follow-up information. Sections
stained with hematoxylin and eosin were studied in all
patients. Special stains were used in selected patients:
periodic acid-Schiff with and without diastase diges-
tion, colloidal iron with and without hyaluronidase di-
gestion, alcian blue at pH 2.5 and 0.4, Manuel reticu-
lum, and Movat pentachrome. Peroxidase-antiperoxi-
dase techniques for cytokeratin using polyclonal
antibodies directed against keratin protein, carcinoem-
bryonic antigen, and S-100 protein were used in 6 pa-
The clinical data are summarized in Table 1. The tumors
were described as slow-growing, asymptomatic masses
or cysts. Seven patients noticed recent enlargement of
the tumor, two of which were rapidly growing. The
duration of the tumors before surgery in 15 patients
ranged from 4 months to 10 years. The clinical diag-
noses submitted before histologic examination included
cyst (7), mass or nodule (B), and lipoma (2). They oc-
curred in 16 male patients and 4 female patients (M:F,
4:1), ranging in age from 10 to 88 years (mean, 45
Table 1. Clinical Features of Pilomatrix Carcinoma
years). The patients were white, with the exception of
one black and one Hispanic. Sites of involvement in-
cluded: neck (7), back (4), face (3), upper extremities (3),
and one each on the occipital scalp, breast, and buttock.
The tumors showed a predilection for the posterior
neck and back. None were found on the lower extrem-
ity. The tumors varied in size from 1 to 10 cm (mean,
Gross. Most tumors were circumscribed dermal
and subcutaneous nodules or cystic masses. The epi-
dermis overlying the tumor was absent in six patients,
thinned and elevated in two, ulcerated in four, and un-
remarkable in the others. The consistency of the tumors
varied from soft and friable to firm and sometimes hard
because of the presence of calcification. The cut sur-
faces were gray-white to tan or yellow and lobulated.
Some were partially cystic and were filled with caseous,
granular, chalky, or gelatinous material. The initial
pathologic diagnoses in 14 patients included calcifying
epithelioma of Malherbe or pilomatrixoma (7), malig-
nant pilomatrixoma (2), adnexal carcinoma (2), se-
baceous epithelioma (l), carcinoma in a dermoid cyst
(l), and squamous cell carcinoma (1).
Microscopic. The tumors were characterized by
proliferating basaloid cells arranged in sheets, irregular
3 Y r
Left post neck
Left lower back
Right occipital scalp
Right post neck
Left upper neck
Left lower eyelid
Right post neck
post: postenor; NK not known.
* Previously reported in reference 14
Pilomatrix CarcinomalSau et al.
islands, and bands (Fig. 1). The basaloid cells infiltrated
the entire dermis and extended into the subcutaneous
fat (Fig. 2). Deep fascia was infiltrated in three patients
(Patients 1, 9, and 114) and skeletal muscle in two (Pa-
tients 13 and 14). The peripheral border of the tumors
were infiltrative in 13 patients (Figs. 3 and 4). In five
patients, the tumors demonstrated a predominantly
pushing border. Holwever, on closer inspection, exten-
sion of small lobules and strands of tumor into the
surrounding stroma was found. In 3 of 11 patients (Pa-
tients 3, 8, and 18) the tumor showed focal connection
with the epidermis or hair follicle. The tumor extended
into the epidermis, resulting in ulceration in four pa-
tients (Patients 10, 16, 18, and 19). The basaloid cells
were large and contained a small amount of pale cyto-
plasm and hyperchromatic nuclei. The nuclei fre-
quently were vesicular and had prominent nucleoli (Fig.
5). The degree of ainaplasia was variable.
In the most actively proliferative basaloid cell areas,
the mitoses varied from 12 to 62 per 10 high power field
(hpf), with an average of 31/10 hpf. Areas of necrosis
were noted frequently. The basaloid cells demonstrated
keratinization and squamous differentiation in the form
of squamous pearls or nests, horn cysts, shadow cells,
and sometimes translucent or hyalinized keratinous
masses (Fig. 6). The keratinization was sometimes
abrupt and at other times gradual through several
layers of squamous, epithelium to laminated keratin. In
several patients, t'he basaloid cells acquired a large
amount of clear cytoplasm before undergoing keratini-
zation (Fig. 7). Many tumor lobules demonstrated cystic
spaces with a rim of basaloid cells at the periphery.
These cystic spaces contained abundant necrotic debris,
keratinous material, calcification and shadow cells.
Figure 2. Islands of basaloid cells infiltrate the dermal collagen and
subcutaneous fat (H & E, original magnification Xl5).
In three patients (Patients 3, 6, and 18), the tumor
resembled a keratinizing basal cell carcinoma, display-
ing irregular islands of keratinizing basal cells with cen-
Figure 1. Basaloid cells infiltrate throughout the tumor mass in
sheets and bands with areas of necrosis forming cystic spaces (H &
E, original magnification XlO).
Figure 3. Pilomatrix carcinoma demonstrates infiltrative peripheral
border and extension of the tumor into the skeletal muscle (lower
end) (H & E, original magnification Xl5).
CANCER April 25, 2993, Volume 71, No. 8
Figure 4. Higher magnification of Figure 3 demonstrates islands of
basaloid cells surrounded by fibrocollagenous stroma (H & E,
original magnification X60).
tral necrosis, peripheral nuclear palisading, and retrac-
tion spaces between the tumor islands and the stroma.
Several areas of transition to shadow cells also were
found in these tumors (Fig. 8).
Trichohyalin granules or trichohyalin-like eosino-
philic globules were observed in 13 patients. These
granules were found within the basaloid cells, espe-
cially in the clear cell and keratinous areas. Keratohya-
lin granules were found less frequently. Shadow cells
were identified in all patients. They were less frequent
in areas showing prominent basaloid cell proliferation
and especially in the recurrent tumors. Three tumors
(Patients 7, 10, and 20) had marked anaplasia with
brisk mitoses (as high as 62/10 hpf) (Fig. 9). These tu-
Figure 6. Pilomatrix carcinoma showing basaloid cells, squamous
nests, shadow cells, keratin cyst, and foreign body giant cell reaction
(H & E, original magnification XlOO).
mors also demonstrated large areas of squamous differ-
entiation and shadow cell formation. These shadow
cells formed a nested pattern (Fig. 10) instead of the flat
sheet-like pattern usually observed in benign piloma-
trixoma. Abundant foreign body giant cell reaction was
observed in association with keratin, shadow cells, and
The tumor islands were surrounded by a moder-
ately cellular fibrocollagenous stroma. A small number
of lymphocytes, histiocytes and plasma cells sprinkled
the stroma. Vascular invasion (Fig. 11) was found in
one patient (Patient 7) and perineural invasion in another
Figure 7. Basaloid cells showing transition to clear cells, central area
of necrosis, and fibrocollagenous stroma (H & E, original
Figure 5. Basaloid cells show pleomorphism. vesicular nuclei, and
prominent nucleoli (H & E, original magnification X400).
Pilomatrix CarcinomalSau et al.
Figure 8. Pilomatrix carcinoma demonstrating islands of keratinizing
basal cells, peripheral palisading of the nuclei, and loose fibroblastic
stroma. Shadow cells and foreign body giant cell reaction are noted
in the upper middle portion of the photomicrograph (H & E, original
Results of Histochemical Procedures. Periodic
acid-Schiff stains before and after diastase digestion
were negative in all 'but two patients. Focal positive reac-
tion was noted in the more differentiated areas of these
two tumors, and thLe substance was removed by dias-
Colloidal iron with and without hyaluronidase di-
gestion, and alcian blue stains at pH 2.5 and 0.4 demon-
strated the presence of mucin in the stroma in the imme-
diate vicinity of the tumor masses. The intensity of the
staining reaction with colloidal iron was reduced after
hyaluronidase digestion and alcian blue at pH 0.4. Elas-
Figure 10. Anaplastic basaloid cells and shadow cells showing a
nested pattern (Patient 7, H & E, original magnification X250).
tic tissue was absent in the tumors stained with Movat
pentachrome. Fine reticulum fibers were demonstrated
in the stroma around the epithelial islands in a few pa-
tients, but this feature was not prominent.
Immunohistochemical staining for cytokeratin was
positive in the areas of squamous differentiation, kerati-
nization, and in the shadow cells; it was negative in the
basaloid cells. The immunohistochemical stains for
S-1 00 protein and carcinoembryonic antigen were nega-
Treatment and Follow-up. Follow-up data are
summarized in Table 2; information was available in 17
patients. The duration of follow-up ranged from 5
months to 18 years. Ten (59%) tumors recurred within
Figure 9. Pilomatrix carcinoma (Patient 7) demonstrates marked
anaplasia and many mitoses (H & E, original magnification X300).
Figure 1 1. Pilomatrix carcinoma demonstrates vascular invasion
(Patient 7, H & E, original magnification XlOO).