SPINDLE CELL LIPOMA

M. ENZINGER,
FRANZ MD," AND DEANA. HARVEY,
MC, USA+

Spindle cell lipoma is a specific type of lipoma that is easily mistaken for a
lipsarcoma. An analysis of 114 cases of this tumor from the files of the Armed
Forces Institute of Pathology reveals that it occurs chiefly in male patients
between 45 and 70 years of age and affects the regions of the shoulder and
posterior neck almost exclusively. Microscopically, it consists of an intricate
mixture of lipocytes and uniform spindle cells within a matrix of mucinous
material traversed by a varying number of birefringent collagen fibers. Ultra-
structural studies in one case support the fibroblastic nature of the spindle
cells. Followup information obtained in 63 patients with this lesion revealed
a uniformly favorable clinical course, indicating that local excision is the treat-
ment of choice, and that there is no need or reason for radical surgical
procedures.
Cancer 36:1852-1859, 1975.

0 VER T H E PAST YEARS O N E OF US(F. M. E.)

has seen in consultation a large number
of lipomas that differed considerably in their
microscopic appearance from the ordinary
lipoma and, because of their unusual features,
were frequently misdiagnosed as liposarcoma.
Yet, despite their cellularity, there was no
evidence that these tumors behaved in an ag-
gressive manner or had a tendency to recur
locally. Judging from our material, spindle
cell lipoma is a relatively common lesion that,
to our knowledge, has never been described
adequately in the literature.
T h e distinguishing clinical and morpho-
logical characteristics of spindle cell lipoma
are reviewed here, and an attempt is made to
provide practical criteria for recognizing this
entity and distinguishing it from liposarcoma.
MATERIALS
AND METHODS
All cases were selected entirely on the basis
of their histologic picture from material sub-
mitted to the Armed Forces Institute of Pa-
thology by both military and civilian con-
tributors during the period from 1948 through
1974. In all cases, the clinical records were re-
From the .Division of Soft Tissue Pathology, Armed
Forces Institute of Pathology, and the tDepartment
of Pathology, Walter Reed Army Medical Center,
Washington, DC.
Address for reprints: F. M. Enzinger, MD. Armed
Forces Institute of Pathology, Washington, DC 20306.
The opinions or assertions contained herein are
the privatc views of the authors and are not to be
construed as official or as reflecting the v i e w of the
Department of the Army or the Department of Defense.
Received for publication April 25, 1975.
1852
viewed, and the pertinent clinical and labora-
tory data were recorded.
Sections stained with hematoxylin and eosin
were studied in each case. I n addition, the
following special staining procedures were
used on selected cases: the Masson trichrome
stain and Snook's reticulum preparation for
the demonstration of collagen; the alcian blue
stain with and without hyaluronidase diges-
tion for mucopolysaccharides; and the alde-
hyde-fuchsin and Giemsa preparations for
mast cells. All stains were performed accord-
ing to methods described in the AFIP Manual
of Histologic and Special Staining Technics.2
In one case a portion of a fresh, surgically
removed specimen was initially fixed in picric
acid-paraformaldehyde. T h e specimen was
then rinsed in phosphate buffer, postfixed in
2yo osmium tetroxide, dehydrated in a series
of graded alcohols, and embedded in epoxy
resin (Epon 812). Sections 0.5 to 1 pm thick,
stained with toluidine blue 0, demonstrated
tissue representative of the tumor. T h i n sec-
tions were stained with uranyl acetate and
lead nitrate and examined with an electron
microscope.
Followup information ranging from 1 year
to 22 years (average 3 years) was available on
63 patients of this series. T h e remainder of
the cases were either lost to followup or were
too recent to be useful for followup purposes.
RESULTS
Clinical Observations
Characteristically, 104 (917,) of the 114
patients with spindle cell lipomas were male
No. 5 SPINDLECELL’LIPOMA
and 10 (9%) female. T h e ages at the time of
excision ranged from 25 to 81 years, and had
a mean of 56 years. Eighty-three percent of
the patients were between 46 and 81 years.
T h e age distribution of spindle cell lipomas is
given in Fig. 1.
I n most cases the neoplasm occurred in the
dermis or subcutis as a single, slow-growing,
superficially or deeply located nodule. Of the
114 cases, 53 affected the shoulder or the back,
and 41 the posterior neck. Other anatomical
sites were rare. Eight lesions were located in
the extremities, particularly in the upper arm,
6 in the trunk, other than the shoulder and
neck regions, and 2 in various portions of the
head. I n 4 cases the location was not given.
Most of the lesions were painless. Many
had been present for considerable periods of
time. T h e median preoperative duration was
3 years; the range was from 1 month to 20
years. A familial history of Iipoma, affecting
male patients only, was given in two cases.
Of the 63 patients who were followed from
1 to 22 years (average 3 years), 54 were alive
without evidence of recurrence or metastasis.
Nine had died of unrelated disease, 6 of myo-
cardial infarction, and 3 of various forms of
carcinoma.
FIG. 1. Age distribution of 114 patients with spindle
cell lipoma (mean 56 years).
Enringer and Haroq, 1853
Gross Observations
Most of the lesions were rounded or dis-
coid nodules that were well circumscribed. I n
rare instances they were less well circum-
scribed and infiltrated the underlying muscle
tissues. Grossly, the lesions were described as
a firm yellow, mottled grayish-yellow, or
yellowish-pink nodule that was often gelat-
inous or glistening on section. Their size
varied from 1.0 to 13 cm, and had a median
of 4.0 cm and a mean of 4.6 cm.
Light-Microscopic Observations
Typically, the lesion consisted of a fairly
well-circumscribed but rarely encapsulated
mass of mature fat cells that were separated
and partly replaced by groups of small, slen-
der spindle cells. In some cases, the prolifera-
tion of spindle cells was localized and affected
only a portion of the lipomatous growth
(Fig. 2); in others, it was diffuse and involved
almost the entire lesion, often concealing the
lipomatous nature of the tumor (Fig. 3). I n
general, the proliferated spindle cells were of
great uniformity, having a single elongated
nucleus and narrow, bipolar cytoplasmic proc-
esses. There was no lipoblastic activity, but in
rare instances one or two minute lipid vacu-
oles were seen within the cytoplasm of the
spindle cells. Mitotic figures were scarce. T h e
matrix surrounding the cells varied greatly
in appearance, depending upon the relative
amounts of mucoid material and collagen.
Some tumors, representing one end of the
morphological spectrum, consisted of mature
fat cells, separated by large amounts of muci-
nous material, a few reticulin fibers, and
sparse and widely scattered spindle cells (Fig.
4A). Others, at the other end of the spectrum,
were composed chiefly of a mixture of more
or less well-oriented spindle cells, thick bun-
dles of collagen, and a small number of in-
terspersed lipocytes (Fig. 4D). T h e appearance
of the majority of the cases, however, was
intermediate between these two extremes, and
consisted of a mixture of slender spindle
cells, hyaluronidase-sensitive,alcian-blue-posi-
tive mucinous material, and randomly ar-
ranged bundles of birefringent collagen (Fig.
4B and C) that stained a deep blue with the
Mason trichrome stain. Usually, the spindle
cells were oriented along the bundles of col-
lagen, sometimes with “palisading” of their
nuclei. There was no evidence of nerve sheath
derivation, however; in particiilar, the Bodian
1854 CANCER
November 1975 Vol. 36
. .._..

FIG. 2. Spindle cell

lipoma of the right
shoulder in a 55-year-
old man showing par-
tial replacement of the
fatty tissue by spindle
cell areas (H & E, ~ 1 0 ;
AFIP Neg. 74-8241).

stain prepared in nine cases, failed to reveal
neuri tes.
Mast cells, characterized by the presence of
Giemsa- and aldehyde-fuchsin-positiveintra-
cellular granules, were numerous in nearly all
cases. Small aggregates of lymphocytes were
seen only occasionally.
T h e vascular pattern was usually incon-
spicuous and consisted of fairly thick-walled
vessels of small or intermediate size. Five of
the neoplasms, however, differed from the re-
mainder of the cases by the presence of a
prominent vascular pattern with branching,
endothelium-lined sinusoidal channels that
divided the tumor into irregular lobules of
small size. Some of these lesions superficially

FIG. 3. Spindle cell

lipoma composed of
mature fat cells sep-
arated by collagen-
forming spindle cells
(H & E, x7; AFIP Neg.
74-19729).
No. 5 SPINDLE
CELLLIPOMA - Enringer and Harvey 1855

FIG.4. Variations in cellularity and collagen content of spindle cell lipoma. A (top left). Tumor
removed from the left shoulder of a 61-year-old man (H & E, ~ 1 8 0 AFIP ; Neg. 74-8227). B
(top right). Same tumor as in Fig. 2. Note the uniformity and regular orientation of the
spindle cells and the mature appearance of the interspersed lipocytes (H & E, x 1 8 0 AFIP
Neg. 74-8239). C (bottom left). Tumor excised from the shoulder of a 64-year-old man. Most
of the lipoma is replaced by collagen-forming spindle cells of uniform appearance. The patient
was well and without recurrence 4 years after local excision (H & E, ~ 2 1 0 ;AFIP Neg. 74-8228).
D (bottom right). Fibrosarcoma-like picture in a spindle cell lipoma of the anterior chest wall
in a 67-year-old man who was well and without recurrence 4 years after removal by local exasion
(H & E, X19.5; AFIP N q . 73-3558).
1856 CANCER
November 1975
resembled a cystic lymphangioma or a heman-
giolxricytoma (Fig. 5).
Electron-Microscopic Observations
T h e tumor was composed predominantly
of spindle-shaped fibroblast-like cells with
long, polar cytoplasmic extensions arranged
in most areas in a parallel fashion; these cells
were separated by amorphous ground sub-
stance and bundles of collagen (Fig. 6). Sev-
eral large, uniloculated fat cells were present,
often near small blood vessels. Mast cells,
lymphocytes, plasma cells, and macrophages
were also noted occasionally. T h e fibroblast-
like cells showed a prominent rough endo-
plasmic reticulum, which was frequently di-
lated and contained an amorphous material.
They also contained a few oval to elongated
mitochondria, a well-developed Golgi ap-
paratus, prominent microfilaments, scattered
ribosomes, and numerous pinocytotic vesicles.
T h e nuclei were oval to spindle shaped, fre-
quently with rounded clefts. T h e chromatin
was evenly dispersed; a perinuclear lamina
was well developed and a single large nu-
cleolus was often apparent (Fig. 7). Many of
the fibroblast-like cells contained one to sev-
eral spherical, strongly osmiophilic lipid drop-
lets (Fig. 6 and 8). Most of the smaller lipid
droplets had an irregular, stellate border with
110 evidence of a limiting membrane. Larger
Vol. 36
FIG.5. A variant: of
spindle cell l i p 0'ma
simulating a vasciilar
neoplasm (H Lk E,
x120; AFIP Neg. 73-
3188).
lipid droplets appeared to be membrane-
bound, but this was difficult to determine
because of their marked electron density. Inclu-
sions that were less electron dense and pre-
sumably contained neutral fats were noted in
several cells, either alone or in addition to the
denser, more unsaturated lipid droplets. These
inclusions appeared to be membrane-bound
and measured u p to 3.4 pm. In addition to
occasional secondary lysosomes containing
whorled membranous structures and various
amounts of lipid debris, there were lipid drop-
lets that showed variability in staining and
internal structure, suggesting the possibility
that they, too, may represent secondary lyso-
somes of high lipid content. Also noted were
rare lipid droplets in the cytoplasm of the
endothelial cells.
T h e intercellular spaces contained collagen
fibrils, including a few bundles of abnormal,
long-banded collagen (with a periodicity of
approximately 1200 A).
Although most fat cells contained a single
large lipid inclusion, smaller lipid droplets
were frequently noted within the scant cyto-
plasm of the cell. A definite membrane be-
tween the large and smaller droplets was not
observed. T h e nuclei were markedly flattened
by the central lipid inclusion and contained
evenly dispersed chromatin with n o perinu-
clear lamella. T h e rim of cytoplasm contained
No. 5 SPINDLECELLLIPOMA - Enzinger and Haruey 1857

FIG. 6. Electron micrograph of a spindle cell lipoma present for approximately 6 years in
the right breast of a 58-year-old man. Two of the fibroblasts contain multiple lipid droplets,
of both the unsaturated (dark-staining) and the more saturated (light-staining) lipid type.
The spindle cells are separated by an amorphous ground substance and bundles of collagen
( ~ 7 7 0 0 ;AFIP Neg. 74-1051-1).

sparse, round to oval mitochondria, a few of ground. Sclerosing liposarcoma contains, in

which had small, densely osmiophilic inclu-
sions. Pinocytotic vesicles were numerous, and
only short segments of rough endoplasmic
reticulum and few free ribosomes were noted.
A well-developed basal lamina surrounded the
entire cell.
DISCUSSION
Although many of the tumors of this series
were thought to be liposarcoma by the initial
reviewer, clear distinction from a liposarcoma
seems possible if attention is paid to the char-
acteristic features of this tumor. These include
not only the great uniformity of the prolif-
erated spindle cells and the absence of lipo-
blasts, but also the presence of thick collagen
fibers within a more or less pronounced mu-
coid matrix. Myxoid liposarcoma, in contrast,
shows a more disorderly cellular picture con-
sisting of “signet-ring” and multivacuolar
lipoblasts, and a prominent plexiform capil-
lary pattern within a richly mucoid back-
addition to typical lipoblasts, multinucleated
giant cells that are surrounded and separated
by a dense and rather uniform meshwork of
delicate collagen fibrils. T h e terms myxo-
lipoma and fibrolipoma were sometimes em-
ployed to classify lipomas of the spindle cell
type, but we believe that these designations
should be reserved for those variants of lipoma
in which portions of the tumor are replaced
,by sparsely cellular mucoid material or col-
lagen. Angiolipoma, a tumor that usually OC-
curs in young adults and chiefly ,manifests
with multiple painful nodules in the upper
extremities,6 is readily recognized by the pro-
liferation of narrow vascular channels and,
frequently, the presence of microthrombi
within some of the vascular lumina.
I n some cases of spindle cell lipoma, palisad-
ing of the nuclei led to an erroneous diagno-
sis of neurilemoma or leiomyoma, but there
was n o evidence in our material suggesting
either neural or smooth muscle origin. Neither
1858 CANCER
November 197.5
- 74- 105-3).
was such an origin supported by the ultra-
structural findings.
Accurate interpretation of the spindle cell
lipoma is also facilitated by its striking pre-
dilection for the regions of the shoulder and
posterior neck and its almost exclusive occur-
rence in men older than 45 years. This is
significant, for lipomas in general have a less
characteristic distribution1 and occur more
commonly in women than in men.3.4 More-
over, according to Adair et al.’si series of 160
subcutaneoiis lipomas, they tend to affect a
younger age group (mean 41 years) than the
tumors of this series (mean 56 years). There
were no patients with multiple spindle cell
lipomas in our material, but in two cases
spindle cell lipomas were associated with typi-
cal lipomas at other sites.
T h e histogenesis and natural evolution of
these tumors is not clear, but-considering
Vol. 36
FIG. 7. Spindle cell
showing ultrastruc-
tural features of a fi-
broblast, including
elongated cytoplasmic
processes, lack of a
basal lamina, a few
small pinocytotic ves-
icles, and prominent
cytofilaments separat-
ing profiles of rough
endoplasmic reticulum
(~10,800; AFIP Neg.
their characteristic sex and age incidence-
it seems likely that they represent a specific
variant of lipoma rather than a lipoma with
secondary spindle cell proliferation. Yet, there
seems to be progressive increase in collagen
content during the course of the disease, as
indicated by the positive correlation of the
degree of collagen formation with the median
age of the patient and with the preoperative
duration of the neoplasm, respectively. Judg-
ing from the histologic appearance of cases
that are known to have been present for many
years, it seems unlikely, however, that a spin-
dle cell lipoma ever becomes transformed into
a typical parvicellular fibrolipoma. As with
other mesenchymal tumors, the histogenesis is
obscure, and one can only speculate whether
endocrine or hereditary factors provide the
stimulus for the growth of this tumor and are
responsible for its almost exclusive occurrence
No. 5 SPINDLECELLLIPOMA * Enringer and Harvey
FIG. 8. Fibroblast
with lipid droplets and
rounded nuclear clefts.
Variation in staining
within t h e l i g h t e r
stained lipid droplet
suggests secondary ly-
sosomes of high lipid
content (~12,500;AFIP
Neg. 74-1051-2).
in male patients between 45 and 70 years of
age. There is no evidence that the Occurrence
of this lesion is related to sudden gain or loss
in weight or other changes in the patient’s
state of health.
From the ultrastructural appearance of the
spindle cells and the loosely associated col-
lagen fibers, there seems to be little doubt that
the spindle cells are fibroblasts or cells closely
related to fibroblasts, possibly arising and dif-
ferentiating from perivascular stores of mesen-
chymal cells. Although mature adipocytes
develop from cells morphologically indistin-
guishable from fibroblasts (preadipose fibro-
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1. Adair, F. E., Pack, G. T., and Farrior, J. H.:
Lipomas. A m . J. Cancer 16:1104-1120, 1932.
2. Armed Forces Institute of Pathology: Manual of
Histologic and Special Staining Technics, 2nd. ed.
New York, McCraw-Hill, Blakiston Division, 1960.
3. Geschickter, C. T.: Benign lipomas and the lipo-
matoses-Tumors of soft tissues and bone. In Treat-
ment of Cancer and Allied Diseases, vol. 8.2nd ed. New
York, Harper, Hoeber Med. Division, 1964; pp. 106-119.
4. Geschickter, C. T.: Lipoid tumors. A m . I . Cancer
21:617-641, 1934.
5. Howard, W. R.,and Helwig, E. B.: Angioliporna.
Arch. Dermatol. 82:92+931, 1960.
1859
blasts), as described by Napolitano,e.7 no good
intermediate stages in this development were
noted in our case studied electron micro-
scopically. Fibroblasts may normally contain
an occasional lipid droplet or lysosome,s the
finding of multiple lipid droplets and/or sec-
ondary lysosomes of high lipid content may
reflect some abnormality of lipid metabolism
rather than differentiation toward mature
adipocytes.
Followup information obtained in 63 pa-
tients with spindle cell lipoma leaves no doubt
that the lesion is a benign process and that it
is readily curable by local excision.
6. Napolitano, L.: T h e differentiation of white
adipose cells-An electron microscope study. 1. Cell
B i d . 18:663-G79, 1963.
7. Napolitano, L.: T h e fine structure of adipose
tissues. In Handbook of Physiology, Section 5 , A. E.
Reynolds and G. F. Cahill, Jr., Eds. Washington, DC,
American Physiological Society, 1965; pp. 109-124.
8. Rhodin, J. A. G.:Organization and ultrastructure
of connective tissue. In T h e Connective Tissue, B. M.
Wagner and D. E. Smith, Eds. Baltimore, Williams
and Wilkins, 1967; pp. 1-16.