>From the evidentiary files of breast implant litigation. Thank you
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CD Image #T-36528.001
Stamped number on image 3624
Handwritten: DC200/?50cs
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MAMMARY SILICONE GRANULOMA
Migration of Silicone Fluid to Abdominal Wall and Inguinal Region
Claude Delage, MD, Wa****ngton DC, John J. Shane, MD, Philadelphia;
Frank B.
Johnson, MD, Wa****ngton DC
Two and one-half years after having had silicone fluid injected into
her breasts, a 22 year old woman noticed two painful m***** in the
subcutaneous tissue of her abdominal wall. Similar lesions appeared
four months later in both breasts and in the inguinal region. Gross
and microscopic aspects of these m***** were identical in all three
anatomic sites. Cystic fluid was identified by infrared
spectrophotometry as an all-methyl silicone polymer.
The presence of silicone fluid in the abdominal wall and inguinal
region is explained by gravitational migration from its initial site
of injection in the breasts-a finding not previously re****ted to our
knowledge.
Several years ago, the injection of liquid silicone for augmentation
mammoplasty was a widespread practice. In 1965 however, silicone
fluids when injected into the tissue were considered a "new drug" by
the Food and Drug Administration, DHEW. A special committee of eight
official investigators, including six plastic surgeons, was appointed
to further examine the safety of the product. Because of the high
incidence of mammary cancer, the use of silicone fluids in breast
augmentation was forbidden. Basically, two types of silicone
preparations have been used: (1) the pure forms such as dimethicone
350 (dimethylpolysiloxane) and (2) a variety of adulterated forms
containing pure silicone fluid to which vegetable oils of fatty acids
are added (Sakurai formula) to induce fibrosis and to assure firmness
and immobilization. In pure form, silicone fluids are said to be
chemically and physically inert, to produce minimal tissue reaction,
to be nonallerginic and non inflammatory and ordinarily, to induce no
foreign body tissue reactions.(12) Migration to distant areas of the
body seems to be the only serious complication. In spite of this,
several re****ts of granulomatous reactions following injections of
silicone fluids in the breast have appeared in the literature over the
recent years. (2-6) In these instances, it was believed that
impurities or additives to the basic pure
silicone could be responsible for the tissue reaction. The following
is a well-do***ented case of silcone granuloma in the breasts and
migration of silicone to the abdominal wall and the inguinal
104 Arch Dermatol, Vol 108, July 1973
Marked T-036528
Mammary Silicone Granuloma/Delage et al
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CD Image #36528.002
region in a young woman who had had injections of silicone fluids for
breast augmentation. Positive identification of the silicone material
in the tissues was made by the infrared absorption spectrophotometry
method.
RE****T OF A CASE
Clinical Findings (First Admission)--A 22 year old white woman was
admitted to the hospital on Sept 14, 1971, with a history of two
m***** in her abdominal wall. They were slightly painful to
palpation, and were noticed initially three days prior to admission.
One mass, located several centimeters below the left subcostal margin
just overlying the left rectus muscle, was hard on palpation, diffuse
and poorly delineated from the surrounding tissues, and somewhat
crepitant; but it had a definite lack of mobility. The other mass was
suprapubic, located just below the midpoint between the umbilicus and
the pubis, and was similar in all respects to the subcostal lesion.
Both lesions were essentially the same size, approximately 2 to 3 cm
in diameter.
Extensive questioning revealed that the patient had had no significant
illness. She had been hospitalized several weeks earlier when a
uterine curettage was performed for menometrorrhagia. Results of all
laboratory tests were within normal limits. Upon surgical removal
both m***** were poorly (word unreadable) and were in the subcutaneous
fatty tissue but were superficial to the rectus fascia.
Gross Findings.--Pieces of tissue were excised, measuring from 1.5cm
to 5.5x2.5cm. They were glistening and crepitant, and on cut section
showed a honeycomb, multicystic pattern. The individual cysts
contained clear, viscid material and varied in size from 1 to 5 mm in
diameter.
Microscopic Findings.--Sections stained with hematoxylin-eosin showed
these cavities to be limited by thin collagenous walls make of
scattered elongated fibroblasts. The tissue between the cavities
consisted of normal or altered fat (serous atrophy) and loose
connective tissue having collagenous areas diffusely infiltrated with
a few lymphocytes, histiocytes, fibroblasts, and an occasional
eosinophil. A rare foreign-body giant cell could be seen. The cystic
structures were optically empty. No doubly refractile material was
seen in either the lumen of the cysts or the cytoplasm of the
surrounding stain for unsaturated fatty acids in the cavities was
negative. An oil red O stain was slightly positive in some areas in
the cavities. Both stains were performed on formaldehyde (formalin)-
fixed frozen sections. A Masson tirchrome stain showed a mild
fibroblastic reaction of the connective tissue.
In some respects the lesion resembled a lymphangioma, although no
endothelial lining was present on the inner surface of the spaces.
Foreign-body granuloma was also a possibility, although multinucleated
giant cells were rare.
The history and findings did not sup****t a definitive diagnosis, and
the patient was discharged.
Clinical Findings (Second Admission).--The young woman returned to the
hospital on Jan 10, 1972, with similar lesions in both breasts and in
the left inguinal area, just superficial to the inguinal ligament.
Gross Findings.--Tissue showing the same honeycomb, multicystic
appearance as that of the initial lesions in September 1971, and
measuring 5x2 cm was excised from the right breast and a number of
fragments varying from 1 to 2 cm in diameter were removed from the
left breast.
>From the left inguinal area, a mass 5x3 cm in dimension was removed
with multiple additional smaller fragments. All specimens were of
identical description and similar to those obtained initially from the
subcutaneous tissue of the abdominal wall.
Microscopic Findings.--The histologic appearance of the m***** from
the breasts and inguinal area was identical to that of the initial
lesions in the abdominal wall. In the breasts, however, some typical
foreign-body giant cells were seen in relation to empty cysts, and the
inflammatory response in the intervening connective tissue was
minimal, consisting of patchy infiltrates of histiocytes, lymphocytes
and a few eosinophils. Most of the cystic spaces were lying in
clusters in the fatty mammary tissue with no significant inflammatory
reaction. The specimens from the inguinal region showed a few typical
multinucleate giant cells in the vicinity of or in the walls of the
empty cysts, in addition to the characteristic multiple cystic
structures. The inflammatory response was more pronounced and diffuse
Produced by DCC & DCW
Arch Dermatol/Vol 108, July 1973
Stamped T-036528
Mammary Silicone Granuloma/Delage et al pg 105
************
in the surrounding fatty and connective tissues. The cellular
infiltrate of lymphocytes, macrophages, histiocytes, and numerous
eosinophils showed a nodular granulomatous pattern in some areas. In
the tissues from both breasts and the ingunal area, there was no
evidence of any crystalline or refractile material in the lumen of the
numerous vacuoles or in the cytoplasm of the giant cells and
histiocytes surrounding the empty vacuoles.
Results of all laboratory tests were within normal limits during this
second hospitalization. The patient confided to the physician when
admitted to the hospital this time, that about 30 months before she
had had silicone injections in both breasts. The name of the silicone
was obtained from the plastic surgeon who injected it. He claimed to
used PURE SILICONE FLUID, dimethicone 350, NOT AN ADULTERATED FORM.
With the clinical history of injections of silicone fluid into the
breasts 2 1/2 years before and with identical morphologic lesions in
all three anatomic sites, it became increasingly evident that the
viscid fluid in the
multicystic m***** was silicone. The fining of these peculiar
honeycomb m***** in the subcutaneous tissue of the abdominal wall and
inguinal region could be explained by gravitational migration of the
fluid to these locations from the original site of injections to the
breast.
Positive identification of the cystic content was made by infrared
absorption spectrophotometry technique.
Infrared Spectrophotometry.--The specimens of tissue were washed
briefly in distilled water, then bottled. Clear viscid fluid was
aspirated from on cystic cavity in each specimen. Approximately 2 ml
of each aspirate was mixed with 200mg of spectrograde potassium
bromide, dried for one hour at 100C, and disks were formed of each for
infrared spectrophotometry. The observations were made with a grating
infrared spectrophotometer.
RESULTS
Samples from each of the tissue specimens yielded infrared absorption
spectra typical for methyl silicones.
The spectrum shows a band at about 3.4u caused by methyl groups. At
7.9u, there is a band resulting from methyl linked to silicon. The
overlapping bands between 9u and 10u are caused by the silicon-oxygen-
silicon configuration. The band at 12.4u is the result of the methyl-
silicon-methyl configuration. This spectrum obtained with the cystic
fluid from the tissue specimens is in all respects similar to the
standard spectrum for methyl silicones.
COMMENT
Dimethicone 350 is an organosilicon polymer, the chemical formula of
which is (O Si (CH3)2)n. In the Si-O polymer chain two methyl groups
are attached to each silicon atom. As the chain lengthens, the
viscosity increases. Dimethicone 350 has a viscosity of 350
centistokes, while that of water is 1. Conflicting re****ts on tissue
reactions to silicone have appeared in the literature. In man or in
animal, silicone has been found alternatively to be well tolerated and
to induce little tissue reaction, to evoke a definite histologic
reaction but without foreign body response, or to be practically
inert.
On the other hand Symmers re****ted two cases of silicone mastitis in
topless waitresses, and the histologic picture was similar to that of
an oleogranuloma. Winer etal re****ted three cases of siliconomas,
two
developing in the breast and one in the skin of the face, having
histologic lesions typical of foreign body granulomas. Nosanchuk
presented one case of silicone granuloma of the breast in a young
woman, and in this case there also was evidence of foreign body giant
cells around the small silicone containing cysts. It has been argued
that the granulomatous reaction is probably caused by the presence of
additives or other adulterants in the silicone preparation, and not by
the silicone itself. This may explain why fine particulate, doubly
refractile material or ****ny crystals have sometimes been found in the
affected tissues. Nosanchuk described a wrinkled film of semiliquid
substance in the lumen of the microcysts, better seen with the
microscope condenser closed, which he identified as silicone. Such a
procedure proved inconclusive in our case. The giant cell reaction
observed in our case was always in relation to empty vacuoles, and no
birefringent material was seen in either the vacuoles or the cytoplasm
of the giant cells.
One of the complications of silicone injection in mammoplasty is the
possible migration of the substance some times.
Produced by DCC & DCW
Page 106 Arch Dermatol/Vol 108, July 1973
Stamped T036530
Mammary Silicone Granuloma/Delage et al
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CD Doc T-36528.004
distance from the site of injection.Migration usually occurs when
large amounts of low viscosity silicone fluid
are administered, and it most probably drifts by gravity to distant
places along tissue planes. In addition, Ben-Hur re****ted evidence of
movement of silicone to the regional lymph nodes following
subcutaneous administration of dimethicone 350 in mice.
No evidence of lymph node involvement was present in our case. To our
knowledge, migration of silicone fluid from the original site of
injection to such remote anatomic sites as the subcutaneous tissue of
the abdominal wall and inguinal region has not been re****ted.
Positive identification of the substance used in supplementation of
anatomy is of prime im****tance, as exemplified by the case of a woman
who developed generalized paraffinoma following numerous injections of
what she thought was silicone into her calves. Spectroscopic and
chromatographic techniques, however, identified the substance as
mineral oil.
In our study, identification for the fluid contained in the cystic
structures was unequivocal. It was identified as an all methyl
silicone compound by infrared absorption spectrophotometric analysis.
The spectra yielded by the fluid aspirated from the multicystic fluid
aspirated fro multicystic spaces in the breasts and the inguinal and
abdominal regions were typical for methyl silicones. Therefore,
seemingly strong evidence favors a foreign body granulomatous reaction
to silicone itself, since no adulterants were identified by
spectrophotometric study. This moreover, would challenge the concept
of tissue inertness of pure silicone.
One should be cautious, however, in interpreting these findings,
because there is still a possibility that unidentified impurities
mixed with the silicone fluid might have produced the mild
granulomatous tissue response in the present case.
This study was sup****ted in part by the AMA, the Food and Drug
Administration contract FDA 67-53(or 33), the National Institute of
General Medical Sciences contract PH 43-65-066, and the Pharmaceutical
Manufacturers Association Foundation, Inc, under the auspices of the
Universities Associated for
Research and Education in Pathology, Inc.
PRODUCED BY DCC & DCW
Arch Dermatol/Vol 108, July 1973
Mammary Silicone Granuloma/Delage et al Page 107
Stamped T-036531
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