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1. Diagnostic Dilemmas Caused by Silicones
Keywords
Systemic complicationsFlu-like symptomsPulmonary emboliDeathsCancerDiagnostic dilemmasEarly diagnosisMammographyBreast ultrasoundThe symptoms and degree of clinical involvement of the breast through the injection of liquid silicones vary widely. Our review of the literature, discussions with other authors, and personal experience all indicate that complications can appear either immediately or late. In the latter instance, the asymptomatic interval ranges widely, from 1 month to 24 years in the series we reviewed, averaging between 5 and 9 years.
In 1969, Chaplin [1] reported on a 31-year-old woman with systemic and local complications 1 year after having had silicone injected into her breasts. She presented with a flu-like syndrome, and in her breasts there were edema, erythema, tautness to palpation, and generalized cutaneous erythema. These findings abated with the administration of antibiotics and corticosteroids. However, when treatment was stopped, they returned with increasing virulence to the point of overlying skin necrosis in both breasts and compromised general health.
Years later, several authors [2, 3] published their experiences with series of patients who had had silicones or other oily substances injected into their breasts, and they reported a variety of symptoms. Systemic complications that were described included both acute and chronic respiratory distress and clinical and subclinical signs of collagen vascular disease. Injections induced acute pneumonia followed, in some patients, by respiratory insufficiency. Even deaths were reported that were deemed to have resulted from the injection of silicones.
By way of illustration, a forensic medical report is transcribed: “The doctor of a health unit described the presentation of a 33-year-old woman, who had been brought to the hospital by two individuals who had attempted to give her breast silicone injections in their home. She arrived in the emergency department already deceased, having experienced respiratory failure almost immediately after silicone had been injected. In the morgue, an apparently home-manufactured breast support was observed, consisting of elastic bands that surrounded and compressed both of the woman’s breasts” (see Chap. 5).
This case implies how the injection of silicones for cosmetic purposes could cause some acute adverse event like a pulmonary thromboembolism that could trigger a patient’s death. The mechanism of pulmonary embolism would be related to the local pressure induced by injecting large volumes of substance, combined with the local massage that frequently accompanies this procedure, resulting in either a migratory effect or direct intravascular injection; the latter was deemed to be the mechanism that triggered death in the above-noted case [4].
In addition to clinically important local and systemic complications, silicone injections seriously complicate the process of diagnosing breast cancer.
Several considerations, both oncological and ethical, warrant discussion.
Breast cancer is the most frequent cancerous tumor in women, with an incidence in Argentina of 71/100000 women, according to the National Cancer Institute [5]. It also ranks first among the causes of cancer death in adult women, with an adjusted mortality rate of 19.9/100000 women in Argentina, and roughly 5600 deaths per year.
In the United States, 24,660 new cases of breast cancer were estimated for 2016, rendering it the second most common cause of cancer mortality among US women, behind lung cancer [6]. It is estimated that one in eight women who reach the age of 85 years old will have developed breast cancer at some point over the course of her life [7].
Breast cancer incidence has increased in recent years, at least partially due to the increased use of mammography, but also due to changes in lifestyle, reproduction history, and the population’s aging, as 50% of breast cancers occurs in people more than 65.8 years old.
Diagnosing breast cancer fundamentally relies on the diagnostic triad of clinical examination, mammography, and tissue biopsy. Other studies, like breast ultrasound, Tc-99 m sestamibi scintimammography, and magnetic resonance imaging (MRI), are merely complementary to the classic diagnostic triad.
Cancer screening programs currently exist that consist of a series of investigations that the public health sector offers to a seemingly healthy population for secondary prevention purposes, that is, for the purpose of diagnosing disease early. For breast cancer, this consists of breast self-examinations, clinical examinations by a physician, and mammography. Most screening programs have been shown to reduce breast cancer mortality by about 40% in women over 50 years of age and by roughly 25% among those between 40 and 49 years.
Mammography is currently the most sensitive diagnostic imaging method for the recognition and differentiation of pathological from normal mammary tissue. But this has not always been the case.
In 1913, Salomon, at the Surgical Clinic in Berlin, initially reported using standard radiographs to assess diseases of the female breast. It was not until 1930, as a result of steady advances in surgery, that mammography publications began to appear with some frequency [7]. It was over the next three decades, up to the year 1960 — the stage known as the second period of mammography — that the diagnostic potential of mammography rose dramatically, as understanding of the anatomical correlation between mammography images and anatomopathological tissues increased. However, it was not until after 1960 —the so-called third period of mammography — when an intense search for better techniques and equipment to collect mammography images began, that real clinical importance was afforded mammography’s subtle radiological findings and their relationship to early breast cancer diagnosis and patient survival [7]. Now, mammography is a routine screening method, of proven value for the early diagnosis of breast cancer, after a century overcoming obstacles.
Mammary ultrasound is an important diagnostic complement to mammography as well as a means with which to guide interventional procedures. It is important to note that between 2% and 3% of breast carcinomas are diagnosed only by ultrasound. To achieve correct diagnoses, 7.5–10.0 MHz transducers are required, with a variable focus depth of 3–4 cm. This allows for the recognition and differentiation of small lesions, breast parenchyma, and adipose tissue. A thorough examination also should include the pectoral muscles and ribs.
Mammography and clinical examinations are, without a doubt, the fundamental tools for the early diagnosis of breast cancer. Nonetheless, one must take into account that, even used together, these tests are imperfect, with false-negative rates estimated between 5% and 15% and the specificity of mammography limited to 30% or less [7].
The breast is comprised of glandular epithelium, fibrous stroma, and a large quantity of adipose tissue. All these tissues have different physiochemical characteristics, for which magnetic resonance imaging (MRI), to date, appears to exhibit the greatest capacity for differentiation. In turn, the potential to inject an intravenous contrast agent (gadolinium) considerably increases MRI’s ability to recognize areas of hypervascularization that could indicate tumor angiogenesis.
With current techniques, MRI allows for the evaluation of inconclusive images that arise from conventional mammography and ultrasound. Moreover, detailed features can be obtained not only from the breasts’ surface but also from the axilla and chest wall. Limitations to the use of MRI include its high cost and relatively limited availability, obliging attending physicians to restrict its use to assessing lesions that are suspicious, but not well-visualized by the previously mentioned conventional examinations.
The screening methods cited in the present review deserve special consideration. The presence of silicone-free material injected into breast generates a chronic inflammatory reaction, of the type of characteristic of foreign body granulomas, with cutaneous erythema, nodules, and cutaneous retractions, all of which impede certainty during breast self-examinations, confuse clinical examinations by physicians, and may alter all the various imaging studies, whether mammography, breast ultrasound, or MRI.
The experience acquired following the patients in this study coincides with the published literature, documenting that mammography, breast ultrasound, and MRI are inconclusive in their evaluation of mammary parenchyma. As such, the presence of other pathologies can often not be ruled out.
The mammography, breast ultrasound, and MRI reports of patients studied at different centers again illustrate these tests’ inability to accurately evaluate mammary parenchyma.
According to Cheung (Department of Radiological Diagnosis, Chang Gung Memorial Hospital, Taiwan), if a lesion is within a granulomatous mass induced by silicone, the detection of breast cancer by means of mammography or conventional ultrasound is essentially impossible. [9]
Many such patients are in an age group highly susceptible to cancer, and some worry that one or more of their silicone-induced lesions are, in fact, neoplastic. It is practically impossible to rule out cancer as the cause of one or more of the hard nodules these patients commonly exhibit. Changing nodule characteristics makes follow-up exams more confusing than helpful [10].
As pointed out by Sadowsky and O’Sullivan, mammograms are inconclusive in such cases, the typical study revealing multiple silicone collections dispersed throughout the glandular tissue and pectoral muscle.
Despite these difficulties, breast ultrasounds performed with state-of-the-art equipment and by highly trained professionals can be of value evaluating suspicious masses, even guiding puncture biopsies.
Advanced, high-resolution MRI techniques also may help clinicians to identify the histological composition of granulomas formed by silicones. Gadolinium injection may enhance the detection of angiogenic lesions, including those caused by cancer or inflammatory reactions, especially among patients with lesions hidden within siliconomas. If there is enhancement of any lesion, the possibility of cancer or angiogenic mastopathy should be considered and a biopsy performed.
The signal intensity of mammary siliconomas can be differentiated from that of most cancers. Unfortunately, whether such differentiated lesions are benign or malignant is often difficult to determine, even when dynamic curves for intensity over time are added.
Many have documented, as we have, that it remains impossible to differentiate, with 100% certainty, if MRI-enhanced angiogenic processes are malignant or benign [9].
On the other hand, MRI can be useful in identifying suspicious lesions and aiding in their biopsy, though false negatives occur, as we have corroborated.
Although there is no evidence yet that injected silicone is involved in the origins of cancer [9], Morgenstern et al. suggest that the presence of silicone may increase tumor spread, secondary to the abnormal opening of lymphatic channels induced by liquid-silicone-related mastopathy, or via other alterations in the immune system associated with silicone-induced granulomatosis [11].
Others claim that prolonged inflammation induced by the injection of silicones is likely to lead to a series of pathological responses, which include carcinogenesis [12].
One thing that is of no doubt is that the prognosis of breast cancer is highly contingent upon its early diagnosis. There also is no doubt that siliconomas interfere with and, thereby, may delay the early detection of breast cancer, due to the numerous difficulties they cause in breast evaluation [13].