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Increasing Pulmonary Infiltrates in a 72-Year-Old Woman With Metastatic Breast CancerPulmonary Infiltrates With Breast Cancer FREE TO VIEW

Melanie C. Bois, MD; Xiaowen Hu, MD; Anja C. Roden, MD; Eunhee S. Yi, MD; Jay H. Ryu, MD, FCCP; Mariam P. Alexander, MD
Author and Funding Information

From the Department of Anatomic Pathology (Drs Bois, Roden, Yi, and Alexander) and the Division of Pulmonary and Critical Care Medicine (Dr Ryu), Mayo Clinic, Rochester, MN; and the Department of Respiratory Disease (Dr Hu), Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China.

CORRESPONDENCE TO: Jay H. Ryu, MD, FCCP, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: ryu.jay@mayo.edu


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(6):e208-e211. doi:10.1378/chest.14-0761
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A 71-year-old woman, nonsmoker, with a history of metastatic breast cancer was referred for evaluation of worsening pulmonary infiltrates. She described slowly increasing exertional dyspnea and cough in the preceding 3 months. Twenty-two years before, she had been diagnosed with invasive ductal carcinoma of the left breast, for which she underwent a left modified radical mastectomy and prophylactic right simple mastectomy and bilateral breast reconstruction using silicone implants. She subsequently underwent combination chemotherapy. She did well during the following 7 years until an enlarging liver lesion was noted that proved to be metastatic breast cancer, for which she underwent a right hepatectomy. Five years later, she developed intrathoracic and supraclavicular lymphadenopathy, a left pleural effusion, and cervical spine lesions. A biopsy specimen from a supraclavicular lymph node showed metastatic breast cancer, for which she started letrozole therapy with resolution of intrathoracic findings. Twelve months before presentation she underwent bilateral capsulectomy with silicone implant exchange because of pain from implant contracture. Her medications included letrozole, 2.5 mg once a day, and vitamin and Chinese herbal supplements. Her family history was positive for breast cancer in her maternal grandmother.

The patient was alert and had normal vital signs. Pulse oximetry showed 94% saturation at rest while breathing ambient air. Chest auscultation revealed few inspiratory crackles over the lung bases. The rest of the examination was unremarkable other than breast implants and the surgical scars on her abdomen.

The CBC count and basic chemistry panel were within normal limits. The serum antinuclear antibody titer and anticyclic citrullinated peptide antibody level were within the normal range, as were screening serologies for hypersensitivity pneumonitis.

Chest radiography showed interstitial infiltrates in the lower lungs. A chest CT scan demonstrated ground-glass and reticular opacities bilaterally, as well as interlobular septal thickening with a lower lung predominance (Fig 1). These abnormalities had increased when compared with a chest CT scan obtained 5 weeks earlier. Mild intrathoracic lymphadenopathy was present. A PET/CT scan showed mild 18flourodeoxy-glucose uptake in the lower lungs and intrathoracic lymph nodes. There was no extrathoracic 18flourodeoxy-glucose uptake. Pulmonary function testing revealed a reduced diffusing capacity for carbon monoxide (43% predicted) with a normal spirometry.

Figure Jump LinkFigure 1 –  Chest CT scan reveals bilateral ground-glass and reticular opacities in the lingula and lung bases. Interlobular septal thickening is present predominantly in the lower lung fields.Grahic Jump Location

Bronchoscopy was performed with BAL of the lingula, transbronchoscopic lung biopsy from the left lower lobe, and an endobronchial ultrasound-guided needle aspiration of 2R lymph node. The BAL was unrevealing. The transbronchial biopsy specimen of the left lower lobe demonstrated a foreign-body giant cell reaction and reactive-appearing pulmonary parenchyma (Fig 2). Spheroid structures of various sizes with a refractile rim were associated with multinucleated giant cells. Grocott methenamine silver stain was negative. Similarly, a transbronchial needle aspiration biopsy specimen of the 2R lymph node demonstrated noncaseating granulomatous inflammation with negative Grocott methenamine silver and acid-fast bacillus stain. Microbiologic studies on the surgical specimens were all negative. Additional studies were performed to confirm the diagnosis.

Figure Jump LinkFigure 2 –  A, Low-power micrograph of a transbronchial biopsy specimen demonstrates interstitial and intraalveolar cellular infiltrates (hematoxylin and eosin [H&E], original magnification × 100). B, High-power view reveals that these infiltrates are predominantly composed of macrophages and clusters of foreign-body giant cells forming nonnecrotizing granulomas. Many of these granulomas harbor spheroidal structures (lipoid vacuoles) (H&E, original magnification × 400). C, Foreign-body material within the giant cells demonstrates a refractile quality with a colorless rim (H&E, original magnification × 600).Grahic Jump Location
What is the diagnosis?
Diagnosis: Silicone pneumonitis

“Silicone” refers to a family of chemically related organosilicon compounds derived from silica. It is an inert material with low immunogenicity used widely in the field of aesthetic and reconstructive surgery. Liquid silicone breast injections were used in the 1950s as a mode of breast augmentation. Breast implants, which became popular in the 1960s, for both cosmetic purposes (80%) and reconstructive surgery (20%) after mastectomy, use fluid dimethylpolysiloxane as the base material for the envelopes or the gels.

Despite its popularity, the use of silicone breast implants can be associated with many complications and has been the focus of criminal and civil litigations. Major local and perioperative complications include fibrous contractures, rupture (intra- and extracapsular), gel migration, silicone exudation through skin or nipple, infection (operative, peri-implant, intraimplant), hematoma or seroma, foreign-body giant cell reaction, siliconomas, fat necrosis, and peri-implant calcifications. Serious and often fatal complications are reported most commonly with direct tissue injection of large quantities of silicone, a procedure that is largely obsolete today. Large quantities of viscous silicone material are often injected into tissue spaces and then massaged locally. The local build-up of pressure forces the silicone into angiolymphatic channels, with resultant distant migration, akin to “fat embolism.” Involvement of the pulmonary and neurologic systems is the most dreaded complication and often warrants emergency management. Other distant complications encountered with breast implants include lymphadenopathy, granulomatous hepatitis, arthritis, and acute serum sickness-like illness.

Silicone lymphadenopathy is reported commonly in the setting of breast implants, most often in the ipsilateral axillary lymph nodes. Following mastectomy, normal lymphatic pathways may be disrupted or obstructed by scarring from surgery and axillary lymph node dissection. Drainage can occur in a retrograde direction through alternate lymphatic pathways and may explain why metastatic and silicone lymphadenopathy occurs in mediastinal and contralateral nodes. This may also explain silicone migration to intrapulmonary sites from breast implant ruptures.

Pulmonary complications include silicone pulmonary embolism with alveolar hemorrhage, diffuse alveolar damage, acute and latent pneumonitis, siliconomas, and progressive granulomatous inflammation. The varied histologic spectrum depends on a complex interplay of cellular inflammation, host response, and quantity of silicone.

Silicone pneumonitis may be seen in an acute form (within days of silicone injections) or, as in this case, in a latent form, which may occur as late as 6 months after the last injection. Aggregates of silicone are noted within macrophages and are localized to capillaries within the interstitium. Some silicone aggregates spill into the airspaces, often associated with neutrophils and mononuclear cells. Silicone pulmonary embolism, with intravascular silicone vacuoles, can be an acute fatal complication that mimics fat embolism syndrome. Patients present clinically with hypoxemia, dyspnea, fever, and alveolar hemorrhage. Siliconomas, cutaneous and intrapulmonary, have been described in the setting of latent and silent implant failure. A very rare expression of silicone pulmonary involvement is progressive granulomatous inflammation, which has been described in the setting of HIV. It may be the expression of an immune reconstitution syndrome and immune modulation.

Radiologic findings vary widely, depending on the type of pulmonary syndrome associated with the silicone. Chronic progressive silicone pneumonitis in association with breast implants has not been reported previously. Histopathologic diagnosis rests on identifying intracellular silicone. It is recognized in tissue as spheroidal bodies surrounded by a refractile rim of colorless material, often engulfed by macrophages. Dark-field microscopy demonstrates its refractile nature; a 48-h or 72-h prolonged staining with oil red O stains the edge of the silicone (because of abundant carbon hydrogen bonds), and energy dispersive spectroscopy studies (as performed in this case) confirm the presence of elemental silica. BAL may yield alveolar macrophages containing silicone.

Clinical Course

Energy-dispersive radiograph microanalysis was used to evaluate this specimen for the possible presence of silicone. Areas of interest were analyzed and the element of silicon was found. The amorphous appearance and the corresponding spectral analysis were consistent with silicone. An MRI study of the breasts was performed, and it revealed intact breast implants without evidence of capsular rupture. Reexamination of the previously resected capsulectomy specimens from the year before, however, revealed evidence of a leak from her earlier implants, with silicone in the pericapsular soft tissue. To our knowledge, this is the first description of chronic progressive silicone pneumonitis associated with breast implants.

Based on these results, management options included observation vs a trial of corticosteroid therapy. The patient chose to observe for now, with a reassessment in several months.

  • 1. Silicone can be associated with several intrathoracic manifestations, including silicone lymphadenopathy, acute silicone embolism with pneumonitis (diffuse alveolar damage), pulmonary alveolar hemorrhage, siliconomas, progressive granulomatous inflammation, and chronic silicone pneumonitis.

  • 2. Acute manifestations associated with silicone usually occur from silicone injections into soft tissue performed for cosmetic purposes.

  • 3. In patients with breast implants, chronic silicone pneumonitis should be considered in the differential diagnosis of interstitial lung disease.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: The authors acknowledge Jon Charlesworth, MA, Microscopy and Cell Analysis Core, for his expertise. CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.

Chastre J, Brun P, Soler P, et al. Acute and latent pneumonitis after subcutaneous injections of silicone in transsexual men. Am Rev Respir Dis. 1987;135(1):236-240. [PubMed]
 
Gurvits GE. Silicone pneumonitis after a cosmetic augmentation procedure. N Engl J Med. 2006;354(2):211-212. [CrossRef] [PubMed]
 
Dragu A, Theegarten D, Bach AD, et al. Intrapulmonary and cutaneous siliconomas after silent silicone breast implant failure. Breast J. 2009;15(5):496-499. [CrossRef] [PubMed]
 
Alva RV, Yacoub WJ. A young woman with pulmonary hemorrhage and hypoxic respiratory failure. Chest. 2010;137(2):484-487. [CrossRef] [PubMed]
 
Hariri LP, Gaissert HA, Brown R, et al. Progressive granulomatous pneumonitis in response to cosmetic subcutaneous silicone injections in a patient with HIV-1 infection: case report and review of the literature. Arch Pathol Lab Med. 2012;136(2):204-207. [CrossRef] [PubMed]
 
Lewin-Smith M, Kalasinsky V, Shilo K, Tomashefski J, Cropp A. Detection of silicone in lung tissue. Arch Pathol Lab Med. 2012;136(10):1179-1180. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 –  Chest CT scan reveals bilateral ground-glass and reticular opacities in the lingula and lung bases. Interlobular septal thickening is present predominantly in the lower lung fields.Grahic Jump Location
Figure Jump LinkFigure 2 –  A, Low-power micrograph of a transbronchial biopsy specimen demonstrates interstitial and intraalveolar cellular infiltrates (hematoxylin and eosin [H&E], original magnification × 100). B, High-power view reveals that these infiltrates are predominantly composed of macrophages and clusters of foreign-body giant cells forming nonnecrotizing granulomas. Many of these granulomas harbor spheroidal structures (lipoid vacuoles) (H&E, original magnification × 400). C, Foreign-body material within the giant cells demonstrates a refractile quality with a colorless rim (H&E, original magnification × 600).Grahic Jump Location

Tables

Suggested Readings

Chastre J, Brun P, Soler P, et al. Acute and latent pneumonitis after subcutaneous injections of silicone in transsexual men. Am Rev Respir Dis. 1987;135(1):236-240. [PubMed]
 
Gurvits GE. Silicone pneumonitis after a cosmetic augmentation procedure. N Engl J Med. 2006;354(2):211-212. [CrossRef] [PubMed]
 
Dragu A, Theegarten D, Bach AD, et al. Intrapulmonary and cutaneous siliconomas after silent silicone breast implant failure. Breast J. 2009;15(5):496-499. [CrossRef] [PubMed]
 
Alva RV, Yacoub WJ. A young woman with pulmonary hemorrhage and hypoxic respiratory failure. Chest. 2010;137(2):484-487. [CrossRef] [PubMed]
 
Hariri LP, Gaissert HA, Brown R, et al. Progressive granulomatous pneumonitis in response to cosmetic subcutaneous silicone injections in a patient with HIV-1 infection: case report and review of the literature. Arch Pathol Lab Med. 2012;136(2):204-207. [CrossRef] [PubMed]
 
Lewin-Smith M, Kalasinsky V, Shilo K, Tomashefski J, Cropp A. Detection of silicone in lung tissue. Arch Pathol Lab Med. 2012;136(10):1179-1180. [CrossRef] [PubMed]
 
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