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A 60-Year-Old Woman With PET Scan-Avid Lung Nodules and a History of a Ruptured Silicone Breast ImplantLung Nodules and Ruptured Breast Implant FREE TO VIEW

Lioudmila V. Karnatovskaia, MD, FCCP; Andras Khoor, MD; Margaret M. Johnson, MD, FCCP; Joseph Kaplan, MD, FCCP
Author and Funding Information

From the Departments of Pulmonary and Critical Care Medicine (Drs Karnatovskaia, Johnson, and Kaplan) and the Department of Pathology (Dr Khoor), Mayo Clinic Florida, Jacksonville, FL.

CORRESPONDENCE TO: Lioudmila V. Karnatovskaia, MD, FCCP, Department of Pulmonary and Critical Care, Mayo Clinic, 200 First Rochester St NW, Gonda 18, Rochester, MN 55905; e-mail: karnatovskaia.lioudmila@mayo.edu


Dr Karnatovskaia is currently at the Department of Pulmonary and Critical Care Medicine, Mayo Clinic (Rochester, MN).

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


Chest. 2014;146(4):e138-e142. doi:10.1378/chest.14-0203
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Published online

A 60-year-old woman was referred to the pulmonary clinic for evaluation of lung nodules. Her medical history was notable for hypothyroidism, anxiety, and a ruptured breast implant for which incomplete surgical resection and evacuation had been performed 10 years previously. She was a lifelong nonsmoker and worked as a gym instructor. The patient denied occupational exposures and had not traveled recently. Medications included levothyroxine and alprazolam. Except for a 1-month history of occasional dry cough, the review of systems was negative. The patient’s physician queried whether the previously ruptured silicone breast implant may have played a role in the genesis of the nodules and referred the patient to our institution for further management. The lack of systemic symptoms relative to the degree of lung involvement provided an early diagnostic clue.

Figures in this Article

On examination, heart rate was 92 beats/min, respiratory rate was 16 breaths/min, BP was 122/70 mm Hg, and oxyhemoglobin saturation on room air was 98%. The patient appeared anxious, but her physical examination was otherwise normal.

The patient’s CBC count and renal function were normal. A chest radiograph revealed an abnormal density in the right midlung anteriorly (Fig 1); a subsequent CT scan confirmed the presence of a pleural-based mass, multiple parenchymal nodules, and mediastinal adenopathy (Fig 2). A CT image-guided transthoracic needle aspiration of the mass demonstrated fibroblastic-myofibroblastic proliferation. A PET scan showed increased metabolic activity in all lesions (Fig 3). A repeat CT image-guided biopsy of the mass revealed findings consistent with inflammatory pseudotumor (Fig 4).

Figure Jump LinkFigure 1 –  A, B, Chest radiograph: (A) posteroanterior and (B) lateral views notable for the presence of a density in the right midlung anteriorly and possible density in the left posterior lung gutter.Grahic Jump Location
Figure Jump LinkFigure 2 –  A, B, CT scan chest views demonstrating (A) the presence of a pleural-based mass (3.48 cm) in the right midlung anteriorly, with multiple smaller bilateral pulmonary densities (A, B).Grahic Jump Location
Figure Jump LinkFigure 3 –  A, B, PET scan views notable for mildly hypermetabolic lymph nodes in the mediastinum; (B) multiple lesions demonstrating metabolic uptake and a hypermetabolic mass in the anterior portion of the right middle lobe with the standardized uptake value uptake of 21.9 (A).Grahic Jump Location
Figure Jump LinkFigure 4 –  CT image-guided needle aspiration of the mass demonstrating inflammatory process with lymphocytes, plasma cells, histiocytes, and neutrophils in the fibrous background without evidence of granulomas, consistent with inflammatory pseudotumor (hematoxylin and eosin, original magnification × 40).Grahic Jump Location

Endobronchial ultrasound-guided aspiration of the mediastinal lymph nodes showed benign lymphoid tissue; flow cytometry results were negative. The patient then underwent robotic-assisted anterior mediastinal mass resection, with wedge resection of the right upper and lower lobes. Surgical pathology images are shown in Figures 5 and 6.

Figure Jump LinkFigure 5 –  Surgical lung biopsy specimen demonstrating benign reactive germinal centers with normal lung replaced by aggregates of lymphoid tissue (hematoxylin and eosin, original magnification × 4).Grahic Jump Location
Figure Jump LinkFigure 6 –  Surgical lung biopsy specimen demonstrating plasma cells and mature lymphocytes. Paraffin immunoperoxidase studies demonstrated a mixture of CD3+ T cells and CD20+ B cells with polyclonal plasma cells. Additional immunostains (CD138, IgG, and IgG4) did not reveal IgG4-related disease. No clonal immunoglobulin gene rearrangement was detected by a polymerase chain reaction-based assay (hematoxylin and eosin, original magnification × 40).Grahic Jump Location
What is the diagnosis?
Diagnosis: Nodular lymphoid hyperplasia with pleural fibrosis and focal organizing pneumonia

Localized densities on imaging studies may have a variety of causes, including malignancy, nonmalignant lesions, an inflammatory or autoimmune process, or infection. Although small biopsy specimens may establish a diagnosis in many cases, a surgical sample is often required to correctly characterize the pathology of lymphoproliferative lesions.

Nodular lymphoid hyperplasia (NLH), a benign localized lesion showing features of reactive lymphoid hyperplasia, is one of the entities that, typically, require a surgical biopsy for diagnosis. In the only published series, to our knowledge, reviewing Armed Forces Institute of Pathology records over a 24-year period, 14 NLH cases were identified. The median age at diagnosis was 65 years (range, 19-80 years) with a slight predominance in women. Of those, most were discovered incidentally on routine chest radiographs and represented a single lesion. In cases with multifocal presentation, the lesions were unilateral. Clinically, only four of the 14 patients had symptoms such as shortness of breath, cough, or pleuritic chest pain. PET scan uptake associated with NLH has been reported as mild to moderate. Grossly, NLH appears as a well-circumscribed rubbery nodule, measuring 2 to 4 cm in its greatest dimension. Histologically, it contains well-developed lymphoid follicles with reactive germinal centers and interfollicular plasma cells; interfollicular fibrosis and scattered granulomas may be present. There can be limited lymphangitic spread along the bronchovascular bundles and interlobular septa. Regional lymphadenopathy may be seen in a third of cases, but the lymph nodes are histologically benign. With surgical resection, the prognosis appears to be excellent. Nonetheless, long-term follow-up is recommended because little is known about the cause and natural history of NLH.

Differential diagnoses of NLH include extranodal marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma, lymphoid interstitial pneumonia, inflammatory myofibroblastic tumor, IgG4-related disease, and other inflammatory pseudotumors. Differentiation between NLH and MALT lymphoma is difficult and often requires ancillary studies. Many cases previously classified as NLH are now recognized as MALT lymphoma. κ/λ reactivity is polyclonal in NLH and frequently monoclonal in MALT lymphoma, where lymphocytes may also exhibit BCL-2 reactivity. In addition, in molecular genetic analysis, NLH, in contrast to MALT lymphoma, shows no clonal immunoglobulin gene rearrangement.

Lymphoid interstitial pneumonia is categorized as an idiopathic interstitial pneumonia, although it is relatively often associated with HIV infection, other immunodeficiency states, and autoimmune diseases. Similar to NLH, it needs to be separated from malignant lymphoma. NLH can be distinguished from lymphoid interstitial pneumonia by the distribution of the lymphoid infiltrate; NLH is localized, whereas lymphoid interstitial pneumonia involves the lung diffusely.

The former category of inflammatory pseudotumor is now separated into inflammatory myofibroblastic tumor, IgG4-related disease, and other inflammatory pseudotumors. Inflammatory myofibroblastic tumor is a neoplasm composed of relatively bland spindle cells and a variable number of admixed lymphocytes, plasma cells, eosinophils, and histiocytes. The neoplastic spindle cells, which are absent in NLH, show cytogenetic aberrations in chromosome 2p23 in 40% of cases. IgG4-related disease is a newly recognized fibroinflammatory condition that has a tendency to form tumefactive lesions. Although the role of the IgG4-positive cells is not entirely known, their presence provides a useful diagnostic tool. The absence of appropriate IgG4 counts and ratios separates NLH from IgG4-related disease. Other inflammatory pseudotumors probably represent tumefactive organizing pneumonia in most instances and are considered a reactive process. Again, the absence of spindle cells in NLH and their presence in inflammatory pseudotumors help distinguish the two entities.

Although the cause of NLH may not be clear, there does not appear to be an association with ruptured silicone implants. “Silicone pseudotumor,” which is not synonymous with “inflammatory pseudotumor,” is the pathologic tissue reaction to the migration of silicone within the body. Silicone tissue spread is thought to occur via multiple routes, including hematogenous and lymphatic and along the fascial planes. Because silicone is not biologically inert, it can elicit a foreign-body granulomatous reaction termed a “siliconoma.” Silicone pseudotumors in a variety of locations have been described. Most are asymptomatic but can manifest with pain, tenderness, and local erythema. Histopathologic analysis shows silicone granulomas with characteristic multiple cystic spaces previously containing silicone vacuoles surrounded by an infiltrate of histiocytes with multinucleated giant cells. None of these findings are seen in NLH. Notably, siliconomas or silicone granulomas can also present with an increased uptake on a PET scan because of the surrounding granulomatous inflammation. Treatment of symptomatic cases is by surgical removal.

Clinical Course

This case represents a unique presentation of NLH with bilateral disease that exhibited avid PET scan uptake. Following resection, the patient made an uneventful recovery. However, her cough continued intermittently for 6 more months before resolving. At 1 year after resection, the patient remains asymptomatic.

  • 1. Nonspecific findings on small sample biopsy specimens are often of limited clinical use and may require confirmatory studies with larger samples.

  • 2. Increased metabolic activity on PET scan can be seen in a variety of settings unrelated to malignancy or infection.

  • 3. Numerous conditions, including lymphoma and IgG4 disease, may cause pulmonary lymphocytic predominant inflammation.

  • 4. NLH is a rare entity. A surgical biopsy is needed to establish the diagnosis, and surgical resection is recommended for treatment.

  • 5. Inflammatory pseudotumoris a histologically distinct entity from the migratorysilicone pseudotumor.

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:CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.

Persellin ST, Vogler JB III, Brazis PW, Moy OJ. Detection of migratory silicone pseudotumor with use of magnetic resonance imaging. Mayo Clin Proc. 1992;67(9):891-895. [CrossRef] [PubMed]
 
Abbondanzo SL, Rush W, Bijwaard KE, Koss MN. Nodular lymphoid hyperplasia of the lung: a clinicopathologic study of 14 cases. Am J Surg Pathol. 2000;24(4):587-597. [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]
 
Yi E, Aubry MC. Pulmonary pseudoneoplasms. Arch Pathol Lab Med. 2010;134(3):417-426. [PubMed]
 
Grubstein A, Cohen M, Steinmetz A, Cohen D. Siliconomas mimicking cancer. Clin Imaging. 2011;35(3):228-231. [CrossRef] [PubMed]
 
Tian X, Yi ES, Ryu JH. Lymphocytic interstitial pneumonia and other benign lymphoid disorders. Semin Respir Crit Care Med. 2012;33(5):450-461. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 –  A, B, Chest radiograph: (A) posteroanterior and (B) lateral views notable for the presence of a density in the right midlung anteriorly and possible density in the left posterior lung gutter.Grahic Jump Location
Figure Jump LinkFigure 2 –  A, B, CT scan chest views demonstrating (A) the presence of a pleural-based mass (3.48 cm) in the right midlung anteriorly, with multiple smaller bilateral pulmonary densities (A, B).Grahic Jump Location
Figure Jump LinkFigure 3 –  A, B, PET scan views notable for mildly hypermetabolic lymph nodes in the mediastinum; (B) multiple lesions demonstrating metabolic uptake and a hypermetabolic mass in the anterior portion of the right middle lobe with the standardized uptake value uptake of 21.9 (A).Grahic Jump Location
Figure Jump LinkFigure 4 –  CT image-guided needle aspiration of the mass demonstrating inflammatory process with lymphocytes, plasma cells, histiocytes, and neutrophils in the fibrous background without evidence of granulomas, consistent with inflammatory pseudotumor (hematoxylin and eosin, original magnification × 40).Grahic Jump Location
Figure Jump LinkFigure 5 –  Surgical lung biopsy specimen demonstrating benign reactive germinal centers with normal lung replaced by aggregates of lymphoid tissue (hematoxylin and eosin, original magnification × 4).Grahic Jump Location
Figure Jump LinkFigure 6 –  Surgical lung biopsy specimen demonstrating plasma cells and mature lymphocytes. Paraffin immunoperoxidase studies demonstrated a mixture of CD3+ T cells and CD20+ B cells with polyclonal plasma cells. Additional immunostains (CD138, IgG, and IgG4) did not reveal IgG4-related disease. No clonal immunoglobulin gene rearrangement was detected by a polymerase chain reaction-based assay (hematoxylin and eosin, original magnification × 40).Grahic Jump Location

Tables

Suggested Readings

Persellin ST, Vogler JB III, Brazis PW, Moy OJ. Detection of migratory silicone pseudotumor with use of magnetic resonance imaging. Mayo Clin Proc. 1992;67(9):891-895. [CrossRef] [PubMed]
 
Abbondanzo SL, Rush W, Bijwaard KE, Koss MN. Nodular lymphoid hyperplasia of the lung: a clinicopathologic study of 14 cases. Am J Surg Pathol. 2000;24(4):587-597. [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]
 
Yi E, Aubry MC. Pulmonary pseudoneoplasms. Arch Pathol Lab Med. 2010;134(3):417-426. [PubMed]
 
Grubstein A, Cohen M, Steinmetz A, Cohen D. Siliconomas mimicking cancer. Clin Imaging. 2011;35(3):228-231. [CrossRef] [PubMed]
 
Tian X, Yi ES, Ryu JH. Lymphocytic interstitial pneumonia and other benign lymphoid disorders. Semin Respir Crit Care Med. 2012;33(5):450-461. [CrossRef] [PubMed]
 
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