Intrathoracic manifestations of breast cancer

Radiología. 2011;53(1):7-17 ISSN: 0033-8338

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Intrathoracic manifestations of breast cancer A. Giménez,* T. Franquet, A. Hidalgo Sección de Radiología Torácica, Servicio de Radiodiagnóstico, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain Received 17 March 2010; accepted 7 July 2010

KEYWORDS Breast; Cancer; Complications; Thorax; Computed tomography; Magnetic resonance imaging; Ultrasonography; Positron emission tomography

Abstract Breast cancer continues to be the most common malignant neoplasm in women in Spain. The radiological study of intrathoracic manifestations, often secondary to complications, is of great interest because intrathoracic manifestations have a high prevalence and diagnosing them early significantly improves the patient’s prognosis. The imaging techniques in current use for this purpose include plain-film chest X-rays, computed tomography (CT), magnetic resonance imaging (MRI), thoracic ultrasonography, and hybrid techniques like positron emission tomography combined with CT (PET/CT). In this article, we review the imaging findings for the different types of intrathoracic complications of breast cancer, classified as: a) complications related to tumor dissemination, b) complications related to treatment, and c) idiopathic complications.

PALABRAS CLAVE Mama; Neoplasia; Complicaciones; Tórax; Tomografía computarizada; Resonancia magnética; Ecografía; Tomografía por emisión de positrones

Manifestaciones intratorácicas del cáncer de mama

© 2010 SERAM. Published by Elsevier España, S.L. All rights reserved.

Resumen En este trabajo se revisan los hallazgos radiológicos de los diferentes tipos de complicaciones intratorácicas del cáncer de mama, clasificadas como: a) complicaciones relacionadas con la diseminación tumoral, b) complicaciones relacionadas con el tratamiento, y c) complicaciones idiopáticas. El cáncer de mama sigue siendo la neoplasia maligna más frecuente en la mujer en nuestro país. El estudio radiológico de las manifestaciones intratorácicas, habitualmente secundarias a complicaciones, es de gran interés debido a su prevalencia, y el diagnóstico precoz de las mismas mejora de forma significativa el pronóstico de la paciente. Actualmente, las técnicas de imagen utilizadas incluyen la radiografía simple de tórax (RXT), la tomografía computarizada (TC), la resonancia magnética (RM), la ecografía torácica, y las técnicas híbridas, como la tomografía por emisión de positrones combinada con la TC (PET/TC). © 2010 SERAM. Publicado por Elsevier España, S.L. Todos los derechos reservados.

*Corresponding author. E-mail: [email protected] (A. Giménez). 0033-8338/$ - see front matter © 2010 SERAM. Published by Elsevier España, S.L. All rights reserved.

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Introduction Breast cancer is the most common malignancy in women. In Spain, this is the cancer with the highest mortality rate among women (18.2 %) and the leading cause of death among women aged 40-55 years. Incidence rates for breast cancer increased until 1991-1992 and have decreased since then. The age-adjusted mortality rates have decreased progressively: 17.8 deaths/100,000 women in 1985; 18.8 deaths/100,000 women in 1995; and 15.5 deaths/100,000 women in 2002. This decrease may be due to several causes, particularly the therapeutic advances and the introduction of breast cancer screening methods. The five-year survival rate has increased significantly: from 75.9 % during 1990-1994 to 80.9 % during 1995-1999. 1-3 The main risk factors for breast cancer are hormonal and reproductive factors; others include gender, age and family history. It has been estimated that 15-20 % of the new cases show familiar aggregation, and 5-10 % of them have a genetic predisposition. In order to achieve early detection, the identification of the genes associated with breast cancer allows us to select the patients with risk of developing the disease and to promote preventive measures and individualized screening. 4,5 The intrathoracic manifestations of breast cancer are the result of both tumor spread and tumor treatment. Presence of metastasis at diagnosis is not common (< 5 % of all cases). However, extraglandular spread may appear several years after the initial diagnosis and treatment of the primary tumor, and even after the administration of a complementary treatment. Metastatic spread is the most common thoracic complication of breast cancer. Routes of intrathoracic dissemination include lymph nodes, pulmonary arteries, bronchi, pleura and chest wall. There are different treatment approaches including surgery, radio- and chemotherapy that involve a variety of thoracic complications. Computed tomography (CT) is the technique of choice for the study of thoracic complications that are not visible on chest X-rays (CXR). Early detection of complications is of great importance for an effective treatment. The purpose of the present work is to offer a review of the radiologic manifestations of the intrathoracic complications of breast cancer related to: a) tumor dissemination; b) treatment (surgery, radio- and chemotherapy) and c) idiopathic causes.

Complications related to tumor dissemination Pulmonary dissemination Solitary or multiple pulmonary nodules The lungs are common sites for metastatic dissemination of breast cancer, being in most cases an incidental finding on radiographic studies. Autopsy studies based

Figure 1 A 48-year-old woman with a history of breast cancer shows cavitation of a pulmonary nodule in juxta-fissural location in the LSL. CT-guided fine needle puncture aspiration (FNA) demonstrated adenocarcinoma metastasis.

on large series of patients with breast cancer show pulmonary metastases in 57-77 % of patients. 6-9 Early detection of lung metastases is crucial to establish an effective treatment. CT is the diagnostic technique of choice. Lung metastases appear as peripheral solitary or multiple nodules of variable size. Solitary nodules require histologic confirmation since a solitary pulmonary nodule in a patient with breast cancer is more likely to be a second primary lung cancer than a metastatic lesion. 10,11 Cavitation of metastatic nodules is an uncommon finding on CXR but not on CT scans (fig. 1). In most cases, necrosis and cavitation are chemotherapyrelated. 12 Alveolar pattern in lung metastases The alveolar pattern of metastases from the breast is an unusual radiologic manifestation. The lepidic growth along the alveolar walls constitutes the histologic basis of this finding. This type of growth has also been described for the bronchioloalveolar carcinoma and for metastases of adenocarcinoma of the gastrointestinal tract. 13 Radiologic findings include ill-defined nodules with acinar features, consolidation containing an air bronchogram, focal or diffuse “ground-glass” opacities, and nodules surrounded by a “ground-glass” halo. The rarity of this type of metastases requires ruling out bronchioloalveolar carcinoma. Lymphangitic carcinomatosis Pulmonary lymphangitic carcinomatosis refers to tumor dissemination through the pulmonary lymphatics. In 25 % of cases is secondary to retrograde dissemination through hilar or mediastinal lymph nodes. However, in most cases it is the result of hematogenous spread of

Intrathoracic manifestations of breast cancer

Figure 2 A 57-year-old woman with a history of breast cancer and lymphangitic carcinomatosis. High-resolution chest CT (lung window) scan shows nodular thickening of the fissure and of the interlobar septa with bilateral involvement and bilateral pleural effusion.

breast cancer. In autopsy series, this pattern appears in 20-83 % of women who died of breast cancer. 14 The presence of lymphangitic carcinomatosis is a bad prognostic factor for chemotherapy response and for survival. Patients usually have dyspnea and nonproductive cough that may sometimes appear prior to the radiologic manifestations of the disease. CXR shows a reticular or reticulonodular pattern, usually with irregular contour, and thickening of the interlobar septa (Kerley B lines). It may have uni- or bilateral involvement. 15 High resolution CT is the most sensitive imaging modality for pulmonary lymphangitic carcinomatosis detection. The most common finding is the smooth or nodular thickening of the interlobar septa and of the peribronchovascular and subpleural interstice with preservation of the normal lung architecture (fig. 2). Endobronchial metastases Endobronchial metastases are uncommon. Breast, renal, thyroid and gastric cancer and melanoma are the most common tumors causing this type of d i s s e m i n a t i o n . 16 T h e i n c i d e n c e o f e n d o b r o n c h i a l metastasis from breast cancer is 2- 5 %. 17,18 Routes of dissemination to the bronchial wall are: a) hilar or mediastinal metastatic lymphadenopathies, b) parenchymal metastasis with bronchial involvement, c) bronchial aspiration of tumor cells, d) direct lymphangitis to the bronchial wall, and e) hematogenous metastases to the bronchi. 19 Clinical manifestations of endobronchial metastases are inespecific and include cough, hemoptysis or dyspnea.

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Figure 3 A 44-year-old woman with a history of left breast cancer treated with mastectomy and subsequent breast reconstruction with implants. CT scan (lung window) shows a pulmonary nodule in the ML, with a tubular image suggestive of endobronchial spread.

Although CXR appears usually normal, sometimes demonstrates different degrees of bronchial obstruction resulting from: endobronchial mucus plugging, atelectasis or obstructive pneumonitis in case of complete obstruction; and lobar oligoemia or air trapping on expiratory CXR in case of incomplete obstruction. CT is a very useful imaging tool to confirm the diagnosis and to rule out other causes of bronchial obstruction (fig. 3). Multiplanar reconstruction and 3D techniques, including virtual bronchoscopy, are also useful in lesion characterization and localization. 12,19,20 Confirmation of the disease is achieved by fibrobronchoscopy that shows solitary or multiple endobronchial nodules of smooth or lobulated margins. Tumor embolism Pulmonary tumor embolism is observed at autopsy in 26 % of patients and occurs most commonly in breast, liver, stomach, kidney cancers and choriocarcinoma. 21 As for breast cancer, tumor embolism is identified in 17 % of cases. 22,23 In the majority of these cases, the CXR is normal or shows unspecific findings. Pulmonary embolism should be suspected when a patient with breast cancer develops progressive dyspnea (present in 70 % of patients), cough, hypoxemia and pulmonary hypertension. Contrast-enhanced chest CT is currently the modality that provides the fastest and most accurate imaging of this complication. Common CT findings of nonthrombotic pulmonary embolism are: a) multifocal dilatation and tortuosity of the subsegmental pulmonary arteries and/or b) subpleural nodular opacities with wedge-shaped morphology, corresponding to pulmonary infarcts. The presence of pulmonary embolism in arteries of large caliber is unusual. 23

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Another type of nonthrombotic pulmonary embolism is the intravascular tumor dissemination. CT findings include centrilobular nodules and branching vascular structures with a “tree-in-bud” appearance very similar to that of cellular bronchiolitis. Morphologically, this finding is characterized by repletion of the distal pulmonary arterioles, of centrilobular location, and intimal hyperplasia induced by tumor embolism. This finding is known as pulmonary tumor thrombotic microangiopathy. 24 Ventilation-perfusion scintigraphy is also a very useful technique in the diagnosis of tumor thromboembolism showing multiple subsegmental infarcts in small peripheral pulmonary arteries, arterioles or capillaries, with no ventilatory abnormalities. 25 Pulmonary angiography is not a routine technique and is only used in very specific cases. Angiographic findings include delayed filling of the segmental arteries and tortuosity of the small peripheral vessels. 26,27

Malignant pleural effusion and pleural metastases Breast cancer is the second most common cause of pleural metastases and of malignant pleural effusion. 28 Autopsy studies reported pleural metastases in 50-75 % of patients with breast cancer. 8,29 In these cases, pleural effusion is secondary to direct pleural infiltration and/or to the obstruction of lymphatic drainage. Clinical manifestations include dyspnea, initially on exertion but that gradually progresses to dyspnea at rest. Chest pain is not common, appearing in less than 25 % of patients. 30 Characteristic radiologic findings include: a) irregular and/or nodular thickening of the pleura and pleural effusion, sometimes encapsulated. The effusion is usually unilateral and ipsilateral to the primary tumor. Sometimes circumferential pleural thickening with extension into the fissure is also present. Less commonly, pleural metastases appear as a pleural mass or nodule that may mimic a peripheral lung carcinoma. Unilateral metastases are indistinguishable from malignant mesothelioma. 31 Chest CT is very useful in the differentiation between benign and malignant pleural disease, since it clearly demonstrates the diffuse nodular or circumferential pleural thickening and the presence of single or multiple seedings (fig. 4). Because of its high ability in tissue differentiation, MR imaging continues to be a valuable complementary modality for the detection of tumor invasion into the chest wall and mediastinal structures. Thoracocentesis combined with pleural biopsy provides the definitive diagnosis. In malignant effusion the fluid is usually an exudate with low glucose concentration, bloody appearance and a variable number of malignant cells. Larger effusions are more likely to be malignant. 11

Bone metastases Bone is the most common site of recurrence of breast cancer. Bone metastases are detected in 30-85 % of patients and can occur in any bone of the skeleton during the course of the disease. 32,33 Bone metastases

Figure 4 Right breast nodule corresponding to breast cancer in a 65-year-old woman. IV contrast-enhanced CT scan (mediastinal window) shows right pleural effusion, with right-sided nodular thickening of the pleura, corresponding to pleural mestastases. Note the spiculated nodular lesion in the right breast.

cause considerable morbidity, with pain, impaired mobility, hypercalcemia, pathologic fractures, spinal cord compression, and bone marrow infiltration. 34 The presuntive diagnosis is based on the medical history, physical examination and imaging studies. Imaging techniques are essential for the detection of bone metastases, but no clear consensus exists on their use. Imaging techniques include plain X-ray, CT, MRI, PET/CT and bone scintigraphy. Radiologic fi ndings include osteolytic, osteoblastic or mixed lesions and pathologic fractures are present in 11 % of cases. 32 However, plain radiographs have a low sensitive for bone metastasis screening and osteolytic lesions are visible only when there is severe bone loss (30-75 %). 35,36 Despite this fact, conventional radiographs are useful to evaluate the therapeutic response of the tumor, demonstranting the presence of sclerotic bone changes and the normalization of the trabecular structure. 37-39 CT, with bone window, allows accurate assessment of the bone structure and bone marrow. The sensitivity of CT in the diagnosis of bone metastases is 71-100 %. 33,40-42 Initially, there is bone marrow involvement via lymphatic or hematogenous spread. At this stage, CT can detect metastases even before bone destruction is evident. CT is even superior to bone scintigraphy in the detection of spinal and calvarial metastases 43,44 and is also useful to assess the favourable response to treatment. MR imaging is a very useful modality for the evaluation of bone marrow (sensitivity: 82-100 %; specificity: 73-100 %). 33,45,46 MR is superior to CT in the assessment of bone marrow, soft tissue and spinal disease. MRI is the

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Figure 5 Left chest wall recurrence in a 61-year-old woman treated with lumpectomy. a) IV contrast-enhanced CT scan shows infiltration into the pectoral muscles and mediastinal fat. b) MRI T1-weighted image demonstrates more clearly the infiltration into the epicardial fat (arrow).

technique of choice for cancer patients with vertebral fractures and spinal cord compression. However, its usefulness in the case of lytic lesions in the cortex of the bone is limited given the absence of signal from this area in T1- and T2-weighted sequences. PET/CT is a very useful technique for the detection of bone metastases (sensitivity: 62-100 %; specificity: 96-100 %) 33,46,47 but it has lower sensitivity for the detection of osteoblastic metastases. Recent studies have proven its clinical value in monitoring the response to chemotherapy. 48

Extension into the chest wall (locally advanced breast cancer and local recurrence) Locally advanced breast cancer may affect the rest of the structures of the chest wall through direct extension, even with parenchymal involvement. Accurate assessment of the disease extent is important for treatment planning, especially for radiotherapy. Local recurrence is the reappearance of tumor at the surgical site with involvement of lymph nodes and chest wall structures. This complication is more common in patients who have not received postoperative radiotherapy and in those with large primary tumors, positive margins and positive lymph nodes, as well as in multicentric carcinomas. 11,49,50 Mammography can help detect local recurrence. However, sometimes postoperative distortion and the increased density of the irradiated breast may compromise its usefulness. For this reason, mammography is able to detect only two-thirds of chest wall recurrences in patients who undergo conservative treatment. 50 Ultrasound (US) is more sensitive (91 %) than mammography (79 %) in the detection of local recurrence following mastectomy. 51 The use of CXR is limited to osteolytic lesions or evident extrapleural lesions.

CT is, however, very superior to the previously mentioned techniques in the determination of disease infiltration into the chest wall, particularly with bone involvement. In addition, CT is of great value in postmastectomy evaluation of local recurrence to plan radiotherapy. CT findings in local recurrence include focal skin thickening, focal areas of soft-tissue density within the subcutaneous fat, and masses within the pectoralis muscles (fig. 5a). 52 At MR examination, tumor invasion of the chest wall shows areas of high/intermediate signal on T1-weighted sequences, and high signal on T2-weighted sequences (fig. 5b). Abnormal enhancement following IV gadolinium is the most valuable diagnostic finding to confirm muscle involvement. Although pectoralis muscle involvement does not change TNM staging (but invasion of the serratus and intercostal muscles is considered T4), this finding should be taken into account for preoperative surgical planning. 53,54 The important role of PET/CT in the early detection of local recurrence has recently been proven (sensitivity, 84 %; specificity, 78 %). 55

Lymph node metastases The degree of lymphatic involvement is one of the most important pronostic factors in breast cancer patients. Breast lymphatics drain via three major routes: axillary, transpectoral and internal mammary. Axillary lymph node dissection continues to be an important approach for breast cancer staging. Preoperative identification of the first draining axillary node (sentinel node) is useful in limiting the extent of surgical resection. The sentinel node is first identified by intratumor injection of technetium-99m radiocolloid or methylene blue and subsequently resected. If this node is negative, further dissection is not performed. 56

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This technique is used in patients with small tumors and clinically negative axillary nodes. The internal mammary lymph chain is an important site of clinically occult metastases. Metastases to this territory can arise from tumors in all breast quadrants and the probability of invasion is directly related to the diameter of the primary tumor and the presence of axillary nodal metastases. 57 Although chest radiography can detect chest lymphadenopathies, CT is the technique of choice for the preoperative evaluation of lymph nodes, allowing easy evaluation of their size and location (fig. 6). Since normal internal mammary lymph nodes are not visible on CT scans, the presence of nodes > 5mm is highly suggestive of mestastes. 57 Parasternal US is a complementary technique in the diagnosis of internal mammary lymph node metastases. 58 In the rest of the mediastinal lymph nodes, node size has low diagnostic sensitivity. MR imaging should be considered a complementary technique in the evaluation of lymph node involvement. In recent years, PET/CT has gained importance in the evaluation of axillary and mediastinal nodal involvement. Recent studies have reported that this technique is superior to CT in the study of mediastinal lymphadenopathies and of the internal mammary chain. 59

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Figure 6 Breast cancer in a 59-year-old woman. Contrast-enhanced sagittal CT scan obtained with multiplanar reconstruction shows a metastatic lymph node in the internal mammary chain, with infiltration of the chest wall structures (arrows).

Complications related to the treatment Surgery complications Complications of breast cancer surgery include: seroma formation, infection, hemorrhage, skin flap necrosis, lymphedema and axillary contracture. Seromas are the most common postoperative complication for patients who undergo mastectomy (25-50 %) or axillary node dissection (25 %). 60 Seromas are secondary to disruption of the lymphatics during surgical procedures and appear as subcutaneous collections of fluid below the surgical area. Mammograms show a dense mass with well-defined or spiculated margins. Mammograms obtained in a 90° projection may demonstrate air-fluid levels. Seromas appear as an anechoic fluid collection at US and as a low attenuation mass at CT (fig. 7). The treatment is US-guided drainage. Wo u n d i n f e c t i o n i s t h e s e c o n d m o s t c o m m o n complication of breast cancer surgery (5.6-14.2 % of patients). 61 Most cases appear immediately after surgery as cellulitis. If antibiotic therapy is not effective, cellulitis may progress to abscess formation and need debridement. This complication is most often caused by S. pneumoniae and S. aureus. At US, cellulitis manifests as edema, with a linear pattern of interposed hypoechoic fluid. At CT, it can manifest as diffuse infiltration at the surgical site with multiple strands of soft tissue density.

At US, abscess manifests as a complex, predominantly cystic, mass with internal echogenic areas. At CT, it appears as a low-attenuation fluid collection with thickened margins and peripheral IV contrast enhancement.

Complications related to radiotherapy Radiotherapy may be used as a curative or palliative treatment in a significant number of thoracic neoplasms, including breast cancer. Radiotherapy, alone or in combination with chemotherapy, is used in postoperative breast cancer patients to reduce the number of locoregional recurrence. Most patients show no thoracic symptoms or subclinical symptoms, mostly secondary to radiotherapy-induced changes. There are four types of complications secondary to radiotherapy: a) pneumonitis and radiation fibrosis, b) organizing pneumonia, c) chest wall sarcomas, and d) radiation osteitis. Pneumonitis and radiation fibrosis Radiologically, the pulmonary damage induced by radiotherapy manifests differently depending on the time elapsed from the completion of the radiation treatment. At the early stage, 1-3 months after treatment, the lesion that appears is known as radiation pneumonitis. At a late or chronic stage, a lesion that

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seems to be an immunologically-mediated pulmonary response. 62

Figure 7 A 45-year-old woman with a recent history of left mastectomy. IV contrast-enhanced CT scan shows a biloculated collection of low-density in the left breast corresponding to a postoperative seroma.

occurs later and takes 12–15 months to stabilize is known as radiation fibrosis. Radiologic manifestations of lung damage are rare with doses lower than 30 Gy, but always appear beyond 40 Gy. Predisposing factors for radiation-induced lung damage include: a) prior irradiation; b) chemotherapy; c) extension of the irradiated area, radiation dose and fraction size; and d) withdrawal of previous steroid therapy. 62 At CXT and CT, radiation pneumonitis manifests as ill-defined pulmonary opacities (ground-glass opacities or alveolar consolidation) that conforms to the shape of the treatment portal. Pleural effusion is a rare finding. Radiographic changes in radiation fibrosis are confined exclusively to the irradiated area and include reticular opacities, consolidation areas, traction bronchiectasis and loss of volume. Characteristically, these findings become stable two years after treatment. 62 Organizing pneumonia Organizing pneumonia is a rare complication in breast cancer patients. Clinically this disorder manifests as a flu-like syndrome, with fever, non-productive cough and dyspnea. Histologic findings include polypoid formations of inflammatory granulation tissue within the alveoli. The most common appearance at chest radiography is ill-defined bilateral opacities of alveolar consolidation or ground-glass infiltration, predominantly of middle or low distribution. Subpleural or peribronchovascular distribution of these opacities is more easily visualized on CT. Typically these areas of increased opacity are changing, may change location, dissapear with no treatment and reappear at a later stage. Unlike radiation pneumonitis, organizing pneumonia develops out of the radiation field (fig. 8). Although its etiopathogenesis is not clear, it

Chest wall sarcomas Radiation-induced sarcomas are an infrequent complication of radiotherapy. Depending on the series, these radiation-induced sarcomas occur in 0.03-1.9 % of patients who receive chest radiotherapy, with higher incidence after breast cancer treatment. 63 Criteria for the diagnosis of this type of sarcoma include: a) origin at the radiation site, b) radiation dose of 25-80 Gy, c) a minimum of three years of latency since completion of radiotherapy, and d) histologic findings different from t h o s e o f t h e p r i m a r y t u m o r. 6 3 T h e m o s t c o m m o n radiation-induced sarcomas are: osteosarcoma, malignant fibrous histiocytoma and fibrosarcoma. Sarcomas exhibit an aggressive behaviour with a marked tendency toward local recurrence and distant metastasis. At radiography, radiation-induced sarcomas are indistinguishable from thre rest of sarcomas. Depending on the histological findings the lesions are predominantly lytic or blastic. Bone changes in previously irradiated areas or the presence of a soft-tissue mass are suggestive of radiation-induced sarcoma. CT and MR findings include a soft-tissue mass associated with a bone tumor of lytic or blastic type (fig. 9). The differential diagnosis includes metastasis, infection and post-radiation necrosis. Histologic findings provide the final diagnosis and the prognosis depends on the histological degree of malignancy. Radiation-induced osteitis Rib fractures, secondary to radiation osteitis, frequently occur (1.8 %) in patients with breast cancer treated with radiation therapy. These fractures are generally multiple and appear in patients who have received radiation doses > 50 Gy. In most cases they are asymptomatic. 64 CT is the imaging modality of choice for their evaluation. Delayed union, fragment resorption and abnormal callus formation—which may be difficult to differentiate from a radiation-induced sarcoma—may be frequently observed.

Complications related to chemotherapy Pulmonary Drug Toxicity Pulmonary drug toxicity, acute and chronic, is a known cause of lung disease. The agents used to treat breast cancer are: cyclophosphamide, methotrexate, 5-fluorouracil, and doxorubicin. 11,65 CT is much more sensitive than CXR in demonstrating pulmonary drug toxicity. CT findings generally correlate closely with the underlying histopathologic processes: nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIN), hypersensitivity pneumonitis, organizing pneumonia, pulmonary hemorrhage, and diffuse alveolar damage (DAD). CT patterns show bilateral alveolar opacities with subpleural or peribronchovascular distribution and patchy areas of

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Figure 8 A 67-year-old woman with a history of left breast cancer treated with lumpectomy and radiotherapy that presented with nonproductive cough and dyspnea on strenuous exertion. a) PA chest radiograph shows opacity of alveolar characteristics in the RSL. b) CT scan (lung window) demonstrates alveolar opacities with peripheral parenchymal retraction in the RSL and LIL, which had not been included in the radiation field. Note a subpleural band of pulmonary fibrosis in the anterior segment of the LSL suggestive of radiation fibrosis. c) After corticosteroid therapy, the follow-up scan shows disappearance of the opacities that corresponded to foci of organizing pneumonia.

“ground-glass” attenuation associated with septal thickening. Sometimes CT shows pulmonary fibrosis mainly involving the lower lobes with traction bronchiectasis and honeycomb pattern. 66

Idiopathic complications Sarcoid reaction Sarcoid reaction is characterized by the development of noncaseating granulomas in patients with malignancies, without clinical symptoms of systemic sarcoidosis. This disorder has been described in breast cancer, lymphoma, clear cell renal carcinoma and bronchogenic carcinoma, among others. 67,68 Although its etiopathogenesis remains u n c l e a r, s i m i l a r c a u s e s h a v e b e e n s u g g e s t e d f o r sarcoidosis and malignancy-associated sarcoid reaction. Understanding of this disease is important in order to help establish a differential diagnosis between sarcoid reaction and metastatic disease. The radiologic features of these two disorders are similar including hilar or

mediastinal lymphadenopathies and pulmonary nodules following perivascular and peribronchial distribution (fig. 10).

Authorship Ana Giménez has contributed to the conception and design of the study, drafting of the paper and has made relevant contributions to its content. Tomás Franquet has contributed to the conception, design and editing of the study. Alberto Hidalgo has contributed to the analysis and critical review of the study and has made relevant contributions to its final content. All the authors have read and approved the final version of the manuscript.

Conflict of interest The authors declare no conflict of interest.

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Figure 9 An 81-year-old woman with a history of breast cancer treated with surgery and radiotherapy 20 years ago. CT scan (mediastinal window) clearly shows a sternal mass with sclerotic areas and soft-tissue component. The histopathologic examination demonstrated a radiation-induced sternal osteosarcoma.

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Figure 10 A 46-year-old woman with a left breast nodule corresponding to breast cancer. Note the bilateral hilar lymphadenopathies whose histopathologic diagnosis was sarcoid reaction.

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