Canadian Association of Radiologists Journal xx (2015) 1e8 www.carjonline.org
Thoracic and Cardiac Imaging / Imagerie cardiaque et imagerie thoracique
Review of Thoracic Imaging Findings Unique to Women Alla Khashper, MDa,*, James M. Gruber, MD, FRCPb, Richard S. Fraser, MD, FRCPc, Federico Discepola, MD, FRSCRd, Alexandre Semionov, MD, PhD, FRCRa b
a Department of Radiology, McGill University Health Centre, Montreal, Quebec, Canada Department of Pulmonology, McGill University Health Centre, Montreal, Quebec, Canada c Department of Pathology, McGill University Health Centre, Montreal, Quebec, Canada d Department of Radiology, Jewish General Hospital, Montreal, Quebec, Canada
Abstract Purpose: Traditionally, indications for imaging studies of women are considered to be related to screening for and evaluation of disease of the female breast and pelvis. However, a number of chest diseases and associated intrathoracic imaging findings are unique to women and should be recognized by general radiologists, as well as chest and women-imaging specialists. Conclusions: The sex-specific findings unique to women include normal anatomical variants, primary lung disease, complications of breast and gynaecological disease, and pregnancy-related conditions. Classification, description, and illustration of gender-specific chest imaging findings are the objective of this article. Resume Objectifs : Traditionnellement, on considere que les indications des examens d’imagerie chez les femmes sont reliees au depistage et a l’evaluation des atteintes du sein et du bassin. Neanmoins, certaines affections thoraciques et anomalies connexes decouvertes a l’imagerie intrathoracique sont propres aux femmes et devraient ^etre reconnues par les radiologistes generalistes ainsi que par les specialistes de l’imagerie thoracique et de l’imagerie chez les femmes. Conclusions : Les observations radiologiques propres aux femmes comprennent les variantes anatomiques normales, les pneumopathies primaires, les complications d’affections du sein et de maladies gynecologiques, ainsi que les affections liees a la grossesse. La classification, la description et l’illustration des aspects d’imagerie thoracique sexospecifiques constituent l’objet du present article. Ó 2015 Canadian Association of Radiologists. All rights reserved. Key Words: Thoracic imaging; Women imaging; Gender specific findings; Women chest
The anatomical and physiological differences between women and men are associated with sex-specific variations in the normal imaging appearance and in differences in the incidence of certain pathological conditions between the 2 groups. These differences are much more extensive than the reproductive system and breast and consist of normal anatomical variants, primary lung disease, complications of breast and gynaecological disease, and pregnancy-related conditions. A number of thoracic pathologies are exclusive
* Address for correspondence: Alla Khashper, MD, Department of Radiology, McGill University Health Centre, 1650 Cedar Avenue, Suite C5 118, Montreal, Quebec H3G 1A4, Canada. E-mail address: [email protected] (A. Khashper).
to women and should therefore be familiar to radiologists at large and to chest and women imaging experts in particular. The goal of this article is to draw attention to what is currently known about female sex-specific chest findings, both normal and pathological. Pathologies that are predominantly seen in women, but can be found in men, as well as primary breast disease are excluded from the discussion. Anatomical Features of the Female Chest The female thoracic cage is generally more rounded and smaller than that of the male. Studies have shown that women have a smaller rib cage size, a greater inclination of ribs, a comparable diaphragm dome position relative to the spine and a shorter diaphragm length than males of the same height.
0846-5371/$ - see front matter Ó 2015 Canadian Association of Radiologists. All rights reserved. http://dx.doi.org/10.1016/j.carj.2014.11.007
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A. Khashper et al. / Canadian Association of Radiologists Journal xx (2015) 1e8
Figure 1. Normal chest radiograph (A) of a 24-year-old woman clearly reflects gender-related features due to prominent breast shadows. Also, note characteristic central pattern of costal cartilage calcification (arrow) seen on coned down and zoomed-image (B).
Female lungs tend to be smaller, but are otherwise undistinguishable from male lungs at surgery or on autopsy [1]. On chest radiography, prominent breast tissue and central pattern of costal cartilage calcification usually allow to readily identify a female patient compared to the lack of breast shadows and peripheral pattern of costal cartilage calcification in men (Figure 1) [2]. That might be important in patient identification in cases of a mislabeled study or ambiguous name. Pregnancy related thoracic anatomical changes are well recognized on imaging. These include upward displacement of the diaphragm compensated by an increased diameter of the thoracic cage that together results in shortening and widening of the lungs [1]. Developmental Anomalies and Genetic Disease Few genetic diseases associated with chest manifestations are seen exclusively in females. The most common of these is Turner syndrome.
Turner syndrome is diagnosed in females with partial or complete absence of one X chromosome (45, XO karyotype). Characteristic thoracic findings in patient with Turner syndrome include a broad chest with widely spaced nipples and short or prematurely fused sternum, cardiovascular abnormalities, and congenital lymphoedema. The congenital cardiovascular anomalies include aortic coarctation (Figure 2), bicuspid aortic valve, aortic dilatation or aneurysm and an increased risk of aortic dissection [3]. Lymphangioleiomyomatosis Lymphangioleiomyomatosis (LAM) is an interstitial lung disease that almost exclusively affects women of reproductive age. It may occur sporadically or in association with tuberous sclerosis complex. Progressive dyspnea, recurrent pneumothoraces, hemoptysis, and chylous pleural effusions are common clinical manifestations [4] in symptomatic patients.
Figure 2. Turner syndrome and a complex aortic malformation. Chest radiograph (A) shows right-sided aortic arch (asterisk in A; Rt arch in B) resulting in deviation of the trachea to the left. Aortic coarctation (AC) and aneurysmal right brachiocephalic artery (RtBCA) are demonstrated on computed tomography 3D volume rendering reconstruction (B). Note is made of normal size of the left common carotid artery (LtCCA).
Unique Thoracic Imaging Findings in Women / Canadian Association of Radiologists Journal xx (2015) 1e8
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patients demonstrate increased lung volumes, while reduced volumes represent an unusual finding [5]. High-resolution computer tomography (HRCT) better than radiography demonstrates the lung cysts, which are typically small (2-5 mm in diameter) and uniform in size without regional sparing (Figure 3C). Cysts are usually round or ovoid in shape, but become polygonal and increase in size with progression of the disease. The surrounding lung parenchyma could be normal or show air trapping and septal thickening. Focal ground-glass opacities also may be seen, due to recurrent pulmonary hemorrhage [4,5]. Thoracic Endometriosis and Catamenial Pneumothorax
Figure 3. Lymphangiomyomatosis. Coronal reconstruction of a computed tomography scan shows diffuse involvement of both lungs with innumerable thin-walled cysts, slightly more pronounced at the lung bases.
In the thorax, LAM is characterized pathologically by abnormal peribronchial, perivascular, and perilymphatic proliferation of immature smooth muscle cells that results in bronchiolar and lymphatic obstruction leading to lung cyst formation. The chest radiograph might demonstrate progressive appearance of faint reticular opacities and thin walled cysts, corresponding to clinical deterioration and increasing pulmonary involvement (Figures 3A and 3B) [4]. Interstitial opacities on chest radiograph have been described as affecting both lungs diffusely with basal predominance due to summation effect of numerous thin-wall cysts, or predominantly involving the lower lung zones. About half of
Endometriosis represents ectopic endometrial cells outside of the uterus, which symptoms are associated with menstrual periodicity [6]. Thoracic endometriosis occurs in 2 distinct clinicopathologic forms: pleurodiaphragmatic and bronchopulmonary. The precise pathogenesis of thoracic endometriosis remains unknown. Two main mechanisms of pathogenesis have been postulated to explain the development of each formdtransplantation of endometrium to ectopic sites and metaplastic differentiation of serosal cells lining pleural cavity. The former hypothesis suggests that endometrial tissue can be transported from the peritoneal cavity to the pleural space through diaphragmatic defects or represent microembolization through pelvic veins [6,7]. Pleural lesions are almost exclusively right-sided, whereas parenchymal lung endometriosis might be found in the right or left lung. Concomitant pelvic endometriosis is present in up to half of women with thoracic endometriosis [7]. Chest pain associated with menstrual periodicity represents the typical clinical presentation of patients with thoracic endometriosis. Catamenial pneumothorax is generally defined as a pneumothorax occurring between 24 hours before, and 72 hours after, the onset of menses. As expected, findings may include pneumothorax in most cases; hemothorax and hemoptysis are seen occasionally (Figure 4) [6].
Figure 4. Catamenial pneumothorax in a 43-year-old woman who presented with 3 episodes of spontaneous pneumothorax, each associated with the onset of menses. Expiratory chest radiograph (A) shows a right-sided pneumothorax (arrows), as well as right apical scar from remote right apical bullectomy (arrowhead). Medium-power photomicrograph (original magnification, 20; hematoxylin-eosin stain) (B) shows an endometriotic implant in the parietal pleura (arrows).
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and postpartum cardiomyopathy. Pulmonary oedema can occur as a complication of tocolytic treatment or in association with pre-eclampsia. Adult respiratory distress syndrome may result from gestational complications such as pre-eclampisa/eclampsia and sepsis [8]. Gestational trophoblastic disease comprises a range of pregnancy-related disorders, including complete and partial hydatidiform mole, invasive mole, choriocarcinoma, and the rare placental trophoblastic tumour. Molar pregnancy can occasionally degenerate into choriocarcinoma. This commonly metastasizes to the lung, producing multiple discrete pulmonary nodules, while pleural effusion is uncommon (Figure 5). Lung nodules are usually well defined or show shaggy, ill-defined borders reflecting hemorrhage. Choriocarcinoma is very sensitive to chemotherapy; therefore, early diagnosis is the key to adequate patient management [9]. Pregnancy can negatively affect the course of some chronic diseases, most notably asthma, sarcoidosis, and systemic lupus erythematosus. Conversely, these conditions, if poorly controlled, can unfavorably affect pregnancy. Figure 5. Metastatic choriocarcinoma. Coronal reconstruction of chest computed tomography reveals a few tiny nodules (arrows) scattered bilaterally, that resolved on follow up exam obtained after chemotherapy (not shown).
Pregnancy-Related Pathology
Thoracic Involvement in Primary Ovarian Tumours The most common thoracic abnormality in patients with metastatic ovarian carcinoma is pleural effusion, which is seen in up to half of patients. Pulmonary parenchymal metastases are rare and usually are preceded by recurrence of the disease
Pregnancy results in a number of anatomical and functional changes in the respiratory and cardiovascular systems. Pregnancy also increases the risk of several pulmonary disorders, such as aspiration and influenza pneumonia. A hypercoagulable state during pregnancy results in increased risk of pulmonary artery embolism. Possible peripartum complications include amniotic fluid pulmonary embolism
Figure 6. Metastatic ovarian cancer. Chest computed tomography demonstrates scattered bilateral pulmonary nodules, some of which underwent cavitation.
Figure 7. Small cell ovarian carcinoma in 28-year-old woman, who presented with chest pain and hyperkalemia. Chest radiograph reveals mediastinal and hilar lymphadenopathy. Positron emission tomography-computed tomography scan (not shown) demonstrates 17 cm left ovarian mass associated with infra- and supradiaphragmatic lymphadenopathy showing avid uptake of radiotracer. Percutaneous biopsy of supraclavicular lymph node proved the presence of small cell ovarian carcinoma.
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Figure 9. Metastatic uterine leiomyoma. Coronal reconstruction of a chest computed tomography reveals several cystic lesions (arrows) scattered in both lungs, as well as a small right pneumothorax.
Figure 8. Meigs syndrome. Sagittal reconstruction of contrast enhanced thoracoabdominal computed tomography reveals a large pelvic mass (arrows) associated with ascites and right pleural effusion. An ovarian fibroma was resected, followed by complete resolution of the effusion and ascites.
in the abdomen or pelvis [10]. Thus, increased number and size of lung nodules might be seen with progression of the primary disease, whereas central cavitation of the lung nodules (Figure 6) and decrease in their size and number usually indicate a response to treatment and are commonly associated with regression of intra-abdominal disease. Ovarian neoplasms can also metastasize to the mediastinum, most commonly resulting in paracardiac lymph node enlargement (greater than 5 mm in diameter). However, extensive mediastinal lymphadenopathy accompanies ovarian cancer rarely. One exception to this statement is small cell carcinoma of the ovary, a rare tumour that is typically associated with hyperkalemia and early metastases to abdominal and mediastinal lymph nodes (Figure 7) [11]. Benign ovarian fibroma may be associated with pleural effusion and ascites, the so-called Meigs syndrome (Figure 8). Both effusion and ascites such as resolve following removal of the ovarian lesion. When other metastatic or primary adnexal or uterine tumours are accompanied by pleural effusion, the term ‘‘pseudo-Meigs syndrome’’ is sometimes used [12]. Thoracic Involvement in Uterine and Cervical Tumours Various malignant tumours of the uterus might present with intrathoracic metastases, resulting in findings of lung
nodules, pleural effusion, and lymphadenopathy. Both benign and malignant uterine tumours metastasize predominantly to the lung [10]. Pulmonary metastases from carcinomas originating from the cervix and endometrium are uncommon. Radiographically, the pulmonary metastases from both cervical and endometrial neoplasms are usually smooth lesions that may have cavitations [10]. So-called ‘‘benign metastasizing leiomyoma’’ is a rare disorder characterized by well-circumscribed nodules of smooth muscle cells in the lungs. Although there is typically no obvious primary site at the time of their identification, the nodules are believed to represent hematogenous metastases from a smooth muscle tumour. Despite this, they show no histologic features of malignancy, including cytologic atypia and mitotic activity. Although the condition has been reported in association with smooth muscle tumours originating in a variety of sites, the most common by far is the uterus. In most cases of benign metastasizing leiomyoma, there is a history of uterine leiomyoma resection several years before development of the pulmonary disease [13]. The characteristic radiographic appearance is that of multiple well-circumscribed pulmonary nodules. However, a solitary nodule, a miliary pattern, cavitary nodules (Figure 9), and interstitial disease have rarely been reported [4]. Uterine leiomyosarcoma comprises about 25% of uterine sarcomas and 1% of all uterine malignancies. The uterus is by far the most common primary site of leiomyosarcoma and hence, pulmonary metastases of such tumours are almost exclusively found in women. Patients are typically young (30-40 years old) and present with gynecologic signs or symptoms such as vaginal bleeding, lower abdominal pain, and a pelvic mass. Parenchymal pulmonary nodules are the typical radiographic manifestation. As with other sarcomas, a subpleural location is often seen and pneumothorax is an occasional complication (Figure 10) [4].
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Figure 10. Metastatic uterine leiomyosarcoma treated with hysterectomy 2 years prior. Chest computed tomography reveals solid (arrowhead) and cavitary (arrow) pulmonary nodules in the left lung. The spontaneous right pneumothorax was thought to be a result of an occult right lung metastasis.
Thoracic Metastases From Breast Cancer Imaging exams of the chest other than mammography may reveal a breast mass in the chest wall or intrathoracic abnormalities resulting from treatment, complications of treatment, or metastases. Thoracic metastases of breast carcinoma can present radiographically as solitary or multiple lung nodules, airspace consolidations, lymphangitic carcinomatosis, or pleural effusion. Lymphangitic carcinomatosis is commonly seen in advanced cases (Figure 11), causing irregular, nodular thickening of interlobular septae and bronchovascular bundles [13]. Bone is the second most common site affected by metastatic breast cancer. Purely lytic, aggressive, and destructive lesions represent early stages of metastatic disease, while multiple, confluent sclerotic bone lesions are a more typical feature of advanced or treated metastatic breast cancer [14].
Figure 11. A 67-year-old woman with metastatic breast cancer. Diffuse interlobular septal thickening (arrows) is consistent with lymphangitic carcinomatosis. Bilateral malignant pleural effusions and diffuse blastic bone metastases (arrowheads) confirm metastatic disease. Treatment-related findings include left mastectomy and axillary lymph node dissection, as well as architectural distortion, traction bronchiectasis, and fibrosis of the left lung secondary to prior radiotherapy.
Figure 12. A 67-year-old woman with history of thyroidectomy. Contrastenhanced chest computed tomography (CT) demonstrates left chest wall mass (arrow) associated with borderline left axillary nodes. Positron emission tomography-CT revealed moderate fluorodeoxyglucose uptake, prompting CT-guided biopsy of the lesion. During the procedure the patient gave the history of previous breast implant removal due to local infection. Fibrosis and granulation tissue was demonstrated in a biopsy sample.
Treatment-Related Findings Various complications occur in the chest following interventional procedures, surgical treatment, and radiotherapy of diseases specific to women. In these cases, clinical history and correlation with details of prior treatment are crucial, as illustrated in Figure 12. The majority of these treatment-related intrathoracic findings complicate management of primary pathology localized within the chest cage. But in some cases distant intrathoracic complications may occur. Ovarian hyperstimulation syndrome is an uncommon, but serious complication of induced ovarian ovulation for infertility treatment. Imaging findings include pleural effusions, ascites, and markedly enlarged ovaries with multiple cysts (Figure 13). Possible thoracic complications include pulmonary thromboembolism, adult respiratory distress syndrome, and pulmonary infection in addition to systemic hypovolemia and exthrathoracic embolic events [15]. Radiotherapy is widely used in breast cancer treatment and may be complicated by radiation pneumonitis, the early stage of which occurs 1-3 months after treatment and is characterized radiologically by ground-glass opacities and consolidation in the irradiated port. Pleural effusion is infrequent at this stage. The late (fibrotic) stage occurs after 3 months and becomes stable 12-15 months after completion of radiation therapy, showing architectural distortion and volume loss, nonsegmental opacities, and traction bronchiectasis (Figure 11). The tangential-beam technique used in the treatment of breast carcinoma results in a characteristic CT appearance of the pulmonary opacities with a sharp
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Figure 15. A 31-year-old woman presented with pleuritic chest pain. Her clinical history was positive for BRCA1 mutation, recent bilateral mastectomy and breast reconstruction surgery, complicated by right reconstructed breast infection. Computed tomography (CT) angiography of the chest ruled out pulmonary embolism, but revealed a new left pulmonary nodule which showed low density (e150 HU), and was visualized on wide window settings (W1500, L-600), but was not seen on narrower, ‘‘abdominal window.’’ Lack of fluorodeoxyglucose uptake on positron emission tomography-CT (not shown) confirmed nonmalignant etiology of the nodule that is compatible with direct injection of fat into lung parenchyma, a rare complication of fat grafting in postmastectomy breast reconstruction.
Figure 13. A 36-year-old woman with ovarian hyperstimulation syndrome. Abdominal computed tomography demonstrates bilateral pleural effusions (arrowheads) and passive atelectasis, ascites (asterisk), and bilateral ovarian cystic lesions (arrows).
posterior border confined to the anterolateral subpleural region of the lung (Figure 14) [14]. Organizing pneumonia is a clinicopathologic entity characterized by multifocal, migratory, peripheral alveolar opacities, which is also occasionally seen following adjuvant radiotherapy of breast cancer. Organizing pneumonia is similar to radiation pneumonitis in clinical presentation, but
occurs outside the radiation field and seems to be related to sensitization of autoreactive lymphocytes in healthy lung due to subpleural location of initial lung injury and damage of lymphatic channels (Figure 14). Radiation therapy can cause various complications in the chest within and outside the radiation field, including cardiac toxicity and premature coronary artery stenosis, arm lymphoedema, neuropathy, skin damage, and osteonecrosis of ribs, sternum, and clavicles. Very late complications, such as mesothelioma, breast and lung cancer, radiation induced lymphoma, and sarcoma are also occasionally reported. Women who undergo thoracic irradiation before the age of 30 years have a high risk of developing a second breast cancer. Complications secondary to breast surgery include seroma, infection, hemorrhage, flap necrosis, lymphoedema, and axillary contracture (Figure 15) and can appear immediately after or in the late postsurgical period [14]. Conclusion Unique for women chest findings and thoracic disease are not comprehensively addressed in the current medical literature. However, sound understanding of anatomical and physiological gender-specific differences and their imaging manifestations should be required of radiologists and pulmonologists, to avoid diagnostic pitfalls. Thorough knowledge of chest pathologies specific to women is equally essential for their correct diagnosis and prompt management. References
Figure 14. Organizing pneumonia, following left partial mastectomy and adjuvant radiotherapy for breast cancer. The computed tomography images demonstrate reversed halo nodules (arrows) in the posterior segment of the right upper lobe and superior segment of the right lower lobe. Also note extensive post radiation changes in the anterior segment of the left upper lobe.
[1] Baraldo S, Saetta M. Sex differences in airway anatomy over human lifespan. In: Buist S, Mapp CE, editors. European Respiratory Society Monograph: Respiratory Diseases in Women. Lausanne, Switzerland: European Respiratory Society; 2003;25. p. 1e7.
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[2] Navani S, Shah JR, Levy PS. Determination of sex by costal cartilage calcification. Am J Roentgenol 1970;108:771e4. [3] Morgan T. Turner’s syndrome: diagnosis and management. Am Fam Physician 2007;76:405e17. [4] Pitts S, Oberstein E, Glassberg MK. Benign metastasizing leiomyoma and lymphangioleiomyomatosis: sex-specific diseases? Clin Chest Med 2004;25:343e60. [5] Abbott GF, Rosado-de-Christenson ML, Frazier AA, Franks TJ, Pugatch RD, Galvin JR. Lymphangioleiomyomatosis: radiologicpathologic correlation. Radiographics 2005;25:803e28. [6] Johnson M. Catamenial pneumothorax and other thoracic manifestations of endometriosis. Clin Chest Med 2004;25:311e9. [7] Rousset-Jablonski C, Alifano M, Plu-Bureau G, et al. Catamenial pneumothorax and endometriosis-related pneumothorax: clinical features and risk factors. Hum Reprod 2011;26:2322e9. [8] Leighton B, Fish J. Pulmonary Disease in Pregnancy. London, England: Global Library of Women’s Medicine; 2008.
[9] Seckl MJ, Sebire NJ, Berkowitz RS. Gestational trophoblastic disease. Lancet 2010;28:717e29. [10] Avdalovic M, Chan A. Thoracic manifestations of common nonpulmonary malignancies of women. Clin Chest Med 2004;25: 379e90. [11] Lu Y, Goldblatt JC. Multiple mediastinal metastasis of ovarian carcinoma. Heart Lung Circ 2005;14:118e20. [12] Abad A, Cazorla E, Ruiz F, Aznar I, Asins E, Llixiona J. Meigs’ syndrome with elevated CA125: case report and review of the literature. Eur J Obstet Gynecol Reprod Biol 1999;82:97e9. [13] Abramson S, Gilkeson RC, Goldstein JD, et al. Benign metastasizing leiomyoma: clinical, imaging, and pathologic correlation. AJR Am J Roentgenol 2001;176:1409e13. [14] Jung JI, Kim HH, Park SH, et al. Thoracic manifestations of breast cancer and its therapy. Radiographics 2004;24:1269e85. [15] McNeary M, Stark P. Radiographic findings in ovarian hyperstimulation syndrome. J Thorac Imaging 2002;17:230e2.
Thoracic and Cardiac Imaging / Imagerie cardiaque et imagerie thoracique
Review of Thoracic Imaging Findings Unique to Women Alla Khashper, MDa,*, James M. Gruber, MD, FRCPb, Richard S. Fraser, MD, FRCPc, Federico Discepola, MD, FRSCRd, Alexandre Semionov, MD, PhD, FRCRa b
a Department of Radiology, McGill University Health Centre, Montreal, Quebec, Canada Department of Pulmonology, McGill University Health Centre, Montreal, Quebec, Canada c Department of Pathology, McGill University Health Centre, Montreal, Quebec, Canada d Department of Radiology, Jewish General Hospital, Montreal, Quebec, Canada
Abstract Purpose: Traditionally, indications for imaging studies of women are considered to be related to screening for and evaluation of disease of the female breast and pelvis. However, a number of chest diseases and associated intrathoracic imaging findings are unique to women and should be recognized by general radiologists, as well as chest and women-imaging specialists. Conclusions: The sex-specific findings unique to women include normal anatomical variants, primary lung disease, complications of breast and gynaecological disease, and pregnancy-related conditions. Classification, description, and illustration of gender-specific chest imaging findings are the objective of this article. Resume Objectifs : Traditionnellement, on considere que les indications des examens d’imagerie chez les femmes sont reliees au depistage et a l’evaluation des atteintes du sein et du bassin. Neanmoins, certaines affections thoraciques et anomalies connexes decouvertes a l’imagerie intrathoracique sont propres aux femmes et devraient ^etre reconnues par les radiologistes generalistes ainsi que par les specialistes de l’imagerie thoracique et de l’imagerie chez les femmes. Conclusions : Les observations radiologiques propres aux femmes comprennent les variantes anatomiques normales, les pneumopathies primaires, les complications d’affections du sein et de maladies gynecologiques, ainsi que les affections liees a la grossesse. La classification, la description et l’illustration des aspects d’imagerie thoracique sexospecifiques constituent l’objet du present article. Ó 2015 Canadian Association of Radiologists. All rights reserved. Key Words: Thoracic imaging; Women imaging; Gender specific findings; Women chest
The anatomical and physiological differences between women and men are associated with sex-specific variations in the normal imaging appearance and in differences in the incidence of certain pathological conditions between the 2 groups. These differences are much more extensive than the reproductive system and breast and consist of normal anatomical variants, primary lung disease, complications of breast and gynaecological disease, and pregnancy-related conditions. A number of thoracic pathologies are exclusive
* Address for correspondence: Alla Khashper, MD, Department of Radiology, McGill University Health Centre, 1650 Cedar Avenue, Suite C5 118, Montreal, Quebec H3G 1A4, Canada. E-mail address: [email protected] (A. Khashper).
to women and should therefore be familiar to radiologists at large and to chest and women imaging experts in particular. The goal of this article is to draw attention to what is currently known about female sex-specific chest findings, both normal and pathological. Pathologies that are predominantly seen in women, but can be found in men, as well as primary breast disease are excluded from the discussion. Anatomical Features of the Female Chest The female thoracic cage is generally more rounded and smaller than that of the male. Studies have shown that women have a smaller rib cage size, a greater inclination of ribs, a comparable diaphragm dome position relative to the spine and a shorter diaphragm length than males of the same height.
0846-5371/$ - see front matter Ó 2015 Canadian Association of Radiologists. All rights reserved. http://dx.doi.org/10.1016/j.carj.2014.11.007
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Figure 1. Normal chest radiograph (A) of a 24-year-old woman clearly reflects gender-related features due to prominent breast shadows. Also, note characteristic central pattern of costal cartilage calcification (arrow) seen on coned down and zoomed-image (B).
Female lungs tend to be smaller, but are otherwise undistinguishable from male lungs at surgery or on autopsy [1]. On chest radiography, prominent breast tissue and central pattern of costal cartilage calcification usually allow to readily identify a female patient compared to the lack of breast shadows and peripheral pattern of costal cartilage calcification in men (Figure 1) [2]. That might be important in patient identification in cases of a mislabeled study or ambiguous name. Pregnancy related thoracic anatomical changes are well recognized on imaging. These include upward displacement of the diaphragm compensated by an increased diameter of the thoracic cage that together results in shortening and widening of the lungs [1]. Developmental Anomalies and Genetic Disease Few genetic diseases associated with chest manifestations are seen exclusively in females. The most common of these is Turner syndrome.
Turner syndrome is diagnosed in females with partial or complete absence of one X chromosome (45, XO karyotype). Characteristic thoracic findings in patient with Turner syndrome include a broad chest with widely spaced nipples and short or prematurely fused sternum, cardiovascular abnormalities, and congenital lymphoedema. The congenital cardiovascular anomalies include aortic coarctation (Figure 2), bicuspid aortic valve, aortic dilatation or aneurysm and an increased risk of aortic dissection [3]. Lymphangioleiomyomatosis Lymphangioleiomyomatosis (LAM) is an interstitial lung disease that almost exclusively affects women of reproductive age. It may occur sporadically or in association with tuberous sclerosis complex. Progressive dyspnea, recurrent pneumothoraces, hemoptysis, and chylous pleural effusions are common clinical manifestations [4] in symptomatic patients.
Figure 2. Turner syndrome and a complex aortic malformation. Chest radiograph (A) shows right-sided aortic arch (asterisk in A; Rt arch in B) resulting in deviation of the trachea to the left. Aortic coarctation (AC) and aneurysmal right brachiocephalic artery (RtBCA) are demonstrated on computed tomography 3D volume rendering reconstruction (B). Note is made of normal size of the left common carotid artery (LtCCA).
Unique Thoracic Imaging Findings in Women / Canadian Association of Radiologists Journal xx (2015) 1e8
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patients demonstrate increased lung volumes, while reduced volumes represent an unusual finding [5]. High-resolution computer tomography (HRCT) better than radiography demonstrates the lung cysts, which are typically small (2-5 mm in diameter) and uniform in size without regional sparing (Figure 3C). Cysts are usually round or ovoid in shape, but become polygonal and increase in size with progression of the disease. The surrounding lung parenchyma could be normal or show air trapping and septal thickening. Focal ground-glass opacities also may be seen, due to recurrent pulmonary hemorrhage [4,5]. Thoracic Endometriosis and Catamenial Pneumothorax
Figure 3. Lymphangiomyomatosis. Coronal reconstruction of a computed tomography scan shows diffuse involvement of both lungs with innumerable thin-walled cysts, slightly more pronounced at the lung bases.
In the thorax, LAM is characterized pathologically by abnormal peribronchial, perivascular, and perilymphatic proliferation of immature smooth muscle cells that results in bronchiolar and lymphatic obstruction leading to lung cyst formation. The chest radiograph might demonstrate progressive appearance of faint reticular opacities and thin walled cysts, corresponding to clinical deterioration and increasing pulmonary involvement (Figures 3A and 3B) [4]. Interstitial opacities on chest radiograph have been described as affecting both lungs diffusely with basal predominance due to summation effect of numerous thin-wall cysts, or predominantly involving the lower lung zones. About half of
Endometriosis represents ectopic endometrial cells outside of the uterus, which symptoms are associated with menstrual periodicity [6]. Thoracic endometriosis occurs in 2 distinct clinicopathologic forms: pleurodiaphragmatic and bronchopulmonary. The precise pathogenesis of thoracic endometriosis remains unknown. Two main mechanisms of pathogenesis have been postulated to explain the development of each formdtransplantation of endometrium to ectopic sites and metaplastic differentiation of serosal cells lining pleural cavity. The former hypothesis suggests that endometrial tissue can be transported from the peritoneal cavity to the pleural space through diaphragmatic defects or represent microembolization through pelvic veins [6,7]. Pleural lesions are almost exclusively right-sided, whereas parenchymal lung endometriosis might be found in the right or left lung. Concomitant pelvic endometriosis is present in up to half of women with thoracic endometriosis [7]. Chest pain associated with menstrual periodicity represents the typical clinical presentation of patients with thoracic endometriosis. Catamenial pneumothorax is generally defined as a pneumothorax occurring between 24 hours before, and 72 hours after, the onset of menses. As expected, findings may include pneumothorax in most cases; hemothorax and hemoptysis are seen occasionally (Figure 4) [6].
Figure 4. Catamenial pneumothorax in a 43-year-old woman who presented with 3 episodes of spontaneous pneumothorax, each associated with the onset of menses. Expiratory chest radiograph (A) shows a right-sided pneumothorax (arrows), as well as right apical scar from remote right apical bullectomy (arrowhead). Medium-power photomicrograph (original magnification, 20; hematoxylin-eosin stain) (B) shows an endometriotic implant in the parietal pleura (arrows).
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and postpartum cardiomyopathy. Pulmonary oedema can occur as a complication of tocolytic treatment or in association with pre-eclampsia. Adult respiratory distress syndrome may result from gestational complications such as pre-eclampisa/eclampsia and sepsis [8]. Gestational trophoblastic disease comprises a range of pregnancy-related disorders, including complete and partial hydatidiform mole, invasive mole, choriocarcinoma, and the rare placental trophoblastic tumour. Molar pregnancy can occasionally degenerate into choriocarcinoma. This commonly metastasizes to the lung, producing multiple discrete pulmonary nodules, while pleural effusion is uncommon (Figure 5). Lung nodules are usually well defined or show shaggy, ill-defined borders reflecting hemorrhage. Choriocarcinoma is very sensitive to chemotherapy; therefore, early diagnosis is the key to adequate patient management [9]. Pregnancy can negatively affect the course of some chronic diseases, most notably asthma, sarcoidosis, and systemic lupus erythematosus. Conversely, these conditions, if poorly controlled, can unfavorably affect pregnancy. Figure 5. Metastatic choriocarcinoma. Coronal reconstruction of chest computed tomography reveals a few tiny nodules (arrows) scattered bilaterally, that resolved on follow up exam obtained after chemotherapy (not shown).
Pregnancy-Related Pathology
Thoracic Involvement in Primary Ovarian Tumours The most common thoracic abnormality in patients with metastatic ovarian carcinoma is pleural effusion, which is seen in up to half of patients. Pulmonary parenchymal metastases are rare and usually are preceded by recurrence of the disease
Pregnancy results in a number of anatomical and functional changes in the respiratory and cardiovascular systems. Pregnancy also increases the risk of several pulmonary disorders, such as aspiration and influenza pneumonia. A hypercoagulable state during pregnancy results in increased risk of pulmonary artery embolism. Possible peripartum complications include amniotic fluid pulmonary embolism
Figure 6. Metastatic ovarian cancer. Chest computed tomography demonstrates scattered bilateral pulmonary nodules, some of which underwent cavitation.
Figure 7. Small cell ovarian carcinoma in 28-year-old woman, who presented with chest pain and hyperkalemia. Chest radiograph reveals mediastinal and hilar lymphadenopathy. Positron emission tomography-computed tomography scan (not shown) demonstrates 17 cm left ovarian mass associated with infra- and supradiaphragmatic lymphadenopathy showing avid uptake of radiotracer. Percutaneous biopsy of supraclavicular lymph node proved the presence of small cell ovarian carcinoma.
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Figure 9. Metastatic uterine leiomyoma. Coronal reconstruction of a chest computed tomography reveals several cystic lesions (arrows) scattered in both lungs, as well as a small right pneumothorax.
Figure 8. Meigs syndrome. Sagittal reconstruction of contrast enhanced thoracoabdominal computed tomography reveals a large pelvic mass (arrows) associated with ascites and right pleural effusion. An ovarian fibroma was resected, followed by complete resolution of the effusion and ascites.
in the abdomen or pelvis [10]. Thus, increased number and size of lung nodules might be seen with progression of the primary disease, whereas central cavitation of the lung nodules (Figure 6) and decrease in their size and number usually indicate a response to treatment and are commonly associated with regression of intra-abdominal disease. Ovarian neoplasms can also metastasize to the mediastinum, most commonly resulting in paracardiac lymph node enlargement (greater than 5 mm in diameter). However, extensive mediastinal lymphadenopathy accompanies ovarian cancer rarely. One exception to this statement is small cell carcinoma of the ovary, a rare tumour that is typically associated with hyperkalemia and early metastases to abdominal and mediastinal lymph nodes (Figure 7) [11]. Benign ovarian fibroma may be associated with pleural effusion and ascites, the so-called Meigs syndrome (Figure 8). Both effusion and ascites such as resolve following removal of the ovarian lesion. When other metastatic or primary adnexal or uterine tumours are accompanied by pleural effusion, the term ‘‘pseudo-Meigs syndrome’’ is sometimes used [12]. Thoracic Involvement in Uterine and Cervical Tumours Various malignant tumours of the uterus might present with intrathoracic metastases, resulting in findings of lung
nodules, pleural effusion, and lymphadenopathy. Both benign and malignant uterine tumours metastasize predominantly to the lung [10]. Pulmonary metastases from carcinomas originating from the cervix and endometrium are uncommon. Radiographically, the pulmonary metastases from both cervical and endometrial neoplasms are usually smooth lesions that may have cavitations [10]. So-called ‘‘benign metastasizing leiomyoma’’ is a rare disorder characterized by well-circumscribed nodules of smooth muscle cells in the lungs. Although there is typically no obvious primary site at the time of their identification, the nodules are believed to represent hematogenous metastases from a smooth muscle tumour. Despite this, they show no histologic features of malignancy, including cytologic atypia and mitotic activity. Although the condition has been reported in association with smooth muscle tumours originating in a variety of sites, the most common by far is the uterus. In most cases of benign metastasizing leiomyoma, there is a history of uterine leiomyoma resection several years before development of the pulmonary disease [13]. The characteristic radiographic appearance is that of multiple well-circumscribed pulmonary nodules. However, a solitary nodule, a miliary pattern, cavitary nodules (Figure 9), and interstitial disease have rarely been reported [4]. Uterine leiomyosarcoma comprises about 25% of uterine sarcomas and 1% of all uterine malignancies. The uterus is by far the most common primary site of leiomyosarcoma and hence, pulmonary metastases of such tumours are almost exclusively found in women. Patients are typically young (30-40 years old) and present with gynecologic signs or symptoms such as vaginal bleeding, lower abdominal pain, and a pelvic mass. Parenchymal pulmonary nodules are the typical radiographic manifestation. As with other sarcomas, a subpleural location is often seen and pneumothorax is an occasional complication (Figure 10) [4].
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Figure 10. Metastatic uterine leiomyosarcoma treated with hysterectomy 2 years prior. Chest computed tomography reveals solid (arrowhead) and cavitary (arrow) pulmonary nodules in the left lung. The spontaneous right pneumothorax was thought to be a result of an occult right lung metastasis.
Thoracic Metastases From Breast Cancer Imaging exams of the chest other than mammography may reveal a breast mass in the chest wall or intrathoracic abnormalities resulting from treatment, complications of treatment, or metastases. Thoracic metastases of breast carcinoma can present radiographically as solitary or multiple lung nodules, airspace consolidations, lymphangitic carcinomatosis, or pleural effusion. Lymphangitic carcinomatosis is commonly seen in advanced cases (Figure 11), causing irregular, nodular thickening of interlobular septae and bronchovascular bundles [13]. Bone is the second most common site affected by metastatic breast cancer. Purely lytic, aggressive, and destructive lesions represent early stages of metastatic disease, while multiple, confluent sclerotic bone lesions are a more typical feature of advanced or treated metastatic breast cancer [14].
Figure 11. A 67-year-old woman with metastatic breast cancer. Diffuse interlobular septal thickening (arrows) is consistent with lymphangitic carcinomatosis. Bilateral malignant pleural effusions and diffuse blastic bone metastases (arrowheads) confirm metastatic disease. Treatment-related findings include left mastectomy and axillary lymph node dissection, as well as architectural distortion, traction bronchiectasis, and fibrosis of the left lung secondary to prior radiotherapy.
Figure 12. A 67-year-old woman with history of thyroidectomy. Contrastenhanced chest computed tomography (CT) demonstrates left chest wall mass (arrow) associated with borderline left axillary nodes. Positron emission tomography-CT revealed moderate fluorodeoxyglucose uptake, prompting CT-guided biopsy of the lesion. During the procedure the patient gave the history of previous breast implant removal due to local infection. Fibrosis and granulation tissue was demonstrated in a biopsy sample.
Treatment-Related Findings Various complications occur in the chest following interventional procedures, surgical treatment, and radiotherapy of diseases specific to women. In these cases, clinical history and correlation with details of prior treatment are crucial, as illustrated in Figure 12. The majority of these treatment-related intrathoracic findings complicate management of primary pathology localized within the chest cage. But in some cases distant intrathoracic complications may occur. Ovarian hyperstimulation syndrome is an uncommon, but serious complication of induced ovarian ovulation for infertility treatment. Imaging findings include pleural effusions, ascites, and markedly enlarged ovaries with multiple cysts (Figure 13). Possible thoracic complications include pulmonary thromboembolism, adult respiratory distress syndrome, and pulmonary infection in addition to systemic hypovolemia and exthrathoracic embolic events [15]. Radiotherapy is widely used in breast cancer treatment and may be complicated by radiation pneumonitis, the early stage of which occurs 1-3 months after treatment and is characterized radiologically by ground-glass opacities and consolidation in the irradiated port. Pleural effusion is infrequent at this stage. The late (fibrotic) stage occurs after 3 months and becomes stable 12-15 months after completion of radiation therapy, showing architectural distortion and volume loss, nonsegmental opacities, and traction bronchiectasis (Figure 11). The tangential-beam technique used in the treatment of breast carcinoma results in a characteristic CT appearance of the pulmonary opacities with a sharp
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Figure 15. A 31-year-old woman presented with pleuritic chest pain. Her clinical history was positive for BRCA1 mutation, recent bilateral mastectomy and breast reconstruction surgery, complicated by right reconstructed breast infection. Computed tomography (CT) angiography of the chest ruled out pulmonary embolism, but revealed a new left pulmonary nodule which showed low density (e150 HU), and was visualized on wide window settings (W1500, L-600), but was not seen on narrower, ‘‘abdominal window.’’ Lack of fluorodeoxyglucose uptake on positron emission tomography-CT (not shown) confirmed nonmalignant etiology of the nodule that is compatible with direct injection of fat into lung parenchyma, a rare complication of fat grafting in postmastectomy breast reconstruction.
Figure 13. A 36-year-old woman with ovarian hyperstimulation syndrome. Abdominal computed tomography demonstrates bilateral pleural effusions (arrowheads) and passive atelectasis, ascites (asterisk), and bilateral ovarian cystic lesions (arrows).
posterior border confined to the anterolateral subpleural region of the lung (Figure 14) [14]. Organizing pneumonia is a clinicopathologic entity characterized by multifocal, migratory, peripheral alveolar opacities, which is also occasionally seen following adjuvant radiotherapy of breast cancer. Organizing pneumonia is similar to radiation pneumonitis in clinical presentation, but
occurs outside the radiation field and seems to be related to sensitization of autoreactive lymphocytes in healthy lung due to subpleural location of initial lung injury and damage of lymphatic channels (Figure 14). Radiation therapy can cause various complications in the chest within and outside the radiation field, including cardiac toxicity and premature coronary artery stenosis, arm lymphoedema, neuropathy, skin damage, and osteonecrosis of ribs, sternum, and clavicles. Very late complications, such as mesothelioma, breast and lung cancer, radiation induced lymphoma, and sarcoma are also occasionally reported. Women who undergo thoracic irradiation before the age of 30 years have a high risk of developing a second breast cancer. Complications secondary to breast surgery include seroma, infection, hemorrhage, flap necrosis, lymphoedema, and axillary contracture (Figure 15) and can appear immediately after or in the late postsurgical period [14]. Conclusion Unique for women chest findings and thoracic disease are not comprehensively addressed in the current medical literature. However, sound understanding of anatomical and physiological gender-specific differences and their imaging manifestations should be required of radiologists and pulmonologists, to avoid diagnostic pitfalls. Thorough knowledge of chest pathologies specific to women is equally essential for their correct diagnosis and prompt management. References
Figure 14. Organizing pneumonia, following left partial mastectomy and adjuvant radiotherapy for breast cancer. The computed tomography images demonstrate reversed halo nodules (arrows) in the posterior segment of the right upper lobe and superior segment of the right lower lobe. Also note extensive post radiation changes in the anterior segment of the left upper lobe.
[1] Baraldo S, Saetta M. Sex differences in airway anatomy over human lifespan. In: Buist S, Mapp CE, editors. European Respiratory Society Monograph: Respiratory Diseases in Women. Lausanne, Switzerland: European Respiratory Society; 2003;25. p. 1e7.
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[2] Navani S, Shah JR, Levy PS. Determination of sex by costal cartilage calcification. Am J Roentgenol 1970;108:771e4. [3] Morgan T. Turner’s syndrome: diagnosis and management. Am Fam Physician 2007;76:405e17. [4] Pitts S, Oberstein E, Glassberg MK. Benign metastasizing leiomyoma and lymphangioleiomyomatosis: sex-specific diseases? Clin Chest Med 2004;25:343e60. [5] Abbott GF, Rosado-de-Christenson ML, Frazier AA, Franks TJ, Pugatch RD, Galvin JR. Lymphangioleiomyomatosis: radiologicpathologic correlation. Radiographics 2005;25:803e28. [6] Johnson M. Catamenial pneumothorax and other thoracic manifestations of endometriosis. Clin Chest Med 2004;25:311e9. [7] Rousset-Jablonski C, Alifano M, Plu-Bureau G, et al. Catamenial pneumothorax and endometriosis-related pneumothorax: clinical features and risk factors. Hum Reprod 2011;26:2322e9. [8] Leighton B, Fish J. Pulmonary Disease in Pregnancy. London, England: Global Library of Women’s Medicine; 2008.
[9] Seckl MJ, Sebire NJ, Berkowitz RS. Gestational trophoblastic disease. Lancet 2010;28:717e29. [10] Avdalovic M, Chan A. Thoracic manifestations of common nonpulmonary malignancies of women. Clin Chest Med 2004;25: 379e90. [11] Lu Y, Goldblatt JC. Multiple mediastinal metastasis of ovarian carcinoma. Heart Lung Circ 2005;14:118e20. [12] Abad A, Cazorla E, Ruiz F, Aznar I, Asins E, Llixiona J. Meigs’ syndrome with elevated CA125: case report and review of the literature. Eur J Obstet Gynecol Reprod Biol 1999;82:97e9. [13] Abramson S, Gilkeson RC, Goldstein JD, et al. Benign metastasizing leiomyoma: clinical, imaging, and pathologic correlation. AJR Am J Roentgenol 2001;176:1409e13. [14] Jung JI, Kim HH, Park SH, et al. Thoracic manifestations of breast cancer and its therapy. Radiographics 2004;24:1269e85. [15] McNeary M, Stark P. Radiographic findings in ovarian hyperstimulation syndrome. J Thorac Imaging 2002;17:230e2.
