Bab 2.docx

BAB 2 TINJAUAN PUSTAKA

2.1 Anatomi Pleura Pleura merupakan membran serosa yang tersusun dari lapisan sel yang embriogenik berasal dari jaringan selom intraembrional dan bersifat memungkinkan organ yang diliputinya mampu berkembang, mengalami retraksi atau deformasi sesuai dengan proses perkembangan anatomis dan fisiologis suatu organisme (Rasad,2015). Pleura viseral membatasi permukaan luar parenkim paru termasuk fi sura interlobaris, sementara pleura parietal membatasi dinding dada yang tersusun dari otot dada dan tulang iga, serta diafragma, mediastinum dan struktur servikal (Moore, 2010). Pleura viseral dan parietal memiliki perbedaan inervasi dan vaskularisasi. Pleura viseral diinervasi saraf-saraf otonom dan mendapat aliran darah dari sirkulasi pulmoner, sementara pleura parietal diinervasi sarafsaraf interkostalis dan nervus frenikus serta mendapat aliran darah sistemik (Light, 2010). Pleura viseral dan pleura parietal terpisah oleh rongga pleura yang mengandung sejumlah tertentu cairan pleura.

Gambar 1 Anatomi Sistem Respirasi

3

4

Gambar 2 Pleura viseral dan parietal serta struktur sekitar pleura

2.1.1 Struktur Mikroskopis Pleura Pleura terbagi menjadi lima lapisan, yaitu lapisan selapis mesotel, lamina basalis, lapisan elastik superfi sial, lapisan jaringan ikat longgar dan lapisan jaringan fibroelastik dalam (Wang, 2010). Kolagen tipe I dan III yang diproduksi oleh lapisan jaringan ikat merupakan komponen utama penyusun matriks ekstraseluler pleura dan merupakan 80% berat kering struktur ini (Wang, 2010). Lapisan jaringan fibroelastik dalam menempel erat pada iga, otot-otot dinding dada, diafragma, mediastinum dan paru (Lee, 2015). Lapisan jaringan ikat longgar tersusun atas jaringan lemak, fibroblas, monosit, pembuluh darah, saraf dan limfatik (Wang, 2010). Pengamatan pada hewan domba mengungkapkan bahwa ketebalan pleura dari permukaan rongga pleura dengan lapisan jaringan ikat yang menaungi pembuluh kapiler dan pembuluh limfatik adalah 25 – 83 μm pada pleura viseral dan 10 – 25 μm pada pleura parietal (Light, 2010). Proses inflamasi mengakibatkan migrasi sel-sel inflamasi harus melewati lapisan jaringan ikat longgar menuju lamina basalis kemudian menuju rongga pleura setelah melewati mesotel (Wang, 2010). Mesotel berdasarkan pengamatan mikroskop elektron berbentuk gepeng, berbenjolbenjol dan berukuran sekitar 4 μm (Wang, 2010). Mesotel memiliki retikulum endoplasma kasar dan halus, mitokondria dan beberapa jenis vesikel mikropinositotik terikat membran sehingga memiliki fungsi fagositik dan eritrofagositik saat terlepas dari tautan antarsel (Wang, 2010). Mesotel saling terhubung oleh desmosom di tautan antarsel bagian basal (Light, 2010). Bentuk komunikasi antar mesotel adalah tautan antar sel bagian apikal

5

dan tautan tipe ZO-1 (Wang, 2010). Mesotel memiliki mikrovili berdiameter sekitar 0,1 μm dan panjang sekitar 1 – 3 μm dengan kepadatan 2 – 3 sel/μm2 yang meningkatkan luas permukaan sel sehingga meningkatkan fungsi-fungsi terkait fi siologi membran dan sekresi asam hialuronat. Mikrovili terutama ditemukan pada mesotel pleura parietal sementara kepustakaan lain menyebutkan lebih banyak ditemukan di pleura viseral (Lee, 2015). Senyawa vascular endothelial growth factor (VEGF) disekresikan mesotel sebagai respons terhadap pajanan lipopolisakarida, trombin dan bakteri menyebabkan peningkatan permeabilitas endotel pleura terutama terhadap protein (Wang, 2010). Senyawa growth factor-β1 dan fibroblast growth factor menyebabkan pleura mengalami transisi menjadi fibroblas (Light, 2010). Senyawa intercellular adhesion molecule (ICAM)-1 yang diekspresikan mesotel sebagai respons terhadap tumor necrosis factor (TNF)-α dan interferon (IF)-γ menyebabkan migrasi netrofi l atau monosit melalui integrin cluster of diff erentiation (CD)-11 atau CD-18 sehingga terjadi perlekatan pleura menyebabkan keadaan pleuritis (Wang, 2010). Mikrovili mesotel mensekresi asam hialuronat untuk mengurangi friksi antara paru, dinding dada dan diafragma saat proses respirasi (Lee, 2015). Senyawa ini juga berfungsi sebagai sawar selektif pertukaran ion-ion dan molekul kecil antara alveolus, jaringan interstitial paru dan rongga pleura, pengaturan respons inflamasi, penyembuhan pleura, fagositosis bakteri dan partikel mineral seperti serat asbestos, lateks dan quartz (Wang, 2010). Reseptor kaderin merupakan reseptor dependen kalsium yang diekspresikan pleura untuk mempertahankan morfologi dan permeabilitas pleura (Wang, 2010). Mesotel memiliki proteinaseactivated receptor-2 (PAR2) yang berperan dalam proses inflamasi dengan melepas kemokin dan menarik netrofi l ke dalam rongga pleura sehingga terjadi fibrosis pleura, adhesi pleura atau fibrotoraks (Lai, 2014). Senyawa-senyawa lain yang diekspresikan mesotel seperti keratin epitelial, fibronektin, vimentin, kolagen, elastin, laminin dan proteoglikan merupakan senyawasenyawa spesies oksidan kerja panjang yang berhubungan dengan integritas sel dan sesuai dengan sifat sel-sel epitel dan fibroblas (Wang, 2010). Sitokin lain yang dapat ditemukan di pleura antara lain interleukin (IL)1 yang berhubungan dengan proses fibrogenesis pleura, IL-2 dan IL-5 yang menginduksi produksi limfosit, IL-3 yang menginduksi proliferasi dan ketahanan eosinofi l, IL-4 yang menahan infiltrasi sel menuju rongga pleura, IL-6 yang

6

menginduksi maturasi limfosit B, IL-8 yang merupakan kemotaksin netrofi l, IL-10 yang merupakan sitokin antiinfl amasi, IL-12 yang akan memperkuat respons imunologis selular dan respons sitotoksik terhadap patogen intraselular dan tumor, IL13 yang merupakan kemoatraktan eosinofi l, IL-16 yang akan menginduksi sitokin proinfl amasi, monocyte chemotactic peptide (MCP-1), transforming growth factor (TGF)-β, basic fibroblast growth factor (b-FGF), endostatin sebagai inhibitor angiogenesis dan platelet-activating factor (PAF) yang bersifat meningkatkan permeabilitas vaskular (Wang, 2010). 2.1.2 Cairan Pleura Cairan pleura mengandung 1.500 – 4.500 sel/ mL, terdiri dari makrofag (75%), limfosit (23%), sel darah merah dan mesotel bebas.2,12,14,15 Cairan pleura normal mengandung protein 1 – 2 g/100 mL.9 Elektroforesis protein cairan pleura menunjukkan bahwa kadar protein cairan pleura setara dengan kadar protein serum, namun kadar protein berat molekul rendah seperti albumin, lebih tinggi dalam cairan pleura.3 Kadar molekul bikarbonat cairan pleura 20 – 25% lebih tinggi dibandingkan kadar bikarbonat plasma, sedangkan kadar ion natrium lebih rendah 3 – 5% dan kadar ion klorida lebih rendah 6 – 9% sehingga pH cairan pleura lebih tinggi dibandingkan pH plasma.3 Keseimbangan ionik ini diatur melalui transpor aktif mesotel.16 Kadar glukosa dan ion kalium cairan pleura setara dengan plasma.3 2.1.3 Struktur Makroskopis Pleura Pleura normal memiliki permukaan licin, mengkilap dan semitransparan. Luas permukaan pleura viseral sekitar 4.000 cm2 pada laki-laki dewasa dengan berat badan 70 kg. Pleura parietal terbagi dalam beberapa bagian, yaitu pleura kostalis yang berbatasan dengan iga dan otot-otot interkostal, pleura diafragmatik, pleura servikal atau kupula sepanjang 2-3 cm menyusur sepertiga medial klavikula di belakang otototot sternokleidomastoid dan pleura mediastinal yang membungkus organ-organ mediastinum. Bagian inferior pleura parietal dorsal dan ventral mediastinum tertarik menuju rongga toraks seiring perkembangan organ paru dan bertahan hingga dewasa sebagai jaringan ligamentum pulmoner, menyusur vertikal dari hilus menuju diafragma membagi rongga pleura menjadi rongga anterior dan posterior. Ligamentum pulmoner memiliki pembuluh limfatik besar yang merupakan potensi

7

penyebab efusi pada kasus traumatik. Pleura kostalis mendapat sirkulasi darah dari arteri mammaria interkostalis dan internalis. Pleura mediastinal mendapat sirkulasi darah dari arteri bronkialis, diafragmatik superior, mammaria interna dan mediastinum. Pleura servikalis mendapat sirkulasi darah dari arteri subklavia. Pleura diafragmatik mendapat sirkulasi darah dari cabang-cabang arteri mammaria interna serta aorta toraksika dan abdominis. Vena pleura parietal mengikut jalur arteri dan kembali menuju vena kava superior melalui vena azigos. Pleura viseral mendapat sirkulasi darah dari arteri bronkialis menuju vena pulmonaris. Ujung saraf sensorik berada di pleura parietal kostalis dan diafragmatika. Pleura kostalis diinervasi oleh saraf interkostalis, bagian tengah pleura diafragmatika oleh saraf frenikus. Stimulasi oleh infl amasi dan iritasi pleura parietal menimbulkan sensasi nyeri dinding dada dan nyeri tumpul pada bahu ipsilateral. Tidak ada jaras nyeri pada pleura viseral walaupun secara luas diinervasi oleh nervus vagus dan trunkus simpatikus. Eliminasi akumulasi cairan pleura terutama diatur oleh sistem limfatik sistemik di pleura parietal. Cairan masuk ke dalam rongga pleura melalui arteriol interkostalis pleura parietal melewati mesotel dan kembali ke sirkulasi melalui stoma pada pleura parietal yang terbuka langsung menuju sistem limfatik. Pleksus limfatikus superfi sialis terletak pada jaringan ikat di lapisan subpleura viseral dan bermuara di pembuluh limfe septa lobularis dan lobaris. Jaringan limfatikus ini dari pleura kostalis menyusur ventral menuju nodus limfatik sepanjang arteri mammaria interna atau dorsal menuju ujung sendi kostosternal, dari pleura mediastinal menuju nodus limfatikus trakeobronkial dan mediastinum, dan dari pleura diafragmatik menuju nodus parasternal, frenikus medialis dan mediastinum superior. Cairan pleura tidak masuk ke dalam pleksus limfatikus di pleura viseral karena pleura viseral lebih tebal dibandingkan pleura parietal sehingga tidak terjadi pergerakan cairan dari rongga pleura ke pleura viseral. Gangguan duktus torasikus karena limfoma maupun trauma menyebabkan akumulasi cairan limfe di rongga pleura menyebabkan chylothorax. 2.2 Fisiologi Pleura Pleura berperan dalam sistem pernapasan melalui tekanan pleura yang ditimbulkan oleh rongga pleura. Tekanan pleura bersama tekanan jalan napas akan menimbulkan tekanan transpulmoner yang selanjutnya akan memengaruhi pengembangan paru dalam proses respirasi (Sureka, 2015). Pengembangan paru terjadi bila kerja otot dan

8

tekanan transpulmoner berhasil mengatasi rekoil elastik (elastic recoil) paru dan dinding dada sehingga terjadi proses respirasi (Knipe, 2015). Jumlah cairan rongga pleura diatur keseimbangan Starling yang ditimbulkan oleh tekanan pleura dan kapiler, kemampuan sistem penyaliran limfatik pleura serta keseimbangan elektrolit (Boyland, 2010). Ketidakseimbangan komponen-komponen gaya ini menyebabkan penumpukan cairan sehingga terjadi efusi pleura (Wang, 2010). 2.3.1 Fisiologi tekanan pleura Tekanan pleura secara fisiologis memiliki dua pengertian yaitu tekanan cairan pleura dan tekanan permukaan pleura (Miserocchi, 2009). Tekanan cairan pleura mencerminkan dinamik aliran cairan melewati membran dan bernilai sekitar -10 cmH2 O.

Gambar 3. Perubahan volume paru, tekanan alveolar, tekanan pleura dan tekanan transpulmoner selama respirasi biasa2

Tekanan permukaan pleura mencerminkan keseimbangan elastik rekoil dinding dada ke arah luar dengan elastik rekoil paru ke arah dalam. Nilai tekanan pleura tidak serupa di seluruh permukaan rongga pleura; lebih negatif di apeks paru dan lebih positif di basal paru. Perbedaan bentuk dinding dada dengan paru dan faktor gravitasi menyebabkan perbedaan tekanan pleura secara vertikal; perbedaan tekanan pleura antara bagian basal paru dengan apeks paru dapat mencapai 8 cmH2 O. Tekanan alveolus relatif rata di seluruh jaringan paru normal sehingga gradien tekanan resultan

9

di rongga pleura berbeda pada berbagai permukaan pleura. Gradien tekanan di apeks lebih besar dibandingkan basal sehingga formasi bleb pleura terutama terjadi di apeks paru dan merupakan penyebab pneumotoraks spontan (Miserocchi, 2009). Gradien ini juga menyebabkan variasi distribusi ventilasi.4 Pleura viseral dan parietal saling tertolak oleh gaya potensial molekul fosfolipid yang diabsorpsi permukaan masingmasing pleura oleh mikrovili mesotel sehingga terbentuk lubrikasi untuk mengurangi friksi saat respirasi (Miserocchi, 2009). Proses tersebut bersama tekanan permukaan pleura, keseimbangan tekanan oleh gaya Starling dan tekanan elastik rekoil paru mencegah kontak antara pleura viseral dan parietal walaupun jarak antarpleura hanya 10 μm.2,5 Proses respirasi melibatkan tekanan pleura dan tekanan jalan napas. Udara mengalir melalui jalan napas dipengaruhi tekanan pengembangan jalan napas yang mempertahankan saluran napas tetap terbuka serta tekanan luar jaringan paru (tekanan pleura) yang melingkupi dan menekan saluran napas. Perbedaan antara kedua tekanan (tekanan jalan napas dikurangi tekanan pleura) disebut tekanan transpulmoner. Tekanan transpulmoner memengaruhi pengembangan paru sehingga memengaruhi jumlah udara paru saat respirasi. Hubungan perubahan tekanan pleura, tekanan alveolus, tekanan transpulmoner dan volume paru ditunjukkan pada gambar 3 (Light, 2010). 2.2.2 Fisiologi cairan pleura Rongga pleura terisi cairan dari pembuluh kapiler pleura, ruang interstitial paru, saluran limfatik intratoraks, pembuluh kapiler intratoraks dan rongga peritoneum (Miserocchi, 2009). Neergard mengemukakan hipotesis bahwa aliran cairan pleura sepenuhnya bergantung perbedaan tekanan hidrostatik dan osmotik kapiler sistemik dengan kapiler pulmoner. Perpindahan cairan ini mengikuti hukum Starling berikut: 5 Jv = Kf × ([P kapiler – P pleura] - σ [π kapiler – π pleura]) Jv : aliran cairan transpleura, Kf : koefisien filtrasi yang merupakan perkalian konduktivitas hidrolik membran dengan luas permukaan membran, P : tekanan hidrostatik, σ : koefi sien kemampuan restriksi membran terhadap migrasi molekul besar, π : tekanan onkotik.

10

Gambar 4. Skema tekanan dan pergerakan cairan pada rongga pleura manusia

Perkiraan besar perbedaan tekanan yang memengaruhi pergerakan cairan dari kapiler menuju rongga pleura ditunjukkan pada Gambar 4. Tekanan hidrostatik pleura parietal sebesar 30 cm H2 O dan tekanan rongga pleura sebesar -5 cm H2 O sehingga tekanan hidrostatik resultan adalah 30 – (-5) = 35 cmH2 O. Tekanan onkotik plasma 34 cmH2 O dan tekanan onkotik pleura 5 cmH2 O sehingga tekanan onkotik resultan 34 – 5 = 29 cmH2 O. Gradien tekanan yang ditimbulkan adalah 35 – 29 = 6 cmH2 O sehingga terjadi pergerakan cairan dari kapiler pleura parietal menuju rongga pleura. Pleura viseral lebih tebal dibandingkan pleura parietal sehingga koefisien filtrasi pleura viseral lebih kecil dibandingkan pleura parietal. Koefisien filtrasi kecil pleura viseral menyebabkan resultan gradien tekanan terhadap pleura viseral secara skematis bernilai 0 walaupun tekanan kapiler pleura viseral identik dengan tekanan vena pulmoner yaitu 24 cmH2 O. Perpindahan cairan dari jaringan interstitial paru ke rongga pleura dapat terjadi seperti akibat peningkatan tekanan baji jaringan paru pada edema paru maupun gagal jantung kongestif (Miserocchi, 2009). 2.3 Tumor Pleura Tumor pleura adalah pertumbuhan abnormal sel yang ditemukan di pleural space. Tumor pleura hampir selalu berupa metastatik (keganasan) dan sulit untuk di evakuasi. Prognosis dari tumor pleura biasanya buruk kecuali Localized Fibrous Tumor (LFTP), hanya satu dari delapan jenis LFTP merupakan keganasan, presentase sembuh setelah operasi pengangkatan sangat tinggi meskipun ukurannya besar.

11

Kanker pleura paling sering terjadi akibat kanker metastasis (kanker sekunder), yang dipicu oleh sel kanker yang menyebar ke pleural space (paling sering dari paru). Pasien yang memiliki riwayat kanker memiliki resiko lebih tinggi terkena kanker pleura, terlebih lagi jika terapi yang sudah dilakukan tidak dapat mengontrol pertumbuhan sel kanker. Meskipun begitu, angka kejadian kanker pleura sangatlah kecil, terjadi pada 1 dari 2000 pasien kanker. Sel kanker dapat berpindah ke pleural space melalui sistem hematogen maupun sistem limfatik. Bisa juga terjadi karena kontak langsung dimana jaringan kanker menekan pleura dari paru-paru. Metastatis tumor plura bisasanya menyebabkan efusi pleura. Biasanya cairan berupa darah, sehingga dapat menunjang penegakan diagnosis. Pengambilan sampel cairan pleura dapat membantu mengetahui kondisi pasien terkini. LFTP mungkin tidak menimbulkan gejala apapun. Biasanya ditemukan pada saat pasien melakukan foto x-ray untuk tujuan yang lain. Tetapi metastasis pleura tumor menimbulkan gejela yang mirip dengan kanker paru-paru seperti: 

Sesak napas



Nyeri dada



Rasa tidak nyaman



Batuk



Penurunan berat badan

Salah satu penyebab metastasis tumor pleura adalah komplikasi dari mesothelioma, yaitu kanker paru yang berhubungan dengan paparan asbestos. Namun kanker yang lain dapat juga menimbulkan metastatik tumor pleura. Sangat sedikit yang diketahui tentang penyebab LFPT, kebanyakan tumor ini bersifat benign.

Radiological assessment of pleural tumors requires complete knowledge of pleural anatomy. Various benign, malignant and tumor-like conditions can involve the pleura. Malignant pleural neoplasms are more common. The most common tumorlike condition involving the pleura is pleural thickening. Radiological features of pleural disease can have varied spectrum including pleural effusion, pleural plaques,

12

and nodular pleural thickening. Differentiation of pleural neoplasms from pulmonary and extrapleural neoplasms is crucial in making appropriate diagnosis. 2.3.1 Differentiating pleural, pulmonary, and extrapleural neoplasms Pulmonary neoplasms usually have acute angles with the chest wall, are centered in the lung, and engulf the pulmonary vasculature. A pleural neoplasm shows obtuse angles with the lateral chest wall with tapered margins [Figures [Figures33 and and4],4], displaces the pulmonary vasculature, changes its location on respiration, and may show incomplete border sign on chest radiograph – i.e., only a portion of the margin of mass is depicted on chest radiograph. Next step lies in differentiation of pleural from extrapleural origin of the mass. Extrapleural neoplasms may arise from extrapleural fat, ribs, intercostal muscles, and neurovascular bundle; typical pleural neoplasms do not cause erosion of ribs and displace the extrapleural fat outward, while extrapleural neoplasms displace the extrapleural fat inward

Loculated empyema: (A) Chest radiograph showing pleural-based opacity (arrow) with tapering obtuse margins in left hemithorax; (B) axial contrast-enhanced CT scan showing loculated collection (arrowhead) with peripherally enhancing thick walls

13

Calcified empyema: (A) Chest radiograph showing volume loss right hemithorax with veillike calcified (arrow) pleural opacity; (B) axial contrast-enhanced CT scan showing evidence of calcified chronic empyema (arrow) with proliferation of extrapleural fat and crowding of ribs suggestive of volume loss in right hemithorax

Differentiating pleural, pulmonary, and extrapleural neoplasms

14

2.3.2 Tumors and tumor-like conditions involving the pleura Various benign, malignant, and tumor-like conditions can involve the pleura [Table 2]. Malignant neoplasms are more common than benign neoplasms. Pleural tumors can have a varied imaging spectrum – may be unilateral or bilateral, calcified, or noncalcified, and focal or diffuse.

Benign and malignant pathologies of pleura

2.3.3 Pleural thickening Pleural thickening may be focal or diffuse. Diffuse pleural thickening is defined as thickening of pleura (more than 5 mm) with combined area of involvement more than 25% of chest wall if bilateral and 50% involvement if unilateral.[1] Apical pleural thickening is a normal aging process, but if the thickening is more than 2 cm, it requires further work-up [Figure 5]. On Computed Tomography (CT) scan, malignant pleural thickening is nodular (>1 cm), shows circumferential involvement, and involves the mediastinal pleura. On imaging, benign pleural thickening appears as a diffuse involvement of pleura. Pleural thickening greater than 5 cm in width, 8 cm in craniocaudal extent, and 3 mm in thickness usually suggests a benign etiology [Table

15

3].[2] Causes of diffuse pleural thickening are empyema, asbestosis, hemothorax, pulmonary fibrosis, irradiation, previous surgery, trauma, and drugs. In developing countries, tuberculosis is an important cause of pleural thickening. Pleural involvement in tuberculosis is either due to rupture of subpleural caseous focus within the lung, hematogenous dissemination, or involvement from an adjacent lymph node. Tubercular pleural involvement may be in the form of pleural effusion, pleural thickening, empyema, bronchopleural or pleurocutaneous fistula, or calcifications. On imaging, volume loss, calcifications, and proliferation of extrapleural fat are suggestive of diffuse benign pleural thickening. Fluorine-18 fluorodeoxyglucose positron emission Computed Tomography (18F-FDG PET CT) cannot reliably differentiate benign and malignant pleural thickening. However, a standardized uptake value (SUVmax) greater than 2 requires further evaluation with clinical correlation or image-guided biopsy.[3,4] Pleural plaques are deposits of hyalinized collagen fibers in the parietal pleura. Pleural plaques may be calcified or noncalcified. On imaging, pleural plaques are seen as focal pleural thickening.

16

Apical pleural thickening: Chest radiograph showing apical pleural thickening (arrowhead) in left apical region

Pleural thickening

17

2.3.4 Solitary fibrous tumor Solitary fibrous tumor of pleura (SFTP) is also known as localized fibrous tumor or localized pleural mesothelioma.[5] It is usually seen in the age group of 45-60 years. Most of these tumors are benign, but in 20% cases, they can be malignant. The tumor usually arises from the visceral pleura in 80% of cases. On imaging, SFTP appears as a soft tissue pleural-based neoplasm with areas of necrosis, hemorrhage, and cystic changes [Figures [Figures66 and and7].7]. Calcification may be seen in up to 26% of cases. Heterogeneous enhancement is seen post-contrast. On magnetic resonance imaging (MRI), hypointense solid mass is seen on T1- and T2-weighted images. Necrosis and cystic degeneration changes show high T2 signal intensity. Differentiation of benign and malignant fibrous tumors is difficult on imaging. Features suggestive of malignant fibrous tumors are presence of calcification, effusion, atelectasis, mediastinal shift, and chest wall invasion [Figures [Figures88 and and99].[6,7] Presence of stalk also suggests benign nature. On CT, the stalk is identified as a linear soft tissue extending into the pleura/interlobar fissure/hilum. Presence of stalk is also confirmed by change in its location on respiration. Associations of SFTP are clubbing, hypertrophic osteoarthropathy (Pierre–Marie– Bamberger syndrome), and hypoglycemia (Doege–Potter syndrome). Hypoglycemia occurs as a result of the production of insulin-like growth factor II (IGF-II) by these tumors.[8] Hypertrophic osteoarthropathy occurs as a result of production of ectopic growth hormone-like substance and is more common with tumors greater than 7 cm. Histologically, morphology is similar to that of a low-grade spindle cell neoplasm.

18

Benign solitary fibrous tumor: (A) Chest radiograph showing pleural-based opacity (arrow) in right hemithorax with peripheral obtuse margins; (B) axial contrast-enhanced CT scan showing heterogeneously enhancing pleural-based mass (arrowhead) proved to be benign fibrous pleural tumor

Pleural fibroma: (A) Chest radiograph showing lobulated pleural-based opacity (arrow) in right apical region; (B) axial contrast-enhanced CT scan showing heterogeneously enhancing peripheral mass lesion (arrow) in a biopsy-proven case of benign pleural fibroma

19

Malignant solitary fibrous tumor of pleura: Plain axial CT scan showing pleural-based soft tissue lesion with peripheral as well as internal calcification (arrow) abutting the liver

20

Malignant fibrous tumor of pleura: Axial contrast-enhanced CT scan showing heterogeneously enhancing mass lesion left hemithorax (arrowhead) causing mediastinal displacement to the right

2.3.5 Malignant mesothelioma Mesothelioma is a highly malignant and locally aggressive tumor seen in the sixth or seventh decade of life. It is associated with asbestos exposure, with an average latency of 35-40 years for its development. Hypertrophic osteoarthropathy and intermittent hypoglycemia are less common than SFTP. Most carcinogenic form of asbestos is crocidolite. Insulation workers, shipyard workers, construction workers, workers in heating trades, and asbestos miners are at greatest risk. Other factors which predispose to development of mesothelioma are radiation therapy, tuberculosis, and chronic empyema. On imaging, diffuse nodular pleural thickening, pleural plaques, and pleural effusion are usually seen [Figures [Figures1010 and and11].11]. The latent period for pleural plaque formation is usually 20 years and presence of pleural plaques is a strong indicator of asbestos exposure. Typically, pleural plaque is seen adjacent to ribs, involving sixth to ninth ribs. Pleurae along the intercostal spaces, costophrenic angles, and lung apices are less frequently involved. Large pleural effusion without mediastinal shift may also be seen [Figures [Figures1212 and and13].13]. Calcifications are seen involving the diaphragmatic parietal pleura [Figure 14].[9,10] On MRI, the lesions show low to intermediate signal intensity on T1-W images and high signal intensity on T2-W images with post-contrast enhancement. Differentiation from metastatic carcinoma is difficult; however, unilateral involvement and volume loss of affected hemithorax favors mesothelioma. Imaging criteria for unresectability includes encasement of diaphragm and involvement of extrapleural fat, ribs, or other mediastinal structures

21

Malignant mesothelioma: Axial contrast-enhanced CT scan showing enhancing nodular pleural thickening (arrows) involving the costal and mediastinal pleura, extending into the major fissure (arrowhead) with crowding of ribs suggestive of volume loss changes in left hemithorax

22

Malignant mesothelioma: Axial contrast-enhanced CT scan showing homogeneously enhancing nodular pleural thickening (arrows) involving the mediastinal and costal pleura with volume loss changes in left hemithorax

23

Mesothelioma presenting as pleural collections: Axial contrast-enhanced CT scan showing nodular thickening of pleura involving right hemithorax with small pleural collections (arrows)

24

Mesothelioma presenting as a pleural effusion: Axial contrastenhanced CT scan showing moderate left pleural effusion as loculated collection with thickening of pleura (arrows) in a case of mesothelioma

25

Mesothelioma and pleural plaques: (A) Axial plain CT scan showing calcified (arrows) and noncalcified (arrowhead) pleural plaques; (B) axial plain CT scan image showing calcified plaque (black arrow) classically involving the diaphragmatic parietal pleura in a construction worker

2.3.6 Lymphoma Both Hodgkin's and non-Hodgkin's lymphoma can involve the pleura. On imaging, effusion, pleural nodules, focal or diffuse pleural thickening may be seen, which show homogeneous

contrast

enhancement.

Associated

mediastinal

and

hilar

lymphadenopathy is also seen [Figures [Figures1515 and and16].16]. Cystic/necrotic changes and calcification are seen post-chemotherapy. Circumferential pleural involvement is less common in lymphoma.

26

Pleural lymphoma: Axial contrast-enhanced CT scan showing heterogeneously enhancing lobulated mass lesion involving the diaphragmatic pleura (arrow) and invading the chest wall in a case of high-grade lymphoma

Pleural lymphoma: Axial contrast-enhanced CT scan showing homogeneously enhancing nodular pleural thickening (arrows) involving the costal pleura with mediastinal lymphadenopathy (asterisk)

2.3.7 Calcifying fibrous pseudotumor The term calcifying fibrous pseudotumor was coined by Fetsch et al. in 1993.[12] Previously, these tumors were termed as “childhood fibrous tumor with psammoma bodies.” These neoplasms occur in children and young adults. History of previous inflammation is a prerequisite for the diagnosis. On imaging, extensive solitary or multifocal masses with calcifications are seen [Figures [Figures1717 and and1818].[13,14]

27

Calcifying fibrous pseudotumor: (A) Chest radiograph showing pleural-based calcified opacity (arrowhead) left hemithorax with incomplete border sign; (B) plain axial CT scan image showing pleural-based calcified lesion (arrow) with no destruction of underlying ribs

28

Calcifying fibrous pseudotumor: Plain axial CT scan showing calcified pleural-based opacity in right hemithorax (arrowhead)

2.3.8 Pleural metastases Adenocarcinomas are known to cause pleural metastasis more frequently than other histological types of cancers. Common primary sites are from lung, breast, lymphoma, and ovary [Figures [Figures1919–21]. Invasive thymoma can also involve the pleura [Figure 22]. On imaging, pleural effusion is the most common finding. Diffuse or focal nodular pleural thickening may be seen. Increased 18F-FDG uptake on PET-CT is seen in malignant pleural thickening and effusion.[2]

Pleural metastases: Axial contrast-enhanced CT scan showing heterogeneously enhancing pleural-based soft tissue (white arrow) with rib destruction (black arrow) in a case of pleural metastases from renal cell carcinoma

29

Pleural metastases: Axial contrast-enhanced CT scan showing nodular pleural thickening (arrows) involving the costal and mediastinal pleura with malignant pleural effusion in a case of metastatic ovarian adenocarcinoma

30

Pleural drop metastases in invasive thymoma: Axial contrast-enhanced CT image showing heterogeneously enhancing anterior mediastinal mass (arrowhead) with mild left pleural effusion and ipsilateral pleural implants (arrows)

31

Pleural metastases: Axial contrast-enhanced CT scan showing heterogeneously enhancing pleural-based mass lesion (arrow) in left hemithorax with extrathoracic extension in a case of metastatic adenocarcinoma

2.3.9 Askin tumor Askin tumor is an aggressive malignant tumor of primitive neuroectodermal origin belonging to the Ewing tumor family. Most of these tumors arise from the soft tissues of the chest wall or lung periphery. It is usually seen in children and adolescents. On histopathology, malignant, small round cells with Homer–Wright rosettes are seen. Balanced reciprocal chromosomal translocation between chromosomes 11 and 22 is diagnostic. On imaging, unilateral involvement is generally seen in the form of nodular pleural thickening. Infiltration into the chest wall, mediastinum, and sympathetic chain is pathognomonic. Pleural effusion and rib destruction may or may not be seen [Figure 23].

32

Askin tumor: (A) Chest radiograph showing inhomogeneous opacity (arrow) right hemithorax obscuring right hemidiaphragm without mediastinal shift; (B) axial contrast-enhanced CT scan showing heterogeneously enhancing nodular pleural-based lesions (arrows) involving the costal and mediastinal pleura with characteristic involvement of the sympathetic chain (arrowhead) in right paraspinal region

2.3.10 Rare pathologies of pleura 2.3.10.1 Pleural lipoma Pleural lipoma is often an incidental finding. It is one of the most common benign tumors of pleura. On CT, lipoma shows fat density and no contrast enhancement. Presence of enhancing septa within the mass suggests liposarcoma. 2.3.10.2 Pleural splenosis Pleural splenosis results from displaced splenic tissue into the thorax following trauma on the left side. On imaging, multiple soft tissue lesions of variable sizes are seen implanted on pleura, with enhancement similar to splenic tissue. Gold standard for diagnosis is scintigraphy with 99mTc heat-damaged tagged erythrocytes. 2.3.10.3 Other Other

rare

pathologies

of

pleura

are

mesothelial

cysts,

epithelioid

hemangioendothelioma, Castleman disease, sarcomas [Figure 24], malignant fibrous

33

histiocytoma, leukemic infiltration, Erdheim–Chester disease, and extraskeletal osteosarcoma. Extraskeletal osteosarcoma is a rare malignant neoplasm and constitutes 1.2% of all soft tissue sarcomas. It should be considered in the differential diagnosis for a rapidly growing calcified pleural mass in an elderly. Other causes of malignant pleural calcification are metastasis from osteosarcoma, chondrosarcoma, parosteal osteosarcoma, and mesothelioma.[15]

Spindle cell sarcoma of pleura: (A) Chest radiograph showing complete opacification of right hemithorax (arrowhead) with mediastinal shift to the left; (B) axial contrast-enhanced CT scan showing heterogeneously enhancing nodular pleural-based lesions with pleural effusion displacing the heart to the left

Pleural pseudotumor[16] is fluid collection within a lung fissure. Most common site for pseudotumor is minor fissure. Common causes of pleural pseudotumor are congestive heart failure, cirrhosis, and renal insufficiency. On chest radiographs, classical lenticular or biconvex opacity is seen in the fissure. It usually resolves after therapy with diuretic agents. An approach to correct diagnosis of pleural tumors depends on the pattern of involvement – focal or diffuse, unilateral or bilateral, and calcified or noncalcified [Table 4]. The role if imaging is to identify pleural thickening, differentiate benign and malignant pleural thickening, and identify the cause if possible. An appropriate

34

clinical history, imaging findings and, if required, image-guided biopsy may be used to clinch the diagnosis.

Approach to diagnosis of pleural pathologies