LOKALIZED FIBROUS TUMORS OF THE PLEURA.

Dr. Refik ÜLKÜDicle University School of Medicine

Thoracic Surgery Department

LOKALIZED FIBROUS TUMORS OF THE PLEURA.

Dr. Refik ÜLKÜDicle University School of Medicine

Thoracic Surgery Department

• 1767 Lieutaud described for the first time a primary tumor of the pleura

• 1870 Wagner- described Primary localized pleural tumor

• 1931-Klemper and Rabin, published the first accurate pathologic description and classified mesothelioma as either ‘Localized’ or ‘diffuse’.

• 1942- Stout and Murray claimed that localized mesothelioma had a mesothelial origin.

• The other studies; Mesothelial layer covering the tumor was intact. Epithelial cells seen could have been trapped within

growing fibrous mesenchymal tumors.Ann Thorac Surg 2002; 74 :285-93

Int J Surgery 2008; 6: 298-301

• The controversy on the origin of these tumorspersisted for several decades and is reflected bythe variety of terms given to the neoplasm.• Localized mesothelioma• Localized fibrous mesothelioma• Localized fibrous tumors• Solitary fibrous mesothelioma• Fibrous mesothelioma• Pleural fibroma• Submesothelial fibroma• Subserosal fibroma Ann Thorac Surg 2002; 74: 285-93

• Recently, Localized fibrous tumor recognized as

nonmesothelial in orgin and mesenchymal origin.

Plevra tümörleri

Diffüz Lökalize

its association with asbestos (+)Poor outcomes (+)

its association with asbestos(-)Good outcomesEtiology ?Solitary benign

Clinical Features• LFTP are rare. They account for 5%- 10% all pleural neoplasms.

• Approximaely 900 cases of LFTP have been reported in the literature.

• LFTP are slow-growing neoplasms.

• About 12 % of LFTP, however, are malignant and eventually lead to death through local reccurence or metastatic disease.

1- Arch Bronconeumol 2004; 40: 329-32 2- Ann Thorac Surg 2002;74:285-93 3- Ann Thorac Surg 2009; 88: 1632-7

• LFTP have been described in all age groups from 5 to 87 years.(Chilhood time

• They peak in the sixth and seventh decades of life.

• LFTP appear equal frequency in men and women..

• LFTP is fortuitous in 50 % of cases.

• Asymptomatic ( They can be asymptomatic 68 months on the avarege prior to referral.)

• Preoperatif diagnosis is extremely difficult or not possible in many cases.

1- Oncology Hematology 2003;47:29-33 2- EJSO 2005; 31: 84-87

SymptomsAsymptomatic(The most of patients)

Cough (%33%)Chest pain (%23%)Dyspnea (%19)ObstructivepneumonitisHemoptysis

Paraneoplastic Syndromes

Pierre-Marie-Bamberg syndrome

Doege-Potter Syndrome

• Digital clubbing and hypertrophic pulmonary osteoarthropathy (Pierre-Marie-Bamberg syndrome) have been described in 10% to 20% of patients with either benign or malignant LFTP

• Hypoglisemia have been described in 4% of patients with large tumor.

• LFTP can also secrete insulin-like growth factorII, which causes refractory hypoglycemia (Doege-Pottersyndrome)

• Hypoglisemia return to normal values within 3 to 4 days after resection of the tumor

• PLEURAL EFFUSION?• Pleural effusion affects 16% of the patients.• Malignant tumors: 32%• Benign tumors: 8 %• PE are generally small of a small size, although

volumes as great as 3 L have been reported in the literature.

Chest radiograph:LFTP usually appear as a well defined,homogeneous, and rounded mass.Rarely pleural effusion (+)Pedunculated SFTP haveoccasionally been reportedto be moving on successivechest radiographs.CT:Well-delineated, homogeneous (small lession), Heterogeneity ( hemorrhage, necrosis )Soft tissue attenuation, Tumors arising in an interlobar fissure may be more difficult to differentiate from an intraparenchymal mass. Calcification : (1/4 patient)Diffuse pulmonary collapse due to compression (+)

MRMRI use in the assessment of pleural disease.The morphology and relationship of LFTP to adjacent mediastinal ,major vascular structures and diaphragm may be better appreciated with magnetic resonance imaging than with computed Tomography. LFTP has low signal intensity on T1-T2 weighted images. High signal intensity: Increase vascularity, edema and cellularity

PET-CT• Limited applicability• To the malignancy assessment: High negative

predictive value

• Generally, 75/80% of tumors develops as a pedunculated growth from the visceral pleura.• In the remaining 20/25% develops from

parietal pleura.• LFTP with an origin from the parietal pleura

and a sessile morphology has more aggressive behavior.

• The size of tumor ?prognostic factor• In study of Perna, out of the 9 tumors with

benign histological features and 4 out of the 6 tumors with malignant histological features were over 10 cm in diameter; They also classified a 23 cm tumor as benign, which indicates that large size is not necessarily a marker of malignancy.

• Some authors have observed that the size of the tumor is a prognostic factor for the clinical behavior of LFTP.

• De Perrot observed that, all the patients reported with a benign tumor larger than 10 cm had a good clinical outcome, whereas 16 out of the 28 malignant tumors larger than 10 cm were associated with recurrence or death.

• CT guided aspiration biopsy is not a reliable diagnostic tool.Cardillo et al. (2009)- 39%Magdeleinat et al. (2002)- 45%Kohler et al. ( 2007)- 40%

1-Arch Bronconeumol 2004; 7: 329-32 2-Int J Surgery 2008; 6: 298-301 3-Eur J Cardiothorac Sur 2002; 21: 1087-93

Histopathology(1)

• Benign SFTP are small pedunculated tumors.• The malignant tumors are often larger than 10 cm and grow

beneath the parietal pleura of the chest wall, diaphragm, or mediastinum.

Macroscopically:• Firm, smoothly lobulated masses (+)• Most of cases are capsulated by a thin, translucent membrane,

containinga reticulated vascular network.• Firm adhesion without signs of invasion (+)• The cut surface appears gray-whiteand may show areas of

hemorrhage and necrosis.

Histopathology(2)

Microscopically• SFTP are not characterized by uniform cell.• Proliferation of elongate spindle cell (+)• Zones of hypercellularity may alternate with

hypocellular• Increased amount of blood vessels within the tumor: Hemangiopericytoma-like pattern

• SFTP are histologically characterized by fibrous areas with low to moderate cellularity with spindle-shaped or oval cells scattered haphazardly among strands of collagen in a typical ‘‘patternless pattern.’’

J Surg Oncol 2006; 94: 40-4.

• Immunohistochemistry has been an extremely useful tool to differentiate SFTP from mesotheliomas and other sarcomas over the last few years .

• SFTP by definition is vimentin positive and keratin ,S-100 negative. In addition, CD34 is positive in most benign and malignant SFTP.

• The antiapoptotic protooncogene bcl-2 is strongly expressed in SFTP.

• Recently, some authors have demonstrated that (CD99) could be expressed by solitary fibrous tumors located in the pleura

Over the last 20 years, immunohistochemical studieshave provided strong evidence for a mesenchymal originof these tumors.

Vimentin (+) Keratin (-)CD34 (+) CD99 (+) bcl-2 (+)

• In studies of England and coworkers;• There were 223 cases.• Eighty-two cases were described as histologically

malignant. • None of the patients with a histologically benign

disease died, 55% of those with a malignant form died because of recurrences or metastases.

• The authors observed complete resectability was the single most important predictor of outcome.

De Perrot reviewed data of 185 patients.19 (10%) of the patients presented at least one recurrence of their tumorOf the 35 patients who presented a recurrence or died of the disease27 had a primary sessile tumor with histologic sign of malignancy5 patients presented with a primary sessile histologically benign tumor2 with a primary pedunculated histologically malignant tumor.One patient with a pedunculated histologically benign tumor presented a recurrence (or a new primary tumor)

Benign saplı Benign sesil Malign saplı Malign sesil0%

10%

20%

30%

40%

50%

60%

70%

Hafif ila belirgin nükleer pleomorfizm, Nukleusların birbirlerine karıştığı artmış

selülarite, Nekrotik veya hemorajik alanların varlığı Stromal veya vasküler invazyon.

High mitotic counts, defined as more than four mitoses per 10 highpower fieldsMild to marked pleomorphism based onnuclear size, irregularity, and nuclear prominenceBundles of high cellularity with crowding and overlapping of nuclei, Presence of necrotic or hemorrhagic zones;Stromal or vascular invasion

Classification of Solitary Fibrous Tumors of thePleura

STAGE

Stage 0 Pedunculated tumor without signs of malignancy

Stage I Sessile or “inverted” tumor without signs of malignancy

Stage II Pedunculated tumor with histologic signs of malignancy

Stage III Sessile or “inverted” tumor with histologic signs of malignancy

Stage IV Multiple synchronous metastatic tumors

Ann Thorac Surg 2002; 74: 285-93

Treatment• Often it is impossible to make a definite pre-operatory

diagnosis for this tumor• The mainstay of therapy en bloc surgical resection.• Thoracotomy diagnostic - therapeutic tool.(A distance of 1 to 2 cm from the tumor is usually recommended to be in healthy tissue.)• Generally, there is no lymph-node involvement• The pedunculated tumors can be safely resected with a wedge resection of the lung.• In order to achieve complete resection in sessile tumors

lobectomy or a pneumonectomy

• Difficulties may arise during surgery due to the size of the tumor, to richly vascularized pleural adhesions and to a wide pedicle attaching the mass to the inside of the lung, the diaphragm, the mediastinum or the thoracic wall.

• Some authors reported cases of relapse 17-20 years after no radical surgery resection.

• The relapses are more aggressive than the primary tumor.

• Frozen section can be helpful to demonstratethat the resection margins are free of tumors, but this is not routinely required.• Tumors adherent to the parietal pleura require

an extrapleural dissection.• If the tumor densely adheres to or invades the

chest wall Chest wall resection

• In 3% or less of the cases, the tumor can be “inverted” and grow inside the lung parenchyma. These tumors may occasionally require a lobectomy or a sleeve lobectomy.

• Thoracoscopic approaches : It can be safely used to remove small pedunculated tumors located on the visceral pleura.(contact metastasis ?)

• Some authors have also recommended the assistance of a video camera (video-assisted thoracic surgery) to obtain a more precise view of the resection margins in some large, broad-based tumors of the parietal pleura

Authors and P.Y PatientsNo

Benign/Malign

VATS Mortality%

Cardillo, 2009 110 95/15 69/110 0,9 67, 10 yıllık 96, 10 yıllık

Perna, 2008 15 9/6 0/15 0 100, 5 yıllık 100, 5 yıllık

Magdeleinat,2002 60 38/22 7/53 3,3 89, 10 yıllık 94, 10 yıllık

Harrison-Phipps, 2009 84 73/11 - 3,6 46, 5 yıllık 89, 5 yıllık

Rena,2001 21 13/8 1/20 0 - -

Carretta, 2006 18 16/2 - 0 - 80, 5 yıllık

Ann Thorac Surg; 2002;74:285-93

ADJUVANT TREATMENT

• The role of adjuvant therapy in LFTP; ? (limited number of patients )• Radio and chemotherapy have shown to be

effective in treating selected patients.• After radical surgery, Cardiollo never

recommed either RT and CT.• RT appears to be indicated only when surgical

resection incomplete.

• Veronesi and colleagues, have observed significant reduction of an inoperable recurrent SFTP with cyclofosfamide and adriamycin.

• Neoadjuvant therapy could be helpful in large malignant tumors, its use is limited by the

difficulty of obtaining a precise preoperative diagnosis even with an open biopsy

• Conclusion: Although LFTP are considered histologically

benign tumors, because of the risk of recurrence and malignant transformation, complete surgical resection is indicated and long-term follow-up is recommended in all patients.