Pier Luigi FILOSSO, MD FECTS Associate Professor University of Torino Dept Thoracic Surgery

Transcription

1 Thank you for viewing this presentation. We would like to remind you that this material is the property of the author. It is provided to you by the ERS for your personal use only, as submitted by the author by the author

2 Modern definition of mediastinal compartments and the current approach to patients with an anterior mediastinal mass Pier Luigi FILOSSO, MD FECTS Associate Professor University of Torino Dept Thoracic Surgery

3 Conflict of interest disclosure I have no real or perceived conflicts of interest that relate to this presentation This event is accredited for CME credits by EBAP and EACCME and speakers are required to disclose their potential conflict of interest. The intent of this disclosure is not to prevent a speaker with a conflict of interest (any significant financial relationship a speaker has with manufacturers or providers of any commercial products or services relevant to the talk) from making a presentation, but rather to provide listeners with information on which they can make their own judgments. It remains for audience members to determine whether the speaker s interests, or relationships may influence the presentation. The ERS does not view the existence of these interests or commitments as necessarily implying bias or decreasing the value ofthe speaker s presentation. Drug or device advertisement is forbidden.

4 Introduction AIMS Mediastinum & Mediastinal Compartments: definition How to approach the mediastinal massess Diagnostic techniques of the mediastinum Evaluation and diagnostic approach according to the mediastinal compartments Take home messages

5 THE MEDIASTINUM The mediastinum extends from the thoracic inlet (I rib) to the diaphragm, between the pleural cavities

6 Mediastinal Compartments Modified 3- compartment model (Shields) Traditional 4-compartment model Traditional 3-compartment model

7 Mediastinal Compartments Anterior Between the back of the sternum and the anterior surface of the pericardium & the great vessels

8 Mediastinal Compartments Middle (visceral) Includes the heart, great vessels, trachea, esophagus, and it is bound posteriorly by the anterior longitudinal ligament (the anterior surface of the vertebral bodies)

9 Mediastinal Compartments Posterior (paravertebral) Extends from the anterior longitudinal ligament to the posterior ribcage

10 Mediastinal Masses Mediastinal tumors are relatively uncommon and there are many different types

11 Mediastinal masses: incidence by Compartments 50-60% 20-25% 23-25% IASLC, Thoracic Oncology, 2014

12 Mediastinal Tumors: Why is this difficult? Incidence of Mediastinal Tumors is low Many years are needed to develop adequate clinical experience Includes a wide variety of lesions Clinical presumptive diagnosis is a matter of pattern recognition This is inherently difficult The approach used by authors is the opposite of what the clinician needs

13 Approach to Mediastinal Tumors Known clinical data, always available: Age, gender Mediastinal compartment location Radiographic characteristics Often available: Duration of symptoms Sometimes available: Characteristic presentation: (Myasthenia Gravis, B symptoms, associated diseases) Laboratory identifiers

14 Symptoms and associated disorders Benign/slow growing neoplasms are often asymptomatic Malignant lesions are frequently symptomatic Local signs/symptoms Cough Chest pain SVC syndrome Dyspnea, Dysphagia Cardiac tamponade Associated paraneoplastic diseases (MG, PRCA, Hypogamma, SLE) Systemic signs/symptoms B symptoms Fever Night sweats Weight loss

15 Symptoms and associated disorders Benign/slow growing neoplasms are often asymptomatic Malignant lesions are frequently symptomatic Local signs/symptoms Systemic signs/symptoms B symptoms Cough Chest pain SVC syndrome Dyspnea, Dysphagia Cardiac tamponade Associated paraneoplastic diseases (MG, PRCA, Hypogamma, SLE) Duration of symptoms (rapid, intermediate or slow) is of paramount importance to suggest a diagnosis Fever Night sweats Weight loss

16 Mediastinum: diagnostic techniques Non-invasive (Imaging) Minimally-invasive pathologic staging techniques CT CT/PET MRI Blind TBNA EBUS-TBNA EUS-TBNA TTNA Surgical techniques Mediastinoscopy Mediastinotomy TEMLA, VAMLA VATS

17 Approach to Mediastinal Tumors Confirmation of diagnosis usually requires tissue, but approach may vary from: No biopsy (Cyst, NSGCT with + AFP, HCG) FNA Core Biopsy Surgical biopsy (Lymphoma) Resection (Stage I,II Thymoma, Teratoma, Schwannoma, Substernal Thyroid)

18 Mediastinum: surgical techniques Mediastinoscopy Accessible regions

19 Mediastinum: surgical techniques Anterior Mediastinotomy (mammary vessels preservation)

20 Mediastinum: surgical techniques Accessible regions Anterior Mediastinotomy (with video-assistance)

21 Mediastinum: surgical techniques VATS (Video-assisted thoracic surgery) Access to all mediastinal regions Useful in case of associated pleural effusion (lymphoma) (Theoretical) risk of seeding of the pleural space/tract

22 Approach to Mediastinal Tumors: the need for histological confirmation 1. In most cases CT findings (+ TM or clinical findings) are sufficient for the diagnosis (teratoma, GCT, thymoma, neurogenic tumor, thyroid mass) 2. Cyto-histologic confirmation is needed in case of Equivocal CT findings Suspected lymphoma Unresectable or advanced thymic tumors (induction, exclusive CT/RT) 3. Non-surgical biopsy may be considered as first attempt (core > FNA) 4. Surgical biopsy is almost always diagnostic and the technique depends upon the anatomical location

23 Anterior mediastinum (epicenter anterior to pericardium/great vessels)

24 Anterior Mediastinum Tumors All Patients Courtesy of Prof. F. Detterbeck

25 Anterior Mediastinum Tumors Women > 40 years 100% 80% 60% Thymoma Thyroid Micellaneous 40% HD/MLC Lymph LB NHL 20% 0% >80 Age (years) Teratoma NSGCT/TeratoCa Seminoma Thymoma and substernal goitres are the most frequent tumor types ESTS Textbook of Thoracic Surgery

26 Anterior Mediastinum Tumors Men> 40 years 100% 80% 60% Thymoma Thyroid Micellaneous 40% HD/MLC Lymph LB NHL 20% 0% >80 Age (years) NSGCT/TeratoCa Teratoma Seminoma Thymoma and substernal goitres are the most frequent tumor types ESTS Textbook of Thoracic Surgery

27 Anterior Mediastinum Tumors Predominantly Thymoma and substernal Thyroid lesions Especially in women, esp. in older age groups A few are lymphoma (HD, MLC NHL > LB NHL) A few are teratoma in age ~15% comprised of miscellaneous rare tumors

28 Anterior Mediastinum Tumors THYMOMA Incidence / person Age onset: yrs (with MG); yrs (without MG) Histotypes: Thymoma (5 subtypes), Thymic carcinoma (TC) and NETT Slow onset of symptoms (exception TC/NETT), 30% asymptomatic 30-50% associated Myasthenia Gravis Paraneoplastic syndrome (PRCA, Hypogamma, SLE) CT signs suggestive for diagnosis

29 Anterior Mediastinum Tumors THYMOMA Stage III Thymoma Stage IVa Thymoma

30 Anterior Mediastinum Tumors THYMOMA RECURRENCE local: anterior mediastinum (25%) regional: intrathoracic (60%) distant: outside the chest or intrapulmonary nodules (15%) usually asymptomatic, incidentally discovered during follow-up, several years after the resection of the primary Thymoma

31 Anterior Mediastinum Tumors: Thymic Cyst

32 Anterior Mediastinum Tumors: Thymic Cyst Well-circumscribed Round/oval Homogeneous Water/fluid attenuation (HU 0-20) the malignant potential of lesions appearing as thymic cyst is CURRENTLY UNKNOWN

33 Anterior Mediastinum Tumors: Cystic Thymoma Sometimes can manifest as higher density and less regular lesions MRI should be therefore performed (internal septations) Paraneoplastic syndrome(s) may also be observed Age > 40 years

34 Anterior Mediastinum Tumors Substernal Goiter

35 Anterior Mediastinum Tumors Substernal Goiter

36 Anterior Mediastinum Tumors Substernal Goiter Thyroid is easy to recognize, extending down from neck on contrast-enhanced CT (presence of calcifications, nodules and colloid) I 131 scan not useful for 6 weeks after contrast CT

37 Anterior Mediastinum Tumors Substernal Goiter Hyperdense (HU: due to iodine) Enhances following IV contrast (prolonged enhancement) Frequently demonstrates continuity with cervical thyroid gland

38 Anterior Mediastinum Tumors If it looks unusual or a lymphoma is suspected: biopsy (usually surgical)

39 Anterior Mediastinum Tumors LYMPHOMA 2001 WHO classification Hodgkin disease (HD), non-hodgkin lymphomas (NHL) and MALT lymphoma 50% HD and 20% NHL involve ALSO the mediastinum 3% HD and 6% NHL involve ONLY the mediastinum 90% of mediastinal lymphomas are in the anterior (superior) region Hystotypes: Hodgkin disease, mediastinal B-large cell NHL and lymphoblastic (T-cell) NHL, pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma

40 Clinical Scenario 1. Consider substernal goiter Should be obvious on CT Resect if symptoms, airway narrowed; rarely consider thyroid malignancy Level of Confidence % of All Certain 10-30% 2. If not substernal goiter Thymoma most likely ~50% a. If MG, other thymic paraneoplastic syndrome Certain b. If lobulated, homogenous/slightly heterogeneous mass High c. If lobulated and with pleural nodules Very high Resect if early stage, core biopsy first if higher stage Male & women > 40 years

41 Clinical Scenario 3. If it does not fit for goiter or thymoma a. If well-circumscribed, round/oval/saccular, homogeneous near thymic bed on CT Consider thymic cyst. get MRI If purely cystic simple thymic cyst, observe for ~2 years If cystic but with soft tissue components on CT/MRI - Multilocular cyst or cystic thymoma - Resection Male & women > 40 years Level of Confidence Very high Uncertain % of All 10-40% <5% <5% b. If heterogeneous with fat (bone) Benign teratoma High <5% Resect if symptomatic or significant organ compression c. If matted, multiple enlarged nodes HD, MLC-NHL Moderate 2-10% If B symptoms core (or surgical)l biopsy High

42 Anterior Mediastinum Tumors Women age years 100% 80% 60% HD/MLC Lymph Thymoma Teratoma 40% Miscellaneous LB NHL 20% 0% Thyroid NSGCT/Teratoca Seminoma Lymphoma and Teratoma are the most frequent lesions Age (years) ESTS Textbook of Thoracic Surgery

43 Anterior Mediastinum Tumors Hodgkin s Lymphoma

44 Anterior Mediastinum Tumors Hodgkin s disease Young adults, years Female predominance (NS type) Intermediate onset of symptoms The most common type is nodular sclerosing (NS) type (60%) HIV-associated in mixed cellularity type (+ EBV) 30% B symptoms (fever, night sweats, weight loss) Bulky involvement with symptoms in 30-35% of the patients Histology (surgical biopsy) is needed for subtype diagnosis

45 Anterior Mediastinum Tumors: Mediastinal large cell non-hodgkin lymphoma Broad age range, most young adults Female predominance Anterior region (>95%) Rapid onset of symptoms (pain, cough, SVC syndrome, pleural effusion) Type B symptoms in 30% of the pts Bulky involvement + pleural/pericardial effusion Extrathoracic involvement in 10-50% of the pts Surgical biopsy often needed (high sclerosis)

46 Anterior Mediastinum Tumors: Germ cell tumors of the mediastinum Primary (extragonadal) or secondary (from gonadal germ cell tumors) 3-5% of all germ cell tumors Teratoma Mature teratoma, Teratomas with malignant elements Teratocarcinoma, with another germ cell tumor Seminoma Nonseminomatous NSGCT Embryonal carcinoma Yolk sac tumor Choriocarcinoma Teratocarcinoma Mixed tumors

47 Anterior Mediastinum Tumors: Teratoma Most common mediastinal germ cell tumor (60-70%) Equal M/F distribution, mean age years More than one of three germ cell layers (ecto, meso, endoderm) Mostly asymptomatic Rarely malignant ( teratocarcinoma ) Surgery is the treatment of choice

48 Anterior Mediastinum Tumors: Seminoma 40% of malignant germ cell tumors of the mediastinum Men in third-fourth decades Only 10% have elevated β-hcg, not AFP Mostly symptomatic (compression symptoms, SVC syndrome) Highly sensitive to CT (cisplatin-based) and RT Nonsurgical therapy is curative in most patients with survival rates of 60-80% (mostly CT, RT for small tumors) Surgery in selected cases (encapsulated forms, residual mass after CT or RT)

49 Anterior Mediastinum Tumors: Nonseminomatous germ cell tumors of the mediastinum (NSGCT) yrs of age, mostly symptomatic (compression, SVC, met) Elevated AFP and β-hcg levels Mets to regional LN, pleura, pericardium and distant sites (25%) Primary CT with bleomycin, etoposide and cisplatin (BEP, VIP) Surgery in case of resectable residual mass Salvage CT for disease progression or unresectable residual mass Challenging surgery and postop (bleomycin-damaged lung) 2-year survival= 67%, 5-year= 50%

50 Anterior Mediastinum Tumors: Teratoma

51 Anterior Mediastinum Tumors: Mature Teratoma

52 Anterior Mediastinum Tumors: female years Most common is Lymphoma (HD, MLC ~ 40%) Also thymoma in older pts, teratoma in younger pts ~ 10% have LB NHL, ~ 5% age have NSGCT Clinical Approach: Surgical Bx needed in most, esp if B symptoms Resection if confident of teratoma or stage I,II thymoma (? MG) FNA is useful if suspected LB NHL Rarely useful to get α-fp, β-hcg

53 Ant Mediast Lymphoma Diagnosis Nodular Sclerosing Hodgkins Disease (NSHD) or Mediastinal Large Cell (MLC) NHL Both have prominent sclerosis Ability to establish diagnosis by FNA, especially the subtype of lymphoma, is difficult Bone Marrow involvement rare (<2%) Surgical biopsy required in most centers Lymphoblastic (LB) NHL Unique cytol & immunophenotypic charac on FNA + bone marrow in 50%, also + pl effus cytol

54 Ant Mediast Lymphoma Diagnosis Issues with Needle Bx of NSHD or MLC NHL prominent sclerosis poor specimens Core Bx and ancillary studies may help, but: Ability to establish dx by FNAB varies from 13-90% (very center specific?) In most series used only as prelim test, to be confirmed w surg Bx to establish subtype Most series incl FNAB done to Dx recurrence

55 Clinical Scenario Level of % of All Confidence 1. If matted, multiple enlarged nodes, B symptoms, LDH HD, MLC-NHL High 30-50% core or surgical biopsy 2. If heterogeneous with fat (bone) Benign teratoma High 10-25% Resect if symptomatic or significant organ compression 3. If MG and lobulated, homogenous mass Thymoma High 5-10% Resect if early stage, core (or surgical) biopsy if higher stage women age years

56 4. If fulminant onset: Clinical Scenario a. Large mass, pleural effusion, B symptoms, LDH LB NHL cytology of pleural effusion, bone marrow b. Heterogeneous mass, lung metastases NSGCT confirm by serum α-fp, β-hcg (± Bx) Level of Confidence % of All Moderate 5-10% Certain Moderate 2-5% Certain c. Everything else various rare tumors Unclear 5-20% core (or surgical)l biopsy women age years

57 Anterior Mediastinum Tumors Men age years 100% 80% 60% 40% NSGCT/TeratoCa HD/MLC Lymph Miscellaneous Thymoma Teratoma 20% Seminoma LB NHL 0% Age (years) Thyroid ESTS Textbook of Thoracic Surgery

58 Anterior Mediastinum Tumors Men age years Men - Relatively even mix of: Malignant Germ cell (seminoma NSGCT) Lymphoma (HD>MLC) Thymoma (esp older groups) Teratoma (esp younger groups) Miscellaneous tumors Also LB NHL in age 10-19

59 Anterior Mediastinum Tumors Men age years Clinical Approach If onset of symptoms rapid suspect NSGCT (bulky inhomogeneous, pulm mets) or LB NHL (bulky mass, freq extrathor invlmt, effus, B symptoms, LDH) Get α-fp, β-hcg / FNA of mass / bone marrow Bx, pleural fluid cytology Occasionally MLC NHL (bulky, few other nodes, effus, B symp)

60 Mediastinal Germ Cell Tumor: Diagnosis Nonseminomatous GCT ~90% have markedly abnormal serum markers α-fp, β-hcg Markers and typical presentation is sufficient for diagnosis without biopsy Seminoma Normal markers (~10% low level β-hcg) Get FNA for diagnosis

61 Clinical Approach Ant Mediast Tumors men Age If asymptomatic or indolent onset of sympt. suspect Thymoma (older age,?mg) or Teratoma (inhomogeneous, fat ± calcium density) Biopsy may not be needed

62 Clinical Approach Ant Mediast Tumors men Age If intermediate onset of symptoms suspect Lymphoma HD cervical, hilar nodes, B symp; WBC, Alk MLC bulky, inhomogeneous, B symp, pl/pericard effusion, few other nodes, ant mediast only in 90% or Seminoma (homogeneous, pulm mets) Surgical Biopsy will probably be needed

63 Ant Mediast Tumors Children

64 Ant Mediast Tumors Age < 10 years Vast majority of teratomas are benign Thymic lesions are generally cysts, hyperplasia LB NHL and HD/MLC NHL lymphomas occur in older children Teratomas, thymic lesions, other cysts, cystic hygromas usually in younger children

65 Ant Mediast Tumors Age < 10 years Issue is to differentiate lymphoma from other lesions If lymphoma, Bx only (may do FNA for LB NHL, or cytol of pleural fluid) Other lesions are generally resected due to compression of chest structures This can usually be determined by age of onset, rapidity of growth, and radiographic appearance

66 Posterior mediastinum (Paravertebral Masses)

67

68 Posterior Mediastinal Tumors: age Vast Majority are benign: Schwannoma Neurofibroma Ganglioneuroma 5-10% Neurofibrosarcoma Usually in setting of familial neurofibromatosis 10-20% of all pts with neurogenic tumors have familial condition; of these 10-20% will develop a malignant tumor Don t forget about other systemic diseases TB, Hematopoetic disorders

69 Posterior Mediastinal Tumors: Neurogenic Tumors Nerve sheath (adults, almost all benign) Benign, Neurilemmoma,Neurofibroma, Melanotic schwannoma, Granular cell t. Malignant, Neurofibrosarcoma Ganglion cell (children, young, 2/3 malignant) Benign, ganglioneuroma Malignant, Neuroblastoma, ganglioneuroblastoma (children) Paraganglionic tissue Benign, chemodectoma, pheochromocytoma Malignant, malignant pheochromocytoma

70 Posterior Mediastinal Tumors: age How to differentiate benign vs malignant: Not helpful: Symptoms (overall) ( 84% adults, 60% children are asympt.) 10% dumbell (both adults/children, benign/malig) Bone changes (displacemen, deformationt seen in 33% of adults) VMA, HVMA (rarely if ever unless N/GN blastoma) Signs of malignancy: Pain, Dyspnea, > 10 cm, major mediastinal shift, pleural effusion, bone destruction

71 Posterior Mediastinal Tumors: age Management - Potentially malignant tumors (Multiple neurofibromatosis, pain, radiographic signs) Chest CT; if close to spinal canal MRI Other imaging (EUS, PET not well defined) Resection, consider multimodality approach Long term survival is unusual Management - Clinically benign, but NeuroFibromatosis: If solitary lesion, resect prophylactically If multiple, difficult to resect Observation Poorly defined whether problem is rate of malignant degeneration or development of new malignant tumor Rate of growth of benign lesions is hard to predict

72 Posterior Mediastinal Tumors: Neurinoma

73 Posterior Mediastinal Tumors: Neurinoma (MRI)

74 Courtesy of Prof. F. Detterbeck Posterior Mediastinal Tumors: Neuroblastoma

75 Posterior Mediastinal Tumors: Age 0 19 years Age 0-5: Neuroblastoma/Ganglioneuroblastoma in vast majority (esp age 0-1) Age 5-19: Ganglioneuroma (Schwannoma, Neurofibroma) 5-10% Neurofibrosarcoma or N/GN blastoma

76 Middle mediastinum (visceral compartment)

77 Middle Mediastinal Tumors Majority are cysts (50%): Pericardial, bronchogenic, esophageal, undifferentiated cyst Communication with other structrues is rare (<10%) Granulomatous/Inflammatory causes common (20%) TB, Sarcoidosis Other benign causes (silicosis, Castleman s disease) Malignant causes less common (20%) BALT,MALT Lymphoma in older pts SCLC/NSCLC in smokers Other causes (10%) Aortic (pseudo)aneurysm, paraganglioma, thyroid, other lymphoma, fungal infection,

78 Conclusions

79 Conclusion 1/2 Optimal evaluation and diagnosis of mediastinal tumors require an integrated clinical, radiological and histological approach Clinical approach includes consideration of the following: age, sex, presence/duration of symptoms and associated paraneoplastic conditions Radiological approach includes CT scan with intravenous contrast; CT scan is essential to assign the tumor to one of the mediastinal anatomic compartments. MRI and PET-CT are used on a selective basis. Histological confirmation is most often needed for suspected lymphomas and in locally advanced/unresectable thymic tumors

80 Conclusion 2/2 More than half of the tumors are in the anterior region, the remaining are equally distributed in the visceral and paravertebral regions In the anterior region the most common tumors are thymomas in adults and lymphomas in patients < 40 years. GCTs are mostly seen in young males In the visceral region more than half of the tumors are cysts. The remaining are mediastinal involvement from lung cancer and granulomatous diseases. In the paravertebral region almost all tumors are from nervous structures. Malignant forms are typical of infancy or in case of familial neurofibromatosis

81 Torino, Italy Thank you very much for your attention

82