Pleural Mesothelioma diagnosis management

Pleural Mesothelioma diagnosis management

1. Pleural
Mesothelioma

2. Mesothelioma
Mesothelioma
tumours develop in
mesothelial or
sub-mesothelial cells
of different tissues

3. Auto and aircraft mechanics
Carpenters and construction
workers
Navy and shipyard workers
Oil Rig and Refinery workers
Power plant and utility
workers
HVAC workers

4. Epidemiology
The World Health Organization (WHO) estimates 125 million people worldwide are exposed to asbestos in the
workplace and over 100,000 people die each year from asbestos-related lung cancer, mesothelioma, and
asbestosis.
Globally, deaths due to mesothelioma have been estimated to be 29,909 globally, out of which 27,447 are due
to occupational exposure.

For every 170 tonnes of asbestos consumed, there is one mesothelioma death.With about 350,000 tonnes of
annual use, India alone shall have 2000 plus mesothelioma deaths.
With asbestos exposure risk increases by 7–8 folds

Nonexposed individuals, the incidence ranges from 2 to 4/100,000 normal population.

Therefore, it can be deduced that incidence may be between 14 and 32/100,000 exposed
individuals depending on the quantum of exposure and type of asbestos

5. What are asbestos ???????
Greek - inextinguishable
Chrysolite Erionite
Actinolite Winchite
Anthophyllite Richterite
Riebeckite Antigorite
Tremolite Fluoro- edenite
Cummingtonite-grunerite

6. Other risk factors
●Ionising radiation exposure1
●Erionite (a mineral found in gravel roads) exposure2
●Exposure to zeolites (similar to asbestos)3
●Genetic factors:
Germline mutation in the BAP1 gene
Some studies have raised the possibility that infection with SV40
might increase the risk of developing mesothelioma5
5BAP1, BRCA1 associated protein 1; SV40, simian virus 40.

9. Symptoms
●Cough
●Dyspnea - pleural effusion in early stages
-Lung encasement by pleural thickening
●Chest pain - Parietal pleural irritation
-Invasion of the intercostal nerves by tumor invading
the chest wall
●Weight loss

15. Pleural effusion
●Exudative
●High proteins 4-5g//dl
●PF glucose <50,pH <7.2 s/o poor prognosis
●High CYFRA -21-1, Low CEA present
●High SMRP
●High PF hyaluronic acid
●High pleural fluid LDH (>carcinomatous pl.eff, >600IU/dl)

16. Diagnosis
Diagnosis = Histology +IHC markers
IHC Markers
Calretinin
Keratin ⅚
Podoplanin
WT1
Blood markers
SMRP Pleural >Blood
Osteopontin
Megakaryocyte Potentiating Growth factor
Osteopontin lacks specificity
SMRP, MPF lacks sensitivity
Not used for screening

17. Subtypes - 3 main subtypes
Epithelial

Sarcomatoid

Biphasic / mixed

18. ●The epithelioid variant is
the most common
● 60 percent of all
mesotheliomas.
●Typical histologic
appearances of this
subtype include
tubulopapillary, acinar
(glandular), adenomatoid
and solid epithelioid
patterns
●Differential diagnosis - Reactive mesothelial hyperplasia,
Metastatic carcinomas and other epithelioid tumors.

19. Sarcomatoid mesotheliomas are composed of malignant
spindle cells - mimic malignant mesenchymal tumors - leiomyosarcoma or
synovial sarcoma.
Desmoplastic mesothelioma is considered to be a subtype of sarcomatoid
mesothelioma.
Differential diagnosis - sarcomatoid carcinoma and other sarcomas, fibrous
pleurisy
Biphasic or mixed mesotheliomas have epithelioid and
sarcomatoid features
Multiple tissue sections or larger samples may be needed to demonstrate both
components
Synovial sarcoma, as well as other mixed or biphasic tumors, are typically
considered within this differential diagnosis

20. Some general principles in
●Pancytokeratin stains majority of mesotheliomas.
●If pancytokeratin negative - screening panel broadened to include stains
to exclude lymphoma, melanoma, angiosarcoma or epithelioid
hemangioendothelioma.
● There are rare sarcomatoid mesotheliomas which are cytokeratin
negative,with osteosarcomatous differentiation.
Epithelioid mesothelioma, common positive IHC marker calretinin, CK5/6,
the Wilms' tumor-I (WT1) antigen (nuclear staining), and D2-40 (podoplanin) .
● Useful markers that are positive in pulmonary adenocarcinoma include
MOC-31, BG8, carcinoembryonic antigen (monoclonal), B72.3, Ber-EP4,
TTF-1, and napsin A (Leu-M1)

21. Sarcomatoid or Biphasic mesothelioma, cytokeratin
expression can be focal, weak or variable.
● does not necessarily differentiate malignant mesothelioma from other
sarcomas.

● Multiple cytokeratin antibodies such as AE1/3 or CAM5.2 should be used
since
●D2-40 and calretinin are the most reliable of the affirmative mesothelioma
markers .
●D2-40 and calretinin do show overlap reactivity with other types of
sarcoma, but a positive result may be useful for confirming a diagnosis of
sarcomatoid mesothelioma when combined with strong cytokeratin
positivity .
●The possibility of synovial sarcoma can usually be confirmed by molecular
testing for the specific X:18 translocation

23. Staging

25. Evaluation
●A multidisciplinary treatment plan - the extent of disease
the patient's overall condition including cardiopulmonary function ,
comorbidities, their desire for aggressive treatment.
●Chemotherapy with pemetrexed plus a platinum compound
(cisplatin or carboplatin) is the standard approach for MPM
●Approximately 20 percent of patients with MPM may be candidates
for surgery with a macroscopic complete resection (MCR; ie, an R0
or R1 resection) as part of a combined-modality approach

26. Surgical candidates
●Limited to one hemithorax
● no medical contraindication to
surgery
● we use a combined-modality
approach = MCR +
chemotherapy and/or radiation
therapy
Nonsurgical candidates
● For patients who have disease in which
an MCR is not feasible
● Not candidates for definitive surgery
because of age, inadequate
cardiopulmonary reserve, or other
comorbidities
● Systemic chemotherapy and/or
symptom-directed treatment may be
beneficial.

28. Surgical procedures

29. ●EPP versus P/D — The choice of a specific procedure, extrapleural
pneumonectomy (EPP) versus pleurectomy/decortication (P/D), is a
function of the surgeon's expertise and judgment on the ability to
achieve an MCR with the respective approaches and multimodal
treatment protocols within that institution.
●There are no randomized trials that compare EPP versus P/D, but
retrospective analyses suggest that survival outcomes are similar.
●For surgical candidates, we suggest a combined-modality approach
that includes chemotherapy (generally a platinum plus pemetrexed )
surgery (MCR) with either pleurectomy/decortication or radical
extrapleural pneumonectomy, and RT. (Grade 2C).

30. systemic chemotherapy and the management of the malignant pleural
effusion may prolong life or provide significant symptom palliation.
Pleurodesis – Pleurodesis can often control symptoms from
pleural effusions by obliterating the pleural space and causing adhesions
between the visceral and parietal pleura. Complete drainage of the pleural
effusion by tube thoracostomy or video thoracoscopy followed by
introduction of an irritative agent into the pleural space to produce pleural
symphysis or obliteration of the pleural space often provides palliation in
this setting.
Non surgical approach

31. Tunneled catheters – Some patients with entrapped lungs
and sizable effusions can get relief from a tunneled catheter
even though the lung does not expand. The mechanism of
this may be relieving pressure on the diaphragm. Patients
may report an improvement in their breathing, decreased
pain, and/or an improvement in early satiety.
VATS pleurectomy – Video assisted thoracoscopic subtotal (VATS)
pleurectomy may also have a role in the palliative management of
pleural effusions in patients with MPM. However, VATS pleurectomy
does not improve OS in patients with MPM. In the randomized
MesoVATS trial, VATS pleurectomy provided better control of pleural

32. Systemic therapy —Combination chemotherapy with a platinum-based
doublet such as cisplatin plus pemetrexed, with or without bevacizumab,
has been shown to prolong survival in patients with unresectable MPM.

The combination of nivolumab plus ipilimumab has also been shown to
improve survival in those with unresectable disease, particularly for those
with nonepithelioid histology.
Radiation therapy — There are only limited data available on the role of RT in
combination with systemic therapy in patients with two intact lungs who are not
candidates for extrapleural pneumonectomy or P/D.

33. ●Patients with malignant pleural mesothelioma (MPM) generally present with locally
extensive disease. Surgery, radiation therapy (RT), and systemic chemotherapy
each may be beneficial as single modalities in selected situations, but the
prognosis for prolonged survival is poor.

●For patients with MPM limited to one hemithorax, a detailed evaluation is
indicated to assess whether disease is amenable to a macroscopic complete
resection (MCR), whether there is adequate cardiopulmonary function to tolerate
such a procedure, and whether there are any medical contraindications.

●For surgical candidates, we suggest a combined-modality approach that includes
chemotherapy (generally a platinum plus pemetrexed , surgery (MCR) with either
pleurectomy/decortication or radical extrapleural pneumonectomy, and RT.
Although this approach has not been demonstrated to improve overall survival in
randomized trials, carefully selected patients may have relatively prolonged
survival.
●For patients who are not surgical candidates, management of symptoms from any
pleural effusion, systemic chemotherapy, and palliative RT may all have a role.

34. Prognosis depends on
Males, Age
Chest pain
Non epitheliod histology
Increase plt count
Increased wbc count
Large tumor volume, advanced stage
Regional LN +, Increased uptake on PET
The prognosis of MPM is poor with a median survival between 9 and 12
months

VEGF

Low PF Hyaluronic acid, Low PH

35. Summary
Malignant pleural mesothelioma (MPM) is a rare insidious neoplasm that typically presents with
advanced disease.

●Most patients with MPM present with the gradual onset of nonspecific symptoms such as chest pain,
dyspnea, cough, hoarseness, or dysphagia, which occur in the setting of extensive intrathoracic disease.

●Chest imaging typically shows unilateral pleural thickening and pleural effusion.

●Cigarette smoking is not a risk factor for the development of MPM.

●Initial evaluation of patients with suspected MPM includes computed tomography (CT) of the chest with
contrast, thoracentesis of any existing pleural effusion, and closed pleural biopsy. However, if insufficient
tissue is acquired to make a diagnosis, surgical intervention via video-assisted thoracoscopic biopsy or
open thoracotomy should be pursued.

●The diagnosis of pleural mesothelioma is established by morphologic and immunohistochemical
features of a cytologic or surgical specimen.

●

36. The differential diagnosis of MPM includes benign processes such as inflammatory
reactions, as well as malignant processes, including metastases from other solid tumors.
Evidence of stromal invasion on biopsy distinguishes mesothelioma from benign etiologies,
while immunohistochemistry can distinguish mesothelioma from other malignancies.

●For diagnosed cases of pleural mesothelioma, we obtain integrated positron emission
tomography (PET) with CT (PET-CT) as the initial staging assessment. For patients in
whom imaging suggests resectable disease, we pursue extended surgical staging prior to
definitive surgery. Specifically, this includes laparoscopy with peritoneal lavage to detect
subdiaphragmatic involvement, followed by mediastinoscopy.

●The prognosis of patients with MPM is poor, with overall survival being on the order of 9 to
17 months after diagnosis. Few patients are cured.

●Several biomarkers are selectively elevated in patients with mesothelioma, including
soluble mesothelin-related peptides, fibulin-3, and osteopontin, although they are not
routinely used in the diagnosis of mesothelioma

37. References
Pleural diseases lights 6th ed

Uptodate

Current asbestos exposure and future need for
palliative care - Indian journal of palliative care

38. No satisfactory management till now
Palliative care
SOB - Therapeutic thoracentasis flb pleurodesis / indwelling catheter
Chest pain - Local palliative radiotherapy, percutaneous cervical corduroy
Prednisolone- overall well being
Chemotherapy - Cisplatin + pemitrexed/ raltitrexed
Intrapleural > Systemic