Malignant Mesothelioma - Report of Two Cases with Different Presentations.

Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm that stems from the mesothelial cells lining the visceral cavities, namely, the pleura, peritoneum, pericardium, and tunica vaginalis of the testes. MPM is the most common variant of these and constitutes up to 80% of all malignant mesotheliomas. It is usually associated with asbestos exposure and is a locally invasive neoplasm that spreads along pleura and can involve lungs with locoregional metastasis. Diagnosis remains challenging due to the latency between asbestos exposure and clinical presentation and the variable clinicoradiological manifestations. Meticulous history taking, high index of, suspicion and multimodality approach toward diagnosis are the keys to better prognosis. We hereby present two interesting cases of MPM with different presentations. Copyright:

INTRODUCTION

Malignant mesothelioma (MM) is an uncommon neoplasm which arises from mesothelial cells lining the pleura, pericardium, and peritoneum and tunica vaginalis of the testes. Malignant pleural mesothelioma (MPM) is its most common subtype. Its occurrence is rare and has been strongly linked to asbestos exposure.[1] However, seldom it has been reported in individuals with no prior exposure to asbestos. This has been attributed to a complex interplay of genetic influences, viral infections, and exposure to other carcinogens.[2] The diagnosis of MM should be based on the results obtained on a tissue biopsy in light of supporting appropriate clinical, radiologic, and surgical findings as recommended by the International Mesothelioma Interest Group (IMIG).[3] An elaborate search of literature revealed the rarity and detection particularly in India.[4] Hence, we grasp this opportunity of presenting two cases of MM with different demeanours worked up by a multidisciplinary approach.

CASE REPORT 1

A 66-year-old lady, resident of Mumbai who used to work in wiring shop, was referred to our outpatient department in view of chest radiographic findings. Pt was symptomatic since 2013 with complaints of predominantly dry cough, nonspecific chest pain, and dyspnea on exertion of Modified Medical Research Council (MMRC) grade 1. In April 2014, in view of persistent symptoms, she was evaluated with chest radiograph (CXR), which showed bilateral lower zone nodular opacities with calcification and a right pleural effusion [Figure 1]. She was empirically treated with antituberculosis therapy for her symptoms. In view of progressive symptoms, she was referred to us. Her general examination was unremarkable, and examination of the respiratory system showed findings of right pleural effusion with thickening in form of volume loss and reduced breath sounds over the right lower chest. Her complete blood count (CBC) revealed elevated platelet count of 650,000/mm3. Her sputum cartridge-based nucleic acid amplification test (CBNAAT) did not detect mycobacterium tuberculosis. Ultrasonography of the thorax was suggestive of right-sided pleural effusion. The pleural fluid was aspirated and evaluated with cytological and biochemical examination which showed exudative lymphocyte predominant pleural effusion with normal levels of adenosine deaminase. Contrast-enhanced computed tomography (CECT) of the thorax was suggestive of heterogeneously enhancing nodular pleural thickening of maximum 9 mm on the right side. One of the largest pleural nodules was between descending aorta and inferior vena cava and measured approximately 3.7 × 2.6 cm with multiple partially calcified pleural plaques with right-sided pleural effusion [Figure 2]. The patient underwent a closed needle pleural biopsy (CNPB) with a Cope's needle. Pleural fluid malignant cytology showed few atypical cells. Pleural biopsy was subjected to histopathological examination and acid-fast bacilli (AFB) culture studies. Histopathology was suggestive of metastatic deposits of dyscohesive malignant cells of epitheloid variety which were positive for calretinin and WT-1 on immunohistochemistry suggestive of mesothelioma [Figure 3]. Pleural biopsy AFB culture did not grow organisms. Hence, final diagnosis of MM stage T4N3M0 stage 4 secondary to asbestos exposure in wiring industry was made. She opted for palliative care with proper counselling.

Figure 1

Case 1 chest radiograph suggestive of right-sided pleural effusion

Figure 2

Case 1 high-resolution computed tomography suggestive of heterogeneously enhancing nodular pleural thickening on the right side with multiple partially calcified pleural plaques with right-sided pleural effusion

Figure 3

(a) Case 1 closed needle pleural biopsy histopathology hematoxylin and eosin stain (×400) suggestive of metastatic deposits of dyscohesive malignant cells of epitheloid variety. (b) Case 1 closed needle pleural biopsy immunohistochemistry (×400) showing malignant cells positive for calretinin (diffuse, nuclear, and cytoplasmic)

CASE REPORT 2

A 47-year-old lady, resident of Mumbai, housewife, was symptomatic since 2 months with complaints of predominantly dry cough, dyspnea on exertion of MMRC grade 1, and left-sided chest pain. She was evaluated with CXR which showed bilateral rounded mass lesions [Figure 4]. Her CBC revealed elevated platelet count of 750,000/lac mm3. CECT of the chest showed multiple large masses in both lungs, the largest was in the right upper lobe measuring 4.3 × 3.7 cm with a small left pleural effusion and multiple solid-enhancing pleural-based masses, the largest being in the right lower hemithorax measuring 11.2 × 9 cm with mediastinal lymphadenopathy and osteolytic lesion in the right eighth rib [Figure 5]. The patient underwent an ultrasound (USG)-guided biopsy of left pleural-based mass. Histopathology of the tissue was suggestive of diffusely arranged spindle-shaped malignant cells which were positive for vimentin and calretinin suggestive of mesothelioma. On the basis of these findings, diagnosis of sarcomatous variety of MM stage T4N3M0 stage 4 was made. However, this patient denied any exposure to asbestos. She did not opt for palliative chemoradiotherapy inspite of counselling.

Figure 4

Case 2 chest radiograph suggestive of bilateral rounded mass lesions

Figure 5

Case 2 high-resolution computed tomography suggestive of multiple large masses in both lungs with a small left pleural effusion and multiple solid-enhancing pleural-based masses with mediastinal lymphadenopathy

DISCUSSION

MPM is a notorious pleural malignancy with a fulminant clinical course and a somber prognosis. Greater than 90% of MPM particularly in industrialized countries and in men are related to a significant asbestos exposure. However, there also exists literature pertaining to the incidence of mesotheliomas in people never exposed to asbestos. Hence, a history of asbestos exposure is contributory and, however, not mandatory in establishing the diagnosis of mesothelioma as per IMIG.[3] Our first patient has a definite history of occupational exposure to asbestos; however, the second did not. A varieties of asbestos fibers can cause MPM areamosite, anthophyllite, crocidolite, and canadian chrysotile. Asbestos is hydrated magnesium silicate fibers. Crocidolite and amosite have greater risk of mesotheliomas than other types of fibers. Most carcinogenic fibers are biopersistent and their size ranges from 0.1 to 1.0 μm in diameter and more than 8 μm in length. Asbestos increases simian virus40 (SV40)–mediated transformation of human mesothelial cells, in vitro. One of the theories regarding asbestos-induced carcinogenesis depicts that asbestos fibers are entangled in mitotic spindle during interphase, which in turn causes chromosomal abnormalities.[5] Mesotheliomas are found more in males than females with a ratio of 3.5:1, but we came across both female patients. The most common age of presentation is 60–80 years due to long latency necessity of significant cumulative asbestos exposure. This was seen in our first case too. While our second patient who had no exposure to asbestos presented early. The common presenting symptoms are intractable pleuritic chest pain dry cough, dyspnea, and fatigue.[6]

It is a locally invasive tumor, relentless spreads along pleura, lung, chest wall, pericardium, diaphragm, and mediastinum. Pleural effusion is usually present and it is exudate; it may be hemorrhagic and may have high levels of hyaluronic acid. Our first patient presented with pleural effusion with nodular thickening, while the second one presented with thoracic masses. Mesotheliomas tend to grow along the aspiration sites of previous intervention like thoracocentesis, thoracotomy, or thoracoscopy.[7] Paraneoplastic syndromes such as hypoglycemia or syndrome of inappropriate ADH secretion (SIADH) can be observed. Thrombocytosis is very common and it is seen in approximately 90% of patients, as it was seen in both of our patients. CXR is the most easily available and often the first imaging modality performed. It may show features such as a unilateral usually right-sided pleural effusion, pleural thickening with ipsilateral hemithoracic shrinkage, pleural plaques, pleural-based, or lung masses.[8] CECT chest is the mainstay imaging modality and plays a crucial role in disease localization, characterization, structuring, staging, therapy decision-making, and prognostication.[9]

The definitive diagnosis of MPM is based on histological demonstration followed by immunohistochemical confirmation. Thoracocentesis and a needle biopsy of the pleura are indicated for the same. Pleural tissue can be biopsied by a CNPB, CT/USG-guided biopsy, or video-assisted thoracoscopic biopsy. CNPB is the least invasive and the most feasible and cost-effective of these. In our first patient, we could obtain a definitive diagnosis based on the histopathological analysis of CNPB tissue itself and more invasive method could be avoided. However, in our second patient, this was not feasible on account of the small pleural effusion. Hence, we resorted to image-guided biopsy of the pleural mass. Conventionally, mesotheliomas are classified into three histological patterns – epithelial (50%), sarcomatous (20%), and mixed or biphasic (30%).[3] Various markers are used for confirmation of diagnosis of mesothelioma. The best positive markers available are calretinin (calcium binding protein), cytokeratin 5/6, and WT1. Other markers which can be useful are thrombomodulin and mesothelin.[10] In our first patient, histopathology was suggestive of metastatic deposits of dyscohesive malignant cells which were positive for Calretinin and WT-1 on immunohistochemistry, and in our second patient, histopathology was suggestive of diffusely arranged spindle-shaped malignant cells which were positive for calretinin. Mesotheliomas in general have poor prognosis with median survival rate of approximately 8–12 months for all patients. Various treatment options are extrapleural pneumonectomy combined with radiation therapy, chemotherapy with gemcitabane and carboplatin or pemetrexed and cisplatin, immunotherapy, and gene therapy.[1112] Most of the patients with pleural mesotheliomas succumb to locoregional metastasis, disease complications, respiratory failure, or distant metastasis. MPM continues to be a diagnostic and therapeutic predicament owing to its long latent period, need for histological confirmation, limited therapeutic options, and grave prognosis. Maintaining a high index of suspicion, a meticulous history taking, an expatiated multimodality workup, and a holistic therapeutic approach are the keys to improving the situation.

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The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.