Diagnostic Utility of Epithelial Membrane Antigen (EMA) and

Calretinin (Cal) in Malignant Pleural Mesothelioma: A Case Report

Noni Novisari Soeroso

, Ade Indriya

, Andika Pradana

, Rahmat Hidayat

Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Sumatera Utara,

Jl. Dr. Mansyur No. 5 Medan 20155, Sumatera Utara, Indonesia

Keywords: Calretinin, epithelial membrane antigen (EMA), malignant pleural mesothelioma, pleuroscopy

Abstract: Malignant pleural mesothelioma (MPM) is a rare disease, but the incidence of this disease has increased

over time. The diagnosis of MPM can be established based on radiological and pleuroscopic findings. The

immunohistochemistry of EMA and Calretinin may confirm the diagnosis of MPM. We reported a case of

70-years-old man, worked as a construction worker for 20 years came with severe left chest pain and

shortness of breath for 1 month. Chest X-ray shows left moderate pleural effusion, and thoracic CT-scan

result revealed mass in left pleura. Pleuroscopy had been performed and mass in the parietal pleura was

found with the histopathology reports suggestive for mesothelioma. Immunohistochemistry staining with

EMA and Calretinin were both positive, confirming the diagnosis of malignant pleural mesothelioma. He

was then scheduled for chemotherapy. However, his condition worsened over time and finally passed away.

1 INTRODUCTION

Mesothelioma is cancer that originates from

mesothelial cells lining the pleural cavity,

peritoneum, pericardium and tunica vaginalis.

Pleural mesothelioma is most commonly found in all

cases of mesothelioma (80% of cases) and asbestos

is believed to be one of the causes of pleural

mesotheliomas.

Australia is one of the countries with the highest

level of mesothelioma cases in the world. The

predicted mortality rate in the UK is estimated at

around 90.000 by 2050. In Japan, around 100.000

deaths over the next 40 years has been predicted.

Men have a risk three times greater than women in

cases of mesothelioma. However, no definite data of

mesotheliome prevalence in Indonesia (American

Cancer Society, 2018).

Malignant pleural mesothelioma is mostly

caused by exposure to asbestos in the workplace.

This is more common in older people, but

ssometimes may occur in younger people (Husain et

al., 2018).

When mesothelioma is diagnosed at an ealry

stage before invading lymph nodes and othe parts of

the body, treatment is more effective and prognosis

is more promising. However, the diagnosis of

mesothelioma appears very challenging. In fact, it is

often misdiagnosed as less serious conditions like

fibrous pleuritis. Thus, more diagnostic modalities

will provide help to estabilish the diagnosis of

mesothelioma accurately. We reported a patient

diagnosed with malignant pleural mesothelioma

based on positive immunohistochemistry findings of

epithelial membrane antigen and calretinin.

2 CASE REPORT

A 70-year-old man, heavy smoker, came with

shortness of breath for 1 month before being

hospitalized, getting worse when coughing or deep-

breathing. Non-productive cough has been

experienced for 3 months. He also felt severe left

chest pain in the last 1 month with VAS 5-6. He

used to work as construction worker. He also

experienced decreased appetite and loss of body

weight about 5 kg in 1 month. He has never taken

anti-tuberculosis drugs. While admission, his vital

sign were within normal limit except for increased

respiratory rate and SpO2 92% in room air.

Complete blood count showed anemia (9.3 mg/dl).

Arterial blood gas shows mild hypoxemia and

respiratory alkalosis (pH: 7.48; pCO2: 38.9 mmHg;

pO2: 70 mmHg; HCO3: 26.9 mmol / L; BE: 2.7

mmol / L; SaO2: 93%). Chest X-ray showed

Soeroso, N., Indriya, A., Pradana, A. and Hidayat, R.

Diagnostic Utility of Epithelial Membrane Antigen (EMA) and Calretinin (Cal) in Malignant Pleural Mesothelioma: A Case Report.

DOI: 10.5220/0009863402050207

In Proceedings of the 2nd International Conference on Tropical Medicine and Infectious Disease (ICTROMI 2019), pages 205-207

ISBN: 978-989-758-469-5

205

moderate left pleural effusion. Thoracentesis was

performed and about 1000ml fluid was drained, with

pleural fluid cytology result was chronic

inflammatory smear. Thoracic CT scan revealed a

suspicion for left pleural tumors in the apex and

medial to lower field along with massive left pleural

effusion and left inferior lobe atelectasis (Figure

1A).

Pleuroscopy was then performed and multiple

masses in the parietal pleura and visceral pleura

were found, continued with biopsy (Figure 1B).

Histopathologic finding supported the diagnosis of

mesothelioma (Figure 2A). Immunohistochemistry

examination with Pancytokeratin, EMA (Figure 2B)

and calretinin (Figure 2C) were conducted with

positive result, confirming the diagnosis of stage

IIIB malignant pleural mesothelioma. He was then

scheduled for chemotherapy using Cisplatin 60mg

BSA and Etoposid 100 mg BSA. However, his

condition worsened over time and he eventually

passed away.

Figure 1: (A) Thoracic CT scan revealed a suspicion for left pleural tumors in the apex and medial to lower field along with

massive left pleural effusion and left inferior lobe atelectasis. (B) Multiple masses in the parietal pleura and visceral pleura

were found.

Figure 2: (A) Histopathologic finding supported the diagnosis of mesothelioma, Immunohistochemistry examination with

Pancytokeratin, EMA. (B) and calretinin. (C) were conducted with positive result, confirming the diagnosis of malignant

pleural mesothelioma.

3 DISCUSSION

Asbestos exposure is highly related to the incidence

of malignant pleural mesothelioma (MPM). It may

affect mesothelial, a thin membrane lining the

organs in the body including the thoracic cavity

(pleura), heart (pericardium) and abdominal cavity

(peritoneum). (American Cancer Society, 2018).

MPM is mostly caused by exposure to asbestos

in the workplace. Pleural mesothelioma is more

common in people over 70 years old, but sometimes

it may affect younger people. Our patient reported in

this case was 70 years old and had a prolonged

exposure to asbestos in the workplace as a

construction worker, thus raised a high suspicion for

mesothelioma.

Asbestos can cause mesothelioma through four

mechanisms. The first mechanism is pleural

irritation. Thin and long fibers (width <0.25 μm and

length> 0.8 μm) penetrating the alveolar epithelium

towards the pleural cavity will cause repeated

ICTROMI 2019 - The 2nd International Conference on Tropical Medicine and Infectious Disease

206

irritation of the mesothelial surface and local

inflammation. The second mechanism is related to

the disorder of the mitotic process. The third

mechanism is the formation of oxygen radicals

which are associated with high iron content in

asbestos fibers. And the last mechanism is

stimulation of macrophages by asbestos fibres to

secrete various cytokines and growth factors that

will induce inflammation and promotion of

malignancy, including tumor necrosis factor-α

(TNFα), interleukin-1β (IL-1β), transforming growth

factor-β (TGF β) and platelets derived from growth

factors (PDGF) (Mossman et al., 2013).

Patients with MPM often feel shortness of breath

and severe chest pain, just like what our patient

reported. The pain is most oftenly localized

accompanied with pleural effusion. Additional

symptoms such as cough, malaise, and decreased

appetite along with weight loss and fever without

any sign of infection (American Cancer Society,

2018).

Diagnostic approaches include chest X-ray and

thoracic CT scan to determine the location of tumor

and metastasis. Cytology of pleural fluid, peritoneal

or pericardial fluid along with tissue biopsy may

help to confirm the diagnosis (American Cancer

Society, 2018; Cancer Council, 2015).

Tumor markers for MPM can be detected by

immunohostochemistry examination with Epithelial

Membrane Antigen (EMA) and Calretinin. Both

give high positive results for mesothelioma. Several

studies stated that the sensitivity and spesificity of

EMA for MPM are 91.8% and 100% respectively

(Nautiyal et al., 2017). Calretinin is currently used

as a marker for mesothelial cells both benign and

malignant and more than 95% are positive for

epitheloid-type mesothelioma. Calretinin is used

primarily to differentiate mesothelioma from

carcinoma or other malignant metastases, especially

those with a similar histopathologic findings with

mesothelioma from tissue biopsy or cytology.

However, other studies have shown that calretinine

is not only positive for mesothelial cells, but may

also be positive in other malignancies such as

metastatic adenocarcinoma or squamous cell

carcinoma (Husain et al., 2018). Barberis et al stated

that anticalretinin staining of pleural fluid yielded

100% positive in malignant mesothelioma and 23%

positive in a metastasis adenocarcinoma (Nautiyal et

al., 2017; Husain et al., 2018).

As a conclusion, we reported a case of malignant

pleural mesothelioma diganosed with the positive

immunohistochemistry findings of EMA and

Calretinin. The use of both modalities may yield a

better sensitivity and spescificity level to confirm the

diagnosis accurately.

FUNDING

No grant support or funding from public institutions

or private enterprises was received for this case

report.

ACKNOWLEDGEMENTS

The researcher would like to thank Universitas

Sumatera Utara Hospital which have allowed the

retrieval of medical history data.

REFERENCES

American Cancer Society. 2018. Malignant Mesothelioma.

[online]. [cited 2016 Mei 14]. Available from:

www.cancer.org/cancer/malignantmesothelioma/detail

edguide/malignant-mesothelioma

Cancer Council. 2015. Understanding Pleural

Mesothelioma. A guide for people with cancer, their

families and friends. [online]. [2016 Mei 14].

Available from:

https://www.cancer.org.au/content/about_cancer/eboo

ks/CAN4798%20Understanding%20Pleural%20Mesot

helioma%20web.pdf

Husain, A. N. et al., 2018. Guidelines for pathologic

diagnosis of Malignant Mesothelioma: 2017 Update of

the consensus statement from the International

Mesothelioma Interest Group. Archives of Pathology

and Laboratory Medicine. 142(1): 89-108. doi:

10.5858/arpa.2017-0124-RA.

Mossman, B. T. et al., 2013. New insights into

understanding the mechanisms, pathogenesis, and

management of malignant mesotheliomas. American

Journal of Pathology. 182(4): 1065-77 doi:

10.1016/j.ajpath.2012.12.028.

Nautiyal, N. et al., 2017. Diagnostic utility of Epithelial

Membrane Antigen (EMA) and Calretinin (CAL) in

effusion cytology. Journal of Clinical and Diagnostic

Research. 11(5): EC36-EC39. doi:

10.7860/JCDR/2017/24339.9888.

Diagnostic Utility of Epithelial Membrane Antigen (EMA) and Calretinin (Cal) in Malignant Pleural Mesothelioma: A Case Report

207