Primary endo-bronchial muco-epidermoid carcinoma in a 22-year-old female: A case report

Abstract

Introduction

Muco-epidermoid carcinomas are primarily the subtypes of salivary gland tumors that can rarely originate within the respiratory tract. Our case highlights the occurrence of an unusual, localized, endo-bronchial muco-epidermoid cancer. We aim to strengthen the evidence of occurrence of this distinct variety of lung cancer in our country as little is known about this rare subclass of lung cancer.

Case presentation

We report a case of a 22-year-old female patient, belonging to Karachi, Pakistan, who presented with respiratory symptoms and upon work-up, was diagnosed with a low-grade, localized muco-epidermoid carcinoma of the lung. She underwent surgical resection successfully and was advised to get evaluated for adjuvant radiotherapy.

Clinical discussion

Localized low-grade MEC respond well to surgical resection in contrast to high-grade MEC which is associated with poor prognosis thus requiring adjuvant radiotherapy to improve survival outcomes.

Conclusion

Lung cancers can be unusually of muco-epidermoid origin. It has been uncommonly found in the world including Pakistan. Special attention with validated data is therefore needed, for developing guidelines for the optimal management of such neoplasms.

Highlights

• •MEC are commonly of salivary gland origin, which in rare circumstances can involve respiratory tree as primary site.
• •Lung MEC are classified on the basis of their grade which is also predictive of their behaviour.
• •We report a case of a patient, who presented with lower respiratory symptoms and was diagnosed with low-grade MEC of the lung.
• •Surgery is the mainstay of treatment in cases of localized MEC.
• •Adjuvant radiotherapy may be required in some cases; however there is no role of adjuvant systemic therapy for resected MEC.

1. Introduction

Muco-epidermoid carcinomas (MEC) of the lung belong to a unique group of primary salivary gland-type tumors (PSGT), that originate from the glandular tissue in sub-mucosa of the tracheo-bronchial tree [1]. They make up to less than 1 % of all lung cancer cases worldwide with a preponderance towards the 3rd or 4th decade of life [2]. There is no gender predisposition. Clinical picture is diverse and can vary from asymptomatic disease to mild symptoms such as cough, shortness of breath or fatigability to severe symptoms such as hemoptysis, hoarseness of voice or wheezes due to complete or partial obstruction of the airway by primary mass [3]. They are classified as either low grade or high grade on the basis of histological features. Low-grade MEC present with disease that is usually limited to trachea or bronchus in contrast to high-grade, which in general are either unresectable at presentation or have distant metastasis.

Pulmonary MEC are rare neoplasms that warrant special discussion as little is known about these pathologic variants of lung cancer. To date, only a handful number of cases have been brought to light, mostly via case reports and few case series.

Here, we report a case of localized pulmonary muco-epidermoid carcinoma in a young female, which is found infrequently and has been rarely reported in our country.

The work has been reported in line with the SCARE criteria [4].

2. Case presentation

A 22 years old female, with no significant medical or surgical history and resident of Karachi, Pakistan, presented to our institution in May 2022 with intermittent episodes of hemoptysis for the past 2 years, which were usually aggravated during the winter seasons. She also had associated productive cough with minute quantity of white to greenish sputum. There was no history of respiratory distress or constitutional symptoms such as weight loss or fever etc. She denied any history of smoking or drug abuse. Her family history of significance included hypertension and coronary artery but did not include malignancy.

General physical and systemic examination was unremarkable with normal vital parameters. An initial chest x-ray (CXR) was done which did not show any abnormality. Relevant investigations including nasal swab for COVID polymerase chain reaction (PCR) and sputum for gene xpert were performed, both of which came out negative, so a computed tomography (CT) scan of chest was performed, which showed a heterogeneous enhancing soft tissue density mass of 8.2 × 3.7 cm in size, involving right lower lobe bronchus with multiple hypo-dense foci having cystic and necrotic components with endo-bronchial extension. She underwent bronchoscopy which showed an endo-bronchial lesion in right main bronchus approximately 2 cm below the carina (Fig. 1). Biopsy sample was taken of this lesion which revealed to be muco-epidermoid carcinoma. Bronchial washing were negative for presence of atypical cells.

Fig. 1.

(A, B): Bronchoscopic visualization of right main endo-bronchial mass.

A staging fluorodeoxyglucose (FDG) - positron emission tomography with computed tomography (PET-CT) scan was then performed which revealed an FDG avid right infra-hilar lesion infiltrating into right main bronchus with underlying right lung collapse. There was no evidence of regional or distant metastases. She underwent right posterolateral thoracotomy and pneumonectomy with ipsilateral level II, IV, VII and IX lymph node dissection. Intra-operative findings revealed tumor involving right lower lobe, extending up to right main bronchus, adherent to pulmonary artery and extending up to superior pulmonary vein. Histopathology revealed low grade MEC being 6 × 6 × 3 cm in size. 8 lymph nodes were taken out which were negative for tumor involvement. The resection margin was also negative and there was no associated lympho-vascular or peri-neural invasion, making this pT3N0M0 i.e. stage II-B.

Post-operatively, she remained well and was discharged from the hospital in a stable state within a week. She initially remained in routine follow-ups with cardiothoracic surgery for post-surgical care. Upon healing of surgical scar, she visited Medical Oncology in outpatient clinic. The case was discussed in multi-disciplinary tumor board meeting. Considering, that there are no established guidelines except for a few case reports suggesting the role of adjuvant chemotherapy in MEC, she was advised to get an input from Radiation Oncology for consideration of adjuvant radiotherapy, on account of having pT3 disease. In view of significant cosmetic adverse effects secondary to radiotherapy, the patient deferred adjuvant treatment. She remains on observation with 3 monthly visits in cardio-thoracic surgery clinic till date and is doing exceptionally well.

3. Discussion

MEC of the lung are rare pulmonary malignancies that mostly arise in the peripheral regions of the lung [5], uncommon presentations do occur with either tracheal or endo-bronchial involvement. Majority of the tumors found in the tracheobronchial tree are malignant including squamous cell carcinomas, adenocarcinomas, carcinoid and less commonly MEC, lymphomas, sarcomas etc. Benign tumors are rare in this region and include neurogenic tumors, pleomorphic adenomas, squamous cell papillomas, hamartomas etc.

Histologically, MEC comprise of a mixture of mucin-producing glandular cells and squamous epithelial cells. Based on the presence or absence of necrosis, the nuclear pleomorphism and mitotic activity, they are grouped into either low or high grade disease. Low-grade MEC are rich in mucus-secreting glandular cells whereas high-grade MEC have abundance of squamous cells arranged in sheets with few mucin-secreting cells in between [6]. Low grade MEC are often found in younger population, in contrast to high grade MEC, which are commonly seen in older population. Immuno-chemically, the tumor cells characteristically stain positive for p63, cytokeratin 5/6, p40 and Muc5A whereas TTF-1, napsin A, cytokeratin 20 and SOX 10 are infrequently found in these tumor cells. MEC are also associated with a fusion gene, called CRTC1-MAML2, which is the result of a chromosomal translocation and may prove to be an important diagnostic marker, especially in low-grade tumors [7].

Pulmonary MEC are predominantly hilar in origin and appear to have regular, well-defined margins on CT chest. The lack of necrosis with moderate to marked enhancement on contrast images is suggestive of pulmonary MEC [8]. Wang et al. reported that pulmonary MEC are predominantly present in the bronchi, with only fewer than 15 % located in the trachea, which leads to fewer symptoms as compared to tracheal tumors, more chances of complete resection, and hence better 5-year survival rate after surgery [9] (see Table 1).

Table 1.

Existing literature involving cases of localized MEC in adults since 2001.

No.	Author	Country	Age & gender	Presenting complaints	Primary site	Grade	Treatment
1	Chen et al. (2001)	Japan	33, M	Asthma like attacks followed by hemoptysis	Carina	Low-grade	Surgery
2	Devbhandari et al. (2002)	UK	19, M	Purulent sputum, hemoptysis, night sweats and weight loss	Left lung	Low-grade	Surgery
3	Martin-Ucar et al. (2003)	UK	23, M	Cough, hemoptysis, recurrent respiratory infections	Right Lung	High-grade	Surgery
4	Yamada et al. (2005)	Japan	63, M	None	Endo-bronchial	High-grade	Surgery
5	Noriyuki et al. (2005)	Japan	38 FM	None	Endo-bronchial	Low-grade	Surgery
6	Minami et al. (2007)	Japan	17 M	Recurrent respiratory infections	Endo-bronchial	Low-grade	Surgery
7	Teo et al. (2010)	Singapore	27, M	Non-productive cough	Endo-bronchial	Low-grade	Surgery
8	Blawat et al. (2010)	Poland	20, FM	Cough with recurrent asthma attacks	Endo-bronchial	Low-grade	Surgery
9	Kitada et al. (2011)	Japan	60, M	None	Left Lung	Low-grade	Surgery
10	Nowak et al. (2012)	UK	27, FM	Severe asthma	Endo-bronchial	Not available	Surgery
11	El-Sameed et al. (2012)	UAE	35, M	Cough and hemoptysis	Endo-bronchial	Low-grade	Surgery
12	Dyhdalo et al. (2012)	USA	45, FM	Productive cough	Endo-bronchial	Low-grade	Surgery
13	Miller et al. (2013)	USA	43, M	Progressive exertional dyspnea, wheezing	Trachea	Low-grade	Surgery
14	Alsidawi et al. (2013)	USA	46, FM	Progressive dyspnea on exertion, dry cough	Right Lung	Low-grade	Surgery
15	Graham et al. (2013)	Ireland	75, FM	None	Left Lung	High-grade	Surgery + Radiotherapy
16	Gutiérrez et al. (2014)	USA	38, M	Hemoptysis	Endo-bronchial	Low-grade	Surgery
17	Ding et al. (2014)	China	18, M	Productive cough	Left Lung	Low-grade	Surgery
18	Al-Zamkan et al. (2015)	UAE	40, M	Dry cough	Right Lung	Low-grade	Surgery
19	Abu Saleh et al. (2015)	USA	65, FM	Cough	Left Lung	Not Available	Surgery
20	Kesrouani et al. (2015)	Lebanon	35, FM	Hemoptysis and severe dyspnea	Trachea	Low-grade	Surgery
21	Belgod et al. (2015)	India	38, FM	Fever and dry cough	Endo-bronchial	Low-grade	Surgery
22	Yokouchi et al. (2015)	Japan	36, M	Pneumonia	Endo-bronchial	Low-grade	Surgery + Radiotherapy
23	Omesh et al. (2018)	USA	21, FM	Productive cough and fever	Endo-bronchial	Low-grade	Surgery
24	Al Kindi et al. (2022)	Oman	43, FM	Productive cough and fever	Endo-bronchial	Low-grade	Surgery
25	Murakami et al. (2021)	Japan	37, FM	Productive cough and fever	Left lower lobe	Low-grade	Surgery
26	Yan Hu et al. (2022)	China	42 Y, M	None	Endo-bronchial	Low-grade	Surgery
27	Yong-Min Ding et al. (2022)	China	28 Y, M	Hemoptysis	Endo-bronchial	Low-grade	Surgery
28	Al Kindi et al. (2022)	Oman	43, FM	Productive cough and fever	Endo-bronchial	Low-grade	Surgery
29	Tamura et al. (2023)	Japan	69, M	None	Endo-bronchial	Low-grade	Surgery + Photodynamic therapy

Low grade MEC usually present with resectable disease for whom surgical resection with negative margins is the standard of care approach. Surgical options include lobectomy, sleeve resection, local resection, segmental resection, or even endoscopic removal based on the local extent. Survival rates vary with stages, with 5-year survival rate of stages I-II being as high as 91 % with surgery alone compared to 32 % in stages III-IV [10]. Hsieh et al., in a review of 41 cases, also reported 5-year disease-free survival rate of 57.9 % and overall survival rate of 57 % with surgical resection, being largely influenced by age, gender and pathological stage [11]. Thus, the prognosis of MEC is determined by a number of factors and is typically poor with older age, large tumor size, high grade and high stage.

Adjuvant radiotherapy is generally reserved for patients who present with a large, high grade or locally invasive tumor, in which case, it results in improved long term survival rate [10]. Apart from these, lymph node sampling or dissection also plays a pivotal role in the incorporation of radiotherapy in adjuvant treatment. The role of chemotherapy in the management of MEC is ambiguous, due to rare occurrence of these tumors. Based on a review of around 700 patients conducted by Li et al., adjuvant chemotherapy can be considered of significance in high grade tumors, especially those with nodal involvement or local spread [12]. Favorable outcomes have been reported in patients treated with combination chemotherapy using platinum [13,14] and taxanes based regimens [15]. Tyrosine kinase inhibitors are also an evolving area of interest in PMEC with MECT1-MAML2 fusion gene, and may result in improved outcomes [12,16]. However, their role still remains unclear and more data is needed to reach a consensus regarding the optimal systemic management of pulmonary MEC.

4. Conclusion

Treatment for localized pulmonary MEC depends primarily on the tumor grade, with low grade disease responding well to surgical resection alone whereas high grade disease requiring adjuvant treatment with the incorporation of radiotherapy or concurrent chemo-radiation. The role of adjuvant chemotherapy without radiotherapy is unclear and reserved for those cases, who present with recurrence or are at high risk of recurrence. Here, we report a case of localized low grade MEC of the lung, that was successfully resected and despite having referred for adjuvant radiotherapy, on account of T3 disease, she opted for observation and continues to be in clinical remission. However, more evidence is needed to guide adjuvant treatment for these infrequent neoplasms with high-risk features such as T3 disease.

Ethical approval

Not applicable as case reports are exempted from the provision of ethical approval in our institute.

Funding

Not applicable.

Consent to participate

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request - added in the revised manuscript.

Guarantor

Mirza Rameez Samar.

Provenance and peer review

Not commissioned, externally peer reviewed.

CRediT authorship contribution statement

• •Mirza Rameez Samar conceptualized and designed the study, drafted the initial manuscript and finalized the manuscript after editing.
• •Aneeqa Ejaz drafted the initial manuscript.
• •Nida Zehra reviewed the manuscript and revised with final editing of the manuscript.
• •Yasmin Abdul Rashid critically reviewed the manuscript for important intellectual content.

Declaration of competing interest

The authors declare that they do not have any competing interests.

Data availability

The data for current study is available from corresponding author at reasonable request.