Mucoepidermoid carcinoma is a rare primary tumour of the lung. Diagnosis can be made after careful exclusion of other lung neoplasms, especially those with overlapping histological and radiological features. https://bit.ly/4fcISSm

A 73-year-old woman presented with loss of appetite and loss of weight of 5?kg over 6?weeks followed by an intermittent cough with a small amount of light yellowish sputum, dyspnoea on exertion, and fever for 2?weeks. There was no history of haemoptysis. She did not have any medical illnesses. She had no recent sick contacts. There was no recent travel history. She does not smoke or consume alcohol. On admission, the patient had a respiratory rate of 32?breaths per min, temperature of 37.8°C, blood pressure of 114/64?mmHg and pulse rate of 108?beats per min. There was no finger clubbing. Lung auscultation revealed scattered bilateral coarse crepitations. Her peripheral oxygen saturation (SpO2) on venturi mask oxygen therapy of 40% was 96%. Her chest radiograph showed patchy consolidations in both lung fields (figure 1), especially over the lower zones. There was minimal blunting of the left costophrenic angle. The heart size appeared normal.

FIGURE 1

The chest radiograph showed patchy consolidations in both lung fields, especially over the lower zones. There was minimal blunting of the left costophrenic angle. The heart size appeared normal.

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She was started on intravenous amoxicillin/clavulanic acid and oral azithromycin for community-acquired pneumonia (CURB-65 (confusion, urea >7?mmol·L-1, respiratory rate ?30?breaths per min, blood pressure <90?mmHg (systolic) or ?60?mmHg (diastolic), age ?65?years) pneumonia severity score of 2). On day two, her condition deteriorated and her SpO2 on venturi mask oxygen therapy of 60% was 84%. She was intubated and put on mechanical ventilation support after experiencing tachypnoea with a respiratory rate of 36?breaths per min when she was tried on high-flow nasal cannula oxygen therapy (50?L/fraction of inspired oxygen of 0.6). Her high-resolution computed tomography (HRCT) of the thorax showed diffuse ground-glass opacities, scattered solid and ground-glass nodules, and consolidation in the upper (figure 2a) and middle zone (figure 2b) of both lungs. Reticulations (black arrowheads) and traction bronchiectasis (black arrows) were also seen predominantly in the lower lobes (figure 2c).

FIGURE 2

The high-resolution computed tomography scan of the thorax showed diffuse ground-glass opacities, scattered solid and ground-glass nodules, and consolidation in the a) upper and b) middle zone of both lungs. c) Reticulations (black arrowheads) and traction bronchiectasis (black arrows) were also seen predominantly in the lower lobes.

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A respiratory septic work-up was negative. This included tracheal aspirates and bronchoalveolar lavage for bacterial and fungal culture and sensitivity, acid-fast bacilli testing, Mycobacterium tuberculosis culture and PCR amplification testing, and a full respiratory viral panel PCR test. Additional screening for HIV and cytomegalovirus infection, myeloma, connective tissue and myositis-related disorders were all negative. Over the next 2?weeks of treatment in the intensive care unit, there was no improvement in her serial chest radiographs, and there was difficulty in weaning her off the ventilator.

A decision was made to perform a fluoroscopy-guided transbronchial lung forceps biopsy due to persistent radiological changes and poor treatment response for 3?weeks. The transbronchial lung forceps biopsy was subsequently converted to transbronchial lung cryobiopsy due to difficulty in obtaining sufficiently sized samples. Using an ultrathin flexible 1.1?mm cryoprobe with oversheath, eight transbronchial lung cryobiopsies were performed with 6?s of cryo-activation under fluoroscopy guidance at 2?cm from the periphery of the anterior and posterior subsegments of the right lower lobe. The biopsy was complicated with a 0.37?cm right-sided pneumothorax which required 2?days of chest drainage. Histological examination of the samples was consistent with the diagnosis of pulmonary mucoepidermoid carcinoma (PMEC) (figure 3).

FIGURE 3

a) Mucoepidermoid carcinoma with mildly cribriforming and partly anastomosing glandular configurations; haematoxylin and eosin (H&E) staining, ×200 magnification. b) Mucoepidermoid carcinoma with dysplastic glands exhibiting intraluminal mucin production as well as intracytoplasmic periodic acid–Schiff (PAS)-positive, diastase-resistant mucin; PAS-D, ×400 magnification. c) Napsin A immunoreactivity, ×400 magnification. d) Outer squamous epithelial p40 immunoreactivity, ×400 magnification. e) p63 expression, ×400 magnification. f) Ki67 overexpression, ×200 magnification.

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Discussion

PMEC is a rare type of cancer that exhibits features similar to salivary gland tumours. The estimated incidence of PMEC is <1% of all primary lung neoplasms [1]. PMEC may affect any age group and is commonly divided into either low or high-grade tumours. In terms of clinical features, there are no specific symptoms for PMEC. The clinical symptoms vary from cough, dyspnoea, wheezing, to pneumonia depending on the location of the tumour. When evaluating a case of PMEC, it is crucial to look for involvement at other sites and to exclude any head and neck tumour as the primary origin of the tumour.

Typically, the tumour presents as a solid and well-defined lesion with no predilection for a specific location in the lung [2, 3]. However, in this case, the radiological features shown were predominantly diffuse ground-glass changes, which is rather unusual for mucoepidermoid carcinoma. Additionally, the basal findings of reticulations and traction bronchiectasis on the patient's HRCT of the thorax mimic an underlying interstitial-related lung disorder.

For diagnosis, the size of the specimen is crucial. The presence of mucus-secreting cells and intermediate cells, along with the absence of frank areas of keratinisation, are essential for diagnosing PMEC and differentiating it from squamous cell carcinoma [1]. PMEC is commonly differentiated into low- or high-grade tumours based on the presence of necrosis, the degree of cellular atypia and mitotic activity. High-grade tumours may present with invasion into the pulmonary parenchyma or lymph nodes [4, 5]. When immunohistochemical testing is carried out, PMEC is commonly positive for p63, CK7, Muc5Ac, p40 and CK5/6. Although not exclusive, Napsin A, thyroid transcription factor- 1 (TTF-1) and human epidermal growth factor receptor 2 (HER2) are commonly negative in PMEC [6]. Hence, immunohistochemical testing can be useful in differentiating PMEC from other salivary gland tumours, which are negative for p63, or primary lung adenocarcinoma, which is positive for TTF-1. In this case, the histology features of the biopsy specimen and the combined immunoreactivity of CK5/6, p40 and p63, and Ki67 proliferation index range of 20–50% led to the diagnosis of high-grade PMEC.

PMEC is associated with the MECT1–MAML2 fusion protein resulting from the translocation t(11; 19) (q21; p13) [7]. Currently, information on epidermal growth factor receptor (EGFR) mutations is limited to small reports, with only the L861Q heterozygous mutation and exon 21L858R mutation being mentioned [8, 9]. Hence, the option of targeted therapy remains controversial. An EGFR-tyrosine kinase inhibitor is considered an option in advanced cases only if tumour cells are found harbouring an EGFR mutation [7, 10]. The role of immunotherapy for PMEC remains unknown. For early-stage (stage I–II) and low-grade tumours, experts prefer surgical resection and systemic lymph node dissection. Adjuvant chemotherapy and radiotherapy remain options for patients with metastatic disease or high-grade tumours.

In conclusion, PMEC is a rare primary neoplasm of the lung which can be challenging to diagnose when presented with atypical radiological features. Hence, the diagnosis can only be established with supporting histological features from a good biopsy specimen. Surgical resection for early disease or low-grade tumours may concur a favourable outcome. However, treatment options for metastatic disease remain poorly established, and the overall prognosis remains guarded.

Outcome of the patient

The patient underwent a CT scan of the brain and neck and a thorough evaluation by the otorhinolaryngology team, with no abnormalities detected. She was empirically started on oral gefitinib while awaiting the results of driver mutation detection by next-generation sequencing (NGS). Unfortunately, the NGS showed the absence of all mutations, and the patient succumbed to her disease 1?week later.

Footnotes

• Conflict of interest: All authors have nothing to disclose.