1 Department of Internal Medicine, Owaisi Hospital and Research centre, India
2 Department of Internal Medicine, Deccan college of Medical Sciences, India
3Department of Internal Medicine, Gian Sagar Medical College and Hospital, India
4Department of Internal Medicine, Karachi Medical and Dental College, Pakistan
5Department of Internal Medicine, Sri Siddhartha Medical College, India
6Department of Internal Medicine, Lokmanya Tilak Municipal Medical College, India
7Department of Internal Medicine, University Hospitals Case Medical Center, USA
Submission: June 06, 2018; Published: June 26, 2018
*Corresponding author: Faisal Uddin M, Department of Internal Medicine, Owaisi Hospital and Research centre, Hyderabad, India.
How to cite this article: Faisal Uddin M, Arastu A, Arshi J, Khan J, Bansal R, et al. High Grade MEC Masquerading as Non Small Cell Lung Cancer. Int
J Pul & Res Sci. 2018; 3(4): 555616. DOI: 10.19080/IJOPRS.2018.03.555616
We present the case of a 52 year old male initially diagnosed with squamous cell carcinoma of the right main bronchus by endobronchial biopsy, who after undergoing a pneumonectomy the surgical biopsy was changed to high grade mucoepidermoid. His post-operative course was complicated by healthcare associated pneumonia and unmasking of symptoms of emphysema.
Mucoepidermoid Carcinoma (MEC) is a salivary gland tumor that rarely presents in the lungs and can be sometimes misclassified as squamous cell carcinoma. While surgical resection is the initial treatment of choice, its tendency to present as a proximal endobronchial lesion requires many patients to undergo lobectomies or pneumonectomies. To the best of our knowledge, this is the only case of high grade MEC of the lung that was previously misdiagnosed as squamous cell carcinoma.
A 52-year-old male smoker presented with complaints of chest pain and persistent cough to his PCP. He had lost 10 pounds over the previous few months. He denied any fever, nausea or vomiting. He worked as a mechanist, with significant history of smoking one pack per day for more than 35 years. He had never been diagnosed with COPD in the past and denied previous use of inhalers. He reported a significant family history of cancer including breast cancer in his mother and melanoma in father. He had no sinus symptoms and no known exposures to tuberculosis. The patient’s vitals were normal and oxygen saturation was 97% on room air. The remaining physical examination was normal.
He underwent a Chest X-Ray (CXR) that was suspicious for a right upper lobe mass (Figure 1) which was subsequently confirmed by Computed Tomography (CT) scan of the chest. His imaging was also significant for bilateral emphysematous changes (Figure 2). His pulmonary function test before the surgery showed a forced vital capacity of 4.6 liters (90% predicted) and an FEV1 of 2.9 liters (79% predicted). FEV1/FVC ratio of 0.63 consistent with a mild obstructive ventilator defect. No significant change was seen in flow rates with administration of bronchodilator. The lung volumes and diffusion capacity were normal. Bronchoscopy was performed, which revealed an endobronchial lesion in the right main bronchus. Endobronchial biopsy was obtained. The histopathological examination revealed poorly differentiated squamous cell carcinoma. Immunohistochemical analysis was
done which showed that the cells were CK 5/6, CK7 and p40
positive as well as CK20 and TTF1 negative. No mutation in EGFR
was detected. Fluorescence in situ hybridization was negative for
a rearrangement involving ALK gene and ROS1 gene. A PET scan
and MRI showed no remote disease. The patient was referred to
thoracic surgery, who performed a staging mediastinoscopy and
then went on to perform a right sided pneumonectomy was done.
His post-operative course was uneventful until the 5th postoperative
day, when he developed hypoxic respiratory failure.
At that time, a CT scan showed fluid accumulation within the
pneumonectomy cavity (Figure 3) and mild left retrocardiac
atelectasis as well as an elevation of white blood cell count.
He was started on broad-spectrum antibiotics for healthcare
associated pneumonia. He underwent a bronchoscopy which
revealed thin purulent secretions in the trachea, left main, left
upper and lower lobes. Later that day, he was intubated due to
increasing respiratory distress. BAL viral and bacterial cultures
were negative and sputum culture grew normal flora.
Leukocytosis would improve, and on the 11th post-operative
day he was extubated. He continued to have wheezing with
minimal exertion despite short acting bronchodilators 16 days
after the surgery, and following this long acting bronchodilators
were initiated (tiotropium and fluticasone/salmeterol and
albuterol as needed) with recommendations from the pulmonary
consult team to get outpatient pulmonary function testing.
He was discharged on home O2 on post-operative day 20. The
histopathology report on the post pneumonectomy specimen
showed findings consistent with the diagnosis of high grade MEC
(Figure 4-6), and one node was positive from the mediastinoscopy.
The patient was subsequently presented at tumor board and
diagnosed with Stage 3A (T3N1M0) mucoepidermoid carcinoma.
Adjuvant chemotherapy was recommended as an outpatient.
Mucoepidermoid carcinoma of the lung is a rare presentation
of the most common salivary gland tumor. It is associated with
smoking and can be classified as either low grade or high grade.
MEC in the trachea bronchial tree is rare, accounting for only
0.1%–0.2% of all pulmonary malignancies [3,4] and is thought
to arise from the minor salivary glands in the trachea bronchial
tree . This tumor is classified as either low grade or high grade
on the basis of histologic criteria . Low-grade MEC shows
minimal or no mitoses, nuclear pleomorphism, or necrosis within
the tumor . High-grade tumors show increased mitoses (more
than four per 10 high-power fields), nuclear pleomorphism,
hyperchromasia, and cellular necrosis [4,6,7].
The diagnosis of MEC can be difficult pathologically based
on several important features. It is a subepithelial tumor which
arises from the bronchial submucosal glands. Low grade tumors
show mucus filled cystic areas as well solid areas. The cysts or
glands are lined by columnar cells and low cuboidal cells with mild
cytologic atypia, with small, round, basally located nuclei. Mitotic
figures are rare in low grade tumors, as is necrosis. The solid
areas are mainly composed of epidermoid and intermediate cells
with minimal cytological atypia. Epidermoid cells have features
of nonkeratinizing squamous cells with eosinophilic cytoplasm.
Intermediate cells may have nuclear clearing.
High-grade mucoepidermoid carcinomas, like our case,
show a predominance of solid areas composed of intermingled
epidermoid and intermediate cells with a lesser representation
of mucin secreting cells. Tumor cells demonstrate nuclear atypia,
hyperchromasia and pleomorphism, as well as higher mitotic
counts. Necrosis and perineural invasion may be observed. The
most problematic differential diagnosis of mucoepidermoid
carcinoma in the lung is adenosquamous carcinoma. In general,
mucoepidermoid carcinomas are centrally located with an
endobronchial growth pattern and are relatively common to
recognize areas of low grade mucoepidermoid carcinoma in
association with the high grade areas which pose difficulties
in diagnosis. In addition, prominent keratinisation, and in situ
carcinoma on the surface of the bronchial epithelium, which
can be present in adenosquamous carcinomas, is not seen in
mucoepidermoid carcinomas of the lung.
Several cytokeratins, including AE1, CK7, CK5/6, CK7 and
CK8, as well as PCNA, Ki-67, p63, p53, CD10 and p27, are common
markers that are used to identify MEC . In our case, histological
staining was performed for CK7 (+), CK5/6 (+), p53 (+), CK 20
(-) and TTF 20 (-). CK5/6 is also positive in 90% of squamous
cell carcinoma and at least 20% are found to be CK7 positive .
Because of considerable overlapping between the markers used
to identify MEC and SCC, immune phenotyping should not be used
alone for histopathologic classification of lung cancer, but only as
an adjunct to light microscopy.
Surgery is the standard treatment for medically operable
patients with clinical stage I and II non small cell lung cancer, in
whom there is no evidence of mediastinal involvement prior to
surgical resection . In our patient, right pneumonectomy was
done by a standard posterolateral thoracotomy. Radical surgery
based on lung cancer treatment is also performed for MEC .
MECs of the lung are often treated by lobectomy, sleeve resection,
local resection, segmental resection, or even endoscopic removal.
Treatment would not have been different pre-operatively even if
MEC was correctly diagnosed (Figure 7).
However, postoperative course may vary in patients with
high grade MEC which is why it is important for post-surgical
specimens to be sent for pathology in addition to bronchoscopy
specimens. Effective treatment for high-grade tumors has not
been established. There are no randomized controlled trials
studying the profit of adjuvant chemotherapy in MECs of the
lung and given the rarity of these tumors, such studies will likely
never be designated . Due to its often proximal endobronchial
location, patients like ours who previously had good pulmonary
function despite parenchymal evidence of emphysema may have
unmasking of COPD symptoms once undergoing a lobectomy or
pneumonectomy due to their limited reserve.