UPMC Digital Pathology CME Courses

CME Credit Hours: 0.50


Target Audience:
Pathologists, Pathology Residents, Medical Students, Pathology Assistants and Pathology Assistant Students


Educational Objectives:

Upon completion of this activity, participants will be able to:

  • As a result of participation in this activity, participants will be able to increase awareness of the pathologic evaluation of pulmonary mucoepidermoid carcinoma.

Additional Readings:

  • Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization classification of lung tumors. J Thorac Oncol (2015) 10(9):1243-60.
  • Kumar, V. et al. A comparative study of primary adenoid cystic and mucoepidermoid carcinoma of lung. Front. Oncol. 8, (2018).
  • Kalhor, N. & Moran, CA. Pulmonary mucoepidermoid carcinoma: diagnosis and treatment. Expert Rev. Respir. Med. 12, 249-255 (2018).
  • Yousem, SA. & Hochholzer, L. Mucoepidermoid tumors of the lung. Cancer 60, 1346-1352 (1987).
  • ElNayal, A. et al. Primary Salivary Gland-Type Lung Cancer: Imaging and Clinical Predictors of Outcome. Am. J. Roentgenol. 201, W57-W63 (2013).
  • Molina, JR. et al. Primary salivary gland-type lung cancer: Spectrum of clinical presentation, histopathologic and prognostic factors. Cancer 110, 2253-2259 (2007).
  • Hsieh, CC, Sun, YH, Lin, SW, Yeh, YC & Chan, M. L. Surgical outcomes of pulmonary mucoepidermoid carcinoma: A review of 41 cases. PLoS One 12, 1-12 (2017).
  • Achcar, RDOD, Nikiforova, MN, Dacic, S, Nicholson, AG & Yousem, SA. Mammalian mastermind like 2 11q21 gene rearrangement in bronchopulmonary mucoepidermoid carcinoma. Hum. Pathol. 40, 854-860 (2009).
  • Roden, AC. et al. Histopathologic, immunophenotypic and cytogenetic features of pulmonary mucoepidermoid carcinoma. Mod. Pathol. 27, 1479-1488 (2014).
  • Brandwein, MS. et al. Mucoepidermoid carcinoma: A clinicopathologic study of 80 patients with special reference to histological grading. Am. J. Surg. Pathol. 25, 835-845 (2001).

Authors:

Daniel Martinez, MD and Paul Ohori, MD

Release Date: 2022-04-16 Review Date: 2022-04-18 Expiration Date: 2025-04-16

No relationships with industry relevant to the content of this educational activity have been disclosed.

The University of Pittsburgh School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

The University of Pittsburgh School of Medicine designates this enduring material for a maximum of 0.50 AMA PRA Category 1 CreditsTM. Each physician should only claim credit commensurate with the extent of their participation in the activity.

Other health care professionals are awarded ( 0.05 ) continuing education units (CEU) which are equivalent to 0.50 contact hours.

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Case 1060 - A Female Patient in Her 50's with Shortness of Breath

Contributed by: Daniel Martinez, MD and Paul Ohori, MD

A maximum of 0.50 AMA PRA Category 1 Credits are available from a quiz on this case from the University of Pittsburgh's Internet-based Studies in Education and Research.

This course is eligible for the American Board of Pathology SAM credit

Click here to take the quiz and earn 0.50 AMA PRA Category 1 Credits
Please review the case before taking the quiz. The site will now ask for your ABPath MOC number before taking the quiz if it was not supplied previously.

CLINICAL HISTORY

The patient is a 54-year-old female presenting with shortness of breath, malaise, and cough.

Initial chest CT scan demonstrated an infrahilar soft tissue mass with compression of the left lower lobe bronchus and resulting atelectasis of the medial basilar segment (See Figure 1). PET-CT scan demonstrated an SUV of 1.28 (non-hypermetabolic) in the lesion. Initial bronchoscopic biopsy demonstrated a neoplastic proliferation of cytologically bland cells with squamoid, mucinous and intermediate differentiation (See Figure 2)

The patient underwent photodynamic therapy and bronchoscopic debridement of the lesion. A follow-up CT scan demonstrated significant regression of the left hilar mass with improvement of the left lower lobe bronchus obstruction. A pneumonectomy was performed.

Gross examination of the pneumonectomy specimen demonstrated that the tumor was arising in the distal left main bronchus with polypoid intraluminal bronchial extension. (See Figure 3)

Microscopically, the mass was found to be arising in the submucosa of the left lower lobe bronchus with exophytic extension into the bronchial lumen and involvement of the distal left main bronchus (see Figure 4A). The mass was re-demonstrated to be formed by a proliferation of cells with squamoid, intermediate, and mucinous differentiation (See Figure 4B).

Immunohistochemical and special studies performed demonstrated the tumor cells to be positive for PASD, mucicarmine, and focally positive for P40 (See Figure 5).



Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Please click the "Final Diagnosis" tab at the top of the screen to view the rest of the case.

FINAL DIAGNOSIS

Pulmonary Mucoepidermoid Carcinoma

FISH for the MALM-2 translocation: positive (See Figure 6)



Figure 6

DISCUSSION

Pulmonary mucoepidermoid carcinoma (MEC) belongs to the category of salivary gland-type tumors of the lung (SGT) which comprise less than 1% of all lung cancers (1). It has been reported in patients from 3-78 years of age; however, it usually present in patients between 10 and 40 years of age (3, 7). SGT of the lung originate from the submucosal glands of the tracheobronchial tree. The most common histologic subtype of SGT of the lung is adenoid cystic carcinoma (ACC) followed by MEC, epithelioid-myoepithelial carcinoma and pleomorphic adenoma. However, theoretically, any tumor found in the salivary glands could arise in the bronchial wall; in fact, cases of clear cell carcinoma, acinic tumors, and carcinoma ex pleomorphic adenoma have been reported (2).

The majority of thoracic MEC arise in segmental bronchi, followed by main bronchi and trachea (2, 5). At the time of initial diagnosis, two-thirds of these tumors present with localized or regional disease, and only a small proportion present with distant organ involvement. Grossly, most tumors measure from 17 to 38 mm with a median diameter of 25 mm (2). Symptoms at the time of presentation are related to the site of primary involvement, with bronchial tumors presenting with dyspnea, cough, wheezing and hemoptysis, and peripheral tumors presenting with chest pain, cough and pneumonia (3). Imaging studies demonstrates a median SUV max of 4.50 (1.5-6.3) compared to a median of 8.6 (3.7 - 17.6) in ACC (5). The prognosis of MEC of the lung is significantly better than that of NSCLC, with cause-specific survival rates of 71% and 58.1 % at 5 and 10 years, respectively (2).

Histopathologically, pulmonary MEC is characterized by different degrees of cystic and solid growth patterns and a proliferation of mucin-secreting, squamoid, and intermediate cells. Tumors are classified into low and high-grade categories; features of low-grade tumors include well-circumscribed borders, a predominance of mucinous cells, and a cystic growth pattern. Features of high-grade tumors include frequent mitoses (usually > 4/10 HPF), atypical squamoid, and intermediate cells (nucleomegaly, hyperchromatism, irregular chromatin) and necrosis (1, 3, 10). Approximately 50% to 75 % of the tumors are low-grade, and 20% are high-grade at initial diagnosis (2, 4).

Preoperative diagnosis of PMEC can be challenging in small biopsies; notably, its distinction with adenosquamous carcinoma, squamous cell carcinoma, and adenocarcinoma can be particularly challenging. Features that suggest the diagnosis of MEC include the presence of exophytic endobronchial growth, a lack of squamous carcinoma in-situ in the contiguous bronchial epithelium, absence of individual cell keratinization and squamous pearls, and the presence of transitional areas to low-grade MEC (9).

A potentially difficult morphological distinction in small biopsies is with mucous gland adenoma and hyalinizing clear cell carcinoma (CCC) (3). Mucus gland adenoma is a bronchial, well-circumscribed, predominantly exophytic nodule arising above the cartilaginous plates of the bronchial wall, and formed by mucin-filled cysts lined by non-atypical mucus-secreting cells (1). The distinction with clear cell carcinoma could be more challenging because CCC might demonstrate areas of squamous and mucinous differentiation. However, CCC usually demonstrates clear cell differentiation, an infiltrative growth pattern with perineural invasion, and abundant sclerotic or hyalinized stroma (15). Additionally, CCC consistently demonstrates EWSR1-ATF1 gene fusion (16).

The distinction of primary pulmonary MEC from a metastatic head and neck MEC is vital. Monaco et al. demonstrated that during six years of study, only 2 of 22 cases of pulmonary salivary gland-type tumors were primary, with the remaining 20 cases being metastases from the parotid, submandibular glands, tongue, nasal cavity and soft palate (14).

Although the diagnosis of PMEC is primarily based on morphologic findings, immunohistochemical evaluation demonstrates the tumor cells to be positive for squamous cell markers such as p40, CK 5/6, and p63, with the mucin-producing cells positive for mucicarmine and PASD (Periodic acid-Schiff, diastase-resistant). Additionally, tumor cells are negative for TTF1 and napsin A (9).

The MAML2 rearrangement (t(11; 19)(q21;p13) is found in 77-100 % of PMEC and has been identified in low and high-grade tumors (8, 9). It involves the fusion of CRTC1, CREB-Regulated Transcription Coactivator1 (formerly MECT1), and mammalian mastermind-like 2 (MAML2) genes located at chromosomes 19p13 and 11q21 respectively (8).

Initial treatment of bronchial obstruction in patients with MEC or endobronchial extension of NSCLC requires the use of a variety of treatment modalities. Among these is photodynamic therapy (PDT). This method involves the intravenous administration of a photosensitizer, after which the tumor is exposed to a light source. PDT has been shown to be effective and safe in the management of hemoptysis or malignant airway obstruction (13).

Surgery is the preferred definitive treatment modality for PMEC; it might consist of endoscopic removal for tumors limited to the bronchial mucosa up to segmental resection, lobectomy, and even pneumonectomy for more centrally located tumors (11, 12). In conclusion, mucoepidermoid carcinomas of the tracheobronchial tree are very rare tumors with a relatively good prognosis. They tend to arise in the in submucosa of segmental airways and frequently demonstrate intraluminal exophytic growth. Their distinction from more common entities like adenosquamous carcinoma is supported by a lack of individual cell keratinization and the presence of intracytoplasmic mucin; features that can be highlighted with special stains like mucicarmine and PASD. The presence of MAML2 fusions assist in the distinction with more rare entities like mucous gland adenoma and hyalinizing clear cell tumor. Finally, radical surgery after management of possible symptomatic bronchial obstruction is the preferred treatment modality for localized disease.

REFERENCES

Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JHM, Beasley MB, et al. The 2015 World Health Organization classification of lung tumors. J Thorac Oncol (2015) 10(9):1243-60.
Kumar, V. et al. A comparative study of primary adenoid cystic and mucoepidermoid carcinoma of lung. Front. Oncol. 8, (2018).
Kalhor, N. & Moran, C. A. Pulmonary mucoepidermoid carcinoma: diagnosis and treatment. Expert Rev. Respir. Med. 12, 249-255 (2018).
Yousem, S. A. & Hochholzer, L. Mucoepidermoid tumors of the lung. Cancer 60, 1346-1352 (1987).
ElNayal, A. et al. Primary Salivary Gland-Type Lung Cancer: Imaging and Clinical Predictors of Outcome. Am. J. Roentgenol. 201, W57-W63 (2013).
Molina, J. R. et al. Primary salivary gland-type lung cancer: Spectrum of clinical presentation, histopathologic and prognostic factors. Cancer 110, 2253-2259 (2007).
Hsieh, C. C., Sun, Y. H., Lin, S. W., Yeh, Y. C. & Chan, M. L. Surgical outcomes of pulmonary mucoepidermoid carcinoma: A review of 41 cases. PLoS One 12, 1-12 (2017).
Achcar, R. D. O. D., Nikiforova, M. N., Dacic, S., Nicholson, A. G. & Yousem, S. A. Mammalian mastermind like 2 11q21 gene rearrangement in bronchopulmonary mucoepidermoid carcinoma. Hum. Pathol. 40, 854-860 (2009).
Roden, A. C. et al. Histopathologic, immunophenotypic and cytogenetic features of pulmonary mucoepidermoid carcinoma. Mod. Pathol. 27, 1479-1488 (2014).
Brandwein, M. S. et al. Mucoepidermoid carcinoma: A clinicopathologic study of 80 patients with special reference to histological grading. Am. J. Surg. Pathol. 25, 835-845 (2001).
Vadasz P and Egervary M. Mucoepidermoid bronchial tumors: a review of 34 operated cas- es. Eur J Cardiothorac Surg 2000; 17: 566- 569.
Chin CH, Huang CC, Lin MC, Chao TY and Liu SF. Prognostic factors of tracheobronchial mucoepidermoid carcinoma-15 years experience. Respirology 2008; 13: 275-280.
Minnich, D. J., Bryant, A. S., Dooley, A. & Cerfolio, R. J. Photodynamic Laser Therapy for Lesions in the Airway. Ann. Thorac. Surg. 89, 1744-1749 (2010).
Monaco, S. E., Khalbuss, W. E., Ustinova, E., Liang, A. & Cai, G. The cytomorphologic spectrum of salivary gland type tumors in the lung and mediastinum: A report of 16 patients. Diagn. Cytopathol. 40, 1062-1070 (2012).
Shahi, M., Dolan, M. & Murugan, P. Hyalinizing Clear Cell Carcinoma of the Bronchus. Head Neck Pathol. 11, 575-579 (2017).
Shah, A. A. et al. EWSR1 Genetic Rearrangements in Salivary Gland Tumors. Am. J. Surg. Pathol. 37, 571-578 (2013).

Click here to take the quiz and earn 0.50 AMA PRA Category 1 Credits
Please review the case before taking the quiz. The site will now ask for your ABPath MOC number before taking the quiz if it was not supplied previously.