May 2014

A 63 year old male with fatigue and shortness of breath

Nariman Nawar, M.D., Judy King, M.D, Ph.D., and H. James Williams, M.D.


A 63 year old male patient with history of asbestos exposure presented to the clinic with a complaint of progressive shortness of breath and fatigue over the last three months. Physical examination showed pallor and decreased vesicular breathing on the right side. Further radiological studies revealed multiple right pleural nodules as shown below:

Figure 1 Computed tomography of the chest. There are multiple right anterior pleural nodules (See arrow).
Figure 2 Cell block preparation from fine needle aspiration of pleural fluid. The fluid is cellular with numerous cohesive groups of cells in large balls. Seen on low power.
Figure 3 On high power cells are seen to have markedly enlarged vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm. Few inflammatory cells are seen in the background.


Figure 4 The cells show strong cytoplasmic and nuclear expression of calretinin.
Figure 5 The cells are also strongly positive for CK5/6.
Figure 6 The cells do not show nuclear positivity for transcription factor-1 (TTF-1).
Figure 7 The cells do not exhibit staining for carcinoembryonic antigen (CEA).


Based on the information provided, the most likely diagnosis is ?


Please select an answer above.


Epithelioid mesothelioma is the most common subtype of malignant pleural mesothelioma (MPM) which is a rare pleural neoplasm that have been linked to asbestos exposure and smoking. Clinically MPM presents with recurrent pleural effusion, rib pain, fatigue and unexplained weight loss. Making a diagnosis of MPM is very challenging as this tumor can mimic other tumors and even benign reactive processes. Therefore diagnosis should always be based on adequate biopsy with correlation to the clinical, radiological and surgical findings.

In reactive mesothelial hyperplasia, mesothelial cells become atypical with high cellularity and mitotic rate mimicking neoplasms. Certain features such as absence of necrosis and uniformity of growth favor a benign process over a malignant process. Absence of stromal and fat invasion is a key feature distinguishing reactive mesothelial hyperplasia from MPM in tissue section.

Although pleural biopsy is the best diagnostic tool for MPM, cytological fluid examination with immunohistochemical studies can provide the diagnosis. Cells in epithelioid mesothelioma tend to clump forming aggregates (balls) of large cells with large nuclei and nucleoli with characteristic berrylike external contours. As morphological features are not sufficient to differentiate mesothelioma from other epithelial tumors such as metastatic adenocarcinoma, immunohistochemical studies should be done in conjunction with cytological studies.  

Mesothelial cells express several markers including calretinin, podoplanin, D2-40, cytokeratin 5/6, WT-1 protein and mesothelin. Because certain epithelial markers are also expressed in MPM it is recommended to test for at least two mesothelial cell markers and two epithelial cell markers known to be negative in mesothelial calls.

MPM treatment modalities include surgery, chemotherapy and radiotherapy. Overall prognosis of MPM is poor with median survival after diagnosis of 5-16 months. 


  1. Nelson G. Ordóñez (2005) Immunohistochemical Diagnosis of Epithelioid Mesothelioma: An Update. Archives of Pathology & Laboratory Medicine: November 2005, Vol. 129, No. 11, pp. 1407-1414.
  2. Ilyssa O. Gordon, Stephanie Sitterding, A. Craig Mackinnon, and Aliya N. Husain (2009) Update in Neoplastic Lung Diseases and Mesothelioma. Archives of Pathology & Laboratory Medicine: July 2009, Vol. 133, No. 7, pp. 1106-1115.