Epithelioid cells with eosinophilic cytoplasm are seen. Interestingly, it is not uncommon for mesothelioma to show only mild to moderate atypia.
Cleft-like spaces are characteristic in this histologic (epithelioid) variant.
Invasion into the skeletal muscle of the chest wall is illustrated here. Invasion may be into visceral or parietal pleura (or beyond), which can be highlighted with pancytokeratin or calretinin. Invasion by mesothelioma may be subtle and limited to only a few layers of collagenous tissue below the mesothelial space. It may also lack a desmoplastic reaction. However, it is emphasized that if a solid piece of malignant tumor with histologic features of MM is identified, the presence of invasion is not necessarily required (Husain).
The mesothelioma appears relatively bland but is invading the chest wall fat.
This different case of malignant mesothelioma appears to grow in a solid and slightly trabecular pattern. Other common patterns of are the tubulopapillary pattern, acinar (glandular) pattern, adenomatoid pattern (also termed microglandular).
The solid pattern consists of sheets and dissecting nests of relatively discohesive polygonal to round cells with uniform nuclei in a slightly myxoid stroma. These cells by cytological criteria along simulate reactive mesothelial cells, and the differential diagnosis may include reactive mesothelial hyperplasia, solid adenocarcinoma, and even squamous cell carcinoma due to the abundant pink cytoplasm.
Positivity for calretinin supports the diagnosis. A panel of stains must be used to distinguish between adenocarcinoma and mesothelioma. No marker is entirely specific and false positives (which often show less than 10% staining) can occur in either direction.
Cytokeratin 5/6 is also positive in mesothelioma.
Some mesotheliomas are heavily inflamed as evidenced by lymphocytes interpersed among the tumor cells and may be termed lymphohistiocytoid mesothelioma by some pathologists (Fletcher).
Invasion into the lung parenchyma (alveoli seen on left) is frequently found in malignant mesothelioma.
Here is a different mesothelioma with a vacuolated appearance.
This mesothelioma has more of a tubulopapillary growth pattern. There is not a lot of atypia appreciated at this power.
A higher power shows dense sclerosis. Some of the nuclei do have noticeable nucleoli.
This tumor has a solid pattern which results from compact trabecular growth. The cells have abundant pink cytoplasm.
Another tumor shows single cells in a myxoid background.
A microglandular growth pattern predominates in this pleural mesothelioma. There is a resemblance to adenocarcinoma.
Another tumor is dominanted by a very definite papillary pattern. The fibrovascular cores are easy to find, and are surrounded by a single layer of malignancy cells which are mesothelial.
This different tumor shows many areas that resemble decidua, and is referred to as the deciduoid variant.
Malignant mesothelioma arises from the mesothelial layer that lines the pleura, peritoneum and pericardium. It is uncertain whether the cell of origin is a differentiated mesothelial cell or a progenitor submesothelial mesenchymal cell. This tumor most commonly affects the pleura, but cases arising in the peritoneum, pericardium and even the tunica vaginalis of the testis have been documented (Zander).
Grossly, the tumors begin as small raised plaques on the pleural surface which then coalesce and eventually form a hardened rind that totally encases the lung. The neoplasm can also form finger-like extensions as it tracks along the fissures of the lung.
Histologically, there are three histologic subtypes: epithelioid (70%), sarcomatoid (25%) and biphasic or mixed (5)%. Desmoplastic mesothelioma is considered a variant of sarcomatoid (Fletcher).
The epithelioid variant consists of round/cuboidal cells with moderate eosinophilic cytoplasm, bland nuclei and absent/rare mitotic activity. The cytologic features are usually less pleomorphic compared to that seen in adenocarcinoma. Epithelioid mesothelioma exhibits a variety of growth patterns including tubulopapillary, pseudoacinar, microglandular, trabecular and sheet-like solid growth. Deciduoid mesotheliomia is an unusual variant consisting of cells with distinctively decidua-like features with round/polygonal cells, abundant cytoplasm and prominent nucleoli.
Immunohistochemistry: It is important to distinguish between malignant mesothelioma and adenocarcinoma which can involve the pleural surface and have a pseudomesotheliomatous growth pattern. An IHC panel will be helpful in sorting this out. Epithelioid mesotheliomas will be positive for calretinin, cytokeratin 5/6, WT1, D240 and negative for CEA, TTF-1, Ber-Ep4, B72.3 and CD15. The converse is true for adenocarcinoma of the pleura (Cheng, Zander).
The International Mesothelioma Panel recommends that at least two mesothelial, two carcinoma markers and pancytokeratin be employed to distinguish between mesothelioma and adenocarcinoma. It is important to remember that "negative" markers (e.g. CEA, MOC31, Ber-EP4 and B72.3) can occasionally be positive in mesothelioma while "positive" markers (e.g. EMA, cytokeratin 5/6, calretinin, MUC43, D2-40, podoplanin) can also be positive in non-mesothelial adenocarcinomas. Furthermore, smooth muscle markers such as actin and desmin can be expressed in the sarcomatoid variant. Thus, no single stain is sufficient and panel of markers must be used.
Electron microscopy: If your institution has this capacity, sending for ultrastructural study can help you secure the diagnosis and is in fact considered the gold standard. Adenocarcinoma is characterized by short, stubby microvilli with well-developed rootlets while mesothelioma exhibits long slender microvilli without microvillous rootlets and abundant tonofilaments (Kumar, Cheng).
Most commonly diagnosed in older adults (over 50) with a strong male predilection. Association with abestos exposure (usually occupational) is well established, however, it must be noted that most asbestos related lung neoplasms are carcinomas.
These tumors can be clinically silent for decades (latency period of 25-45 years) and when symptoms develop, the tumor has usually reached an advanced stage with invasion into the lung parenchyma and hilar lymph nodes. Symptoms include insidious pleuritic pain, dyspnea and pleural effusions.
Interestingly, smoking does increase the risk of developing mesothelioma in abestos-exposed persons, however, smoking significantly amplifies the risk of absestos-related lung carcinoma in these workers (Kumar).
Very poor prognosis with death occurring within 18 months of diagnosis (Fletcher). Very few cases are resectable.
Fletcher CDM, ed. Diagnostic Histopathology of Tumors. 3rd Ed. Philadelphia, PA: Elsevier; 2007: 205-7.
Husain AN et al. Guidelines for pathologic diagnosis of malignant mesothelioma: a consensus statement from the International Mesothelioma Interest Group. Arch Pathol Lab Med. 2009 Aug;133(8):1317-31.
Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease. 7th Ed. Philadelphia, PA: Elsevier; 2005: 768-770.
Zander DS, Farver CF. Pulmonary Pathology: Foundations in Diagnostic Pathology. Philadelphia, PA: Elvesier; 2008: 693-702.