Desmoplastic mesothelioma
Wednesday, February 14, 2018
Desmoplastic mesothelioma: Specimen obtained from the pleural effusion has limited value in establishing the diagnosis because the mesothelioma cells are not shed into the fluid.7 The most common histologic type of malignant mesothelioma is epithelioid, which is associated with the best prognosis, whereas sarcomatoid variant is associated with the worse.8 The term “desmoplastic” refers to the growth of fibrous or connective tissue and accounts for 5% to 10% of all mesotheliomas.1 This type of tumor lies in between epithelioid and sarcomatous subtypes of mesothelioma and may mimic fibrous pleuritis. Spindle cell proliferation involving the pleura, bland necrosis, frank sarcomatoid areas, and invasion of the adipose tissue, the muscle, or the lung allow us to distinguish desmoplastic malignant mesothelioma from reactive serositis.1 For a definitive diagnosis, we used pan-cytokeratin, calretinin, and cytokeratin 5/6 as mesothelial-associated immunohistochemistry antibodies with a reported sensitivity of 95% and specificity of 87% for malignant mesothelioma. Lung adenocarcinoma was excluded with negativity to carcinoembryonic antigen, thyroid transcription factor-1, and CD15, which are not expressed in mesotheliomas.8 Thyroid transcription factor-1 is the only 100% specific antibody with no published cases of positive staining for mesothelioma. Melanoma was excluded with negativity to HMB-45.1
DMM presents similarly to other cell types of pleural mesothelioma, with a few differences. In most cases, a patient with DMM will have little or no pleural effusion with cancer spread to distant organs or lymph nodes at time of diagnosis. A typical pleural mesothelioma diagnosis is characterized by large pleural effusions with regional lymph node involvement.
Mesothelioma has been described as an insidious neoplasm because of its long latency period—up to 40 years in some series—after exposure to asbestos.2 The disease is endemic in some villages of Central and Southeast Anatolia in Turkey (Fig. 3), where asbestos is used to distemper the inner walls of the houses, in pottery (using the contaminated soil), and as a substitute for baby powder.2,3 There is also an additional mineral fiber “erionite” that belongs to a group of minerals called zeolites. It is found particularly in the Cappadocian region of Central Anatolia and is held responsible for the high incidence of pleural mesothelioma.
Patients often question if desmoplastic mesothelioma, like malignant pleural mesothelioma, is caused by asbestos. The relationship between asbestos and DMM is still controversial. However, most patients have had a history of asbestos exposure and autopsies have revealed asbestos fibers in the thickened pleura.
YO and KH acquired the clinical data and drafted the manuscript. YO and YH were responsible for the clinical management of the patients. TH was responsible for the pathological diagnoses. YO, KH, YH, and TH were responsible for interpretation of the data and critical revision of the manuscript. All authors have read and approved the final manuscript.
A 69-year-old man was referred to the Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, with complaints of cough with hemoptysis, weight loss, and an abnormal chest radiograph. He also had diabetes, dyslipidemia, and a history of tuberculosis. He had been diagnosed with non-specific pleural thickness by video-assisted thoracoscopic surgery (VATS) at a different institution 3 years previously. Chest computed tomography (CT) revealed pleural effusion with thickened pleura. VATS of the pleura was performed, and the histopathological examination revealed thickening with collagen fibrous hyperplasia and invasion of inflammatory cells, mainly comprising plasma cells. The collagen fibers were irregular, with poor alignment. These characteristics were consistent with DMM. He was also diagnosed with T4N0M0 stage IV according to iMig stage. The patient was initially treated with hyperthermic intrathoracic chemotherapy at a dose of 10 Gy in 10 fractions, with palliative intent. Although his tumor shrank by 13 %, he died suddenly of cardiopulmonary arrest at home at 11.6 months after starting the treatment.
The separation of sarcomatoid and desmoplastic malignant mesotheliomas from sarcomatoid carcinomas of the lung metastatic to the pleura may be difficult, since both types of tumor can be morphologically similar and are frequently positive only for pan-keratin. GATA binding protein 3 (GATA3) is most commonly used as an immunohistochemical marker of breast and urothelial carcinoma, but is also known to stain other types of tumors including some mesotheliomas. In this study we asked whether GATA3 stains could be used to distinguish sarcomatoid/desmoplastic malignant mesotheliomas (N=19) from sarcomatoid carcinomas of the lung (N=13). Tumor staining was scored for diffuseness and intensity, with a maximum possible score of 6. All 19 sarcomatoid/desmoplastic malignant mesotheliomas examined showed strong diffuse staining for GATA3 (no case scored
Related Pages MesotheliomaDiagnosisTypesPleuralPeritonealPericardialTesticularCell TypesAdenomatoidBenignBiphasicCysticDeciduoidDesmoplasticEpithelialHeterologousLymphohistiocytoidPapillarySarcomatoidSmall CellPrognosisStaging & MetastasisSurvivorsSupport for PatientsCausesSymptomsStatistics & FactsAwareness This rare subtype was initially described in 1980 and represents 5 to 10 percent of all mesothelioma cases. Its cells are often described as bland or “patternless” in appearance and are usually found once they have invaded the chest wall adipose tissue. Diagnosis To accurately diagnose any case of an asbestos cancer, a sample of tumor tissue (called a biopsy) is essential. Doctors like to take a large tissue biopsy so that enough cells are reviewed. A large biopsy is particularly important to diagnosing the desmoplastic subtype because fibrous regions of this tumor can hide cell variations that are important to an accurate diagnosis. The presence of this dense fibrous tissue, in addition to minimal cellularity (patterns formed by cells), characterize the desmoplastic variant of mesothelioma. This pattern makes it challenging for doctors to accurately diagnose desmoplastic malignant mesothelioma (DMM). It’s sometimes misdiagnosed as fibrous pleurisy, pleural fibrosis, rheumatoid disease or spindle cell sarcoma. Doctors and pathologists have specific criteria to look for when a patient is suspected of having this subtype. This criterion includes: At least 50 percent of the tumor must be made up of dense fibrous tissue that frequently forms nodules Areas of increased cellularity that have sarcomatoid mesothelioma characteristics Spread of neoplastic spindle cells to the lung or chest wall Metastasis to nearby fat tissue, skeletal muscle or the lung Presence of the p53 tumor suppressor gene protein Doctors warn that when this subtype metastasizes, it can look bland and may be confused as benign fibrous tissue. Imaging scans like a CT or MRI may help a pathologist identify spread to the lung or chest wall to diagnose DMM in difficult cases. Get a Free Mesothelioma Guide Free information, books, wristbands and more for patients and caregivers. Get Yours Today Symptoms, Treatment and Prognosis Although symptoms of mesothelioma are not profoundly affected by the cell type of the tumor, the primary symptom of desmoplastic mesothelioma is chest pain, often caused by a buildup of fluid in the lungs. Treatment for this particular type of mesothelioma is typically not surgical. Treatments for DMM aim to reduce symptoms, prolong survival and improve quality of life without taking aggressive action. Quick Fact In a study that analyzed 709 cases of mesothelioma from 1998 to 2002, the desmoplastic subtype was diagnosed in 2 percent of cases – less than the average 5 to 10 percent typically diagnosed. Common treatments include the use of chemotherapy and radiation to shrink tumors and kill cancerous cells. A pleurodesis or paracentesis may be recommended to extract excess fluid from the lungs or abdomen. Desmoplastic mesothelioma is categorized as a sarcomatoid cancer, which is typified by a poor prognosis. In this case, the life expectancy following diagnosis is usually less than one year. In one seven-year study (1982-1989) that evaluated 255 cases of mesothelioma, researchers identified 17 cases of desmoplastic mesothelioma. Of those, 11 were sarcomatoid and six were biphasic. The mean survival from the onset of symptoms to death was 5.8 months for the sarcomatoid variant and 6.8 months for the biphasic variant. Additional research on this rare mesothelioma subtype is needed so that doctors can make a more accurate diagnosis and patients can extend their survival. Desmoplastic patients who are looking for new or unique ways of treating cancer can consider clinical trials and alternative therapies.