5. Discussion
Many tumors feature metastases to the pleural membranes in the late stage of the disease, but predominant serosal involvement mimicking malignant mesothelioma is a rare presenting sign [2]. Various malignant pseudomesotheliomatous tumors have been reported, including different types of primary lung carcinomas [2], a variety of sarcomas [4], thymic epithelial tumors [4], melanoma [5], hematopoietic neoplasms [4, 6], and many metastatic tumors [2, 4]. Pseudomesotheliomatous carcinomas originating in the lung tend to be peripherally located and are characterized by extensive pleurotropic growth and inconspicuous parenchymal involvement [7]. Pseudomesotheliomatous lung carcinomas are a heterogenous group of tumors. Attanoos and Gibbs reported 47 cases of primary pulmonary carcinoma with extensive pleural spread of which 70% were adenocarcinomas [2]. Other reported types of lung carcinomas mimicking malignant mesotheliomas include various high-grade carcinomas such as pleomorphic carcinoma, small-cell carcinoma, basaloid carcinoma, carcinosarcoma [2], high-grade neuroendocrine carcinoma [8], and large-cell carcinoma [9]. Also, squamous cell carcinoma, signet ring-cell carcinoma [10], and atypical carcinoid [11] have been reported. Pleural pseudomesotheliomatous tumors have poor prognosis with a median survival of 8 months, similar to stage IV non-small cell lung cancer [2, 12].
The presented case featured subpleural interstitial growth and a pleural spread of discohesive tumor cells. In addition, there were atypical BAC-like pneumocytes lining the alveoli in and around the interstitial component of the infiltrative tumor. These cells showed no nuclear stratification, (micro)papillary or glandular differentiation present but were strongly positive for TTF-1 and keratin markers, suggestive of a BAC-component in a poorly differentiated adenocarcinoma. Whether this represents a true in situ component of the same adenocarcinoma, or reactive atypia, cannot be distinguished with certainty. If considered to be in situ carcinoma, then it can only be speculated as to whether the interstitial component or the in situ component came first, or even whether there could be an ongoing interchange between the two. The constellation of an interstitial TTF-1 positive tumor together with atypia of the alveolar lining cells is rarely observed in lung carcinomas. This combination, however, is reminiscent of pneumocytoma [13]. Clearly, this case differs from pneumocytoma in that it represents a high-grade and rapidly progressive tumor, a feature that has not been described in pneumocytoma.
Our patient presented with a massive hemothorax which required thoracotomy and wedge resection to control the bleeding. After removal of the ulcerating lung lesion, the hemorrhage recurred, resulting in severe anemia together with circulatory failure and postoperative infection, causing death 21 days after presentation. Bleeding from a lung cancer usually presents as hemoptysis resulting from necrosis and vascular rupture or tumor erosion of pulmonary vessels. Approximately 7% of patients with lung cancer manifest with hemoptysis, and centrally located bronchial tumors are much more frequently associated with hemoptysis than peripheral tumors [14, 15]. Patients with pseudomesotheliomatous carcinoma have not been reported to present with hemoptysis [16].
Lung carcinoma is a distinctly uncommon cause of hemothorax [17], and we found only one case reported hitherto [1]. Spontaneous neoplasia-associated hemothorax has most commonly been associated with neurofibromatosis type 1, angiosarcoma, and hepatocellular carcinoma, the latter known for its vascular stroma [17]. Mediastinal tumors have also been reported to cause hemothorax [17]. Bleeding caused by these tumors has been attributed to several mechanisms. One is direct oozing or exsanguination of the tumor into the pleural space, and another is acute bleeding due to rupture of the primary tumor [18]. We believe that both mechanisms could explain the intractable bleeding in the present case, considering the serosal ulceration of the primary lesion and multiple small blood-filled clefts and vessels between the discohesive tumor cells. In addition, tumor invasion into larger vessels including arteries, causing vascular lesions, may have played a role [19].
Pleural effusions are often seen together with pseudomesotheliomatous carcinomas of the lung [16, 20], and these are frequently blood-stained (serosanguinous). True hemothorax is defined as pleural fluid with a hematocrit equal to or greater than 50% of the blood hematocrit [17]. Values of less than 50% have sometimes been called bloody pleurisy [18]. Measuring the hematocrit (or hemoglobin concentration) to distinguish between true hemothorax and bloody pleurisy is important as these two conditions have different etiologies and therapeutic options [17].
Primary treatment of true hemothorax is by chest tube drainage, which evacuates blood and prevents the formation of a clotted hemothorax with restricted lung function. This approach decreases the risk of empyema, and drainage allows monitoring the amount of blood loss. However, in case of persistent blood loss, as determined by chest drain production or hemodynamic instability, surgical exploration should be considered. Treatment of neoplasia-associated hemothoraces depends on the tumor and frequently involves resection of the lesion. The prognosis of malignancy-associated hemothorax, as with pseudomesotheliomatous carcinoma, is poor [17].
We have presented a case of a rare type of poorly differentiated pseudomesotheliomatous carcinoma originating in the lung, complicated by massive true hemothorax and persistent blood loss that proved rapidly fatal in spite of surgery. Awareness of this rare complication is important for an early diagnosis and intervention. Continued case reporting is necessary to determine which protocols would be optimal for treating this tumor.