Pulmonary carcinosarcoma is a malignant tumor with a mixture of carcinoma and sarcoma [1
]. In the WHO classification of lung tumors, it is included in a group of poorly differentiated non-small cell lung carcinomas that contain a component of sarcomatoid differentiation, so called sarcomatoid carcinoma. The average age of diagnosis is 60 years with men to women ratio of 4:1 and more than 90% of these patients have a history of heavy smoking [2
]. Pulmonary carcinosarcoma accounts for < 1% of all primary pulmonary neoplasms [6
The carcinomatous component is more often squamous cell carcinoma, followed by adenocarcinoma and large cell carcinoma; whereas the most common mesenchymal component is poorly differentiated spindle cell sarcoma. Nevertheless, foci of rhabdomyosarcoma, osteosarcoma, and chondrosarcoma are often found [3
In a retrospective analysis of 2,400 lung cancer patients between 1975 and 1995 conducted by Huwer H et al, only seven patients (0.3%) had pulmonary carcinosarcoma [4
]. Diaconita reported eight cases among 3000 patients with malignant pulmonary tumors [5
Immunohistochemical (IHC) staining enhances the distinction of carcinomatous from sarcomatous components within the tumor. When heterologous sarcoma elements such as cartilage or skeletal muscle are present, it is easier to confirm the biphasic nature of the tumor, although immunostains can be of further help such as Myogenin and Myo D1 (rhabdomyosarcoma); smooth muscle actin and desmin (leiomyosarcoma); and S100 (chondrosarcoma). However, carcinosarcomas are difficult to diagnose preoperatively. Biopsy of the tumor, especially when centrally located, often shows only one component, and peripheral tumors are difficult to reach endoscopically [4
Histogenetically, Carcinosarcomas may represent malignant epithelial neoplasms undergoing divergent tissue differentiation originating from a single clone [7
]. The prognosis of these patients is unfavorable based on a small number of cases described in literature. Ishida et al reported a 9-month median survival of 5 patients [8
]. Davis et al reported a 12 month median survival time in 15 patients post resection [6
]. Huwer et al reviewed seven patients with pulmonary carcinosarcoma out of 2,400 cases of lung cancers and found that mortality was related to tumor recurrence or distant metastasis of the sarcoma component [4
]. In a clinicopathologic study, Koss et al retrospectively reviewed 66 patients with pulmonary carcinosarcoma from the archives of the Armed Forces Institute of Pathology (AFIP), and compared them to 33 cases of pleomorphic carcinoma and found that carcinosarcomas had poor prognosis with a 5-year survival rate of 21.3%. Of several clinical and pathologic parameters, only tumor size (6 cm or more) appeared to be related to reduced survival (p = 0.0195) [3
Invasive Aspergillosis, is a major cause of morbidity and mortality in the severely immunocompromised. Risk factors include prolonged and severe neutropenia, hematopoietic stem cell and solid organ transplantation, advanced AIDS, and chronic granulomatous disease [9
]. It is rarely found in patients with solid tumors and in the absence of the afore mentioned major risks factors. In retrospective microbiology studies of patients with "proven" and "probable" invasive aspergillosis based on the European Organization for Research and Treatment of Cancer, and the Mycosis Study Group of the National Institute of Allergy and Infectious Diseases criteria between 1993-2003, only 1 of a total of 13 patients who met the criteria for invasive aspergillosis was found to have lung cancer [10
]. Steroid use and lymphopenia were common risk factors among the patients with solid tumors and invasive aspergilosis [10
]. An autopsy review at M. D. Anderson Caner Center of 588 patients with hematologic malignancies and 144 patients with solid tumors done between 1993-2002 revealed that 102 (17.3%) had hematologic malignancies, while only 1 patient (0.68%) had solid tumor (p < 0.01) [10
]. The findings of this studies, as in our case, are in agreement with previous studies that invasive aspergillosis is much more common in patients with hematologic than in solid malignancies.
Nivoix Y et al retrospectively analyzed 289 patients with presentation that fulfilled the criteria for possible, probable, or proven invasive aspergillosis according to the international definitions. The predictors of increased overall mortality were in patients who received allogenic hematopoietic stem cell or solid-organ transplant, prior respiratory disease, corticosteroid therapy, renal impairment, low monocyte counts, disseminated aspergillosis, diffuse pulmonary lesions, pleural effusion, and proven or probable aspergillosis [11
In our case, the invasive aspergillosis and the subsequently diagnosed carcinosarcoma occupied the same location of the left upper lobe. The typical tissue reaction in aspergillus pneumonia is known to be hemorrhagic infarction with a sparse inflammatory infiltrate [13
], and our case revealed similar features. In addition, despite complete course of antifungal therapy, occasional foci of residual aspergillus hyphae were identified in such areas of hemorrhagic infarction.
In conclusion, the combination of invasive aspergillosis and solid malignancies is an extremely rare occurrence. To the best of our knowledge, there has not been any reported case of pulmonary carcinosarcoma and invasive aspergillosis in the literature. Furthermore, this case report is significant because the patient did not have any of the commonly described risk factors for developing invasive aspergillosis. Limited studies found in literature have shown poor prognosis in patients with either invasive aspergillosis or pulmonary carcinosarcoma. Whether the coexistence of these two entities in a patient increases mortality remains to be determined in case series, retrospective or prospective studies.