Pulmonary carcinosarcoma initially presenting as invasive aspergillosis: a case report of previously unreported combination

0 Department of Medicine, Sinai Grace Hospital/Detroit Medical Center , Detroit, Michigan , USA 1 Department of Medicine, Division of Infectious Diseases, Sinai Grace Hospital/Detroit Medical Center , Detroit, Michigan , USA 2 Department of Pathology, Wayne State University and Detroit Medical Center/Sinai Grace Hospital Detroit Michigan , USA Carcinosarcoma of the lung is a malignant tumor composed of a mixture of carcinoma and sarcoma elements. The carcinomatous component is most commonly squamous followed by adenocarcinoma. The sarcomatous component commonly comprises the bulk of the tumor and shows poorly differentiated spindle cell features. Foci of differentiated sarcomatous elements such as chondrosarcoma and osteosarcoma may be seen. Aspergillus pneumonia is the most common form of invasive aspergillosis and occurs mainly in patients with malignancy, immunocompromizing or debilitating diseases. Patients with Aspergillus pneumonia present with fever, cough, chest pain and occasionally hemoptysis. Tissue examination is the most reliable method for diagnosis, and mortality rate is high. We describe a case of primary carcinosarcoma of the lung concurrently occurring with invasive pulmonary aspergillosis in a 66-year old patient. - Background Primary carcinosarcoma of the lung is exceedingly rare [1-8]. In the new World Health Organization (WHO) classification of lung tumors, it is described as malignancy composed of a mixture of carcinoma and sarcoma elements. The sarcomatous is usually spindle cell but may contain cartilage, bone or skeletal muscle components. However, controversy exists in the classification of this tumor and some authors may include sarcomatoid carcinoma in this category. Invasive pulmonary aspergillosis is a spectrum of reactions that depend on a combination of patient immunologic status, underlying lung condition and the nature of exposure to aspergillus fungus. It most often presents as aspergillus pneumonia and almost always involves immunoecompromized or debilitated patients with underlying malignancy [9]. Acute leukemia patients are very susceptible particularly during times of neutropenia. Patients with cirrhosis, chronic obstructive pulmonary disease (COPD), autoimmune deficiency syndrome (AIDS) and prolonged steroid treatment are at increased risk. Here we report a case of primary pulmonary carcinosarcoma with synchronous aspergillous pneumonia in a patient with previous prostate cancer. On review of the literature, this combination has not been reported before. Case Report A 66 years old African American man presented to the hospital with 1 week history of progressive shortness of breath and bilateral calf pain. He complained of occasional productive cough but denied any chest pain, hemoptysis, night sweats, palpitation, or dyspnea. He had a history of peripheral vascular disease and prostate cancer Gleasons score 6(3+3) about 8 years ago for which he had prostatectomy and subsequent penile implant for erectile dysfunction. He had an extensive smoking history but no alcohol or street drug abuse. Furthermore, he had a prior 8-year history of incarceration and a family history of lung cancer. Due to his chest symptoms, he had a chest x-ray followed by Computerized Tomography (CT) scan of the chest which showed a left upper lung mass (4.5 5.5 5 cm) with mediastinal and right hilar adenopathy [Fig.1]. No pleural or pericardial effusion was noted. CT of the head and bone scan revealed no metastasis. Figure 1 A CT scan with contrast of the chest showing large left upper lobe lung mass involving the pleural surface. A CT guided fine needle aspiration cytology of the left lung mass showed inflammatory necrotic background with several large aggregates of fungi. On Gomori Methanamine Silver (GMS) stain, the hyphae had uniform diameter, septation and branching at 45 degree, morphologically compatible with aspergillus species [Fig. 2]. A special stain for Acid Fast Bacilli (AFB) was negative, and no tumor cells were identified. Based on these findings, he was commenced on liposomal Amphotericin B for 2 weeks followed by Voriconazole to complete a 6 week course of antifungal therapy for pulmonary aspergillosis. His hemoglobin was 7.7 g/dl, white blood cell count 7.7 k/mm3, and absolute neutrophil, monocyte and lymphocyte count of 4.6 k/mm3, 0.6 k/mm3 and 3.2 k/mm3 respectively. Serum creatinine was 1.4 mg/dl and blood urea nitrogen 14 mg/dl. HIV and Hepatitis C serology were negative. He improved and was discharged on voriconazole. However, he presented again after about 8 weeks with new onset hemoptysis and night sweats. He subsequently had bronchoscopy with bronchoalveolar lavage (BAL) which returned negative for mycobacterium, fungus, legionella and cytomegalovirus on culture. Direct Fluorescent Antibody of BAL fluid was negative for Parainfluenza 1, Adenovirus, Herpes Simplex I&II, Respiratory Syncytial Virus, Varicella Zoster Influenza A&B and Adenovirus. BAL fluid was negative for malignant cells and Pneumocystis carinii. Pulmonary function test showed an obstructive pattern (FEV1/FVC ratio 58% of reference). He subsequently had a thoracotomy with a left upper lobectomy revealing biphasic malignant tumor (carcinosarcoma). Pathology description A left upper lobectomy (20 15.5 5.5 cm) was done. Sectioning revealed a large tan-white circumscribed partly hemorrhagic mass with central necrotic cavity. The mass was abutting the pleural surface and measured 8.5 6.5 5.5 cm of which intra-operative frozen section was diagnosed as poorly differentiated squamous cell carcinoma. Interestingly, final surgical pathology examination revealed a poorly differentiated biphasic malignant neoplasm with epithelial and spindle cell components and necrosis [Fig. 3]. The carcinomatous component showed predominantly squamous cell differentiation with foci of aborted glandular structures. The sarcomatous component displayed interlacing short fascicles of malignant spindle cells with areas of marked cellular pleomorphism and bizarre giant tumor cells. Numerous atypical mitoses and large areas of geographic necrosis were evident. Morphologically, the differential included poorly differentiated lung carcinoma with sarcomatoid growth pattern, primary pulmonary carcinosarcoma and biphasic poorly differentiated Figure 2 A GMS stain showing aspergillus fungal hyphae with uniform septated hyphae, and branching at 45 degrees (100, Gomori Methanamine Silver stain). Figure 3 Carcinosarcoma with areas of sarcomatous spindle cell proliferation (left) and an epithelial carcinoma component (right). (100, Hematoxylin and Eosin). Figure 4 Epithelial carcinoma component of the tumor positive for cytokeratin AE1/AE3 immunostain (100). synovial sarcoma. The tumor involved the pleural surface and the surgical bronchial margin. An extensive panel of immunostains was performed for further classification and more precise diagnosis. The epithelial carcinomatous tumor cells sh (...truncated)