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Ovarian cancer complicated by invasive pulmonary aspergillus
Gynecologic Oncology 100 (2006) 216 – 217 www.elsevier.com/locate/ygyno
Case Report
Ovarian cancer complicated by invasive pulmonary aspergillus Heather Scott, David Griffin * Wake Forest University School of Medicine, Department of Obstetrics and Gynecology, Winston Salem, NC 27157, USA Received 4 August 2005 Available online 19 September 2005
Abstract Background. Invasive aspergillus is a rarely reported infection in patients with solid tumors. Case. A 59-year-old woman developed invasive pulmonary aspergillus after surgical debulking of an advanced ovarian adenocarcinoma and initiation of adjuvant combination chemotherapy. Conclusion. Invasive pulmonary aspergillus is rarely diagnosed in patients with solid tumors such as ovarian cancer. Risk factors for development of the disease can include neutropenia, immunosuppression and chronic steroid use. Successful treatment of the infection relies upon prompt diagnosis and utilization of effective antifungal medications for a prolonged period of time. D 2005 Elsevier Inc. All rights reserved. Keywords: Ovary; Cancer; Pulmonary; Aspergillus; Chemotherapy
Introduction Pulmonary aspergillosis is a condition typically reported in patients with prolonged neutropenia or exposure to high dose steroids. It is most commonly associated with hematologic malignancies and has rarely been reported in patients with solid tumors. In this report, we describe a patient with advanced papillary serous adenocarcinoma and polymyalgia rheumatica on chronic steroid therapy that develops clinical findings consistent with invasive pulmonary aspergillosis. A fine-needle aspiration of the pulmonary lesion confirmed the diagnosis. Case The patient, a 59-year-old woman, presented to the clinic with a diagnosis of probable ovarian cancer. Her past medical history was significant for polymyalgia rheumatica, which had been controlled for several years on chronic prednisone therapy. Over the preceding 1.5 months, she had undergone extensive testing including both a colonoscopy and a CT scan for diffuse abdominal pain. The colonoscopy did not reveal any abnormality, but the CT scan showed a 4– 5 cm pelvic mass. The * Corresponding author. Current address: Gynecologic Oncology Associates, Greenville, SC 29605, USA. Fax: +1 864 716 6316. E-mail address: [email protected] (D. Griffin). 0090-8258/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2005.08.022
patient was then taken for laparoscopy which confirmed the pelvic mass and revealed carcinomatosis. A biopsy was obtained, and pathology showed a serous adenocarcinoma with papillary features. Further workup resulted in a serum CA-125 > 900 and a repeat CT with extensive abdominal disease consistent with ovarian cancer. A chest CT and a preoperative X-ray demonstrated no lesions but did have findings consistent with ‘‘biapical scarring’’. The patient subsequently underwent a laparotomy and debulking procedure, which was suboptimal due to extensive carcinomatosis and residual disease of approximately 2 cm. The patient did receive stress dose steroids perioperatively and was maintained on prophylactic antibiotics for 48 h. She was discharged in good condition on postoperative day 5. One week later, she presented for placement of a subcutaneous venous access device in her left chest without complications. This was followed by her first course of chemotherapy with carboplatin and docetaxel. When the patient presented for her second course of combination chemotherapy on day 21, she complained of several days of left-sided chest pain without sputum production, hemoptysis, fever or chills. Laboratory studies showed a normal D-dimer, A-a gradient and white blood cell count. A chest X-ray revealed a left upper lobe infiltrate, and she was treated with Augmentin for 10 days for a presumptive pneumonia. Her pain resolved within 24 h of initiating
H. Scott, D. Griffin / Gynecologic Oncology 100 (2006) 216 – 217
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treatment, and the airspace disease was improving on a repeat chest X-ray. She received her second course of chemotherapy without incident but subsequently developed recurrent leftsided pleuritic chest pain. A CT scan performed at that time showed interval development of a cavitary lesion within the left lung apex that was worrisome for aspergillosis. Diagnostic studies including cryptococcal antigen, histoplasmosis antigen, serum aspergillosis g. antigen and coccidioides antibody were negative. After a CT-guided fine-needle aspiration, multiple stains were also negative, but final cytology exhibited fungal organisms consistent with aspergillus. The patient refused inpatient parenteral antifungals, so she was started on voriconazole 200 mg bid. Due to concerns regarding progression of the invasive aspergillus, cytotoxic chemotherapy was temporarily discontinued, and tamoxifen was initiated. After 3 weeks of therapy, the lesion in the left upper lobe appeared to be resolving on a repeat CT scan. Unfortunately, it also revealed progression of her metastatic disease, and chemotherapy was reinitiated with single agent carboplatin and pegfilgrastim along with continuing voriconazole. Initially, the patient did well with a decreasing CA-125 and stable or improving pulmonary aspergillosis by CT scan. After three cycles of single agent carboplatin, the patient was clinically noted to have progressive disease, and this was confirmed by CA-125 and CT scan. Chemotherapy with Topotecan was then began with continued clinical deterioration and the development of a small bowel obstruction. As her performance status continued to decline, a gastrostomy tube was placed transcutaneously to relieve the symptoms of obstruction, and the patient entered hospice care. The patient continued on oral voriconazole and did not show evidence of aspergillosis relapse prior to her demise approximately 6 months after the diagnosis of pulmonary aspergillosis. No postmortem examination was performed.
The symptoms of pulmonary aspergillus can include cough, fever and pleuritic chest pain [3]. Hemoptysis can also occur and may be associated with increased mortality. A cavitary lesion on imaging studies may suggest the diagnosis which can be confirmed by serology or direct sampling of the lesion by bronchoscopy or fine-needle aspiration. The treatment of invasive aspergillus is typically parenteral and prolonged using single of combination antifungals [1]. Once stabilized, newer antifungal agents such as voriconazole allow for prolonged oral treatment. Monitoring during treatment typically relies on both clinical impression and imaging. Despite aggressive treatment, the mortality rate from invasive aspergillus remains high and depends on both the clinical condition of the patient and the extent of disease at diagnosis. In fact, the only previously reported case identified in a gynecologic oncology patient occurred in a patient with ovarian cancer receiving an autologous bone marrow transplant who died 11 days after transplant despite therapy with Amphotericin B [4]. The described case illustrates several important features of invasive pulmonary aspergillus. The patient had several risk factors for developing the disease including chronic steroid therapy, cytotoxic chemotherapy and malignancy (although not the more common hematologic type). The initial presentation was pleuritic chest pain, and imaging studies suggested consolidation. When the patient’s symptoms quickly recurred despite antibacterial therapy, imaging (CT) then revealed the characteristic cavitary lesion of invasive aspergillus. Fineneedle aspiration confirmed the diagnosis, and treatment for the fungal infection was initiated successfully. Although the diagnosis of invasive aspergillus is relatively rare in solid tumors, it should be entertained when ‘‘pneumonia’’ is unresponsive to antibacterials and/or the patient’s clinical condition deteriorates despite adequate therapy.
Discussion
References
Although it is one of the most common invasive mycosis, invasive aspergillus is a relatively rare disease [1]. It typically manifests with pulmonary involvement, although the remainder of the respiratory tract along with the skin and brain can also be involved. It has most often been reported in patients with significant immunosuppression such as that encountered during treatment of hematologic malignancies and after transplantation [2]. Prolonged and/or high-dose steroid therapy along with cytotoxic chemotherapy has also been implicated.
[1] Maschmeyer G, Ruhnke M. Update on antifungal treatment of invasive Candida and Aspergillus infections. Mycoses 2004;47:263 – 76. [2] Silveira F, Paterson DL. Pulmonary fungal infections. Curr Opin Pulm Med 2005;11(3):242 – 6. [3] Schwartz S, Thiel E. Clinical presentation of invasive aspergillus. Mycosis 1997;40(Suppl. 2):21 – 4. [4] Stiff P, Bayer R, Camarda M, Tan S, Dolan J, Potkul R, et al. A phase 2 trial of high dose mitoxantrone, carboplatin, and cyclophosphamide with autologous bone marrow rescue for recurrent epithelial ovarian carcinoma: analysis of risk factors for clinical outcome. Gyn Oncol 1995;57:278 – 85.
Case Report
Ovarian cancer complicated by invasive pulmonary aspergillus Heather Scott, David Griffin * Wake Forest University School of Medicine, Department of Obstetrics and Gynecology, Winston Salem, NC 27157, USA Received 4 August 2005 Available online 19 September 2005
Abstract Background. Invasive aspergillus is a rarely reported infection in patients with solid tumors. Case. A 59-year-old woman developed invasive pulmonary aspergillus after surgical debulking of an advanced ovarian adenocarcinoma and initiation of adjuvant combination chemotherapy. Conclusion. Invasive pulmonary aspergillus is rarely diagnosed in patients with solid tumors such as ovarian cancer. Risk factors for development of the disease can include neutropenia, immunosuppression and chronic steroid use. Successful treatment of the infection relies upon prompt diagnosis and utilization of effective antifungal medications for a prolonged period of time. D 2005 Elsevier Inc. All rights reserved. Keywords: Ovary; Cancer; Pulmonary; Aspergillus; Chemotherapy
Introduction Pulmonary aspergillosis is a condition typically reported in patients with prolonged neutropenia or exposure to high dose steroids. It is most commonly associated with hematologic malignancies and has rarely been reported in patients with solid tumors. In this report, we describe a patient with advanced papillary serous adenocarcinoma and polymyalgia rheumatica on chronic steroid therapy that develops clinical findings consistent with invasive pulmonary aspergillosis. A fine-needle aspiration of the pulmonary lesion confirmed the diagnosis. Case The patient, a 59-year-old woman, presented to the clinic with a diagnosis of probable ovarian cancer. Her past medical history was significant for polymyalgia rheumatica, which had been controlled for several years on chronic prednisone therapy. Over the preceding 1.5 months, she had undergone extensive testing including both a colonoscopy and a CT scan for diffuse abdominal pain. The colonoscopy did not reveal any abnormality, but the CT scan showed a 4– 5 cm pelvic mass. The * Corresponding author. Current address: Gynecologic Oncology Associates, Greenville, SC 29605, USA. Fax: +1 864 716 6316. E-mail address: [email protected] (D. Griffin). 0090-8258/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2005.08.022
patient was then taken for laparoscopy which confirmed the pelvic mass and revealed carcinomatosis. A biopsy was obtained, and pathology showed a serous adenocarcinoma with papillary features. Further workup resulted in a serum CA-125 > 900 and a repeat CT with extensive abdominal disease consistent with ovarian cancer. A chest CT and a preoperative X-ray demonstrated no lesions but did have findings consistent with ‘‘biapical scarring’’. The patient subsequently underwent a laparotomy and debulking procedure, which was suboptimal due to extensive carcinomatosis and residual disease of approximately 2 cm. The patient did receive stress dose steroids perioperatively and was maintained on prophylactic antibiotics for 48 h. She was discharged in good condition on postoperative day 5. One week later, she presented for placement of a subcutaneous venous access device in her left chest without complications. This was followed by her first course of chemotherapy with carboplatin and docetaxel. When the patient presented for her second course of combination chemotherapy on day 21, she complained of several days of left-sided chest pain without sputum production, hemoptysis, fever or chills. Laboratory studies showed a normal D-dimer, A-a gradient and white blood cell count. A chest X-ray revealed a left upper lobe infiltrate, and she was treated with Augmentin for 10 days for a presumptive pneumonia. Her pain resolved within 24 h of initiating
H. Scott, D. Griffin / Gynecologic Oncology 100 (2006) 216 – 217
217
treatment, and the airspace disease was improving on a repeat chest X-ray. She received her second course of chemotherapy without incident but subsequently developed recurrent leftsided pleuritic chest pain. A CT scan performed at that time showed interval development of a cavitary lesion within the left lung apex that was worrisome for aspergillosis. Diagnostic studies including cryptococcal antigen, histoplasmosis antigen, serum aspergillosis g. antigen and coccidioides antibody were negative. After a CT-guided fine-needle aspiration, multiple stains were also negative, but final cytology exhibited fungal organisms consistent with aspergillus. The patient refused inpatient parenteral antifungals, so she was started on voriconazole 200 mg bid. Due to concerns regarding progression of the invasive aspergillus, cytotoxic chemotherapy was temporarily discontinued, and tamoxifen was initiated. After 3 weeks of therapy, the lesion in the left upper lobe appeared to be resolving on a repeat CT scan. Unfortunately, it also revealed progression of her metastatic disease, and chemotherapy was reinitiated with single agent carboplatin and pegfilgrastim along with continuing voriconazole. Initially, the patient did well with a decreasing CA-125 and stable or improving pulmonary aspergillosis by CT scan. After three cycles of single agent carboplatin, the patient was clinically noted to have progressive disease, and this was confirmed by CA-125 and CT scan. Chemotherapy with Topotecan was then began with continued clinical deterioration and the development of a small bowel obstruction. As her performance status continued to decline, a gastrostomy tube was placed transcutaneously to relieve the symptoms of obstruction, and the patient entered hospice care. The patient continued on oral voriconazole and did not show evidence of aspergillosis relapse prior to her demise approximately 6 months after the diagnosis of pulmonary aspergillosis. No postmortem examination was performed.
The symptoms of pulmonary aspergillus can include cough, fever and pleuritic chest pain [3]. Hemoptysis can also occur and may be associated with increased mortality. A cavitary lesion on imaging studies may suggest the diagnosis which can be confirmed by serology or direct sampling of the lesion by bronchoscopy or fine-needle aspiration. The treatment of invasive aspergillus is typically parenteral and prolonged using single of combination antifungals [1]. Once stabilized, newer antifungal agents such as voriconazole allow for prolonged oral treatment. Monitoring during treatment typically relies on both clinical impression and imaging. Despite aggressive treatment, the mortality rate from invasive aspergillus remains high and depends on both the clinical condition of the patient and the extent of disease at diagnosis. In fact, the only previously reported case identified in a gynecologic oncology patient occurred in a patient with ovarian cancer receiving an autologous bone marrow transplant who died 11 days after transplant despite therapy with Amphotericin B [4]. The described case illustrates several important features of invasive pulmonary aspergillus. The patient had several risk factors for developing the disease including chronic steroid therapy, cytotoxic chemotherapy and malignancy (although not the more common hematologic type). The initial presentation was pleuritic chest pain, and imaging studies suggested consolidation. When the patient’s symptoms quickly recurred despite antibacterial therapy, imaging (CT) then revealed the characteristic cavitary lesion of invasive aspergillus. Fineneedle aspiration confirmed the diagnosis, and treatment for the fungal infection was initiated successfully. Although the diagnosis of invasive aspergillus is relatively rare in solid tumors, it should be entertained when ‘‘pneumonia’’ is unresponsive to antibacterials and/or the patient’s clinical condition deteriorates despite adequate therapy.
Discussion
References
Although it is one of the most common invasive mycosis, invasive aspergillus is a relatively rare disease [1]. It typically manifests with pulmonary involvement, although the remainder of the respiratory tract along with the skin and brain can also be involved. It has most often been reported in patients with significant immunosuppression such as that encountered during treatment of hematologic malignancies and after transplantation [2]. Prolonged and/or high-dose steroid therapy along with cytotoxic chemotherapy has also been implicated.
[1] Maschmeyer G, Ruhnke M. Update on antifungal treatment of invasive Candida and Aspergillus infections. Mycoses 2004;47:263 – 76. [2] Silveira F, Paterson DL. Pulmonary fungal infections. Curr Opin Pulm Med 2005;11(3):242 – 6. [3] Schwartz S, Thiel E. Clinical presentation of invasive aspergillus. Mycosis 1997;40(Suppl. 2):21 – 4. [4] Stiff P, Bayer R, Camarda M, Tan S, Dolan J, Potkul R, et al. A phase 2 trial of high dose mitoxantrone, carboplatin, and cyclophosphamide with autologous bone marrow rescue for recurrent epithelial ovarian carcinoma: analysis of risk factors for clinical outcome. Gyn Oncol 1995;57:278 – 85.