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Gynecologic Oncology 10

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 abnor-

mality, but the CT scan showed a 4–5 cm pelvic mass. The

0090-8258/$ - see front matter D 2005 Elsevier Inc. All rights reserved.

doi:10.1016/j.ygyno.2005.08.022

* Corresponding author. Current address: Gynecologic Oncology Associates,

Greenville, SC 29605, USA. Fax: +1 864 716 6316.

E-mail address: dgriffin@anmed.com (D. Griffin).

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 produc-

tion, 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

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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 left-

sided 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, histo-

plasmosis 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 antifun-

gals, 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 deteriora-

tion 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.

Discussion

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 transplanta-

tion [2]. Prolonged and/or high-dose steroid therapy along with

cytotoxic chemotherapy has also been implicated.

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 treat-

ment 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. Fine-

needle 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.

References

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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

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[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.