Isolated bone marrow mycosis in a patient presenting with consumptive symptoms
- 1Institute of Pathology, University of Innsbruck, 6020 Innsbruck, Austria
- 2Department of Internal Medicine, Helios Hospital, A-6370 Kitzbühel, Austria
- 3Laboratory of Microbiology Doz. J. Möst, A-6020 Innsbruck, Austria
- 4Institute of Pathology, University of Basel, CH-4031 Switzerland
- 5Institute of Pathology, University of Innsbruck;
The incidence of systemic mycoses is increasing as a result of the escalating number of patients who are immunocompromised because of diabetes mellitus, haemodialysis, organ and bone marrow transplants, chemotherapy for cancer, and infections with human immunodeficiency virus (HIV), in addition to the broad use of antibiotics.1 If such predisposing factors for fungaemia are absent, fungal infections are rarely considered in the differential diagnosis when clinical status non-specifically worsens. The diagnosis of fungal infections is based on histology, cultural evidence, or serological tests.2 Histological proof of mycosis is regarded as very reliable, because the pathogenic agent can be unequivocally detected within the affected structures.3 Bone marrow examination might be a useful tool for the examination of cryptic infections, especially in HIV positive patients, with an overall diagnostic yield of 32% and 6% for fungal diseases, respectively.4 However, so far, isolated bone marrow mycoses in non-neutropenic, immunocompetent patients, without evidence of fungaemia or septicaemia, have not been reported.
We report the case of a 76 year old female patient who had experienced a 13% weight loss over six months. She complained of increasing tiredness and night sweats but denied having dyspnoea or pains. Her body temperature was 37.3°C. Laboratory examination revealed a raised platelet count (582 × 109/litre), C reactive protein (154 mg/litre), and sedimentation rate (21 mm/hour), but normal parameters for electrolytes, glucose, haemoglobin A1c, serum proteins, and liver enzymes; in addition, she was negative for hepatitis (hepatitis B virus (HBV) and HCV) and HIV serology, and had a normal differential blood count. Transferrin was slightly reduced and ferritin was raised. Thus, an underlying malignant disease was suspected. Both computerised imaging of the chest and abdomen and coloscopy were normal. A gastric biopsy revealed minimal reactive mucosal changes without Helicobacter pylori infection. An x ray of the skull showed right maxillary sinusitis. Histological examination of the nasal mucosa revealed mucocele without evidence of fungal structures. Blood culture analyses, including specific subcultures for fungi, were negative on three different occasions. Finally, a trephine bone marrow biopsy was performed to exclude lymphoma or leukaemia. Myelopoiesis was left shifted, but the remaining haemopoiesis was otherwise unremarkable. Notably, scattered within the bone marrow interstitium and around vascular structures, elongated budding yeast and pseudohyphae with branching and constriction at the septa and production of oval blastospores near the septa were histologically detected (fig 1). The microorganisms stained positively in the periodic acid Schiff reaction, but remained to a great extent negative in the Grocott stain and, therefore, were considered consistent with candida species. A minimal interstitial bone marrow necrosis close to the pseudohyphae3 was observed (fig 1, lower left). Because the biopsy was formalin fixed, it was not submitted for culture. The angiocentricity of the mycotic elements and the discrete interstitial necrosis close to the pseudohyphae were notable for their pathogenicity. Nevertheless, the possibility of contamination was considered. However, the patient’s skin was clinically unremarkable and thoroughly disinfected before performing the biopsy, and the bone marrow trephine had been fixed immediately. Thus, an isolated bone marrow mycosis highly suspicious for candida species was diagnosed. Aimed serological examination revealed raised anti-Candida albicans IgG and IgM antibodies (enzyme linked immunosorbent assay; IBL, Hamburg, Germany). The patient was given amphotericin B (0.3 mg/kg) and flucytosine (150 mg/kg) intravenously for 50 days and her clinical condition gradually improved. No fungal structures could be detected in two control bone marrow biopsies two and three months after initial diagnosis. No obvious portal of entry for this fungal infection could be elucidated. Except for the advanced age of the patient, all other risk factors for fungaemia, such as an infection with HIV, HBV, or HCV, diabetes, or immunosuppression were excluded.1
A trephine bone marrow biopsy can play a key role in the diagnostic investigation of patients with obscure consumptive symptoms. Isolated bone marrow mycosis can occur in immunocompetent patients even without an obvious portal of entry.