Candida glabrata infection in gastric carcinoma patient mimicking cutaneous histoplasmosis
Department of Pathology, University of Miami, Jackson Memorial Hospital. firstname.lastname@example.org
Candida glabrata is the second most common Candida species detected among hospitalized patients in USA. In tissue C. glabrata present as yeasts, 3-5 microns in size, which are difficult to visualize on H&E stained slides but can be detected on Grocott methenamine silver (GMS) stained slides. The presence of yeasts only, without any hyphal elements, makes C. glabrata difficult to distinguish from Histoplasma capsulatum yeasts that are of similar size. Mycology culture is the method of choice for definitive identification of C. glabrata. Rapid identification is necessary, as mortality rate due to C. glabrata infection in immunocompromised patients is particularly high. We herein report a patient with inoperable gastric carcinoma, who developed cutaneous and septic form of C. glabrata infection.
We present the case of 62 year-old Haitian man diagnosed with infiltrating, poorly differentiated gastric carcinoma. The tumor was found to be inoperable and patient was given palliative therapy. At the time of diagnosis, the patient had a fever of 39.5°C. On the lateral side of his right arm, an indurate, pale tan plaque, measuring 0.8 cm in largest diameter, was seen. A punch biopsy of skin lesion was obtained for histological evaluation as well as for bacterial, mycobacterial and fungal cultures. Histological examination showed deep dermal and subcutaneous necrosis with acute neutrophilic inflammation. No infectious organisms could be readily appreciated on routine hematoxylin-eosin (H&E) stained slides (Figs. 1 and 2). However, the GMS revealed numerous yeasts, 3-5 microns in size, present within the dermis and subcutis (Fig. 3). Because only yeasts without hyphal and pseudohyphal elements were found, histoplasmosis was suspected. Mycology culture was recommended to further classify the fungal elements. Candida glabrata was identified in the culture whilst no cultures were positive for Histoplasma spp. At the same time C. glabrata and Klebsiella pneumoniae were found in the blood culture. The patient was treated with caspofungin (50 mg IV) and ceftriaxone (2 mg IV). Given the persistent infection that did not improve despite the administered drugs, he was not started on chemotherapy. A month after initial diagnosis the patient expired.
The risk of opportunistic infections is greatly increased in patients who are immunocompromised because of AIDS, cancer, chemotherapy and organ or bone-marrow transplantation [1, 2]. In the last few decades the importance of candidemia in oncology patients, its changing epidemiology patterns, and significant morbidity and mortality rate has been recognized [3-18]. In humans, candidiasis is caused by 13 species, most frequently by the following: C. albicans, C. tropicalis, C. glabrata, C. krusei, C. parapsilosis, C. lusitanie and others. Historically, C. albicans accounted for over half of the isolates recovered from infected patients. However, more recent epidemiological data reveal a mycological shift from C. albicans to the non-albicans Candida spp, especially C. glabrata and C. krusei [3-8, 19, 20]. The results of the 2003 longitudinal SENTRY antimicrobial surveillance program positioned C. glabrata, with 12.7 percent of isolates, as the second ranked among Candida species in patients from North America. Most of C. glabrata infections arise from the host's endogenous microflora . During a prospective evaluation of Candida species associated with either clinically significant colonization or infection, 26.9 percent of C. glabrata isolates showed in vitro resistance to fluconazole (MIC of > or = 64 μg/ml) and reduced susceptibility to newer azoles (ravuconazole, voriconazole) [12, 21].
Clinically, candidiasis may present as acute and chronic mucocutaneous form, and as disseminated disease . C. albicans can cause localized and disseminated disease whereas other Candida species are associated with systemic disease more commonly then localized disease. Histologically, mucocutaneous candidiasis has following features: 3-6μm yeasts, pseudohyphae and hyphae in stratum corneum, subcorneal pustules, and vesicles . Occasionally, candidal granuloma may form with prominent hyperkeratosis and papillomatosis, together with dense dermal infiltrate of giant cells. Disseminated candidiasis, on the other hand, demonstrates pseudohyphae, hyphae, and yeasts (which may show budding) localized in dermis near blood vessels with perivascular inflammatory infiltrate and leukocytoclastic vasculitis . In contrast to C. albicans tissue, infection with C. glabrata present as yeasts 3-5 microns in size that are difficult to visualize on H&E stained slides but can be detected on GMS or PAS stained slides. The presence of yeasts only, without any hyphal elements, makes C. glabrata difficult to distinguish from Histoplasma capsulatum yeasts that are just slightly smaller (2-4 microns).
Patients with solid tumors (such was in our case), with acute leukemia, and hematological patients on antifungal prophylaxis are significantly associated with non-albicans candidemia. The reported overall 30-day mortality is 39 percent. In a univariate analysis, C. glabrata is associated with the highest mortality rate (odds ratio 2.6) .
Dermatopathologists may not be familiar with the histological presentation of C. glabrata. This case highlights that for immunocompromised cancer patients presenting with cutaneous lesions with histomorphology resembling H. capsulatum infection, one should always take into consideration the following: first (i) the possible presence of underlying life-threatening systemic mycosis and second (ii) Candida glabrata may be the infectious agent (especially in the light of new epidemiology trends which indicate increased frequency of mucosal and systemic infections caused by this agent). Early and accurate classification of fungal elements should secure a choice of an efficient antimycotic drug and, ultimately, a higher survival rate for the patient. Mycology culture is still the gold standard for identification of fungi, especially species that do not form pseudohyphae in vivo.
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