Liquid-Based Cytology of the Cerebrospinal Fluid in a Case of Cryptococcal Meningitis

Cryptococcus neoformans is the most common microorganism found in cerebrospinal fluid (CSF) cytology and causes life-threatening infections in immunocompromised hosts. Although its cytomorphologic features in conventional smear cytology have been well described, those in liquid-based cytology have rarely been. A 73-year-old woman with diffuse large B-cell lymphoma presented with mental confusion and a spiking fever. To rule out infectious conditions, CSF examination was performed. A cytology slide that was prepared using the ThinPrep method showed numerous spherical yeast-form organisms with diameters of 4–11 μm and thick capsules. Occasional asymmetrical, narrow-based budding but no true hyphae or pseudohyphae were observed. Gomori methenamine silver staining was positive. Cryptococcosis was confirmed in blood and CSF through the cryptococcal antigen test and culture. Liquid-based cytology allows for a clean background and additional slides for ancillary testing, facilitating the detection of microorganisms in CSF specimens, particularly when the number of organisms is small.

Acid-Fastness of Histoplasma in Surgical Pathology Practice

BACKGROUND: Histoplasmosis (HP) is diagnosed by visualizing intracellular microorganisms in biopsy and/or culture. Periodic-acid Schiff (PAS) and Gomori methenamine silver (GMS) staining methods are routinely used for identification. The acid-fast property of Histoplasma was identified decades ago, but acid-fast staining has not been practiced in current surgical pathology. Awareness of the acid-fast property of Histoplasma, which is due to mycolic acid in the cell wall, is important in distinguishing Histoplasma from other infective microorganisms. Here, we examined acid-fastness in previously diagnosed cases of Histoplasma using the Ziehl-Neelsen (ZN) stain and correlated those findings with other known fungal stains. METHODS: All cases diagnosed as HP were retrieved and reviewed along with ZN staining and other fungal stains. We also stained cases diagnosed with Cryptococcus and Leishmania as controls for comparison. RESULTS: A total of 54 patients ranging in age from 11 to 69 years were examined. The most common sites of infection were the skin, adrenal tissue, and respiratory tract. Of the total 43 tissue samples, 20 (46.5%) stained positive with the ZN stain. In viable cases, a significant proportion of microorganisms were positive while necrotic cases showed only rare ZN-positive yeasts. In comparison to PAS and GMS stains, there was a low burden of ZN-positive yeasts. Cryptococcus showed characteristic ZN staining and all cases of Leishmania were negative. CONCLUSIONS: Although the morphology of fungal organisms is the foundation of identification, surgical pathologists should be aware of the acid-fast property of fungi, particularly when there is the potential for confusion with other infective organisms.

Cryptococcus Species Infection in a Bone Marrow Transplant Patient and Review of the Literature / 대한의진균학회지

Cryptococcosis is caused by several Cryptococcus species, including C. neoformans and C. gattii. Skin involvement is seen in 10~20% of systemic cryptococcosis. There are also rare cases of primary cutaneous cryptococcosis in which skin-penetrating trauma is the alleged mechanism of infection. A 16-year-old male presented with multiple, 0.2~0.3 cm-sized, brownish papules on the whole body for 2 weeks. He had past history of acute lymphoblastic leukemia and received bone marrow transplant 1 year ago. After leukemia had recurred 1 month ago and after chemotherapy, multiple brownish papules developed. Histopathologic examinations revealed narrow-based budding yeasts in hematoxylin and eosin, Periodic acid-Schiff, and Gomori methenamine silver stains. Also in mucicarmine stain there were pink-colored capsules around the cell walls. Finally it was diagnosed as deep fungal infection due to Cryptococcus species. In spite of administrating fluconazole, the patient expired due to respiratory failure caused by pneumonia. Herein, we report a case of Cryptococcus species infection in a bone marrow transplant patient.

A Case of Localized Skin Infection due to Purpureocillium lilacinum / 대한의진균학회지

Purpureocillium lilacinum, formerly Paecilomyces lilacinus, is a saprophytic fungus found in soil and rotting vegetation and rarely pathogenic to humans. Only 4 cases of cutaneous infection caused by Purpureocillium lilacinum have been reported in the name of Paecilomyces lilacinus. Herein, we report a case of localized cutaneous infection due to Purpureocillium lilacinum. A healthy 81-year-old immunocompetent male presented with an erythematous scaly and pustular plaque on his left dorsal hand that had begun 3 months ago. Histopathologic examination showed suppurative granulomatous inflammation with hyphae and round spores in the dermis. Periodic acid-Schiff and methenamine silver stain revealed fungal spores. Fungus culture from the biopsy specimen revealed velvety pink to white colonies after 15 day-incubation period. The slide culture stained with lactophenol-cotton blue showed typical long hyphae and flask-shaped phialides with oval conidia in chains. The result of DNA sequencing from the colony was identical to that of Purpureocillium lilacinum.

Candida famata Infection Presenting as an Erosive Patch on the Sole of an Immunocompetent Patient / 대한피부과학회지

Candida famata previously called Torulopsis famata or Debaryomyces hansenii, is usually found in natural substrates. It was earlier considered nonpathogenic in humans; however, a number of clinical cases of human infection have been reported showing isolation of this yeast. Dermatologic literature contains only a few reports regarding cutaneous infection caused by Candida famata. An 18-year old woman presented with a 4-month history of a 4.0×3.0 cm sized erythematous erosive patch on her left sole. A skin biopsy revealed numerous spores and hyphae in the epidermis. Histopathological specimens showed positive findings using the Periodic acid-Schiff and Gomori methenamine silver stains but negative findings using acid-fast bacilli stain. Cultures from skin scrapings yielded numerous colonies. Identification of the fungus was processed up to species level using VITEK 2 (bioMérieux, Inc. Hazelwood, MO, USA), and Candida famata was isolated. She was administered itraconazole at a dose of 200 mg once daily, and following 5 weeks of therapy, the erosive lesion was noted to have completely healed with postinflammatory hyperpigmentation.

Pneumocystis jirovecii Pneumonia with Granulomatous Reaction in the Lung and the Liver Discovered at Autopsy / 대한법의학회지

We report the case of a 42-year-old woman who died in hospital from severe respiratory failure, 10 days after the onset of symptoms. Autopsy and microscopic examination identified features of diffuse alveolar damage in both lungs including hyaline membranes and intra-alveolar exudate. Gomori's methenamine silver stain of pink frothy materials in these exudates revealed thin-walled and cup-shaped microorganisms and a diagnosis of Pneumocystis jirovecii pneumonia was made. There were small granulomas in the pulmonary interstitium and hepatic lobules representing an unusual inflammatory reaction against Pneumocystis jirovecii. Extrapulmonary involvement with pneumocystis infection is a rare event occurring in 1% to 2% of all pneumocystis cases. Screening and confirmatory tests for human immunodeficiency virus (HIV) detection were positive. There was no information available regarding the patient's medical history or the possibility of HIV infection prior to the autopsy, because the patient was a foreign worker who arrived in Korea 2 months before her death. Medical examiners often perform autopsies with limited information regarding the deceased person, even when person is a Korean national. Therefore, an awareness of protection protocols during autopsy, as well as of the atypical patterns of critical diseases, is crucial.

A Case of Disseminated Cryptococcosis Mimicking Lung Cancer and Prostate Cancer in an Immunocompetent Patient: A Review of the Literature / 대한내과학회지

Cryptococcosis can occur in immunocompetent patients; in fact, it accounts for 20% of all cryptococcal infections. In immunocompetent patients, although clinical symptoms may not be obvious, cryptococcosis should be considered in the differential diagnosis for cancer and other diseases. We recently encountered a case of disseminated cryptococcosis involving the lung and prostate. A 71-year-old male patient was referred for evaluation of a large pleural effusion. He was a 40 pack-years ex-smoker, and showed no evidence of immunodeficiency. Chest computed tomography and positron emission tomography images suggested primary lung cancer with pleural metastases and prostate cancer. Tuberculous pleurisy was suspected due to a lymphocyte-dominant exudative pleural effusion and high level of adenosine deaminase. Prostate and bronchoscopic biopsies demonstrated chronic granulomatous inflammation, and periodic acid Schiff's and Grocott's methenamine silver staining confirmed cryptococcosis in both specimens. Antifungal therapy with fluconazole was started, and follow-up images showed complete resolution of the pleural effusion.

Spontaneous Pneumomediastinum, Pneumopericardium, and Pneumothorax with Respiratory Failure in a Patient with AIDS and Pneumocystis jirovecii Pneumonia / 감염과화학요법

Spontaneous pneumothorax occurs in up to 35% of patients with Pneumocystis jirovecii pneumonia. However, spontaneous pneumomediastinum and pneumopericardium are uncommon complications in patients infected with human immunodeficiency virus, with no reported incidence rates, even among patients with acquired immunodeficiency syndrome (AIDS) and P. jirovecii pneumonia. We report a case of spontaneous pneumomediastinum, pneumopericardium, and pneumothorax with respiratory failure during treatment of P. jirovecii pneumonia in a patient with AIDS; the P. jirovecii infection was confirmed by performing methenamine silver staining of bronchoalveolar lavage specimens. This case suggests that spontaneous pneumomediastinum and pneumopericardium should be considered in patients with AIDS and P. jirovecii pneumonia.

A Case of Isolated Orbital Sarcoidosis

PURPOSE: The authors report a case of orbital sarcoidosis without evidence of systemic involvement. CASE SUMMARY: A 33-year-old female had a 1 month history of erythematous eyelid swelling. On physical examination, a firm and non-tender mass was observed diffusely along the upper, lower and medial canthal areas. A computed tomography (CT) scan showed a diffuse mass in the anterior orbit. We performed an incisional biopsy and histopathological examination revealed non-caseating granulomas and no evidence of a foreign body. Acid-fast-bacilli (AFB), methenamine silver and periodic-acid-schiff (PAS) stain showed no evidence of infection and chest radiograph was normal. Polymerase chain reaction (PCR) and interferon gamma secretion test showed no evidence of tuberculosis. Antinuclear antibody (ANA) and antineutrophil cytoplasmic antibody (ANCA) were negative and angiotensin converting enzyme (ACE) was within the normal range. Further systemic evaluations were compatible with a diagnosis of orbital sarcoidosis and oral prednisone was prescribed. Six weeks later, the erythematous eyelid swelling had disappeared and there was no evidence of recurrence to date.

A Case of Cutaneous Infection by Alternaria alternata / 대한의진균학회지

Alternaria(A.) species are common saprophyte found in the environment such as soil, air, and plants. They are not usually pathogenic in humans but recently, infections by these fungi have occasionally been reported, occurring mostly in immunocompromised patients. They can cause hypersensitivity pneumonitis, bronchial asthma, or allergic rhinitis and rarely skin infection. A 76-year-old man presented with multiple erythematous papules, plaque and pustules with purpuric patches on both forearms and dorsal hands for 6 months. He had been treated for Parkinson's disease and dementia for 3 years but had not been taking any immunosuppressants. Direct smear with KOH was negative. Histopatholoigically, neutrophilic abscess, suppurative granulomatous inflammation and round spores were observed in the dermis. Periodic acid-Schiff and Methenamine silver stains revealed round to oval shaped spores. The biopsy specimen was cultured in potato dextrose agar and a cottony olive green to gray colored colony with black to brown reverse grew at 7 days of culture. The slide culture stained with lactophenol-cotton blue showed brown septated hyphae and obclavate conidia with brown muriform septation. The nucleotide sequences of the ribosomal internal transcribed spacer region of cultured colonies and paraffin blocks of biopsy specimen were identical to that of A. alternata. He was treated with topical ketoconazole cream application for 4 months, and healed leaving hyperpigmentation with scales.

A Case of Invasive Pulmonary Aspergillosis with Direct Invasion of the Mediastinum and the Left Atrium in an Immunocompetent Patient / 결핵및호흡기질환

We report a case of invasive pulmonary aspergillosis invading the mediastinum and the left atrium. A 70-year-old woman was hospitalized for dyspnea. She had been well controlled for her diabetes mellitus and hypertension. The chest X-ray disclosed mediastinal widening, and the computed tomography scan of the chest showed that there was a large mediastinal mass and this lesion extended into the left atrium and right bronchus. The cardiac echocardiography showed that a huge mediastinal cystic mass compressed in the right atrium and a hyperechoic polypoid lesion in the left. The pathology from the bronchoscopic biopsy observed abundant fungal hyphae which was stained with periodic acid-Schiff and Gomori's methenamine silver. Despite the treatment with antifungal agents, she died from cardiac tamponade after three months. Invasive pulmonary aspergillosis, which involves the mediastinum and the heart, is very rare in immunocompetent patients.

A Case of Invasive Pulmonary Aspergillosis with Direct Invasion of the Mediastinum and the Left Atrium in an Immunocompetent Patient / 결핵및호흡기질환

We report a case of invasive pulmonary aspergillosis invading the mediastinum and the left atrium. A 70-year-old woman was hospitalized for dyspnea. She had been well controlled for her diabetes mellitus and hypertension. The chest X-ray disclosed mediastinal widening, and the computed tomography scan of the chest showed that there was a large mediastinal mass and this lesion extended into the left atrium and right bronchus. The cardiac echocardiography showed that a huge mediastinal cystic mass compressed in the right atrium and a hyperechoic polypoid lesion in the left. The pathology from the bronchoscopic biopsy observed abundant fungal hyphae which was stained with periodic acid-Schiff and Gomori's methenamine silver. Despite the treatment with antifungal agents, she died from cardiac tamponade after three months. Invasive pulmonary aspergillosis, which involves the mediastinum and the heart, is very rare in immunocompetent patients.

Pulmonary Cryptococcosis in Rheumatoid Arthritis Patient Treated With Leflunomide

Leflunomide, a disease-modifying antirheumatic drug, is effective for rheumatoid arthritis as monotherapy or combination therapy with methotrexate. The most common adverse effects are diarrhea, dyspepsia, nausea, abdominal pain, oral ulcer, hepatotoxicity, skin rash, hypertension, weight loss, and interstitial lung disease. The occurrence of pulmonary cryptococcosis in leflunomide treatment has not been reported in Korea. A 74-year-old woman was admitted to hospital due to asymptomatic pulmonary nodule. She was diagnosed rheumatoid arthritis and treated with leflunomide 5 months ago due to treatment failure with methotrexate, hydroxychloroquine, and sulfasalazine. Chest radiograph and computed tomography showed solitary pulmonary nodule in her right lower lung. Pulmonary cryptococcosis was confirmed by needle biopsy of lung stained with Gomori methenamine silver and mucicarmine. The lesion was improved after antifungal therapy for 3 months.

Pneumonia Caused by Corynebacterium macginleyi in HIV-infected Patient / 감염과화학요법

Corynebacterium macginleyi is usually isolated from the eye surfaces and causes ocular infections such as conjunctivitis, keratitis, and endophthalmitis. However, cases that describe C. macginleyi as the causative agent for significant and life-threatening infections in immunocompromised patients are increasingly reported. Herein we report the first documented case of C. macginleyi pneumonia in a human immunodeficiency virus (HIV) patient. A 42-year-old homosexual man with HIV infection was hospitalized with a 1-month history of fever and dry cough. Chest radiograph revealed ill defined ground glass opacities in both lung fields. Methenamine silver stain of bronchoalveolar lavage fluid was negative. He showed clinical improvement after treatment with trimethoprim/sulfamethoxazole and prednisolone for three weeks, and was discharged. One month later, he presented with dyspnea and more progressive pulmonary infiltrations. Bronchial washing fluid culture yielded >100,000 colonies/mL of C. macginleyi, and he was given a 14-day course of antibiotic therapy with vancomycin, after which the patient fully recovered. This case suggest the importance of not overlooking the significance of positive cultures for C. macginleyi obtained from representative clinical samples in patients with signs and symptoms of bacterial infection.

The Clinical, Histopathologic and Mycologic Characteristics of Dermatophytosis Which were Initially Diagnosed by Skin Biopsies / 대한피부과학회지

BACKGROUND: Dermatophytosis is sometimes difficult to definitively diagnose if it has atypical clinical characteristics or the mycological tests are negative. For these cases, skin biopsy will be helpful to diagnose a fungal infection. OBJECTIVE: The purpose of the present study was to evaluate the clinical, histopathologic and mycologic characteristics of dermatophytosis patients who were initially diagnosed by skin biopsies. METHODS: We performed a retrospective study of the clinical characteristics and the histopathologic and mycologic features of 16 patients with dermatophytosis and who were initially diagnosed by skin biopsy. RESULTS: The final diagnosis of dermatophytic infections were tinea incognito (7 cases) and Majocchi's granuloma (9 cases). The main symptoms were pruritus (4 cases) and pain (2 cases). The skin lesions of tinea incognito and Majocchi's granuloma mimicked inflammatory skin disease, lupus vulgaris or deep mycosis. The most common site of involvement was the face. The possible predisposing factors causing tinea incognito and Majocchi's granulomas appeared to be application of steroid ointment (6 cases), physical trauma (2 cases) and diabetes mellitus (1 case). The histopathologic features of tinea incognito revealed the sandwich sign (100%) and neutrophils in the epidermis (71.5%) and dermis (71.5%). Majocchi's granuloma showed rupture of hair follicles (88.9%) and suppurative folliculitis (66.7%). With Periodic acid Schiff and methenamine silver staining, hyphae and spores could be identified on the horny layers, within the hair follicles and/or on the dermis in the biopsy specimens of all the cases. Culture of the causative organisms using dermal fragments and skin scales on Sabouraud media demonstrated Trichophyton rubrum (4 cases), T. mentagrophytes (3 cases) and Microsporum canis (3 cases). Systemic treatment with itraconazole or terbinafine for 2~10 weeks was effective, except for two cases. CONCLUSION: We consider that the histopatholgic findings may be of great help to diagnose a dermatophytosis that has atypical clinical characteristics or negative mycological tests. Fungal culture is also important for making an accurate diagnosis of dermatophytosis.

Subcutaneous Candidal Abscess in the Patient with Iatrogenic Cushing Syndrome / 대한의진균학회지

Candida albicans is a dimorphic yeast which is responsible for 70 percent to 80 percent of all candidial infection, and is the most common cause of superficial and systemic candidiasis. Invasive candidiasis occurs under certain circumstances such as immunosuppression, prolonged hospitalization, and previous antibiotics use. We report a case of candidiasis with a unusual presentation of subcutaneous abscess. A 54 year-old woman came to our clinic with painful erythematous swelling plaques and nodules on the face and arms. She was hospitalized with generalized edema and weakness of both leg. She had a history of herbal medication for 1 year and was finally diagnosed with iatrogenic Cushing syndrome in department of the endocrinology. Biopsy of the lesion revealed chronic inflammation in dermis and subcutis and budding yeasts with pseudohyphae were shown in Gomoris Methenamine silver stain. And Candida albicans was identified by fungus culture.

Pneumocystis jiroveci Pneumonia Mimicking Miliary Tuberculosis in a Kidney Transplanted Patient / 결핵및호흡기질환

Bilateral interstitial infiltration in chest radiography, which may be fine granular, reticular or of ground glass opacity, is the typical radiographic findings of Pneumocystis jiroveci pneumonia. Recently, atypical radiographic features, including cystic lung disease, spontaneous pneumothorax or nodular opacity, have been reported intermittently in patients with P. jiroveci pneumonia. We report the case of a 29-year-old woman with a transplanted kidney whose simple chest radiography and HRCT scan showed numerous miliary nodules in both lungs, mimicking miliary tuberculosis (TB). Under the presumptive diagnosis of miliary TB, empirical anti-TB medication was started. However, Grocott methenamine silver nitrate staining of a transbronchial lung biopsy tissue revealed P. jiroveci infection without evidence of TB. These findings suggest that even in TB-endemic area other etiology such as P. jiroveci as well as M. tuberculosis should be considered as an etiology of miliary lung nodules in immunocompromised patients.

Cervicovaginal microbial flora in methenamine silver staining method

Vagina like all other mucosal organs owns its especial bacterial/microbial flora. Though may be pathogen in other circumstances, members of vaginal normal flora do not cause disease on healthy vaginal mucosa. In this study, we tried to determine the relationship between microscopic findings on Methenamine silver stained cervicovaginal smears and clinical symptoms. A total of 389 cervicovaginal smears were examined cytologically from April to August 2005, among which 103 satisfactory smears of patients who were normally enstruating were subsequently selected. The originally Papanicolaou-stained smears were stained with Methenamine silver method. The cervicovaginal flora in symptomatic and asymptomatic patients was classified into four groups. The relationship between the type of genital flora and the presence of Candida or Actinomyces spp was also determined. Data were analyzed with SPSS software using Chi-square test. In 103 evaluated patients, 46 [44.7%] were symptomatic and the rest were asymptomatic. The most prevalent genital microbial flora in both symptomatic [21.7%] and asymptomatic [37.9%] patients was type II [Lactobacilli]. Microbial frequency differences were significant for types II [P = 0.034] and III [P = 0.039] in both groups. Coexistence of microbial flora of type I [P = 0.02] and type IV [P = 0.033] with Candida was statistically significant. Coexistence of all types of microbial flora with Actinomyces was not proved significant. Symptomatic women, except those with potential pathogens, tend to have Lactobacillus flora. Therefore, it is advisable that all Lactobacilli types be investigated through microbiological methods in symptomatic patients. In silver stained slides, there was a clear relationship between the type of vaginal microbial flora and the presence of Candida spp

A Case of Cutaneous Alternariosis in Liver Transplant Patient / 대한의진균학회지

A case of cutaneous alternariosis is reported in a 61-year-old female who underwent liver transplantation one year earlier. The infection manifested as a crusted papule about 1 cm in diameter on the right knee. Histological examination with silver methenamine and periodic acid-Schiff diastase revealed fungal spores and hyphae with chronic granulomatous inflammation. Biopsy fragments inoculated on Sabouraud-glucose agar with chloramphenicol produced colonies which were identified as Alternaria species on the basis of macroscopic and microscopic characters. Complete excision and treatment with 250 mg/day oral terbinafine for one month resulted in a satisfactory course with no signs of local recurrence over follow-up period of one year.