Richard E. Sobonya

Cardiac Sarcoidosis Masquerading as Right Ventricular Dysplasia

Patients with cardiac sarcoidosis may present with clinical and morphological features similar to arrhythmogenic right ventricular dysplasia (ARVD) or cardiomyopathy (ARVC). Three cases of cardiac sarcoidosis are presented that clinically mimicked ARVD or ARVC until a pathology diagnosis of sarcoidosis was made at biopsy or autopsy. A diagnostic distinction, while often difficult to make, is important since treatment with corticosteroids may benefit those with sarcoidosis but is not expected to be useful in cases with ARVD or ARVC. (PACE 2003; 26[Pt. I]:1498–1503)

Pulmonary lymphangioleiomyomatosis: Quantitative analysis of lesions producing airflow limitation

The lungs of three patients dying of lymphangioleiomyomatosis (LAM), which in two of the patients was associated with tuberous sclerosis, were studied to characterize better the sites of airflow limitation in this condition. Quantitative studies showed that small airways were narrowed and collapsed because of the surrounding emphysema, but few airways contained excess smooth muscle. These findings suggest that the airspace lesions are more important than muscular proliferation in small airways in producing airflow limitation. In the two patients who had LAM with tuberous sclerosis, sex steroid assays were negative. Pleurodesis controlled pleural effusions in all three patients but may have contributed to reductions in lung volume.

Prenatal ultrasound diagnosis of hypoplastic left heart syndrome in utero associated with hydrops fetalis

Abstract Ultrasound is widely used in obstetrics as a screening technique for fetal size and maturity, placental structure and function, and for detection of fetal congenital malformations in complicated pregnancies. 1–3 Our own work on qualitative and quantitative fetal echocardiography 4,5 and the work of others 6 has suggested that high resolution ultrasound can be used to assess fetal heart rhythm and function, and can detect congenital heart malformations before birth. In this report, we delineate prenatal diagnosis of hypoplastic left heart syndrome in a fetus with signs of hydrops fetalis, who was found after cesarean section to have associated trisomy 13. Additionally, we diagnosed the ususual occurrence of an intraventricular thrombus within the hypoplastic left ventricular cavity. The fetal ultrasound evaluation was of major importance in the perinatal management of both mother and unborn child.

Fatal anhydrous ammonia inhalation

The morphologic and morphometric pulmonary alterations in a patient with anhydrous ammonia inhalation dying two months after exposure are described. Major pathologic findings included cylindrical bronchiectasis of the lower lobes, fibrous obliteration of small airways, and terminal nocardial pneumonia. Normal density of small airways was found, but the average diameter (0.50 mm.) was significantly less than that of controls (0.66 +/- 0.02). Fibrous obliteration of small airways may be characteristic of a late stage of bronchiolitis obliterans and is probably responsible for the chronic obstructive lung disease in the survivors of an episode of ammonia inhalation.

Bronchoscopic diagnosis of pulmonary coccidioidomycosis comparison of cytology, culture, and transbronchial biopsy

The results of all fiberoptic bronchoscopic examinations that detected Coccidioides immitis at two medical centers in an area endemic for coccidioidomycosis were retrospectively reviewed. Coccidioides immitis was detected by cytologic examination of fluid from either bronchial wash or bronchoalveolar lavage (BAL) fluid in eight (42%) of 19 HIV-infected patients and in 11 (31%) of 35 patients without HIV infection (P = 0.627). In all cases, the fluid samples grew C. immitis. The median time to positive identification of the fungus was 25 days. Preliminary identification of C. immitis, however, took a median of 3.5 days (range, 2-9 days) in 10 patients on whom these data were available. Transbronchial biopsy was performed simultaneously in eight cases, and C. immitis was identified by morphologic examination in all eight. These results indicate that cytologic examination of bronchial wash or BAL fluid from patients with and without HIV infection is diagnostic in less than half of cases of pulmonary coccidioidomycosis. Culture of the same fluid appears to be more sensitive than cytologic examination in establishing this diagnosis.

Quantitative pathology of coccidioidomycosis in acquired immunodeficiency syndrome

This study examines the laboratory aspects of diagnosis of coccidioidomycosis in 11 patients with acquired immunodeficiency syndrome (AIDS) and the qualitative and quantitative differences between host responses of AIDS and non-AIDS patients who died with disseminated coccidioidomycosis. Material obtained at bronchoscopy confirmed the diagnosis of pulmonary coccidioidomycosis in 67% (6/9) of the patients. Patients with AIDS had a generally poor granulomatous response and statistically significantly increased numbers of spherules in lung tissue compared with non-AIDS patients. Neither antifungal therapy nor duration of clinical disease influenced the number of organisms present. The findings suggest a parallel between AIDS-associated coccidioidomycosis and other granulomatous diseases such as leprosy and schistosomiasis, in which the type of granuloma formation and organism numbers are influenced by the T-lymphocyte milieu.

Histochemical and ultrastructural features of an unusual pulmonary carcinosarcoma

An autopsy case is presented in which a pulmonary carcinosarcoma filled the left chest of a 61 year old man. The extensive pleural involvement that this neoplasm exhibited has not been reported previously. By light microscopy the neoplasm initially was considered a mesothelioma because of the pattern of glands and undifferentiated sarcomatous stroma. However, by electron microscopy the sarcomatous component was found to show rhabdomyoblastic differentiation. Neither histochemical stains nor electron microscopy supported a mesothelial origin for the glandular component. Differential diagnostic considerations of pleuropulmonary neoplasms showing rhabdomyosarcomatous differentiation are discussed. This case illustrates the importance of detailed study in order to characterize and properly classify these neoplasms.

Postmortem candidaemia: marker of disseminated disease

Aim The significance of finding Candida species in heart blood cultures obtained at postmortem examination has never been studied. This article describes the findings of autopsy patients with postmortem candidaemia and it compares them with findings in autopsy patients with antemortem candidaemia. Method 23 patients with Candida species isolated from heart blood at autopsy were identified over a 10-year period. These patients were compared with 10 autopsy patients found during the same time period with antemortem blood cultures isolating Candida species, but not positive postmortem heart blood cultures. Antemortem and postmortem records were reviewed. Results All 23 patients with Candida species isolated from postmortem blood culture had one or more antemortem risk factors for disseminated candidiasis, such as positive antemortem blood cultures, isolation of Candida from sterile internal sites, neutropenia, recent abdominal surgery, broad-spectrum antibiotic administration or the use of central venous catheters or other invasive devices. Eight patients showed histological proof of invasive candidiasis in addition to the positive heart blood cultures. This group did not differ with respect to risk factors from 10 autopsy patients with disseminated candidiasis and antemortem blood cultures with Candida species. However, all the patients with antemortem candidaemia had histological evidence of disseminated candidiasis at autopsy. Conclusion Candidaemia, when documented by heart blood culture performed at autopsy or by antemortem blood culture, is an insensitive, but highly specific, indicator of disseminated candidiasis.

New Features of Invasive Candidiasis in Humans: Amyloid Formation by Fungi and Deposition of Serum Amyloid P Component by the Host

BACKGROUND Invasive candidiasis occurs in the gastrointestinal tract, especially in neutropenic patients. We were interested in determining whether invasive fungi formed amyloid in humans as they are known to do in vitro. We also sought to characterize the consequence(s) of such amyloid formation. METHODS Tissue from 25 autopsy patients with invasive candidiasis of the gastrointestinal tract was stained with amyloidophilic dyes and for the presence of serum amyloid P component (SAP). Confirmation of the interaction of SAP and Candida was demonstrated using Candida albicans and mutants for amyloid formation. RESULTS Amyloid was present on the cellular surface of fungi invading gut tissue. Moreover, SAP bound to the fungal cell walls, confirming the presence of amyloid. In vitro observations showed SAP bound avidly to fungi when amyloid formed in fungal cell walls. An unexpected result was the lack of host neutrophils in response to the invading fungi, not only in neutropenic patients but also in patients with normal or increased white blood counts. CONCLUSIONS We report the first demonstration of functional fungal amyloid in human tissue and the binding of SAP to invading fungi. It is postulated that fungal amyloid, SAP, or a complex of the proteins may inhibit the neutrophil response.

Peptide Detection of Fungal Functional Amyloids in Infected Tissue

Many fungal cell adhesion proteins form functional amyloid patches on the surface of adhering cells. The Candida albicans Agglutinin-like sequence (Als) adhesins are exemplars for this phenomenon, and have amyloid forming sequences that are conserved between family members. The Als5p amyloid sequence mediates amyloid fibril formation and is critical for cell adhesion and biofilm formation, and is also present in the related adhesins Als1p and Als3p. We have developed a fluorescent peptide probe containing the conserved Als amyloid-forming sequence. This peptide bound specifically to yeast expressing Als5p, but not to cells lacking the adhesin. The probe bound to both yeast and hyphal forms of C. albicans. Δals1/Δals3 single and double deletion strains exhibited reduced fluorescence, indicating that probe binding required expression of these proteins. Additionally, the Als peptide specifically stained fungal cells in abscesses in autopsy sections. Counterstaining with calcofluor white showed colocalization with the amyloid peptide. In addition, fungi in autopsy sections derived from the gastrointestinal tract showed colocalization of the amyloid-specific dye thioflavin T and the fluorescent peptide. Collectively, our data demonstrate that we can exploit amyloid sequence specificity for detection of functional amyloids in situ.