Richard E Sobonya

Interests

Research

diagnostic cardiac and pulmonary pathology

Teaching

cardiac and pulmonary pathology; the autopsy; residency training

Courses

Scholarly Contributions

Journals/Publications

• Aly, F. Z., Millius, R., Sobonya, R., Aboul-Nasr, K., & Klein, R. (2016). Cytologic diagnosis of coccidioidomycosis: Spectrum of findings in Southern Arizona patients over a 10 year period. Diagnostic cytopathology, 44(3), 195-200.
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  The largest series examining the cytological diagnosis of coccidioidomycosis was reported more than 20 years ago and only considered fine needle aspiration (FNA) specimens from pulmonary nodules. Since then, there has been a substantial increase in the incidence of the disease in endemic regions. The aims of this study were to examine the spectrum of Coccidioides in all cytologic specimens and detail their diagnostic and clinical features. The prevalence of infection is also examined against temperature and precipitation data.
• Garcia-Sherman, M. C., Lundberg, T., Sobonya, R. E., Lipke, P. N., & Klotz, S. A. (2016). A unique biofilm in human deep mycoses: fungal amyloid is bound by host serum amyloid P component. NPJ biofilms and microbiomes, 1.
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  We have demonstrated the presence of Candida cell surface amyloids that are important in aggregation of fungi and adherence to tissue. Fungal amyloid was present in invasive human candidal infections and host serum amyloid P component (SAP) bound to the fungal amyloid. SAP is a protease-resistant glycoprotein that binds avidly to amyloid and interferes with host defence, especially against bacterial pathogens for which neutrophils are important. In this study, we investigated whether biofilm of fungal amyloid and SAP was a feature of other disseminated fungal infections.
• Ihnat, C. L., Zimmerman, H., Copeland, J. G., Meaney, F. J., Sobonya, R. E., Larsen, B. T., Blair, B., Lax, D., & Barber, B. J. (2016). Left ventricular assist device support as a bridge to recovery in young children. Congenital heart disease, 6(3), 234-40.
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  Left ventricular assist device (LVAD) experience and follow-up data in children are limited. We report the deployment and successful weaning from LVAD in young children with severe heart failure (HF).
• John, S. G., Thorn, J., & Sobonya, R. (2016). Statins as a potential risk factor for autoimmune diseases: a case report and review. American journal of therapeutics, 21(4), e94-6.
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  Association of statins with autoimmune disorders is rarely reported. We report a case of an apparently healthy 76-year-old woman who was on long-term statin therapy presenting with severe rhabdomyolysis, autoimmune hepatitis, and positive lupus antibodies. Patient presented with complaints of worsening fatigue, leg cramps, and progressive weakening of lower extremities over 3 weeks. The patient was on simvastatin daily for several years. Clinical examination on admission included muscle tenderness, lower extremity edema, and ascites. Her laboratory values on admission showed elevated creatine kinase and transaminases. Immunologic workup revealed positive ANA, anti-dsDNA and anti-SSA antibodies. F-actin antibody was also positive at high titer. Magnetic resonance imaging of the lower extremities showed findings consistent with myositis. Patient underwent biopsy of the thigh muscles, which showed inflammatory myositis. Liver biopsy was characteristic of autoimmune hepatitis. Patient responded well to immunosuppressive therapy with azathioprine and prednisone. Although statins are generally considered safe, recent data from long-term follow-up on patients who are on statins for long duration suggest that prolonged exposure to statins may trigger autoimmune reactions. The exact mechanism of statin-induced autoimmune reaction is unclear. Statins, as proapoptotic agents, release nuclear antigen into the circulation and may induce the production of pathogenic autoantibodies. The role of statins in inducing an endoplasmic reticular stress response with associated upregulation of major histocompatibility complex-1 expression and antigen presentation by muscle fibers has also been reported. Systemic immunosuppressive therapy has proven to be effective in many reported cases.
• Klotz, S. A., Sobonya, R. E., Lipke, P. N., & Garcia-Sherman, M. C. (2016). Serum Amyloid P Component and Systemic Fungal Infection: Does It Protect the Host or Is It a Trojan Horse?. Open forum infectious diseases, 3(3), ofw166.
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  It is a striking observation that tissue of patients invaded by the deep mycoses often lacks evidence of an inflammatory response. This lack of host response is often attributed to neutropenia secondary to chemotherapy. However, systematic studies do not support this simplistic explanation. However, invasive fungal lesions are characterized by abundant fungal functional amyloid, which in turn is bound by serum amyloid P component (SAP). We postulate that SAP is important in the local immune response in invasive fungal infections. The interaction between fungal functional amyloid, SAP, and the immune response in deep mycoses is discussed.
• Pasha, A. K., Snyder, B. A., Zangeneh, T. T., Thompson, J. L., Sobonya, R. E., & Abidov, A. (2015). A distinctly rare case of candida endocarditis involving the bioprosthetic pulmonary and the Eustachian valve diagnosed on 3D transesophageal echocardiography. Echocardiography (Mount Kisco, N.Y.), 32(3), 607-9.
• Garcia-Sherman, M. C., Lysak, N., Filonenko, A., Richards, H., Sobonya, R. E., Klotz, S. A., & Lipke, P. N. (2014). Peptide detection of fungal functional amyloids in infected tissue. PloS one, 9(1), e86067.
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  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.
• Ricciotti, R. W., Shekhel, T. A., Blair, J. E., Colby, T. V., Sobonya, R. E., & Larsen, B. T. (2014). Surgical pathology of skeletal coccidioidomycosis: a clinical and histopathologic analysis of 25 cases. The American journal of surgical pathology, 38(12), 1672-80.
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  Skeletal coccidioidomycosis is a rare complication of pulmonary coccidioidomycosis that remains incompletely characterized, and its histopathologic features have not been systematically evaluated. All skeletal coccidioidal infections (2000 to 2012) were retrieved from the University of Arizona and Mayo Clinic in Arizona pathology archives. Clinical history and histologic features were reviewed. Among 25 patients (median age 40 y; 17 men), infections involved bones (2 cases), joints (6), or both (17), usually in the distal extremities (68%), especially the wrist (32%). History included previously documented coccidioidomycosis (13), autoimmune disease (8), diabetes (6), malignancy (4), and iatrogenic immunosuppression (10). Common symptoms (median 3 mo) included pain/arthralgia (21) and swelling (10). Cultures and serology were positive in 15 of 17 (88%) and 19 of 22 patients (86%), respectively. Treatment included surgical debridement(s) and chronic antifungal medication(s). Histologic review showed granulomas in all cases, ranging from poorly to well formed, with or without necrosis. Spherule density varied widely (mean 4.8/HPF; range
• Satyanarayan, A., Klotz, S., Han, L., Sobonya, R., & Zangeneh, T. T. (2014). Coccidioidomycosis of the genitourinary tract: a case report and discussion. Urology, 84(6), e30-1.
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  Coccidioides species (Coccidioides immitis and Coccidioides posadasii) are dimorphic fungi endemic to the Southwestern United States. Initial infection ranges from asymptomatic to mild upper respiratory tract symptoms and may disseminate to other organs including the genitourinary tract. Genitourinary complaints may be the initial presenting signs and symptoms among a minority of patients. We report a case of genitourinary coccidioidomycosis and discussion of genitourinary disease with coccidioidomycosis.
• Shekhel, T. A., Ricciotti, R. W., Blair, J. E., Colby, T. V., Sobonya, R. E., & Larsen, B. T. (2014). Surgical pathology of pleural coccidioidomycosis: a clinicopathological study of 36 cases. Human pathology, 45(5), 961-9.
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  Most pulmonary coccidioidal infections are intraparenchymal; the pleurae are rarely involved. Pleuritis is a recognized complication of ruptured cavitary infections and occasionally occurs in other settings but has not been fully characterized. To define the clinical and histopathologic characteristics of pleural coccidioidomycosis as encountered by surgical pathologists, we reviewed the clinical history, imaging, and histology of 36 biopsy-, resection-, or autopsy-confirmed cases (with coccidioidal spherules present in pleural tissue; median age, 39 years; 22 men). These represented 7% of all pulmonary coccidioidal infections and showed 2 modes of presentation, including ruptured cavitary infection (26) and pleural-predominant disease with milder parenchymal involvement (10). Risk factors included immunodeficiency, smoking, and occupational exposure to soil. Common symptoms (median, 5 weeks) included cough (47%), chest pain (44%), and dyspnea (39%). Imaging often showed pleural adhesions (64%) and effusions (61%). Treatment included lobectomy or decortication, with antifungal medications. All cases showed granulomatous pleuritis. Both modes of presentation showed similar histologic features, including the composition of inflammatory infiltrates, degree of fibrosis, and extent of necrosis. Spherules were usually few (mean density,
• Sobonya, R. E., Yanes, J., & Klotz, S. A. (2014). Cavitary pulmonary coccidioidomycosis: pathologic and clinical correlates of disease. Human pathology, 45(1), 153-9.
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  Cavitary pulmonary coccidioidomycosis is a difficult diagnosis to establish due to the poor sensitivity of serological tests and rarity of culture from sputum. A pathologic and clinical analysis was performed of 21 consecutive patients with surgically resected cavities that proved to be coccidioidomycosis. Ten patients (48%) had serological evidence of Coccidioides infection, and 1 patient cultured Coccidioides spp. from sputum. The definitive diagnosis of coccidioidomycosis was made in the remaining 10 patients (48%) upon microscopic examination of tissue. The pleura showed fibrous pleuritis in 7 patients (33%) and eosinophilic pleuritis in 4 cases (19%); granulomas without microorganisms were demonstrated in 4 cases (19%). The cavity wall showed chronic inflammation and occasional giant cells but no granulomas and no microorganisms. The cavity contents included a mycetoma in 6 cases (28%); the cavity lining showed neutrophils and caseous necrosis; Coccidioides hyphae were present in 13 (62%) and spherules in 16 (76%) cases but often were rare. Adjacent lung showed lymphoid hyperplasia with chronic bronchiolitis in all cases; satellite granulomas with diagnostic spherules were variably present. The histopathology of cavitary coccidioidomycosis is strikingly variable depending on what area is sampled by biopsy, and microorganisms may be rare. This may explain the high rate of failure of diagnosis by fine needle aspiration and bronchoalveolar lavage. Pathologists in nonendemic areas must be aware of these findings, as this disease is now diagnosed worldwide.
• Dalabih, M. R., Sobonya, R. E., Arteaga, V. A., Snyder, L. S., & Carr, G. E. (2013). A 48-year-old woman with headache and respiratory failure. Chest, 144(4), 1411-6.
• Larsen, B. T., Maleszewski, J. J., Edwards, W. D., Cooper, L. T., Sobonya, R. E., Thompson, V. E., Duckett, S. G., Peebles, C. R., Simpson, I. A., & Tazelaar, H. D. (2013). Atrial giant cell myocarditis: a distinctive clinicopathologic entity. Circulation, 127(1), 39-47.
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  Giant cell myocarditis (GCM) typically causes fulminant heart failure, arrhythmias, or heart block, necessitating aggressive immunosuppression, ventricular assist device insertion, or cardiac transplantation. We describe a novel variant of GCM, primarily involving the atria, that displays distinctive clinical features and follows a more benign course than ventricular GCM.
• Gilchrist, K. B., Garcia, M. C., Sobonya, R., Lipke, P. N., & Klotz, S. A. (2012). New features of invasive candidiasis in humans: amyloid formation by fungi and deposition of serum amyloid P component by the host. The Journal of infectious diseases, 206(9), 1473-8.
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  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.
• Smith, G., Hoover, S., Sobonya, R., & Klotz, S. A. (2011). Abdominal and pelvic coccidioidomycosis. The American journal of the medical sciences, 341(4), 308-11.
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  Coccidioidomycosis is a fungal infection endemic to the Southwestern United States that has a clinical presentation resembling community-acquired pneumonia. Disease occurs after inhalation of airborne arthroconidia. Dissemination to a variety of organ systems via hematogenous spread from a primary pulmonary focus may then occur. Coccidioidomycosis rarely involves the abdominal cavity. The authors review the spectrum of abdominal and pelvic presentations of coccidioidomycosis and report 6 unusual cases, including acute appendicitis, hepatitis and adnexal masses. Pathologists played a critical role in the diagnosis of these presentations by recognizing spherules in tissue. In only 2 of the cases were Coccidioides species cultured.
• Thorn, J. L., Gilchrist, K. B., Sobonya, R. E., Gaur, N. K., Lipke, P. N., & Klotz, S. A. (2010). Postmortem candidaemia: marker of disseminated disease. Journal of clinical pathology, 63(4), 337-40.
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  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.
• Delis, A., Pollard, C. M., Prasad, A., Sobonya, R. E., & León, L. R. (2009). Isolated superficial temporal artery dissection masquerading as giant cell arteritis. Vascular, 17(5), 296-9.
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  A 79-year-old male presented with symptoms suggesting giant cell arteritis (GCA) and elevation of acute-phase reactants. Bilateral superficial temporal artery (STA) biopsies were negative for GCA. However, the right-sided biopsy showed a STA dissection. Spontaneous isolated STA dissection has never been reported previously. The pertinent available literature is also discussed.
• Tempkin, A. D., Sobonya, R. E., Seeger, J. F., & Oh, E. S. (2006). Cerebral aspergillosis: radiologic and pathologic findings. Radiographics : a review publication of the Radiological Society of North America, Inc, 26(4), 1239-42.
• Baruch, A. C., Steinbronn, K., & Sobonya, R. (2005). Pulmonary adenocarcinomas associated with rheumatoid nodules: a case report and review of the literature. Archives of pathology & laboratory medicine, 129(1), 104-6.
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  Necrobiotic lung nodules and primary lung carcinoma both occur with some frequency in patients with rheumatoid arthritis; however, few reports exist of a primary lung carcinoma occurring within a rheumatoid nodule. We report a case of a 62-year-old woman with multiple pulmonary nodules discovered incidentally by computed tomography. Although 2 of the lesions were composed solely of necrotizing granulomas, 2 additional lesions contained malignant glands at the periphery of necrobiotic nodules. Immunohistochemical staining supported the diagnosis of both tumors as primary lung carcinomas. Our literature search revealed only 2 other reported cases of adenocarcinoma occurring in association with a rheumatoid nodule; these cases, as well as the association between rheumatoid disease and malignancy, are briefly reviewed.
• Ott, P., Marcus, F. I., Sobonya, R. E., Morady, F., Knight, B. P., & Fuenzalida, C. E. (2003). Cardiac sarcoidosis masquerading as right ventricular dysplasia. Pacing and clinical electrophysiology : PACE, 26(7 Pt 1), 1498-503.
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  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.
• Indik, J. H., Smith, D. E., Sobonya, R. E., & Marcus, F. I. (2002). Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a case report of identical twins with heart failure. Pacing and clinical electrophysiology : PACE, 25(9), 1387-90.
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  Arrhythmogenic right ventricular cardiomyopathy/dysplasia is characterized by the progressive replacement of myocardium by fatty or fibrofatty tissue. Presenting symptoms are generally related to ventricular arrhythmias, including sudden cardiac death. Heart failure due to right ventricular and sometimes left ventricular dysfunction is uncommon in the early stages of the disease, but is known to occur in advanced cases. This case report describes identical adolescent twins with presenting symptoms related predominantly to right heart failure.
• Lui, C. Y., Marcus, F. I., & Sobonya, R. E. (2002). Arrhythmogenic right ventricular dysplasia masquerading as peripartum cardiomyopathy with atrial flutter, advanced atrioventricular block and embolic stroke. Cardiology, 97(1), 49-50.
• Sobonya, R. E., & Weinstein, R. S. (2001). Pathology manpower: a few rays of sunshine. Human pathology, 32(7), 669-70.
• Babar, S. I., Sobonya, R. E., & Snyder, L. S. (1998). Pulmonary microvascular cytology for the diagnosis of pulmonary tumor embolism. The Western journal of medicine, 168(1), 47-50.
• Witten, M. L., Tinajero, J. P., Sobonya, R. E., Lantz, R. C., Quan, S. F., & Lemen, R. J. (1997). Human alveolar fractal dimension in normal and chronic obstructive pulmonary disease subjects. Research communications in molecular pathology and pharmacology, 98(2), 221-30.
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  We have determined that fractal analysis of the alveolar perimeter (Df) changes with aging in human lung tissue in twenty-nine patients, age range of 25 hours to 76 years, who died of non-respiratory related causes. There was a very significant difference (p = 0.0004) in Df between the young (less than 16 years old, N = 9, mean Df of 1.047 [0.01]) and adult (greater than 16 years old, N = 20, mean Df of 1.093 [0.013]) groups. Furthermore, there was a significant difference in Df between the Adult group and the group of patients who died of chronic obstructive pulmonary disease (COPD, N = 10) (p = 0.012). Additionally, the Df values for the COPD and cystic fibrosis (CF, N = 5) groups were virtually identical; 1.061 and 1.070, respectively. Regression analysis showed a significant (p = 0.0041) exponential relationship with a correlation coefficient of 0.59 between aging and Df. We have demonstrated that the correlation between Df and aging in humans is an exponential function and that the end-stage pulmonary diseases of COPD and CF decrease Df.