Patients Who Take Home Their Surgical Pathology Specimens: A Preliminary Study.

Patients regularly request to take possession of their human tissues after they have become surgical pathology specimens. To date, few formal research studies have examined the prevalence of this practice or the reasoning patients' request that their specimens to be returned to them. This study interviews patients from 2015 to 2017 at one US academic medical center who requested their surgical pathology specimens. Of the 22 eligible patients, 8 patients agreed to be interviewed. Interviews lasted 10 to 30 minutes and included 5 questions. The questions were: (1) What motivated your decision to obtain your surgical pathology specimen, (2) What, if anything, did you do with your specimen, (3) What were positive aspects of your experience, (4) What were negative aspects of your experience, (5) What can the pathology department change to better support patients who request their surgical pathology specimens? Verbatim transcripts were generated and a mixed-methods analysis was performed. The type of specimens included products of conception, placenta and cord, costal cartilage and ribs, loop explant recorder, pacemaker, below knee amputation, and cervix, uterus, Fallopian tubes, and ovaries. The dominant themes included adversity, medical interest, souvenir, cultural beliefs, and curiosity. Subthemes included becoming whole in the afterlife, preservation, my body, restoration, honoring, and regret. In conclusion, pathologists can expand their role as patient advocates and advance patient-centered pathology by supporting patient's individual needs, motivations, and goals, when they request their surgical pathology specimens.

Fatal Disseminated Herpes Simplex in a very premature neonate

Herpes Simplex Virus infections (HSV) are ubiquitous. The neonatal HSV infection (NHSV) is rare. The incidence is estimated globally at only 10.3 per 100,000 births, but it can cause devastating disease in premature infants. Both HSV-1 and HSV-2 can be the etiologic agents in this type of vertically transmittted NHSV infection. Here we describe the pathological findings from a complete autopsy of a very low birth weight infant who succumbed to the infection despite early institution of antiviral treatment. We urge more awareness of this disease with continued surveillance; every effort should be taken to make an early diagnosis and thus prevent this devastating disease.

Do Pentraxins Bind to Fungi in Invasive Human Gastrointestinal Candidiasis?

Tissue from 13 autopsy cases with invasive gastrointestinal candidiasis was studied for the binding of the pentraxins, C-reactive protein (CRP), pentraxin 3 (PTX3), and serum amyloid P component (SAP) to fungal surfaces. Invasive candidal infection was demonstrated using a hematoxylin and eosin stain and a Gomori methenamine silver stain (GMS). Immunohistochemistry was performed with CRP and PTX3 monoclonal antibodies and did not demonstrate CRP or PTX3 bound to fungi (0 of 13 cases), although CRP was extensively deposited on human tissue. A polyclonal antibody to SAP showed that SAP was bound to fungi in 12 of 13 cases. Although all three pentraxins have been reported to bind to fungi or bacteria, only SAP was bound to filamentous and yeast forms of Candida in human tissue, as detected by immunohistochemistry. SAP was abundantly present on fungi and may have affected the host innate immune response to the invading fungi.

Fatal Disseminated Herpes Simplex in a very premature neonate.

Herpes Simplex Virus infections (HSV) are ubiquitous. The neonatal HSV infection (NHSV) is rare. The incidence is estimated globally at only 10.3 per 100,000 births, but it can cause devastating disease in premature infants. Both HSV-1 and HSV-2 can be the etiologic agents in this type of vertically transmittted NHSV infection. Here we describe the pathological findings from a complete autopsy of a very low birth weight infant who succumbed to the infection despite early institution of antiviral treatment. We urge more awareness of this disease with continued surveillance; every effort should be taken to make an early diagnosis and thus prevent this devastating disease.

Serum Amyloid P Component and Systemic Fungal Infection: Does It Protect the Host or Is It a Trojan Horse?

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.

A unique biofilm in human deep mycoses: fungal amyloid is bound by host serum amyloid P component.

BACKGROUND/OBJECTIVES: 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. METHODS: Tissue specimens from 15 autopsies were systematically evaluated with multiple histochemical stains including thioflavin T and Congo red (dyes that stain amyloid), as well as antibody to SAP. We studied specimens with disseminated aspergillosis, mucormycosis and coccidioidomycosis. The structure of the lesions, host inflammatory cells and the presence of fungal amyloid and SAP were determined. RESULTS: The structure of the lesions was characteristic in aspergillosis ('starburst') and mucormycosis (closely apposed bundles of hyphae). Host inflammatory cells were absent or few in number within these lesions. In Coccidioides lesions, host inflammation was sparse as well. Fungal amyloid was a prominent feature of all lesions along with abundant SAP bound to hyphae and spherules. Fungal amyloid and SAP perhaps contributed to persistence in caseous necrosis lesions. SAP also bound to Aspergillus and Mucorales amyloid in vitro. CONCLUSIONS: A biofilm including amyloid and SAP is present in invasive fungal infections. This biofilm may dampen host defence leading to the characteristic sparse inflammatory reaction found in these infections.

Surgical pathology of skeletal coccidioidomycosis: a clinical and histopathologic analysis of 25 cases.

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 <0.1 to 13.5/HPF). Composition of inflammatory infiltrates, degree of necrosis, and extent of fibrosis did not significantly differ between immunocompetent and immunocompromised patients. Eosinophils were only seen in one third of cases; when present, eosinophils were almost always rare. 10 patients experienced recurrent infection, 8 of whom were immunocompromised; the remaining patients recovered. In conclusion, distal extremities are the most common sites of skeletal coccidioidomycosis encountered by surgical pathologists. This condition is strongly associated with autoimmune disorders and immunosuppression. Spherules are sometimes rare, and multiple modalities including serology, culture, and histology may be required for diagnosis.

Surgical pathology of pleural coccidioidomycosis: a clinicopathological study of 36 cases.

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, <1/10 high-power field). Three deaths occurred (all with ruptured cavities); the remaining patients recovered. Differential diagnosis of pleural effusions should include coccidioidomycosis, particularly in endemic areas, even without significant intrapulmonary disease. Most cases of coccidioidomycotic pleuritis are encountered by pathologists after resection of ruptured cavities with decortication, but pleural-predominant infections may be biopsied for diagnostic purposes. Spherules are usually rare in pleural tissue, and liberal sampling, cultures, or serologic studies may be required to confirm the diagnosis.

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.

Cavitary pulmonary coccidioidomycosis: pathologic and clinical correlates of disease.

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.

Atrial giant cell myocarditis: a distinctive clinicopathologic entity.

BACKGROUND: 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. METHODS AND RESULTS: We identified 6 patients (median age 67.5 years, 4 male) with atrial GCM in our pathology consultation practices from 2010 to 2012. Clinical history, imaging, and pathology materials were reviewed. Clinically, 4 patients had atrial fibrillation, 1 had acute heart failure, and 1 had incidental disease at autopsy. Among the 5 living patients, echocardiography revealed severe atrial dilatation (5 cases), mitral/tricuspid regurgitation (5), atrial mural thrombus (3), atrial wall thickening (2), and atrial hypokinesis (2). Ventricular function was preserved in all 5. Histological review of surgically resected atria showed giant cell and lymphocytic infiltrates, lymphocytic myocarditis-like foci, cardiomyocyte necrosis, and cardiomyocyte hypertrophy in all cases. Other features included interstitial fibrosis (5), poorly-formed granulomas (4), eosinophils (4), neutrophils (1), and vasculitis (1). Treatment consisted of steroids and cyclosporine (1), pacemaker placement for sick sinus syndrome (1), and supportive care (3). All 5 living patients returned to baseline exercise tolerance after 6 to 16 weeks of follow-up. CONCLUSIONS: Atrial GCM represents a distinct clinicopathologic entity with a more favorable prognosis than classic ventricular GCM. This disorder should be included in the differential diagnosis of atrial dilatation, particularly when associated with atrial wall thickening. The utility of immunomodulatory therapy for this condition remains unknown.

Left ventricular assist device support as a bridge to recovery in young children.

OBJECTIVE: 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). DESIGN: From 2004--2009, 13 children suffering from HF were placed on LVAD. All presented with a dilated left ventricle (LV) with severely reduced contractility, secondary to myocarditis, atrial arrhythmia or idiopathic HF. This study reports their outcomes and longitudinal follow-up. RESULTS: Of 13 young children with HF (ages 1 month--6 years; mean 19.2 months) placed on LVAD: eight weaned to recovery and successful hospital discharge, one was transplanted and four died. Echo follow-up in the weaned patients (mean age 22.1 months) revealed significant improvements from pre-LVAD measurements: LV end-diastolic dimension (LVED) mean z-score decreased from +4.8 to +0.95 (P < .001); fractional shortening (FS %) improved from a mean of 9.3% to 33% (P < .001); and the degree of mitral regurgitation (MR) significantly improved (P < .05). Time to LVAD deployment from HF diagnosis was more likely to be less than 30 days in the successfully weaned patients (100%) than patients who died or were transplanted (20%); P = .007. CONCLUSIONS: LVAD support can be utilized as a bridge to recovery in young children with HF. Following LVAD weaning, children sustain improvements in LV size, function and degree of MR. LVAD deployment less than 30 days from HF diagnosis improves the likelihood of successful weaning and illustrates that children with acute etiologies of HF are more likely to achieve recovery.

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.

Isolated superficial temporal artery dissection masquerading as giant cell arteritis.

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.

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.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a case report of identical twins with heart failure.

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.