Clinically occult amyloidosis derived from leukocyte chemotactic factor 2 (ALECT 2) with cardiac involvement complicating renal transplantation: case report and literature review.

INTRODUCTION: Amyloidosis derived from leukocyte chemotactic factor 2 (ALECT2) may be associated with slowly progressive renal failure that is clinically unsuspected at the time of transplantation. While this is typically clinically insignificant, we report a case with extensive systemic ALECT2 amyloidosis that also involved the myocardium, contributing to perioperative death post renal transplantation. CASE DESCRIPTION: A 72-year-old Hispanic woman presented for renal transplantation due to end-stage renal disease secondary to hypertension. She was bradycardic on admission. Cardiac workup prior to transplantation had not identified an infiltrative process. Post-transplant hypotensive bradycardic arrests lead to multiorgan failure, anoxic brain injury, and death. Autopsy revealed massive amyloid deposition in the native kidneys, adrenals, spleen, and less extensive infiltration of liver and myocardium. Cardiac intramural vasculature from venules to capillaries, arterioles, and arteries showed amyloid deposition. Mass spectrometry revealed ALECT2 as the amyloidogenic protein. DISCUSSION: ALECT2 is a systemic amyloidosis that typically involves kidneys, adrenals, spleen, and liver. It may be clinically unsuspected at the time of renal transplantation and should be considered in older patients, especially from higher ALECT2 amyloid prevalence populations. Complications related to systemic disease may add to morbidity or mortality post-transplantation. Cardiac involvement in ALECT2 amyloidosis has not been previously identified as a significant clinical or autopsy finding, but our case demonstrates that the cardiovascular system may indeed rarely be involved by ALECT2 amyloidosis in cases with extensive systemic disease, and it may be associated with significant clinical sequelae.

Case report: surgical resection of right ventricular cardiac fibroma in an adult patient.

BACKGROUND: Cardiac fibromas are rare benign cardiac neoplasms, most frequently occurring in the pediatric population; with very rare cases identified in adults. The tumors are comprised of spindled cells with myofibroblastic ultrastructural features embedded in generally collagenous and elastic stroma. The tumors are intramural in the ventricles, most commonly the left ventricle. Clinical symptoms vary by location and size of tumor and some are asymptomatic. Surgical resection is curative, but rare cases require cardiac transplantation. CASE PRESENTATION: We report an asymptomatic, large, right ventricular fibroma in a 64-year-old woman. The patient underwent open incisional tumor biopsy via lower hemi-sternotomy, followed by complete tumor resection via full sternotomy a week later after confirming the tumor is benign. The tumor was resected using cardiopulmonary bypass, and the defect of right ventricular free wall was repaired using a prosthetic double-patch technique. The postoperative course was uneventful. The patient was discharged to home on day 4 post-complete tumor resection. CONCLUSION: This report expands the existing literature for better comprehension and detection of cardiac fibroma patients and also highlights the various imaging modalities, surgical management, and histological analysis.

The Many Faces of Cardiac Sarcoidosis.

OBJECTIVES: The objective of this study was to review and illustrate the sometimes diagnostically challenging features of cardiac sarcoidosis. We emphasize variable phenotypes presented at explant and biopsy evaluation and review literature regarding ancillary clinical and pathologic studies to enhance diagnostic accuracy. METHODS: A literature review was performed and two cardiac sarcoidosis cases were illustrated. RESULTS: Our cases and literature review demonstrate the pathologic spectrum of cardiac sarcoidosis. Irregular left ventricular free wall involvement is most common, followed by the interventricular septum and right ventricle. Although granulomas are often composed of tight epithelioid macrophage aggregates, early granulomas comprise loosely associated macrophages with lymphocyte predominance. Chronic disease leads to fibrosis and end-stage heart failure. Sampling errors and variable histology cause low endomyocardial biopsy sensitivity. CONCLUSIONS: Current guidelines use clinical, radiologic, and immunohistologic criteria for diagnosing cardiac sarcoidosis. Knowledge of these guidelines will assist pathologists in making accurate diagnosis of this disease.

Hepatic Silicone Granulomas Secondary to Ruptured Breast Implants: A Report of Two Cases.

The differential diagnosis of hepatic granulomas is vast and includes infections, drugs, immunologic diseases, foreign material exposure, and neoplasia. Silicone, whether directly injected into tissues or used as a filler in breast implants, is known to cause localized granulomatous reactions. It can also migrate to other anatomic locations resulting in granulomatous inflammation at a distance. We report two cases of unsuspected hepatic silicone granulomas in patients undergoing liver biopsy for isolated elevated alkaline phosphatase levels, both with a history of ruptured breast implants. These cases highlight the need for awareness of hepatic silicone granulomas as an etiology of elevated liver enzymes in patients with a history of surgical interventions utilizing silica, such as cosmetic surgery.

Analysis and Comparison of Tissue-Marking Dye Detection via Light Microscopy, Telemicroscopy, and Virtual Microscopy.

Objectives: To examine the fidelity of ink color identification using light microscopy (LM), telemicroscopy (TM), and virtual microscopy (VM). Methods: Twenty H&E-stained frozen section slides, prepared after tissue inking with five stain combinations, were assessed by three pathologists using LM, TM, and VM. TM was performed using Mikroscan D2 slide scanner/LiveQ software with various objectives. VM was performed using Mikroscan D2 scanner/Qumulus software, specimens digitized at20×. Results: Sensitivity/specificity by LM was 100%/100% for all colors. TM showed high overall specificity but poor sensitivity, particularly red (54%). VM showed high specificity for all colors except black (69%) and, consequently, poor sensitivity for all colors except black (96%). Conclusions: TMD identification via telepathology showed loss of sensitivity/specificity vs LM and highlighted the need for caution when interpreting TMDs with digital technologies and the need for validation protocols.

Report and Recommendations of the Association of Pathology Chairs' Autopsy Working Group.

Autopsy has been a foundation of pathology training for many years, but hospital autopsy rates are notoriously low. At the 2014 meeting of the Association of Pathology Chairs, some pathologists suggested removing autopsy from the training curriculum of pathology residents to provide additional months for training in newer disciplines, such as molecular genetics and informatics. At the same time, the American Board of Pathology received complaints that newly hired pathologists recently certified in anatomic pathology are unable to perform an autopsy when called upon to do so. In response to a call to abolish autopsy from pathology training on the one hand and for more rigorous autopsy training on the other, the Association of Pathology Chairs formed the Autopsy Working Group to examine the role of autopsy in pathology residency training. After 2 years of research and deliberation, the Autopsy Working Group recommends the following:Autopsy should remain a component of anatomic pathology training.A training program must have an autopsy service director with defined responsibilities, including accountability to the program director to record every autopsy performed by every resident.Specific entrustable activities should be defined that a resident must master in order to be deemed competent in autopsy practice, as well as criteria for gaining the trust to perform the tasks without direct supervision.Technical standardization of autopsy performance and reporting must be improved.The current minimum number of 50 autopsies should not be reduced until the changes recommended above have been implemented.

The Pathology of Acute Liver Failure.

Varied injuries may manifest clinically as acute liver failure. The pathologic features include variable amounts of necrosis and regeneration. This article reviews pathologic classification of patterns of necrosis and associated inflammatory and regenerative responses in specimens from patients with acute liver failure. Detailed pathologic examination of these specimens with clinical pathologic correlation can give the multidisciplinary team vital information regarding etiology and timing as well as extent of injury, and regenerative response. Pathologists are a vital component of the health care team for patients with acute liver failure.

A case report of mesenteric heterotopic ossification: Histopathologic and genetic findings.

Mesenteric heterotopic ossification (MHO) is very rare and occurs in mid- to late-adulthood, usually in the context of prior abdominal surgery. The mechanisms of MHO are unknown. Here we describe the case of a 72-year-old man with MHO. Standard histological staining revealed that MHO occurred through an endochondral process. By comparison to known mutations in genetic conditions of HO such as fibrodysplasia ossificans progressiva (FOP) and progressive osseous heteroplasia (POH), DNA sequencing analysis demonstrated the presence of a commonly occurring heterozygous synonymous polymorphism (c.690G>A; E230E) in the causative gene for FOP (ACVR1/ALK2). However, no frameshift, missense, or nonsense mutations in ACVR1, or in the causative gene for POH (GNAS), were found. Although genetic predisposition may play a role in MHO, our data suggest that mutations which occur in known hereditary conditions of HO are not the primary cause.

Vanishing Bile Duct Syndrome in a Patient with Uterine Cancer and Paraneoplastic Systemic Sclerosis.

Vanishing bile duct syndrome (VBDS) is a rare entity of acquired disorders resulting in cholestasis secondary to progressive destruction of intrahepatic bile ducts. The syndrome has been described in the setting of autoimmune disorders, medication toxicities, genetic disorders, infectious etiologies, and in rare cases, neoplastic processes. There are no known case reports of VBDS in the setting of uterine malignancy. We present a case of VBDS in a patient with underlying uterine cancer complicated by paraneoplastic systemic sclerosis.

Virtual microscopy improves sharing of deceased donor kidneys.

BACKGROUND: Donor kidney biopsies used for offer evaluation may lengthen cold ischemia time. Our organ procurement organization began processing wedge biopsies and having them read using virtual microscopy (VM), as opposed to its prior routine of processing/reading at local hospitals. We hypothesized that VM would decrease time to biopsy results and kidney acceptance. METHODS: All donor kidneys biopsied over 1 year were compared with those biopsied during the previous year (n = 43, 40). RESULTS: Time to biopsy result was shortened using VM (5:04 vs 6:30, P = .04), and especially for those cases with cross-clamp between 5 pm and 5 am (4:49 vs 8:12, P < .01). Time to local acceptance was also significantly improved using VM for both the entire group (7:01 vs 9:52, P < .01) and the overnight subset (7:25 vs 11:10, P < .01). CONCLUSIONS: Use of VM decreased time to biopsy result, with the most prominent effects seen during the overnight hours, resulting in shortened time to local acceptance of organs.

Eculizumab and recurrent C3 glomerulonephritis.

BACKGROUND: Hyperactivity of the alternative complement pathway is the principle defect in C3 glomerulopathies (C3G). Eculizumab, a monoclonal antibody that binds C5 to prevent formation of the membrane attack complex, has been shown to be beneficial in some patients with this disease. METHODS: In this open-label, proof-of-concept efficacy-and-safety study, a patient with the initial diagnosis of dense deposit disease (DDD) and allograft recurrence of C3 glomerulonephritis (C3GN) was treated with eculizumab every other week for 1 year. The patient had pathological evidence of C3GN and proteinuria >1 g/day at enrollment. He underwent graft biopsy before enrollment and repeat biopsy at 6 and 12 months. RESULTS: Although no mutations were identified in complement genes, functional studies were positive for C3 nephritic factors and elevated levels of soluble membrane attack complex (sMAC). On therapy, sMAC levels normalized and although proteinuria initially decreased, it increased reaching pre-treatment levels at 12 months. Although serum creatinine remained stable, repeat allograft biopsies showed progression of disease. CONCLUSIONS: Clinical and histopathologic data suggest a partial response to eculizumab in this patient. While eculizumab blocked activation of the terminal complement cascade, persistent dysregulation of the alternative pathway remained, indicating eculizumab alone cannot control disease in this patient. Additional research is required to identify effective anticomplement therapy for this group of C3G patients.

Fluorescence microscopy is superior to polarized microscopy for detecting amyloid deposits in Congo red-stained trephine bone marrow biopsy specimens.

The classic gold standard for detecting amyloid deposits is Congo red-stained bright field and polarized microscopy (CRPM). A prior study showed that Congo red fluorescence (CRF) microscopy had increased sensitivity compared with traditional CRPM when analyzing fat pad specimens. The purpose of the current study was to determine the sensitivity of CRF for evaluating Congo red-stained bone marrow biopsy specimens, and to compare these results with those of CRPM. We compared the CRPM and the CRF analyses of 33 trephine bone marrow biopsy specimens with clinical or morphologic suspicion of amyloid deposits. These results were verified against immunohistochemical staining with anti-amyloid P antibody. CRF achieved 100% sensitivity, and CRPM achieved 75% sensitivity. Both groups showed 100% specificity compared with amyloid P immunohistochemical staining. The results show that CRF is a sensitive method to analyze trephine bone marrow biopsy specimens for amyloid deposits.

Pulmonary tumor thrombotic microangiopathy with cor pulmonale due to desmoplastic small round cell tumor.

A 12-year-old boy presented acutely after an episode of syncope with perioral cyanosis. He died 19 hours after admission due to cor pulmonale as a complication of metastatic desmoplastic small round cell tumor in the lungs with associated tumor thrombotic microangiopathy.

Nonseptal right atrial aneurysm: case report and review of literature.

An aneurysm of the portion of the right atrium classically referred to as the subeustachian sinus is reported in a 75-year-old man with cardiac amyloidosis, AL phenotype, related to underlying multiple myeloma. A review of literature confirms the rarity of nonseptal right atrial aneurysms and their propensity to involve the subeustachian area of the right atrium which may be an intrinsic area of weakness in the atrial wall. The coincident amyloidosis in our current case suggests that hemodynamic factors may have played a role in the development of the aneurysm.

Infective endocarditis complicating hypertrophic obstructive cardiomyopathy: an unusual mural pattern.

A patient with hypertrophic obstructive cardiomyopathy (HOCM) and an unusual right ventricular mural pattern of endocarditis that clinically mimicked a neoplasm is presented. To our knowledge, this is the first report of right ventricular mural endocarditis complicating HOCM.

Diabetic microangiopathy in the liver: an autopsy study of incidence and association with other diabetic complications.

Diabetic hepatosclerosis (DH) is a recently described form of diabetic microangiopathy with hepatic sinusoidal fibrosis and basement membrane deposition without cirrhosis. The objective was to investigate the frequency of DH and its correlation with other diabetic microangiopathic complications. Complete autopsies from 57 adults with diabetes were reviewed for liver pathology and other diabetic complications. Basement membrane deposition in the liver was highlighted using laminin and type IV collagen immunostains. Only 1 case of DH was identified. Other diabetic end-organ damage in this case included nodular glomerulosclerosis and hepatic hyaline arteriolosclerosis, which were the most severe in the series. DH is an uncommon pattern of liver disease in patients with diabetes and is associated with severe end-organ damage. This study supports the presumed vascular etiology of DH, confirms the rarity of the lesion, and supports the suggestion that it is usually accompanied by other end-organ damage.

Thymolipoma: clues to pathogenesis revealed by cytogenetics.

The pathogenesis of thymolipoma is controversial and unclear despite numerous reports. A case report of thymolipoma with cytogenetic analysis is herein presented. The lesion demonstrated a translocation involving the HMGA2 gene on chromosome 12q15, which is seen in two thirds of solitary lipomas. This finding supports the theory that this case of thymolipoma is a neoplasm of thymic fat.

Clinical resolution of glycogenic hepatopathy following improved glycemic control.

Glycogenic hepatopathy is an underrecognized complication of long-standing poorly controlled diabetes mellitus. It is characterized by abnormal glycogen accumulation in hepatocytes, elevated liver enzymes and hepatomegaly. This is a distinct entity from other causes of hepatomegaly and elevated liver enzymes in diabetics such as nonalcoholic fatty liver disease. It is important to distinguish this entity as it has the potential for resolution following improved glycemic control as described by this case report.