Caseous Calcification of the Mitral Annulus: Calcified Toothpaste of the Heart.

ABSTRACT: Caseous calcification of the mitral annulus (CCMA) is a rare variant of mitral annular calcification (MAC) usually described as an antemortem finding. We report a case of sudden cardiac arrest in a 39-year-old male with end-stage renal disease undergoing hemodialysis with a history of Fabry disease by kidney biopsy. Autopsy revealed significant circumferential annular calcification in both mitral and aortic valves with a caseous gross appearance. Histologically, these areas consisted of amorphous basophilic material accompanied by a surrounding granulomatous-appearing infiltrate. Von Kossa staining on non-decalcified tissue revealed strong positive staining, confirming CCMA diagnosis. While identifiable, the atrioventricular node was displaced and distorted by caseous deposits. Toluidine blue staining of myocardium showed osmophilic accumulations, and electron microscopy (EM) showed myeloid/zebra bodies, consistent with Fabry disease. We posit that Fabry disease leads to end-stage kidney disease, altering calcium phosphate metabolism, a proposed mechanism for CCMA. This case highlights the multifactorial nature of sudden cardiac death in decedents with various structural cardiac changes and potential renal-disease-induced electrolyte imbalances. We aim to bring awareness to this rare entity, its potential role in a sudden cardiac death, and to highlight the need to use non-decalcified tissue when staining for calcium to establish the diagnosis.

A rare case of diffuse crescents in fibrillary glomerulonephritis
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Diffuse crescentic involvement in fibrillary glomerulonephritis (FGN) is very rare. We describe a case of FGN with diffuse crescents in a patient who presented with clinical findings concerning for rapidly progressive kidney failure and pathologic findings suggestive of anti-glomerular basement membrane (GBM) disease. Serologies for anti-neutrophil cytoplasmic antibody (ANCA) and anti-GBM were negative. IgG subtyping showed IgG1 dominance, which has not been described in FGN. We present this unique case to emphasize the importance of considering FGN in biopsies showing diffuse crescentic glomerulonephritis with linear IgG staining of glomerular capillary walls, especially in the absence of other significant proliferative changes.

Myeloid bodies is not an uncommon ultrastructural finding.

The presence of myeloid bodies (MBs) is classically associated with Fabry disease (FD). However, MBs are also identified in patients without clinical evidence of FD. We attempt to further understand the clinicopathologic significance of incidental MBs in those without FD. Among the 4400 renal biopsies accessioned at the University of Rochester Medical Center from 2010 to 2021, we identified 32 cases showing MBs, 6 of which had FD. Medications were compared between a non-FG and a control-group of randomly selected cases without MBs (non-MBs). Both Fabry-group (FG) and non-Fabry-group (non-FG) were predominantly middle-aged (mean 48 years vs 56, respectively). Non-FG had slight female predominance (1:4), while all in FG were female. The majority of both non-FG and non-MBs cohort were on the same medications reported to cause phospholipidosis except sertraline and hydralazine (p = .04), which were more frequent in non-FG. Ultrastructurally, non-FG tended to show focal MBs in predominantly podocytes, while FG showed more extensive MBs in not only podocytes but also parietal, tubular, endothelial, and myocyte cells (p = .03). In addition, half of FG had another superimposed renal disease including kappa-light chain deposition disease, thin-basement membrane nephropathy, and lithium-related changes. MBs are encountered not only in FD but in other settings including CADs, toxins, and other inheritable diseases. Although secondary causes of MBs typically show less extensive involvement compared to FD, these features overlap. Given the challenges in diagnosing female carriers, the finding of MBs, though not specific to FD, may be the only clue that leads to further work-up and timely diagnosis, underscoring the importance of considering FD among other etiologies in differential diagnosis.

Subepithelial deposits with microspherular structures in membranous glomerulonephritis.

Rare cases of membranous glomerulopathy (MGN) with subepithelial deposits consisting of microspherular structures identified by electron microscopy have been described in the literature as either MGN with spherules or podocyte infolding glomerulopathy (PIG). The paucity of available studies shows a strong association with underlying autoimmune disease. To further understand the significance of subepithelial microspherular deposits, we retrospectively identified native kidney biopsies from 10 patients diagnosed as MGN with subepithelial microspherular structures identified by ultrastructural examination at the University of Rochester Medical Center (URMC) during an 11-year period. The majority were Caucasian (80%) with a mean age of 51.3 (±12.9) years. 50% had an autoimmune disorder, of which 80% were SLE. Two SLE cases had concomitant rheumatoid arthritis and Sjogren's syndrome. One additional case had antiphospholipid syndrome and showed lupus-like features on biopsy. 40% were idiopathic and negative for PLA2R, NELL1, and THSD7A. MGN with subepithelial microspherular structures is frequently associated with an underlying autoimmune disease. The majority are negative for markers of primary MGN (PLA2R, THSD7A, and NELL1) and show features suggestive of secondary MGN.

The spectrum of renal diseases with lupus-like features: a single-center study.

BACKGROUND: A subset of patients without overt systemic lupus erythematosus (SLE) present with biopsy findings typically seen in lupus nephritis (LN). Although a minority eventually develops SLE, many do not. It remains unclear how to classify or treat these patients. Our study attempted to further understand the clinical and pathological characteristics of cases with lupus-like nephritis (LLN). METHODS: Among 2700 native kidney biopsies interpreted at University of Rochester Medical Center (URMC) from 2010 to 2019, we identified 27 patients with biopsies showing lupus-like features (LL-fx) and 96 with LN. Of those with LL-fx, 17 were idiopathic LLN and 10 were associated with a secondary etiology (e.g., infection/drugs). RESULTS: At the time of biopsy, the LLN-group tended to be slightly older (44 vs. 35), male (58.8 vs. 17.7%, p = .041), and Caucasian (47.0 vs. 28.1%, p = .005). Chronic kidney disease was the most common biopsy indication in LLN (21.4 vs. 2.8%, p = .001). Both LN and LLN presented with nephrotic-range proteinuria (mean 5.73 vs. 4.40 g/d), and elevated serum creatinine (mean 1.66 vs. 1.47 mg/dL). Tubuloreticular inclusions (TRIs; p < .001) and fibrous crescents (p = .04) were more often seen in LN, while more tubulointerstitial scarring was seen in LLN (p = .011). At mean follow-up of 1684 d (range: 31-4323), none of the LLN patients developed ESRD. A subset of both LN and cases with LL-fx overlapped with other autoimmune diseases. CONCLUSIONS: Lupus-like pathologic features are seen in a wide array of disease processes. The findings suggest that LLN may be a manifestation of an autoimmune process that overlaps with SLE.

Segmental membranous nephropathy.

Most cases of membranous nephropathy (MGN) present with global and diffuse distribution of subepithelial deposits. However, segmental MGN, in which there is focal or diffuse segmental subepithelial deposits, are occasionally encountered. The clinical and pathologic significance of segmental MGN is not well understood and thought to be more likely due to either early or resolving phase of the global form of MGN. Several case reports and literature available suggest that it may be a manifestation of secondary causes based on pathologic features such as presence of C1q and mesangial deposits, extra-glomerular deposits involving tubular basement membranes, absence of PLA2R and THSD7A, IgG1 and IgG3 subclass dominance, and the presence of other co-existing renal disease. Other reports, however, suggest that some of these cases may be a variant of the primary form of MGN. In this review, we integrate what is known about segmental MGN in order to better direct interpretation of renal biopsies in which it is identified.

Social Behavior in Naked Mole-Rats: Individual Differences in Phenotype and Proximate Mechanisms of Mammalian Eusociality.

Naked mole-rats (Heterocephalus glaber) are small rodents native to east Africa, living in subterranean colonies of up to 300 individuals. Within each colony, reproduction is restricted to a single breeding female and 1-3 breeding males; all other colony members are reproductively suppressed and socially subordinate unless removed from the suppressive cues of the colony. Due to their striking reproductive skew, naked mole-rats are often considered eusocial mammals. Consistent with this idea, there are behavioral specializations and at least some evidence for morphological distinctions within and between the breeding and non-breeding members of the colony. Importantly, naked mole-rats show plasticity in their behavioral phenotype whereby changes in the social environment influence expression of both type and amount of social behavior. Thus, naked mole-rats provide the opportunity to examine the proximate mechanisms controlling individual differences in social behavior, shedding light on how mammals live in complex social groups.

Neutrophils Slow Disease Progression in Murine Lupus via Modulation of Autoreactive Germinal Centers.

Neutrophils are well characterized as mediators of peripheral tissue damage in lupus, but it remains unclear whether they influence loss of self-tolerance in the adaptive immune compartment. Lupus neutrophils produce elevated levels of factors known to fuel autoantibody production, including IL-6 and B cell survival factors, but also reactive oxygen intermediates, which can suppress lymphocyte proliferation. To assess whether neutrophils directly influence the progression of autoreactivity in secondary lymphoid organs (SLOs), we characterized the localization and cell-cell contacts of splenic neutrophils at several stages in the progression of disease in the NZB/W murine model of lupus. Neutrophils accumulate in SLO over the course of lupus progression, preferentially localizing near T lymphocytes early in disease and B cells with advanced disease. RNA sequencing reveals that the splenic neutrophil transcriptional program changes significantly over the course of disease, with neutrophil expression of anti-inflammatory mediators peaking during early-stage and midstage disease, and evidence of neutrophil activation with advanced disease. To assess whether neutrophils exert predominantly protective or deleterious effects on loss of B cell self-tolerance in vivo, we depleted neutrophils at different stages of disease. Neutrophil depletion early in lupus resulted in a striking acceleration in the onset of renal disease, SLO germinal center formation, and autoreactive plasma cell production. In contrast, neutrophil depletion with more advanced disease did not alter systemic lupus erythematosus progression. These results demonstrate a surprising temporal and context-dependent role for neutrophils in restraining autoreactive B cell activation in lupus.

Potassium conservation is impaired in mice with reduced renal expression of Kir4.1.

To better understand the role of the inward-rectifying K channel Kir4.1 (KCNJ10) in the distal nephron, we initially studied a global Kir4.1 knockout mouse (gKO), which demonstrated the hypokalemia and hypomagnesemia seen in SeSAME/EAST syndrome and was associated with reduced Na/Cl cotransporter (NCC) expression. Lethality by ~3 wk, however, limits the usefulness of this model, so we developed a kidney-specific Kir4.1 "knockdown" mouse (ksKD) using a cadherin 16 promoter and Cre-loxP methodology. These mice appeared normal and survived to adulthood. Kir4.1 protein expression was decreased ~50% vs. wild-type (WT) mice by immunoblotting, and immunofluorescence showed moderately reduced Kir4.1 staining in distal convoluted tubule that was minimal or absent in connecting tubule and cortical collecting duct. Under control conditions, the ksKD mice showed metabolic alkalosis and relative hypercalcemia but were normokalemic and mildly hypermagnesemic despite decreased NCC expression. In addition, the mice had a severe urinary concentrating defect associated with hypernatremia, enlarged kidneys with tubulocystic dilations, and reduced aquaporin-3 expression. On a K/Mg-free diet for 1 wk, however, ksKD mice showed marked hypokalemia (serum K: 1.5 ± 0.1 vs. 3.0 ± 0.1 mEq/l for WT), which was associated with renal K wasting (transtubular K gradient: 11.4 ± 0.8 vs. 1.6 ± 0.4 in WT). Phosphorylated-NCC expression increased in WT but not ksKD mice on the K/Mg-free diet, suggesting that loss of NCC adaptation underlies the hypokalemia. In conclusion, even modest reduction in Kir4.1 expression results in impaired K conservation, which appears to be mediated by reduced expression of activated NCC.

Social cues elicit sexual behavior in subordinate Damaraland mole-rats independent of gonadal status.

Damaraland mole-rats (Fukomys damarensis) are among a small number of eusocial mammals. Eusociality is a social system where only a few individuals within a colony engage in direct reproduction, while remaining subordinate members are non-breeders and support reproductive efforts of breeding individuals. Inbreeding avoidance precludes mating between subordinate siblings and between offspring and parents. Interestingly, non-breeders readily attempt to mate with unrelated opposite-sex individuals. This is unusual since the non-breeding females do not attain puberty while in their natal colony. Based on this finding, the present study investigated the role of the gonads in the regulation of mating behaviors in this species and identified the mechanism of inbreeding avoidance. Gonadal-intact and gonadectomized non-breeders from different colonies were removed from their colonies and tested for the expression of sexual behavior. Results indicated that gonadal status had only minor effects on the expression of sexual behavior in either males or females. In a second experiment, sexual behaviors were absent between opposite-sex siblings so long as they had frequent contact with each other; however, following 5 weeks of separation, sexual behavior between these siblings was robustly expressed. Thus, Damaraland mole-rats avoid establishing mating relationships with familiar individuals but will readily mate with unfamiliar individuals of the opposite sex, with genetic relatedness apparently playing little role. The initiation of sexual behavior in Damaraland mole-rats does not require the presence of the gonads, but does require that the members of the pair have not been in contact with one another for at least several weeks.

Protein kinase Cß is required for lupus development in Sle mice.

OBJECTIVE: To evaluate the requirement for protein kinase Cß (PKCß) in the development of lupus in mice, and to explore the potential of targeting PKCß as a therapeutic strategy in lupus. METHODS: Congenic mice bearing the disease loci Sle1 or Sle1 and Sle3, which represent different stages of severity in the development of lupus, were crossed with PKCß-deficient mice. The effect of PKCß deficiency in lupus development was analyzed. In addition, the effects of the PKCß-specific inhibitor enzastaurin on the survival of B cells from mice with lupus and human 9G4-positive B cells as well as the in vivo effect of enzastaurin treatment on the development of lupus in Sle mice were investigated. RESULTS: In Sle mice, PKCß deficiency abrogated lupus-associated phenotypes, including high autoantibody levels, proteinuria, and histologic features of lupus nephritis. Significant decreases in spleen size and in the peritoneal B-1 cell population, reduced numbers of activated CD4 T cells, and normalized CD4:CD8 ratios were observed. PKCß deficiency induced an anergic B cell phenotype and preferentially inhibited autoreactive plasma cells and autoantibodies in mice with lupus. Inhibition of PKCß enhanced apoptosis of both B cells from Sle mice and human autoreactive B cells (9G4 positive). Treatment of Sle mice with the PKCß-specific inhibitor enzastaurin prevented the development of lupus. CONCLUSION: This study identifies PKCß as a central mediator of lupus pathogenesis, suggesting that PKCß represents a promising therapeutic target for the treatment of systemic lupus erythematosus. Moreover, the results indicate the feasibility of using a PKCß inhibitor for the treatment of lupus.

Beneficial effect of novel proteasome inhibitors in murine lupus via dual inhibition of type I interferon and autoantibody-secreting cells.

OBJECTIVE: To investigate the hypothesis that proteasome inhibition may have potential in the treatment of SLE, by targeting plasmacytoid dendritic cells (PDCs) and plasma cells, both of which are critical in disease pathogenesis. METHODS: Lupus-prone mice were treated with the nonselective proteasome inhibitors carfilzomib and bortezomib, the immunoproteasome inhibitor ONX 0914, or vehicle control. Tissue was harvested and analyzed by flow cytometry using standard markers. Nephritis was monitored by evaluation for proteinuria and by histologic analysis of kidneys. Serum anti-double-stranded DNA (anti-dsDNA) levels were measured by enzyme-linked immunosorbent assay (ELISA), and total IgG and dsDNA antibody-secreting cells (ASCs) by enzyme-linked immunospot assay. Human peripheral blood mononuclear cells or mouse bone marrow cells were incubated with Toll-like receptor (TLR) agonists and proteasome inhibitors, and interferon-α (IFNα) levels were measured by ELISA and flow cytometry. RESULTS: Early treatment of lupus-prone mice with the dual-targeting proteasome inhibitors carfilzomib or bortezomib or the immunoproteasome-specific inhibitor ONX 0914 prevented disease progression, and treatment of mice with established disease dramatically abrogated nephritis. Treatment had profound effects on plasma cells, with greater reductions in autoreactive than in total IgG ASCs, an effect that became more pronounced with prolonged treatment and was reflected in decreasing serum autoantibody levels. Notably, proteasome inhibition efficiently suppressed production of IFNα by TLR-activated PDCs in vitro and in vivo, an effect mediated by inhibition of both PDC survival and PDC function. CONCLUSION: Inhibition of the immunoproteasome is equally efficacious as dual targeting agents in preventing lupus disease progression by targeting 2 critical pathways in disease pathogenesis, type I IFN activation and autoantibody production by plasma cells.

A Rare Case of Renal Thrombotic Microangiopathy and Focal Segmental Glomerulosclerosis Secondary to Plasma Cell Leukemia.

Plasma cell dyscrasias are a subset of hematological malignancies involving the production of monoclonal immunoglobulins. This spectrum of disorders includes asymptomatic conditions such as monoclonal gammopathy of unknown significance as well as extremely aggressive malignancies such as plasma cell leukemia. Monoclonal gammopathies are occasionally associated with renal failure, which can occur via many pathophysiological processes. The most common of these is light chain cast nephropathy, but many rare renal complications exist, including thrombotic microangiopathy (TMA) and focal segmental glomerulosclerosis (FSGS). Here, we report a patient with new renal failure with features of TMA and FSGS on biopsy and found to be secondary to plasma cell leukemia.

Error codes at autopsy to study potential biases in diagnostic error.

OBJECTIVES: Current autopsy practice guidelines do not provide a mechanism to identify potential causes of diagnostic error (DE). We used our autopsy data registry to ask if gender or race were related to the frequency of diagnostic error found at autopsy. METHODS: Our autopsy reports include International Classification of Diseases (ICD) 9 or ICD 10 diagnostic codes for major diagnoses as well as codes that identify types of error. From 2012 to mid-2015 only 2 codes were used: UNDOC (major undocumented diagnoses) and UNCON (major unconfirmed diagnoses). Major diagnoses contributed to death or would have been treated if known. Since mid-2015, codes included specific diagnoses, i.e. undiagnosed or unconfirmed myocardial infarction, infection, pulmonary thromboembolism, malignancy, or other diagnosis as well as cause of death. Adult autopsy cases from 2012 to 2019 were assessed for DE associated with reported sex or race (nonwhite or white). 528 cases were evaluated between 2012 and 2015 and 699 between 2015 and 2019. RESULTS: Major DEs were identified at autopsy in 65.9 % of cases from 2012 to 2015 and in 72.1 % from 2015 to 2019. From 2012 to 2015, female autopsy cases showed a greater frequency in 4 parameters of DE, i.e., in the total number of cases with any error (p=0.0001), in the number of cases with UNDOC errors (p=0.0038) or UNCON errors (p=0.0006), and in the relative proportions of total numbers of errors (p=0.0001). From 2015 to 2019 undocumented malignancy was greater among males (p=0.0065); no other sex-related error was identified. In the same period some DE parameters were greater among nonwhite than among white subjects, including unconfirmed cause of death (p=0.035), and proportion of total error diagnoses (p=0.0003), UNCON diagnoses (p=0.0093), and UNDOC diagnoses (p=0.035). CONCLUSIONS: Coding for DE at autopsy can identify potential effects of biases on diagnostic error.

The Clinicopathologic Spectrum of Membranous Nephropathy with Lupus-Like Features.

INTRODUCTION: The pathologic features of membranous lupus nephritis (MLN) are occasionally encountered in secondary membranous nephropathy (sMN) without overt clinical evidence of systemic lupus erythematosus. Moreover, some sMN with lupus-like features (lupus-like membranous nephropathy [LL-MN]) have a clinical presentation more typical of primary membranous nephropathy (pMN). Based on the confounding clinical and pathologic presentation, it is unclear how to categorize and treat these patients. METHODS: We performed immunohistochemical staining for recently discovered target antigens associated with MN -NELL-1, THSD7A, and EXT1/2 and compared the clinicopathologic presentation of patients with LL-MN to those with pMN and MLN. RESULTS: From 2015 to 2020, there were 21 patients with MLN and 99 with MN, of which 59% were diagnosed pMN and 41% sMN. 44% of sMN patients showed lupus-like features (LL-fx). All LL-MN patients were negative for PLA2R and NELL1, but 12% were positive for EXT1/2. 50% of LL-MN patients had an identifiable systemic disease, of which 56% were autoimmune disease (AD) and 44% infection. Compared to pMN, LL-MN had a higher incidence of underlying AD (p = 0.02). Within pMN, 24% also had LL-fx (LL-pMN), and all but 1 were PLA2R- (78%) or NELL1-positive (15%). Only 5% of pMN patients had an AD, 66% of which showed LL-fx. Most idiopathic LL-MN were treated and behaved clinically similarly to pMN. There were no differences in outcome in terms of progression toward end-stage renal disease or mortality between LL-MN versus pMN and MLN. CONCLUSION: LL-MN appears to have a significant association with underlying AD and has a subset showing EXT1/2 positivity, whereas most LL-pMN and idiopathic LL-MN likely represent an atypical pathologic presentation of pMN.

The spectrum of macrophage-predominant inflammatory myocardial disease presenting as fulminant heart failure.

BACKGROUND: Endomyocardial biopsy results are integral for diagnosis and management of myocarditis. Current diagnostic classifications of myocarditis are based on the microscopic and immunochemical characterization of inflammation do not include monocyte/macrophage-predominant (i.e. "histiocytic") myocarditis as a histologic subtype. METHODS: Endomyocardial biopsies from 6 patients with sudden heart failure were reviewed by 3 cardiac pathologists. Routine stains and immunostains to identify T cells and monocytes/macrophages, complement C4d, and endothelium were applied. Electron microscopy was performed in 2 cases. RESULTS: The 6 patients included 2 with diagnoses of systemic lupus erythematosus (SLE) and 4 without known disease. Microscopy showed space-occupying inflammation in 2 cases and interstitial inflammation in 4. No giant cell myocarditis or eosinophilic myocarditis was found. Immunostains showed infiltration predominantly by macrophages and/or monocytes with markedly fewer T cells. In 4 of 6 cases necrotic cells were immunopositive for complement C4d. Monocytes we identified immunochemically within the microvasculature in 5 cases and by electron microscopy in 2. Patients with SLE had microvascular C4d positivity or interstitial/sarcolemmal staining. Clinical outcomes ranged from spontaneous resolution to persistent heart failure requiring an internal cardioverter/defibrillator. CONCLUSIONS: (1) Heart failure with CD68 predominant inflammation ("histiocytic" myocardial inflammatory disease, HMID) occurs with variable clinical presentation and outcome; (2) HMID may be primary or secondary; (3) some cases of HMID show features suggestive of antibody and/or complement mediated myocardial injury, and (4) HMID is a diagnosis distinct from those in classification systems currently in use.

A pilot study comparing in-person and remote outpatient substance use treatment services on quality-of-life outcomes.

Background: The widespread shift from in-person to Telehealth services during the Covid-19 pandemic irreversibly shifted the landscape of outpatient substance use treatment. This shift was necessitated by health, rather than data-driven, reasons. As we reflect on whether to continue providing Telehealth services moving forward, we require empirical support on the effectiveness of Telehealth services (compared to in-person services) in terms of patient outcomes, such as Quality of Life (QOL), to support this decision. Objective: To present data from a pilot project comparing changes in QOL across patients receiving outpatient in-person versus Telehealth substance use treatment in five clinics across New York State. Method: To retrospectively compare total self-reported QOL scores from admission to 3-months later utilizing the Quality-of-Life Enjoyment and Satisfaction scale during in-person (pre-pandemic, n = 298) and Telehealth (pandemic, n = 316) services with a mixed repeated measures ANOVA. Results: Self-reported QOL scores significantly improved across the first three months, regardless of treatment modality. Conclusion: Telehealth and in-person treatment appear comparable on QOL outcomes over the first 3 months of outpatient treatment. Both modalities are associated with improved QOL scores. Scientific significance: These preliminary findings provide evidence that Telehealth services are associated with positive patient outcomes and appear comparable to QOL outcomes among patients receiving in-person services. Future directions include further assessment of additional clinical outcomes and investigation into causal mechanisms.

An untapped resource: characteristics of thrombus recovered from intermediate or high risk pulmonary embolus patients.

INTRODUCTION: Response to anticoagulation varies during management of acute hospitalized pulmonary embolism. We aimed to study thrombus histology in pulmonary embolism samples removed during acute surgical embolectomy to evaluate whether thrombus morphology was similar between patients and whether there was an association with duration of symptoms and/or resolution on follow up imaging. METHODS: This was a retrospective observational single center study at the University of Rochester Medical Center. We evaluated patients that underwent acute surgical embolectomy and followed up in our clinic 2 - 4 months after the event with Ventilation/Perfusion (V/Q) scan obtained for all regardless of symptoms. Thromboemboli were formalin fixed and processed for light microscopy in the hospital histopathology laboratory. Four-micron thick sections were stained with hematoxylin and eosin, Masson trichrome, and Verhoeff elastic tissue stains. Immunohistochemistry was performed using anti-CD31 and anti-CD68. Slides were independently evaluated for time-dependent microscopic changes using Irniger's classification by two blinded pathologists. RESULTS: Sixteen patients underwent embolectomy with fifteen having V/Q imaging at follow up. The majority of patients were female. Samples showed a generally similar overall architecture that included a central core composed primarily of red blood cells and fibrin and an outer layer of platelets and monocytes. Two samples had evidence of fibrosis and recanalization. CONCLUSIONS: We found heterogeneous histopathology in samples obtained during acute embolectomy. Further prospective studies should systematically characterize clot morphology and evaluate treatment response and outcomes. Careful thrombus specimen measurement and consistent sampling for sections will be required to draw firm conclusions.

Light chain deposition disease masquerading as smoking-associated nodular glomerulosclerosis with deposits identified by electron microscopy only.

Light chain deposition disease (LCDD) is a form of monoclonal gammopathy of renal significance. The diagnosis is based on the immunofluorescence (IF) findings of linear monoclonal light chain staining of basement membranes throughout the kidney, which appear as non-organized, granular punctate to powdery electron dense deposits by electron microscopy (EM). Although "LCDD by IF only" without EM deposits has been well-described, LCDD identified by EM with negative IF is very rare and hardly mentioned in the literature. Herein we describe a case of lambda-type LCDD that appeared negative by IF and showed light microscopic findings of nodular glomerulosclerosis, which was initially attributed to the patient's history of significant tobacco use and uncontrolled hypertension. However, EM later showed powdery electron dense material in focal glomerular and tubular basement membranes and mesangium. Subsequent bone marrow analysis revealed greater than 60% lambda-restricted plasma cells. We report this case to illustrate that within the differential diagnosis of nodular sclerosis, monoclonal immunoglobulin deposition disease (MIDD) should remain in the differential even if immunofluorescence appears negative as EM can prove to be crucial in identifying cases of MIDD.