A Case of Anti-neutrophil Cytoplasmic Antibody-Associated Vasculitis Presenting With Diffuse Alveolar Hemorrhage and Renal Sparing.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a necrotizing vasculitis disease that traditionally includes three variants classified based on their clinical and pathological appearance: microscopic polyangiitis (MPA), granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis (alternatively, Churg-Strauss syndrome). The mainstay of AAV treatment is immunosuppressive treatments, which improve survival and lower rates of end-stage kidney disease. Here we describe a patient with MPA ANCA who presented with diffuse alveolar hemorrhage and, six months later, recurrent pulmonary hemorrhage with renal sparing while off therapy.

Endocarditis-Associated C3-Dominant Glomerulonephritis in a Patient With a Solitary Kidney.

Infective endocarditis (IE) is still seen globally with acute kidney injuries remaining a common complication of the disease. Histological specimens often display either diffuse or focal endocapillary proliferation as well as neutrophilic infiltration in endocarditis-related renal disease. C3-dominant glomerulonephritis (C3GN) utilizes mechanisms of complement activation unique from IE-associated glomerulonephritis. In C3GN, micrographic review may reveal scattered accumulation of C3 fragments with subepithelial hump formation and mesangial electron-dense deposits that help solidify the diagnosis of this recently discovered pathological phenomenon. Herein, we summarize a clinical case of likely IE-related C3GN without hypocomplementemia in a patient with a single kidney to help compare and contrast the key elements of each process. A 27-year-old Hispanic man with a past medical history of nephrectomy for renal donation presented to a community hospital with a high fever and altered sensorium. A serum creatinine of 6.98 mg/dL with unknown baselines, nephrotic-range proteinuria, and severe rhabdomyolysis plus methicillin-sensitive Staphylococcus aureus bacteremia were quickly discovered after admission. A later transesophageal echocardiogram showed a hypermobile vegetation along the anterior mitral valve leaflet confirming suspected IE. The patient's serum C3 and C4 complement levels and antinuclear, myeloperoxidase, and proteinase-3 antibody titers were all within normal limits. A renal biopsy pursued in the etiological investigation of this non-oliguric acute kidney injury revealed a single subepithelial electron-dense deposit and granular immunofluorescent C3 staining in peripheral mesangial segments. Dominant C3 deposition without associated immunoglobulins can result from in situ localization of bacterial antigens promoting plasmin activation to recruit neutrophils and monocytes to initiate leukocyte-mediated damage. Immunosuppressive therapies for C3GN triggering antibody-independent activation of the alternative or lectin complement pathways may be merited where disease remission becomes difficulty to achieve.

Severe Erosive Esophagitis Secondary to Gastric Outlet Obstruction Related to Pseudomyxoma Peritonei.

Pseudomyxoma peritonei (PMP) is a rare clinical condition characterized by a mucin-producing tumor. PMP tumor cells migrate to abdominal and pelvic sites, eventually enveloping intra-abdominal organs and compressing the gastrointestinal tract. Patients with PMP are often asymptomatic in early stages of the disease, but in later stages develop symptoms including abdominal pain, acute abdomen, increased abdominal girth, vomiting, and bowel obstruction. Nonspecific symptoms combined with a relatively modest accuracy of imaging modalities frequently lead to delay in PMP diagnosis and treatment, thereby increasing morbidity. We present a case demonstrating severe erosive esophagitis as a result of PMP-associated gastric antrum compression.

Thrombotic Microangiopathy and Venous Thrombosis in a Patient With Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic pauci-immune small vessel vasculitis. Its various presentations make AAV diagnosis challenging. Here, we present a case of AAV with thrombotic microangiopathy (TMA) and deep venous thrombosis (DVT). An 82-year-old Hispanic woman presented to the emergency department with malaise, lower extremity pain, and oliguria for three days. Her vital signs were normal, and her physical examination was unremarkable. The initial laboratory revealed thrombocytopenia (18 x 103/µL), elevated creatinine (8.35 mg/dL), high lactic acid dehydrogenase (1627.5 U/L), an international normalized ratio of 1.6, and an activated partial thromboplastin time of 49 seconds. Urinalysis showed microscopic hematuria and proteinuria, and peripheral smear revealed schistocytes. She was admitted with concern for TMA. Further workup revealed an antinuclear antibody titer of 1:80, an ADAMTS13 level of 62%, a rheumatoid factor level of 151.7 IU/L, and myeloperoxidase (MPO)-ANCA level of 173 AU/mL. A computed tomography scan of the chest/abdomen/pelvis revealed pulmonary fibrosis and multifocal consolidations. She was also found to have extensive DVT of the lower extremities. Renal biopsy revealed early changes of TMA with one cellular crescent. She was diagnosed with AAV based on the kidney and lung findings, as well as the high titer MPO-ANCA. Her platelet count and creatinine improved significantly following treatment with plasma exchange, steroids, and rituximab. Unfortunately, she was then found to have an acute bowel perforation and expired. Even though typically rare, an increased incidence of venous thromboembolism (VTE) and TMA has been reported in patients with AAV. Its prompt recognition and treatment by clinicians are critical to mitigate the unfavorable outcomes from this condition.

High-grade microsteatosis and delay in hepatic function after orthotopic liver transplantation.

Macrovesicular steatosis may be used to exclude potential donor livers from use in transplantation. Livers with more than 50% macrovesicular steatosis are believed to be at risk for delayed graft function and primary graft nonfunction. However, the significance of even extensive microsteatosis is uncertain. The hematoxylin and eosin-stained slides of postperfusion donor liver biopsies from 161 transplants were examined. The type of steatosis (macrovesicular, low-grade microvesicular, and high-grade microvesicular ) was determined, and the extent of each type was semiquantitated into 3 groups (none, ≤50%, and >50%). These were analyzed in conjunction with the donor and recipient age and the recipient's sex and MELD score against postoperative outcome parameters, including serial measures of serum lactate, days in the intensive care unit and overall in hospital, and death less than 3 months posttransplant. High-grade microsteatosis usually coexisted with macrosteatosis and infrequently with low-grade microsteatosis. There was no significant association between the extent of either macrosteatosis or low-grade microsteatosis (even when >50%) and any of the outcome parameters. In contrast, the presence of high-grade microsteatosis was significantly associated with delayed hepatic function, but not with the other outcome parameters. Donor age greater than 60 years was associated with late postoperative rise in serum lactate, and higher recipient MELD score was associated with extended stay in the intensive care unit and in the hospital. In this patient population, the association of steatosis with adverse outcomes was largely restricted to delay in postoperative hepatic function, and was due to the subgroup that displayed high-grade microsteatosis.

Clinical array-based karyotyping of breast cancer with equivocal HER2 status resolves gene copy number and reveals chromosome 17 complexity.

BACKGROUND: HER2 gene copy status, and concomitant administration of trastuzumab (Herceptin), remains one of the best examples of targeted cancer therapy based on understanding the genomic etiology of disease. However, newly diagnosed breast cancer cases with equivocal HER2 results present a challenge for the oncologist who must make treatment decisions despite the patient's unresolved HER2 status. In some cases both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are reported as equivocal, whereas in other cases IHC results and FISH are discordant for positive versus negative results. The recent validation of array-based, molecular karyotyping for clinical oncology testing provides an alternative method for determination of HER2 gene copy number status in cases remaining unresolved by traditional methods. METHODS: In the current study, DNA extracted from 20 formalin fixed paraffin embedded (FFPE) tissue samples from newly diagnosed cases of invasive ductal carcinoma referred to our laboratory with unresolved HER2 status, were analyzed using a clinically validated genomic array containing 127 probes covering the HER2 amplicon, the pericentromeric regions, and both chromosome 17 arms. RESULTS: Array-based comparative genomic hybridization (array CGH) analysis of chromosome 17 resolved HER2 gene status in [20/20] (100%) of cases and revealed additional chromosome 17 copy number changes in [18/20] (90%) of cases. Array CGH analysis also revealed two false positives and one false negative by FISH due to "ratio skewing" caused by chromosomal gains and losses in the centromeric region. All cases with complex rearrangements of chromosome 17 showed genome-wide chromosomal instability. CONCLUSIONS: These results illustrate the analytical power of array-based genomic analysis as a clinical laboratory technique for resolution of HER2 status in breast cancer cases with equivocal results. The frequency of complex chromosome 17 abnormalities in these cases suggests that the two probe FISH interphase analysis is inadequate and results interpreted using the HER2/CEP17 ratio should be reported "with caution" when the presence of centromeric amplification or monosomy is suspected by FISH signal gains or losses. The presence of these pericentromeric copy number changes may result in artificial skewing of the HER2/CEP17 ratio towards false negative or false positive results in breast cancer with chromosome 17 complexity. Full genomic analysis should be considered in all cases with complex chromosome 17 aneusomy as these cases are likely to have genome-wide instability, amplifications, and a poor prognosis.