Assessing the Effects of Geniculate Artery Embolization in a Nonsurgical Animal Model of Osteoarthritis.

PURPOSE: To create a nonsurgical animal model of osteoarthritis (OA) to evaluate the effects of embolotherapy during geniculate artery embolization (GAE). MATERIALS AND METHODS: Fluoroscopy-guided injections of 700 mg of sodium monoiodoacetate were performed into the left stifle in 6 rams. Kinematic data were collected before and after induction. At 10 weeks after induction, Subjects 1 and 4-6 underwent magnetic resonance (MR) imaging with dynamic contrast enhancement (DCE) and Subjects 1, 3, and 4-6 underwent angiography with angiographic scoring to identify regions with greatest disease severity for superselective embolization (75-250-µm microspheres). Target vessel size was measured. At 24 weeks after angiography, DCE-MR imaging, angiography, and euthanasia were performed, and bilateral stifles were harvested. Medial/lateral tibial and femoral condylar, patellar, and synovial samples were cut, preserved, decalcified, and scored using the Osteoarthritis Research Society International criteria. The stifle and synovium Whole-Organ Magnetic Resonance Imaging Score and Multicenter Osteoarthritis Study score were determined. The volume transfer constant (Ktrans) and extracellular volume fraction (ve) were calculated from DCE-MR imaging along the lateral synovial regions of interest. RESULTS: The mean gross and microscopic pathological scores were elevated at 38 and 61, respectively. Mean synovitis score was elevated at 9.2. Mean pre-embolization and postembolization angiographic scores were 5 and 3.8, respectively. Mean superior, transverse, and inferior geniculate artery diameters were 3.1 mm ± 1.21, 2.0 mm ± 0.50, and 1.6 mm ± 0.41 mm, respectively. Mean pre-embolization and postembolization cartilage and synovitis scores were elevated at 35.13 and 73.3 and 5.5 and 9.2, respectively. The Ktrans/ve values of Subjects 4, 5, and 6 were elevated at 0.049/0.38, 0.074/0.53, and 0.065/0.51, respectively. Altered gait of the hind limb was observed in all subjects after induction, with reduced joint mobility. No skin necrosis or osteonecrosis was observed. CONCLUSIONS: A nonsurgical ovine animal knee OA model was created, which allowed the collection of angiographic, histopathological, MR imaging, and kinematic data to study the effects of GAE.

Deficiency of the Angiotensinase Aminopeptidase A Increases Susceptibility to Glomerular Injury.

Aminopeptidase A (APA) is expressed in glomerular podocytes and tubular epithelia and metabolizes angiotensin II (AngII), a peptide known to promote glomerulosclerosis. In this study, we tested whether APA expression changes in response to progressive nephron loss or whether APA exerts a protective role against glomerular damage and during AngII-mediated hypertensive kidney injury. At advanced stages of FSGS, fawn-hooded hypertensive rat kidneys exhibited distinctly increased APA staining in areas of intact glomerular capillary loops. Moreover, BALB/c APA-knockout (KO) mice injected with a nephrotoxic serum showed persistent glomerular hyalinosis and albuminuria 96 hours after injection, whereas wild-type controls achieved virtually full recovery. We then tested the effect of 4-week infusion of AngII (400 ng/kg per minute) in APA-KO and wild-type mice. Although we observed no significant difference in achieved systolic BP, AngII-treated APA-KO mice developed a significant rise in albuminuria not observed in AngII-treated wild-type mice along with increased segmental and global sclerosis and/or collapse of juxtamedullary glomeruli, microcystic tubular dilation, and tubulointerstitial fibrosis. In parallel, AngII treatment significantly increased the kidney AngII content and attenuated the expression of podocyte nephrin in APA-KO mice but not in wild-type controls. These data show that deficiency of APA increases susceptibility to glomerular injury in BALB/c mice. The augmented AngII-mediated kidney injury observed in association with increased intrarenal AngII accumulation in the absence of APA suggests a protective metabolizing role of APA in AngII-mediated glomerular diseases.

Pseudotumors of the placenta.

The placenta is one of the most common gross pathology specimens encountered by surgical pathologists, yet primary tumors are exceptionally rare and even rarer are entities with the potential to mimic malignancy. There are many nonneoplasticmass forming lesions in the placenta that are important to be aware of as many of these can be associated with adverse outcomes in the mother and fetus. Also important are entities which may be observed microscopically in the placenta and potentially confused as a malignancy. Knowledge of these potential pitfalls is essential to avoid making an incorrect diagnosis and causing undue alarm.

Benign soft tissue lesions that may mimic malignancy.

Soft tissue lesions which mimic malignancy (pseudosarcomas), represent a significant diagnostic challenge for pathologists. Many features often associated with malignancy including rapid and infiltrative growth, increased cellularity and mitotic activity, and nuclear pleomorphism are present in benign and reactive conditions. This review highlights repair reactions including nodular fasciitis, proliferative fasciitis/myositis, intravascular papillary endothelial hyperplasia, and fat necrosis; lipoma and spindle cell/pleomorphic lipoma; fibroepithelial stromal (pseudosarcomatoid) polyp; phosphaturic mesenchymal tumor; and myxoma. While not inclusive of every pseudoneoplastic soft tissue lesion, this review emphasizes important diagnostic pitfalls and stresses the value of clinical, pathologic, and radiologic correlation.

The pathologic diagnosis of carcinoma in various tissues.

Carcinoma is defined as cancer arising from the epithelial cells that line an organ or tissue. The most common carcinoma in males arises in the prostate and breast in females; while the most significant cause of cancer related mortality in the United States is carcinoma of the lung. Cancers typically begin as a clonal proliferation of cells that have acquired distinct mutations, which then progress to invasive carcinoma as the cells breach the underlying basement membrane associated with the tissue of origin. This transition to invasive carcinoma carries with it the potential to invade blood vessels or lymphatic channels and metastasize to lymph nodes or distant tissues resulting in increased morbidity and mortality. The histologic diagnosis of carcinoma is rendered based on both the cytologic and architectural features of the tumor, as well as the location of the proliferating cells and the interaction with the surrounding stromal elements.

Endocrine mucin-producing sweat gland carcinoma: a systematic review and meta-analysis.

BACKGROUND: Endocrine mucin-producing sweat gland carcinoma is a rare, under-reported cutaneous adnexal tumor that is often misdiagnosed and has an unknown incidence of metastasis. OBJECTIVE: To determine the incidence of metastasis and tumor recurrence, as well as diagnostic accuracy and current trends in treatment modality. METHODS: A search was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Tumor pathology and clinical data concerning demographics, presentation, diagnosis, treatment and follow-up were assessed. RESULTS: A total of 36 publications with 110 cases were identified. Initial pathological diagnosis was incorrect in 45.5% of cases. One case of metastatic disease was reported. The incidence of locoregional recurrence was 10.6% over a mean follow-up period of 21.3 months. Of cases with known methods of resection, 34.6% were resected by excisional biopsy, 42.8% were resected by wide surgical excision, and 31.3% were cleared by Mohs micrographic surgery. LIMITATIONS: The low reported incidence and level of evidence was suboptimal with only case reports and retrospective case studies being reported. CONCLUSION: Reported cases of this pathology demonstrate poor diagnostic accuracy. High rates of misdiagnosis and inadequate definitive treatment suggest the need for more comprehensive work-up and management of lesions suspicious for this pathology.

Cytologic features of malignant rhabdoid tumor of the liver: A case report and literature review.

As one of the SMARCB1-deficient tumors, malignant rhabdoid tumor (MRT) of the liver is a rare and aggressive malignancy, typically in young children below the age of 3 years. The diagnosis of MRT of the liver is challenging both clinically and pathologically due to the rarity of the tumor and misdiagnosing it as a hepatoblastoma is not uncommon. Although MRT of the liver and hepatoblastoma share some similar clinical and morphological features, their prognosis and the clinical management are significantly different. Therefore, an accurate diagnosis of MRT or hepatoblastoma is critical for patient care. Here we report a case of an 8-month-old female with MRT of the liver diagnosed by fine needle aspiration and core biopsy. The cytologic and histological features, the results of immunohistochemical studies, and clinical follow-up information are presented. Recent literature regarding the diagnosis and treatment of this tumor were reviewed.

Development of a lupus nephritis suboptimal response prediction tool using renal histopathological and clinical laboratory variables at the time of diagnosis.

OBJECTIVE: Lupus nephritis (LN) is an immune complex-mediated glomerular and tubulointerstitial disease in patients with SLE. Prediction of outcomes at the onset of LN diagnosis can guide decisions regarding intensity of monitoring and therapy for treatment success. Currently, no machine learning model of outcomes exists. Several outcomes modelling works have used univariate or linear modelling but were limited by the disease heterogeneity. We hypothesised that a combination of renal pathology results and routine clinical laboratory data could be used to develop and to cross-validate a clinically meaningful machine learning early decision support tool that predicts LN outcomes at approximately 1 year. METHODS: To address this hypothesis, patients with LN from a prospective longitudinal registry at the Medical University of South Carolina enrolled between 2003 and 2017 were identified if they had renal biopsies with International Society of Nephrology/Renal Pathology Society pathological classification. Clinical laboratory values at the time of diagnosis and outcome variables at approximately 1 year were recorded. Machine learning models were developed and cross-validated to predict suboptimal response. RESULTS: Five machine learning models predicted suboptimal response status in 10 times cross-validation with receiver operating characteristics area under the curve values >0.78. The most predictive variables were interstitial inflammation, interstitial fibrosis, activity score and chronicity score from renal pathology and urine protein-to-creatinine ratio, white blood cell count and haemoglobin from the clinical laboratories. A web-based tool was created for clinicians to enter these baseline clinical laboratory and histopathology variables to produce a probability score of suboptimal response. CONCLUSION: Given the heterogeneity of disease presentation in LN, it is important that risk prediction models incorporate several data elements. This report provides for the first time a clinical proof-of-concept tool that uses the five most predictive models and simplifies understanding of them through a web-based application.

Extramedullary Plasmacytoma of the Right Main Bronchus.

Extramedullary plasmacytomas are rare tumors that typically involve the head and neck region. Only three reports exist in the literature of extramedullary plasmacytomas that involve the lower airways. We report the case of a 54-year-old woman with EMP of the right mainstem bronchus treated with sleeve resection.

Success in Implementation of a Resident In-Service Examination Review Series.

OBJECTIVES: Primary pathology board certification has been correlated with senior resident in-service examination (RISE) performance. We describe our success with an annual, month-long review series. METHODS: Aggregate program RISE performance data were gathered for 3 years prior to and 3 years following initiation of the review series. In addition, mean United States Medical Licensing Examination Step 1 and 2 Clinical Knowledge scores for residents participating in each RISE examination were obtained to control for incoming knowledge and test-taking ability. Linear models were used to evaluate differences in average RISE performance prior to and following the initiation of the review series in addition to controlling for relevant covariates. RESULTS: Significant improvement was noted in the grand total, anatomic pathology section average, clinical pathology section average, and transfusion medicine section. Although not statistically significant, improvement was noted on the cytopathology and clinical chemistry sections. There was no significant difference in scores in hematopathology, molecular pathology, and the special topics section average. In addition, improvement in primary pathology board certification rates was also noted. CONCLUSIONS: Institution of a month-long RISE review series demonstrated improved overall performance within our training program. The success could easily be replicated in any training program without significant disruption to an annual didactic series.