Catherine S. Abendroth

Variance in the Interpretation of Cervical Biopsy Specimens Obtained for Atypical Squamous Cells of Undetermined Significance

We sought to determine whether the variability in dysplasia rates in cases of atypical squamous cells of undetermined significance (ASCUS) reflects variability in interpretation of cervical biopsy specimens. In phase 1, 124 biopsy specimens obtained because of a cytologic diagnosis of ASCUS were reviewed independently by 5 experienced pathologists. Diagnostic choices were normal, squamous metaplasia, reactive, indeterminate, low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL). The rate of dysplasia ranged from 23% to 51%. All pathologists agreed in 28% of cases. In 52% of cases, the diagnoses ranged from benign to dysplasia. The overall interobserver agreement was poor. In phase 2, 60 cervical biopsy specimens (21 obtained for ASCUS, 22 for LSIL, and 17 for HSIL) were evaluated using the same diagnostic choices. Agreement was better in biopsies performed for HSIL and LSIL compared to those for ASCUS. Intraobserver reproducibility in the interpretation of biopsies performed for ASCUS ranged from poor to excellent. We conclude that variability in the interpretation of biopsy specimens plays an important role in the differences in rates of dysplasia reported for the follow-up of ASCUS.

Acute Renal Failure following Immunoglobulin Therapy

Intravenous IgG infusion has infrequently been reported to cause acute renal failure. In almost all these reports, a sucrose containing IgG product was believed to be the cause of renal injury. Sucrose-induced osmotic nephrosis has been well described in the literature. In this report, we describe a case of acute anuric renal failure following a large infusion of intravenous IgG containing sucrose. Urine cytology demonstrated typical osmotic injury to the renal tubular epithelial cells. Early recovery of renal function was achieved by dialytic removal of sucrose from the circulation.

Peloisis hepatis due to Bartonella henselae in transplantation : a hemato-hepato-renal syndrome

BACKGROUND Bacillary peliosis hepatis is an uncommon but well recognized disease due to disseminated Bartonella infections occurring predominantly in immunocompromised individuals infected with human immunodeficiency virus, type 1. A similar condition in the absence of Bartonella infection when described in organ transplant patients was felt to be secondary to azathioprine and/or cyclosporine. METHODS Herein, we report the first case of bacillary peliosis hepatis due to systemic Bartonella henselae infection in a patient after kidney transplant. The patient presented with severe anemia, persistent thrombocytopenia, and hepato-renal syndrome. DNA-based polymerase chain reactions (PCR), which allowed direct detection of both B henselae and quintana DNA in patients peripheral blood and liver tissue, were used. Indirect immunofluorescence assay for Bartonella serology was performed on peripheral blood. RESULTS Histopathology of the liver biopsy demonstrated peliosis hepatis. Indirect immunofluorescence assay for Bartonella serology was positive, and B henselae DNA was identified by PCR in the peripheral blood and liver tissue. Treatment with a 3-month course of oral erythromycin resulted in an excellent clinical response. CONCLUSIONS The present case suggests that although various anti-rejection therapies and opportunistic infections are associated with hepatic and renal dysfunction along with bone marrow suppression, the diagnostic evaluation in this situation should include liver biopsy and a careful search for evidence of systemic Bartonella infection, e.g., exposure to cats, Bartonella serology, and Bartonella DNA by PCR. A reduction in immunosuppression and prolonged therapy with antibiotics such as erythromycin will often result in early recovery.

Cytologic features of deep juvenile xanthogranuloma

Juvenile xanthogranuloma (JXG) is a rare lesion of the skin and deep tissues whose cytologic features have not previously been published. We report on 2 cases of JXG in patients aged 5 days and 5 yr who presented with an axillary mass and enlarged supraclavicular lymph node, respectively. Fine‐needle aspiration and touch imprints made from the surgical biopsies yielded cellular specimens composed of histiocytes, multinucleated Touton‐type giant cells, and variable admixtures of lymphocytes and eosinophils. One lesion was composed primarily of benign‐appearing histiocytes with admixed multinucleated giant cells and a few lymphocytes. The second lesion consisted of a few histiocytes, occasional Touton giant cells, many lymphocytes, and scattered fibroblasts. The histiocytes were CD68‐positive and S100‐negative. Histologic follow‐up confirmed the diagnosis of juvenile xanthogranuloma. One patient was lost to follow‐up; the other is alive without evidence of recurrence 1 yr after surgery. We conclude that deep JXG has characteristic and diagnostic cytologic features. Diagn Cytopathol 1996;15:329–333.

Endocervical involvement in endometrial adenocarcinoma is not prognostically significant and the pathologic assessment of the pattern of involvement is not reproducible

OBJECTIVES Since 1988, cervical gland involvement and stromal invasion defined stage IIA and stage IIB endometrial carcinoma. In 2009, FIGO changed the criteria for stage II disease to include only those with cervical stromal invasion. We wished to: 1) assess the reproducibility of pathologists to distinguish patterns of cervical spread, and 2) determine the prognostic significance of cervical involvement. METHODS Slides from 46 women with cervical involvement by endometrial adenocarcinoma were scored for 5 patterns of involvement by 6 experienced pathologists to determine reproducibility. To assess prognostic significance, 206 patients with FIGO 1988 stage II adenocarcinoma formed the study population with matched FIGO stage I controls. RESULTS At least 5 of the 6 pathologists agreed that the cervix was involved in the 46 cases. The reproducibility for cervical gland involvement and endocervical stromal invasion was slight (kappas of 0.15 and 0.28). The survival with any type of cervical involvement was not significantly different from that of matched stage I controls (p=0.18). The 5year recurrence-free survival rates were 84% for FIGO 1988 stage I, 73% for stage IIA, and 82% for stage IIB (FIGO 2009 stage II). CONCLUSIONS Pathologists reliably recognize cervical involvement by endometrial carcinoma. However, reproducibility for the determination of pattern of cervical spread by experienced pathologists is too low to be of clinical utility. Women with spread of carcinoma to the cervix do not have a significantly lower survival than matched stage I controls. Cervical spread should not be the basis for determination of stage II disease.

Renal crystal storing histiocytosis in a patient with multiple myeloma

Dear Editor, Crystal storing histiocytosis (CSH) is a very rare disorder characterized by accumulation of monoclonal immunoglobulin light chains within histiocytes. Herein, we present a case of CSH associated with multiple myeloma (MM). A 66-year-old Caucasian male patient was found to have monoclonal serum proteins during the work-up of acute renal insufficiency. His past medical history was significant for hypertension and multiple cysts in kidneys and liver. Polycystic kidney disease was ruled out, and the radiologic appearance of his liver cysts was consistent with Caroli’s disease, a rare inherited disorder characterized by bile duct dilatation. Laboratory tests showed a serum creatinine at 2.5 mg/dL, serum immunofixation was positive for monoclonal IgG-kappa proteins, IgG level was 1,946 mg/dL (normal, 700–1600), M component was 1.89 g/dL, and serum free kappa level was 60 mg/dL (normal, 0.33–1.94). In the urine, total proteins were 55 mg/dL (normal, <12), and urine free kappa level was 194 mg/dL (normal, <2.4). The monoclonal IgG-kappa protein belonged to the IgG4 subclass. Bone marrow biopsy provided the diagnosis of MM, because the aspirate contained 35% of plasma cells, kappa-restricted at flow cytometry. Cytogenetic analysis was normal, and Congo Red staining was negative for amyloidosis. The bone marrow contained crystalline and globular histiocytes, CD68+ at immunohistochemistry staining, with morphologic features typical of CSH (Fig. 1). A kidney biopsy was done, to clarify whether patient’s renal insufficiency was related to MM or, instead, to nephrosclerosis from his longstanding hypertension. The renal core biopsy demonstrated global glomerulosclerosis, tubular atrophy, interstitial fibrosis, and a cytologically benign lymphoplasmacytic interstitial infiltrate. Histiocytes were sparse to absent on light microscopy. Congo Red staining for amyloid deposition was negative, and there were no MM-type casts. The thick descending limbs of the proximal tubules in the outer medulla showed expansion of cytoplasmic volume and bright eosinophilia on H&E staining. Small irregular crystals were identified in the apical cytoplasm on Jones silver staining (Fig. 2). Electron microscopy revealed variably shaped crystals, ranging in size from 0.8 to 5.0 μm, in the epithelial cell cytoplasm, in the tubular lumina (Fig. 3a), and within histiocytes (Fig. 3b). Some of the crystals had internal defects, apparent layering, or entrapped cytoplasm, sugAnn Hematol (2009) 88:807–809 DOI 10.1007/s00277-008-0660-z

Diabetic Glomerulosclerosis and Chronic Renal Failure With Absent-to-Minimal Microalbuminuria

We report the case of an elderly black woman with a 20-year history of insulin-independent diabetes mellitus (IDDM), chronic renal failure, hypertension, proliferative retinopathy, and classical histologic features of diabetic glomerulosclerosis on renal biopsy. Repeat determinations of urinary albumin excretion rates failed to disclose significant microalbuminuria. This presentation should remind the clinician that a small minority of patients with IDDM of long duration may have severe diabetic glomerulosclerosis and renal insufficiency without detectable microalbuminuria.

Fatal malignant metastastic epithelioid angiomyolipoma presenting in a young woman: case report and review of the literature

Epithelioid angiomyolipomas (EAMLs) are rare mesenchymal tumors whose malignant variant is extremely uncommon and highly aggressive. Treatment strategies include chemo radiation, transcatheter arterial embolization and surgical resection, which has remained the mainstay treatment. Targeted therapies including mammalian target of rapamycin (mTOR) inhibitors such as Temsirolimus may offer some hope for progressive malignant EAMLs that are not amenable to other treatment modalities. We report a fatal case in a young female who presented with rapidly progressive metastatic EAML that did not respond to mTOR therapy. The literature has shown reduction in tumor burden with the use of mTOR inhibitors, but unfortunately due to the rarity of malignant EAML, a meaningful approach to treatment remains challenging.

Multiple fine-needle biopsies using a coaxial technique: Efficacy and a comparison of three methods

PurposeCompare the success of three coaxial fineneedle biopsy techniques in obtaining multiple cytologic specimens of high quality.MethodsFor each of three different biopsy needle and technique combinations (aspiration: 22-gauge Chiba; capillary: 22-gauge Chiba; 22-gauge Autovac aspiration biopsy gun), 30 sites (15 liver, 15 kidney) were selected for coaxial fine-needle biopsy in cadaveric liver and kidneys. For each coaxial technique, three sequential biopsies were performed through an 18-gauge coaxial needle at each of multiple sites. The quality of the resultant 270 specimens was graded by a blinded cytopathologist using a previously published grading scheme.ResultsUsing the coaxial technique, there was no significant dropoff in the cytologic specimen quality among the first, second, and third biopsies at a specific site, regardless of the order of the techniques/needles used. This was true for organs, the overall data, and for the individual five grading criteria. There was, however, a significant difference among the biopsy techniques themselves. Though there was no difference in the quality of cytopathologic specimen obtained with the Autovac aspiration gun and the aspiration technique with a 22-gauge Chiba needle, both were statistically better than the nonaspiration, capillary technique utilizing a 22-gauge needle (p = 0.0001).ConclusionThe use of a coaxial technique with a fineneedle, 22-gauge biopsy offers unique advantages in obtaining a nearly unlimited amount of high-quality material for cytopathologic analysis. In this study, no dropoff was found in specimen quality with subsequent biopsies.

How we conduct ongoing programmatic evaluation of our medical education curriculum

Evaluation of undergraduate medical education programs is necessary to meet accreditation standards; however, implementation and maintenance of an adequate evaluation process is challenging. A curriculum evaluation committee (CEC) was established at the Penn State University College of Medicine in 2000 to complement the already established activities of the Office of the Vice Dean for Medical Education and the Committee on Undergraduate Medical Education. Herein, we describe the methodology used by the CEC at our academic medical center and outcomes attributable to the curriculum evaluation process that was enacted. Strengths of our process include ongoing, regular assessments that guarantee a course is reviewed at least every two years and a feedback loop whereby course directors are held accountable for implementing changes when necessary. Our evaluative process has proven effective, sustainable, and has identified additional areas for curricular improvements.