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.

Hybrid tumors or salivary gland tumors sharing common differentiation pathways? Reexamining adenoid cystic and epithelial-myoepithelial carcinomas.

Three adenoid cystic carcinomas and two epithelial-myoepithelial carcinomas, which focally shared common histologic features, were studied to examine the common differentiation pathways manifested by these tumors and to discuss criteria for hybrid salivary gland tumors. Regions of the adenoid cystic carcinomas had cellular features ranging from simple clear cell change of basal/myoepithelial cells to combined clear cells and prominent ductal structures mimicking epithelial-myoepithelial carcinoma. Conversely, two epithelial-myoepithelial carcinomas had adenoid cystic carcinoma-like regions caused by the formation of "pseudocysts"; this resulted in a focal cribriform pattern. Electron microscopy of two additional but typical epithelial-myoepithelial carcinomas revealed both excess basal lamina at the margins of cellular nests and widened intercellular spaces containing reduplicated basal lamina and accumulations of glycosaminoglycans; these ultrastructural features were identical to those seen in adenoid cystic carcinomas. The five current cases are not examples of hybrid tumors, but they demonstrate the effects of gene expression and the resulting differentiation of synthetic products and tumor cells that are generally restricted to one or the other of these two tumor types by as-yet-unknown means. To avoid misdiagnosis and its prognostic implications, adenoid cystic carcinoma-like regions in epithelial-myoepithelial carcinoma and epithelial-myoepithelial-like regions in adenoid cystic carcinoma should be recognized simply as anomalous differentiation.

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 patient's 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.

Immunocytochemistry on the Thinprep processor.

INTRODUCTION: For cytologic specimens, the vast majority of immunocytochemical studies (ICC) are performed on non-gynecologic specimens for diagnostic purposes, and they can be performed on unstained or previously stained direct smears. Although the ThinPrep processor (TPP) has been approved for the preparation of non-gynecologic specimens, there is scant literature describing the utility of ICC methodology on cytology specimens fixed and processed by this method. MATERIALS AND METHODS: Forty-one fresh specimens were obtained from the surgical gross room and aspirated or scraped to collect cells for thin layer (TL) and direct smears (DS). Specimens included a variety of neoplastic and nonneoplastic samples that were either Papanicolaou (P) stained or unstained (US). One group of US TL slides was subjected to antigen retrieval (AR). Staining was graded semiquantitatively. Each sample acted as its own control. Antibodies (abs) included: CAM5.2, AE1/3, K903, vimentin, MSA, desmin, s-100, HMB45, PSA, PAP, chromogranin, NSE, insulin, synaptophysin, pCEA, mCEA, mCEAD14, LCA, L26, UCHL-1, OPD-4, thyroglobulin, GCDFP, ER/PR, laminin, collagen IV, PLAP, HCG, CD68, HAM56, and MAC387. RESULTS: Semiquantitative staining overall results comparisons: TLP > DSP TLP < DSP TLP = DSP TLUS > DSUS 11/25 (44%) 6/25 (24%) 8/25 (32%) 9/24 (38%) TLUS < DSUS TLUS = DSUS 3/24 (12%) 12/24 (50%) TLP Vs. TLUS TLP > TLUS TLP < TLUS TLP = TLUS 8/41 (20%) 9/41 (22%) 24/41 (58%) There were five false-negative results, 2 with TL and 3 with DS, and 1 false-positive TL. DISCUSSION: Immunocytochemistry performed on the ThinPrep Processor showed equal or greater intensity and distribution of proper staining when compared to direct smears with the following advantages: (1) cleaner background, easier to interpret; (2) less abs required in a smaller area; (3) IPX can be done on Papanicolaou-stained thin layer slides; (4) thin layer slides can be modified for multiple abs tests; (5) additional thin layer slides can be prepared for ICC bases on needs. No significant differences of immunostaining were seen when comparing thin layer Papanicolaou-stained and unstained slides. Antigen retrieval offered no advantage in this study.

Successful reversal of acute vascular rejection in a renal allograft with combined mycophenolate mofetil and tacrolimus as primary immunotherapy.

Despite the use of newer immunosuppressive drugs, early allograft rejection is still a major cause of graft loss and diminished graft survival. The pathological picture of acute interstitial rejection usually responds to high dose steroids, whereas the treatment of acute vascular (AVR) rejection characterized by an intense vasculitis and/or endotheliolitis is more formidable. The use of newer monoclonal antibodies specific for T lymphocytes and their subsets has only been occasionally successful in reversing AVR. Here we report a case of successful reversal of acute vascular renal allograft rejection with mycophenolate mofetil (MMF) and tacrolimus as primary therapy.

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.

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.

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

PURPOSE: Compare the success of three coaxial fine-needle biopsy techniques in obtaining multiple cytologic specimens of high quality. METHODS: For 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. RESULTS: Using 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). CONCLUSION: The use of a coaxial technique with a fine-needle, 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.

Fine-needle aspiration biopsy versus fine-needle capillary (nonaspiration) biopsy: in vivo comparison.

PURPOSE: To evaluate, in vivo, the efficacy of fine-needle capillary (nonaspiration) biopsy (FNCB) versus fine-needle aspiration biopsy (FNAB) when performed at the same site with a coaxial technique. MATERIALS AND METHODS: In 91 patients, biopsy was performed at 140 sites in 93 lesions mostly throughout the chest and abdomen with either FNCB or FNAB, or both (98 sites). A coaxial technique with a 22-gauge needle was used. The quality of the specimen was graded by a blinded pathologist, who also made a pathologic diagnosis. RESULTS: No statistically significant difference was noted in the graded criteria performance plus diagnostic yield between the two techniques. When performed before FNAB, FNCB yielded a better quality specimen of a particular site. However, there was no difference in the graded quality of FNAB whether performed before or after FNCB. Insufficient specimens were obtained at 30 (21.4%) of 140 sites with FNCB versus only 18 (12.8%) with FNAB. CONCLUSION: FNCB is an alternative to FNAB and provides a cellular diagnostic specimen from most lesions. When a coaxial method is used and both techniques are employed, the diagnostic accuracy of these techniques is 84%.

Nodular fasciitis of the parotid gland. Report of a case with presentation in an unusual location and cytologic differential diagnosis.

The histomorphology of nodular fasciitis (NF), a benign proliferation of myofibroblasts, is well described in the surgical pathology literature. The cytomorphology, however, has been reported infrequently. Cytologic interpretation of this pseudosarcomatous lesion is subject to the same pitfalls so frequently reported for histologic material. NF arises most commonly in the extremities or trunk; occurrence in the parotid gland is relatively uncommon. We describe a case of NF arising in association with the parotid gland; review the clinical, cytologic, histologic and immunohistochemical features of NF; and offer a differential diagnosis, based on cytologic features, of other benign and malignant lesions likely to be encountered at this location.

Immunocytochemical staining of unstained versus previously stained cytologic preparations.

Immunoperoxidase (IP) staining of fine needle aspiration specimens may provide useful adjunct information in cytodiagnosis. IP may be used on unstained direct smears or cell block material if available. In the absence of such material, IP is sometimes used on previously stained (Papanicolaou) smears. Few studies have examined the adequacy of such preparations, however. We compared IP staining results on unstained, alcohol-fixed or air-dried smears versus alcohol-fixed, previously Papanicolaou stained smears and versus alcohol-fixed, decolorized, Papanicolaou-stained smears, using antibodies to keratin (CAM 5.2, AE1/AE3 and K903), epithelial membrane antigen, monoclonal carcinoembryonic antigen, desmin, muscle-specific actin (HHF-35), vimentin, leukocyte common antigen, B and T cell markers L26 and UCHL-1, and prostate-specific antigen. Seventy-five sets of smears were made from various neoplastic or nonneoplastic tissues received as surgical specimens, and antibodies were selected for anticipated positive staining. The results were graded in a semiquantitative fashion. All the methods gave comparable results regarding expected positive staining, background staining and preservation of cellularity. We conclude that these methods of smear preparation are of equal utility in adjunctive immunocytochemical studies.

Intraoperative immunocytochemistry of cytologic scrape specimens. A rapid immunoperoxidase method for triage and diagnosis.

We investigated a rapid immunoperoxidase (IPX) method utilizing a wide variety of antibodies for use on cytologic scrapings of fresh tissue that were submitted for intraoperative frozen section. The handling, fixation and IPX staining of these cytologic scrape specimens are more rapid and convenient than frozen tissue sections and spare tissues that may be of small quantity for appropriate special diagnostic studies (flow cytometry, cell markers, genetic studies, electron microscopy, and so forth). Fresh tissues from normal organs and tumors were scraped with a scalpel blade, smeared on an uncoated glass slide and immersed in 95% alcohol for one minute. Antibodies investigated by this method included: CAM 5.2, AE1/3, keratin 903, desmin, vimentin, HHF-35, CEA, PLAP, NSE, S-100, HMB45, LCA, L26 and UCHL-1. Twenty-three fresh epithelial and mesenchymal tissues from the uterus, colon, tonsil, lymph node, kidney and adrenal gland were examined, along with 29 tumors. There were 21 carcinomas, 3 melanomas, 3 sarcomas and 2 lymphomas. Using the streptavidin-biotin technique with aminoethylcarbazole localization, IPX results were available in 15-20 minutes, comparable to the time required for the reporting of a frozen section diagnosis. Keratins, vimentin, desmin and LCA gave the best results. HMB45 was weakly reactive in one case. This rapid cytologic IPX method may be used as an adjunct to frozen sections and cytologic imprints for intraoperative diagnosis or for efficient triage of poorly differentiated tumors for special studies at the time of frozen section.

CT percutaneous biopsy guns: comparison of end-cut and side-notch devices in cadaveric specimens.

OBJECTIVE: The purpose of this study was to compare the efficacies of four different types of end-cut biopsy guns with the side-notch Tru-cut biopsy gun. MATERIALS AND METHODS: A total of 25 liver, 15 kidney, 10 pancreas, and 15 breast biopsies were performed in the tissue from five autopsies with each of 12 different biopsy devices/biopsy depths. The tissue obtained was evaluated by an experienced cytopathologist who, not knowing which gun was used to obtain each specimen, used a predetermined grading scheme. RESULTS: When tissue was obtained, the end-cut biopsy guns performed equivalently to the side-notch biopsy gun in all four tissues. However, the end-cut guns had a significant number of "zero" biopsies (biopsy attempts during which no tissue was obtained). The proportion of zero biopsies with the end-cut guns ranged from up to 28% in the liver to 60% and 73% in the breast and kidney, respectively. CONCLUSION: The end-cut biopsy guns are easy to use and potentially can obtain high-quality specimens. However, the rate of zero biopsies during which no tissue is obtained is a serious deficiency. As a result, the use of the end-cut biopsy gun should be encouraged only for use with an introducer, with which multiple biopsy specimens can easily be obtained without additional needle punctures.

Blinded comparison of biopsy needles and automated devices in vitro: 1. Biopsy of diffuse hepatic disease.

OBJECTIVE: The purpose of this study was to compare several of the commonly used needles with several of the new automated biopsy devices (biopsy guns) for biopsy of diffuse hepatic disease. MATERIALS AND METHODS: Nine different biopsy needles or automated devices were each used to do three biopsies of 10 cadaveric livers. The specimens were reviewed in a blinded fashion by a pathologist who did not know which needle or device was used, and they were compared on the basis of a previously published histopathologic grading scale. RESULTS: The three conventional biopsy needles (16-gauge Jamshidi, 18-gauge Sure-Cut, and 14-gauge Tru-Cut) obtained a large amount of tissue with an average of 4.1 intact portal triads per biopsy. The 18-gauge Biopty gun obtained equivalent results. The 18-gauge Autovac gun with a 2-cm biopsy depth did not obtain any tissue in 18.5% of attempts. The 14- and 16-gauge Biopty guns and the 18-gauge Autovac gun with a 4-cm biopsy depth performed best with respect to fragment size and number of intact portal triads. CONCLUSION: Automated biopsy devices can provide more diagnostic specimens than can manual or conventional needles in biopsy for diffuse hepatic disease.

Blinded comparison of biopsy needles and automated devices in vitro: 2. Biopsy of medical renal disease.

OBJECTIVE: The purpose of this study was to compare several of the commonly used manual biopsy needles with several of the new automated biopsy devices (biopsy guns) for biopsy of medical renal disease. MATERIALS AND METHODS: Ten different biopsy needles or automated devices were each used to do two biopsies of 10 cadaveric kidneys. The specimens were reviewed in a blinded fashion by a pathologist using a previously published histopathologic scale. RESULTS: Of the four conventional biopsy needles tested (16-gauge Jamshidi, 18-gauge Sure-Cut, 14-gauge Tru-Cut, and 14-gauge Vim Silverman), the Jamshidi needle obtained the greatest average number of glomeruli (5.64). Results similar to those obtained with the conventional needles were obtained with the 16- and 18-gauge Biopty and Ultra-Cut biopsy guns. The 18-gauge Autovac gun with either a 2- or 4-cm depth of biopsy suffered from a significant number of biopsies from which no tissue was obtained. The 14-gauge Biopty gun was clearly superior, leading in all graded categories including the average number of glomeruli (8.11) per biopsy. CONCLUSION: The automated biopsy device, or biopsy gun, can provide more diagnostic specimens than can manual or conventional needles in biopsy for medical renal disease.

Automated biopsy devices: a blinded evaluation.

To evaluate 20 different automated biopsy devices with respect to the quality of tissue obtained for histopathologic analysis, a total of 1,470 18-gauge biopsy specimens were obtained from 10 fresh autopsy cases, including 30 liver, 20 kidney, 10 pancreas, and 10 psoas muscle biopsy specimens per device and per biopsy depth. There was no statistical difference in the performance of the long-throw Biopty, ASAP 18, 1.9-cm UltraCut, long-throw Monopty, and 2.5-cm ABS biopsy guns. All obtained a large amount of tissue with minimal fragmentation or crush artifact. Most of the short-throw biopsy guns (depth of biopsy < or = 1.1 cm) did not perform as well. Although the other guns performed adequately, less than optimal results were obtained with the Temno, Bio-Gun, Roth, Klear Kut, ABC, and Urocut biopsy guns. Most 18-gauge automated biopsy devices with a biopsy excursion of at least 2.0 cm provide a high-quality, diagnostically adequate specimen for histopathologic analysis.

Fine-needle aspiration biopsy for cytopathologic analysis: utility of syringe handles, automated guns, and the nonsuction method.

The performances of seven techniques and devices used with 22-gauge needles to obtain biopsy specimens for cytologic analysis were compared by means of single-blinded evaluation with an objective, previously published grading scheme. A total of 420 specimens were obtained from 10 fresh human cadavers (42 specimens per cadaver), including 30 hepatic, 20 renal, and 10 pancreatic specimens per technique or device. No statistical differences existed in the liver, kidney, or pancreas or in the combined data in the performance of the aspirator gun, syringe holders, vacuum needle, and end-cut gun versus the manual aspiration biopsy technique performed with a 22-gauge Chiba needle. However, nonaspiration, fine-needle capillary biopsy (FNCB) performed statistically significantly worse than any other technique or device in the kidney and pancreas and in comparison with the overall combined data. In the liver, no statistically significant difference existed in the overall performance of FNCB versus conventional aspiration biopsy, but the amount of cellular material obtained with FNCB was statistically significantly less.

Focal fatty infiltration of the liver in a healthy child.

Fatty infiltration of the liver may occur in healthy children. The ultrasonographic, CT, and MRI findings are identical to those already described in the adult population.