Clinicopathological Analysis of Uterine Allografts Including Proposed Scoring of Ischemia Reperfusion Injury and T-cell-mediated Rejection-Dallas UtErus Transplant Study: A Pilot Study.

BACKGROUND: Uterus transplantation (UTx) enables pregnancy in infertile women. This study describes the histopathological changes of ischemia reperfusion injury and mostly acute T-cell-mediated rejection (TCMR) in UTx and proposes modification toward a working formulation grading system with associated treatments. METHODS: Protocol and indication biopsies from 11 living and 2 deceased donor UTx recipients were analyzed. Serving as a control were 49 age-matched nontransplanted uteri. All posttransplant histopathological specimens were evaluated in a blinded fashion by 3 pathologists. Response to treatment was assessed by follow-up biopsies. Serial serum donor-specific antibody (DSA) responses were also recorded. RESULTS: Changes attributed to ischemia reperfusion resolved within 2 wk of UTx in most of the patients. For TCMR grading, perivascular inflammation, focal capillary disruption, and interstitial hemorrhage were added to interface inflammation, intercellular edema, stromal inflammation, and epithelial apoptotic bodies. Of the 173 protocol biopsies, 98 were classified as negative for TCMR; 34 as indeterminate-borderline; 35 as mild; 3 as moderate; and 3 as severe, 1 of which occurred in a DSA-positive recipient and also showed microvascular injury. Corticosteroids successfully treated all moderate-to-severe TCMR episodes. Mild TCMR was treated by increasing existing baseline immunosuppression. Indeterminate-borderline episodes were not treated. Neither ischemia-reperfusion injury nor TCMR with DSA adversely affected embryo transfer. CONCLUSIONS: Relying on a modified histopathological grading system, we developed a treatment strategy resulting in resolution of TCMR and successful pregnancies.

Diagnosis of sarcoidosis from a biopsy of a dilated mammary duct.

Sarcoidosis is an immunologic disease of unknown etiology that manifests most frequently within the lungs or associated lymph nodes. Sarcoidosis involving the breast is seen in <1% of cases and usually is diagnosed in patients with multisystem disease. The clinical and imaging presentations of sarcoidosis of the breast can be variable. Though uncommon, sarcoidosis should be considered in the differential diagnosis of a breast lesion, and given that imaging characteristics cannot distinguish between sarcoidosis and malignancy, all breast lesions in patients with sarcoidosis should be biopsied. Our case study demonstrates a diagnosis of sarcoidosis in an asymptomatic patient presenting with a single dilated duct and associated filling defect within the right breast.

The sensitivity and specificity of sentinel lymph node biopsy for breast cancer at Baylor University Medical Center at Dallas: a retrospective review of 488 cases.

Sentinel lymph node (SLN) biopsy has become the standard of care for breast carcinoma management, as it precludes the negative morbid effects-including decreased shoulder range of motion, lymphedema, and paresthesias-of unnecessary axillary lymph node dissection. However, the method of pathologic evaluation of the lymph node has been scrutinized to obtain the greatest sensitivity, specificity, and negative predictive value, ultimately for the benefit of the patient. This retrospective study analyzed 488 biopsies completed by two surgeons and read by multiple pathologists affiliated with Pathologists Biomedical Laboratories. When metastatic disease was not grossly obvious, analysis of the SLN began with touch imprint cytology and, if necessary, a frozen section analysis. On the subsequent day, three levels of the SLN were analyzed with hematoxylin and eosin stain and immunohistochemistry with cytokeratin AE1-3 and the appropriate control. Touch imprint cytology and/or frozen section analysis (where applicable) correctly identified 78 of 89 macrometastases, with a sensitivity of 88%, specificity of 100%, and negative predictive value of 97%. Sensitivity was 72% for micrometastases and 60% for isolated tumor cells, each with 100% specificity. In conclusion, the sensitivity and specificity of SLN biopsy at our institution compares with the higher end of percentages reported in the literature.

Subcutaneous beta2-microglobulin amyloid shoulder nodulesin a long-term hemodialysis patient.

beta2-Microglobulin accumulation with resultant tumor formation is a known albeit rare complication of long-term hemodialysis. Although these tumors may occur in various locations, subcutaneous shoulder nodules are very infrequent. We report a patient with end-stage kidney failure who had been on hemodialysis for 16 years and noted left shoulder nodules after initiation of hemodialysis; these nodules had slowly grown larger. Biopsy of one of these nodules revealed beta2-microglobulin amyloidosis by histopathology, Congo red stain, electron microscopy, and immunohistochemistry.

Mediastinal germ cell tumors with an angiosarcomatous component: a report of 12 cases.

The development of an angiosarcomatous component in germ cell tumors is rare. Here we studied 12 cases of mediastinal germ cell tumors with an angiosarcomatous component. All patients were men with a mean age of 34 years (range, 24-49 years). No patient had a documented testicular germ cell tumor. The mean size of mediastinal tumors was 12.9 cm (range, 5.5-16.0 cm). Grossly, the tumors were cystic with variegated hemorrhagic, mucinous, and fleshy solid areas. Microscopically, all tumors were composed of germ cell tumor. The most common germ cell tumor component was teratoma (n = 10); and other germ cell tumor components included seminoma (n = 3), yolk sac tumor (n = 3), embryonal carcinoma (n = 2), and choriocarcinoma (n = 1). The angiosarcomatous component was present in primary mediastinal tumors (n = 6), metastasis (n = 3), or both primary mediastinal tumor and metastasis (n = 3). The angiosarcomatous component accounted for an average of 30% (range, 5%-95%) of the primary mediastinal tumor. In addition, other non-germ cell components, including rhabdomyosarcoma (n = 3), leiomyosarcoma (n = 1), and poorly differentiated carcinoma (n = 1), were also present in the tumors. Of the 10 patients with follow-up available, all patients developed metastasis (n = 8) or local recurrence (n = 2); 7 died of disease at a mean of 33 months (range, 21-75 months), and 3 patients were alive at a mean of 75 months (range, 5-120 months). Our findings suggest that the presence of an angiosarcomatous component in mediastinal germ cell tumor, even in a small amount, is associated with a poor clinical outcome.

Testicular germ cell tumors with sarcomatous components: an analysis of 33 cases.

The development of sarcomatous component (SC) in testicular germ cell tumor (GCT) is an uncommon phenomenon. We searched our surgical pathology files from 1985 to 2007 and identified 33 cases of testicular GCTs with SC. The average age of patients was 31 years. All patients underwent radical orchiectomy, which demonstrated a GCT in all patients except for 3 patients who had received neoadjuvant chemotherapy. All testicular GCTs contained a teratomatous component. The GCTs were pure teratomas in 3 cases, and were mixed GCTs in the other cases. The SC was observed in primary testicular tumor (n=19), in metastasis (n=11), or in both primary testicular tumor and metastasis (n=3). The average percentage of the SC in the primary testicular GCT was 32% (range: 5% to 99%). The most common histologic type of SC was rhabdomyosarcoma (n=24), followed by high-grade unclassified sarcoma (n=5), rhabdomyosarcoma admixed with high-grade unclassified sarcoma (n=2), angiosarcoma (n=1), and low-grade myxoid sarcoma (n=1). Clinical follow-up information was available for 27 patients. Of the 13 patients whose SC was limited to the testicular GCT, 2 patients died of GCT not otherwise specified at 37 and 68 months, respectively; and 11 patients were free of disease at a mean of 46 months. Of the 14 patients with a SC in the metastasis, 7 patients died of GCT not otherwise specified at a mean of 95 months, and 7 patients were free of disease at a mean of 104 months. These results suggest that patients with a SC confined to the primary testicular GCT may not have a higher risk of mortality than those at a comparable stage without a SC. However, patients with a SC in the metastasis have an increased risk of mortality.

Susceptibility patterns of enterococci causing infections.

Enterococci are among the common organisms associated with hospital-acquired infections. We examined in vitro activities of different antibiotics to 103 enterococcal isolates. Minimal inhibitory concentrations (MICs) of penicillin G, ampicillin, gentamicin, ciprofloxacin, ofloxacin, levofloxacin, grepafloxacin, trovafloxacin and gemifloxacin were determined by broth microdilution testing method. Among the isolates 71 (69%) were identified as E. faecalis and 32 (31%) as E. faecium. While over 75% of E. faecium isolates were resistant to penicillin and ampicillin, approximately 25% of E. faecalis isolates were resistant to penicillin and ampicillin. None of the E. faecalis and E. faecium isolates were resistant to vancomycin. While 17 (52%) of E. faecium isolates exhibited high-level gentamicin resistance (HLGR), high level streptomycin resistance (HLSR) was detected in 24 (74%) of the isolates. In contrast, HLGR and HLSR rates for E. faecalis were 14 (20%) and 22 (31%), respectively. Both HLGR and HLSR were detected with higher frequency in ampicillin resistant isolates. Among fluoroquinolones, gemifloxacin and trovafloxacin were the most potent antibiotics tested. There was no increase in MIC90 values of the fluoroquinolones in ampicillin resistant isolates in comparison with ampicillin susceptible isolates. Our data suggest newer fluoroquinolones would be good alternative agents to use especially for combination drug therapy where enterococci with ampicillin resistance and HLAR are prevalent.

Comparative activities of beta-lactam antibiotics and quinolones for invasive Streptococcus pneumoniae isolates.

BACKGROUND: Streptococcus pneumoniae is a leading pathogen causing pneumonia, meningitis, otitis media, bacteremia and sinusitis resulting in significant morbidity and mortality. We examined in vitro activities of five quinolones in comparison with other antibiotics against 85 invasive pneumococcal isolates. METHODS: Minimal inhibitory concentrations (MICs) of penicillin G, cefuroxime, azithromycin, clarithromycin, trimethoprim-sulfamethoxazole (SXT), ciprofloxacin, ofloxacin, levofloxacin, trovafloxacin and gemifloxacin were determined using a broth microdilution method. RESULTS: The overall rates of resistance to penicillin (46%), cefuroxime (20%), azithromycin (20%), clarithromycin (18%) and SXT (46%) were considerable. Among all of the isolates, 9 isolates (11%) were highly resistant (MIC >/=2 mg/l) and 30 isolates (35%) had intermediate resistance (MIC 0.12- 1.0 mg/l). Of the quinolones gemifloxacin and trovafloxacin had the highest activity. The penicillin resistance status of the isolates did not have any effect on the resistance pattern of new quinolones. CONCLUSION: The new quinolones show great potential in the treatment of invasive infections caused by both penicillin-susceptible and penicillin-resistant pneumococci.

Characterization of antibodies to PspA and PsaA in adults over 50 years of age with invasive pneumococcal disease.

We characterized antibody responses to two Streptococcus pneumoniae surface proteins, PspA and PsaA, in 14 adults over 50 years of age hospitalized with invasive pneumococcal disease (IPD), and in two groups of age-matched controls (18 patients with invasive disease due to other microorganisms and 35 patients hospitalized for non infectious conditions). All patients with IPD and all control subjects had detectable antibodies to both proteins on hospital admission. Three weeks later, the geometric mean concentrations of antibodies to PspA and PsaA in IPD patients were respectively 10 and 25 times higher than on admission. In contrast, acute and convalescent antibody levels were similar in control patients with invasive diseases due to other microorganisms.

Neisseria meningitidis with decreased susceptibility to penicillin in Istanbul, Turkey.

This study was conducted to estimate the rate of decreased susceptibility to penicillin (MIC > 0.06-1 microg/ml) in Neisseria meningitidis isolates in Istanbul, Turkey. A total of 30 isolates collected during a 1-y period from patients with meningitis and from nasopharyngeal carriers were tested for penicillin and cefotaxime susceptibility using the E-test. Two out of 12 (17%) clinical isolates and 11/18 (61%) nasopharyngeal isolates showed decreased susceptibility to penicillin with MICs in the range 0.094-1.0 microg/ml, giving an overall resistance of 43% (n = 13). These data show that continued surveillance of trends in antimicrobial susceptibility of N. meningitidis is important for detecting the emergence of N. meningitidis strains with MICs > 1 microg/ml which may pose serious therapeutic problems.