Spectrum of findings in orchiectomy specimens of persons undergoing gender confirmation surgery.

Gender confirmation surgery is increasingly common in persons with gender dysphoria. We describe changes seen in gonads from individuals seeking male-to-female physical adaptation. We studied 99 orchiectomies from 50 persons. The average age was 33 years (range, 21-63 years). Eighty-six (86.8%) of 99 testes were normal in size with an average size of 3.87 cm (range, 3.0-5.5 cm). Thirteen (13.1%) of 99 testes were hypotrophic and measured up to 2.5 cm. Seminiferous tubules were reduced in diameter compared with controls (0.137 mm versus 0.237 mm; P < .001) and showed peritubular fibrosis in 41 (82%) of 50 persons. In 40 (80%) of 50 persons, there was maturation arrest at the spermatogonia level. In 10 (20%) of 50 persons, the seminiferous tubules showed focal spermatids/spermatozoa up to 7 per 10 tubules mixed with partial maturation arrest at primary spermatocytes. Twenty-six (26%) of 99 testes showed seminiferous tubules with rare cells with large nuclei (3× size of Sertoli cells nuclei) and degenerative chromatin (cytomegaly). Leydig cells were absent in 50 (50%), markedly reduced in 30 (30%), and similar to controls (mean, 33/high-power field) in 20 (20%). A subset (20/99; 20%) of testes had epithelial hyperplasia of the proximal epididymis with stratification and micropapillae. There was no germ cell tumor, sex cord stromal tumors, or germ cell neoplasia in situ. In summary, the histologic changes include (1) decreased diameter of seminiferous tubules and expansion of the interstitium, (2) marked hypoplasia of germ cells, (3) rare cytomegaly, (4) hypoplasia or absence of Leydig cells, and (5) epididymal hyperplasia.

Inhibition of IFN-γ promotes anti-asthma effect of Mycobacterium bovis Bacillus Calmette-Guerin neonatal vaccination: a murine asthma model.

OBJECTIVE: The Mycobacterium bovis Bacillus Calmette-Guerin (BCG) neonatal vaccination inhibits allergy-induced pathologic changes. However, the mechanisms underlying this process are unclear. This study aimed to investigate the role of interferon (IFN)-γ and interleukin (IL)-17 in the protective effects of the BCG neonatal vaccination on allergic pulmonary inflammation and airway hyperresponsiveness (AHR). METHODS: Wild type (WT)-neonate and IL-17 knock out (KO) neonate mice were vaccinated with BCG. A murine asthma model was developed by sensitization and then challenging with ovalbumin (OVA). Recombinant IL-17 or recombinant IFN-γ was delivered to the airway to overexpress IL-17 or IFN-γ. An anti-IFN-γ neutralizing antibody was used to block the effects of IFN-γ. RESULTS: We found exogenous IL-17 delivered to the airway reversed the anti-asthma effects of the neonatal BCG vaccination. BCG neonatal vaccination further reduced OVA-induced inflammation and AHR in IL-17 KO mice. Inhibition of IFN-γ in BCG neonatal vaccinated OVA-induced asthma model mice led to a further reduction in airway inflammation and AHR. In addition, airway inflammation and AHR were robust following treatment with exogenous IFN-γ. Neutralizing IL-17 was not sufficient to block OVA-induced airway inflammation and AHR. In IL-17 KO mice, airway inflammation and AHR did not occur following treatment with an anti-IFN-γ neutralizing antibody. CONCLUSIONS: In an OVA-induced murine asthma model, inhibition of IFN-γ enhanced the anti-asthma effects of BCG neonatal vaccination.

Expression of S100A4 in renal epithelial neoplasms.

Expression of S100A4 has been associated with progression and poor clinical outcome in a variety of malignancies including those of the breast, pancreas, bladder, and thyroid. To date, the expression of S100A4 protein in renal epithelial neoplasms is poorly understood. In this study, we evaluated the expression of S100A4 protein and mRNA in the nontumoral kidney and renal epithelial neoplasms of different types and correlated its expression with patient outcome. The study population included 155 clear cell renal cell carcinomas (cRCC), 22 papillary renal cell carcinomas (pRCC), 13 chromophobe renal cell carcinomas and 13 oncocytomas. In nontumoral kidney, nuclear and cytoplasmic S100A4 staining was detected in the glomerular epithelium and endothelium, distal tubules and collecting ducts, and loops of Henle. A different expression pattern was noted in the various neoplasms. S100A4 expression was significantly increased in the stromal cells in cRCC (83%) and pRCC (73%) compared with paired nontumoral kidney tissue (P<0.001). There was no increased stromal cell expression of S100A4 in oncocytomas and chromophobe carcinomas. Positive epithelial staining was more common in pRCC (58%) than cRCC (11%) (P=0.01). The level of mRNA detected by reverse transcription-polymerase chain reaction was significantly higher in the tumor as opposed to normal tissue in cRCC but not in the other neoplasms (P=0.03). Multivariate analysis revealed that epithelial S100A4 protein expression is an independent poor prognostic factor along with grade and stage only in cRCC (P<0.01). Although S100A4 protein was expressed in a minority of cRCC, its expression was associated with shorter overall patient survival.

Expression of the glucocorticoid receptor in renal cell neoplasms: an immunohistochemical and quantitative reverse transcriptase polymerase chain reaction study.

Glucocorticoid receptors mediate the action of steroid hormones in a variety of tissues, including the kidney. Our goal was to determine the expression pattern and prognostic significance of glucocorticoid receptor in renal cell neoplasms. Paraffin-embedded microarrays from 200 patients with RCNs including 147 clear cell renal cell carcinomas, 23 papillary, 16 chromophobe renal cell carcinoma, and 14 oncocytomas were analyzed for glucocorticoid receptor expression by immunohistochemistry. Glucocorticoid receptor expression was also quantitated by real-time reverse transcriptase polymerase chain reaction in 45 cases (33 clear cell renal cell carcinomas, 5 chromophobe renal cell carcinomas, and 3 oncocytomas). Strong nuclear glucocorticoid receptor expression was present in normal glomeruli and in the proximal convoluted tubules. Nuclear glucocorticoid receptor expression was found in most clear cell renal cell carcinomas (66%), in 26% of papillary renal cell carcinomas, and in only 6% of chromophobe renal cell carcinomas and 14% of oncocytoma (P < .005). Within the clear cell renal cell carcinoma group, most positive cases (87%) demonstrated strong immunoreactivity (2+ and 3+), whereas only 1 papillary renal cell carcinoma, 1 chromophobe renal cell carcinoma, and none of the oncocytomas showed strong expression. Glucocorticoid receptor α messenger RNA expression was significantly higher in clear cell renal cell carcinoma than in chromophobe renal cell carcinoma, oncocytoma, or in the normal kidney. Significantly more frequent glucocorticoid receptor expression was associated with tumors of low nuclear grade (Fuhrman grade 1 and 2) and low stage (stages 1 and 2; P = .0068 and P = .0002). Survival analysis revealed a significant direct correlation between glucocorticoid receptor expression and overall survival in clear cell renal cell carcinoma (P = .01). In summary, strong glucocorticoid receptor expression was most commonly seen in clear cell renal cell carcinoma and only rarely seen in other subtypes. The glucocorticoid receptor expression pattern in RCNs seems to reflect the histogenetic origin of clear cell renal cell carcinoma from the proximal nephron. Finally, glucocorticoid receptor expression proved to be a marker of less aggressive behavior in clear cell renal cell carcinoma.

Phase-coherent frequency comparison of optical clocks using a telecommunication fiber link.

We have explored the performance of 2 "dark fibers" of a commercial telecommunication fiber link for a remote comparison of optical clocks. These fibers establish a network in Germany that will eventually link optical frequency standards at PTB with those at the Institute of Quantum Optics (IQ) at the Leibniz University of Hanover, and the Max Planck Institutes in Erlangen (MPL) and Garching (MPQ). We demonstrate for the first time that within several minutes a phase coherent comparison of clock lasers at the few 10(-15) level can also be accomplished when the lasers are more than 100 km apart. Based on the performance of the fiber link to the IQ, we estimate the expected stability for the link from PTB to MPQ via MPL that bridges a distance of approximately 900 km.

Comparison of thyroid transcription factor-1 expression by 2 monoclonal antibodies in pulmonary and nonpulmonary primary tumors.

Thyroid transcription factor-1 (TTF-1) is a transcription factor that plays a role in the development and physiology of the thyroid and lungs. Expression of TTF-1 is used as a marker of lung and thyroid clinically. Commercially available clones of TTF-1 monoclonal antibodies, 8G7G3/1 and SPT24, have been reported to have different sensitivities for the detection of neoplasms of different origins. Although they are used extensively in daily practice, a comprehensive comparative study of these antibodies in a wide variety of neoplasms is lacking. We examined TTF-1 expression in primary tumors of the lung, prostrate, pancreas, stomach, salivary glands, breast, bladder, colon, and squamous cell carcinoma of the head and neck and compared the results obtained with both TTF-1 clones. The SPT24 clone detected more primary lung tumors of all histologic subtypes. Importantly, the SPT24 clone detected a significantly higher number of squamous cell carcinomas and carcinoid tumors of the lung. Among nonpulmonary primary tumors, a significant number of invasive urothelial carcinoma of the bladder (5.1%) was TTF-1 positive. In addition, a small proportion of prostate (1.2%), stomach (0.9%), salivary gland (1.8%), and colon (2.5%) carcinomas were positive with both clones. Of note, both clones stained the same nonpulmonary tumors with similar intensity and distribution. Carcinomas of the pancreas, breast, and squamous cell carcinomas of the head and neck were negative with both clones. In summary, the SPT24 clone detected a higher number of pulmonary non-small cell tumors of all histologic subtypes whereas both clones stained a similar proportion of nonpulmonary tumors.

Renal sinus myelolipoma coexistent with renal pelvis papillary transitional cell carcinoma: a case report.

A unique case of renal sinus myelolipoma presenting as a mass coexistent with papillary transitional cell carcinoma is reported. The patient was a 64-year-old man with a history of bladder transitional cell carcinoma. He presented with gross hematuria and a filling defect in the renal pelvis on computed tomography scan. Pathological findings revealed an irregular myxoid fatty mass, in addition to high-grade papillary transitional cell carcinoma. The differential diagnosis included myxoid liposarcoma, myxoid variant of malignant fibrous histiocytoma (myxofibrosarcoma), and angiomyolipoma. Immunoperoxidase staining confirmed the presence of hematopoietic cells, whereas diagnostic histological and immunohistochemical features of liposarcoma, myxofibrosarcoma, and angiomyolipoma were absent. Myelolipoma and papillary transitional cell carcinoma appear to be unrelated coexistent entities in this case.

Malakoplakia of the spleen: a case report.

Malakoplakia is an uncommon chronic inflammatory disorder, which is characterized by the presence of histiocytes containing concentric concretions known as Michaelis-Gutmann bodies in a background of mixed inflammation. The urinary tract is the most commonly involved site. However, malakoplakia can be found in a wide range of other organs throughout the body. Its occurrence has been attributed to a defect in the bactericidal capacity of phagocytic cells, and it is usually seen in patients with some degree of immunologic compromise. A case of malakoplakia of the spleen in a patient with Crohn's disease is reported in this article.

GCDFP-15 positive and TTF-1 negative primary lung neoplasms: a tissue microarray study of 381 primary lung tumors.

Gross cystic disease fluid protein (GCDFP-15) is currently used as an immunohistochemical marker of breast cancer, whereas thyroid transcription factor (TTF-1) is commonly used as a marker of primary lung neoplasms. Traditionally, a GCDFP-15+/TTF-1- immunohistochemical profile in lung tumors has been considered as highly suggestive of metastatic carcinoma of the breast. Here, we investigated the expression of GCDFP-15 and TTF-1 on a tissue microarray consisting of 381 primary lung carcinomas. GCDFP-15 was expressed in normal bronchial submucosal glands and bronchial epithelium, which were negative for TTF-1. Seventeen tumors (4.5%) were positive for GCDFP-15, including 11 of 186 (5.9%) adenocarcinomas, 1 of 97 (1%) squamous cell carcinomas, 1 of 23 (4.3%) carcinoid tumors, 2 of 47 (4.3%) large cell carcinomas, and 2 of 17 (11.8%) adenosquamous carcinomas. Of the 11 GCDFP-15 positive adenocarcinomas, 10 (91%) were TTF-1 negative. On whole sections, about half (55%) of GCDFP-15 positive cases were negative and one-third (33%) revealed focal TTF1 staining in areas distinct from the tumor regions that expressed GCDFP-15. All GCDFP-15 positive tumors were negative for mammaglobin, estrogen receptor, and progesterone receptor. Our study confirms that a small subset of primary lung adenocarcinomas exhibits a GCDFP-15 positive phenotype. Expression of TTF-1 in this group is not uniform and frequently negative in small specimens. Thus a GCDFP-15 positive/TTF-1 negative phenotype may not be indicative of metastatic breast carcinoma in every case. It is critical that pathologists be aware of this phenotypic subset of lung adenocarcinomas, especially when faced with small tissue or cytologic samples.

The diagnostic and prognostic utility of claudin expression in renal cell neoplasms.

This study evaluated the expression patterns of claudins 1, 3, 4, 7, and 8 in human renal cell carcinomas and oncocytomas and correlated expression with patient prognosis. Tissue microarrays were created from paraffin-embedded tissue samples from 141 patients with renal cell carcinomas or oncocytoma (90 clear cell, 22 papillary, 17 chromophobe renal cell carcinomas, and 12 oncocytomas). The staining pattern for claudins 3, 4, 7, and 8 was membranous and/or cytoplasmic, whereas claudin 1 was predominantly membranous in both nonneoplastic renal tissue and tumors. Negative to weak claudin 3 staining was predominantly detected in Fuhrman's grade 1 and 2 clear cell renal cell carcinomas (78%; P=0.016), suggesting that upregulation of claudin 3 potentially occurs concomitantly with increasing grade of clear cell renal cell carcinomas. In addition, Kaplan-Meier univariate analysis showed a significant inverse correlation between moderate to strong claudin 3 and 4 expression with overall survival in clear cell renal cell carcinomas (P=0.038 and P=0.031). Moderate to strong claudin 7 expression was significantly more common in chromophobe renal cell carcinomas (94%) than in oncocytomas (55%; P=0.041). Claudin 8 staining was moderate to strong in 92% of oncocytomas, which differentiated them from papillary and clear cell renal cell carcinomas (14 and 12%; both P<0.0001). Only negative to weak claudin 8 staining was detected in all chromophobe renal cell carcinomas, whereas there were no claudin 8 negative oncocytomas and 8% exhibited a weak staining pattern (P<0.0001). Due to their distinctive expression patterns, claudins 7 and 8 can be used as useful immunohistochemical markers for the separation of chromophobe renal cell carcinomas from oncocytomas, whereas claudins 3 and 4 may serve as indicators of prognosis in clear cell renal cell carcinomas.

Mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type II expression in renal cell neoplasms: a tissue microarray and quantitative RT-PCR study.

The kidney is an important target for mineralocorticoids. Aldosterone, the major endogenously secreted mineralocorticoid, acts by binding to mineralocorticoid receptor (MR) in the distal renal tubule. The enzyme 11beta-hydroxysteroid dehydrogenase type II (11beta-HSD2) prevents the binding of glucocorticoids to the MR by inactivating cortisol to cortisone. Our goal was to determine whether MR and 11beta-HSD2 expression could be used to characterize the major types of renal cell neoplasms. Using immunohistochemistry we analyzed tissue microarray specimens from 132 patients with renal cell neoplasms, stratified into 84 clear cell renal cell carcinomas (CRCC), including 9 cases clear cell carcinoma with predominantly granular cytoplasm; 14 papillary RCC (PRCC); 20 chromophobe RCC (CHRCC); and 14 oncocytomas (OCs). MR and 11beta-HSD2 expression were also quantitated by real-time reverse transcription-polymerase chain reaction. Expression of both MR and 11-betaHSD2 was detected in the distal nephrons of normal kidneys. The CHRCC group stained for 11-betaHSD2 in a membranous and cytoplasmic pattern whereas diffuse cytoplasmic reactivity was seen in OCs. MR and 11beta-HSD2 were coexpressed in most of CHRCC (90% and 95%) and oncocytomas (93% and 100%). No MR staining was detected in CRCC, including clear cell carcinoma with predominantly granular cytoplasm, or in PRCC. Only 2 cases of CRCC (2.6%) showed focal positivity for 11beta-HSD2, whereas all PRCCs were negative. CHRCC and OC demonstrated significantly higher levels of MR and 11beta-HSD2 expression than CRCC and PRCC by real-time polymerase chain reaction. Moreover, CHRCC showed higher expression of MR and 11beta-HSD2, as compared with OC. Our study indicates MR and 11beta-HSD2 are both sensitive and specific markers of the distal nephron and its related neoplasms (CHRCC and OC). Additionally, the staining pattern and the level of MR and 11beta-HSD2 expression seems to be useful in the distinction of CHRCC from OC. MR and 11beta-HSD2 should be considered in the immunohistochemical panel to more accurately subtype renal cell tumors.

Photosynthetic response to low sink demand after fruit removal in relation to photoinhibition and photoprotection in peach trees.

Diurnal variations in photosynthesis, chlorophyll fluorescence, xanthophyll cycle, antioxidant enzymes and antioxidant metabolism in leaves in response to low sink demand caused by fruit removal (-fruit) were studied in 'Zaojiubao' peach (Prunus persica (L.) Batch) trees during the final stage of rapid fruit growth. Compared with the retained fruit treatment (+fruit), the -fruit treatment resulted in a significantly lower photosynthetic rate, stomatal conductance and transpiration rate, but generally higher internal CO(2) concentration, leaf-to-air vapor pressure difference and leaf temperature. The low photosynthetic rate in the -fruit trees paralleled reductions in maximal efficiency of photosystem II (PSII) photochemistry and carboxylation efficiency. The midday depression in photosynthetic rate in response to low sink demand resulting from fruit removal was mainly caused by non-stomatal limitation. Fruit removal resulted in lower quantum efficiency of PSII as a result of both a decrease in the efficiency of excitation capture by open PSII reaction centers and an increase in closure of PSII reaction centers. Both xanthophyll-dependent thermal dissipation and the antioxidant system were up-regulated providing protection from photo-oxidative damage to leaves during low sink demand. Compared with the leaves of +fruit trees, leaves of -fruit trees had a larger xanthophyll cycle pool size and a higher de-epoxidation state, as well as significantly higher activities of antioxidant enzymes, including superoxide dismutase, ascorbate peroxidase, monodehydroascorbate reductase, dehydroascorbate reductase, glutathione reductase and a higher reduction state of ascorbate and glutathione. However, the -fruit treatment resulted in higher hydrogen peroxide and malondialdehyde concentrations compared with the +fruit treatment, indicating photo-oxidative damage.

Sclerosing polycystic adenosis of the salivary gland: a report of 16 cases.

Sclerosing polycystic adenosis is a recently described, extremely rare, reactive, sclerosing, inflammatory process somewhat similar to fibrocystic changes and adenosis tumor of the breast. To date, there have been 22 cases described in the literature. Because of the infrequency of this lesion, we describe our combined experience with 16 cases, 1 of which has been previously reported. Thirteen tumors arose in the parotid gland, two involved the submandibular gland, and one arose in the buccal mucosa. There were 9 men and 7 women. Patients ranged in age from 9 to 75 years. Fourteen patients presented with a primary mass. Two were incidental findings in patients with a mixed tumor and an oncocytoma. Tumors ranged in size from 0.3 to 6 cm in greatest dimension. They are typically well circumscribed and are composed of densely sclerotic lobules with prominent cystic change. Hyperplasia of ductal and acinar elements and areas of apocrine-like metaplasia are frequent. Foci with mild ductal epithelial atypia were frequent with >50% of cases demonstrating at least focal areas of duct epithelial hyperplasia with atypia. Follow-up ranged from 1.5 to 40 years. One tumor recurred twice; no patient has developed metastases or died of disease.