The clinical history and crystal characteristics of three published cases and three new cases of phosphoglyceride (PG) crystal deposition disease of soft tissues and bones were compared. All patients (age range, 51-64 years) were generally healthy without a genetic background of congenital immunodeficiency or lipidosis. Foreign body granulomas grew slowly, predominantly at postoperative or repeat injection lesions. In two cases, crystals were deposited in multiple locations, and in one case, lipophage accumulations were found in the bone marrow. The crystals characteristically dissolved in acetic acid with oxygen gas formation, easily dissolved in alkalis and showed positive staining for PG by the gold hydroxamic acid method. All crystals examined by infrared microscopy, mass spectrometry and X-ray microanalysis showed similar results, supporting the theory that the crystals were PG. Phosphoglyceride deposition disease is a lipid metabolic disorder in which PG crystals are slowly deposited, predominantly in injured soft tissues, forming foreign body granulomas. The diagnosis can be based on histological characteristics. The prognosis is favorable, although some cases showed systemic depositions with repetitions. Lysosomal phosphoglyceride metabolism in macrophages might be affected.

Cytomegalovirus (CMV) is the most significant infectious cause of brain disorders in humans. Although the brain is the principal target organ for CMV infection in infants with congenital infection and in immunocompromised patients, little has been known about cellular events in pathogenesis of the brain disorders. Mouse models have been developed by the authors for studying the cell tropism, infectious dynamics of CMV infection and the effects of CMV infection on proliferation, regeneration and differentiation of neural cells. It has been shown, using brain slice cultures and neurospheres, that neural stem progenitor (NSP) cells are the most susceptible to CMV infection in developing brains. The NSP cells are also susceptible to CMV infection in adult and aged brains. The susceptibility can be enhanced by stimulation of neurogenesis. It was shown that latent murine CMV infection occurs in NSP cells by demonstrating the reactivation in brain slice culture or neurospheres. It is hypothesized that CMV brain disorder such as microcephaly is caused by disturbance of cellular events in the ventricular regions, including proliferation and differentiation of the neural stem cells, whereas neurons are also targets in persistent CMV infection, presumably resulting in functional disorders such as mental retardation.

Congenital cytomegalovirus (CMV) infection is the most common infectious cause of sensorineural hearing loss in children. Here, we established an experimental model of hearing loss after systemic infection with murine CMV (MCMV) in newborn mice. Although almost no viral infection was observed in the inner ears and brains by intraperitoneal (i.p.) infection with MCMV in newborn mice, infection in these regions was induced in combination with intracerebral (i.c.) injection of bacterial lipopolysaccharide (LPS). The susceptibility of the inner ears was higher than that of the brains in terms of viral titer per unit weight. In the labyrinths, the viral infection was associated with the mesenchymal vessels and accompanied by inflammatory cells induced by LPS, causing hematogenous targets of infection in the labyrinths. Viral infection also spread in the perilymph regions such as the scala tympani and scala vestibuli, probably from infected brains via meningogenic and cochlear nerve routes. Viral infection was not observed in the scala media in the endolymph, including the Corti organ. However, viral infection was observed in the spiral limbus, including the stria vascularis. These results suggest that hearing loss caused by labyrinthitis after congenital CMV infection may be enhanced by inflammation caused by systemic bacterial infection in the neonatal period.

We report on a primary endodermal sinus tumor (EST) (yolk sac tumor) combined with a focal seminoma of the prostate occurring in a 24-year-old man. The prostate was widely infiltrated with neoplasms that penetrated the capsule and invaded into the bladder wall and urethra. Most areas of the tumor were composed of papillary and glandular epithelium in the fibrous or myxoid stroma. Schiller-Duval bodies and periodic acid-Schiff-positive hyaline bodies were focally present. In addition to yolk sac tumor, solid nests of seminoma were found in some areas. Immunohistochemistry using specific antibodies for alpha-fetoprotein and cytokeratin showed positive reaction on the EST portion, and placental alkaline phosphatase revealed positive staining in the seminoma portion and a part of EST. Tumor cells exhibited negative staining for prostate-specific antigen, prostatic acid phosphatase, carcinoembryonic antigen, vimentin, chromogranin A, and human chorionic gonadotropin. Despite radical surgery and ordinary cisplatin-based chemotherapy, the patient died 8 months after operation. At autopsy, only EST elements had metastasized to the lungs, liver, and brain, and no tumors were found in either testis. To our knowledge, this is the first reported case of a primary EST combined with a focal seminoma in the prostate.

BackgroundTo evaluate the expression levels of Cyclin D1 in breast papillomas and papillary carcinomas, and to analyze the types of cells that co-express Cyclin D1 with Cytokeratin 5/6 (CK 5/6) or with Cytokeratin 8/18(CK 8/18).MethodsFifty-nine cases of papillary lesions including 36 papillomas and 23 intracystic papillary carcinomas were examined. Cyclin D1, CK 5/6 and CK 8/18 expression levels were evaluated by double immunostaining.ResultsCyclin D1 is highly expressed in papillary carcinomas (27.54% ± 15.43%) compared with papillomas (8.81% ± 8.41%, p < 0.01). Cyclin D1 is predominantly expressed in Cytokeratin 8/18- expressing cells, rather than in Cytokeratin 5/6-expressing cells, regardless of the type of lesion. In Papillomas, Cyclin D1 exhibited a mean 11.42% (11.42% ± 10.17%) co-expression rate with Cytokeratin 8/18 compared with a mean 2.50% (2.50% ± 3.24%) co-expression rate with Cytokeratin 5/6 (p < 0.01). In papillary carcinomas, Cyclin D1 exhibited a mean 34.74% (34.74% ± 16.32%) co-expression rate with Cytokeratin 8/18 compared with a co-expression rate of 0.70% (0.70% ± 0.93%) with Cytokeratin 5/6 (p < 0.01).ConclusionsThe increase in Cyclin D1 suggests an association of Cyclin D1 staining with papillary carcinomas. Although Cyclin D1 is an effective marker for the differential diagnosis of other papillary lesions, it cannot be used to distinguish between papilloma and papillary carcinoma lesions because its expression occurs in both lesions. Our results show that Cyclin D1 and CK 5/6 staining could be used in concert to distinguish between the diagnosis of papilloma (Cyclin D1 < 4.20%, CK 5/6 positive) or papillary carcinoma (Cyclin D1 > 37.00%, CK 5/6 negative). In addition, our data suggest that Cyclin D1 is expressed only in the cancer stem or progenitor cells that co-immunostained with CK 8/18 in papillary carcinomas, and predominantly with CK 8/18 in the papillomas.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7299340558756848