Granular cell tumor of the penis: clinicopathologic evaluation of 9 cases

The occurrence of granular cell tumor (GCT) in penile tissue is very rare, with only 9 examples reported to date in the English-language literature. Herein, we describe the clinicopathologic and immunohistochemical findings in 9 additional cases. The patients ranged in age from 20 to 60 years (mean, 42 years; median, 40 years) at time of diagnosis. All penile tumors were solitary and arose in the dermis of the penile shaft (n=4), prepuce (n=3), and corona (n=2). A patient had a history of multiple cutaneous GCTs. Duration of symptoms before surgery ranged from 5 days to 2 years with the presence of an asymptomatic nodule representing the most common tumor-related complaint (n=8). The lesions ranged in size from 0.6 to 2.5 cm (mean, 1.5 cm; median, 1.5 cm). Microscopically, the tumors were moderate to highly cellular and were composed of oval to polygonal-shaped cells with abundant coarsely granular eosinophilic cytoplasm. Tumor cells grew in infiltrating nests, cords, and trabeculae and showed neural (n=2) and vessel wall (n=1) invasion or formed a relatively well-marginated solid nodule. Bland cytological features with only rare cells showing nucleomegaly (n=7) or spindling (n=3) were exhibited by 8 tumors. A tumor demonstrated diffuse nuclear atypia and was classified as "atypical." Mitotic activity ranged from 0 to 8 mitoses (mean, 1.4 mitoses) per 50 high-powered fields with no atypical division figures identified. All tumors tested showed moderate to strong immunohistochemical expression of S100 protein (n=6) and low-affinity nerve growth factor receptor (n=5), which was useful for detecting small deposits of tumor and helpful in evaluating surgical margins. Focal tumor cell immunoreactivity was observed for calretinin (4/6 cases) and glial fibrillary acidic protein (1/6 cases). All patients underwent simple (local) excision of their tumor. Complete follow-up data (mean, 21 years; interval range, 0.5-28 years) were available for 6 patients. No patient experienced recurrence or metastatic spread of tumor although surgical margins were microscopically involved by tumor in 5 cases. Benign GCT involving superficial soft tissue of the penis can be adequately managed by a simple excision. Patients with microscopically involved surgical margins can be clinically followed without immediate additional surgery.     

Managed care and children with special health care needs

The implementation of managed care for children with special health care needs is often associated with apprehension regarding new barriers to health care services. At times, these barriers may overshadow opportunities for improvement. This statement discusses such opportunities, identifies challenges, and proposes active roles for pediatricians and families to improve managed care for children with special health care needs.     

Epithelioid hemangioma of the penis: a clinicopathologic and immunohistochemical analysis of 19 cases, with special reference to exuberant examples often confused with epithelioid hemangioendothelioma and epithelioid angiosarcoma

Epithelioid hemangiomas of the penis are very rare. To date, less than 10 examples have been reported in the English language literature. In this report, we describe the clinical, histopathologic, and immunohistochemical findings in 19 cases retrieved from our files. The patients ranged in age from 23 to 75 years (median age, 45 years) at the time of initial surgical resection. Seventeen patients presented with a solitary mass, and two presented with two separate, but closely approximated, lesions. The process involved the glans penis (n = 3), shaft (n = 11), base of the penis (n = 2), or penis, not otherwise specified (n = 3). The lesions ranged in size from <0.5 to 2.5 cm (median size, approximately 1.2 cm) in greatest dimension. Eleven examples were specifically noted to be dorsally located, and only one was stated to be ventral. Localized pain or tenderness was the most common complaint, documented in 12 cases. The preoperative duration of the lesions ranged from 5 days to 1 year (median 4.5 months). Microscopically, all examples contained a tumefactive proliferation of epithelioid endothelial cells, often in a nodular or lobular configuration and associated with an inflammatory infiltrate containing lymphocytes and eosinophils. In 14 cases, the vascular proliferation was associated with a small arterial segment, sometimes with mural damage and frequently (n = 13) with intraluminal epithelioid endothelial cells. Based on the growth pattern of the epithelioid endothelial cells, 13 cases were considered "typical," and six were considered exuberant or "atypical." The latter examples had a prominent centrally located zone where nests or sheet-like aggregates of epithelioid endothelial cells did not form discrete vessels. Immunohistochemical data are available for 15 tumors. The epithelioid endothelial cells usually had strong reactivity for CD31, lesser reactivity for factor VIIIrAg, and minimal reactivity for CD34. In 9 of 12 cases, a small number of epithelioid endothelial cells expressed keratins. In all cases tested, at least focal muscle-specific actin-positive myopericytic cells were present bordering the endothelial cells, and this was especially notable peripherally. Initial surgical intervention consisted of either a shave biopsy (n = 1), excisional biopsy (n = 2), or local excision (n = 16). A complete follow-up history is available for 12 patients, and incomplete follow-up information is available for an additional four patients. One patient developed a new epithelioid hemangioma at a site within the penis separate from the initial lesion, but no patient is known to have experienced a true metastasis or to have died of complications of this process. Optimal management appears to be complete local excision with periodic follow-up visits to monitor for local recurrence.     

Deficient brain RNA polymerase and altered nucleolar structure persists until day 8 after perinatal asphyxia of the rat

RNA polymerases (POL) are integral constituents of the protein synthesis machinery, with POL I and POL III coding for ribosomal RNA and POL II coding for protein. POL I is located in the nucleolus and transcribes class I genes, those that code for large ribosomal RNA. It has been reported that the POL system is seriously affected in perinatal asphyxia (PA) immediately after birth. Because POL I is necessary for protein synthesis and brain protein synthesis was shown to be deranged after hypoxic-ischemic conditions, we aimed to study whether POL derangement persists in a simple, well-documented animal model of graded global PA at the activity, mRNA, protein, and morphologic level until 8 d after the asphyctic insult. Nuclear POL I activity was determined according to a radiochemical method; mRNA steady state and protein levels of RPA4O-an essential subunit of POL I and III-were evaluated by blotting methods; and the POL I subunit polymerase activating factor-53 was evaluated using immunohistochemistry. Silver staining and transmission electron microscopy were used to examine the nucleolus. At the eighth day after PA, nuclear POL I decreased with the length of the asphyctic period, whereas mRNA and protein levels for RPA4O were unchanged. The subunit polymerase activating factor-53, however, was unambiguously reduced in several brain regions. Dramatic changes of nucleolar morphology were observed, the main finding being nucleolar disintegration at the electron microscopy level. We suggest that severe acidosis and/or deficient protein kinase C in the brain during the asphyctic period may be responsible for disintegration of the nucleolus as well as for decreased POL activity persisting until the eighth day after PA. The biologic effect may be that PA causes impaired RNA and protein synthesis, which has been already observed in hypoxic-ischemic states.     

Operative Therapie am Becken und an der Wirbelsäule bei primär malignen Knochentumoren

Despite standardization of surgical treatment of primary malignant tumors of the pelvis and spine, prognosis in these centrally located tumors still is inferior compared to those located in the extremities. This fact may be attributed to delayed diagnosis in many cases and the resulting increase in tumor volume as well as to difficulties of resection due to the anatomical situation. The frequency of local recurrence after resection of primary malignant tumors is reported to be between 4 and 41% and the 5-year survival rate below 40%. Whereas the latter has remained almost unchanged during the past 20 years, amputation has been replaced by limb-salvage surgery except for a minimal amount of less than 10%. For reconstruction, biological techniques are increasingly preferred to endoprosthetic replacement or use of bulk allografts because of the high complication rate. Even in the spine wide resections are feasible provided at least one lamina is healthy in order to prepare and save the neural structures without touching the tumor. Compared to the widely used technique of curettage, en bloc resection may provide a significantly better oncologic result with respect to local tumor control. Failure of the dorsoventral stabilization with delayed union is the most frequent complication of these challenging procedures. In order to improve the long-term prognosis of these groups of patients in the future, early diagnosis and immediate admission to a specialized tumor service has to be attempted.     

Painful soft-tissue reaction to injectable Norian SRS calcium phosphate cement after curettage of enchondromas

A prospective single-cohort study was designed to include 20 patients with enchondromas but was stopped because of poor early results. Four patients with an enchondroma, three in the proximal humerus and one in the distal femur, were treated by curettage and filling of the defect with Norian SRS cement. Clinical and radiological follow-up including CT and MRI was carried out for 18 months. All three patients with lesions in the proximal humerus had severe pain and limited movement of the shoulder. The radiological and CT appearances of the cement were unchanged at follow-up. There were characteristic appearances of synovitis and periosteitis on MRI in two patients. Since the cement induces a soft-tissue reaction the bony cavity should be sealed with the curetted and burred bone after curettage and introduction of Norian cement, especially in sites where a tourniquet cannot be applied.     

Analysis of pregnancy and other factors on detection of human papilloma virus (HPV) infection using weighted estimating equations for follow-up data

Generalized estimating equations have been well established to draw inference for the marginal mean from follow-up data. Many studies suffer from missing data that may result in biased parameter estimates if the data are not missing completely at random. Robins and co-workers proposed using weighted estimating equations (WEE) in estimating the mean structure if drop-out occurs missing at random. We illustrate the differences between the WEE and the commonly applied available case analysis in a simulation study. We apply the WEE and reanalyse data of a longitudinal study of pregnancy and human papilloma virus (HPV) infection. We estimate the response probabilities and demonstrate that the data are not missing completely at random. Upon use of the WEE, we are able to show that pregnant women have an increased odds for an HPV infection compared with non-pregnant women after delivery (p=0.027). We conclude that the WEE are useful for dealing with monotone missing data due to drop-outs in follow-up data.     

Venous thrombosis after hallux valgus surgery

BACKGROUND: Although surgery for the treatment of hallux valgus is frequently performed, the exact rate of deep vein thrombosis following this procedure is unknown. We performed a single-center, prospective, phlebographically controlled study to quantify the rate of venous thrombosis following operative correction of hallux valgus. METHODS: Consecutive patients undergoing chevron bunionectomy for correction of hallux valgus deformity were enrolled in the study. Patients with clinical or hematological risk factors for venous thrombosis were excluded. One hundred patients with a mean age of 48.9 years were operated on and did not receive medical prophylaxis against thrombosis. All patients were assessed with phlebography at a mean of twenty-nine days postoperatively. RESULTS: Venous thrombosis was found in four patients (4%). The mean age of these patients (and standard deviation) was 61.7 +/- 6.1 years compared with a mean age of 48.4 +/- 13.9 years for the patients in whom thrombosis did not develop (p = 0.034). CONCLUSIONS: Patients are at a low risk for venous thrombosis following surgical treatment of hallux valgus. The need for prophylaxis against thrombosis should be calculated individually for each patient according to his or her known level of risk. Routine medical prophylaxis against thrombosis might be justified for patients over the age of sixty years.