[18-year-old woman with an ovarian tumour detected by coincidence]. / 18-jährige Frau mit zufällig entdecktem Ovarialtumor.

Massive ovarian edema (MOE) is a rare, benign disease of young women. Because preoperatively in most cases the differential diagnosis primarily appears to indicate the presence of a malignant tumour, there is a risk that these patients will be subjected to unnecessary overtreatment. In the case of the 18-year-old patient described here, on the basis of the preoperative data the suspected clinical diagnosis was polycystic ovarian (PCO) syndrome. In the MRI the enlarged ovary was interpreted as a mucous tumour. The laparotomy showed a smooth-walled, opalescent ovarian tumour with adnexal torsion. Histopathological examination of the adnexectomy specimen gave the diagnosis of a massive ovarian edema (MOE). Therapeutically, a wedge-shaped excision, immediate-section histology and derotation and suspension of the ovary would have been sufficient. Unnecessary overtreatment can be avoided in young women with enlarged ovaries, if MOE is included in the differential diagnosis and if the characteristic sonography, MRI and macroscopy findings are known.

[Placental site trophoblastic tumor: case report and review of literature]. / Placental site trophoblastic tumor--Ein Fallbericht und Literaturübersicht.

A 32-year-old para 3 patient is presented having suffered from a silent uterine rupture on the occasion of her second and third Caesarean sections. After the third Caesarean section, there was light uterine bleeding whilst the patient breastfed for five months. Amenorrhoea then ensued due to oral contraception. Regular clinical and ultrasound checks revealed negative serum beta-HCG values and retrovesicular resistance, which increased in size after 18 months and became symptomatic. Because the patient's family was complete, abdominal hysterectomy without adnexectomy was performed. Histology revealed a placental site trophoblastic tumour (PSTT). This is a rare tumour with malignant potential, whose prognosis depends on the stage of the primary tumour, the period of time between the last pregnancy and onset of disease, the patient's age, and the rate of mitosis, and whose progress cannot be assessed using the WHO Prognostic Index Score for Gestational Trophoblastic Disease. In therapeutic terms, hysterectomy is recommended. Chemosensitivity is low and, due to the infrequency of the tumours, the most suitable chemotherapy scheme is unknown. In the case of metastasising or recurrent PSTT, the EP/EMA regime has proved to be most effective.

Giant Sertoli cell nodule of the testis: distinction from other Sertoli cell lesions.

The case of a 33-year-old man with a clinically suspected testicular neoplasm is reported here. The radical orchidectomy specimen showed a sharply demarcated, firm, yellow-white 1-cm nodule beneath the tunica albuginea at the upper pole. Microscopical examination showed the encapsulated nodule to be composed of tubules lined by immature Sertoli cells with interspersed spermatogonia and an interwoven network of hyalinised basement membrane having foci of calcification. Immunohistochemical studies verified the fetal phenotype of the Sertoli cells and the non-neoplastic nature of the germ cell component. Except for the large size, the findings were identical to those of a Sertoli cell nodule-a typically microscopic, unencapsulated lesion commonly detected in cryptorchid testes. The term "giant Sertoli cell nodule" is used for this unique, hitherto undescribed lesion and its distinction from other Sertoli cell lesions of the testis is considered here.

Expression of the hMSH6 mismatch-repair protein in colon cancer and HeLa cells.

PRINCIPLES: 10 to 15% of human colon cancers are associated with an inherited or somatic defect of the DNA Mismatch Repair (MMR) system, which has evolved to correct biosynthetic errors such as nucleotide mis-incorporations or misalignments arising during DNA replication in the S phase of the cell-cycle. Although expression of the MMR genes was expected to be cell-cycle dependent, we and others observed that the MMR proteins hMSH2 and hMLH1 are expressed constitutively in proliferating cells. METHODS: In this study we extend our observations to another essential MMR protein, hMSH6. We used immunohistochemistry to evaluate the expression pattern of this protein in human colorectal mucosa and tumours, as well as in synchronised HeLa-S3 cells, in which we analysed its steady-state levels during the cell-cycle. RESULTS: We show that the immunohistochemical pattern of expression of hMSH6 in normal colorectal crypts and in colon cancers differs significantly from that of the other MMR proteins, with a much lower percentage of replicating cells being hMSH6-positive. This implies that hMSH6 could be cell-cycle regulated. In order to test this hypothesis in a model system, we synchronised HeLa-S3 cells with mitotic shake-off and found that the hMSH6 protein was detectable throughout the cell-cycle, but that its steady-state level increased when cells progressed from G1 to S-phase. DISCUSSION: The increase of hMSH6 steadystate level when cells enter S-phase was expected, since MMR acts during DNA replication. However, the overall low level of oscillations of hMSH6 during the cell-cycle in this cellular model apparently does not fit the immunohistochemical phenotype. We believe that this discrepancy is due to the fact that human cell lines proliferate at a much higher rate than normal and neoplastic colorectal cells in vivo.

Prognostic and predictive significance of ErbB-2 breast tumor levels measured by enzyme immunoassay.

PURPOSE: A retrospective analysis to assess the prognostic and predictive clinical value of breast tumor ErbB-2 receptor expression quantified by enzyme immunoassay (EIA), to compare levels measured by EIA with ErbB-2 status determined by immunohistochemistry (IHC), and to correlate receptor content with levels of phosphorylated (Y1248-P) ErbB-2, a measure of functional tyrosine kinase activity. MATERIALS AND METHODS: EIA quantification of ErbB-2 was performed on membrane extracts from 3,208 well-characterized primary breast cancers. Overall, relapse-free, distant disease-free, and local/regional-free patient survival data were available on 1,123 of these tumors. IHC scoring for ErbB-2 status (HercepTest; DAKO, Glostrup, Denmark) was performed on adjacent sections of 151 cases, and receptor functionality was measured in 230 tumors by an antibody specific for phosphorylated (Y1248-P) ErbB-2. RESULTS: Unlike nonmalignant breast tissues, breast tumors showed increased ErbB-2 levels in a bimodal distribution, with 12% constituting a distinct set of ErbB-2-overexpressing tumors. The intermodal threshold value for ErbB-2 overexpression distinguished tumors with reduced estrogen and progesterone receptor content, high IHC score for ErbB-2, and significantly increased levels of phosphorylated (Y1248-P) ErbB-2 receptor. By multivariate analysis, EIA-determined ErbB-2 overexpression predicted significantly reduced patient survival that was unaffected by tamoxifen or cyclophosphamide, methotrexate, and fluorouracil adjuvant therapy. CONCLUSION: Determination of ErbB-2 receptor expression by EIA offers a clinically valuable alternative to semiquantitative IHC assessment of breast tumor ErbB-2 overexpression and affords the opportunity to evaluate ErbB-2 phosphorylation, which may represent an important predictive parameter of receptor functionality.

An uncommon cause of recurrent strokes: Tropheryma whippelii endocarditis.

BACKGROUND: Cardiac involvement in Whipple's disease is not an uncommon phenomenon in autopsies, but its clinical occurrence is often overshadowed by gastrointestinal symptoms. We report a very atypical manifestation of this disorder. SUMMARY OF REPORT: An extraordinary presentation of an extremely long-lasting, culture-negative endocarditis caused by Tropheryma whippelii is described, the clinical consequence of which has become apparent in recurrent strokes. CONCLUSIONS: Cardiac involvement of Whipple's disease should always be considered in culture and serologically negative endocarditis. The polymerase chain reaction technique may be a useful tool to confirm a presumed diagnosis of T whippelii endocarditis and consequently to apply an effective treatment regimen.

Early orchiopexy: prepubertal intratubular germ cell neoplasia and fertility outcome.

OBJECTIVES: To investigate the prepubertal prevalence of intratubular germ cell neoplasia of the unclassified type (ITGCNU) and its significance as a predictor of testicular cancer and to evaluate the effect of early orchiopexy (at younger than 2 years of age) on subsequent fertility of patients with bilateral cryptorchidism. METHODS: Testicular biopsies (n = 660) from 440 prepubertal patients with cryptorchidism who underwent orchiopexy between January 1, 1970 and December 31, 1979 were evaluated for ITGCNU using placental-like alkaline phosphatase (PLAP) antibody. The clinical outcome in 15 patients with PLAP-positive germ cells was evaluated in 1997. In addition, the effect of age at surgery on the fertility of patients with bilateral cryptorchidism was assessed by clinical follow-up until 1997 and was correlated with the histologic data at orchiopexy. RESULTS: PLAP-positive germ cells morphologically identical with adult ITGCNU were found in the biopsies of 22 patients (5%). After more than two decades, none of the 15 patients with successful follow-up developed testicular cancer. The fertility outcome in the patients with bilateral cryptorchidism correlated with the number of spermatogonia at orchiopexy (P = 0.018), but correlated inversely with age at orchiopexy (P = 0.021). CONCLUSIONS: PLAP-positive germ cells in prepubertal testicular biopsy specimens are not necessarily precursors of testicular cancer after orchiopexy. In addition, our data support the idea that early orchiopexy may be beneficial in preventing infertility.

Clinical significance of interobserver differences in the staging and grading of superficial bladder cancer.

OBJECTIVE: To assess the reliability of the histological diagnosis of bladder cancer by assessing the interobserver variability of staging and grading in pTa/pT1 tumours and evaluating the clinical significance of discrepancies. MATERIALS AND METHODS: All sections from 301 superficial bladder carcinomas were reviewed by one pathologist. The prognostic relevance of grade and stage from both the initial and review diagnosis were determined in 128 patients for whom there was long-term follow-up information. RESULTS: There were significant interobserver differences in both the grading and staging of tumours. From a total of 235 tumours that were initially considered pT1, the reviewer classified 35% as pTa, 56% as pT1, 6% as pT1- (at least pT1), and 3% as pT2-4. In 39% of all biopsies there were interobserver differences in tumour grade. The prognostic significance of grade and stage differed between the initial pathology report and the reviewer's diagnosis. The reviewer's staging allowed a better estimate of the risk of subsequent tumour progression than the initial staging. Progression was significantly more common in 49 tumours in which the reviewer agreed with stage pT1 than in 29 tumours that were down-staged from pT1 to pTa (P = 0.0116). However, the initial tumour grade (P = 0.0386) but not the reviewer's grade (P = 0.2645) was significantly linked to progression. CONCLUSIONS: These results show that grading and staging by different pathologists have varying prognostic implications. If possible, biopsies from bladder tumours should be independently evaluated by two different pathologists before radical therapy is administered.

Whipple endocarditis without overt gastrointestinal disease: report of four cases.

BACKGROUND: Cardiac manifestations of Whipple disease are rarely diagnosed before death. OBJECTIVE: To describe four patients with endocarditis caused by Tropheryma whippelii who did not have overt gastrointestinal disease. DESIGN: Case series. SETTING: Five hospitals in eastern Switzerland. PATIENTS: Three men and one woman undergoing replacement of insufficient heart valves. MEASUREMENTS: Histologic characteristics of heart valves and intestinal biopsy; broad-range and specific polymerase chain reaction for T. whippelii. RESULTS: Tropheryma whippelii was found in the heart valves (three aortic valves and one mitral valve) of four patients with culture-negative endocarditis necessitating valve replacement. All patients had arthralgia for different lengths of time. Only one patient had mild gastrointestinal symptoms. Histologic characteristics of intestinal mucosa were normal in all patients, and polymerase chain reaction on intestinal biopsy was positive for T. whippelii in only one patient, who did not have diarrhea. In all patients, arthralgia resolved promptly after institution of antibiotic therapy. Disease did not recur in any patient after prolonged antibiotic therapy with cotrimoxazole. CONCLUSION: In patients with culture-negative endocarditis, the absence of clinical, microscopic, or microbiological evidence of gastrointestinal disease did not rule out T. whippelii.

Incidental choriocarcinoma confined to a near-term placenta.

A large solitary choriocarcinoma was found incidentally in a placenta from a 36-week gestation following caesarean section performed because of intrauterine fetal distress. Macroscopically, there appeared to be a large old infarct in the centre of the placenta proper. Microscopically, there was extensive central necrosis with a rim of viable trophoblastic tumour that had the typical morphology of choriocarcinoma. Although the tumour was floating within maternal blood and was also detected in direct contact with fetal vessels, no metastatic disease was reported in the subsequent 1 1/2 years either in the mother or in the child. Placental infarcts are often not examined histologically, and an intraplacental tumour may thus be missed. Central friability and an unusual colour should alert the pathologist and lead to histological clarification. The management of an incidentally discovered intraplacental choriocarcinoma should be an expectant one, consisting of extensive workup for any evidence of metastases and serial beta-HCG measurements in both mother and child.

Primary mediastinal germ cell tumor with intratubular germ cell neoplasia of the testis--further support for germ cell origin of these tumors: a case report.

BACKGROUND: The histogenesis of extragonadal germ cell tumors remains an enigma. The majority of patients with retroperitoneal tumors are male, and careful histologic evaluation reveals preinvasive intratubular germ cell neoplasia (ITGCN) or scars in the testis suggesting a so-called "burnt out" germ cell tumor. However, in the testes of patients with primary mediastinal germ cell tumors, no ITGCN has been described in the literature to date. The authors report the first case of simultaneous germ cell neoplasia in the mediastinum and the testis, providing further insights into the biology and origin of these lesions. METHODS: The authors report the pathologic features and cytogenetic findings in an adult male with a mediastinal germ cell tumor and asymmetric testis. This patient died shortly after diagnosis. RESULTS: A locally invasive mediastinal nonseminomatous germ cell tumor was associated with ITGCN in one testis. Metastases were not present clinically or on autopsy during a detailed and systematic examination of retroperitoneal lymph nodes and other viscera. Neither an invasive germ cell tumor nor a scar was found in either testis (both testes were serially sectioned and entirely examined histologically). CONCLUSIONS: The findings of this study suggest that the mediastinal tumor is a primary neoplasm with concomitant in situ lesion in one testis, suggesting a more generalized defect of germ cell and thus providing new information about the unresolved issue of the histogenesis of extragonadal germ cell tumors. This article presents a review of the literature concerning the issues highlighted by this case and discusses the hypotheses regarding the development of extragonadal germ cell tumors.

[Chronic cholestatic liver disease and grand mal seizures]. / Chronische cholestatische Hepatopathie und Grand-mal-Anfall.

HISTORY AND CLINICAL FINDINGS: A 48-year-old woman was hospitalised because of grand-mal seizures. 3 years previously a malignant melanoma had been resected from the skin of the back. She was also known to have chronic cholestasis of unknown cause. On physical examination there were postictal signs, but no neurological abnormalities and no jaundice. INVESTIGATIONS: Biochemical tests demonstrated greatly increased alkaline phosphatase (576U/I). gamma-GT (1556U/I) and leucine aminopeptidase (258U/I). The transaminases were only slightly raised (GOT 113U/I, GPT 82U/I). Magnetic resonance imaging of the brain revealed a single intracerebral space-occupying lesion, compatible with a melanoma metastasis. Endoscopic retrograde cholangiopancreatography discovered a filiform, short stenosis in the choledochal duct, histologically an adenocarcinoma. TREATMENT AND COURSE: The cerebral metastasis was removed stereotactically without complications. A Whipple-type gastroduodenopancreatectomy was performed 2 months later. Histology of an intraoperative liver biopsy revealed Caroli's syndrome (focal intrahepatic biliary dilatation) with congenital hepatic fibrosis. Cholestasis persisted after the operation and was treated with ursodeoxycholic acid. The patient has now been free of symptoms for 3 years. CONCLUSIONS: Caroli's syndrome should be included in the differential diagnosis of chronic cholestasis of unknown cause. The case also demonstrates the justification, under certain conditions, of aggressive treatment even when there are two different malignancies.

Loss of heterozygosity on chromosome 16q, expression of her2/neu and p53 mutations in endometrial cancer.

We analyzed endometrial adenocarcinomas for mutations of the p53 anti-oncogene, expression of the HER2/neu oncogene and for loss of heterozygosity on chromosome 16q. p53 mutations were found in 3 of 25 tumors. Elevated expression of HER2/neu found in 7 of 24 tumors involves a mechanism other than gene amplification. LOH on chromosome 16q22-24 was observed in 4 of 13 informative tumors. Four of 25 endometrial tumors exhibited two or more alterations. Tumors with the highest HER2/neu protein level exhibited a negative progesterone receptor status. Accumulation of these changes may determine the biological behaviour of a subset of endometrial tumors.

P53 mutations and loss of heterozygosity on chromosomes 8p, 16q, 17p, and 18q are confined to advanced prostate cancer.

We analysed 39 prostatic carcinomas for loss of heterozygosity on chromosomal arms 8p, 10q, 16q, 17p and 18q and for mutations in the p53 anti-oncogene. Loss of heterozygosity (LOH) on 8p was detected in one out of 5 informative tumors, LOH on 16q in 3 out of 21 tumors, LOH on 17p in 2 out of 18 tumors, and LOH on 18q in 2 out of 17 tumors. No deletions were observed on 10q in 14 informative tumors. p53 alterations occurred in 3 out of 38 examined tumors, comprising two point mutations and a small deletion. Chromosomal deletions and p53 mutations were confined to locally invasive prostatic carcinomas, suggesting that they are associated with the progression of some prostate cancers rather than with tumor initiation.

[Primary malignant melanoma of the male urethra. Case report and discussion of the literature]. / Primäres malignes Melanom der männlichen Urethra. Fallbericht und Diskussion der Literatur.

We report the case of a 77-year-old man who presented with a polypoid tumor in the distal urethra. It was excised, and a histological diagnosis of malignant melanoma was made. The patient had no history of previous cutaneous biopsies or suspicious pigmented lesions; therefore, the melanoma was considered to be primary in the urethra. The patient declined therapy and died 28 months later with local tumor progression. The autopsy revealed a widespread metastatic disease. The male urethra is rarely the primary site of a malignant melanoma. This event has so far been described in about 45 patients. The case is discussed in view of the pertinent literature.

[Spontaneous recanalization after vasectomy]. / Spontane Rekanalisation nach Vasektomie.

Two cases of spontaneous recanalisation could be reoperated. The recanalisation was proved histologically. The reasons were analysed. The own technique is presented: resection of at least two centimeters of the vas, ligature, electrocoagulation, proximally turning-up fixation of the end, distally immersing the end in a tobacco-pouch.

[Febrile status and micronodular changes of the lung parenchyma in HIV infection]. / Status febrilis und feinnoduläre Lungenparenchymveränderung bei HIV-Infektion.

This 49-year-old man with the acquired immunodeficiency syndrome (AIDS) was admitted to the hospital because of fever, weight loss and respiratory symptoms. The radiograph of the chest showed diffuse fine nodular opacities. Histology of lung and lymph node revealed a necrotising granulomatosis and yeasts suggesting histoplasmosis. It's identity was confirmed by positive cultures for Histoplasma capsulatum in blood, urine, lung specimen and lymph node. There was a successful induction treatment and a maintenance therapy with amphotericin B. We discuss disseminated histoplasmosis in the immunodeficiency syndrome.