[Centrifugal plaques with central atrophy and peripheral scale on the scalp]. / Zentrifugale Plaques mit zentraler Atrophie und peripherem Hornwall am Capillitium.

A 62-year-old man presented with slowly progredient, centrifugal, peripherally hyperkeratotic, centrally atrophic, slightly pruritic lesions on his scalp for at least 9 months. A punch biopsy stained with hematoxylin-eosin (HE) revealed minimal epidermal acanthosis and chimney-like parakeratosis (cornoid lamella) around a follicle. Discrete spongiosis of the epidermis was observed, as well as a lymphocytic cell infiltration in the papillary dermis. Based on the clinical picture and the histopathological examination the diagnosis of porokeratosis of Mibelli was made. Topical treatment was started using an urea and vitamin A acid preparation.

Micronucleated cells during the growth of the Ehrlich ascites tumour on spontaneous and by titanocenedichloride-induced conditions.

The micronucleus assay was used to investigate the activity of the Ehrlich-ascites tumour (EAT) of mice to produce chromosomal aberrations under spontaneous and chemically induced conditions. Titanocene dichloride (TDC), a cytostatic drug similar to cis-platinum, was injected in several dosages into the peritoneal cavity of mice carrying the tumour (40, 60 or 80 mg/kg). Our results show that there exists a constant spontaneous level of micronucleated cells (MNC), and that TDC is a potential dose-related inductor of micronuclei (MN). The highest amounts of MN are registered 48 h after application. We discuss the results in context with basic cytokinetic data of our tumour. This leads to the postulation of a dynamic balance of generating and eliminating factors producing the actual level of MNC.

[Inflammatory juvenile conjunctival nevus (IJCN)]. / Inflammatorischer juveniler Bindehautnävus (IJCN).

BACKGROUND: Pathologists may occasionally have difficulties in reliably assessing the dignity of tumour cells in histological sections, especially in nevi with junctional activity. PATIENT HISTORY: This case history of a boy suffering from an inflammatory juvenile conjunctival nevus (IJCN) is reported with a follow-up period of 25 years. Seven years after first surgical treatment of a histologically proven nevus, a recurrent pigmented lesion within the former operation area aroused the suspicion of it being a malignant melanoma. Logically, a second excision was performed followed by cryotherapy with liquid nitrogen (spray freezing). The histological diagnosis performed by a pathologist resulted in a malignant melanoma. A second recurrent pigmented conjunctival tumour developed fourteen years later. This lesion again aroused another strong clinical suspicion of malignant transformation into a melanoma. However, the histological examination of the biopsy at this time only showed benign nevus cells and areas of conjunctival melanosis without atypia. DISCUSSION: Especially in young patients, IJCN must be regarded as an independent type of nevus, which might lead even experts in ophthalmic pathology to over-diagnose this lesion as a malignant melanoma. This could mean that the wrong therapeutic steps were taken with surgical procedures that cause unnecessary mutilation. A reappraisal of the former histological specimens of the first recurrent tumour by other pathologists came to the conclusion that the initial diagnosis of melanoma could not be maintained. Nevertheless, we also strongly recommend follow-up examinations at regular intervals in cases of IJCN since we are aware of the fact that melanocytic tumours of the conjunctiva behave unpredictably.

[Atypical mycobacteriosis of the skin caused by Mycobacterium abscessus in an immunocompetent woman]. / Atypische Mykobakteriose der Haut durch Mycobacterium abscessus bei einer immunkompetenten Frau.

Mycobacterium abscessus is the most pathogenic of the fast-growing mycobacteria, and it is resistant to most of the antimicrobial and tuberculostatic drugs available. This non-tuberculous mycobacterium is significant in medicine because it can contaminate post-traumatic wounds and be a causative agent in chronic skin and soft tissue infection after surgical procedures.A 60-year-old immunocompetent woman was suffering from chronic ulcers and abscesses on the heels and malleoli of both feet. Histological examination revealed a granulomatous inflammation with detection of acid-fast rods, albeit without fibrinoid necrosis. The repeated detection of atypical mycobacteria, which were ultimately identified as Mycobacterium abscessus, allowed the diagnosis of an atypical mycobacteriosis of the skin. This was successfully treated first with clarithromycin and rifabutin and later with a combination of ethambutol, minocycline, clofazimine and azithromycin.

[Acute blindness caused by fungal infection in chronic myeloid leukemia]. / Akute Erblindung durch Pilzinfektion bei chronisch myeloischer Leukämie.

PATIENT: A 35-year-old man had suffered from leukemia since September 1990. A transplantation of bone marrow was carried out in February 1994. He developed a graft-versus-host disease in November 1995. In December 1995 a keratoplasty was necessary because of a perforated corneal ulcer. 17 days later the patient noted a complete loss of vision, first in the left and one day later in the right eye. The optic nerve head was white and the retina looked ischaemic like in central retinal artery occlusion. A hypodensic area was found in the frontal brain reaching up to the optic chiasm in computer tomography. Inspite of intensive treatment the immunosuppressed patient died 4 days after he had become blind. Autopsy showed a mycotic infiltration by mucormycosis of the brain and the right optic nerve sheath. This human- pathogenic fungal infection belongs to the group of mould as well as aspergillus. CONCLUSION: Mycosis should be considered in the differential diagnosis of acute visual loss in immunosuppressed patients.

Predictive value of DNA cytometry in CIN 1 and 2. Image analysis of 193 cases.

OBJECTIVE: To investigate DNA image cytometry for predicting the prognosis of cervical intraepithelial neoplasia (CIN). STUDY DESIGN: Smears from 151 women affected by CIN 1 or 2 on cytology with minimal follow-up of three years were included. Sixty-seven showed progression, with histologically confirmed carcinoma in situ or invasive cancer. Eighty-four cases showed regression of the disease, which was cytologically, histologically and colposcopically confirmed. Papanicolaou-stained smears were destained, and the Feulgen reaction was performed with consecutive image DNA cytometry of suspicious cells using an image analysis system (Cires, Zeiss, Germany). The DNA index of the greatest stemline and the number of single aneuploid cells, using 9c exceeding events, were computed. RESULTS: In the group with progression, an aneuploid DNA stemline was found in 25 smears (26.9%). In 64 cases (66.7%) more than one aneuploid event was detected. The total number of aneuploid cases in this group was 76 (81%). In the group without progression, the number of aneuploid stemlines was 2 (2%). Single aneuploid cells could be found in five cases (5%). The overall number of aneuploid cases in that group was five. The sensitivity was 74.3%, positive predictive value 85.2% and negative predictive value 77%. CONCLUSION: Aneuploidy is a marker for prospective malignancy in cervical Papanicolaou smears. DNA image cytometry, as an additional method, can be used to predict outcome in patients with CIN 1 and 2 of the cervix. DNA cytometry is not a screening method but can add further information for a treatment decision in doubtful cases.

[Value of cytometric parameters the planning of therapy of urothelial carcinoma]. / Die Bedeutung zytometrischer Parameter bei der Therapieplanung von Urothelkarzinomen.

The prognostic value of cytometric DNA parameters and their possible influence on the planning of treatment were investigated in 44 patients with transitional carcinoma of the urinary bladder (17 G1 tumours, 15 G2 tumours, 12 G3 tumours) as compared with normal urothelium of 7 patients. The nuclear DNA content was measured by scanning cytophotometry in Feulgen stained cytological smears. A statistically significant correlation was found to exist between the combination of the DNA parameters stem line quotient, 5c exceeding rate and DNA malignancy grade and the appearance of recurrences. A discrimination of a low grade and a high grade tumour group was based on this result within the G1 and the G2 transitional carcinomas as well. All patients with a carcinoma classified as low grade were recurrence-free within an observation period of more than 10 years. Further studies should clarify if this group can be treated without a topic chemotherapy after transurethral electroresection in contrast to the high grade group in which a topic chemotherapy is necessary.

Heterogeneity of DNA distribution pattern in renal tumours.

The presence of intratumoural heterogeneity in DNA distribution patterns has been accepted. However, most previous studies have not taken this fact into consideration. The value of DNA cytometry depends on its reproducibility. This could be influenced by heterogeneity failure. The aim of the present study is to evaluate intratumoural heterogeneity in renal cell cancer. A sample of 22 tumours of the kidney was investigated by means of static DNA cytometry: 21 tumours were carcinomas, one was an angiomyolipoma. Probes from seven different locations of each tumour were Feulgen-stained and measured. The variability of DNA features was determined and correlated with histological grade and type and with tumour size. There was considerable intratumoural heterogeneity with respect to DNA distribution pattern in 45% of the tumours. Additional non-diploid tumour-stemlines and deviation of computed DNA features could be found in several cases by measuring more than one slide per tumour. A correlation between tumour heterogeneity, grading or typing, and tumour size could not be found. Because these DNA parameters could serve as the foundation of a risk-adapted treatment, tumour heterogeneity could have clinical consequences. Based on the results of this study we suggest measuring at least three slides per tumour to avoid misinterpretation of DNA measurements in renal cell cancer.

Postpartal gestational choriocarcinoma fatally misdiagnosed as squamous cell cancer of the uterine cervix.

Gestational choriocarcinoma (CCA) is a well-defined tumor, but there may be a surprising variation in its morphologic appearance. A 33-year-old woman with term-pregnancy six months before presented with dysfunctional bleedings that lasted about five weeks. Cervical punch biopsy and currettage revealed a polymorphic tumor which was initially diagnosed as poorly differentiated squamous cell cancer of the cervix. Methotrexat monochemotherapy was performed after histology definitely revealed CCA on the radical abdominal hysterectomy-specimen (Wertheim-Meigs). Immediately after HE, the patient developed diffuse pulmonary metastases and died of respiratory insufficiency after two courses of MTX-therapy. The autopsy confirmed metastatic CCA. The second patient, a 48-year-old women with pregnancy 24 years before, was initially treated with radical HE after misdiagnosis of cervical currettage as squamous cell cancer of the uterine cervix. The patient showed complete remission after two courses of medium risk-protocol and seven courses of high risk-protocol (CHAMOCA). All cervical curettage specimens which did not show typical squamous cell cancer. even in older women, were suspicious of CCA. CCA often shows degenerative changes or predominantly intermediate or cytotrophoblastic cellular elements. To detect the cells of most diagnostic value in CCA, the syncytiotrophoblastic elements, HCG-immunohistochemistry may be helpful.

[Mycotic retrobulbar neuritis]. / Mykotische Retrobulbärneuritis.

BACKGROUND: Fungal disease is one of the most common complications of malignant haematologic disease. In the major part of the patients the lungs and the gastrointestinal tract are affected. Infections of the eyes and adnexa are very rare. PATIENT AND METHODS: A 75-year-old woman presented with acute unilateral loss of vision. The history revealed an anaplastic anemia. Vision of the affected eye decreased to light perception. The ophthalmoscopic findings were normal. A retrobulbar tumor was diagnosed by ultrasonography and CT. It was regarded as a glioma or a meningioma. A Non-Hodgkin lymphoma of low malignancy was proven by biopsy of bone marrow; hence a retrobulbar lymphoma was included in the differential diagnosis. Radiation was started, but the general state of health worsened and the patient died. AUTOPSY FINDINGS: A severe mycotic infiltration of the left optic nerve sheath was found, which had broadened the spatium intervaginale. Cause of death was a pneumonia by generalized immunocytoma. CONCLUSIONS: In cases with retrobulbar tumors and malignant haematologic diseases fungal infections should be included in the differential diagnosis. Serologic investigations are useful. The prognosis is poor and depends on the course of the basic disease.

[Vaginal hemorrhage after hysterectomy as a complication of alcohol-induced liver cirrhosis]. / Vaginale Blutung nach Hysterektomie als Komplikation einer alkoholbedingten Leberzirrhose.

We report on a 50-year-old woman with a decompensated alcoholic liver cirrhosis and Korsakow syndrome since 1991. In July 1992, an abdominal hysterectomy with bilateral salpingoophorectomy was made because of an endometrial carcinoma pT1NOMO. A postoperative abscess of the vaginal stump was evacuated. The patient was admitted three years later with a massive vaginal bleeding. Her general appearance and nutritional status were bad. The vaginal bleeding was caused from ruptured varicose pelvic veins secondary to portal hypertension. Neither conservative (vaginal tamponade, infusions) nor operative (laparotomy with an intraabdominal and transvaginal tamponade) therapy was successful. The patient died as a result of severe bleedings. We discuss differential diagnostics and planning therapy.

DNA cytometry in renal cell carcinoma.

The course of patients suffering from renal cell carcinoma depends on various factors. The measurement of the nuclear DNA content has been considered as a prognostic indicator in addition to morphologic and clinical parameters. The meaning of this parameter is under discussion today. The aim of the present study is to investigate the influence of nuclear DNA parameters of renal cell carcinoma on the prognosis. It should be searched for such parameters which give us the possibility to divide the patients into a low-risk-group and a high-risk-group. 110 clear cell renal carcinomas were investigated by means of image analysis and flow cytometry. Stemline ploidy, 5c-exceeding-rate, DNA grade of malignancy, S-phase-fraction, proliferating fraction, and nuclear area have been determined. A significant correlation between the size of the tumor, lymph node metastases and distant metastases on the one hand and the computed DNA parameters on the other hand was found. A similar correlation between histologic grading and DNA parameters could be found. There were pieces of information about the clinical follow-up in 87 patients (mean follow-up time 15,5 months). Local recurrence occurred in 12 cases. The computed differences between DNA parameters and local recurrence were not significant. Further clinical follow-up and clinical re-examination of all patients will be performed. Then we can decide, if it is possible to make a division into low-risk and high-risk cases based on DNA parameters.

False positive cervical smears: a cytometric and histological study.

The evidence of exfoliative cytology of the cervix uteri depends on various factors. The rate of false positive cervical smears is on average 8.8%. We have reviewed 170 false positive routinely Papanicolaou-stained cervical smears and the corresponding histological specimens. The aim was to look for non-neoplasic changes explaining the cytological over-interpretation. In addition, nuclear Feulgen-DNA measurements of the smears were made to look for changes in DNA pattern. In 50% of all cases, a cause was found for the false positive cytological diagnosis by means of histological reexamination: non-neoplastic nuclear and cellular polymorphia, severe purulent-erosive inflammation, a higher reclassification or a positive presurgical biopsy. In 51.9% of these cases, there were signs of an infection with human papilloma virus (HPV). In cases without histological explanation of the cytological findings, DNA measurements were made on the suspicious cells. By means of single cell algorithm (5c/9c exceeding events), a general rate of 62.7% of aneuploid specimens was detected. The number of aneuploid single cells ranged between 5 and 63 per slide. Of these cases, 23.1% showed signs of HPV infection. As a result of the study, the number of real 'false positive' cytological diagnoses decreased from 170 to 97 as a result of histological reexamination and DNA measurement. In doubtful cases, DNA measurement of suspicious smears should be made.

[Cytophotometric investigations in recurrent gliomas: correlation of DNA-parameters with WHO-grade, proliferation index and recurrence-free interval]. / Zytophotometrische Untersuchungen an Rezidivgliomen. Korrelation der DNA-Parameter mit dem WHO-Grad, dem Proliferationsindex und der Länge der rezidivfreien Intervalle.

DNA-cytophotometry is one of the methods that may contribute to a more precise evaluation of the biological behaviour of tumours in addition to the WHO-classification. In this study 121 tumour specimens of 50 patients suffering from gliomas with one or up to three recurrencies were investigated. In all cases the histological type and WHO-grade and the Ki-67/MIB1 labeling index were determined. DNA cytophotometry was performed after single cell preparation on Feulgen-stained preparations, and the following parameters were calculated: stemline ploidy, 5c-exceeding rate, and 2c-deviation index. Statistical evaluation revealed a highly significant correlation between recurrence-free interval and WHO-grade only. The DNA parameters, however, furnished additional information about increasing genetic instability in the majority of the recurrencies independently of changes in the WHO-grade. They thus seem to be useful as additional parameters for the determination of glioma progression.

Relations between various DNA-parameters and degree of malignancy in endometrial carcinoma.

120 imprint-cytology specimens obtained from standardized areas of 20 endometrial carcinomas were investigated by use of a computed-controlled image analysis system to determine special quantitative DNA-parameters. The stem line ploidy, the 2c deviation index (2cDI), the DNA-associated graduation of malignancy (DNA-MG) as well as the 5c exceeding rate (5cER) were calculated for each preparation. 85% of the imprint-cytology preparations had diploid stem lines, and aneuploidy was found in 15%. There were statistically significant correlations between the DNA-MG, the 5cER and the stem line ploidy as well as between the DNA-MG and the 5cER. The sensitivity of the 5cER was 76.6% in our study and so we cannot regard this parameter as prouding accurate information about tumor malignancy in endometrial carcinoma. Special DNA-parameters defined mathematically should be utilized for objective grading of tumor malignancy.

Benign mesenteric lipoblastoma.

An unusual case of benign intraperitoneal lipoblastoma in a 10-months-old girl is presented. Cytologically and histologically, the tumor had no malignant features. By means of DNA cytometry, it was regarded as diploid without signs of malignancy and of low proliferative potential. The tumor was treated by complete surgical excision.

The value of DNA cytometry in transitional cell carcinoma of the urinary bladder.

Transitional cell carcinomas are tumors with a high tendency of local recurrence. The extent of the primary tumor and histopathologic grade incompletely predict the individual outcome. In several studies, measurement of nuclear DNA content has been found to be of prognostic value in bladder cancer. We performed static DNA cytometry on transitional cell carcinomas of 130 patients. DNA parameters were correlated with stage and grade. There was a good correlation between local tumor extent (T category), grading, and DNA parameters. Ta and T1 tumors had significantly lower levels of 5c exceeding rate and DNA grade of malignancy than muscle invasive carcinoma. Well-differentiated carcinoma (G1) also had lower levels than G2 and G3 tumors. As a result of earlier studies, a DNA-based risk-adapted concept for treatment has been developed for superficial tumors. First preliminary results of a clinical study are given in the present paper.

[Examination by image analysis for determining quantitative DNA parameters of serous papillary adenocarcinoma of the endometrium--a single case analysis]. / Bildanalytische Untersuchungen zur Bestimmung quantitativer DNA-Parameter eines serös-papillären Adenokarzinoms des Endometrium--eine Einzelfallanalyse.

Serous-papillary adenocarcinoma of the endometrium are rare tumors. We describe DNA-parameters of such a tumor. Imprint-cytologies were taken from 6 different tumor sites (myometrial invasion and 5 additional tumor localizations) and subjected to image-cytophotometry in order to determine their DNA-parameters. All histograms showed an aneuploid DNA-pattern. The DNA-malignancy grade (DNA-MG) was 2.21 +/- 0.11 on median and the 5c exceeding rate (5c ER) was 15.37 +/- 4.17 on median. These results and the slight variability of DNA-pattern at the reported serous-papillary adenocarcinoma support the hypothesis of an own entity of this tumor. Additionally, the high values of DNA-MG and 5c ER confirm the well known aggressive behavior of this tumor entity.

Rhinocerebral zygomycosis following bone marrow transplantation in chronic myelogenous leukaemia. Report of a case and review of the literature.

We report on a man suffering from chronic myelogenous leukaemia treated by allogeneic bone marrow transplantation who, in the late post-transplantation phase, developed a hyperacute fatal invasive rhinocerebral zygomycosis. The origin of the ascending infection was the sinus sphenoidalis from which fungal hyphae spread to the central nervous system via the skull and the dura mater. The first symptoms of this severe infection were cerebral convulsions and a bilateral total amaurosis. The isolation of the pathogen from post mortem tissue was not successful. The present case is compared with previous reports of zygomycoses after bone marrow transplantation.