Carcinomas and sarcomas of Bartholin gland. A report of nine cases and review of the literature.

UNLABELLED: The greater vestibular gland, also called Bartholin's gland after the Danish anatomist Caspar Bartholin the Younger who first described it in the 17th century, is the site of tumours arising from different types of epithelium and characterized by a different clinical course. In the years 1980-2009, 1,296 patients with vulvar carcinoma were treated at the Oncology Centre in Warsaw, Poland and nine of them had carcinoma of Bartholin's gland, including three patients with squamous cell carcinoma (SCC), three patients with adenoid cystic carcinoma (ACC) and three patients with sarcoma. In this paper the authors present the signs and symptoms, clinical course, treatment outcomes, and recurrence of these three malignant tumours of different histopathology. Own observations and evaluation of treatment results are compared with published reports from other centres. Interestingly, there is no consensus regarding diagnostic criteria or a uniform approach to management. Relatively poor knowledge of malignant tumours of Bartholin's gland seems to be responsible for delays in proper diagnosis and hence optimal management. When instituted, the treatment is usually aggressive and involves adjuvant radio- and chemotherapy, while the chances of longer disease-free survival after treatment may be compromised. CONCLUSION: Bartholin sarcomas grow fast and invasive, SCC, and ACC infiltrate slowly and systematic. All types are curable at high interest rates if they are originally from the surgically removed lymph nodes on both sides and irradiated.

Assessment of the tumor-associated trypsin inhibitor (TATI) marker in patients with carcinoma of the uterine body 17 years after treatment.

On the basis of literature review, the structure of the tumor-associated trypsin inhibitor (TATI) marker and its usefulness in diagnosing and monitoring of various malignant neoplasms has been described. The authors' own experiences are presented stemming from evaluation of TATI levels in a group of 305 patients suffering from carcinoma of the uterine body, who were primarily operated and then subjected to supplementary therapy in the Center of Oncology in Warsaw, classified in accordance with the FIGO 1988 protocol in the years 1994-1995, and who were observed for 17 years after discontinuation of treatment. A statistical analysis of the level of the TATI marker was carried out in the group of patients with unfavorable prognostic factors, that is the presence of cancerous infiltration in the uterine body, also found in the parametrium, ovaries, as well as diagnosed metastases to the lymphatic nodes found on the basis of postoperative histopathological protocol. The marker was determined three to seven times in serum after each stage of supplementary treatment, and at the beginning of the follow-up. Strong significance and elevation of the TATI marker were affirmed for the mean of four initial collections in patients, who had a relapse or metastases within one month to 11 years after termination of therapy.

Maternal urinary steroid profiles in prenatal diagnosis of Smith-Lemli-Opitz syndrome: first patient series comparing biochemical and molecular studies.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder caused by reduced activity of 7-dehydrocholesterol (7DHC) reductase, resulting in a decreased level of cholesterol and increased concentrations of 7DHC and 8DHC in body fluids and tissues. Ten pregnancies at 25% risk of SLOS underwent prenatal testing. Diagnostic studies included DHCR7 mutation analysis in chorionic villus samples, amniotic fluid sterol analysis and serial measurements of oestriol (E3), pregnanetriol (PT), 7-dehydropregnanetriol (7DHPT) and 8-dehydroesteriol (8DHE3) concentrations in maternal urine samples obtained between 9 and 20 weeks of gestation. All tests were diagnostic and revealed nine unaffected foetuses (two normal homozygotes and seven DHCR7 heterozygotes) and one affected foetus. In the affected pregnancy, 7DHC and 8DHC in amniotic fluid were 9.87 and 3.7 microg/ml, respectively [reference range (RR) 0.0026 +/- 0.0015 microg/ml and not detectable, respectively] and maternal urinary steroid analyses showed increased ratios of 7DHPT/PT and 8DHE3/E3 of 0.74 and 1.7, respectively (RR 0-0.0147 and 0-0.019). In the heterozygous foetuses, 7DHPT/PT and 8DHE3/E3 ratios did not exceed those found in 48 normal controls. This is the first series of prenatal diagnostic testing for SLOS where non-invasive biochemical testing was performed in tandem with invasive diagnostic testing. We conclude that steroid measurements in maternal urine are a reliable means of prenatal diagnosis for SLOS.

SLOS carrier frequency in Poland as determined by screening for Trp151X and Val326Leu DHCR7 mutations.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis caused by mutations in the DHCR7 gene. Previous studies estimated the prevalence of SLOS between 1 in 10,000 to 1 in 70,358 based on case frequency surveys. Although panethnic, SLOS appears to be most frequent in Central European populations (Czech Republic 1 in 10,000, Slovakia 1 in 15,000 - 1 in 20,000). In Polish individuals with SLOS two DHCR7 mutations, c.452G>A (p.Trp151X) and c.976G>T (p.Val326Leu), account for 65.2% of all observed DHCR7 mutations. We analyzed 2169 samples for the p.Trp151X mutation and 2087 for the p.Val326Leu mutation. The combined carrier frequency of these two mutations of was 2.40+/-0.32%, yielding a calculated incidence of SLOS in Poland of 2.5 4x10(-4)-4.3 5x10(-4) (1 in 2,300 to 1 in 3,937) placing SLOS among the most common recessive genetic disorders in Poland.

p16(INK4a) prevents centrosome dysfunction and genomic instability in primary cells.

Aneuploidy, frequently observed in premalignant lesions, disrupts gene dosage and contributes to neoplastic progression. Theodor Boveri hypothesized nearly 100 years ago that aneuploidy was due to an increase in centrosome number (multipolar mitoses) and the resultant abnormal segregation of chromosomes. We performed immunocytochemistry, quantitative immunofluorescence, karyotypic analysis, and time-lapse microscopy on primary human diploid epithelial cells and fibroblasts to better understand the mechanism involved in the production of supernumerary centrosomes (more than two microtubule nucleating bodies) to directly demonstrate that the presence of supernumerary centrosomes in genomically intact cells generates aneuploid daughter cells. We show that loss of p16(INK4a) generates supernumerary centrosomes through centriole pair splitting. Generation of supernumerary centrosomes in human diploid epithelial cells was shown to nucleate multipolar spindles and directly drive production of aneuploid daughter cells as a result of unequal segregation of the genomic material during mitosis. Finally, we demonstrate that p16(INK4a) cooperates with p21 through regulation of cyclin-dependent kinase activity to prevent centriole pair splitting. Cells with loss of p16(INK4a) activity have been found in vivo in histologically normal mammary tissue from a substantial fraction of healthy, disease-free women. Demonstration of centrosome dysfunction in cells due to loss of p16(INK4a) suggests that, under the appropriate conditions, these cells can become aneuploid. Gain or loss of genomic material (aneuploidy) may provide the necessary proproliferation and antiapoptotic mechanisms needed for the earliest stages of tumorigenesis.

Loss of chromosomal integrity in human mammary epithelial cells subsequent to escape from senescence.

The genomic changes that foster cancer can be either genetic or epigenetic in nature. Early studies focused on genetic changes and how mutational events contribute to changes in gene expression. These point mutations, deletions and amplifications are known to activate oncogenes and inactivate tumor suppressor genes. More recently, multiple epigenetic changes that can have a profound effect on carcinogenesis have been identified. These epigenetic events, such as the methylation of promoter sequences in genes, are under active investigation. In this review we will describe a methylation event that occurs during the propagation of human mammary epithelial cells (HMEC) in culture and detail the accompanying genetic alterations that have been observed.

Normal human mammary epithelial cells spontaneously escape senescence and acquire genomic changes.

Senescence and genomic integrity are thought to be important barriers in the development of malignant lesions. Human fibroblasts undergo a limited number of cell divisions before entering an irreversible arrest, called senescence. Here we show that human mammary epithelial cells (HMECs) do not conform to this paradigm of senescence. In contrast to fibroblasts, HMECs exhibit an initial growth phase that is followed by a transient growth plateau (termed selection or M0; refs 3-5), from which proliferative cells emerge to undergo further population doublings (approximately 20-70), before entering a second growth plateau (previously termed senescence or M1; refs 4-6). We find that the first growth plateau exhibits characteristics of senescence but is not an insurmountable barrier to further growth. HMECs emerge from senescence, exhibit eroding telomeric sequences and ultimately enter telomere-based crisis to generate the types of chromosomal abnormalities seen in the earliest lesions of breast cancer. Growth past senescent barriers may be a pivotal event in the earliest steps of carcinogenesis, providing many genetic changes that predicate oncogenic evolution. The differences between epithelial cells and fibroblasts provide new insights into the mechanistic basis of neoplastic transformation.

A case of Prader-Willi syndrome arising as a result of familial unbalanced translocation t(11;15)(q25;q13).

We report on a case of Prader-Willi syndrome (PWS) with a true reciprocal unbalanced translocation, 45,XX,-15,der(11)t(11;15)pat. The proposita was diagnosed clinically as having severe PWS. Molecular studies revealed loss of the paternal methylation pattern at locus D15S63 and a deletion encompassing the loci from at least D15S10 to D15S97 of paternal chromosome 15. FISH studies confirmed the deletion of 15q11q13 region and the presence of two telomeres on all chromosomes. The proposita's father, the father's sister and their mother are all carriers of the same balanced translocation t(11;15)(q25;q13). By genomic imprinting we would expect that if the father's sister were to give birth to a child with the same unbalanced translocation as the proband, it would be affected by Angelman syndrome. To date, a similar familial unbalanced translocation due to loss of the small chromosome15 derivative has not been described.

Eleven Polish patients with microcephaly, immunodeficiency, and chromosomal instability: the Nijmegen breakage syndrome.

We report on 11 patients from 8 independent families (3 pairs of sibs) with a complex clinical pattern including microcephaly, peculiar "bird-like" face, growth retardation, and, in some cases, mild-to-moderate mental deficiency. Most of the patients have recurring respiratory tract infections. One girl has developed B-cell lymphoma. A detailed anthropometric study of 15 physical parameters, including 3 cephalic traits, was performed. It was possible to study the chromosomes of PHA-stimulated lymphocytes in all of the patients. We found structural aberrations with multiple rearrangements, preferentially involving chromosomes 7 and 14 in a proportion of metaphases in all individuals. Profound humoral and cellular immune defects were observed. Serum AFP levels were within normal range. Radioresistant DNA synthesis was strongly increased in all 8 patients who were hitherto studied in this respect. Our patients fulfill the criteria of the Nijmegen breakage syndrome, which belongs to the growing category of ataxia telangiectasia-related genetic disorders. In light of the increased predisposition to malignancy in this syndrome, an accurate diagnosis is important for the patient.

Attempt at classification of hysteroscopic pictures of corpus uteri carcinoma.

When comparing types of hysteroscopic pictures--"cauliflower" fatty and multifocal--with prognostic features whose importance is already known (clinical advance, histological maturity, size of uterus, number of cses cured, and number of distant metastases). I have found that "cauliflower" and fatty types are diagnosed in patients with good prognostic features because they appear more often at I degree of advance and at highly matured carcinoma (G1). The survival rates are the highest--93% and 87%. The changes I have described as multifocal appeared in patients with high degree of advance of disease (III--78% I--21%) and with low matured carcinoma. The survival rate was much lower--74% and distant metastasis more frequent (15%) than in other groups of patients. So the pictures of the multifocal infiltrates have the most negative prognostic factors. Such diagnosis obliges to choose particularly precise, conscientious method of therapy and hysterography can be very useful to it. The problem which requires further investigations is the relatively high frequency of detectability of the multifocal changes on hysteroscopic pictures. It may be assumed that some additional, still unexplained features must exist in this form which, might possibly limit the frequency of diagnosis of hysteroscopic pictures with negative prognostic factors.

[Effect of low temperatures on the viability of Cysticercus bovis]. / Badania wplywu niskich temperatur na zywotnosc Cysticercus bovis.

For investigations under laboratory conditions freezers specially prepared for this aim were used. The material for these investigations were alive Cysticercus bovis recovered from skeletal muscles of a bull infected with 500,000 eggs of Taenia saginata. The viability of C. bovis was determined on the basis of routine laboratory investigations. For investigations under conditions of an industrial cold storage plant 6 cattle carcasses intensively invaded by C. bovis were used, i.e. 5 animals infected under natural conditions and one bull specially infected with 500,000 eggs of T. saginata. The temperatures of cattle carcasses were measured with a thermograph. Every 24 hours sections of muscles were collected, from which C. bovis were recovered and examined on the viability by the above-mentioned method. It was found that at low temperatures the necrobiosis time of C. bovis isolated from skeletal muscles was 15 min. at -35 degrees C and as long as 10 hours at -5 degrees C. However, C. bovis died within 72-96 hours in muscles of cattle carcasses subjected to the activity of the temperatures minus 18-19 degrees C at a relative humidity of 86-90% under conditions of an industrial cold storage plant. From the obtained results the author concluded that the regulations hitherto obligatory in Poland, concerning the treatment of cattle carcasses with C. bovis by means of cooling or freezing, should be amended.