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1/50. Exfoliative cytology of a lymphoepithelioma-like carcinoma in a cervical smear. A case report.

    BACKGROUND: Lymphoepithelioma-like carcinoma of the cervix (LELC) is cytologically identical to its counterparts at other sites, such as the nasopharynx. LELC can be suspected on a cervical cytologic smear. The differential diagnosis includes nonkeratinizing squamous cell carcinoma with prominent stromal inflammation, carcinoma with intense stromal eosinophilia, glassy cell carcinoma, malignant lymphoma (especially lymphoepitheloid-Lennerts lymphoma) and metastatic Schmincke-Regaud tumor. CASE: A 55-year-old female presented with an ulcerated endophytic tumor in the cervix. Exfoliative cytology showed uniform, large tumor cells, often associated with inflammatory cells, with round or oval nuclei and one or more prominent nucleoli. The cytoplasm was finely granular to flocculent, and the nuclei were uniformly vesicular. The chromatin was peripherally marginated. The cell borders were indistinct. There was no evidence of dyskeratotic or keratinized cells, koilocytes or glandlike formations. These findings were highly suspicious for LELC and were confirmed by biopsy. flow cytometry showed DNA aneuploidy, with a DNA index of 1.08. in situ hybridization was negative for human papillomavirus 16 and 18. CONCLUSION: LELC of the uterine cervix has cytologic features that are sufficiently characteristic for a specific cytologic diagnosis. The diagnosis, nevertheless, has to be proven by histology.
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keywords = hybridization
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2/50. An unusual cervical carcinoma showing exception to epitheliotropism of human papillomavirus.

    Human papillomaviruses (HPV) infect epithelial tissues but have not been previously detected within mesenchymal cells. During a systematic investigation of FIGO stage Ib cervical cancers with colorimetric in situ hybridization, we detected HPV 16 DNA within the stromal compartment of an unusual undifferentiated carcinoma. The mesenchymal nature of the HPV-containing cells was confirmed by immunohistochemistry and electron microscopy. No viral particles were identified. Sequencing the majority of the HPV 16 genome identified few changes from the revised reference clone; all previously reported in other HPV 16 variants. These viral changes are unlikely to explain the exceptional mesenchymal localization of the HPV 16 DNA in this case.
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ranking = 1
keywords = hybridization
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3/50. HPV in situ hybridization with catalyzed signal amplification and polymerase chain reaction in establishing cerebellar metastasis of a cervical carcinoma.

    We report an unusual case of cerebellar metastasis from a cervical adenosquamous carcinoma in which molecular techniques assisted in establishing the correct diagnosis. The patient was a 43-year-old woman with surgically unresectable cervical carcinoma diagnosed 2 years before presenting with neurological symptoms. A magnetic resonance imaging scan showed a large, enhancing cerebellar lesion with significant brain stem compression. The excised cerebellar tumor resembled a small cell carcinoma and was initially not thought to be a metastasis from the cervical adenosquamous carcinoma. in situ hybridization with catalyzed signal amplification and polymerase chain reactions with primers specific for human papilloma virus (HPV) types 16 and 18 were used to determine the relationship between the cervical and the cerebellar neoplasms. A positive signal was present in the nuclei of both neoplasms by in situ hybridization using HPV16/18 dna probes. Polymerase chain reaction revealed the presence of HPV-18 DNA sequences in the cervical and cerebellar neoplasms confirming that the cerebellar neoplasm was a metastasis from the cervical primary.
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ranking = 6
keywords = hybridization
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4/50. Cervical adenoid cystic carcinoma coexisting with multiple human papillomavirus-associated genital lesions. A common etiology?

    Adenoid cystic carcinoma of the uterine cervix is a rare tumor with unknown etiology. We report a case of adenoid cystic carcinoma occurring in a young woman, associated with multiple human papillomavirus (HPV)-related lesions including condyloma acuminata, vulvar intraepithelial neoplasm, cervical intraepithelial neoplasm and invasive basaloid squamous cell carcinoma. While adenoid cystic carcinoma has previously been found to coexist with squamous cell carcinoma or cervical intraepithelial neoplasia, its association with such a variety of HPV-related lesions in our case has not been previously reported, and raises the speculation that HPV may also be the causative factor for adenoid cystic carcinoma. However, in situ DNA hybridization and polymerase chain reaction in our current study failed to demonstrate the existence of HPV DNA in adenoid cystic carcinoma.
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keywords = hybridization
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5/50. Related case report: in vivo suppression of thyrotropin by 9-cis retinoic acid.

    Treatment of a 48-year-old woman with advanced cervical cancer with the synthetic vitamin a derivative, 9-cis retinoic acid (9cRA), resulted in thyroid-stimulating hormone suppression without clinical evidence of thyrotoxicosis, which resolved spontaneously when the drug was withdrawn. 9cRA, which is a pan-retinoid (RAR and RXR) agonist, has previously been implicated in induction of interactions between the thyroid receptor and the retinoid receptor, RXR, with endocrine target organ specificity. Furthermore, 9cRA has been shown to down-regulate thyroid-stimulating hormone messenger rna in a pituitary-specific fashion in a murine model, a finding consistent with the pituitary-restricted thyrotoxicosis observed in our patient. This is the first reported case of thyroid-stimulating hormone suppression by 9cRA and suggests that patients receiving this agent should be monitored for pituitary and thyroid function abnormalities.
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ranking = 0.0017452295367697
keywords = acid
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6/50. Carcinoid syndrome caused by an atypical carcinoid of the uterine cervix.

    neuroendocrine tumors of the cervix are rare and are often under- or misdiagnosed. Because these tumors are very aggressive, early diagnosis and subsequent treatment are warranted. We describe a 46-yr-old woman with carcinoid syndrome caused by an atypical carcinoid of the uterine cervix. At age 44, she had dysplasia on Pap smear and underwent total abdominal hysterectomy with the diagnosis of adenocarcinoma. Fourteen months postoperatively, she developed the carcinoid syndrome and was found to have numerous liver metastases. Histological and immunohistochemical investigations of biopsy specimens from the patient's liver lesions and original cervical lesion ("adenocarcinoma") suggested that this woman had a primary atypical carcinoid of the uterine cervix with metastases to the liver. Treatment with octreotide and alkylating agents decreased the episodes of flushing and diarrhea within 8 weeks. If an adenocarcinoma of the uterine cervix is diagnosed, atypical carcinoid should be in the differential diagnosis. Symptoms of the carcinoid syndrome should be pursued and, if present, a urinary 5-hydroxyindolacetic acid level should be obtained. Timely diagnosis of a neuroendocrine tumor of the cervix may improve survival.
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ranking = 0.00034904590735394
keywords = acid
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7/50. Lymphoepithelioma-like carcinoma of the uterine cervix: a case report studied by in situ hybridization and polymerase chain reaction for Epstein-Barr virus.

    Lymphoepithelioma-like carcinomas have been reported outside the nasopharynx in many sites, including the uterine cervix. The association with the Epstein-Barr virus in the latter site is still controversial. To date, Epstein-Barr virus genome has only been demonstrated in Asian patients. We report a case of lymphoepithelioma-like carcinoma of the uterine cervix in a white woman in whom the Epstein-Barr virus infection was tested for by in situ hybridization and polymerase chain reaction. The results of both techniques were negative. Our case and a review of the literature support the contention that cervical lymphoepithelioma-like carcinoma is not associated with Epstein-Barr virus infection in non-Asian patients.
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ranking = 5
keywords = hybridization
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8/50. p53 intronic point mutation, aberrant splicing and telomeric associations in a case of B-chronic lymphocytic leukaemia.

    We report a case of chronic lymphocytic leukaemia (CLL) with telomeric associations and a p53 intronic point mutation. Karyotypic analysis revealed clonal and non-clonal telomeric associations, accompanied by clonal cytogenetic abnormalities and also in isolation. The p53 mutation, which occurred at the invariant base pair -2 of the splice acceptor site in intron 7 resulted in the abolition of correct splicing of exon 7 to exon 8. Multiple aberrant splice products were characterized, all of which differed from wildtype in the DNA binding domain. fluorescence in situ hybridization demonstrated that the clone retained two copies of the p53 gene and wild-type p53 transcript was detected on cloning of reverse transcriptase polymerase chain reaction (RT-PCR) product, indicating that one wild-type allele remained. However, a plasmid clone with correct splicing at the exon 7/8 boundary, but with a 21 bp deletion in exon 8, was also found at low frequency. This finding indicates clonal evolution, resulting in complete loss of wild-type p53. The intronic point mutation was not present in DNA extracted from cervical tissue indicating that it was a leukaemic phenomenon. This is the first case of an intronic point mutation to be reported in CLL. This mutation led to chaotic p53 expression and, interestingly, occurred in a case showing telomeric associations, a rare phenomenon in B-CLL.
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ranking = 1
keywords = hybridization
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9/50. Utilization of the human genome sequence localizes human papillomavirus type 16 DNA integrated into the TNFAIP2 gene in a fatal cervical cancer from a 39-year-old woman.

    PURPOSE: The purpose of our study was to characterize a human papillomavirus (HPV) 16 DNA integration in the genome of a rapidly progressive, lethal cervical cancer in a 39-year-old woman. EXPERIMENTAL DESIGN: An HPV 16 integration site from cervical cancer tissue was cloned and analyzed using Southern blot hybridization, nucleotide sequencing, fluorescence in situ hybridization analysis for chromosomal localization and comparison with the draft human genome sequence. RESULTS: HPV 16 DNA (3826 bp) was integrated into the genome of the tumor sample and contained an intact upstream regulatory region and E6 and E7 open reading frames. Both 5' and 3' viral-cell junction regions contained direct repeat and palindrome sequences. The chromosomal location of the viral integration and cellular deletion was mapped to chromosome 14q32.3 using both a somatic cell hybrid panel and fluorescence in situ hybridization. Search of the draft human genome sequence confirmed the chromosomal location and revealed a disruption of the TNFAIP2 cytokine/retinoic acid-inducible gene. CONCLUSIONS: On the basis of the lack of sequence homology between the viral and cellular site of integration and the structure of the viral-cell junctions, it seems that HPV 16 DNA integrates into the host genome by a mechanism of nonhomologous recombination. We suggest that, taken together, maintenance of E6 and E7 expression, loss of the E2 gene and disruption of the TNFAIP2 gene through viral integration contributed to the rapid progression of cervical cancer in this patient. Availability of the human genome sequence will facilitate identification of cellular genes involved in cervical cancer by high-throughput analysis of viral integration sites.
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ranking = 3.0003490459074
keywords = hybridization, acid
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10/50. Metastatic endocervical adenocarcinoma presenting as a virilizing ovarian mass during pregnancy.

    BACKGROUND: We report a case of metastatic endocervical adenocarcinoma that presented as a virilizing ovarian mass in a young pregnant woman and simulated a primary ovarian endometrioid tumor. CASE: A 34-year-old woman underwent cesarean delivery and right salpingo-oophorectomy at 34 weeks' gestation for a 32-cm androgen-producing ovarian mass. The ovarian tumor, initially interpreted as a primary ovarian endometrioid carcinoma, was demonstrated to represent metastatic endocervical endometrioid adenocarcinoma based on detection of human papillomavirus 16 (HPV-16) deoxyribonucleic acid in the tumor by in situ hybridization. The hysterectomy specimen demonstrated an endocervical adenocarcinoma associated with adenocarcinoma in situ that also contained HPV-16. CONCLUSION: Human papillomavirus is considered an etiological agent in the development of endocervical adenocarcinomas, having been demonstrated in greater than 90% of tumors. In contrast, recent studies have concluded that HPV is unlikely to play an etiological role in ovarian neoplasia. The demonstration of HPV-16 in both the endocervical and ovarian carcinomas in this patient supports the interpretation that the ovarian tumor is a metastasis.
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ranking = 1.0003490459074
keywords = hybridization, acid
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