Cases reported "Carcinoma in Situ"

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1/12. Human papillomavirus types 16 and 39 in a vulval carcinoma occurring in a woman with Hailey-Hailey disease.

    A woman with Hailey-Hailey disease, suffering from carcinoma of the vulva, was examined by histology and for the presence of human papillomavirus (HPV) DNA by polymerase chain reaction (PCR) and in situ hybridization. Our diagnosis by histological examination revealed the vulval carcinoma to be a squamous cell carcinoma (SCC), adjacent to lesions of Hailey-Hailey disease and severe dysplasia/carcinoma in situ [vulval intraepithelial neoplasia (VIN) III]. The PCR with consensus primers for the L1 region (L1-PCR) successfully amplified HPV DNA using total DNA extracted from formalin-fixed and paraffin-embedded tissue specimens. Restriction fragment length polymorphism analysis and sequencing of L1-PCR products revealed HPV types 16 and 39. HPV 16-specific primers for the E6 region identified HPV 16 DNA. in situ hybridization analysis with biotinylated HPV 16 and 39 dna probes revealed the presence of the HPV 39 genome in the nuclei of the tumour cells in the SCC. These results indicate that HPV 16 and 39 are associated with lesions in vulval carcinoma. Regarding the patient's susceptibility to infection in the case of Hailey-Hailey disease, there is a possibility that HPV was inoculated into the lesions of Hailey-Hailey disease and induced those of VIN III and SCC.
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2/12. Diagnostic value of anti-alpha FP antibody levels in a metastatic germ cell tumor of unknown primary site.

    BACKGROUND: A 21 year old man with a metastatic germ cell tumor of unknown primary not responding to chemotherapy was scheduled to have a blind bilateral orchiectomy to eradicate the possible primary site although palpation and ultrasonography of the testicles had always been normal. METHOD: The patient underwent a radioimmunoscintigraphy with Anti-alpha FP antibody scan (AFP-Scan). RESULTS: On the basis of the scintigraphic results the patient underwent a left orchiectomy and additionally removal of the lymph node metastases. histology revealed the presence of an in situ carcinoma in the left testis and a mixed tumor present in the abdominal lymph node metastases. Fluorescent in situ hybridization on tumor cells did not show any abnormalities related to chromosome 12, a finding connected with the somatic type of germ cell tumors. CONCLUSION: Anti-alpha FP antibody scan was helpful in detecting the primary site and saving the life of the patient without resulting in hypogonadism.
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3/12. Human papillomavirus type 16 in a homosexual man. association with perianal carcinoma in situ and condyloma acuminatum.

    BACKGROUND--The association of anal carcinoma with human papillomavirus (HPV) type 16 infection is well documented. Anal carcinoma is also frequently associated with a history of anogenital condylomata. More than 90% of anogenital condylomata contain HPV type 6 or 11. It is rare for a condylomatous lesion to contain HPV 16. We report the unusual case of a homosexual man, testing positively for human immunodeficiency virus, with carcinoma in situ evolving within perianal condylomata infected with HPV 16. OBSERVATIONS--Microscopic examination of tissue specimens from ulcerated verrucous lesions on the perianal mucosa revealed changes of classic condylomata acuminata with contiguous focal squamous cell carcinoma in situ. Testing for HPV DNA by in situ hybridization identified HPV 16 in both the condylomatous and carcinoma in situ areas. CONCLUSIONS--The association of HPV 16-infected condylomata and adjacent carcinoma in situ implies that cutaneous genital condylomata may progress to high-grade lesions. Given that homosexual men are at high risk for perianal carcinomas, HPV typing of perianal condylomata specimens may help identify immunocompromised patients who are at risk for the development of carcinomas.
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4/12. Clinical application of array-based comparative genomic hybridization to define the relationship between multiple synchronous tumors.

    Array-based comparative genomic hybridization (CGH) is a technique that allows genome wide screening of gains and losses in DNA copy number. In cases where multiple tumors are encountered, this genetic technique may prove useful in differentiating new primary tumors from recurrences. In this case report, we used array-based CGH to examine the genomic relationships among two leiomyosarcomas and two breast cancers in the same patient, three of which were diagnosed synchronously. Array-based CGH was performed on the four tumor samples using random prime amplified microdissected DNA. Samples were hybridized onto bacterial artificial chromosome arrays composed of approximately 2400 clones. Patterns of alterations within the tumors were compared and genetic alterations among the leiomyosarcomas and breast lesions were found. overall, three distinct genetic profiles were observed. While the two leiomyosarcomas shared a similar pattern of genetic alterations, the two invasive breast lesions did not. The nearly identical pattern of genetic alterations belonging to the two metachronous leiomyosarcomas confirmed metastatic recurrence while the two different genetic profiles of the invasive ductal carcinomas suggest that the two lesions represented two distinct foci of multifocal disease rather than clonal extension of the primary tumor. We conclude that genetic analysis by array-based CGH can clearly elucidate the relationships between multiple tumors and may potentially serve as an important clinical tool.
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5/12. Superficial (early) endocervical adenocarcinoma in situ: a study of 12 cases and comparison to conventional AIS.

    Although established histologic criteria for the diagnosis of endocervical adenocarcinoma in situ (AIS) have been published, some lesions are not readily classified or present with more subtle degrees of epithelial atypia. Lesions confined to the surface mucosa may be particularly challenging, possibly because they represent early disease. Twelve cases of superficial AIS (SAIS) confined to the surface mucosa or crypt openings culled from the in-house and consultation practices were examined histologically, immunostained for MIB-1 and p16, and analyzed (when possible) for HPV nucleic acids by DNA-DNA in situ hybridization (INFORM). The mean age was 26.7 years for SAIS versus 37.0 years for 42 consecutive cases of conventional AIS from the same practice (P < 0.001). Seven and five were biopsies and conization specimens, respectively. Five coexisted with CIN, four arose in endocervical papillae, and two arose in endocervical polyps. Nuclear hyperchromasia was conspicuous in 10 and mitoses were present in all; however, apoptosis was rare or absent in four, and six exhibited only mild nuclear atypia. Mib-1 staining exceeded 40% in 5 of 7 cases tested, and all (8 of 8) were strongly positive for p16(ink4). Five of five were positive for HPV by ISH with an "integrated" dot-like pattern. SAIS is an early variant of AIS that 1) occurs at a younger mean age, 2) exhibits variable atypia, and 3) arises adjacent to morphologically normal columnar epithelium. Diffuse p16 expression and integrated HPV pattern are identical to that seen in more extensive forms of the disease. Superficial AIS should be suspected in endocervical columnar epithelium with segmental nuclear hyperchromasia with mitotic activity, and confirmed by biomarker staining (p16 and Mib-1) if the pathologist is uncertain of the diagnosis.
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6/12. Laryngeal carcinoma associated with human papillomavirus type 16.

    The advent of molecular hybridization technology has provided evidence supporting human papillomavirus as an etiologic agent of laryngeal carcinoma. Using Southern blot analysis, we identified human papillomavirus type 16 DNA associated with an invasive laryngeal carcinoma. The virus genome did not appear to be integrated into the host genome, as is often the case with anogenital tumors. Laryngeal carcinoma usually arises on the true vocal cords of individuals who demonstrate demographic and lifestyle risk factors for this cancer. The patient, an adult male, has no identifiable risk factors for laryngeal carcinoma other than papillomavirus infection. Our finding suggests that the application of hybridization analysis to all cases of laryngeal cancer would promote understanding of the association between human papillomavirus and laryngeal carcinoma.
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7/12. Multifocal invasive carcinoma of the vulva in a 25-year-old woman with Bowenoid papulosis.

    This case report documents malignant progression associated with wart virus infection of the vulva in a 25-year-old female. The initial condition of Bowenoid papulosis and carcinoma in situ of the vulva was diagnosed on colposcopic biopsies performed to investigate chronic pruritus and superficial dyspareunia. This condition failed to resolve with local ablative therapy and progressed over a period of 8 months to multifocal invasive carcinoma of the vulva requiring radical surgery. Deoxyribonucleic acid hybridization studies on the operative specimen revealed the presence of human papilloma virus type 16. The role of human papilloma virus in the aetiology of Bowenoid papulosis and neoplasia of the vulva is discussed.
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8/12. Simultaneously occurring condylomata acuminata, carcinoma in situ and verrucous carcinoma of the vulva and carcinoma in situ of the cervix in a young woman. A case report.

    A case of simultaneously occurring condylomata acuminata, carcinoma in situ and verrucous carcinoma of the vulva and carcinoma in situ of the cervix was seen in a 26-year-old woman. In situ DNA hybridization on sections of the condyloma acuminata and verrucous carcinoma yielded DNA sequences for human papillomavirus 6.
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9/12. Isolation of a human papillomavirus from a patient with epidermodysplasia verruciformis: presence of related viral DNA genomes in human urogenital tumors.

    The DNA genome of a human papillomavirus (HPV), tentatively designated HPV-EV, was molecularly cloned from hand to leg lesions of a patient with epidermodysplasia verruciformis, a chronic skin disease associated with a 30% risk of developing cancer. Using stringent hybridization conditions, we observed less than 5% homology between HPV-EV and the cloned genomes of HPV-1, HPV-4, HPV-5, and HPV-5a. HPV-EV DNA showed approximately 6% homology with HPV-2 and 36% homology with HPV-3. These data suggest that HPV-EV is partially related to HPV-3. Using 32P-labeled cloned HPV-EV as probe in Southern blot hybridization experiments, we detected HPV-EV-related DNA in the carcinoma in situ (Bowenoid lesion) of the vulva of the patient from which HPV-EV was isolated. HPV-EV-related DNA was detected in 2 of 10 vulva carcinomas and in 2 of 31 cervical carcinomas. Related DNA sequences were found in papillomas from each of two patients with condyloma acuminata (anogenital warts), which is of interest considering that condylomas have been reported to convert occasionally to carcinomas. The positive vulva DNAs were also probed with other cloned HPV DNAs: HPV-1, HPV-4, and HPV-5a-related sequences were not detected; HPV-3 and HPV-2 dna probes detected strong and weak DNA bands, respectively, of the same size as found with HPV-EV. The HPV DNA sequences were present in the positive tumors mainly as free viral DNA molecules; no evidence for integration into cellular DNA was found. The emerging biological picture with papillomaviruses is that cells transformed by these viruses are maintained in a transformed state by free episomal genomes. Thus, our findings are consistent with the idea, but by no means establish, that HPVs play a role in human cancer by a similar mechanism.
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10/12. Squamous cell carcinoma of the oral cavity derived from a skin graft: a case report.

    A case of oral cancer that had derived from a 19-year skin graft on the left buccal mucosa is reported. The patient had had three previous operations due to squamous cell carcinoma, erosion, and squamous cell carcinoma of the left buccal mucosa, respectively. In the last two operations, skin was transplanted, and the present cancer is believed to have derived from the latter one. The tumor was resected, and a new skin was grafted. in situ hybridization of human papilloma virus (HPV) was carried out; the HPV 16 DNA could not be detected in the specimen. Eight months later, a cervical lymph node metastasis was detected; thus, a radical neck dissection was performed.
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