Descriptive epidemiology of vulvar and vaginal cancers in Vaud, Switzerland, 1974-1994

Background: To analyse trends in incidence, survival and risk of second neoplasms following vaginal and vulvar cancers using data collected by the Swiss Cancer Registry of Vaud over the 21-year period 1974-1994. Materials and methods: Subjects were 257 vulvo-vaginal cancers. Of these, 69 were vaginal, 153 vulvar cancers, and 35 non-specified lower genital tract neoplasms; 94 in situ neoplasms were also registered (85 for the vulva). Results: Invasive vaginal cancer incidence decreased from 0.8 in 1974-1984 to 0.4/100,000 women in 1985-1994, while invasive vulvar cancer incidence remained approximately stable around 1.2/100,000 (world standard); incidence of in situ vulvar cancer increased from 0.8 to 1.3/100,000, the rise being larger in younger women. Significant excesses for second primary neoplasms were observed for oro-pharyngeal and lung cancer, and for non-melanomatous skin neoplasms, as well as for invasive vulvar cancers following in situ cancers. Conclusions: This population-based dataset confirms that the incidence of in situ vulvar (but not invasive vulvar or vaginal cancer) has been increasing over the last 20 years. The excess second primary neoplasms supports the hypotheses that human papillomavirus and cigarette smoking are related to vulvo-vaginal neoplasm

Progress against non-Hodgkin lymphoma in the Netherlands: Incidence, patterns of care and prognosis since 1989 (Studies with cancer registry data)

Cancers arising from the haematopoietic and lymphoid tissue comprise a heterogeneous group of malignancies with diverse clinical and biological features. The World Health Organization (WHO) classification of Haematopoietic and Lymphoid tissue, classified these cancers based on histologic characteristics. Lymphoid neoplasms are divided into precursor, mature indolent B-cell, mature aggressive B-cell, mature T- and NK-cell, plasma cell, and Hodgkin lymphoma. Myeloid neoplasms are divided into myeloproliferative, myelodysplastic, myeloproliferative/myelodysplastic neoplasms, acute myeloid leukaemia, and other acute leukaemias. Furthermore, a group of histiocytic and dendritic cell neoplasms is specified. All mature B-cell neoplasms (minus plasma cell neoplasm) and all Tand NK-cell neoplasms together are called non-Hodgkin lymphomas (NHL)

Systematic assessment of HER2/neu in gynecologic neoplasms, an institutional experience.

BackgroundHER2/neu overexpression and/or amplification has been widely studied in a number of solid tumors, primarily in the breast. In gynecologic neoplasms, determination of HER2/neu status has not been well studied as a predictive biomarker in anti-HER2/neu treatment.MethodsWe systematically evaluated the HER2/neu reactions by immunohistochemistry and fluorescent in situ hybridization in malignant gynecologic neoplasms as experienced in our institution.ResultsThe HER2/neu overexpression or amplification occurred in 8 % of the cancers of the gynecological organs in our series. Majority of the HER2/neu overexpression and/or amplification occurred in clear cell (27 %) and serous (11 %) carcinomas. HER2/neu positivity was also seen in undifferentiated as well as in mixed clear cell and serous carcinomas. Discordant IHC and FISH results (positive by FISH but not IHC) was seen in 2 cases. Majority of the HER2/neu overexpression and/or amplification occurs in the endometrium rather than the ovary. Heterogeneity of the HER2/neu by IHC staining was in < 2 % of the tumors in our series.ConclusionsWe recommend the HER2/neu studies on Müllerian carcinomas of clear cell, serous, and undifferentiated types, particularly when they arise in the endometrium. Since there are some discordant IHC/FISH results, we also propose performing the HER2/neu testing by FISH when the IHC score is less than 3 + 

NF2/merlin in hereditary neurofibromatosis 2 versus cancer: biologic mechanisms and clinical associations.

Inactivating germline mutations in the tumor suppressor gene NF2 cause the hereditary syndrome neurofibromatosis 2, which is characterized by the development of neoplasms of the nervous system, most notably bilateral vestibular schwannoma. Somatic NF2 mutations have also been reported in a variety of cancers, but interestingly these mutations do not cause the same tumors that are common in hereditary neurofibromatosis 2, even though the same gene is involved and there is overlap in the site of mutations. This review highlights cancers in which somatic NF2 mutations have been found, the cell signaling pathways involving NF2/merlin, current clinical trials treating neurofibromatosis 2 patients, and preclinical findings that promise to lead to new targeted therapies for both cancers harboring NF2 mutations and neurofibromatosis 2 patients

A novel combination of triple metachronous malignancies of the kidney, oropharynx and prostate. A case report

Synchronous or metachronous malignancies are a rare event, with an incidence rate that increases with age. The present study reports the case of a 70-year-old Caucasian male who was referred to the outpatient office of the Urology Unit, Sapienza University of Rome (Latina, Italy) due to lower urinary tract symptoms. An abdominal ultrasound investigation was performed that demonstrated the presence of a right renal mass. The patient underwent right radical nephrectomy, which resulted in the definitive diagnosis of clear cell type renal cell carcinoma. The patient was eventually diagnosed with triple primary metachronous cancer consisting of renal clear cell carcinoma, prostate adenocarcinoma and squamous cell carcinoma of the oropharynx (palatine tonsil). To the best of our knowledge, this combination of primary neoplasms has not previously been documented

A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors.

PurposeImmune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (nonpancreatic) neuroendocrine neoplasm cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).Patients and methodsWe performed a prospective, open-label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (nonpancreatic) neuroendocrine cohort reported here. Response assessment by grade was not prespecified. The primary endpoint was overall response rate [ORR; RECIST v1.1; complete response (CR) and partial response (PR)]; secondary endpoints included progression-free survival (PFS), overall survival (OS), stable disease >6 months, and toxicity.ResultsThirty-two eligible patients received therapy; 18 (56%) had high-grade disease. Most common primary sites were gastrointestinal (47%; N = 15) and lung (19%; N = 6). The overall ORR was 25% [95% confidence interval (CI) 13-64%; CR, 3%, N = 1; PR, 22%, N = 7]. Patients with high-grade neuroendocrine carcinoma had an ORR of 44% (8/18 patients) versus 0% in low/intermediate grade tumors (0/14 patients; P = 0.004). The 6-month PFS was 31% (95% CI, 19%-52%); median OS was 11 months (95% CI, 6-∞). The most common toxicities were hypothyroidism (31%), fatigue (28%), and nausea (28%), with alanine aminotransferase elevation (9%) as the most common grade 3/4 immune-related adverse event, and no grade 5 events.ConclusionsIpilimumab plus nivolumab demonstrated a 44% ORR in patients with nonpancreatic high-grade neuroendocrine carcinoma, with 0% ORR in low/intermediate grade disease

P53 mutations in human adrenocortical neoplasms

The mechanisms of tumorigenesis of adrenocortical neoplasms have not been elucidated as yet. However, loss of heterozygosity at chromosomal locus 17p has been consistently observed in adrenocortical cancer. p53 is a recessive tumor suppressor gene located on chromosome 17p. Mutations in the p53 gene play an important role in the tumorigenesis of diverse types of human neoplasms including breast and colon cancers. More than 90% of all mutations discovered in such tumors have been detected in 4 hot spot areas that lie between exons 5 and 8. In contrast to wild-type p53, mutant p53 accumulates intracellularly and can be easily detected by immunohistochemistry. We therefore investigated the frequency of p53 mutations in human adrenocortical neoplasms using molecular biology and immunohistochemistry techniques. Five patients with adrenocortical adenomas (5 female; ages 39-72 yr), 11 patients with adrenocortical carcinomas (8 female, 3 male; ages 15- 50 yr), and two adrenocortical tumor cell lines were studied. After DNA extraction from frozen tumor tissue or paraffin-embedded material, exons 5 through 8 were amplified using the polymerase chain reaction and directly sequenced by the dideoxy termination method. Immunohistochemistry was performed on paraffin-embedded tumor specimens obtained during adrenalectomy using a monoclonal antibody reacting with both wild-type and mutant p53. Prevalence of mutations was adenomas, 0/5, carcinomas, 3/11, and adrenocortical cell lines, 2/2. Single point mutations were detected in 3 cases (exons 5, 6, and 7, respectively), and rearrangements of exon 7/8 and 8 were found in 2 cases. Immunohistochemistry detected strong nuclear and/or cytoplasmic p53 immunoreactivity in all adrenocortical carcinomas with point mutations of the p53 gene but not in adenomas and carcinomas with the wild-type sequence or with deletion/rearrangement of the p53 gene. We conclude that p53 plays a role in the tumorigenesis of adrenocortical carcinomas but is of less importance to benign adenomas