Endometrial mullerian adenosarcoma after toremifene treatment in breast cancer patients: a case report

Toremifene is an anti-estrogen which has been shown to be effective in the treatment of breast cancer, and is thought to be a less uterotrophic agent than tamoxifen. The risk assessment concerning endometrial cancer has been inconclusive because of its rare use up to the mid-1990s. We report a case of an adenosarcoma, which is a very rare type of uterine malignancy, after toremifene treatment for 5 years in a breast cancer patient. After 1 year of toremifene use, the patient had a benign Mullerian adenofibroma. After an additional 4 years of toremifene treatment, the endometrial polypoid lesion was transformed into a Mullerian adenosarcoma. Although toremifene is a promising anti-estrogenic agent in the treatment of breast cancer patients, clinicians should not neglect the possibility of a uterine malignancy.     

Does the revised International Federation of Gynecology and Obstetrics staging system for endometrial cancer lead to increased discrimination in patient outcomes?

BACKGROUND:

Recent changes were made to the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer. The objective of this study was to compare survival outcomes for patients who were staged according to the 1988 FIGO staging system versus the 2009 FIGO staging system.

METHODS:

Data were obtained from the Surveillance, Epidemiology, and End Results Program for the years 1998 to 2006. Patients who had a diagnosis of adenocarcinoma of the uterus with complete staging information were included. Patients were staged according to the 1988 and 2009 FIGO staging systems, and Kaplan‐Meier estimates were derived for cause‐specific survival (CSS). Univariate and multivariate analyses using Cox proportional hazards models were used to identify the factors associated with survival.

RESULTS:

In total, 47,284 patients were included. The median follow‐up was 37 months. The 5‐year CSS rates for patients who had 2009 FIGO stage IA and IB disease were 96.6% and 89.9%, respectively (P < .0001). After accounting for age, grade, and race, this survival difference remained significant (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.74‐2.24; P < .0001). Patients who had 1988 FIGO stage IIA disease had a 5‐year CSS rate similar to that of patients who had 1988 FIGO stage IC disease (88.6% vs 89.9%, respectively; P = .09). Patients who had positive pelvic washings had a 5‐year CSS rate similar to that of patients who had stage IIIA disease according to the 2009 FIGO system (74.2% vs 72.1%, respectively; P = .37). The 5‐year CSS rate for patients who had stage IIIC1 disease was significantly improved compared with that for patients who had stage IIIC2 disease (68.2% vs 57.3%, respectively; P < .0001). In the multivariate model, the survival difference remained (HR, 1.49; 95% CI, 1.26‐1.76; P < .0001).

CONCLUSIONS:

The 2009 staging system for endometrial cancer produced better discrimination in CSS outcomes compared with the 1988 system. Cancer 2011;. © 2011 American Cancer Society.     

p53 mutations as a marker of malignancy in bladder washing samples from patients with bladder cancer

The diagnosis and follow-up of patients with bladder cancer rely on invasive procedures (cystoscopy with biopsy). Polymerase chain reaction (PCR)-based technologies may allow the sensitive detection of cancer-related genetic mutations in exfoliated tumour material, potentially allowing the development of less invasive techniques. This pilot study investigated the feasibility of detecting mutations in exons 5-8 of the p53 gene using single-stranded conformational polymorphism (SSCP) analysis in bladder-washing specimens from patients with bladder cancer. Bladder-washing samples (31) were collected from patients (27) with bladder cancer. An abnormal additional SSCP band was detected in five samples from five different patients suggesting the presence of a p53 mutation. In all five cases the same abnormal SSCP pattern was demonstrated in samples of the corresponding bladder tumour. In one case bladder washings were available from the same patient on two separate occasions with one washing demonstrating a mutation and the other not. In two further cases a mutation was demonstrated in the bladder tumour but not in the corresponding washing. It is concluded that it is possible to detect and characterize p53 mutations in bladder-washing samples from patients with bladder cancer. Improved sensitivity in detecting mutations in a sample containing a mixture of normal and malignant cells may lead to the clinical applicability of molecular methods of disease monitoring.     

21例子宫恶性苗勒氏管混合瘤临床分析

［目的］探讨子宫恶性苗勒氏管混合瘤（ＭＭＴ）的诊断与治疗,寻求改善预后的方法。［方法］回顾性分析１９６３年１０月至１９９７年１０月收治的２１例子宫ＭＭＴ的临床资料。［结果］子宫ＭＭＴ无特异临床表现,术前诊断困难,必须重视术前诊刮、宫颈口结节活检及术中冰冻检查。单纯手术６例,手术加化疗１０例,手术加放疗和化疗３例。总的２年、５年生存率为５７％和 ３０％,Ⅰ和 Ⅱ期 ５年生存率分别为 ４５．４％和 ９％,Ⅲ和 Ⅳ期病人均于 ２年内死亡。子宫小于 ３个月妊娠, ５年生存率为４６％,大于３个月妊娠为２５．５％,绝经前与绝经后的５年生存率分别为３３％和２１．４％。［结论］预后与临床期别、病理类型、子宫大小、绝经情况和治疗方法等相关。治疗以手术为主,术后辅以化疗可减少和延缓肿瘤复发和转移。化疗和放疗对治疗局部复发和远处转移有一定疗效。     

Paclitaxel-ifosfamide-carboplatin combination chemotherapy regimen in advanced uterine and adnexal malignant mixed Mullerian tumours

Background:

Malignant mixed Mullerian tumours (MMMTs) of the uterus and adnexa represent aggressive gynaecologic malignancies with a high rate of loco-regional and distant failure. For that reason, we evaluated the paclitaxel–ifosfamide–carboplatin (TICb) combination in patients with advanced MMMTs.

Methods:

Female patients with advanced MMMTs, WHO-PS 0–2, no prior chemotherapy for systemic disease, unimpaired haemopoietic and organ function were eligible. Chemotherapy was administered at the following doses; paclitaxel: 175 mg m^–2 on day 1, ifosfamide: 2.0g m^–2 day^–1 – days 1 and 2, and carboplatin at a target area under the curve 5 on day 2, with prophylactic G-CSF from day 3.

Results:

Forty patients of a median age 61 (45–72) years, performance status 0–2 with advanced MMMTs of the uterus (n=34), tubes (n=2) or ovary (n=4) have entered and all were evaluable for response and toxicity. Responses were as follows: 27 out of 40 (67.5%) evaluable patients responded, with 11 complete responses and 16 partial responses, while 10 had stable disease, and 3 developed progressive disease. The median response duration was 9 months (range, 4–40 months), median progression-free survival 13 months (range, 3–42 months), while median overall survival 18 months (range, 4–48 months). Grade 3/4 neutropenia was recorded in 22 out of 40 (55%) – with 13 developing grade 4 (⩽7 days) and 7 out of 40 (17.5%) of patients at least one episode of febrile neutropenia.

Conclusion:

In this study, it appears that the TICb combination, yielded important activity with manageable toxicity in females with advanced MMMTs warranting further randomised comparison with current standard regimens.     

Detection of microsatellite alterations in bronchial washings in squamous cell lung cancer: the first study from India

BACKGROUND: In recent times, the possibility of detecting lung cancer using microsatellite alterations (microsatellite instability and loss of heterozygosity) in DNA of bronchial washings has been explored. However, no data regarding the presence of microsatellite alterations in lung cancer are available from India, a country which contributes significantly to the lung cancer burden of the world. METHODS: Bronchial washings as well as tumor specimens obtained on bronchoscopy were analyzed for the presence of loss of heterozygosity (LOH) and microsatellite instability (MSI) using the D3S1300 microsatellite marker on chromosome 3p and the TP53 marker on chromosome 17p. RESULTS: The sensitivities of the TP53 and D3S1300 loci in bronchial washings were 35% and 45% (combined 50%), respectively, which was significantly better than conventional cytology (positive for malignant cells in 15%). The presence of these microsatellite alterations was not related to the age, cumulative smoking exposure or smoking status (current or former) of patients. CONCLUSION: Microsatellite alterations, particularly LOH, occur in a significant proportion of Indian patients with squamous cell carcinoma of the lung.     

Multi-target fluorescence in situ hybridization in bladder washings for prediction of recurrent bladder cancer

The objective of this study was to evaluate the diagnostic value of chromosomal analysis by fluorescence in situ hybridization (FISH) for predicting recurrence of urothelial carcinoma (UC) after transurethral resection. One hundred and thirty-eight patients (median age 68.5 years) with a history of UC were eligible for this prospective study. FISH was applied to cytospin specimens prepared from bladder washings taken during a negative control cystoscopy. The multi-target FISH test UroVysion (Abbott/Vysis) containing probes to the centromeres of chromosomes 3, 7, 17 and the 9p21 locus was used. UC recurrence was defined as a positive biopsy during follow-up. The median follow-up time was 19.2 (4-52) months. FISH was positive in 50 (36%) patients and negative in 88 (64%) patients. A recurrence occurred in 39% of the patients with a positive FISH test and in 21% of patients with a negative FISH test. FISH positivity according to manufacturer's criteria, at the time of a negative cystoscopy, was not significantly associated with the risk of recurrence (p = 0.12). However, the sensitivity of the FISH test to predict recurrence was significantly improved by considering specimens with rare (< or =10) tetraploid cells as negative (p < 0.006). In addition, presence of 9p21 deletion was significantly associated with recurrence (p < 0.01). Notably, positive standard cytology was an independent factor for subsequent recurrence in this study (p < 0.001). Taken together, multi-target FISH may help to stratify the risk of recurrence of UC at the time of a negative follow-up cystoscopy. Defining the optimal threshold for FISH positivity requires consideration of tetraploid pattern and 9p21 deletion. Our results also emphasize the paramount importance of conventional cytology for UC surveillance.     

A novel and non-invasive approach utilising nasal washings for the detection of nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is an epithelial cancer of the nasopharynx which is highly associated with Epstein–Barr virus (EBV). Worldwide, most of the top 20 countries with the highest incidence and mortality rates of NPC are low- and middle-income countries. Many studies had demonstrated that EBV could be detected in the tissue, serum and plasma of NPC patients. In this study, we explored the potential of assays based on non-invasive nasal washings (NW) as a diagnostic and prognostic tool for NPC. A total of 128 patients were evaluated for NW EBV DNA loads and a subset of these samples were also tested for 27 EBV and human miRNAs shortlisted from literature. EBV DNA and seven miRNAs showed area under the receiver operating characteristic curve (AUC) values of more than 0.7, suggestive of their potential utility to detect NPC. Logistic regression analyses suggested that combination of two NW assays that test for EBNA-1 and hsa-miR-21 had the best performance in detecting NPC. The trend of NW EBV DNA load matched with clinical outcome of 71.4% (10 out of 14) NPC patients being followed-up. In summary, the non-invasive NW testing panel may be particularly useful for NPC screening in remote areas where healthcare facilities and otolaryngologists are lacking, and may encourage frequent testing of individuals in the high risk groups who are reluctant to have their blood tested. However, further validation in an independent cohort is required to strengthen the utility of this testing panel as a non-invasive detection tool for NPC.     

HOXA methylation in normal endometrium from premenopausal women is associated with the presence of ovarian cancer: A proof of principle study

DNA methylation of polycomb group target (PCGT) genes is an early step in carcinogenesis and could potentially be assayed to determine cancer risk prediction. To assess whether methylation changes in PCGT genes in normal tissue is able to predict the presence of cancer, we studied HOXA gene methylation in normal endometrium from premenopausal ovarian cancer patients and age‐matched healthy controls without ovarian cancer. DNA methylation of HOXA9 and HOXA11 genes in normal endometrium was associated with ovarian cancer in an initial test set and this was subsequently confirmed in independent validation sample sets. The overall risk of ovarian cancer was increased 12.3‐fold by high HOXA9 methylation for all stages, and 14.8‐fold for early stage ovarian cancers, independent of age, phase of the menstrual cycle and histology of the cancer. The results of this proof of principle study demonstrate the potential to detect ovarian cancer via analysis of normal endometrial cells and provide insight into the possible contribution of this novel approach in ovarian cancer risk prediction and prevention. © 2009 UICC     

Mullerian adenosarcoma (heterologous) of the cervix with sarcomatous overgrowth: a case report with review of literature

Mullerian adenosarcoma is a rare biphasic malignant neoplasm of the cervix characterized by an admixture of benign epithelial elements and a malignant sarcomatous stromal component, which may be either homologous or heterologous. An aggressive variant of adenosarcoma, mullerian adenosarcoma with sarcomatous overgrowth (MASO) is extremely rare, with only two such cases being reported in the English literature to date. In this report we present a case of MASO of uterine cervix with heterologous elements in a 15-year-old unmarried girl presenting with foul smelling menstrual bleeding and passage of fleshy masses. Because MASO with heterologous elements seems to appear at the earliest stages of reproductive lifespan in women, and have an uncertain malignant potential, gynecologists and pathologists should be aware and think about the possibility of this tumor.     

Prognostic factors and treatment outcomes in 93 patients with uterine sarcoma from 4 centers in Turkey

Introduction: Uterine sarcomas are a group of heterogenous and rare malignancies of the female genitaltract and there is a lack of consensus on prognostic factors and optimal treatment. Objective and Methodology:To perform a retrospective evaluation of clinicopathological characteristics, prognostic factors and treatmentoutcomes of 93 patients with uterine sarcomas who were diagnosed and treated at 4 different centers fromNovember 2000 to October 2010. Results: Of the 93 patients, 58.0% had leiomyosarcomas, 26.9% malignantmixed Mullerian tumors, 9.7% endometrial stromal sarcomas, and 5.4% other histological types. Accordingto the last International Federation of Gynecology and Obstetrics (FIGO) staging, 43.0% were stage I, 20.4%were stage II, 22.6% were stage III and 14.0 % were stage IV. Median relapse free survival (RFS) was 20 months(95% confidence interval (CI), 12.4-27.6 months), RFS after 1, 2, 5 years were 66.6%, 44.1%, 16.5% respectively.Median overall survival (OS) was 56 months (95% CI, 22.5-89.5 months), and OS after 1, 2, 5 years was 84.7%,78%, 49.4% respectively. Multivariate analysis showed that age ≥60 years and high grade tumor were significantlyassociated with poor OS and RFS; patients administered adjuvant treatment with sequential chemotherapyand radiotherapy had longer RFS time. Among patients with leiomyosarcoma, in addition to age and grade,adjuvant treatment with sequential chemotherapy and radiotherapy after surgery had significant effects on OS.Conclusion: Uterine sarcomas have poor progrosis even at early stages. Prognostic factors affecting OS werefound to be age and grade.     

11例正常大小卵巢癌综合征的临床及病理分析

目的探讨正常大小卵巢癌综合征的临床特点、诊断标准、有效的治疗方法及其预后。方法回顾性分析１９８４～１９９３年在我院治疗及病理复核证实的１１例正常大小卵巢癌综合征,其中７例为性腺外苗勒氏管肿瘤,也称卵巢外腹膜浆液性乳头状腺癌（ＥＰＳＰＣ）,２例卵巢浆液性腺癌,１例恶性间皮瘤,１例原发灶不明的转移性腺癌。上述无论何种类型,均宜最大限度切除肿瘤,术后残存肿瘤＜２ｃｍ,并辅以有效多程综合化疗。结果１例恶性间皮瘤存活９０个月,随访至１９９７年６月仍健在。１例ＥＰＳＰＣ已存活８７个月,随访至１９９７年１１月仍健在。９例已死亡患者平均生存１７．８个月,比文献报道存活时间长。结论对此综合征患者必须高度重视鉴别诊断,首选手术治疗,尽量切除癌灶（残存肿瘤＜２ｃｍ）,术后辅以有效化疗或放疗,以获得最佳生存和预后。     

Dermatomycosis in Goats in India

Summary: In an extensive survey involving 2176 goats 1.56% of goats manifested clinical lesions of ringworm infection. Animals below the age of 6 months were affected most (4.20%). The incidence of infection was higher during the winter months. T. verrucosum, T. mentagrophytes and M. gypseum were isolated from the skin scrapings of 12, 4, and 2 goats respectively. It is suggested that the infected animals could be a source of disease to human population in which the zoophilic dermatophyte invasion is characterized by severe inflammatory lesions of the skin. The zoonotic importance of different dermatophytes is stressed.
Zusammenfassung: In einer ausgedehnten Untersuchung an 2176 Ziegen wurden bei 1,56% klinische Zeichen einer Hautmykose festgestellt. Tiere, die jühger als 6 Monate alt waren, zeigten mit 4,20% am häfigsten Krankheitssymptome. In den Wintermonaten war die Erkrankungshäufigkeit am gröBten. T. vermcosum, T. mentagrophytes and M. gypseum wurden jeweils von 12,4 bzw. 2 Ziegen isoliert. Die inflzierten Tiere köinnen eine Infektionsquelle für die menschliche Bevölkerung darstellen und dort Mykosen mit stark entzündlichen Veränderungen auslösen. Die Bedeutung verschiedener Dermatophyten als Erreger von Zoonosen wird hervorgehoben.     

Trends in zygomycosis in children

Zygomycosis, or mucormycosis, is associated with significant morbidity and mortality in both children and adults. Studies in adults have shown an increase in the incidence of zygomycosis, particularly among haemtopoietic stem cell transplant (HSCT) recipients and patients with haematologic malignancies. There is a paucity of data on the epidemiology of zygomycosis in children. We performed a retrospective analysis to describe trends in zygomycosis between 1 January 2003 and 31 December 2010. We used the Pediatric Health Information System (PHIS) database to identify paediatric patients who were diagnosed with zygomycosis during the study period. Administrative data on diagnoses, demographics, underlying conditions and clinical experiences were collected. Summary statistics were calculated and tests for trend were conducted. We identified 156 unique patients with zygomycosis. The prevalence of zygomycosis did not significantly increase over time (P=0.284). The most common underlying condition was malignancy (58%) and over half received intensive care. Voriconazole utilisation among all hospitalised children significantly increased during the period (P=0.010). Our study demonstrates that the incidence of zygomycosis is not significantly increasing. During the time period there was a significant increase in the use of voriconazole among children.