18F-FDG PET/CT in Patients with Vulvar and Vaginal Cancer: A Preliminary Study of 20 Cases.

INTRODUCTION: Despite the growing evidence supporting the use of 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography in cervical and ovarian malignant tumours, data on vulvar and vaginal cancer is sparse. Our aim was to assess the role of 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography in patients with vulvar and vaginal cancer. MATERIAL AND METHODS: A retrospective study was conducted on a cohort of 20 patients with biopsy-proven vulvar (n = 17) and vaginal (n = 3) cancer who performed 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography, between January 2013 and April 2018. We collected the clinical data of all patients, as well as the indication for 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography, its results, and the main lesion maximum standard uptake value (SUVmax). In addition, we correlated the results of 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography with other diagnostic modalities, namely histological findings, computed tomography and magnetic resonance imaging. Patients were divided into two groups, one with newly diagnosed disease and another with recurrent disease. RESULTS: Six patients had newly diagnosed disease and 14 had recurrent disease. The main lesion was detected by 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography in five out of six patients with newly diagnosed disease and in all 14 patients with recurrent disease. Additional sites of 2-[F-18]-fluor-2-desoxi-D-glucose uptake were identified in inguinal and iliac lymph nodes and in distant lesions. Magnetic resonance imaging and computed tomography were performed in 12 cases. In four patients with recurrent disease, abnormalities (main lesion/ metastatic lymph nodes) identified by 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography were not detected as suspicious by computed tomography. DISCUSSION: In our study, 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography identified abnormalities more often than conventional computed tomography scans in recurrent disease. In comparison with histology, 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography had a sensitivity of 95% and a positive predictive value of 100% in identifying the primary tumour and the recurrent main lesion. Little data is available regarding the usefulness of 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography in the management of vulvar and vaginal cancers. The existing evidence supports a high accuracy in detecting lymph node metastases and a change of 36.0% - 61.5% in patient management. Our findings reinforce the usefulness of this technique in vulvar and vaginal cancer. Limitations of our study include its retrospective nature and the rareness of both vulvar and vaginal cancer, which leads to a small sample size and few comparative imaging tests. CONCLUSION: In this preliminary study, 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography demonstrated it can be a useful method in patients with vulvar and vaginal cancers, namely in defining the extent of disease and contributing to accurate staging and restaging.

Introdução: Apesar da crescente evidência que suporta o uso da tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose em tumores malignos do colo do útero e do ovário, os dados sobre o carcinoma da vulva e da vagina são escassos. O nosso objetivo foi avaliar o papel da tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose em doentes com carcinoma da vulva e da vagina. Material e Métodos: Entre janeiro de 2013 e abril de 2018 foi realizado um estudo retrospetivo numa coorte de 20 doentes com carcinoma da vulva (n = 17) e da vagina (n = 3), comprovados por biópsia, que efetuaram tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose. Recolheram-se os dados clínicos de todos os doentes, bem como a indicação clínica para a realização da tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose, os seus resultados e o valor de captação padronizado máximo da lesão principal (SUVmax). Para além disso, correlacionaram-se os resultados da tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose com os de outras modalidades diagnósticas, nomeadamente com os achados histológicos, a tomografia computadorizada e a ressonância magnética. Os doentes foram divididos em dois grupos, um com doença recém diagnosticada e outro com doença recorrente. Resultados: Seis doentes tinham doença recém diagnosticada e 14 tinham doença recorrente. A lesão principal foi detetada em cinco dos seis doentes com doença recém diagnosticada e nos 14 com doença recorrente. Foram identificados outros locais de captação de 2-[F-18]-fluor-2-desoxi-D-glucose, nomeadamente gânglios linfáticos ilíacos e inguinais, e lesões à distância. Em 12 casos foram realizadas ressonância magnética e tomografia computadorizada. Em quatro casos com doença recorrente, as anomalias (lesão principal /gânglios linfáticos metastáticos) identificadas na tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose não haviam sido descritas como suspeitas pela tomografia computadorizada. Discussão: No nosso estudo, a tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose identificou mais anomalias que a tomografia computadorizada na doença recorrente. Comparando com os resultados histológicos, a tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose apresentou sensibilidade de 95% e um valor preditivo positivo de 100% na identificação do tumor primário/ lesão principal recorrente. Poucos dados estão disponíveis sobre a utilidade da tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose no seguimento de carcinomas da vulva e da vagina. As evidências atuais sugerem uma elevada exatidão na deteção de metástases ganglionares e uma mudança de 36,0% - 61,5% no tratamento destes doentes. Os nossos achados reforçam a utilidade desta técnica no carcinoma da vulva e da vagina. As limitações do nosso estudo decorrem da sua natureza retrospetiva e da raridade das patologias estudadas, o que condiciona o tamanho da amostra e a quantidade de exames de imagem comparativos. Conclusão: Neste estudo preliminar, a tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose demonstrou poder ser um método útil em doentes com carcinoma da vulva e da vagina, nomeadamente na definição da extensão da doença e na contribuição para o estadiamento e restadiamento precisos.

Lower-Limb Lymphedema after Sentinel Lymph Node Biopsy in Cervical Cancer Patients.

BACKGROUND: To prospectively assess LLL incidence among cervical cancer patients treated by uterine surgery complemented by SLN biopsy, without PLND. METHODS: A prospective study in 150 patients with stage IA1-IB2 cervical cancer treated by uterine surgery with bilateral SLN biopsy. Objective LLL assessments, based on limb volume increase (LVI) between pre- and postoperative measurements, and subjective patient-perceived swelling were conducted in six-month periods over 24-months post-surgery. RESULTS: The cumulative incidence of LLL at 24 months was 17.3% for mild LLL (LVI 10-19%), 9.2% for moderate LLL (LVI 20-39%), while only one patient (0.7%) developed severe LLL (LVI > 40%). The median interval to LLL onset was nine months. Transient edema resolving without intervention within six months was reported in an additional 22% of patients. Subjective LLL was reported by 10.7% of patients, though only a weak and partial correlation between subjective-report and objective-LVI was found. No risk factor directly related to LLL development was identified. CONCLUSIONS: The replacement of standard PLND by bilateral SLN biopsy in the surgical treatment of cervical cancer does not eliminate the risk of mild to moderate LLL, which develops irrespective of the number of SLN removed.

Sentinel lymph node mapping and intraoperative assessment in a prospective, international, multicentre, observational trial of patients with cervical cancer: The SENTIX trial.

BACKGROUND: SENTIX (ENGOT-CX2/CEEGOG-CX1) is an international, multicentre, prospective observational trial evaluating sentinel lymph node (SLN) biopsy without pelvic lymph node dissection in patients with early-stage cervical cancer. We report the final preplanned analysis of the secondary end-points: SLN mapping and outcomes of intraoperative SLN pathology. METHODS: Forty-seven sites (18 countries) with experience of SLN biopsy participated in SENTIX. We preregistered patients with stage IA1/lymphovascular space invasion-positive to IB2 (4 cm or smaller or 2 cm or smaller for fertility-sparing treatment) cervical cancer without suspicious lymph nodes on imaging before surgery. SLN frozen section assessment and pathological ultrastaging were mandatory. Patients were registered postoperatively if SLN were bilaterally detected in the pelvis, and frozen sections were negative. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02494063). RESULTS: We analysed data for 395 preregistered patients. Bilateral detection was achieved in 91% (355/395), and it was unaffected by tumour size, tumour stage or body mass index, but it was lower in older patients, in patients who underwent open surgery, and in sites with fewer cases. No SLN were found outside the seven anatomical pelvic regions. Most SLN and positive SLN were localised below the common iliac artery bifurcation. Single positive SLN above the iliac bifurcation were found in 2% of cases. Frozen sections failed to detect 54% of positive lymph nodes (pN1), including 28% of cases with macrometastases and 90% with micrometastases. INTERPRETATION: SLN biopsy can achieve high bilateral SLN detection in patients with tumours of 4 cm or smaller. At experienced centres, all SLN were found in the pelvis, and most were located below the iliac vessel bifurcation. SLN frozen section assessment is an unreliable tool for intraoperative triage because it only detects about half of N1 cases.

Tumor Testing for Somatic and Germline BRCA1/BRCA2 Variants in Ovarian Cancer Patients in the Context of Strong Founder Effects.

Deleterious variants in the BRCA1/BRCA2 genes and homologous recombination deficiency (HRD) status are considered strong predictors of response to poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). The introduction of PARPi in clinical practice for the treatment of patients with advanced ovarian cancer imposed changes in the molecular diagnosis of BRCA1/BRCA2 variants. BRCA1/BRCA2 tumor testing by next-generation sequencing (NGS) can detect simultaneously both somatic and germline variants, allowing the identification of more patients with higher likelihood of benefiting from PARPi. Our main goal was to determine the frequency of somatic and germline BRCA1/BRCA2 variants in a series of non-mucinous OC, and to define the best strategy to be implemented in a routine diagnostic setting for the screening of germline/somatic variants in these genes, including the BRCA2 c.156_157insAlu Portuguese founder variant. We observed a frequency of 19.3% of deleterious variants, 13.3% germline, and 5.9% somatic. A higher prevalence of pathogenic variants was observed in patients diagnosed with high-grade serous ovarian cancer (23.2%). Considering the frequencies of the c.3331_3334del and the c.2037delinsCC BRCA1 variants observed in this study (73% of all BRCA1 pathogenic germline variants identified) and the limitations of NGS to detect the BRCA2 c.156_157insAlu variant, it might be cost-effective to test for these founder variants with a specific test prior to tumor screening of the entire coding regions of BRCA1 and BRCA2 by NGS in patients of Portuguese ancestry.

Central Pathology Review in SENTIX, A Prospective Observational International Study on Sentinel Lymph Node Biopsy in Patients with Early-Stage Cervical Cancer (ENGOT-CX2).

The quality of pathological assessment is crucial for the safety of patients with cervical cancer if pelvic lymph node dissection is to be replaced by sentinel lymph node (SLN) biopsy. Central pathology review of SLN pathological ultrastaging was conducted in the prospective SENTIX/European Network of Gynaecological Oncological Trial (ENGOT)-CX2 study. All specimens from at least two patients per site were submitted for the central review. For cases with major or critical deviations, the sites were requested to submit all samples from all additional patients for second-round assessment. From the group of 300 patients, samples from 83 cases from 37 sites were reviewed in the first round. Minor, major, critical, and no deviations were identified in 28%, 19%, 14%, and 39% of cases, respectively. Samples from 26 patients were submitted for the second-round review, with only two major deviations found. In conclusion, a high rate of major or critical deviations was identified in the first round of the central pathology review (28% of samples). This reflects a substantial heterogeneity in current practice, despite trial protocol requirements. The importance of the central review conducted prospectively at the early phase of the trial is demonstrated by a substantial improvement of SLN ultrastaging quality in the second-round review.

Benign Metastasizing Leiomyoma of the Uterus: Rare Manifestation of a Frequent Pathology.

Benign Metastasizing Leiomyoma (BML) is a rare condition with few cases reported in the literature. It is usually incidentally diagnosed several years after a primary gynecological surgery for uterine leiomyoma. Differential diagnosis of BML is complex requiring an extensive work-up and exclusion of malignancy. Here, we report two cases of BML based on similarity of histopathological, immunohistochemical, and genetic patterns between lung nodules and uterine leiomyoma previously resected, evidencing the variability of clinical and radiological features of BML. We highlight the importance of 19q and 22q deletions as highly suggestive of BML. These findings are particularly relevant when there is no uterine sample for review.

Extensive peritoneal keratin granuloma in stage IV B endometrial carcinoma with an outstanding survival: A case report and review of the literature.

► Unusual survival of IVB endometrial carcinoma with peritoneal keratin granuloma(PKG). ► PKG can be secondary to endometrioid adenocarcinoma with squamous differentiation. ► Prognosis meaning of lesions is difficult to assess because few cases are published.

[Wertheim-Meigs operation for cervical cancer and complementary therapy: critical analysis of 5 years]. / Operação de Wertheim-Meigs em carcinoma do colo do útero e tratamento complementar: análise crítica de cinco anos.

OBJECTIVES: Review and critical analysis of the Wertheim-Meigs Operations performed at our institution in the context of cervical cancer and to assess the proportion who underwent treatment with adjuvant radiotherapy (with or without chemotherapy) and the main indications. MATERIAL AND METHODS: Retrospective review of Wertheim-Meigs operations, conducted in the context of carcinoma of the cervix, between 01.01.2005 and 31.12.2010, through consultation with clinical processes. It was later performed a descriptive statistical analysis of the cases. RESULTS: During this period 119 Wertheim-Meigs Operations were performed. Four were excluded: two, for primary indication for adjuvant therapy due to histological subtype; two for the inability to exclude invasive disease preoperatively and the invasion was not confirmed after surgery. A total of 115 cases were reviewed and analyzed, and of these 50 (43.5%) underwent complementary therapy, the main indication being the presence of lymphovascular invasion in 21 cases (42% of cases submitted to complementary therapy ). CONCLUSIONS: The mean age of patients undergoing radical surgery is 49 years, with stage IB1 most often determining its performance. Complementary therapy was performed in 43.5% of cases, the main indication being lymphovascular invasion (42%) followed by lymph node invasion (16%). Internal audit to the Service is satisfactory, with 16.5% surgical complication rate and high technical performance.

[Pelvic exenterations for gynaecological cancer--a 10 year institutional review]. / Exenteração pélvica no cancro ginecológico. Retrospectiva de dez anos.

UNLABELLED: Pelvic exenteration consists in a radical surgical procedure for patients with advanced cancer but limited to central pelvis. It is used for treatment of primary or recurrent tumours, or, more usually in treatment of recurrent cervical cancer. MATERIAL AND METHODS: Retrospective study of medical charts of patients underwent pelvic exenteration for gynaecological cancer between January 1995 and April 2005. RESULTS: Twenty-one pelvic exenterations were performed in this period. The mean age of the patients was 55.7 years. Indication for surgery included 14 (67%) recurrent cervical cancers; 2 uterine cancers (recurrent), 2 vulvar cancer (one recurrent and one primary), 2 vagina carcinoma (one primary and one recurrent) and one patient with synchronous recto and uterine tumours. Exenteration was nine anterior, 3 posterior and 9 totals. The median length of hospitalization was 27 days. Most common postoperative complications were associated with urinary diversion. After surgery 19% of patients develops persistent lesion, 24% develops recurrent lesion with a middle free interval of 12.4 months. After a median follow-up of 29 months, 10 patients (47%) are alive and free of disease. CONCLUSION: Pelvic exenteration can be offered as a surgical salvage therapy to patients with locally advanced gynaecological cancer.