The dilemma of managing thyroid gland after incidental diagnosis of malignant struma Ovarii. Is radical thyroidectomy and radioactive iodine Necessary? A case report and literature review.

•Struma ovarii is a rare ovarian teratoma which consists of at least 50% thyroid tissue.•In 0.5-1% of cases the thyroid tissue in the struma ovarii undergoes a malignant transformation.•Patients should be divided into low and high-risk groups for synchronous thyroid carcinoma.•Patients with abnormalities on thyroid imaging should be considered as high-risk.•A thyroidectomy and radioactive iodine treatment can decrease the risk of recurrence.

The value of human epididymis 4, D-dimer, and fibrinogen compared with CA 125 alone in triaging women presenting with pelvic masses: a retrospective cohort study.

INTRODUCTION: CA 125, the biomarker in common clinical use for ovarian cancer, is limited by low sensitivity for early disease and high false positives. The aim of this study was to evaluate several candidate biomarkers, alone or in combination, compared with CA 125 in the prediction of malignant/borderline vs benign tumor status in premenopausal and postmenopausal women with pelvic masses. MATERIAL AND METHODS: This was a retrospective observational cohort study set in St James's Hospital, a tertiary referral center for gynecological malignancy in Dublin, Ireland. Women undergoing surgery for pelvic masses between 2012 and 2018 were included. Preoperative human epididymis protein 4 (HE4), the Risk of Ovarian Malignancy Algorithm, the Risk of Malignancy Index I and II, D-dimer, and fibrinogen were assessed. Logistic regression models were fitted for each biomarker alone and in combination. Receiver operating characteristics-area under the curve (ROC-AUC) and partial AUCs in the 90%-100% specificity range were determined. RESULTS: In all, 89 premenopausal and 185 postmenopausal women were included. In premenopausal women, no biomarker(s) outperformed CA 125 (AUC 0.73; 95% CI 0.63-0.84). In postmenopausal women, HE4 had a partial AUC (pAUC) of 0.71 (95% CI 0.64-0.79) compared with 0.57 (95% CI 0.51-0.69) for CA 125 (p = 0.009). HE4 + D-dimer had an improved pAUC of 0.74 (95% CI 0.68-0.81, p < 0.001) and HE4 + D-dimer + fibrinogen had a pAUC of 0.75 (95% CI 0.68-0.82). CONCLUSIONS: A novel biomarker panel of HE4 ± D-dimer ± fibrinogen outperformed CA 125 alone as a high-specificity biomarker in postmenopausal women and could aid in the preoperative triaging of pelvic masses. No biomarker(s) outperformed CA 125 in premenopausal women.

HE4 and CA125 as preoperative risk stratifiers for lymph node metastasis in endometrioid carcinoma of the endometrium: A retrospective study in a cohort with histological proof of lymph node status.

OBJECTIVES: To investigate whether HE4 and CA125 could identify endometrioid adenocarcinoma patients who might most benefit from full staging surgery with lymphadenectomy. METHODS: Sequential patients with a preoperative banked serum and histology of endometrioid adenocarcinoma of endometrium who had undergone surgical staging with lymph node dissection over a 5-year period between 2011 and 2016 were included from a tertiary Gynaecological Cancer Centre, Dublin, Ireland. Preoperative serum HE4 and CA125 were measured using ELISA, with the cut-offs HE4 81 pmol/L and CA125 35 U/ml. Predictive values were estimated using AUC, sensitivity, specificity and odds ratios. RESULTS: 9.5% of the cohort had lymph node metastases. A HE4 cut-off of 81 pmol/L yielded a sensitivity of 78.6% and specificity of 53.4% for predicting lymph node metastases. Sensitivity of CA125 at 35 U/ml was 57% and specificity 91.4%. The AUC was 0.66 (0.52-0.80) for HE4 and 0.74 (0.58-0.91) for CA125. Sensitivity was 92.8% and specificity 51.1% when an elevation of either HE4 or CA125 was included, AUC was 0.72 (0.61-0.83), this combination yielded the highest NPV of 98.6%. Sensitivity was 42.9% and specificity 93.8% if both markers were elevated simultaneously, AUC was 0.68 (0.51-0.86). Preoperative clinical predictors of high-grade preoperative histology and radiology had sensitivities of 21.4% and 41.7%, respectively. Patients with a HE4 above 81 pmol/L had an odds ratio of 4.2 (1.12-15.74), p < 0.05, of lymph node metastases and CA125 had an odds ratio of 14.2 (4.16-48.31), p < 0.001. CONCLUSIONS: Serum HE4 and CA125 improved on existing methods for risk stratification of endometrioid carcinomas and warrant further investigation.

A risk score for prediction of venous thromboembolism in gynecologic cancer: The Thrombogyn score.

BACKGROUND: Gynecologic cancers are associated with high rates of venous thromboembolism (VTE), which is exacerbated by pelvic surgery and chemotherapy. OBJECTIVES: The aim of this study was to develop and validate a risk score for VTE in patients with gynecologic cancer and to test the predictive ability of the score following addition of procoagulant biomarker data. PATIENTS AND METHODS: Clinical and laboratory variables were used to develop a risk score for the prediction of VTE in patients with gynecological cancer (n = 616), which was validated in a separate cohort of patients (n = 406). Endogenous thrombin potential and D-dimer levels were determined in a subset (n = 290) of patients and used to produce an extended score in the validation cohort. RESULTS: Multivariable regression analysis identified BMI >30, hemoglobin <11.5 g/dL and chemotherapy as independent predictors of VTE, which formed the Thrombogyn score. Following competing risk regression analysis, subdistribution hazard ratios (SHRs), adjusted for cancer stage, were 8.16 (95% confidence interval [CI], 1.69-43.77) in the high-risk group (score = 2-3) and 4.12 (95% CI, 0.85-20.15) in the intermediate-risk group (score = 1) compared with the low-risk group (score = 0). SHRs for the validation cohort were 6.26 (95% CI, 1.24-31.39) and 3.00 (95% CI, 0.67-13.32), respectively. Cumulative incidence of VTE in the validation cohort high-risk group was 10.34% (95% CI, 6.51-16.41) per women-years compared with 1.06% (95% CI, 0.26-4.26) in the low-risk group. Using the extended Thrombogyn score, adjusted SHRs were 16.83 (95% CI, 4.20-67.37) in the high-risk group with a cumulative incidence of 21.15% (95% CI, 10.32-45.24). External validation of the score is required. CONCLUSIONS: The Thrombogyn score identifies patients with gynecologic cancer at high and low risk of VTE. Addition of biomarker data improves the predictive power of the score.

Sister Mary Joseph nodule: an unusual site for endometrioid cancer metastasis.

Sister Mary Joseph (SMJ) nodules are rare malignant metastatic umbilical nodules, indicating disseminated disease and associated with a poor prognosis. This is the case of an 80-year-old woman who presented with umbilical discomfort and an ulcerated umbilical nodule. She was noted to have a bulky uterus and vaginal bleeding. CT abdomen-pelvis showed an enlarged uterus and right-sided lymphadenopathy, extending from the groin to the para-aortic area. Upper and lower endoscopies were normal. Biopsy of the umbilical nodule revealed metastatic endometrioid adenocarcinoma grade 1-2 with the endometrium and the ovary suggested as potential primary sites. The patient had cytoreductive surgery including en bloc resection of the umbilical tumour. Final histology confirmed Stage IVb endometrioid adenocarcinoma of the uterus. This unusual case highlights the diagnostic challenges faced with the presentation of an umbilical nodule. Gynaecological malignancy should always be considered within the initial differential diagnosis of an SMJ nodule.

Lung metastases from benign uterine leiomyoma: does 18-FDG-PET/CT have a role to play?

Uterine leiomyomas are the most common benign gynaecological tumours. However, 0.13 to 6% of them have malignant potential (Robboy et al. Environ Health Perspect 108(Suppl 5):779-784, 2000). Uterine smooth muscle tumours with unusual growth patterns include a spectrum of lesions such as intravenous leiomyomatosis, benign metastasizing leiomyoma and disseminated peritoneal leiomyomatosis (Vaquero et al. J Minim Invasive Gynecol 16:263-268, 2009). Benign metastasizing leiomyoma (BML) is a very rare condition with around 100 cases reported to date. BML is a cytologically bland, mitotically inactive smooth muscle tumour in extra uterine sites, occurring in conjunction with similarly appearing or previously removed uterine leiomyomas (Beck et al. Hong Kong Med J = Xianggang yi xue za zhi 18:153-155, 2012). Pulmonary metastases are the most common sites of metastases, but other sites include skin, bladder, liver, lymph nodes, oesophagus, skeletal muscles, heart, bones and central nervous system (Jo et al. Korean J Int Med 21:199-201, 2006; Arai et al. Chest 117:921-922, 2000; Kwon et al. Korean J Int Med 21:173-177, 2006; Rivera et al. J Clin Endocrinol Metab 89:3183-3188, 2004; Jautzke et al. Pathol Res Pract 192:215-223, 1996; Goyle et al. Am J Clin Oncol 26:473-476, 2003; Schneider et al. Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen 72:308-311, 2001; Andrade et al. Pathol Oncol Res: POR 4:44-47, 1998; Abramson et al. AJR Am J Roentgenol 176:1409-1413, 2001; Yoon et al. Cancer Res Treat 43:131-133, 2011; Egberts et al. Arch Gynecol Obstet 274:319-322, 2006). The condition is more common in late childbearing age, mean age of diagnosis is 43 years (Kwon et al. Korean J Int Med 21:173-177, 2006), suggesting that it is hormone related. Lung metastases in BML are usually an incidental finding during the preoperative assessment; however, on rare occasions, patients are symptomatic with cough, chest pain, haemoptysis or dyspnoea. The differential diagnosis includes pulmonary metastases from leiomyosarcoma, intravenous leiomyomatosis or metastasis from other malignancies. Lung biopsy is the only way to confirm the benign nature of these lesions. Recently, positron emission tomography (PET) scan showed promise in differentiating these benign lesions from malignant lung lesion (Sawai et al. Oncol Lett 14:3641-3646, 2017). We present three cases with pulmonary metastases from BML and discuss the pathogenesis and management of this rare condition.

Paravaginal aggressive angiomyxoma.

A 34-year-old nulliparous woman with a long-standing history of uterine fibroids and infertility had undergone prior open myomectomy, then uterine artery embolisation in treatment of an apparent large fibroid. Imaging on referral revealed an atypical 12×11×10 cm pelvic mass with the appearance of a fibroid. At laparotomy, the lesion was encapsulated but softer than a fibroid and located deep in the paravaginal space. The histopathological outcome was an aggressive angiomyxoma.

Suspected ovarian molar pregnancy after assisted reproductive technology conception: a diagnostic challenge.

A 32-year-old patient with primary infertility received in vitro fertilisation (IVF) therapy. Four weeks later she developed intermittent left iliac fossa pain. Transvaginal ultrasound showed an empty uterus and an adnexal mass adjacent to the right ovary. Serum ß-human chronic gonadotropin was 33,492 IU/L. At laparoscopy a mass attached to right ovary, suggestive of a right ovarian ectopic pregnancy, was excised. Histological examination confirmed an ovarian ectopic gestation, but noted enlarged chorionic villi and trophoblastic atypia, which raised the suspicion of molar pregnancy. Subsequent p57 immunohistochemistry and DNA ploidy studies excluded a mole, however. Cases of suspected molar disease in ectopic pregnancy present a diagnostic challenge for both clinicians and histopathologists, and establishing a definitive diagnosis may be difficult.

An unusual relapse in acute myeloid leukaemia.

A 40-year-old nulliparous woman, with a history of acute myeloid leukaemia (AML), presented at a gynaecological clinic with an incidental finding of a 5 cm pelvic mass on ultrasound during workup for subfertility. Biopsies confirmed a myeloid sarcoma. The patient underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy, followed by chemotherapy and radiotherapy. She recovered well from her surgery, 21 months postsurgery with no evidence of recurrence.

Could sentinel node mapping of the groin cause extranodal metastasis in vulva cancer?

Groin node lymphadenectomy in vulva cancer carries a substantial risk of morbid sequelae. Sentinel lymph node (SLN) mapping is a valid alternative in patients with squamous cancer of diameter <4 cm and nonsuspicious lymph nodes. SLN are mapped according to the combined technique of radioscintigraphy using technetium-labelled colloid and blue dye. We describe early extranodal recurrence in 2 patients undergoing SLN mapping. They had lymph node metastases at their original dissection. We question whether rapid lymph flow promoted by injection of colloid and dye could cause retrograde flow of cancer cells along the lymphatics draining from the pubis to the groin and extravasation of cancer cells into the dermis since these metastases arose anterior to the pubis and medial to the groin. These recurrence sites were more medial and cephalad than would be expected for skin bridge metastasis. CT imaging shows the metastases are within the dermis. No lymphatic tissue was identified around these subcuticular cancer deposits at repeat resection. Body wall extension occurs in recurrent vulva cancer, but we never saw such an early recurrence when full inguinofemoral lymphadenectomy without SLN was the standard approach. These 2 cases raise a caveat in the application of SLN mapping in vulva cancer, especially when metastasis is detected on SLN as the afferent channels to the lymph nodes may be already blocked or flow impaired by the tumour.

An unusual presentation of endometriosis.

A 25-year-old nulliparous woman attended an orthopaedic clinic with a 12-month history of right hip pain and was found to have a hard tender mass in her right groin. Fine-needle aspiration yielded a diagnosis of endometrial glands. The lesion was excised completely and the final diagnosis was round ligament endometriosis. The patient was pain free 3 months postsurgery.

Tumour expresion of tissue factor and tissue factor pathway inhibitor in ovarian cancer- relationship with venous thrombosis risk.

INTRODUCTION: Ovarian cancer is known to display a particular association with venous thromboembolism (VTE) with reports up to 42% of patients developing thromboembolic complications. Tissue Factor (TF) and its inhibitor Tissue Factor Pathway Inhibitor (TFPI) have been implicated in VTE risk in cancer. The aim of this study was to measure tumour derived TF and TFPI and to investigate their potential role in VTE in ovarian cancer patients. METHODS: TF and TFPI mRNA expression was measured using TaqMan real time PCR in 99 ovarian tumour samples. Nineteen cases complicated by VTE were matched to 19 cases without VTE. TF and TFPI protein levels were measured using ELISA and immunohistochemistry was used to localize TF expression. The role of TF expression on overall survival was also determined. RESULTS: TF mRNA and protein expression was increased in tumours from patients with clear cell carcinoma (p<0.001). TF protein expression was also increased in endometroid carcinoma (P<0.01) compared with benign tumours. TFPI mRNA expression was increased in clear cell carcinoma (P<0.01). TF mRNA and antigen level was increased in malignant tumours of patients who developed VTE compared with matched malignant õtumours of patients who remained thrombosis free (P<0.01). There was no difference in TFPI expression between the two groups. CONCLUSION: TF expression in ovarian cancer is significantly higher in patients who develop VTE. TF expression was increased in clear cell ovarian cancer and endometroid cancer and this may explain the higher risk of VTE in these subgroups. TF derived from these tumours may be the trigger for VTE in ovarian cancer.

Venous thromboembolism in ovarian cancer: incidence, risk factors and impact on survival.

OBJECTIVES: Ovarian cancer has a higher incidence of venous thromboembolism (VTE) than other cancers. Clear cell cancers carry the highest risk at 11-27%. The aim of this study was to identify the predisposing factors for VTE in a population of ovarian cancer patients and to determine the influence of VTE on overall survival. STUDY DESIGN: VTE events were identified from hospital and general practice/community care records for all patients with ovarian cancer who were diagnosed and treated in a tertiary cancer center between 2006 and 2010. RESULTS: The overall incidence of VTE was 9.7% (33) in 344 patients. Sixteen (48%) had pulmonary embolism. Six (18%) presented with VTE. Five (15%) had VTE diagnosed during pre-treatment routine CT scanning. Eleven (33%) developed VTE following surgery and eleven (33%) developed VTE during chemotherapy. Risk factors associated with the occurrence of VTE were BMI≥30 (p<0.01), clear cell carcinoma (p<0.05), advanced stage (p<0.01), high grade (p<0.01) and CA125>500 IU/ml (p<0.001). The occurrence of VTE was associated with decreased overall survival time (p<0.001). CONCLUSION: The incidence of VTE is high in ovarian cancer especially in the clear cell subtype. VTE adversely affects survival in ovarian cancer. Obesity, high grade and stage of cancer, clear cell subtype and high CA 125 level should be incorporated into protocols of VTE prophylaxis in women with ovarian cancer.