Weibliche Reproduktionspathologie

Clinical HistoryA 76-year old female presented to the emergency department sudden loss of consciousness. She had signs of a left sided cerebrovascular accident. She was intubated and her stroke was treated. During her admission in ICU she was noted to have a fixed mass in her left breast with palpable lymphadenopathy in her left axilla. She died from a respirator associated pneumonia.PathologyThe specimen is the patient’s left breast mounted to display the cut surface. Immediately beneath and attached to the skin is a large oval tumour mass 11cm in maximum diameter. The tumour is adherent to the underlying muscle. The tumour is not encapsulated and has a variegated cut surface with areas of necrosis, haemorrhage and cyst formation. This is a breast adenocarcinoma, which involved the regional lymph nodes.Further InformationBreast carcinoma is the second most commonly diagnosed cancer in women worldwide. It is rare in women under 30 years of age but the incidence increases significantly after 30 with the peak occurring at 70 to 80 years. Incidence has been decreasing since the introduction of breast cancer screening programmes, which offer mammography to women at risk and public awareness and education in self-examination of the breast. However, breast cancer remains one of the leading causes of cancer-related death in women.Major risk factors for developing breast carcinoma include being of female gender (men account for 1% of breast cancer diagnosis), exposure to estrogen (early menarche, late menopause, exogenous estrogen), family history of breast cancer, being nulliparous, not breastfeeding, radiation exposure and obesity. Germline mutations in tumour suppressor genes, such as BRCA1, BRCA2, TP53, ATM, CDH1 and CHEK2 are linked with some hereditary cases of breast cancer.Most breast neoplasms are adenocarcinomas that begin in the duct/lobular system as carcinoma in situ (DCIS). These malignancies are further subdivided according to their expression of estrogen receptors (ER) and Human epidermal growth factor 2 (HER2), which guides treatment. The most frequent sites if distant metastasis occur are bone, liver, lung and brain.In developed countries with screening programmes most patients present following an abnormal mammogram. Symptomatic patients present with a breast mass which is classically hard, irregular, immovable. Other clinical symptoms are axillary lymphadenopathy, overlying skin changes (erythematous or thickened skin, dimpled skin (peau d‘orange) and nipple retraction. Symptoms of distant spread of disease may also cause patient presentations.Treatment depends on the stage of the disease and the ER and HER2 status of the tumour. Surgical treatments include uni- or bilateral mastectomy or breast conserving lumpectomy. Surgical axillary node clearance is performed in cases with positive nodal disease. Radiotherapy is given to patients with high risk of local recurrence. Patients with HER2 positive cancers are treated with targeted drugs, such as trastuzumab (Herceptin). Patients with ER positive tumors can be treated using anti-estrogen therapy, such as tamoxifen. Systemic chemotherapy is also used to treat some patients with breast cancer.

Clinical HistoryA 63-year old woman presented with a history of dull lower abdominal pain for 2 months and heavy persistent vaginal bleeding for 1 week. The menopause had occurred 13 years previously. Radical abdominal hysterectomy and bilateral salpingo-oophorectomy were commonly performed for the treatment of endometrial cancer following confirmation of endometrial carcinoma in biopsy.PathologyThe specimen consists of uterus, fallopian tubes and ovaries. The endometrial cavity and endocervical canal have been opened on the anterior aspect. The endometrial lining is grossly abnormal especially on the right side and a brown polypoid tumour has invaded the myometrium and extends inferiorly into the cervical canal. Histologically this was a well-differentiated adenocarcinoma of the endometrium. The left ovary, which has been sectioned in the coronal plane, is enlarged and has several large follicular cysts/cavities.Further InformationEndometrial carcinoma is the most common gynecological malignancy in developed countries and the second most common in developing countries after cervical cancer. There are two major types of endometrial carcinoma. Endometroid carcinoma account for almost 80% of endometrial carcinoma. They usually present early and so have a more favourable outcome. These tumours may arise from atypical endometrial hyperplasia. Common genetic abnormalities seen in endometrioid tumours are mutations in the PTEN, PIK3Ca and ARID1A genes. Serous carcinoma are a less common form of endometrial carcinoma. These tumours are associated with mutations in TP53 gene and carry a poorer prognosis. Endometrioid tumours tend to affect women aged 55 to 65 years. Risk factors for developing endometrioid endometrial cancer include obesity, impaired glucose tolerance, infertility, unopposed estrogen therapy (e.g. early menarche, late menopause or exogenous sources). Serous neoplasms affect older women aged 65 to 75 years with other risk factors for development include having a lower BMI and an atrophic uterus. Women with Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) have a significantly higher risk of developing endometrial cancer.The most common symptom of endometrial cancer is abnormal vaginal bleeding. Most frequently it presents as post-menopausal bleeding, which often allows early presentation. Others may be asymptomatic or an incidental finding of an abnormal endometrium on abdominopelvic imaging. The main radiological sign of endometrial cancer is abnormally thickened endometrium on pelvic ultrasound or CT scan. Diagnosis is made on endometrial biopsy, endometrial curettage or hysterectomy. Treatment depends on the stage of the cancer and includes local radiotherapy, systemic chemotherapy and surgical hysterectomy +/- salpingo-oophorectomy.

Clinical HistoryA 30-year old female presents with inability to conceive. She also reports a history of intermittent pelvic discomfort, menorrhagia and painful periods. On examination a pelvic mass was palpable. All of her blood tests were within normal ranges. A pelvic ultrasound showed a hypoechoic mass within the myometrium of her uterus. She went for hysteroscopic myomectomy but unfortunately complications meant her surgery was converted to an emergency hysterectomy. She made a full recovery post-op.PathologyThe specimen includes the cervix, body and fundus of the uterus. The uterus, which is of normal size, has been cut in the sagittal plane. A large ovoid mass approximately 4cm x 2cm protrudes into the uterine cavity and extends as far inferiorly as the opening of the cervix. It originates from the posterior aspect of the uterus. The cervical canal is clearly visible.Further InformationUterine leiomyomas , also called fibroids, are the most common pelvic tumours in females. They are present in almost 25% of reproductive females. They are benign tumours arising from smooth muscle and fibroblasts of the myometrium. They usually involve the myometrium of the uterine body. Rarely they can affect the lower uterus or cervix. Leiomyomas can occur as single lesions or multiple and can grow very large. There are rare variants, which can extend and spread distally but are still considered benign: e.g. the benign metastasizing leiomyoma, which commonly spread to the lining; or disseminated peritoneal leiomyomatosis, which appears on the peritoneum covering the uterusRisk factors for developing fibroid include being of reproductive age, being a black woman and early menarche. Higher parity has been found to be protective. Most leiomyomas have normal karyotypes but there are some which show mutation in the HMG genes. Transformation into malignant leiomyosarcoma is very rare.Common symptoms of uterine fibroids include abnormal vaginal bleeding, pelvic pain, dyspareunia, dysmenorrhea and symptoms of pelvic structure compression such as urinary symptoms or venous compression symptoms. Leiomyomas can decrease fertility and in pregnant females increase the rate of early pregnancy loss, fetal malpresentation and postpartum hemorrhage. Pelvic ultrasound is usually used to diagnose leiomyomas. CT and MRI scans are rarely used to diagnose.Leiomyomas can grow but can also regress. Treatment is reserved for persistently or severely symptomatic fibroids. Hormonal treatment may be used to regulate irregular menstrual bleeding symptoms. Surgical treatments include myomectomy (removal of fibroids from myomectomy), hysterectomy, myolysis (thermal ablation of leiomyoma) and uterine artery ablation/embolisation.

Clinical HistoryA 36-year old female has a large postpartum hemorrhage after the birth of her 4th child by breech delivery. Her previous 3 children have all been breech deliveries, and no miscarriages. She has a history of intermittent mild abdominal pain. The obstetricians were unable to stop the bleeding and performed an emergency radical hysterectomy and bilateral salpingo-oophorectomy. The patient and baby made a full recovery.PathologyThis hysterectomy specimen is of a bicornuate uterus, fallopian tubes and ovaries; sliced coronally and mounted to display cut and external surfaces. Both uterine bodies are equal in size and share a common cervical canal. A few small cysts are present in the cervix.Further InformationA bicornuate uterus is a congenital uterine malformation where the uterus fundus has an indentation of more than 1 cm. The vagina and cervix are usually normal. There is generally one cervix. There are usually two moderately separate endometrial cavities. Bicornuate uterus develop during embryogenesis when the Mullerian ducts only partially fuse instead of completely fusing.The risk of developing these malformation increases if exposed to diethylstilbestrol (DHS) in-utero, a synthetic estrogen previously used to prevent pregnancy loss. The karyotype of most women with uterine malformations is 46,XX.These malformations are present in around 0.5% of women, although the actual number may be greater as not all women are symptomatic. Symptoms may include pelvic pain (cyclic and non-cyclic), abnormal uterine bleeding and discharge and urinary tract infection (UTI). In pregnancy bicornuate uterus may lead to recurrent miscarriage, pre-term labour, fetal growth restriction, fetal malpresentation and placenta previa. Malpresentation of the fetus leads to increased need for caesarean section. There is increased risk postpartum or placental retention and postpartum hemorrhage.Bicornuate uterus is usually diagnosed with pelvic ultrasound scan. MRI scanning is rarely used to consolidate the diagnosis. Most cases do not require any treatment.