Nonseminomatous germ cell tumours
Yolk sac tumour
Primary peritoneal carcinoma
Paraneoplastic syndromes These are symptom complexes in cancer patients. They may represent earliest manifestation of an occult neoplasm or mimic metastatic disease. Some of the syndromes are characteristic of certain tumours. Hypercalcaemia is probably the most common paraneoplastic syndrome. Others include Cushing’s syndrome associated with small cell carcinoma of the lung, polycythaemia associated with renal cell carcinomas and carcinoid syndrome associated with bronchial adenomas.
Neoplasms of the female genital tract
Cervical carcinoma This is a disease that is common in less-developed countries. In developed countries, the incidence of cervical carcinoma is low because of early intervention and treatment of the preinvasive disease. The precursor lesion of cervical squamous cell carcinoma is cervical intraepithelial neoplasia (CIN) and of adenocarcinoma is cervical glandular intraepithelial neoplasia (CGIN). Both types of carcinoma are HPV-related lesions. Cervical carcinoma is associated with a number of risk factors, including age at first intercourse, number of sexual partners and frequency of intercourse. All of these are interrelated with the major independent risk factor, which is infection with HPV. The other major independent risk factor is cigarette smoking. There are more than 100 subtypes of HPV. Some of these show a predilection for infecting the lower female genital tract, notably HPV 6, 11, 16 and 18. HPV 6 and 11 are implicated in benign condylomata and rarely implicated in malignancy. HPV 16 and, to a lesser extent, 18 are found in CIN and in cervical carcinomas. The area of the cervix where cancers arise is the transformation zone. CIN and CGIN can be recognised in cervical smears and this forms the basis of the cervical screening programme. The aim of the programme is to reduce cervical carcinoma by detection and treatment of the preneoplastic disease. Treatment of preinvasive conditions reduces the incidence of cervical carcinoma. HPV testing is now used to triage low-grade abnormalities detected on cervical smears. It is also used as test of cure of treatment of high-grade abnormalities. A HPV vaccination programme has been introduced in the UK.
Endometrial carcinoma This is emerging as a disease of more affluent populations. Endometrial carcinomas are broadly categorised as Type 1 and Type 2 carcinomas. Type 1 carcinoma occurs in younger perimenopausal women and is associated with unopposed estrogenic stimulation. Other associations include diabetes, hypertension and obesity. The prototypic Type 1 endometrial carcinoma is endometrioid carcinoma, of which early stage and low grade disease has a good prognosis. There is a premalignant state for this cancer that is termed atypical hyperplasia. The other type of hyperplasia is termed non‐atypical hyperplasia and includes formerly termed simple and complex hyperplasia. Type 2 cancers occur in older postmenopausal women and has no association with estrogen excess. The prototypic Type 2 endometrial carcinoma is serous carcinoma. Serous carcinoma can present with extrauterine disease even in early stages. The preinvasive condition is known as serous endometrial intraepithelial carcinoma (SEIC).
The commonest tumour of the uterus arises in the uterine wall. These are the benign smooth muscle tumours that are commonly referred to as fibroids. Histologically they are known as leiomyomas. Their malignat counterpart leiomyosarcoma is an uncommon malignant neoplasm. Malignant tumours of the endometrial stroma are endometrial stromal sarcoma. These tumours tend to spread through vascular channels of the myometrium. They are hormone sensitive and recur locally at the first instance.
Tumours of the ovary A plethora of tumour types are seen in the ovary. These include epithelial tumours, sex cord stromal tumours, germ cell tumours, miscellaneous tumours and metastatic tumours.
Primary ovarian carcinomas These are the commonest ovarian malignancy and can be of many different epithelial types. Ovarian carcinomas are divided into two groups designated Type I and Type II. Type I tumours are slow growing, generally confined to the ovary at diagnosis and develop from well-established precursor lesions that are termed borderline tumours. Type I tumours include mucinous and endometrioid carcinomas. They are genetically stable and are characterised by mutations in a number of different genes including KRAS and BRAF. Type II tumours are rapidly growing highly aggressive neoplasms for which well-defined precursor lesions have not been described. Type II tumours include high-grade serous carcinoma. This group of tumours has a high level of genetic instability and is characterized by mutation of p53.
Risk factors for ovarian cancers include nulliparity and family history. Women from families with BRCA gene are monitored with imaging and serum CA-125 studies because of the definitely increased risk of ovarian cancer. These families also have an increased risk of cancers of the fallopian tube and the peritoneum.
Serous carcinomas of the ovary These are the commonest epithelial tumour. They often present late. Spread to the omentum is common. There is an increasing acceptance that most ovarian serous carcinomas arise in the fallopian tube and spread secondarily to the ovary.
Sex cord stromal tumours The commonest malignant sex cord stromal tumour is the adult type of granulosa cell tumour. They are usually unilateral tumours and can be haemorrhagic. These tumours are characterised by their propensity for late recurrence.
Germ cell tumours Germ cell tumours constitute 15–20% of all ovarian tumours. Benign mature cystic teratomas, also known as ovarian dermoid cysts, are common ovarian neoplasms and occur at all ages. Other tumours in this category are mainly seen in children and young adults.
Metastatic tumours The ovary is a common site for metastatic tumours. Some of these tumours can closely mimic primary ovarian cancers and pose problems for the pathologist. The commonest tumours presenting as metastatic carcinomas are from the uterus, colon, stomach, biliary tract and pancreas. The classic example of metastatic gastrointestinal neoplasia to the ovaries is termed Krukenberg tumour and defines bilateral ovarian enlargement with diffuse infiltrating malignant cells containing intracellular mucin.
Vulva squamous cell carcinoma is the commonest epithelial malignancy of the vulva. The appearances are similar to squamous carcinomas anywhere in the body, and a three-tier grading is done on the basis of resemblance to normal squamous cells. The prognosis is determined by the size, depth of invasion and the degree of differentiation and the presence and extent of nodal metastases. The inguinal lymph nodes are commonly affected. Carcinomas invading to a depth of less than 1 mm are sometimes referred to as superficially invasive and have virtually no risk of metastasis. The preinvasive condition is termed vulvar intraepithelial neoplasia (VIN). It is recognised that there are two distinct types of VIN – classical VIN (also sometimes referred to as uVIN or usual type VIN) and differentiated VIN (dVIN) (Table 25.3).
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