Uterine serous carcinoma
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Uterine serous carcinoma is a
malignant Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...
form of serous tumor that originates in the
uterus The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...
. It is an uncommon form of
endometrial cancer Endometrial cancer is a cancer that arises from the endometrium (the epithelium, lining of the uterus or womb). It is the result of the abnormal growth of cells (biology), cells that can invade or spread to other parts of the body. The first s ...
that typically arises in postmenopausal women. It is typically diagnosed on endometrial biopsy, prompted by
post-menopausal bleeding Vaginal bleeding is any expulsion of blood from the vagina. This bleeding may originate from the uterus, vaginal wall, or cervix. Generally, it is either part of a normal menstrual cycle or is caused by hormonal or other problems of the reproductiv ...
. Unlike the more common low-grade endometrioid endometrial adenocarcinoma, uterine serous carcinoma does not develop from
endometrial hyperplasia Endometrial hyperplasia is a condition of excessive proliferation of the cells of the endometrium, or inner lining of the uterus. Most cases of endometrial hyperplasia result from high levels of estrogens, combined with insufficient levels of th ...
and is not hormone-sensitive. It arises in the setting of endometrial
atrophy Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), malnutrition, poor nourishment, poor circulatory system, circulation, loss of hormone, ...
and is classified as a type II endometrial cancer.


Cause

Initially there is a precursor lesion called serous endometrial intraepithelial carcinoma. Mutation is found in TP53 gene which is a tumor suppressor gene even in precursor lesion suggesting early involvement of this gene. Also many missense mutation and mutation in PI3K and PP2A genes are involved which also contribute to this tumor.


Diagnosis

The lesion is found in patients who present typically with abnormal or postmenopausal bleeding. Such bleeding is followed by further evaluation leading to a tissue diagnosis, usually done by a dilatation and curettage. A work-up to follow would look for metastasis using imaging technology including sonography and magnetic resonance imaging. The median age at diagnosis in a study of 138 women was 67 years, of these 54 had stage I, 20 stage II, 41 stage III, and 23 stage IV disease.


Histopathology

Histopathological Histopathology (compound of three Greek language, Greek words: 'tissue', 'suffering', and ''-logy, -logia'' 'study of') is the light microscope, microscopic examination of Tissue (biology), tissue in order to study the manifestations of dis ...
ly, uterine serous carcinomas is typically characterized by (1) nipple-shaped structures (papillae) with fibrovascular cores (2) marked nuclear atypia (irregularities in the nuclear membrane, enlarged nuclear size), (3) psammoma bodies and (4)
cilia The cilium (: cilia; ; in Medieval Latin and in anatomy, ''cilium'') is a short hair-like membrane protrusion from many types of eukaryotic cell. (Cilia are absent in bacteria and archaea.) The cilium has the shape of a slender threadlike proj ...
. These are general findings in serous tumors which are also seen in such tumors in other anatomic locations.


Staging

Uterine papillary serous carcinoma is staged like other forms of endometrial carcinoma at time of surgery using the International Federation of Gynecology and Obstetrics cancer staging system. *Stage IA: tumor is limited to less than half the myometrium *Stage IB: invasion of more than half the
myometrium The myometrium is the middle layer of the uterine wall, consisting mainly of uterine smooth muscle cells (also called uterine myocytes) but also of supporting stromal and vascular tissue. Its main function is to induce uterine contractions. Stru ...
*Stage II: cervical stromal invasion *Stage IIIA: tumor invades serosa or adnexa *Stage IIIB: vaginal or parametrial metastasis *Stage IIIC1: metastasis to pelvic lymph nodes *Stage IIIC2: metastasis to para-aortic lymph nodes *Stage IVA: invasion of the bladder or bowel *Stage IVB: distant metastasis, including intra-abdominal or inguinal lymph nodes


Survival

In the older literature survival rates have been given as 35–50% for stage I–II and 0–15% for stage III and IV uterine papillary serous carcinoma, More recently it was reported that forty-two percent of 138 patients were found disease-free at five years. In 2009, the journal of "
Gynecologic Oncology ''Gynecologic Oncology'' is a Peer review, peer-reviewed medical journal covering all aspects of gynecologic oncology. The journal covers investigations relating to the etiology, diagnosis, and treatment of female cancers, as well as research from ...
" reported the following 5-year survival rates based upon stage of cancer: *Stage I: 50–80% *Stage II: 50% *Stage III: 20% *Stage IV: 5% - 10%


Treatment

The primary treatment is surgical. FIGO- cancer staging is done at the time of surgery which consists of peritoneal cytology, total
hysterectomy Hysterectomy is the surgical removal of the uterus and cervix. Supracervical hysterectomy refers to removal of the uterus while the cervix is spared. These procedures may also involve removal of the ovaries (oophorectomy), fallopian tubes ( salpi ...
, bilateral salpingo-oophorectomy, pelvic/para-aortic
lymphadenectomy Lymphadenectomy, or lymph node dissection, is the surgical removal of one or more groups of lymph nodes. It is almost always performed as part of the surgical management of cancer. In a regional lymph node dissection, some of the lymph nodes in ...
, and omentectomy. The tumor is aggressive and spreads quickly into the
myometrium The myometrium is the middle layer of the uterine wall, consisting mainly of uterine smooth muscle cells (also called uterine myocytes) but also of supporting stromal and vascular tissue. Its main function is to induce uterine contractions. Stru ...
and the
lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lympha ...
. Thus even in presumed early stages, lymphadenectomy and omentectomy should be included in the surgical approach. If the tumor has spread surgery is cytoreductive followed by radiation therapy and/or chemotherapy. In a study to determine if adjuvant therapy should be used in patients with stage I uterine papillary serous carcinoma who had undergone surgery, no increased survival was seen when
radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...
was added versus observation, while the postsurgical treatment with chemotherapy may be beneficial but more data are needed. A study of the usefulness of
platinum Platinum is a chemical element; it has Symbol (chemistry), symbol Pt and atomic number 78. It is a density, dense, malleable, ductility, ductile, highly unreactive, precious metal, precious, silverish-white transition metal. Its name origina ...
-based chemotherapy as an adjuvant after surgery of stage I patients showed that patients with stage 1A who had no residual disease in the hysterectomy specimen had no recurrence regardless if chemotherapy was used or not, however, patients with stage 1A disease with residual disease in the hysterectomy specimen had no recurrence with platinum-based therapy, but those who had no such chemotherapy showed recurrence in 43%. Similarly, patients with stage 1B disease with chemotherapy had no recurrence, while those without chemotherapy had a high degree (77%) of recurrence.


Trastuzumab

In a recent study, about 60% of uterine serous carcinomas were found to overexpress the protein
HER2/neu Receptor tyrosine-protein kinase erbB-2 is a protein that normally resides in the membranes of cells and is encoded by the ''ERBB2'' gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The ...
—the same one that is overexpressed in some
breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...
s. The monoclonal antibody
trastuzumab Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together ...
(Herceptin) is currently being tested as a therapy for this subset of uterine serous carcinomas. The antibody
trastuzumab Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together ...
(Herceptin), which is used to treat breast cancers that overexpress the HER2/neu protein, has been tried with some success in a phase II trial in women with uterine papillary serous carcinomas that overexpress HER2/neu.


Prognosis

Prognosis of uterine papillary serous carcinoma is affected by age, stage, and histology as well as treatment.


References


External links

{{DEFAULTSORT:Uterine Serous Carcinoma Gynaecological cancer Rare cancers