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Kornhauser Health Sciences Library

Greer Manning: The Case

Problem Based Learning guide for 1st Year medical students.

 

The Case

 

Greer Manning is a 46-year-old female patient who is seen at her OB/GYN office for her annual well woman physical exam with Dr. Pfyfe. Her OB’s office has started using a new online patient portal where patients can fill out their family medical history ahead of time.

Ms. Manning fills it out and describes the following family history:

  • Mother-uterine cancer, age 50, colon polyp diagnosed age 65, and basal cell carcinoma, age 70
  • Maternal aunt-colon polyp, age 58
  • Maternal cousin, leukemia, age 2 years
  • Maternal grandfather, colon cancer, age 55
  • Maternal grandmother, breast cancer, age 70
  • Paternal uncle, kidney cancer, age 70

 

She has no complaints and no new symptoms. Her pelvic examination and Pap smear have been completed on a routine basis.

Her personal medical history is reviewed in light of her family history, and Dr. Pfyfe confirms that Ms. Manning had a history of an abnormal Pap smear 15 years ago treated with cryotherapy and has had normal Pap smears since.

She has had multiple miscarriages in the 6- to 8-week gestation range and attempted in-vitro fertilization twice ten years ago without carrying a pregnancy to term. She has not had any abnormal bleeding and has regular monthly periods. She took combination oral contraceptives in her twenties but stopped around the age of 30. She smokes several cigarettes a day and drinks about 7 alcoholic beverages a week.

 

A week after this visit, Ms. Manning receives a call from the OB’s office asking her to come in for an appointment that week to discuss abnormal results on her Pap smear. When she meets with Dr. Pfyfe, she tells her that she had an abnormal type of cell on her Pap smear that raises concern for endometrial health. Ms. Manning asks what kind of cell and the OB shows her the report, which says “atypical glandular cells seen, evaluation of endometrial neoplasia recommended.” Dr. Pfyfe explains that the significance of the finding will not be known unless additional tests are performed, and sets up an appointment for the patient to have cervical cone biopsy with dilation and endometrial curettage in the operating room. This procedure is performed a week later and the specimens are sent for pathologic analysis.

Results return in one week. The cone biopsy pathology report shows chronic cervicitis and squamous metaplasia. The endocervical curettage pathology report shows dysplastic glandular mucosa, and the endometrial curettage pathology shows moderately differentiated adenocarcinoma, with positive staining for estrogen- and progesterone-receptor proteins.

 

Dr. Pfyfe meets with Ms. Manning at the follow-up visit for her procedure and discusses this new diagnosis with her. Ms. Manning is shocked and tearful and asks several questions about what to expect. Dr. Pfyfe explains that with a new diagnosis of cancer, the priority is to complete a search to see if the cancer has had a chance to spread into the walls of the uterus or outside of the uterus.  Since her cancer has progesterone and estrogen receptors, Dr. Pfyfe also recommends that an additional surgery be done to remove her ovaries and then use medications to block the receptors on the tumor for these hormones. This type of care requires a specialist, so Ms. Manning has an appointment made with Dr. Parker, a gynecologic oncologist, to help complete the next steps in her care.

Ms. Manning meets with Dr. Parker the following week, tearfully telling her that it has only been a month since she went to her regular annual visit thinking nothing was wrong. Dr. Parker is very kind but gets down to business, reviewing her family and personal history and performing a pelvic examination. She explains to Ms. Manning that more diagnostic testing is needed to see the extent of surgery required and if additional treatment with chemotherapy or radiation might be needed, as well as to measure her baseline health.

 

Dr. Parker orders a CT of the chest, abdomen, and pelvis as well as an EKG, complete blood count (CBC), comprehensive metabolic panel (CMP), and coagulation profile.

Ms. Manning follows up the next week and receives further bad news. There is a 3 x 2 cm lesion in a lobe of the liver concerning for possible metastatic disease, as well as heterogeneous enhancing mass of the lower uterine segment extending into the endocervix and overall uterine enlargement. Dr. Parker shows Ms. Manning images from her CT scan that show the abnormal appearance of her uterus.

She also notes that Ms. Manning has a microcytic anemia, with a hemoglobin of 9.5 and an MCV of 67. Review of prior blood work from two years ago shows this is a new finding. She tells Ms. Manning that since she has a normal diet and no history of heavy periods or other source of blood loss, she wants her to get an evaluation by a gastroenterologist, Dr. Frazier, before any surgery is planned.

Dr. Frazier has an appointment available a couple of days later, and meets with Ms. Manning. She is scheduled for an esophagogastroduodenoscopy (EGD) and a colonoscopy the following week. When she wakes up from these procedures, Dr. Frazier tells her that there was a partially-obstructing mass of the mid-descending colon, about 3 cm in size, that he biopsied and is very suspicious for colon cancer based on its general appearance and her newly diagnosed anemia. Her procedures did not reveal any polyps or other abnormalities. The  gastroenterologist orders a CA-125 level to be drawn that day and refers her to Dr. Snell, a general surgeon, to follow up on the results and plan a possible surgery in conjunction with Dr. Parker.

Dr. Frazier calls Ms. Manning 2 days later and confirms that the biopsy returned positive for a low-grade adenocarcinoma of the colon and that her CA-125 level is 93 (normal range is 0-35). He tells her this means she has an additional diagnosis of a second cancer and that he is very concerned about the lesion in her liver possibly being a metastatic colon cancer. Ms. Manning is devastated and submits paperwork for an unpaid medical leave from work as a teacher for the public-school system, which is approved since she is missing work multiple times a week to follow up on medical tests and procedures. Dr. Parker and Dr. Snell discuss Ms. Manning’s care and present a plan for a team surgery that will consist of a hysterectomy and bilateral salpingo-oophorectomy, partial colectomy with temporary colostomy, and abdominal cavity and lymph node exploration. Ms. Manning consents to the surgery and undergoes surgery two weeks later, 9 weeks after her initial visit to the OB/GYN. Her surgery goes as expected, and her liver lesion is also biopsied during the operation.

The pathology report and appearance of the surgical specimens is shown.

Pathological examination of the uterus and cervix: stage IB invasive endometrial adenocarcinoma (endometrioid histologic subtype), with squamous metaplasia.

Pathologic examination of the ovaries: shows stage 1B serous adenocarcinoma, low grade, with endometriosis in both ovaries.

Pathologic examination of the colon resection: low-grade adenocarcinoma of the descending colon, 2.5 cm in diameter, extending into the muscularis propria but not into the subserosa. Surrounding lymphocytic infiltrate.

low power view

higher power view

Cytological examinations of regional lymph nodes and pelvic washings were negative for carcinoma, and her liver biopsy was found to be an adenoma requiring no additional follow-up.

 

Ms. Manning recovers from her surgery well and meets with her doctors in follow-up. They recommend genetic evaluation for a possible underlying cause for her multiple simultaneous cancers. Ms. Manning is evaluated by Dr. Hersh, a geneticist with the Adult Genetic Diseases program at UofL. He creates a family pedigree and then tells her that based on her family and personal history, she meets criteria for a diagnosis of a genetic cancer syndrome and he recommends genetic confirmatory testing. He offers two forms of testing:

  1. Testing of the tumor tissue to look for patterns typical for specific forms of familial cancer.
  2. Direct genetic analysis of a blood sample to test for the specific genes she may have inherited that increased her risk for cancer.

Dr. Hersh explains that the first form of testing will confirm that HNPCC mechanisms were responsible for the formation of her specific colon cancer. The second form of germline testing will help identify the specific gene in her family and give other family members the option to get tested for the disorder.

Histological studies revealed reduced expression of MSH2 in tumors relative to adjacent healthy tissue. Tumor tissue also showed a reduction in MSH6 expression, whereas the expression of MLH1 was comparable in tumors relative to healthy tissue. Testing for microsatellite instability showed high instability in the samples of the endometrial and colonic tumors. (see below)

Analysis of Ms. Manning’s blood sample showed a loss-of-function germline mutation 942+3AT in the MSH2 gene, consistent with it being the pathogenic lesion in Ms. Manning and her affected family members.

Ms. Manning asks what this information means to her in terms of risk of future additional cancer, or cancer recurrence. She also asks what these findings mean to her family members and if they need to get tested or take any special precautions.

Clinical Librarian

Ansley Stuart's picture
Ansley Stuart
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