- Update confirms survival benefit with trastuzumab in uterine serous carcinoma
- Confirmed benefit
- PFS, OS, and toxicity
- Uterine Sarcoma
- Types of Endometrial Cancer
- Endometrial Cancer Prevention
- Endometrial Cancer Symptoms
- Endometrial Cancer Diagnosis
- Endometrial Cancer Treatment
- The Importance of Second Opinions for Sarcoma
- Second Opinion of the Initial Diagnosis
- The Impact of the Diagnosis on the Treatment Plan
- Financial Assistance for Second Opinions
- Endometrial stromal sarcoma presenting as large bleeding left upper quadrant mass
- Clinical case
- Johns Hopkins Gazette | March 21, 2005
- Disparities seen in access to minimally invasive surgeries for uterine cancer
Update confirms survival benefit with trastuzumab in uterine serous carcinoma
Adding trastuzumab to carboplatin/paclitaxel improved survival in patients with advanced or recurrent HER2/Neu-positive uterine serous carcinoma (USC), according to an updated analysis from a phase 2 trial.
At a median follow-up of 25.9 months, the median progression-free survival (PFS) was 12.9 months in patients who received trastuzumab plus carboplatin/paclitaxel and 8.0 months in patients who received only carboplatin/paclitaxel. The median overall survival (OS) was 29.6 months and 24.4 months, respectively.
Amanda Nickles Fader, MD, of Johns Hopkins Medicine, Baltimore, and colleagues reported these findings in an abstract that was slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.
The phase 2 trial was designed to assess whether trastuzumab, a humanized monoclonal antibody that targets HER2/neu – a growth factor receptor found in almost all USC cases and overexpressed in 30% of cases – would improve survival in patients with USC, Dr. Nickles Fader explained in an interview. She noted that trastuzumab has been shown to provide benefit in breast cancer patients with HER2/neu overexpression.
“[U]terine serous carcinoma … is a very aggressive high-grade endometrial cancer subtype that is associated with really poor clinical outcomes and significant mortality,” Dr. Nickles Fader said. “It represents fewer than 10% of all uterine cancer cases, but it actually accounts for a disproportionate 40% of all deaths from uterine cancer.”
The overall survival among USC patients is about 45%, compared with 91% for more common lower-grade types of uterine cancers, she added.
“The conventional treatments for uterine serous carcinoma include surgery and then chemotherapy, but we’ve only really gotten so far by using a sort of one-size-fits-all treatment philosophy,” Dr. Nickles Fader said.
preliminary findings from the current trial (J Clin Oncol. 2018 Jul 10;36:2044-51), trastuzumab plus carboplatin/paclitaxel is now recognized as an alternative standard in treating advanced or recurrent HER2/Neu-positive USC, and this updated analysis confirms the benefits of adding trastuzumab, she said.
PFS, OS, and toxicity
There were 58 evaluable patients with primary stage III-IV or recurrent USC who were randomized to receive six cycles of carboplatin/paclitaxel alone or in combination with intravenous trastuzumab given until toxicity or progression.
The median PFS at a median follow-up of 25.9 months “very significantly favored” the trastuzumab arm, Dr. Nickles Fader said. The median PFS was 12.9 months in the trastuzumab arm and 8.0 months in the carboplatin/paclitaxel arm (hazard ratio, 0.46; P = .005).
In the 41 patients undergoing primary treatment, the median PFS was 17.7 months in the trastuzumab arm and 9.3 months in the control arm (HR, 0.44; P = .015). In the 17 patients with recurrent disease, the median PFS was 9.2 months and 7.0 months, respectively (HR, 0.12; P = .004).
“We were very pleased to see that there was also an overall survival benefit of about 5 months in the trastuzumab arm, compared to the control arm,” Dr. Nickles Fader said. The median OS was 29.6 months and 24.4 months, respectively (HR, 0.58; P = .046).
The PFS and OS benefit was “particularly striking” in the stage III-IV patients, according to Dr. Nickles Fader and colleagues. In this subgroup, the median OS was not reached in the trastuzumab arm, and it was 25.4 months in the control arm (HR, 0.49; P = .041).
Long-term toxicity did not differ between the treatment arms.
Endometrial cancer is the most commonly diagnosed gynecologic cancer. About 50,000 American women are diagnosed with the disease every year. Endometrial cancer is also the most common form of uterine cancer, so it is frequently referred to as uterine cancer.
What You Need to Know
- Endometrial cancer starts in the lining of the uterus — the endometrium.
- Being overweight or obese greatly increases a woman’s chance of developing endometrial cancer. Other risk factors include age, family history, a diagnosis of polycystic ovary syndrome and prior use of the breast cancer treatment drug tamoxifen.
- Symptoms include abnormal vaginal bleeding, pain during intercourse, difficult or painful urination, and pain in the pelvic area.
- Endometrial cancer is highly treatable when found early.
The lining of the uterus is called the endometrium. Cancer of the endometrium is the most common cancer of the female reproductive organs.
Cancer of the endometrium is different from cancer of the connective tissue or muscle of the uterus, which is called uterine sarcoma. About 80 percent of all endometrial cancers are adenocarcinomas. This means the cancer occurs in the cells that develop the glands in the endometrium. Endometrial cancer is highly curable when found early.
Uterine carcinosarcoma is a very rare type of uterine cancer, with characteristics of both endometrial cancer and uterine sarcoma. It is also known as a malignant mixed mesodermal tumor.
Types of Endometrial Cancer
Endometrial cancers are usually grouped into one of four categories:
- p53 mutation
- POLE mutation
- Copy number high
- Copy number low
Clinical trials are being used to assess treatments for cancers found within each of these groups, including novel immunotherapy trials.
Endometrial Cancer Prevention
The exact cause of endometrial cancer is not known. However, doctors believe that avoiding the known risk factors when possible, using oral contraceptives or other forms of hormonal birth control, controlling obesity and controlling diabetes are the best ways to lower the risk of developing endometrial cancer.
Endometrial Cancer Causes and Risk Factors
The following factors may increase a woman’s risk of developing endometrial cancer:
- Diet high in animal fat
- Family history of endometrial, ovarian and/or colon cancers (hereditary nonpolyposis colorectal cancer)
- Starting monthly periods before age 12
- Late menopause
- Infertility (inability to become pregnant)
- Never having children
- Being treated with tamoxifen for breast cancer
- Hormonal imbalance — having too much estrogen and not enough progesterone
- Estrogen replacement therapy for treatment of effects of menopause
- Personal history of breast cancer
- Personal history of ovarian cancer
- Prior radiation therapy for pelvic cancer
- Personal history of polycystic ovary syndrome or atypical endometrial hyperplasia
The risk for endometrial cancer increases as women get older, and it is most common in white women.
Endometrial Cancer Symptoms
Consult a doctor if you experience any/all of the following symptoms:
- Bleeding or discharge not related to your periods (menstruation) — over 90 percent of women diagnosed with endometrial cancer have abnormal vaginal bleeding
- Postmenopausal bleeding
- Difficult or painful urination
- Pain during intercourse
- Pain and/or mass in the pelvic area
Endometrial Cancer Diagnosis
Diagnosis of endometrial cancer includes a review of your medical history and a general physical exam. It may also include one or more of the following.
- Internal pelvic exam: This is done to feel for any lumps or changes in the shape of the uterus.
- Pap test (also called Pap smear): This test involves microscopic exam of cells collected from the cervix, used to detect changes that may be cancer or may lead to cancer and to show noncancerous conditions, such as infection or inflammation. However, the Pap test does not detect endometrial cancer.
- Endometrial biopsy: This procedure uses a small, flexible tube that is put into the uterus to collect an endometrial tissue sample. The sample is examined under a microscope to see if cancer or other abnormal cells are present. An endometrial biopsy procedure is often done in a doctor’s office.
- Dilation and curettage (also called D&C): Your doctor may recommend a D&C if an endometrial biopsy is not possible or if further diagnostic information is needed. This is a minor operation in which the cervix is dilated (opened) so that the cervical canal and uterine lining can be scraped with a curette (spoon-shaped instrument). The pathologist examines the tissue for cancer cells.
- Transvaginal ultrasound (also called ultrasonography): This ultrasound test uses a small instrument, called a transducer, which is placed in the vagina. The doctor may do a biopsy if the endometrium looks too thick.
Endometrial Cancer Treatment
Specific treatment for endometrial cancer will be determined by your doctor(s) :
- Your overall health and medical history
- Extent of the disease
- Your tolerance for specific medications, procedures or therapies
- Expectations for the course of the disease
- Your opinion or preference
The choice of treatment depends on the stage of cancer — whether it is only in the endometrium, or if it has spread to other parts of the uterus or body. Most people will be treated with surgery first. Some may need additional therapy. Generally, treatment for people with cancer of the endometrium includes one or more of the following.
- Hysterectomy — surgical removal of the uterus
- Salpingo-oophorectomy — surgery to remove the fallopian tubes and ovaries
- Pelvic lymph node dissection — removal of some lymph nodes from the pelvis
- Para-aortic lymphadenectomy — removal of lymph nodes that surround the aorta, the main artery of the heart
- Laparoscopic lymph node sampling — removal of lymph nodes through a narrow viewing tube called a laparoscope, which is inserted through a small incision (cut) in the abdomen (belly)
- Sentinel lymph node mapping — use of fluorescent imaging to identify potentially cancerous lymph nodes that would otherwise go undetected
- Radiation therapy: the use of X-rays, gamma rays and charged particles to fight cancer. Brachytherapy and external beam radiation are the most common radiation therapies used to treat endometrial cancer. Novel techniques in image-based brachytherapy with directed magnetic resonance (MR) guidance offer better patient outcomes and fewer side effects.
- Chemotherapy: the use of anticancer drugs to treat cancerous cells
- Immunotherapy: the process of activating the immune system’s natural ability to fight cancer
- Hormone therapy: medication or surgical procedures that interfere with hormone activity
Did you know that up to one-third of cancer deaths in women are attributed to excess body weight? Director of Gynecologic Oncology Amanda Fader and oncology dietitian Mary-Eve Brown discuss the correlation between the two. Learn what you can do to reduce your risk.
The Importance of Second Opinions for Sarcoma
Because sarcoma is a rare cancer, most physicians may only encounter a few instances of it in their lifetime, if any at all. Patients need to be diagnosed and treated by physicians and interdisciplinary teams that have experience with sarcomas.
If you are diagnosed with sarcoma, we encourage you to obtain a second opinion about your initial diagnosis and your proposed treatment plan from a sarcoma center. Good physicians are not offended when patients seek a second opinion about a rare cancer; it is fairly standard procedure.
Moreover, some insurance companies require a second opinion before they will reimburse costs for a proposed treatment plan.
Patients, family and caregivers dealing with cancer get advice from a lot of people.
They get advice about their eating habits (where to buy food, how to cook it, what’s healthy, and what’s not), their lifestyles (not enough of this, too much of that, too dangerous, too sedentary), the way they manage changes to their bodies (especially their hair! wig, no wig?) and how to settle their affairs (not just legally, but with the great beyond).
They also get advice regarding whether or not they should get a second opinion. While getting a second opinion is generally considered a useful thing to do, there is a common misconception that it is a time-consuming and possibly expensive activity that often produces no change to treatment plans or long-term prognosis.
However, several studies show that, for sarcoma patients, getting input from more than one medical professional can indeed make a difference, not only in medical decision-making, but also in the patient’s ultimate outcome.
This article examines evidence which proves the value of obtaining a second opinion from a sarcoma specialist at critical junctures in the diagnosis and treatment of sarcoma.
Second Opinion of the Initial Diagnosis
Once a lesion has been determined to be a tumor that requires further evaluation, the patient’s journey begins. Getting a precise clinical assessment and finding out the exact type of a tumor is essential in getting patients onto the right treatment path quickly. The ideal time for a second consultation is before any incision has been made into the tumor.
In a 2005 article “Surgical Management of Soft Tissue Tumors: Avoiding the Pitfalls,”Drs. Fritz and Frederick Eilber of the UCLA School of Medicine state that, “In the presence of any clinical features that raise the suspicion of a sarcoma, appropriate cross-sectional imaging and tissue diagnosis are critical in guiding additional care.
” They go on to specify that “CT-guided core biopsy is the best method to obtain an accurate tissue diagnosis.”1 Because the biopsy is guided by CT imaging, surgeons are able to collect samples with precision, improving the accuracy of the initial diagnosis.
1 The view that excisional biopsy is superior to needle biopsy is at best controversial and not reflective of practice at most major centers.
The authors of a study conducted by researchers at St Thomas Hospital in London, England link the use of excisional biopsies (in which an attempt is made to remove the entire lesion or tumor), instead of needle biopsies, to contamination of surrounding tissue, making it difficult to ensure that sufficient margins are achieved during initial surgery for soft tissue sarcoma.2
Further support for a second opinion of an initial diagnosis is found in a study of over 600 patients having sarcoma-related surgery at BG University Hospital Bergmannsheil in Bochum, Germany.
3 The researchers first note the difficulty in obtaining a definitive diagnosis for soft tissue sarcoma because there are so many different types, stating “approximately 50 different histological subtypes of soft tissue sarcomas have been described.
“3 The results of their study reveal how important it is that the diagnosing pathologist has experience with the pathology of sarcoma. The findings of expert second opinions agreed with those of the primary diagnosis, by non-expert pathologists, as follows:
|Academic Medical Centers||36.8%|
|Department of Pathology at BG University Hospital||70.5%|
These results make a striking case for review of initial diagnosis before treatment is selected. Regarding treatment, one popular web-based medical information resource, WebMD, lists a rare cancers diagnosis as the number one reason to see a specialist for a second opinion on the diagnosis. “After all,” the authors state “the diagnosis will determine which treatment is best.”4
Another very interesting study advocates for mandatory second opinions of the original tissue samples before any treatment is given. This study, “Mandatory Second Opinion Surgical Pathology at a Large Referral Hospital” was conducted at John Hopkins Medical Institution in Baltimore, MD.
In this study, a changed diagnosis was defined as one that “resulted in a significant change in therapy or prognosis.”5 It found not only that, “Of 6,171 cases reviewed, second opinion surgical pathology resulted in 86 changed diagnosis (1.
4%)”, but also estimates that “The financial benefit averaged $2-4 saved for every $1 spent to obtain the second opinion!”5
The studies discussed above certainly make the case that initial diagnoses can be wrong and should be double-checked. The question then becomes: what difference does it make if a sarcoma diagnosis is a bit off, maybe just in the determination of subtype or grade? How different are sarcoma treatment protocols? Are these differences significant? We will now address these questions.
The Impact of the Diagnosis on the Treatment Plan
Indeed, one significant risk of an incorrect or imprecise diagnosis is the impact on the treatment plan, including the choice to employ chemotherapy, whether to radiate, if and when to perform surgery and the surgical method to be used.
An area of particular concern is the risk of surgical error in the initial surgery done to remove the primary tumor.
In the study “Surgical Resection of Primary Soft-Tissue Sarcoma,” researchers from St Thomas’ Hospital in London examine records of patients who had previously undergone surgery to remove sarcoma tumors, but then had to have additional surgery because the initial surgery failed to remove all of the sarcoma cells from the area around the tumor.2 Of the patients studied, over 56% were found to have residual tumor and 33% had tumors visible to the naked eye.2 How does this happen?
What they found was that the first surgery had often used what is called a “shell out” procedure, done without having first obtained a complete pathological diagnosis.
2 They state “… the commonest reason was surgical excision without a prior biopsy for histological diagnosis, and … this had led to the use of a shell-out procedure.”2 The shell-out procedure is a surgical method used for benign tumors that are well-defined masses.
They’re easy to scoop out along the existing division between the tumor and the healthy tissue around it.
Because some sarcomas look as if they have clear boundaries, surgeons can get the misleading impression that the tumor is benign and that it can safely be removed along its borders without excising additional tissue around it.2 That study concludes, in part, that “surgical assessment of the adequacy of excision is very inaccurate and that most local recurrences are the consequence of inadequate primary surgery.”2
The National Comprehensive Cancer Network provides Clinical Practice Guidelines in Oncology, which are detailed yet concise planning documents that are extremely useful in understanding how decisions are made in the management of sarcoma therapy.
6-7 The guidelines cover the various activities and principles associated with sarcoma treatment, including initial diagnostic evaluation, primary treatment, pre- and post- surgical therapy, radiation therapy, chemotherapy, progressive and recurrent disease, and follow-up.
6 Unique guidelines exist for soft tissue sarcomas of the extremities, retroperitoneal/abdominal, intra-abdominal and desmoid types.6 For bone-related sarcomas, there are separate guidelines for chondrosarcoma, Ewing’s sarcoma, osteosarcoma, plus some variants.
7 Even a quick overview of these guidelines makes it clear that the assessments of the disease must be accurate in order for treatment these guidelines to be effective.
Financial Assistance for Second Opinions
Patients, caregivers and families grappling with the enormity of their diagnosis and the strain of day-to-day care may not believe they have the means or the energy to advocate on their own behalf and actively search for the best source(s) of a second opinion. However, help is available.
Sarcoma support groups are great resources to get up-to-date information from people who are familiar with the process.
They can help members locate local resources as well as connect each other with national programs that provide assistance with the costs of travel, lodging, and other expenses that insurance won’t cover.
A good example is the Sarcoma Alliance’s Hand in Hand program. This program “offers financial assistance for second opinion consultations by reimbursing expenses related to travel, phone bills, costs of the evaluation, and related expenses.”
Major sarcoma centers can supply information on the availability of free or discounted housing provided by organizations including The American Cancer Society's Hope Lodge, the Ronald McDonald Houses, and the local hotel industry.
Expenses (and patient stress!) can be further reduced when a working relationship is developed between a local oncology practice and a major sarcoma center. Sarcoma centers are often willing to provide the expert diagnosis and the treatment protocol, which can then be carried out closer to the patient’s home. For adults, outpatient treatment may also be an option.
In summarizing the results of the “Mandatory Second Opinion” study, John Hopkins researchers point out that “Although a policy of mandatory second opinion surgical pathology for referred patients makes good clinical and risk management sense …. current trends in medical economics has placed this and other quality assurance practice at possible risk.”5
From a caregiver perspective, this author sees that patients with a new sarcoma diagnosis need to be advised of the value of a second opinion on the diagnosis. There is always a great sense of urgency to begin treatment as soon as possible, so patients and their families may be wary of any delays.
They need to be assured that expedited communication between the diagnosing facility and a major sarcoma center regarding diagnosis will reduce the amount of time between diagnosis and treatment and this is time well spent. No patient can afford to lose time pursuing the wrong treatment due to incorrect diagnosis.
Remediating the effects of wrong treatments and procedures, after the mistake is recognized, cannot always be done.
by Elizabeth Goldstein-Rice Last revised: 12/2008
Last medical review: 12/2008
1. “Should Soft Tissue Sarcomas Be Treated at High-volume Centers? An Analysis of 4205 Patients”, by Juan C. Gutierrez, MD, Eduardo A. Perez, MD, Frederick L. Moffat, MD, Alan S. Livingstone, MD, Dido Franceschi, MD, and Leonidas G. Koniaris, MD, Annals of Surgery, Volume 245, Number 6, June 2007.
2. “Should Soft Tissue Sarcomas be Treated at a Specialist Centre?”, by A. A. Bhangu, J. A. S. Beard, and R. J. Grimer, Sarcoma, V. 8 (2004), Issue 1, Pages 1-6.
3. “Surgical Management of Soft Tissue Tumors: Avoiding the Pitfalls”, By Fritz C. Eilber, MD, and Frederick R. Eilber, MD, American Society of Clinical Oncology Educational Book. ASCO 2005.
4. “Delays in Referral of Soft Tissue Sarcomas”, by G. D. Johnson, G. Smith, A. Dramis, and R. J. Grimer, Sarcoma, V. 2008, Article ID 378574, 7 pages.
V5N6 ESUN. Copyright © 2008 Liddy Shriver Sarcoma Initiative.
Endometrial stromal sarcoma presenting as large bleeding left upper quadrant mass
Endometrial stromal tumors can be classified into three categories: endometrial stromal nodules, endometrial stromal sarcoma (ESS) and undifferentiated ESS (1). ESSs are rare, comprising only approximately 0.
2% of all uterine malignancies with an annual incidence of 1-2 per million women (2). Even fewer cases have been reported on patients presenting with symptomatic disease.
We report the case of an ESS in a young lady presenting with a large bleeding abdominal mass.
A 29-year-old African-American woman presented to the emergency department with complaints of abdominal pain, anorexia and weight loss. A CT scan revealed a mass that measured over 24 cm in the left upper quadrant that extended into the mid-abdomen and pelvis.
The mass abutted the greater curvature of the stomach; it had heterogeneous density with soft tissue components, neo-vascularity and elements of hemorrhage (Figure 1). The differential diagnosis included malignant gastrointestinal stromal tumor (GIST) arising from the stomach, retroperitoneal sarcoma (RPS), medullary carcinoma of the left kidney, and renal angiomyolipoma.
Because the clinical suspicion of a GIST or RPS was highest, a needle biopsy was performed but was not diagnostic.
Figure 1 CT with IV contrast in the axial (A) and coronal (B) planes showing a large left upper quadrant mass (arrows) with heterogeneous enhancement, ly due to hemorrhage and necrosis. The mass engulfs the pancreas (arrow heads) and markedly compresses the stomach (asterisk). The mass is intimately associated with the left kidney. Maximum intensity projection (C) reveals prominent arterial feeders form the aorta and left renal artery (arrow) and internal vascularity (arrow heads).
One week later a repeat biopsy was scheduled, however the patient presented at that time with worsening left upper quadrant pain radiating to the flank, associated with nausea, vomiting, night sweats, and fatigue. She was tachycardic and her hemoglobin was 5.5 g/dL.
The patient was urgently admitted to the intensive care unit, transfused, and stabilized. The patient was taken to the angiography suite where an on table CT confirmed a rupture, bleeding tumor. Embolization of the tumor mass, including occlusion of multiple feeding vessels from the left renal artery, was performed.
After further stabilization and optimization, the patient was taken to the operating room 2 days later. At the time of surgery, the mass involved multiple intra-abdominal structures and had ruptured through the transverse mesocolon with old blood in the pelvis.
An en bloc excision of the mass with a partial pancreatectomy, splenectomy, transverse colectomy, left nephrectomy, left adrenalectomy and resection of the diaphragm was performed.
The final pathology revealed a malignant spindle and epithelial cell neoplasm with features favoring a variant of ESS. Most of the tumor had features of low-grade malignant spindle cell neoplasm.
Some areas with greater nuclear atypia, mitotic index of up to 15 in 10 high power fields and epitheloid features as well as the presence of necrosis suggest a higher grade component.
This morphology and the diffuse expression of CD10 with variable estrogen receptor (ER) expression were characteristic of ESS with low-grade and high-grade components.
On immunohistochemistry the tumor was focally positive for Cyclin-D1, BCL-2 and CD99, while it was negative for progesterone receptor, EMA, AE/AE3, CAM5.2, PAX8, Inhibin, C-Kit, DOG-1, Melan-A, SOX10, GFAP, CD21, desmin, MDM2, Myogenin, CD34, MUC4, SMA, HMB45, ALK, S100 and beta-catenin (Figure 2).
Figure 2 Extra-uterine endometrial stromal sarcoma (ESS). (A) Hematoxylin and eosin stain. Most of the neoplasm was low-grade, composed of bland monotonous spindle cells (original magnification, ×20); (B) Hematoxylin and eosin stain. At high magnification the tumor cells show smooth nuclear membranes (original magnification, ×100); (C) Hematoxylin and eosin stain. This image shows a focus of the high-grade component at the lower left (original magnification, ×100); (D) Hematoxylin and eosin stain. The nuclei in the high-grade component are enlarged compared to those in the low-grade component. There is a mitosis in the center of the field. Since this is a translocation sarcoma, mitoses are normal (original magnification, ×100); (E) CD10 stain. There is diffuse strong cytoplasmic labeling (original magnification, ×20); (F) extra-uterine ESS, estrogen receptor (ER) stain. There is strong nuclear expression. The nuclei of vascular endothelial cells in the lower part of the field serve as internal negative controls (original magnification, ×20).
The patient was referred to gynecologic oncology. She had a normal pelvic physical exam, as well as a pelvic MRI that demonstrated no evidence of a primary uterine tumor. Due to the concern of an occult primary uterine cancer, a hysterectomy was recommended, as well as adjuvant chemotherapy with hormonal therapy.
The differential diagnosis of left upper quadrant tumors typically should include GIST, RPS, or lesions involving the pancreas, adrenal or kidney. Given the size, location, and involvement of other structures, obtaining a preoperative diagnosis may be helpful.
Specifically, patients diagnosed with advanced GIST or RPS tumors may benefit from neo-adjuvant treatment (3,4).
Other diagnostic possibilities included medullary renal cancer, which can be associated with sickle cell anemia (5), or AML, which can present with retroperitoneal hemorrhage known as Wunderlich syndrome (6).
ESS is one of the rarest gynecological tumors, representing only 0.2% of all uterine cancers. While the risk factors associated with ESS are poorly defined, African-American women have been noted to be 2 times more ly to get these rare uterine cancers (7).
While women with primary ESS may present with pelvic pain and uterine bleeding, “extra-uterine” ESS is a much more uncommon initial presentation of disease. Moreover, the retroperitoneal hemorrhage is another uncommon manifestation for ESS.
The prognosis of patients with ESS can be varied. Patients with ESS can be low-grade, which tends to be indolent, or high-grade (as in the current case), which can be more aggressive.
Adjuvant therapy typically may include hormone therapy with medroxy progesterone, tamoxifen, gonadotropin releasing hormone analogues and aromatase inhibitors (8).
This case highlights how ESS can present in an atypical fashion as an intra-abdominal mass, as well as the importance of a multi-disciplinary treatment approach for patients with this disease.
- The differential diagnosis a left upper quadrant mass typically should include GIST, RPS, or lesions involving the pancreas, adrenal or kidney. ESS can, however, present as an intra-abdominal mass extending in the abdominal cavity;
- Patients with a bleeding intra-abdominal mass are often served best with stabilization, embolization of the bleeding mass, and interval surgical resection;
- An interdisciplinary approach to patients with ESS is critical in managing this rare entity.
Conflicts of Interest: The authors have no conflicts of interest to declare.
Informed Consent: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the editor-in-chief of this journal.
- Rauh-Hain JA, del Carmen MG. Endometrial stromal sarcoma: a systematic review. Obstet Gynecol 2013;122:676-83. [PubMed]
- Hendrickson MR, Tavassoli FA, Kempson RL, et al. Mesenchymal tumors and related lesions. In: Tavassoli FA, Devilee P, editors. World Health Organization Classification of Tumors.
Pathology and Genetics of Tumors of the Breast and Female Genital Organs. Lyon: IARC Press, 2003:233-44.
- Yang W, Yu J, Gao Y, et al. Preoperative imatinib facilitates complete resection of locally advanced primary GIST by a less invasive procedure. Med Oncol 2014;31:133. [PubMed]
- Pawlik TM, Vauthey JN, Abdalla EK, et al.
Results of a single-center experience with resection and ablation for sarcoma metastatic to the liver. Arch Surg 2006;141:537-43; discussion 543-4. [PubMed]
- Daher P, Bourgi A, Riachy E, et al. Renal medullary carcinoma in a white adolescent with sickle cell trait. J Pediatr Hematol Oncol 2014;36:e285-9.
- Bissler JJ, Kingswood JC. Renal angiomyolipomata. Kidney Int 2004;66:924-34. [PubMed]
- Sherman ME, Devesa SS. Analysis of racial differences in incidence, survival, and mortality for malignant tumors of the uterine corpus. Cancer 2003;98:176-86. [PubMed]
- Linder T, Pink D, Kretzschmar A, et al.
Hormone treatment of endometrial stromal sarcomas: A possible indication for aromatase inhibitors. J Clin Oncol 2005;23:abstr 9057.
Cite this article as: Spolverato G, Montgomery E, Kamel I, Pawlik TM. Endometrial stromal sarcoma presenting as large bleeding left upper quadrant mass.
Hepatobiliary Surg Nutr 2015;4(5):363-366. doi: 10.3978/j.issn.2304-3881.2015.06.04
Johns Hopkins Gazette | March 21, 2005
Johns Hopkins Medicine has opened a new center for treating and investigating the causes of uterine fibroids, a medical condition that afflicts millions of American women.
The center will specialize in state-of-the-art therapies for the condition and in the rapid application of new research to the treatment of these mostly benign growths of the wall of the uterus.
Fibroids, which can vary in number and range in size from as small as a pea to as large as a grapefruit or small melon, may result in excessive bleeding, anemia, infertility and excessive pressure on the bladder and bowel. An estimated one-third of the 600,000 hysterectomies performed each year in the United States are due to fibroids.
“Linking clinical practice to medical research is the best way we have of determining why fibroids affect some women and not others, and in deciding when to intervene medically or surgically,” said gynecologic surgeon John Griffith, an assistant professor at the School of Medicine and director of the new Fibroid Center, which is located at Johns Hopkins facilities at Green Spring Station. “We anticipate using the vast epidemiological and genetics expertise at Hopkins to learn more about why fibroids disproportionately afflict more black American women. We also hope to be able to predict growth patterns so that there will be less of an impact on childbearing.
Johns Hopkins' research-based resources distinguish its program from others in the field, said Griffith, who will lead a team of a dozen faculty and 40 staff that includes interventional radiologists, reproductive endocrinologists, geneticists, nurses and public health experts.
On the treatment side, the Hopkins team will emphasize minimally invasive techniques that focus on removing or shrinking fibroids instead of surgically removing the entire uterus. Particular attention will be paid to preserving the uterus for women who have not completed childbearing.
The cause of fibroids is unknown, but excess estrogen is believed to play a role in their development, and hormone therapy is often used to shrink tumors.
“For benign fibroids, many women undergo hysterectomy, the most common abdominal surgery for women in the United States, said interventional radiologist Hyun Kevin Kim, an assistant professor. “Our goal is to develop and offer new, minimally invasive therapies for women.”
Kim added that laparoscopic, or minimally invasive, procedures are the current trend, allowing physicians to shrink fibroids and avoid the complications, inconvenience and pain associated with open surgical options.
Uterine artery embolization is one such procedure, in which tiny plastic pellets are used to block blood flow to the fibroid tumors, starving them of nutrients and oxygen. The pellets are implanted using a thin catheter threaded from the groin to the uterine arteries.
Although embolization requires pain medication and an overnight hospital stay, the recovery period lasts slightly longer than one week.
Another current treatment option uses ultrasound energy to shrink fibroid tumors. Magnetic resonance imaging is used to guide the focused ultrasound therapy to fibers of the tumor. Although the procedure can require the patient to spend up to three hours in the MRI, there are no incisions or hospital stayovers.
Griffith said that the goal of the Hopkins center is to conduct evidence-based research comparing treatment to determine which procedure is best for particular women. No definitive answer to what should be done currently exists, he said, either for patients or physicians.
More information about Hopkins Fibroid Cen-ter and its services is available at womenshealth.jhmi.edu/gyn/conditions/fibroids.html.
Disparities seen in access to minimally invasive surgeries for uterine cancer
Despite years of evidence showing the advantages of minimally invasive hysterectomies, access to the surgeries remains limited for uterine cancer patients nationwide—particularly for poor and minority women.
A recent study by Johns Hopkins researchers revealed wide racial and economic disparities in access to minimally invasive surgeries for hysterectomies in treating uterine cancer. Additionally, the study found that hospitals categorized as “low-volume” performed the surgeries very rarely. The findings are published in the January 2016 issue of Obstetrics and Gynecology.
More than 54,000 women are diagnosed with uterine cancer each year in the U.S., the researchers say, and surgery alone cures 60 to 70 percent of women with early-stage disease.
Over the last decade, a number of medical experts have considered minimally invasive procedures to be the standard of care for nonmetastatic uterine cancer.
Research has demonstrated that minimally invasive hysterectomies (either laparoscopic or robotic-assisted surgeries) result in fewer complications, higher quality of life, and equal rates of survival when compared to open procedures that call for making large surgical incisions into the abdomen.
Researchers found that open hysterectomies requiring large incisions were more than twice as ly as minimally invasive surgeries to result in complications such as infections, pneumonia, blood clots, major blood loss, and longer hospital stays.
The Hopkins team analyzed data from more than 1,000 hospitals in 45 states, on 32,560 patients who underwent either minimally invasive hysterectomies or open hysterectomies for uterine cancer between 2007 and 2011. Researchers saw that 33.6 percent of patients who underwent surgery for nonmetastatic uterine cancer had minimally invasive surgeries, with the percentage rising from 22 percent in 2007 to 50.8 percent in 2011.
“We were encouraged to see that utilization of minimally invasive surgery for endometrial cancer rose significantly since 2007, but we still have a long way to go to provide most patients access to these procedures,” says Amanda Fader, director of the Johns Hopkins Kelly Gynecologic Oncology Service and member of The Sidney Kimmel Comprehensive Cancer Center.
Fader's team found that black and Hispanic women were less ly to receive minimally invasive surgeries, along with patients who were on Medicaid or uninsured. In addition, the study revealed that minimally invasive procedures occurred only 23.
6 percent of the time in hospitals considered low-volume, which in this sampling performed fewer than 10 hysterectomies for uterine cancer annually.
In contrast, patients treated at medium- and high-volume hospitals were up to four times as ly to undergo minimally invasive procedures.
“At Johns Hopkins, we perform minimally invasive surgeries in approximately 91 percent of early-stage endometrial cancers,” Fader says. “A small percentage of women with a very large uterus or severe cardiopulmonary disease may not be able to undergo minimally invasive procedures, but this is rare.”
Fader notes that the proliferation of robotic surgical equipment in hospitals has helped to increase minimally invasive surgeries, but she places less importance on whether a surgeon uses a robot or traditional laparoscopy.
“The goal is to increase the overall rate of minimally invasive surgery for these patients, irrespective of the specific type of procedure offered,” she says.
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cancer, women's health