Case Conference March 28th 2018

28-Mar-2018, Divisi Ginekologi Onkologi RSCM

 

 

Mrs. I, 42 years old, MR 4271515

 

Diagnostic approach in endometrial malignancy

 

 

 

Case Description

 

Mrs. I, 42 yo, P0A0 complained of vaginal bleeding since 3 years before. Patient went to Obgyn, in RS Juliana (on 2015 and 2016), had US exam and said she was in normal condition. She only got anti bleeding medicine from the doctors. Patient thought that her condition was normal, until on May 2017 she got vaginal bleeding for 1 month. She went to RS Juliana, had US exam, and doctor told her that she had myoma and they need to perform surgery (hysterectomy) to stop the bleeding. During surgery (October 2017) doctor told that there was also ovarian cyst from the right ovary, therefore the doctor decided to perform subtotal hysterectomy and right salpingo oophorectomy. The specimen was sent for histopathology examination with result: well differentiated endometrial adenocarcinoma, invasion to more than > ½ uterine wall. Patient then referred to RSF with endometrial cancer st IB. Due to unavailable radiotherapy in RSF she then referred to RSCM.  Patient already performed slide review and MRI examination in RSCM. There was no complain during October 2017-March 2018.

 

RS Juliana US exam:

 

 

Description by the Obgyn in RS Juliana:

 

-          Uterus size 9,6 x 6,06 cm

 

-          Endometrial line (+), thick

 

-          Adnexa within normal limit

 

Conclusion: uterine myoma.

 

 

 

Physical Exam February 8th 2018

 

CM. BP: 131/72 HR 84 bpm, RR 20x/m,  T:36 C, BW: 105 kg, BH: 156 cm. BMI: 43 kg/ m²: morbid obesity.

 

General status:

 

•       Eye: no anemic conjunctiva, no icteric sclera

 

•       No lymph nodes palpable

 

•       Lung: vesicular breath sound, no rhales nor wheezing

 

•       Cor: regular heart sound I-II, no murmur nor gallop

 

•       Abdomen:  supple, no pain on palpation

 

Gynecology status:

 

•              Inspection: calm vulva & external urethral orifice, no vaginal bleeding

 

•              Inspeculo: smooth portio, closed external ostium, flour, fluxus

 

•              RVT: smooth portio, no mass was palpated on cervical stump, both parametrium were loose, no mass palpable on both adnexa, no mass palpable intra rectal lumen.

 

 

 

Supporting data

 

Review of pathology slide February 12^th 2018:

 

Endometrioid carcinoma grade I of endometrium. Tumor invasion until surface the epithel and cervical stroma. No tumor mass was found on tube and ovary.

 

 

 

US exam February 9^th 2018:

 

Left hydrosalping with endometrioid possibility.

 

No mass and neovascularization found in abdominopelvic.

 

 

 

Chest x-ray February 8^th 2018 : cardiomegaly, both lungs within normal limit

 

 

 

Assesment:

 

Endometrial cancer stage IB

 

 

 

 

 

Clinical Question

 

How to predict an endometrial malignancy in AUB?

 

 

 

Introduction

 

In premenopausal or postmenopausal women with abnormal bleeding, malignancy must be excluded, specially for those who have the risk factor for either endometrial hyperplasia and endometrial carcinoma. Inadequate diagnostic will lead to unsatisfied management and result. The main purpose of endometrial assessment is to exclude carcinoma of the endometrium, and premalignant endometrial hyperplasia so we can avoid the development to become malignant.¹

 

 

 

Methods

 

Search strategy

 

The search was conducted on Pubmed, Science Direct and Clinical key on March 20^th, 2018 using the search tool containing the keywords Diagnostic AND Endometrial malignancy AND AUB (Table 1). Search results were filtered by the engine according to the following criteria: articles published in English language with human population, and last 5 years published articles. Search strategy, result, and the inclusion and exclusion criteria are shown in the flowchart (Figure 1).

 

 

 

Table 1. Search strategy used in Pubmed, Science Direct and Clinical Key conducted on March 20^th, 2018

 

 

 

Engine	Search Terms	Results
Pubmed   Science Direct   Clinical Key	Diagnostic AND Endometrial malignancy AND AUB   Diagnostic AND Endometrial malignancy AND AUB   Diagnostic AND Endometrial malignancy AND AUB	4   11   8

 

 

 

 

 

 

 

 

 

Figure 1. Flowchart of search strategy

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Selection

 

The titles of the filtered results from Pubmed, Science Direct, Clinical Key were screened using the inclusion criteria. A second screening was conducted by reading the abstract, and read the full text articles and finally 2 article were included.

 

 

 

Critical Appraisal

 

	Questions	Remark
Validity	·         Was the diagnostic test evaluated in a representative spectrum of patients (like those in whom it would be used in practice)? ·         Was the reference standard applied regardless if the index test result? ·         Was there an independent, blind comparison between the index test and a appropriate reference (gold) standard of diagnosis?	Yes       Yes     Yes
Importancy	What were the result?	Accuracy (Sensitivity, Spesifity, PPV and NPV) for endometrial assessment.
Applicability	Were the methods for performing the test described in sufficient detail to permit replication?	Yes

 

 

 

Discussion

 

In diagnosis AUB generally: a structured history, general examination, and exclusion of cervical and other causes of AUB has to be performed before imaging. Methods to investigate the endometrium include non-invasive and invasive procedures. ^2,3

 

Speculum examination and palpation should always be done first to exclude non-endometrial

 

gynaecological pathology. The main purpose of invasive methods is to obtain endometrial tissue for histological or cytological examination. ³

 

Non-invasive procedures relate to imaging. A structured image evaluation by TVS include description of the endometrial cavity, the myometrium, and ovaries are the most important first step to diagnose-structural abnormalities including malignancy (hyperplasia and cancer) in the uterus as a cause of abnormal bleeding.³ In assessing endometrium: endometrial thickness (ET), homogeneity, and endo-myometrial borders are evaluated. The endometrium is best visualized by trans-vaginal sonography, with the probe close to the endometrium. Most abnormalities can be diagnosed by a gynecologist in ultrasonography when a systematic approach is obtained in performing sonography, that is why ultrasound evaluation is dependent on the experience of the examiner, and nevertheless the equipment and the quality of visualization. ^2,3

 

Saline contrast sonohysterography is also relevant when investigating the cause of AUB, and useful for triage of patients for either blind biopsy or hysterocopic biopsies/resection, but it is not generally available in hospitals in Indonesia. In a meta-analysis including 2278 procedures, a sensitivity of 95% (95%CI 93–97%) and specificity 88% (95%CI 85–91%) for identifying focal lesions was reported. Implementation of 3D ultrasound has so far not increased the diagnostic performance of ultrasound in ruling out endometrial malignancy or in the specific diagnosis of focal lesions. The combination of 3D and power Doppler analysis allows an estimation of the vascularized endometrial volume and has been demonstrated to be superior to ET alone in ruling out endometrial malignancy. ³

 

Endometrial assessment is primarily indicated to diagnose or exclude endometrial cancer and its precursors: endometrial hyperplasia with or without atypia and the intra-epithelial neo- plasia. Diagnosing malignant and premalignant changes in the endometrium requires histology. For decades, dilatation and curettage (D&C) has been used for endometrial sampling. It is a simple procedure, yet  typically requires hospital admission. In more than half of examinations D&C samples less than 50% of the endometrial surface, and fails to detect approximately half (43–66%) of cases with hyperplasia. The sensitivity of DC is 46%, specificity of 100%, (positive predictive value PPV) of 100% and (negative predictive value

 

NPV) of 7.1%. ³

 

Hysteroscopy has the advantage of making visually guided biopsies possible and allows identification and removal of focal lesions in the uterine cavity. Hysteroscopy is regarded the golden standard for evaluation of the endometrial cavity. COH and hysteroscopy have the same high efficiency for exclusion of abnormalities in the endometrial cavity. In general the diagnostic specificity of hysteroscopy in cancer and other endometrial pathology is high (92% to 95.8%) as is sensitivity (78.4% to 98%).³

 

In any case it is suggested that women insufficiently diagnosed or with recurrent or persistent symptoms should be followed up e.g. after 6 months.

 

The second question is what investigation is recommended: a combination of transvaginal ultrasound (as there may be new pelvic pathology) and hysteroscopy to directly visualize the uterine cavity with biopsy appears to be advisable. It is also important to ensure that other causes of bleeding are excluded such atrophic vaginitis, cervical lesions, urinary tract or rectal bleeding. ³

 

When investigating the endometrium, factors such as patient history, age and menopausal age should be taken into account. Endometrial cancer is rare before the menopause, but when it occurs it is often found in patient with risk factors for endometrial cancer include unopposed oestrogen use, tamoxifen treatment, obesity, polycystic ovary syndrome (PCOS) and genetic factors.³

 

Based on the review above, some pitfalls that may found in this case is:

 

-          Inadequate endometrial assesment

 

-          Missed follow up of the high risk patient with persistent bleeding.

 

 

 

Conclusion

 

None of the available methods are perfect. Ultrasound evaluation is dependent on the experience of the examiner, the equipment and the quality of visualization. Hysteroscopy too is dependent on the examiner and the availability of the tools in rural hospital. Blind endometrial biopsy procedures often miss focal lesions. Thus re-examination is necessary when symptoms persist and no explanation for these has been identified.

 

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