Low-volume lymphatic metastasis (isolated tumor cells) in endometrial cancer: management and prognosis

BackgroundThere is a strong correlation between disease mortality and the depth of myometrial invasion in stage I endometrial cancer (EC). Current assessment of the depth of invasion relies on light microscopy. Tumor cells can evade detection by light microscopy if they are vastly outnumbered by myometrial cells. Immunohistochemical (IHC) techniques against pancytokeratins (PCKs) have a great potential in the detection of such isolated cells.ObjectivesTo investigate the application of IHC techniques in the identification of isolated infiltrating tumor cells within myometrium and assess its significance in clinically stage I EC.MethodsA single representative tissue block containing the deepest myometrial invasion by the tumor was selected for 90 patients with stage I EC. Sections from each block were immunostained in accordance with established streptavidin–biotin peroxidase method using a mouse monoclonal antikeratin clone AE1/AE3. Myometrium was re-examined to identify deeper myometrial invasion that had escaped detection on hematoxylin and eosin (H&E) section. The clinical records were reviewed, and following data were collected: age, race, parity, presentation, associated medical disorders (obesity, diabetes, and hypertension), use of tamoxifen or hormone replacement therapy, menopausal state, recurrence, and survival.ResultsOf 90 cases, deeper myometrial invasion was detected on IHC sections in seven cases (7.7%). In five of these seven cases, isolated tumor cells surrounded by inflammatory cells were noted 0.2–1.2 mm deeper within the myometrium than that detected by H&E staining. In the remaining two cases, the deeper extension seen was the result of examining serial levels through the tumor block; in these cases, deeper infiltration should have been apparent on H&E sections. Follow-up data was available in 72 of the 90 cases. A trend was noted between the presence of isolated tumor cells deeper within myometrium on IHC and tumor recurrence (P = 0.056). The 2-year recurrence-free survival was 40% for the group with IHC evidence of deeper invasion compared with 89% for the group without (P = 0.005). Similarly, analysis of cause-specific and overall survival revealed significant differences between the two groups (P = 0.038 and P = 0.026, respectively).ConclusionsIn this study, we have shown that it is possible to identify deeper level of myometrial invasion by tumor cells using an IHC technique. IHC-detected deeper invasion is an uncommon event and may be a feature of more aggressive tumors with greater potential for recurrence and lower survival.

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Sentinel lymph node (SLN) isolated tumor cells (ITCs) in otherwise stage I/II endometrioid endometrial cancer: To treat or not to treat?

Gynecologic Oncology ◽

10.1016/j.ygyno.2021.02.017 ◽

2021 ◽

Author(s):

F.J. Backes ◽

A.S. Felix ◽

M. Plante ◽

J. Grégoire ◽

S.A. Sullivan ◽

...

Keyword(s):

Endometrial Cancer ◽

Lymph Node ◽

Sentinel Lymph Node ◽

Tumor Cells ◽

Stage I ◽

Isolated Tumor Cells ◽

Endometrioid Endometrial Cancer

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Factors influencing the adoption of the sentinel lymph node technique for endometrial cancer staging: an international survey of gynecologic oncologists

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2018-000020 ◽

2019 ◽

Vol 29 (1) ◽

pp. 60-67 ◽

Cited By ~ 10

Author(s):

Jvan Casarin ◽

Francesco Multinu ◽

Nadeem Abu-Rustum ◽

David Cibula ◽

William A Cliby ◽

...

Keyword(s):

Endometrial Cancer ◽

Lymph Node ◽

High Risk ◽

Sentinel Lymph Node ◽

Tumor Cells ◽

Gynecologic Oncology ◽

Gynecologic Cancer ◽

Cancer Staging ◽

Isolated Tumor Cells ◽

Factors Influencing

ObjectiveTo explore the factors influencing adoption of the sentinel lymph node (SLN) technique for endometrial cancer staging among gynecologic oncologists.MethodsA self-administered, web-based survey was sent via email (April 20 through May 21, 2017) to all members of European Society of Gynecologic Oncologists, International Gynecologic Cancer Society, and Society of Gynecologic Oncologists. Surgical and pathologic practices related to SLN and reasons for not adopting this technique were investigated.ResultsOverall, 489 attending physicians or consultants in gynecologic oncology from 69 countries responded: 201 (41.1%), 118 (24.1%), and 117 (23.9%) from Europe, the USA, and other countries, respectively (10.8% did not report a country). SLN was adopted by 246 (50.3%) respondents, with 93.1% injecting the cervix and 62.6 % using indocyanine green dye. The National Comprehensive Cancer Network SLN algorithm was followed by 160 (65.0%) respondents (USA 74.4%, Europe 55.4%, other countries 71.4%). However, 66.7% completed a backup lymphadenectomy in high-risk patients. When SLN biopsy revealed isolated tumor cells, 13.8% of respondents recommended adjuvant therapy. This percentage increased to 52% if micrometastases were detected. Among the 243 not adopting SLN, 50.2% cited lack of evidence and 45.3% stated that inadequate instrumentation fueled their decisions.ConclusionsSLN with a cervical injection is gaining widespread acceptance for staging of endometrial cancer among gynecologic oncologists worldwide. Standardization of the surgical approach with the National Comprehensive Care Network algorithm is applied by most users. Management of isolated tumor cells and the role of backup lymphadenectomy for ‘high-risk’ cases remain areas of investigation.

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OUTCOME OF ISOLATED TUMOR CELLS (ITC) IDENTIFIED BY SENTINEL LYMPH NODE MAPPING IN ENDOMETRIAL CANCER

10.26226/morressier.5770e29ed462b80290b4c6e8 ◽

2016 ◽

Author(s):

jonathan stanleigh

Keyword(s):

Endometrial Cancer ◽

Lymph Node ◽

Sentinel Lymph Node ◽

Tumor Cells ◽

Sentinel Lymph Node Mapping ◽

Isolated Tumor Cells ◽

Lymph Node Mapping

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Recurrence Risk of Occult Micrometastases and Isolated Tumor Cells in Early Stage Endometrial Cancer: A Case Control Study

Gynecologic Oncology Reports ◽

10.1016/j.gore.2021.100846 ◽

2021 ◽

pp. 100846

Author(s):

Tara CASTELLANO ◽

Lewis HASSELL ◽

Rachel CONRAD ◽

Conner S. DAVEY ◽

Sunam HUSAIN ◽

...

Keyword(s):

Endometrial Cancer ◽

Tumor Cells ◽

Case Control Study ◽

Early Stage ◽

Recurrence Risk ◽

Case Control ◽

Isolated Tumor Cells ◽

Early Stage Endometrial Cancer ◽

Control Study

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Endometrial cancer patients have a significant risk of harboring isolated tumor cells in histologically negative lymph nodes

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200605000-00058 ◽

2006 ◽

Vol 16 (3) ◽

pp. 1336-1341 ◽

Cited By ~ 3

Author(s):

C. A. Amezcua ◽

H. R. Macdonald ◽

C. A. Lum ◽

W. Yi ◽

L. I. Muderspach ◽

...

Keyword(s):

Endometrial Cancer ◽

Lymph Nodes ◽

Cancer Patients ◽

Tumor Cells ◽

Significant Proportion ◽

Significant Risk ◽

Isolated Tumor Cells ◽

Regional Lymph Nodes ◽

Alive With Disease ◽

Negative Lymph Nodes

In this study, we examine the prevalence of finding isolated tumor cells (ITCs) in negative lymph nodes of endometrial cancer patients using immunohistochemistry. Seventy-six endometrial cancer patients with lymph nodes histologically negative for metastatic disease were examined. Nodal tissue sections were stained with anticytokeratin antibodies AE-1 and CAM 5.2. Nodes with single or groups of cells (two to four cells) ≤0.2 mm and showing cytokeratin reactivity were positive for ITCs. Findings were compared to features of the primary tumor and patient outcome. ITCs were present in 31 of 1712 lymph nodes. Fifteen (19.7%) patients had ITC-positive nodes. ITCs involved only pelvic nodes in nine cases, only para-aortic nodes in five cases, and pelvic and para-aortic in one case. Tumor in adnexa was the only pathologic feature associated with nodal ITCs (P = 0.0485). All 15 patients with nodal ITCs were alive at follow-up. One (6.7%) patient suffered recurrent disease but was alive at last encounter. Disease recurred in 5 (8.8%) of 57 patients without nodal ITCs. Two are alive without disease, two alive with disease, and one died from her cancer. In summary, a significant proportion of endometrial cancer patients have ITCs detected by immunohistochemistry in histologically negative regional lymph nodes.

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Low-Volume Lymph Node Metastases in Endometrial Carcinoma

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001016 ◽

2017 ◽

Vol 27 (6) ◽

pp. 1165-1170 ◽

Cited By ~ 10

Author(s):

Lani K. Clinton ◽

Jordan Kondo ◽

Michael E. Carney ◽

Pamela Tauchi-Nishi ◽

Keith Terada ◽

...

Keyword(s):

Lymph Node ◽

Lymph Nodes ◽

Endometrial Carcinoma ◽

Tumor Cells ◽

Detection Rate ◽

Myometrial Invasion ◽

Isolated Tumor Cells ◽

Metastatic Deposit ◽

Node Metastases ◽

Low Volume

ObjectiveThe aim of this study was to determine the histopathologic characteristics of patients with endometrial carcinoma with low-volume metastases (micrometastases and isolated tumor cells) compared with macrometastases.MethodsWe performed a retrospective review of patients with endometrial carcinoma.ResultsAmong 350 robotic-assisted hysterectomies for endometrial cancer, 187 (53%) underwent attempted sentinel lymph node (SLN) biopsy. At least 1 SLN was detected in 185, a 99% overall detection rate; 108 (58%) also had non-SLNs removed. Among 91 patients with SLNs and non-SLNs from the ipsilateral hemipelvis, both were negative in 74 (81%) and positive in 7 (8%), and 10 (11%) had a positive SLN with negative non-SLNs. Among 17 patients with SLNs and non-SLNs from the contralateral hemipelvis, both were negative in 12 (71%), both were positive in 3 (18%), and 2 patients (12%) had negative SLNs with contralateral positive non-SLNs. Among 79 patients with only a SLN dissection, 4 (5%) were positive; among 69 patients with only a non-SLN dissection, 14 (20%) had positive lymph nodes. Among 24 patients with metastatic SLNs, 9 (38%) had isolated tumor cells, 3 (13%) had micrometastases, and 12 (50%) had macrometastases. Among the 40 total patients with metastatic lymph nodes, low-volume metastases represented the largest metastatic deposit in one third of patients, all of which had SLN dissection. All 12 with low-volume metastases had endometrioid histology compared with less than half (46%) of those with macrometastases (P < 0.01). Grade 1 carcinoma was present in 7 (58%) of the patients with low-volume metastases compared with 4 (14%) of those with macrometastases (P < 0.01) Furthermore, significantly more patients with low-volume metastases versus macrometastases had less than 50% myometrial invasion (67% vs 4%, P < 0.001).ConclusionsLow-volume disease was present in one third of patients with nodal metastases, the largest metastatic deposit only in patients who had SLN dissection; these patients were significantly more likely to have grade 1 endometrioid carcinoma with less than 50% myometrial invasion, traditional “low-risk” features.

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