Successful management of cutaneous lymphangitis carcinomatosa arising from cervical cancer with paclitaxel-cisplatin and bevacizumab combination therapy: a case report and review of the literature
Globally, cervical cancer is the fourth most common cancer in women. Here, we report a case of cutaneous lymphangitis carcinomatosa arising from cervical cancer, an extremely rare and treatment-resistant condition.
A 64-year-old Japanese woman presented with genital bleeding. She was diagnosed as having stage IB1 squamous cell cervical cancer and subsequently treated with radiotherapy. Approximately 2 years after the curative radiotherapy, she developed itching, skin rash, and small nodules on her left femoral and pubic area. Slight 18F-fluorodeoxyglucose uptake was detected at her left femoral skin on positron emission tomography with computed tomography. A histopathological examination was performed on a biopsy sample from an erythematous macule on her left femoral skin and vulva. Consequently, she was diagnosed as having cutaneous lymphangitis carcinomatosa arising from cervical cancer. Paclitaxel (135 mg/m2), cisplatin (50 mg/m2), and bevacizumab (15 mg/kg) combination therapy was administered every 21 days. Both itching and rash improved after three treatment cycles. After the completion of six cycles, skin erythema in the femoral and vulval area disappeared completely. Our patient experienced a 25-month symptom-free interval after the last chemotherapy session.
Our findings suggest that combination chemotherapy plus bevacizumab is an effective therapeutic option in patients with cutaneous lymphangitis carcinomatosa arising from cervical cancer.
KeywordsCervical cancer Cutaneous lymphangitis carcinomatosa Skin metastasis Bevacizumab
Cervical cancer is the fourth most common cancer in women worldwide , resulting in approximately 275,000 deaths per year . The incidence and mortality rates of cervical cancer in Japan were 16.1 and 4.4 per 100,000 people, respectively. The recurrence rate of cervical cancer was 8–26%, and overall survival after recurrence ranged from 7 to 12 months .
The common sites of recurrence are local, lung, liver, bone, and lymph node metastasis . In contrast, cutaneous metastasis, especially cutaneous lymphangitis carcinomatosa arising from cervical cancer, is extremely rare. It is caused by occlusion of the lymphatic channels of the dermis by cancer cells . Skin metastasis, including cutaneous metastasis due to lymphangitis carcinomatosa, is associated with a poor prognosis. The average survival period after the appearance of skin metastasis is as short as 3 to 8.5 months [5, 6, 7, 8].
The treatment for recurrent cervical cancer depends on the site of recurrence (local or distant recurrence). Systemic chemotherapy is chosen for the treatment of distant recurrence or local recurrence within the irradiation field. In addition, bevacizumab (BV) has been approved for targeted therapy in patients with recurrent or advanced cervical cancer on the basis of the results of the Gynecologic Oncology Group (GOG) 240 trial . BV is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor (VEGF)-A . VEGF-C, a subfamily within the VEGF family, is expressed in human cancers. VEGF-C promotes tumor angiogenesis and lymphangiogenesis in vivo, and drives tumor growth and metastasis [11, 12]. BV has potential antitumor effects against metastatic lesions in the lymph system.
Here, we report a case of cutaneous lymphangitis carcinomatosa arising from cervical cancer that was successfully treated with paclitaxel-cisplatin and BV (TP + BV) combination therapy. We believe that TP + BV therapy can be effective against lymphangitis carcinomatosa arising from cervical cancer.
To the best of our knowledge, this is the first case report on TP + BV therapy for skin metastasis from cervical cancer. Skin metastasis occurs in 0.7–9% of all patients with cancer . Skin metastases have the following distribution in women with primary malignancies: breast (69%), large intestine (9%), melanoma (5%), lung (4%), ovary (4%), sarcoma (2%), pancreas (2%), and uterine cervix (2%) . The most common sites of skin metastases in patients with cervical cancer are the abdominal wall, vulva, anterior chest wall, and lower extremities . Although skin metastasis mainly presents as nodules or masses, these lesions may sometimes appear as nodules or inflammatory disease [5, 14]. The morphologic patterns are nodules, plaques, and inflammatory telangiectatic lesions . It is difficult to distinguish lymphangitis carcinomatosa from dermatitis. If the lesion is refractory dermatitis, a skin biopsy should be performed.
Literature for patients treated with chemotherapy against skin metastasis arising from squamous cervical carcinoma without other metastasis
Site of skin metastasis
Thigh and vulva
Özcan et al. /2017
1st line; PTX-CBDCA
2nd line; GEM-BV
Umbilicus (incisional scar), abdominal wall
1st line; PTX-CBDCA
2nd line; GEM-BV + RT
Benoulaid et al. /2016
Basu and Mukherjee /2013
Thigh, inguinal region
CDDP-PTX + palliative RT
Behtash et al. /2008
Behtash et al. /2002
Abdominal wall (drain site)
Cisplatin-5FU + palliative RT
Palaia et al. /2002
Palliative chemotherapy (PTX)
Kagen et al. /2001
Freeman et al. /1982
RT + Bleomycin-MTX -cyclophosphamide
In a mouse model of suture-induced corneal neovascularization, BV decreased cell proliferation of corneal lymphatic vessel cells through an anti-angiogenic effect . Although the evidence supporting the anti-lymphangiogenic effects of BV in cancer is limited , BV has an antitumor effect in patients with breast cancer with lymph node metastasis . Regarding lymphangitis carcinomatosa arising from other cancers, long survival has been reported in two cases treated with chemotherapy in combination with BV [29, 30]: paclitaxel and carboplatin (TC) in one patient with lung cancer and 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) in a patient with colorectal cancer. Thus, BV may be more effective in metastases through lymph vessels, including lymphangitis carcinomatosa.
In general, lymphangitis carcinomatosa is resistant to various therapies and has a poor prognosis. In the current case, TP + BV combination therapy was extremely effective against lymphangitis carcinomatosa. Our findings indicate that a chemotherapy regimen that includes bevacizumab should be considered an effective therapeutic option in patients with cutaneous lymphangitis carcinomatosa arising from cervical cancer.
All authors analyzed the patient data regarding the disease and conducted patient care. FN collected patient data, described it in the case report with literature review. FN, MS, and SN performed literature review and made significant contributions to the writing of the manuscript. All authors read and approved the final manuscript.
No funding available.
Ethics approval and consent to participate
Consent for publication
Written informed consent was obtained from the patient for the 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.
Author, S Nagase, received lecture fees from Chugai Pharmaceutical Co., Ltd. and AstraZeneca. The other authors declare that they have no competing interests.
- 1.Rosen VM, Guerra I, McCormack M, Nogueira-Rodrigues A, Sasse A, Munk VC, Shang A. Systematic review and network meta-analysis of bevacizumab plus first-line topotecan-paclitaxel or cisplatin-paclitaxel versus non-bevacizumab-containing therapies in persistent, recurrent, or metastatic cervical cancer. Int J Gynecol Cancer. 2017;27:1237–46.CrossRefGoogle Scholar
- 9.Penson RT, Huang HQ, Wenzel LB, Monk BJ, Stockman S, Long HJ 3rd, et al. Bevacizumab for advanced cervical cancer: patient-reported outcomes of a randomised, phase 3 trial (NRG Oncology-Gynecologic Oncology Group protocol 240). Lancet Oncol. 2015;16:301–11. https://doi.org/10.1016/S1470-2045(15)70004-5.CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Mandriota SJ, Jussila L, Jeltsch M, Compagni A, Baetens D, Prevo R, Banerji S, Huarte J, Montesano R, Jackson DG, et al. Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumor metastasis. EMBO J. 2001;20:672–82. https://doi.org/10.1093/emboj/20.4.672.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Suzuki E, Tanahashi M, Yukiue H, Yohii N, Shitara M, Fujino T, Niwa H. A patient with lung adenocarcinoma, lymphangitis carcinomatosa, and multiple bone metastases who achieved long-term survival after successful treatment with carboplatin, paclitaxel, and bevacizumab. Gan To Kagaku Ryoho. 2016;43:617–20.PubMedGoogle Scholar
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.