Case Report
Lung Cancer Lymphatic Drainage and Bilateral Lung Transplantation
Kaoutar Ghammad, Ciprian Pricopi, Antoine Legras, Marc Riquet* and Françoise Le Pimpec Barthes
Department of General Thoracic Surgery, Georges Pompidou European Hospital, Paris, France
*Corresponding author: Marc Riquet, Department of General Thoracic Surgery, Georges Pompidou European Hospital, 20 rue Leblanc, Paris, 75908, France
Published: 03 Apr, 2017
Cite this article as: Ghammad K, Pricopi C, Legras A,
Riquet M, Le Pimpec Barthes F. Lung
Cancer Lymphatic Drainage and
Bilateral Lung Transplantation. Clin
Oncol. 2017; 2: 1257.
Abstract
A 25-year-old female patient with cystic fibrosis underwent bilateral lung transplantation. A
solitary lung nodule was discovered in the left upper lobe two years following transplantation. After
thorough work-up and a biopsy proving the nodule to be an adenocarcinoma, a left upper lobectomy
including complete mediastinal lymphadenectomy was performed. The analysis demonstrated
adenocarcinoma with hilar and mediastinal metastatic lymph nodes, confirming that the lymphatic
vessels draining the transplanted lungs restored their continuity to the mediastinum. However, the
immunological response to the lymphatic system of donors is poorly understood and the genetics of
cancers occurring in such lungs deserve further study.
Keywords: Lung transplantation; Donor derived cancer; NSCLC; Lymph nodes
Introduction
Unlike normal lungs, there is little data on the anatomy and physiology of Lymph Nodes (LN) and Lymphatic Vessels (LV) that drain the transplanted lungs (LTx). The edema observed immediately after LTx ("primary graft failure"), is mainly the consequence of LVs interruption [1]. The regeneration of LVs might play a role in the rejection induction, local immune response and occurrence of obliterative bronchiolitis [1]. Lung Cancer (LC) is a disease that can now be encountered in recipients of a graft lung: we observed a NSCLC that occurred after a bilateral LTx and whose pathological examination recalled a more banal role of the LV regenerated after their interruption.
Case Report/Description
A 25-year-old woman with cystic fibrosis diagnosed at birth, suffered from history of chronic
methicillin-resistant Staphylococcus aureus and Pseudomonas related colonization. She presented
several episodes of allergic bronchopulmonary aspergillosis and a progressive chronic respiratory
failure that finally evolved towards severe hypoxemia with acute respiratory distress syndrome.
Despite continuous non invasive ventilation and antibiotic therapy, no improvement was observed:
the partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2) was 65 mmHg and 80 mmHg,
respectively, with a pH of 7, 28. She was treated by veno-venous Extracorporeal Membrane
Oxygenation (ECMO) as a bridge to lung transplantation and inscribed on the high-emergency
national waiting list.
Three days after the inscription, in June 2014, she underwent bilateral LTx. The donor was
a 48-year-old man, with smoking history (28PA) and discrete diffuse pulmonary emphysema.
The PaO2/FiO2 ratio (oxygen fraction of inspired air) was correct (517 with 100% FiO2).
Postoperative course was marked by hemodynamic instability requiring ECMO support for
five days. Immunosuppressive treatment was conventional with Prednisone, Tacrolimus and
Mycophenolatemofetil. The patient was discharged 31 days after surgery.
Eighteen months after LTx, a pulmonary embolism was diagnosed. The chest CT revealed a
solitary pulmonary nodule in the left upper lobe measuring 12mm, with 18F-FDG uptake SUV
(standardized uptake value) max of 6.5. There were two suspect peribronchial LNs, one near the
lower lobe bronchus – behind the left main bronchus (SUVmax of 5.4), and the other one, on the
bifurcation of upper and lower lobe bronchi (SUV max of 5.2). The cerebral magnetic resonance
imaging was normal, and the bronchial fibroscopy was not contributive. Lung scintigraphy
showed a left lung perfusion of 42%. Spirometry was subnormal with forced expiratory volume in
one second of 71% and vital capacity of 93% of predicted values. The CT-guided biopsy revealed an adenocarcinoma. After multidisciplinary discussion, surgery.
was decided. Intra-operative examination revealed a para-aortic
LN (mediastinal LN station 6) besides the clinically identified LNs
(station 11 and 10). An isolated 5 mm posterior parietal pleural lesion
was also discovered and completely resected. A left upper lobectomy
with complete mediastinal lymphadenectomy was performed. The
postoperative course was uneventful.
Pathologic analysis confirmed a poorly differentiated invasive
adenocarcinoma measuring 20mm with lymphovascular involvement.
All resected LNs were tumoral. The cross section of the left upper
bronchus presented some lymphatic emboli. Pathology classification
was pT1N2M1a, the visceral pleura was not involved, and the parietal
pleural nodule was metastatic. Cytogenetic analysis of the tumor
confirmed that the cancer originated from the donor cells. A k-Ras
mutation was also discovered. Because of massive lymphovascular
involvement, the multidisciplinary team decided a platinum-based
chemotherapy associated with Paclitaxel and Bevacizumab. The
Tacrolimus treatment was reduced and the MycophenolateMofetil
was stopped. Paclitaxel treatment was stopped for peripheral
neuropathy. The patient developed multiple hepatic and bone
metastasis and died 8 months after surgery.
Comment
The incidence of cancers in 1000 person-years after LTx is 19.8
and LC is the one with the highest incidence (5.94%), followed by
posttransplant lymphoproliferative disorder (5.72%) and colorectal
cancer (1.38%) [2]. LC may be observed on the explanted lung [3].
More frequently, it is observed on the native lung after single LTx.
Dickson and colleagues [4] observed that 6.9% of the single LTx
recipients developed primary NSCLC as compared with 0% of the
bilateral LTx recipients after a mean of 52 months: it is worth stressing
that the NSCLC were present in the native lung of patients with
smoking history. Grewal and colleagues [3] reported similar results.
However, they also observed one LC originating in the allograft and
potentially donor related [3]. LC in the donor lung is not frequent. In
a series of 13 patients who developed LC, 9 occurred in the native lung
in 92 single LTx and 4 were donor related, all after bilateral LTx (n =
224) [5]. The incidence of post LTx NSCLC will probably increase in
the future. The limited number of available donor compared to the
increase of patients on the waiting list leads to liberalization of donor
criteria with older patients, tobacco history and chest radiograph
with abnormality as was the case in our observation. In addition, it
was a highly urgent lung transplant: the condition of our patient was
extremely serious and her life dramatically endangered which urged
to accept a donor of an advanced age with tobacco history and lung
emphysema.
During the donor lung transplantation the LVs are overlooked
and their anastomosis not performed. It has been demonstrated in
dogs that lung lymphatic drainage is re-established 7-28 days after
auto LTx and becomes relatively sufficient shortly thereafter [6].
Although such study does not exist in man, it is logical to postulate
that LVs are similarly regenerating. However, the immunological
response to transplanted donor LNs and LVs is poorly known
and remains a topic of research [1]. Similarly, the genetics and
immunogenicity of NSCLC from such lungs may be those of the
recipient or donor, as many questions as future studies may elucidate
further. Whatever it may be, the NSCLC generally occurs due to risks
factors inherent to the donor of the lung, mainly the tobacco smoking
habits. The presence of the k-ras mutation supports this theory. In fact,
NSCLC is not induced by posttransplantation immunosuppressive
drug therapy, and in the same way, NSCLC postoperative course
was demonstrated to be independent from a continuation of this
treatment [7]. In 2006, Sleeman JP [8] reminded that there was an
active relationship between the tumor and the lymphatic system. To
form LN metastasis, the tumor is able to produce some growth factors
(VEGF-C, VEGF-D) that lead to activation of some receptors as
VEGFR-3. In our observation, the pulmonary LNs involved originate
from the donor and the mediastinal LNs are from the recipient. The
relationship between the tumor and the lymphatic system does not
seem to have been altered.
To our knowledge, this is the first case report describing a
metastatic NSCLC to mediastinal LN that comes from a donor lung
and demonstrates the recovery of lymph drainage after LTx. Such an
observation raises the problem of the immunological response to the
transplanted lymphatic system and the genetics of cancer in the lung
of the donor.
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