Primary Lymphedema Research Articles

Yellow Nail Syndrome: An Unusual Cause of Pleural Effusion

Yellow Nail Syndrome (YNS) is a rare clinical syndrome charecterised by the classical triad of thickened and dystrophic yellow nails, pleural effusion and primary lymphoedema. It usually occurs in older adults of over 50 years but there is no sex predilection. This was a case report of a 21-year-old male, who presented with dyspnea on exertion, dry cough and abdominal distension for past 15 days and bilateral lower limb swelling for past two years. On general examination, patient had pallor with bilateral non pitting oedema of lower limbs and had yellow thick and dystrophic nails. There was clinical evidence of pleural effusion and ascites. Pleural fluid analysis showed lymphocytic and exudative picture with low Lactate Dehydrogenase (LDH) and Adenosine Deaminase (ADA) levels and was negative for malignancy. Duodenum Second part (D2) biopsy showed Primary Intestinal Lymphangiectasia (PIL). Hence, a final diagnosis of yellow nail syndrome was confirmed. Symptomatic management was done following which patient had relief of symptoms and in subsequent follow-ups patient was doing better. A detailed clinical history with investigations helps in attaining the diagnosis. Although there is no definitive treatment but diagnosis helps in avoiding unnecessary treatment and symptom based management helps in improving the quality of life of the patient.

Stimulation of Synthesis and Lysis of Extracellular Matrix Proteins in Fibrosis Associated with Lymphedema.

Background: Fibrotic diseases pose a problem for overall health due to their chronic, progressive nature; the lack of a cure; and the fact that such conditions are largely refractory to current medical and surgical treatment practices. Objective: The aim of the present study was to report the physiological stimulation of synthesis and lysis of extracellular matrix proteins during the treatment of primary lymphedema. Material and Methods: A clinical trial was conducted involving the analysis of changes in type I and III collagen fibers and elastic fibers as well as the thickness of the epidermis and dermis in 10 histological fields. Samples were taken from the skin before and after intensive treatment using the Godoy Method® and adapted to the treatment of fibrosis in a patient with a clinical diagnosis of lower limb lymphedema. Slides were stained with orcein, hematoxylin and eosin, picrosirius red, and Gomori’s reticulin stains. Weibel’s multipoint method was used for the morphometric evaluation. The data were compared using the t-test with a 95% confidence interval. Results: Significant changes were detected in all aspects of interest (thickness of the epidermis and dermis, type I and III collagen fibers, and elastic fibers). Conclusion: The present findings demonstrate the physiological stimulation of synthesis and lysis of the main components of an extracellular matrix, such as type I and III collagen fibers and elastic fibers, as well as a reduction in the thickness of the epidermis and dermis in cases of fibrosis through adequate stimulation of the lymphatic system.

Autologous peripheral blood mononuclear cells for the treatment of lower extremity lymphedema: a preliminary report

Lymphedema is a chronic devastating disease characterized by the accumulation of fluid in the extremities, tissue progressive changes such as adipose tissue deposition and fibrosis. To restore the functionality and structural integrity of the damaged lymphatic vessels, autologous peripheral blood mononuclear cells (PBMNC) was implanted in 3 sessions, 4 weeks apart, in the affected limb. Each patient was followed for 6 months, monitoring changes in the limb volume. Lymphangiogenesis was evaluated by lymphoscintigraphy, and the monitoring of quality of life. A rapid reduction in the volume of the limbs was observed: 24.5% of volume reduction after the first implant, 18.5% after the second, and 15.3% at 6 months after the third (p<0.05 vs baseline).
 Lymphoscintigraphy showed a hyper fixation of the tracer along the ipsilateral iliac axis not appreciable at baseline. Implants of autologous PBMNC in patients with primary lower limb lymphedema seems to be a feasible, effective therapy option.

Biallelic ANGPT2 loss-of-function causes severe early-onset non-immune hydrops fetalis

BackgroundHydrops fetalis, a pathological fluid accumulation in two or more body compartments, is aetiologically heterogeneous. We investigated a consanguineous family with recurrent pregnancy loss due to severe early-onset non-immune hydrops...

Improvement of quality of life by intake of hydroxytyrosol in patients with lymphedema and association of lymphedema genes with obesity.

Lymphedema is a debilitating disease and may be a comorbidity of obesity. New molecules have been investigated for the treatment of lymphedema; one of the most promising molecules is hydroxytyrosol. The aim of this study was to evaluate the association between mutations in genes mutated in lymphedema and the presence of obesity and making an estimate of the quality of life in lymphedema patients. We recruited 71 Caucasian individuals with the diagnosis of primary lymphedema, and they undertook a questionnaire to assess their quality life. For this purpose, we developed a NGS custom-made panel comprising genes associated with lymphedema. An obesity rate of 20% was detected. The average Lymph-ICF-LL value for patients who consume olive oil daily was 20 with a better quality of life. Twenty-three patients resulted positive to the genetic test. Genetic variants with a likely association with obesity have been identified in PROX1, FOXC2 and FLT4. A obesity rate, higher than that reported by ISTAT, was detected. The use of olive oil enhances the quality of life of lymphedema patients. Moreover, a diagnostic approach by a NGS panel shows an association of lymphedema with obesity.

Primary lymphedema of breast, a case report.

IntroductionLymphedema affects the extremities of breast cancer patients post-surgical or radiation therapy. This study aims to report a case of primary lymphedema of breast.Case presentationA 41-year-old female presented with right breast swelling. It associated with hotness and intermittent mastalgia for the past 8 years. Ultrasound (US) examination showed diffuse trabeculate, skin thickening and edematous with normal glandular tissue. Magnetic resonance imaging (MRI) showed diffuse homogeneous parenchymal enhancements with diffuse tranecular and skin edema (high signal on Short-TI Inversion Recovery (STIR)). The result of the biopsy showed normal breast tissue and lymph node.DiscussionThe major risk factors of lymphedema are breast cancer surgery, radiation therapy, axillary lymph node dissection, length and location of breast incision, taking biopsy, trauma, wound infection. Forearm is the most common site of swelling. Primary lymphedema of the breast is a very rare condition without a known risk factor.ConclusionAlthough it is rare, primary lymphedema can affect the breast. US and MRI are necessary to exclude other pathologies. It is managed conservatively.

ABNORMAL LYMPHATIC PHENOTYPE IN A CRISPR MOUSE MODEL OF THE HUMAN LYMPHEDEMA-CAUSING CONNEXIN47 R260C POINT MUTATION

Connexin proteins form gap junctions controlling exchange of ions and small molecules between cells and play an important role in movement of lymph within lymphatic vessels. Connexin47 (CX47) is highly expressed in lymphatic endothelial cells and CX47 missense mutations, i.e., R260C, cosegregate with primary lymphedema in humans. However, studies utilizing CX47 knockout mice have failed to demonstrate any lymphatic anomalies. To unravel the lymphatic consequences of expressing a mutant CX47 protein, we used CRISPR technology to create a mouse carrying a Cx47 missense mutation (Cx47R259C) equivalent to the human CX47R260C missense mutation associated with human primary lymphedema. Intradermal Evans Blue dye injection identified a 2-fold increase in regional lymph nodes in homozygous Cx47R259C mice compared to wildtype, particularly in the jugular region (4.8 ± 0.4 and 2.0 ± 0.0, respectively, p<0.01). Associated lymphatic channels were increased in Cx47R259C mice and mesenteric lymph reflux occurred in homozygous Cx47R259C mice but not in wildtype. Contractility of superficial cervical lymphatics, assessed by pressure myography, was reduced in homozygous Cx47R259C mice compared to wildtype. In conclusion, our data are the first to demonstrate a role for the Cx47 protein in lymphatic anatomy and function. This phenotype is similar to that found with other valve deficient mouse mutants, e.g., in Foxc2. Of significance, this study is the first to use CRISPR technology to develop a pre-clinical model of primary lymphedema and demonstrates the importance of distinguishing between lack of and presence of mutant protein when developing clinically relevant animal models for translation of pre-clinical findings.

Commentary: Lymph-axiality concept awareness reduces trauma-induced lymphedema (commentary on JPRAS-D-20-01255: Lymph-interpositional-flap transfer (LIFT) based on lymph-axiality concept: simultaneous soft tissue and lymphatic reconstruction without lymph node transfer or lymphatic anastomosis)

Depending on the stage of secondary lymphedema, surgical treatments can be categorized into reconstructive (e.g., lymphovenous bypass and vascularized lymph nodes transfers 1 Cheng M.H. Chen S.C. Henry S.L. et al. Vascularized groin lymph node flap transfer for postmastectomy upper limb lymphedema: flap anatomy, recipient sites, and outcomes. Plast Reconstr Surg. 2013; 131: 1286-1298 Google Scholar ) and debulking procedures (e.g., lipoaspiration 2 Brorson H. Svensson H. Liposuction combined with controlled compression therapy reduces arm lymphedema more effectively than controlled compression therapy alone. Plast Reconstr Surg. 1998; 102 (discussion 1068): 1058-1067 Google Scholar , modified Charles’ procedures 3 van der Walt J.C. Perks T.J. Zeeman B.J. et al. Modified Charles procedure using negative pressure dressings for primary lymphedema: a functional assessment. Ann Plast Surg. 2009; 62: 669-675 Google Scholar ). Lymph-interpositional-flap transfer (LIFT) based on lymph-axiality concept: Simultaneous soft tissue and lymphatic reconstruction without lymph node transfer or lymphatic anastomosisJournal of Plastic, Reconstructive & Aesthetic SurgeryVol. 74Issue 10PreviewLymphatic system is important to maintain homeostasis. Lymph-axiality concept has been reported, which suggests possibility of lymphatic reconstruction using flap transfer without lymph node or supermicrosurgical lymphatic anastomosis. Full-Text PDF

Lymphaticovenous Anastomosis for Age-Related Lymphedema.

Introduction: Primary lymphedema is usually caused by intrinsic disruption or genetic damage to the lymphatics but may also be the result of age-related deterioration of the lymphatics. The aims of this study were to determine the characteristics of age-related lymphedema and to assess the effectiveness of lymphaticovenous anastomosis (LVA) in its treatment. Methods: Eighty-six patients with primary lymphedema affecting 150 lower limbs were divided into three groups according to whether the age of onset was younger than 35 years, 35–64 years, or 65 years or older. Indocyanine green (ICG) lymphography was performed, followed by LVA surgery. ICG lymphography images were visually classified according to whether the pattern was linear, low enhancement (LE), distal dermal backflow (dDB), or extended dermal backflow (eDB). The lower extremity lymphedema (LEL) index score was calculated before and after LVA. Lymphatic vessel diameter and detection rates were also recorded. Results: In the ≥65 group, the lymphedema was bilateral in 54 patients and unilateral in 1 patient. There was statistically significant deterioration in the LEL index score with progression from the linear, LE, dDB through to the eDB pattern in the ≥65 group. The lymphatic vessel diameter was significantly greater in the ≥65 group. The rate of improvement was highest in the ≥65 group. Conclusion: Age-related lymphedema was bilateral and deterioration started distally. The lymphatic vessels in patients with age-related lymphedema tended to be ectatic, which is advantageous for LVA and may increase the improvement rate.

Lymphatic system and adipose tissue: Crosstalk in health and disease

The lymphatic system (LS) is one of the main integrative systems of the body, providing protective and transport functions. In recent years, interactions between LS and adipose tissue (AT) have been of particular interest. Lymphatic vessels play an important role in metabolic and regulatory functions of AT, acting as a collector of lipolysis products and adipokines. In its turn, hormones and adipocytokines that produced in adipocytes (including leptin, adiponectin, IL-6, TNF-α, etc.) affect the function of lymphatic endothelial cells and control the growth of lymphatic vessels. Cooperation between LS and AT becomes pathogenetically and clinically important in lymphedema and obesity. It is known that both primary and secondary lymphedema are characterized by increased fat accumulation which is associated with the severity of lymphostasis and inflammation. Similarly, in obesity, the drainage function of LS is impaired, which is accompanied by perilymphatic mononuclear infiltration in the AT. The development of these changes is facilitated by endocrine dysfunction of adipocytes and impaired production of adipocytokines. The increase in the production of inflammatory mediators and the disruption of the traffic of inflammatory cells causes a further deterioration in the outflow of interstitial fluid and exacerbates the inflammation of the AT, thereby forming a vicious circle. The role of lymphangiogenesis in AT remodeling in obesity needs further research. Another promising area of research is the study of the role of intestinal LS in the development of obesity and related disorders. It has been shown that the transport of chylomicrons from the intestine depends on the expression of a number of molecular mediators (VEGF-C, DLL-4, neuropilin-1, VEGFR-1, CD36/FAT, etc.)in the endotheliocytes of the intestinal lymphatic vessels, as well as the functioning of «push-button» and “zippering” junctions between endothelial cells. New approach to the treatment of obesity based on blockade of lymphatic chylomicrontransport has been experimentally substantiated. Further identification of the molecular mechanisms and signaling pathways that determine the remodeling of AT in lymphedema and obesity are likely to provide new approaches to the treatment of these diseases.

Digenic Inheritance of a FOXC2 Mutation and Two PIEZO1 Mutations Underlies Congenital Lymphedema in a Multigeneration Family

BackgroundThe lymphatic system is essential for maintaining the balance of interstitial fluid in tissues and for returning protein-rich fluids (lymph) to the bloodstream. Congenital lymphatic defects lead to accumulation of lymph in peripheral tissues and body cavities, termed primary lymphedema. To date, only a limited number of individual genes have been identified in association with primary lymphedema. However, variability of age of onset and severity of lymphatic abnormalities within some families suggests that multiple mutations or genes may be responsible, thus hampering efforts to identify individual associated genes. MethodsWhole exome sequencing (WES) was performed in 4 members of a large multigeneration family with highly variable lymphedema and followed by Sanger sequencing for identified mutations in 34 additional family members. Genotypes were correlated with clinical and lymphangioscintigraphic phenotypes. ResultsWES uncovered 2 different mechanotransducer PIEZO1 mutations and one FOXC2 transcription factor mutation in various combinations. Sanger sequencing confirmed the presence/absence of the 3 variants in affected and unaffected family members and co-segregation of one or more variants with disease. Genetic profiles did not clearly correlate with the highly variable severity of lymphatic abnormalities. ConclusionsWES in lymphedema families can uncover unexpected combinations of several lymphedema-associated mutations. These findings provide essential information for genetic counseling and reveal complex gene interactions in lymphatic developmental pathways. These can offer insights into the complex spectrum of clinical and lymphatic lymphedema phenotypes and potential targets for treatment.

LIMPRINT in Italy.

Background: To define the profile of patients presenting with chronic edema (CE) in three centers in Italy (Lymphoedema IMpact and PRevalence INTernational). Methods and Results: Data were collected in patients referred for CE between September 2016 and July 2017. A total of 1637 were recruited, 86.7% (1419) outpatients and 13.3% (218) inpatients with 80.6% (1319) female and mean age 54 years. Primary lymphedema occurred in 28.2% (461). In the 71.8% (1176) with secondary CE cancer occurred in 72% (846) and 28% (330) due to other causes. Data showed that 84.2% (226) had full upper body mobility, 15.5% (41) had limited mobility and 0.2% (2) had lost all mobility. Lower limb mobility status: 90.4% (1205) complete mobility, 8.4% (112) reduced mobility and 1.2% (21) wheelchair bound. Concurrent leg ulceration occurred in 32.9% (322) with 3.1% (51) having antibiotics. Treatment patterns varied with only 32.4% (530) receiving instructions in skin care, 61.2% (1002) multilayer compression and a further 67.8% (1110) compression garment with 17.6% (288) having sequential pressure therapy. Only 1.4% (23) had received psychological support. Out of the total 481/1637 (29.4%) were not prescribed any treatment. Only 50.4% (825) had access to subsidized treatments within the National and Regional Health Care System, whereas 49.6% (81) had to pay themselves with only half (50.9%) having access to treatment centers that were near their home. Conclusion: Results from this study and active lobbying have led to changes in reimbursement of care for primary and secondary lymphedema in Italy; this has led to a much more optimistic picture for those affected.

Primary Lymphedema: A Newborn Case

Lymphedema is a condition characterized by generalization or regional accumulation of protein-rich interstitial fluid as a result of impaired lymphatic circulation due to congenital or acquired reasons. Lymphedema infection may occur as a result of secondary neoplasm, surgery, trauma, and radiation while most childhood cases are primary lymphedema. In cases of primary lymphedema, there is an erroneous development or function of the lymphatic system and most of them are thought to have a genetic predisposition. We aim to present a case of primary congenital lymphedema with a history of kinship between parents and no dysmorphic findings, born with lymphedema on both feet.

Outcomes of Lymphovenous Anastomosis for Upper Extremity Lymphedema: A Systematic Review.

Background:Lymphovenous anastomosis (LVA) is an accepted microsurgical treatment for lymphedema of the upper extremity (UE). This study summarizes and analyzes recent data on the outcomes associated with LVA for UE lymphedema at varying degrees of severity.Methods:A literature search was conducted in the PubMed database to extract articles published through June 19, 2020. Studies reporting data on postoperative improvement in limb circumference/volume or subjective improvement in quality of life for patients with primary or secondary lymphedema of the UE were included. Extracted data consisted of demographic data, number of patients and upper limbs, duration of symptoms before LVA, surgical technique, follow-up, and objective and subjective outcomes.Results:A total of 92 articles were identified, of which 16 studies were eligible for final inclusion comprising a total of 349 patients and 244 upper limbs. The average age of patients ranged from 38.4 to 64 years. The duration of lymphedema before LVA ranged from 9 months to 7 years. The mean length of follow-up ranged from 6 months to 8 years. Fourteen studies reported an objective improvement in limb circumference or volume measurements following LVA, ranging from 0% to 100%. Patients included had varying severity of lymphedema, ranging from Campisi stage I to IV. The maximal improvement in objective measurements was found in patients with lower stage lymphedema.Conclusion:LVA is a safe, effective technique for the treatment of UE lymphedema refractory to decompressive treatment. Results of LVA indicate greater efficacy in earlier stages of lymphedema before advanced lymphatic sclerosis.

Quality of life evaluation and lack of correlation with volumetric results after lymphovenous anastomoses in lymphedema therapy of the lower extremity

ObjectiveChronic primary or secondary lymphedema has huge effects on patients' quality of life (QOL) because of the associated swelling and pain, decreased range of motion, and depression and anxiety and generally requires numerous adaptations. Many studies have shown a positive objective effect of lymphovenous anastomoses (LVAs) on chronic lymphedema. In the present study, we assessed the effect of LVAs on QOL in patients with primary or secondary lymphedema of the lower extremity at 6 months after surgery and examined the correlation between changes in the QOL and volumetric measurements. MethodsOnly patients with either primary or secondary lymphedema of the lower extremity who had undergone LVAs were included in the present study. To assess QOL, a specially designed questionnaire based on the Lymphedema Quality of Life Inventory was used to evaluate the subjective therapeutic results from the patients' perspective. Objective therapy success was assessed using three-dimensional volumetric measurements of the lower leg. The measuring points, for both the subjective and the objective measurements, were the day before and 6 months after therapy. ResultsThe mean change in volume at 6 months after LVA was −6.5% ± 5.6% (P < .001). Significantly better QOL in terms of physical (37.6% ± 25.2%) and psychosocial (27.0% ± 43.0%) domains and practical restrictions (22.3% ± 24.8%) was found (P < .001 for all). No correlation was found between QOL improvement and volume decrease (P > .05). ConclusionsFor patients with lymphedema of the lower extremity, LVAs can lead to a significant volumetric decrease and QOL improvement at 6 months after treatment with no demonstrable relationship between QOL improvement and volume reduction.

An inducible Cldn11-CreERT2 mouse line for selective targeting of lymphatic valves.

Luminal valves of collecting lymphatic vessels are critical for maintaining unidirectional flow of lymph and their dysfunction underlies several forms of primary lymphedema. Here, we report on the generation of a transgenic mouse expressing the tamoxifen inducible CreERT2 under the control of Cldn11 promoter that allows, for the first time, selective and temporally controlled targeting of lymphatic valve endothelial cells. We show that within the vasculature CLDN11 is specifically expressed in lymphatic valves but is not required for their development as mice with a global loss of Cldn11 display normal valves in the mesentery. Tamoxifen treated Cldn11-CreERT2 mice also carrying a fluorescent Cre-reporter displayed reporter protein expression selectively in lymphatic valves and, to a lower degree, in venous valves. Analysis of developing vasculature further showed that Cldn11-CreERT2 -mediated recombination is induced during valve leaflet formation, and efficient labeling of valve endothelial cells was observed in mature valves. The Cldn11-CreERT2 mouse thus provides a valuable tool for functional studies of valves.

Regulation of VEGFR Signalling in Lymphatic Vascular Development and Disease: An Update.

The importance of lymphatic vessels in a myriad of human diseases is rapidly gaining recognition; lymphatic vessel dysfunction is a feature of disorders including congenital lymphatic anomalies, primary lymphoedema and obesity, while improved lymphatic vessel function increases the efficacy of immunotherapy for cancer and neurological disease and promotes cardiac repair following myocardial infarction. Understanding how the growth and function of lymphatic vessels is precisely regulated therefore stands to inform the development of novel therapeutics applicable to a wide range of human diseases. Lymphatic vascular development is initiated during embryogenesis following establishment of the major blood vessels and the onset of blood flow. Lymphatic endothelial progenitor cells arise from a combination of venous and non-venous sources to generate the initial lymphatic vascular structures in the vertebrate embryo, which are then further ramified and remodelled to elaborate an extensive lymphatic vascular network. Signalling mediated via vascular endothelial growth factor (VEGF) family members and vascular endothelial growth factor receptor (VEGFR) tyrosine kinases is crucial for development of both the blood and lymphatic vascular networks, though distinct components are utilised to different degrees in each vascular compartment. Although much is known about the regulation of VEGFA/VEGFR2 signalling in the blood vasculature, less is understood regarding the mechanisms by which VEGFC/VEGFD/VEGFR3 signalling is regulated during lymphatic vascular development. This review will focus on recent advances in our understanding of the cellular and molecular mechanisms regulating VEGFA-, VEGFC- and VEGFD-mediated signalling via VEGFRs which are important for driving the construction of lymphatic vessels during development and disease.

Value of one additional injection at the root of the limb in the lymphoscintigraphic evaluation and management of primary and secondary lower-limb lymphedemas.

IntroductionThe classical lymphoscintigraphic investigations of lower-limb lymphatic edema [LLLE] sometimes reveal either no or few lymph nodes [LNs] at the root of the limb[s] and/or in the abdomen. The aim of the present paper is to report the results of performing one additional injection at the root of the edematous limb[s] to force the visualization of the LNs and/or to demonstrate the collateral lymphatic pathways in such patients.Methods and findingsWe retrospectively reviewed our database and found 99 patients [44 primary LLLE with 47 limbs injected and 55 with LLLE secondary to treatments for cancer with 64 limbs injected] where such an additional injection had been performed.In the 43 LLLE patients where no LNs were seen at the end of the classical exam [15 primary LLLE and 28 secondary LLLE], the extra injection showed lymphatic drainage toward LN[s] in all except 3 and when at least one LN was seen, the injection showed lymphatic drainage in every case toward the same ipsilateral [inguinal and/or iliac] LNs [as shown by the classical injection] and/or toward additional LNs.In 40.7% of patients, we observed one or more additional lymphatic pathways: prepubic superficial lymphatic vessels [LV] crossing the midline anteriorly toward contralateral inguinal LNs in 21 [18.9%], “posterior” LV [toward contralateral inguinal LNs and/or ipsi- or contralateral lumbo-aortic and/or para-renal LNs] in 14 [12.6%], but deep LV toward the ipsilateral common iliac LNs passing between the gluteal muscles in 32 [28.8%].ConclusionOur work pinpoints one limitation of classical bipedal radionuclide lymphangiography. In patients with primary and secondary LLLE where inguinal and/or iliac LNs cannot be seen on bipedal radionuclide lymphangiography, this additional injection reveals the true lympho-nodal status and shows unexpected collateral lymphatic pathways in 40% of cases. Such information is of the utmost importance in LLLE management and its acquisition is consequently recommended in these patients.

BI09: Immune dysfunction in primary lymphoedema

BI09: Immune dysfunction in primary lymphoedema

Mise au point sur l’anatomie de la région axillaire : l’arc musculaire du grand dorsal ou muscle de Carl Langer, un grand oublié dans la formation des internes

ObjectiveThe Carl Langer muscle is the main anatomical variation of the walls of the axillary area, its incidence being about 7%. The presence of this muscle crossing the anterior edge of the axillary vessels can induce difficulties of exposure, location and dissection during axillary surgery. In addition, it may be responsible for primary lymphedema of the upper limb, venous thrombosis of the axillary vein or thoracic outlet syndrome due to vascular or nervous compression. The objective of this work was to evaluate the state of knowledge on Carl Langer muscle of the gynecology-obstetrics medical residents of the French Eastern Region. Material and methodsAll the medical residents enrolled in the specialized diploma in gynecology-obstetrics in the 5 regions (Alsace, Bourgogne, Lorraine, Champagne-Ardenne and Franche-Comté) were questioned by means of a questionnaire sent by e-mail. ResultsFrom February to March 2021, 94 of the 160 medical residents interviewed answered to the questionnaire. Ninety-one of them (97%) did not know Carl Langer's muscle. Three medical residents thought they knew this muscle (3%) but their knowledge was imperfect. ConclusionOur work has highlighted the general lack of knowledge of this anatomical variation, which is relatively frequent, among French gynecology-obstetrics medical residents who are required to examine or perform surgery on this area. This updated review of the literature should optimize the knowledge of the anatomy of the axillary area and consequently its surgery.