Bilateral axillary web syndrome in a patient with primary lymphoedema of upper limbs and non-Hodgkin lymphoma.

Primary lymphoedema, axillary web syndrome (AWS) and yellow nail syndrome may be related. Mr B is a 66-year-old gentleman with genital lymphoedema and lymphoedema of all four extremities. In 2023, he was diagnosed with non-Hodgkin lymphoma and also underwent cardiac surgery. In November 2023, he completed an inpatient rehabilitation at the Földi clinic in Germany, where he received intensive treatment for his lymphoedema and was also diagnosed with bilateral AWS. The presence of AWS in a patient with primary lymphoedema and no history of axillary surgery is unique. Although AWS typically presents after axillary surgery, this case highlights that it can also occur in patients without lymph node surgery. While the precise cause of this presentation of AWS is not known, it may be connected to yellow nail syndrome or potentially the recent chemotherapy treatment. This article will describe the clinical case, highlighting the need for further research on AWS present in primary lymphoedema.

MR Lymphangiography in Lymphatic Disorders: Clinical Applications, Institutional Experience, and Practice Development.

Lymphatic flow and anatomy can be challenging to study, owing to variable lymphatic anatomy in patients with diverse primary or secondary lymphatic pathologic conditions and the fact that lymphatic imaging is rarely performed in healthy individuals. The primary components of the lymphatic system outside the head and neck are the peripheral, retroperitoneal, mesenteric, hepatic, and pulmonary lymphatic systems and the thoracic duct. Multiple techniques have been developed for imaging components of the lymphatic system over the past century, with trade-offs in spatial, temporal, and contrast resolution; invasiveness; exposure to ionizing radiation; and the ability to obtain information on dynamic lymphatic flow. More recently, dynamic contrast-enhanced (DCE) MR lymphangiography (MRL) has emerged as a valuable tool for imaging both lymphatic flow and anatomy in a variety of congenital and acquired primary or secondary lymphatic disorders. The authors provide a brief overview of lymphatic physiology, anatomy, and imaging techniques. Next, an overview of DCE MRL and the development of an MRL practice and workflow in a hybrid interventional MRI suite incorporating cart-based in-room US is provided, with an emphasis on multidisciplinary collaboration. The spectrum of congenital and acquired lymphatic disorders encountered early in an MRL practice is provided, with emphasis on the diversity of imaging findings and how DCE MRL can aid in diagnosis and treatment of these patients. Methods such as DCE MRL for assessing the hepatic and mesenteric lymphatic systems and emerging technologies that may further expand DCE MRL use such as three-dimensional printing are introduced. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Back to the Future II-A Comprehensive Update on the Rapidly Evolving Field of Lymphatic Imaging and Interventions.

ABSTRACT: Lymphatic imaging and interventional therapies of disorders affecting the lymphatic vascular system have evolved rapidly in recent years. Although x-ray lymphangiography had been all but replaced by the advent of cross-sectional imaging and the scientific focus shifted to lymph node imaging (eg, for detection of metastatic disease), interest in lymph vessel imaging was rekindled by the introduction of lymphatic interventional treatments in the late 1990s. Although x-ray lymphangiography is still the mainstay imaging technique to guide interventional procedures, several other, often less invasive, techniques have been developed more recently to evaluate the lymphatic vascular system and associated pathologies. Especially the introduction of magnetic resonance, and even more recently computed tomography, lymphangiography with water-soluble iodinated contrast agent has furthered our understanding of complex pathophysiological backgrounds of lymphatic diseases. This has led to an improvement of treatment approaches, especially of nontraumatic disorders caused by lymphatic flow abnormalities including plastic bronchitis, protein-losing enteropathy, and nontraumatic chylolymphatic leakages. The therapeutic armamentarium has also constantly grown and diversified in recent years with the introduction of more complex catheter-based and interstitial embolization techniques, lymph vessel stenting, lymphovenous anastomoses, as well as (targeted) medical treatment options. The aim of this article is to review the relevant spectrum of lymphatic disorders with currently available radiological imaging and interventional techniques, as well as the application of these methods in specific, individual clinical situations.

Breast-implant Related Silicone Lymphadenopathy: Asteroid Bodies do not Always Equal Sarcoidosis!

Silicone breast implants are frequently used for breast augmentation for cosmetic purposes, as well as for breast reconstruction after prophylactic or therapeutic mastectomy. Silicone lymphadenopathy is a well-known complication of silicone breast implants. Silicone droplets are present in the breast tissue through 'silicone bleeding' of the implant or because of implant rupture. These silicone particles can migrate from the breast to the regional lymph nodes. Silicone lymphadenopathy is caused by a substantial foreign body reaction against these silicone particles, and is frequently associated with asteroid body-containing multinucleated giant cells. Similar multinucleated giant cells are often observed in the capsule surrounding the silicone breast implant, and the number of associated asteroid bodies is highly variable. Here, we discuss a series of twelve women with breast implant-related asteroid bodies in their lymph nodes and/or breast tissue. This pictorial essay illustrates that the presence of asteroid bodies in a lymph node does not necessarily suggests a diagnosis of sarcoidosis. Clinical information about the patient having (or having had) silicone breast implants is often lacking. The encounter of asteroid body-containing giant cells in lymph node cytology, biopsies or resections should therefore lead to reflex clinical-pathological correlation, before establishing a final diagnosis.

[Fluorescence-guided Lymph Vessel Sealing in Systematic Nodal Dissection: a New Surgical Technique to Prevent Lymphorrhea and Lymphocele.] / Fluoreszenzgesteuerte Lymphgefäßversiegelung bei der systematischen Lymphknotendissektion zur Vermeidung von Lymphfisteln und Lymphozelen.

INTRODUCTION: The primary morbidities of inguinal and axillary systematic nodal dissection are lymphatic fistulas and seromas. Intraoperative fluorescence imaging-guided sealing of lymph vessels may prevent these postoperative complications. METHODS: Indocyanine dye was injected intracutaneously into the distal limb before the beginning of the lymphadenectomy. Systematic nodal dissection was performed according to standard protocols. Near-infrared imaging was applied throughout the procedure and real-time fluorescence-guided lymph vessel sealing was performed. RESULTS: Fluorescence-guided lymph vessel sealing was implemented in three patients undergoing axillary systematic lymph node dissection. No adverse events occurred following fluorescence dye injection. All patients could be discharged free of wound complications. CONCLUSION: Fluorescence-guided lymph vessel sealing might be a promising new technique for preventing lymphatic fistulas and lymphocele after systematic lymphadenectomy.

State-of-the-art imaging for lymphatic evaluation in children.

The lymphatic system has been poorly understood and its importance neglected for decades. Growing understanding of lymphatic flow pathophysiology through peripheral and central lymphatic flow imaging has improved diagnosis and treatment options in children with lymphatic diseases. Flow dynamics can now be visualized by different means including dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL), the current standard technique to depict central lymphatics. Novel imaging modalities including intranodal, intrahepatic and intramesenteric DCMRL are quickly evolving and have shown important advances in the understanding and guidance of interventional procedures in children with intestinal lymphatic leaks. Lymphatic imaging is gaining importance in the radiologic and clinical fields and new techniques are emerging to overcome its limitations.

Understanding Lymphatic Anatomy and Abnormalities at Imaging.

Lymphatic abnormalities encompass a wide range of disorders spanning solitary common cystic lymphatic malformations (LMs) to entities involving multiple organ systems such as lymphangioleiomyomatosis. Many of these disorders are rare, yet some, such as secondary lymphedema from the treatment of malignancy (radiation therapy and/or lymph node dissection), affect millions of patients worldwide. Owing to complex and variable anatomy, the lymphatics are not as well understood as other organ systems. Further complicating this is the variability in the description of lymphatic disease processes and their nomenclature in the medical literature. In recent years, medical imaging has begun to facilitate a deeper understanding of the physiology and pathologic processes that involve the lymphatic system. Radiology is playing an important and growing role in the diagnosis and treatment of many lymphatic conditions. The authors describe both normal and common variant lymphatic anatomy. Various imaging modalities including nuclear medicine lymphoscintigraphy, conventional lymphangiography, and MR lymphangiography used in the diagnosis and treatment of lymphatic disorders are highlighted. The authors discuss imaging many of the common and uncommon lymphatic disorders, including primary LMs described by the International Society for the Study of Vascular Anomalies 2018 classification system (microcystic, mixed, and macrocystic LMs; primary lymphedema). Secondary central lymphatic disorders are also detailed, including secondary lymphedema and chylous leaks, as well as lymphatic disorders not otherwise easily classified. The authors aim to provide the reader with an overview of the anatomy, pathology, imaging findings, and treatment of a wide variety of lymphatic conditions. ©RSNA, 2022.

A randomized comparison of sample adequacy and diagnostic yield of various suction pressures in EBUS-TBNA.

INTRODUCTION: The evidence for using vacuum suction during EBUS is sparse and the optimal suction pressure for obtaining adequate samples has not yet been determined. Our aim was to assess the influence of suction on the adequacy and diagnostic yield of EBUS-TBNA. MATERIAL AND METHODS: This single-center, prospective, randomized, non-inferiority trial assessed whether no-suction and 10 mL suction are inferior to 20 mL suction for adequacy and diagnostic yield of EBUS-TBNA aspirates. RESULTS: Three hundred twenty three lymph nodes were sampled using EBUS-TBNA. Baseline characteristics of lymph nodes were comparable in the three suction groups. The overall adequacy of EBUS-TBNA aspirates in the no-suction, 10 mL, and 20 mL suction was 90%, 83.49%, and 77.88%, respectively. The differences in adequacy were 12.1% (95% CI: 3.9-20.3) and 5.6% (95% CI: -3.3-14.5) for no-suction vs 20 mL, and 10 mL vs 20 mL suction, respectively. No-suction and 10 mL were not inferior to 20 mL suction in terms of sample adequacy. At a superiority margin of 3.92%, no-suction was superior to 20 mL suction in terms of sample adequacy (p < 0.05). The overall diagnostic yield was comparable (63.6%, 52.3%, and 57.7% in 0, 10 mL, and 20 mL, respectively; p-value was not significant). The proportion of aspirates which were predominantly bloody was similar (no-suction - 10.9%, 10 mL - 13.8%, 20 mL - 15.4%; p = 0.62). CONCLUSIONS: EBUS-TBNA with or without the application of vacuum suction does not influence specimen adequacy and diagnostic yield.

Infection-Associated Thymic Atrophy.

The thymus is a vital organ of the immune system that plays an essential role in thymocyte development and maturation. Thymic atrophy occurs with age (physiological thymic atrophy) or as a result of viral, bacterial, parasitic or fungal infection (pathological thymic atrophy). Thymic atrophy directly results in loss of thymocytes and/or destruction of the thymic architecture, and indirectly leads to a decrease in naïve T cells and limited T cell receptor diversity. Thus, it is important to recognize the causes and mechanisms that induce thymic atrophy. In this review, we highlight current progress in infection-associated pathogenic thymic atrophy and discuss its possible mechanisms. In addition, we discuss whether extracellular vesicles/exosomes could be potential carriers of pathogenic substances to the thymus, and potential drugs for the treatment of thymic atrophy. Having acknowledged that most current research is limited to serological aspects, we look forward to the possibility of extending future work regarding the impact of neural modulation on thymic atrophy.

Functional lymphatic reserve capacity is depressed in patients with a Fontan circulation.

BACKGROUND: Lymphatic abnormalities play a role in effusions in individuals with a Fontan circulation. Recent results using near-infrared fluorescence imaging disclosed an increased contraction frequency of lymphatic vessels in Fontan patients compared to healthy controls. It is proposed that the elevated lymphatic pumping seen in the Fontan patients is necessary to maintain habitual interstitial fluid balance. Hyperthermia has previously been used as a tool for lymphatic stress test. By increasing fluid filtration in the capillary bed, the lymphatic workload and contraction frequency are increased accordingly. Using near-infrared fluorescence imaging, the lymphatic functional reserve capacity in Fontan patients were explored with a lymphatic stress test. METHODS: Fontan patients (n = 33) were compared to a group of 15 healthy individuals of equal age, weight, and gender. The function of the superficial lymphatic vessels in the lower leg during rest and after inducing hyperthermia was investigated, using near-infrared fluorescence imaging. RESULTS: Baseline values in the Fontan patients showed a 57% higher contraction frequency compared to the healthy controls (0.4 ± 0.3 min-1 vs. 0.3 ± 0.2 min-1 , p = 0.0445). After inducing stress on the lymphatic vessels with hyperthermia the ability to increase contraction frequency was decreased in the Fontan patients compared to the controls (0.6 ± 0.5 min-1 vs. 1.2 ± 0.8 min-1 , p = 0.0102). CONCLUSIONS: Fontan patients had a higher lymphatic contraction frequency during normal circumstances. In the Fontan patients, the hyperthermia response is dampened indicating that the functional lymphatic reserve capacity is depressed. This diminished reserve capacity could be part of the explanation as to why some Fontan patients develop late-onset lymphatic complications.

Micronodular thymic carcinoma with lymphoid hyperplasia: relevance of immunohistochemistry with a small panel of antibodies for diagnosis-a RYTHMIC study.

Micronodular thymic carcinoma with lymphoid hyperplasia (MNTCLH) is a rare form of thymic carcinoma. We present the experience of RYTHMIC, the French national network devoted to the treatment of thymic epithelial tumors through multidisciplinary tumor boards with a review of all tumors by pathologists for classification and staging. Six cases of MNTCLH were diagnosed during a review of 1007 thymic epithelial tumors. Histologically, epithelial cells with atypia and mitoses formed micronodules that were surrounded by an abundant lymphoid background with follicles. There was neither obvious fibro-inflammatory stroma nor necrosis. Spindle cells areas were common. Initial diagnosis was micronodular thymoma in two cases, cellular atypia being overlooked, eclipsed by the micronodular pattern. Immunohistochemistry with a panel of five antibodies showed that cytokeratins (AE1-AE3) and p63-positive epithelial cells also expressed CD5 and that there was no TdT-positive cells within the tumors. CD20 highlighted the lymphoid hyperplasia. Additionally epithelial cells also expressed CD117 and diffusely Glut 1. Twenty-seven micronodular thymomas with lymphoid stroma diagnosed during the same period did not show the CD5 and CD117 positivities seen in MNTCLH and contained TdT-positive lymphocytes. Three of the 6 patients with MNTCLH had adjuvant radiotherapy. Three patients with follow-up information were alive without recurrence at 38, 51, and 95 months. Our study shows that immunohistochemistry, such as that used in the RYTHMIC network with a small panel of antibodies, may easily help to confirm the correct diagnosis of MNTCLH, a rare and low-aggressive form of thymic carcinoma, and avoid the misdiagnosis of micronodular thymoma.

Endosalpingiosis Is Negative for GATA3.

CONTEXT.­: Endosalpingiosis is a benign Müllerian inclusion that can mimic metastatic low-grade mammary carcinoma, particularly when encountered in axillary lymph nodes excised for breast cancer staging. Immunohistochemistry can be useful in histologically ambiguous cases, and a targeted immunopanel should include a marker of gynecologic tract origin and a marker of mammary origin. GATA3 is a sensitive immunomarker for breast carcinoma, but the immunoreactivity of GATA3 in endosalpingiosis has not been systematically evaluated. OBJECTIVE.­: To evaluate whether GATA3 immunohistochemistry could be used to differentiate endosalpingiosis from metastatic mammary carcinoma. DESIGN.­: Whole slide sections of 15 cases of endosalpingiosis involving nonneoplastic tissues were subjected to GATA3 immunohistochemistry. Nuclear GATA3 labeling was scored as percentage and intensity labeling, with any labeling considered positive; GATA3 labeling was recorded in all cells present in the sections. RESULTS.­: Half (47%, n = 7 of 15) of the endosalpingiosis cases involved lymph nodes (2 axillary, 5 pelvic) and half (53%, n = 8 of 15) involved pelvic organs or soft tissue (3 myometrial, 2 paratubal, 2 periadnexal soft tissue, and 1 pelvic sidewall). GATA3 immunohistochemistry was negative in all cases of endosalpingiosis, with intact, positive control labeling in lymphocytes. The benign fallopian tube epithelium present on the sections of paratubal endosalpingiosis displayed focal (<5%), weak labeling for GATA3, specifically within the ciliated and secretory cells. CONCLUSIONS.­: These findings support the diagnostic utility of GATA3 immunohistochemistry and its use in a targeted immunopanel to resolve the differential diagnosis of metastatic low-grade mammary carcinoma (GATA3+) and nodal endosalpingiosis (GATA3-).

The Application of Fine Needle Aspiration Biopsy in the Diagnosis of Axillary Masses.

INTRODUCTION: We intend to determine the diagnostic power of fine needle aspiration biopsy (FNAB) for differentiation between malignant and benign lesions on axillary masses and draw the physicians' attention to the benefits of FNAB cytology in the diagnosis of axillary masses. METHODS: In this study, 1,328 patients with an axillary mass diagnosed by FNAB were retrospectively reviewed. These cases were registered at the affiliated hospital of Southwest Medical University (China), July 2014 to June 2017. Cytological results were verified either by histopathology following surgical resection or clinical follow-up. RESULTS: Of the 1,328 patients affected by axillary masses, 987 (74.3%) cases were female, and 341 (25.7%) cases were male. The highest incidence of patients was in the age group of 41-50 years (375, 28.2%). There were 1,129 (85.0%) patients with benign lesions and 199 (15.0%) with malignant lesions. Of the 199 malignant lesions cases, 21 cases were lymphomas, 2 cases were accessory breast cancers, and 176 cases were lymph node metastatic tumors. Under lymph node metastases, the most frequent primary tumors were breast cancer (141, 80.1%), followed by lung cancer (21, 11.9%). According to the study, the characters of 1,328 cases showed statistically significant difference (χ2 = 4.534, p = 0.033), and the incidence of females with axillary mass was significantly higher than that of males. There was a statistically significant difference in the distribution of benign and malignant cases in the patient age groups (χ2 = 1.129, p = 0.000), and the incidence of patients of 41-50 years of age was significantly higher than that of other patients. The diagnostic accuracy of FNAB in axillary masses was analyzed with the results of 95.98% of sensitivity, 99.56% of specificity, 97.45% of positive predictive value, and 99.29% of negative predictive value. CONCLUSION: Our results confirm that FNAB is a valuable initial screening method regarding pathologic diagnosis of axillary mass, in particular with respect to malignancy in 41- to 50-year-old female patients.

Comparative immunohistochemical study of deep infiltrating endometriosis, lymph node endometriosis and atypical ovarian endometriosis including description of a perineural invasion.

AIM: Endometriosis is an inflammatory condition that shares a number of similarities with malignant diseases, such as an abnormal morphology, migration along the nerve bundles and metastatic spread to lymph nodes and distant organs. Endometriotic lesions are associated with oestrogen and progesterone imbalance which seems to play a key role in the pathogenesis of endometriosis. The aim of this study was to compare the status of both oestrogen and progesterone receptors in tissue of deep infiltrating endometriosis, lymph node endometriosis and atypical ovarian endometriosis using immunohistochemical methods, as well as to investigate the relationship between endometriosis and protein p53. METHODS: A total of 40 cases with deep infiltrating endometriosis were included in our study. Based on histopathological analysis of resected specimens, the cases were divided into 2 groups: group 1 - lymph node endometriosis (cases with lymph node involvement; n=12) and group 2 - deep infiltrating endometriosis (cases without lymph node involvement; n=28). As a control group, eutopic endometrium of adenomyosis- and endometriosis-free women were used (n=16). Five cases of atypical ovarian endometriosis as well as descriptions of the nerve involvement in endometriosis were also included. Immunohistochemical staining with a total of 4 markers was performed - oestrogen and progesterone receptors (ER, PR), p53 and Ki-67 (proliferation index). RESULTS: The immunophenotype of the cases in groups 1 and 2 and in the control group was virtually identical in the proliferative phase - strong nuclear ER and PR expression in more than 90% of endometrial glandular and stromal cells. In the early and mid secretory phase, ER expression only slightly decreased (80%) in endometrial glandular cells in group 2 and the control group, whereas in the late secretory phase, significant decrease of ER expression only in the control group was observed (15-50%; P<0.001). In group 2 and the control group, significant decrease of PR expression only in endometrial glandular cells was observed in the mid and late secretory phase (less than 15%; P<0.001). Differences in receptor content were found only in isolated cases in group 2. In group 1, no secretory changes were found. In all three groups, sporadic and weak nuclear p53 expression in less than 3% in both endometrial glandular and stromal cells was detected (regardless of the phase of the menstrual cycle). In atypical ovarian endometriosis, higher and strong p53 expression (on average 26%) and decrease in ER (on average 56%) and PR (less than 1%) expression was observed; compared to the control group and groups 1 and 2, the differences for all 3 markers were highly significant (P<0.001). In all groups, the proliferation index (Ki-67) reached the highest values in the proliferation phase and decreased during the cycle. However, in endometriotic tissue, it was widely variable in the individual phases of the cycle. Perineural spread of endometriosis with significant neural hypertrophy, hyperplasia and involvement of the ganglia of the autonomic nervous system was detected in 5 cases (12.5%). Conlusion. From a histological and immunohistochemical point of view, deep infiltrating endometriosis and lymph node endometriosis appear to represent the same entity. For the first time, a simple immunohistochemical panel with antibodies against ER, PR and p53 useful in diagnosing atypical endometriosis has been described. The marked endometriosis-associated neural changes (endometriotic neuropathy) could be one of the causes of impaired function of the affected organs after debulking surgery with macroscopic negative resection margins as well as pain symptomatology in macroscopic inapparent endometriotic lesions.

Assessing functional status of cardiac lymphatics: From macroscopic imaging to molecular profiling.

Here we describe various techniques for visualization of the lymphatic vasculature, particularly in the heart. Addressing macro-, microscopic, and molecular levels of lymphatic organization, we give examples of how to explore the roles of specific antigens/markers expressed in lymphatic vessels and their extracellular matrix as structural and functional elements involved in various biological functions of lymphatics. Some obstacles and technical challenges related to lymphatic visualization are also discussed.

Hyperdense Thymic Atrophy After Chemotherapy in Pediatric Patients With Extrathoracic Malignancies.

OBJECTIVE: The aim of the study was to evaluate computed tomography (CT) imaging findings of hyperdense thymic atrophy after chemotherapy in pediatric patients with extrathoracic malignancies. METHODS: Seventy-eight pediatric patients with extrathoracic malignancies, who developed thymic atrophy after chemotherapy, were included in this study. All patients underwent CT imaging before and after chemotherapy. We retrospectively reviewed the CT images. Hyperdense thymic atrophy was defined as thymic atrophy with high CT attenuation (≥80 HU). RESULTS: Hyperdense thymic atrophy after chemotherapy was observed in 7 (9%) of 78 patients. Age (4.3 ± 2.4 vs 8.4 ± 5.4 years, P < 0.01), thymic CT attenuation before chemotherapy (70.4 ± 18.8 vs 55.2 ± 11.9 HU, P < 0.01), reduction rate in thymic area (0.76 ± 0.06 vs 0.60 ± 0.22, P < 0.01), and thymic CT attenuation change (30.3 ± 15.2 vs -16.8 ± 24.0 HU, P < 0.01) were significantly different between patients with and without hyperdense thymic atrophy after chemotherapy. Thymic CT attenuation after chemotherapy (61.2 ± 23.8 vs 33.8 ± 30.1 HU, P < 0.01) and thymic CT attenuation change (-1.3 ± 21.2 vs -19.3 ± 27.9 HU, P < 0.01) were significantly different between patients 5 years or younger (n = 29) and 6 years or older (n = 49). CONCLUSIONS: Hyperdense thymic atrophy after chemotherapy was observed in 9% of pediatric patients with extrathoracic malignancies. It was associated with younger age, greater thymic CT attenuation before chemotherapy, larger reduction rate in thymic area, and greater thymic CT attenuation change.